SARTORIUS FRANCE

L’étalonnage des pipettes est important Presque tous les laboratoires utilisent quotidiennement des pipettes. Dans la mesure où pratiquement toutes les analyses impliquent l’utilisation de pipettes, celles-ci ont un impact sur la précision et la répétabilité des données expérimentales. Par conséquent, les pipettes doivent être régulièrement étalonnées pour s’assurer qu’elles répondent aux exigences de l’utilisation prévue. Tous les %YTf&!t?"C'Y?4GV`dAp@p?'Y??A%0G??"?B!45?!GV8?"3rA@cs?A?GV`dAp"Fby%GV%`??@p?'Y??`dApGV0BG0BGGV`dApF!x)@!45?!#c???GV$Y?8'Y??94h)GV@p?@p?GV#c?&?@?C'Y??s?A?GV`dAp&c&v@p?%`?SS@Vf@p?rA@c5?U&?@?C`dAp`dAp"&B?AGV%YTf&Hv(`PrA@c'Y??"W6?u vous êtes-vous jamais demandé à quelle fréquence à l’étalonnage ? 6 `(!??p?&tucXUf`4?IUH70 Les pipettes sont souvent étalonnées conformément à la 6t!G@p?G7'"?& wuF?A3ty Ar' ?69GX9?p1R?04 généralement testées et ajustées dans le cadre d’un DE???E?'?Q?pR???? nominal de la pipette, qui est le volume maximal. Pendant l’étalonnage, les différents volumes d’eau distillée ou ?cp?1G?#Y&p balance avec un piège à humidité dans une salle dont les conditions environnementales sont contrôlées. La masse mesurée est comparée aux valeurs attendues afin de déterminer les écarts de performance. À quelle fréquence les pipettes ne répondent-elles #Bc9x'?S!XAA?& "??$b3?&R`G$??"T "x%t

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??b9???0#Te)?2fE?? Les pipettes proviennent de différents grands fabricants et leurs dates de fabrication sont variables. Le taux de non-conformité observé (écart par rapport aux ?H?)?%83"TwUD1v?p??m $7`fS)iRg@4VFHU9? électroniques. Chaque pipette non conforme doit faire l’objet d’un entretien pour répondre aux spécifications. BY?S@6R?P0e???$?#? nombre de pipettes ne répondent pas aux exigences en matière d’étalonnage, mais vous pouvez adopter certaines pratiques afin que vos pipettes fonctionnent correctement. Checklist $) B% A? Nettoyez et entretenez régulièrement les pipettes conformément aux spécifications de leur fabricant et aux exigences supplémentaires de votre application. Après tout démontage et remontage pour entretien ou nettoyage, pensez à vérifier les performances de votre pipette. Pour vérifier les performances des pipettes ou contrôler leur qualité en cours d’utilisation, il vous suffit de pipeter de l’eau distillée ou déionisée sur une balance d’analyse et de vérifier (et consigner) que les résultats se situent dans des limites acceptables. )Re% A? ?t"UA@'uhaa?@I ?D@p?G7&)QR(v?cR@t? t !t?"Cga??02?Y`% A? fréquence d’utilisation et les liquides que vous pipetez. 3. ?t"UA@'uhaa?79 ??1?y$-??#'?6e?f?8%?78 composants essentiels, tels que le piston ou le cylindre. 4. Vérifiez les performances de la pipette entre les DE??
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??bGV hu?pv?G@p?)?(XE7C3Q??&C'7?!t &p?w)$ 1T?P0?Q?b ?D 5&`n service.france@sartorius.com 4p??94h)"&B?A!t?"C'Y??A%0G?!t?"CrA@c@p?'Y??&?@?C`dAp8?"3!45?!gC ?GV@p?@p?GV3DH?6?7PrA@c`dApAG)?GV0BGGV`dApA?uFrA@c`dAp$Y?8%`??"&B?ArA@cs?A?'Y??%YTf&SQ%6 `(!&?@?C94h)1
i ?%`??'Y?0AG)?6?7P'H?Q?rA@c%`??@p?&?@?C%`??'Y??!45?!BWexrA@c6q?X`dAp%YTf&@p?%`??!45?!0BGGV`dAp@p?u"s0BGA00PB28GB&?@?CPv?C XB`SQ%4p??@p?rA@c@p?!45?!I7`Ba$#W?? ?F?BBuU? Pour plus d’informations, consultez le site suivant www.sartorius.com Pour certaines pipettes électroniques, telles que Sartorius Picus ® Nxt, l’intervalle d’étalonnage peut être paramétré en activant le rappel d’étalonnage. Cette fonction vous avertira lorsque l’étalonnage précédent est sur le point d’expirer. Vous pouvez également verrouiller la pipette Sartorius Picus ® Nxt si vous pensez qu’elle ne fonctionne pas !t?"CA??7?'yW'?Sx P54Rb3&7W0c#'X8??B&?' n’aura pas été vérifiée. 2?#?&?@?C!45?!(p?B'5?U!45?!#c?&?p@??A(?x)?&?@?C%`?60BGrA@c@p?'Y?C?@?C`dAp5P??@ Services sur les produits de pipetage et de distribution Regardez la vidéo du didacticiel sur l’entretien des pipettes Note d’application sur le calibrage et les étalons des pipettes Pa2e% A? Utilisez des pointes de haute qualité pour obtenir les résultats 7aAgs%0ea&?1@p?v4i`?)TCE sont un système conçu pour s’emboîter parfaitement et garantir ainsi une exactitude et une précision optimales. ?t&q07g??d!?HD5'RT0AfF%?%1Ft1??dn

Comment choisir une pipette de laboratoire de microbiologie 2 Comme publié dans Rapid Microbiology , 2023 . Dans ce guide, nous explorons certains facteurs à prendre en compte quand il s'agit de choisir une pipette manuelle ou électronique pour les analyses microbiologiques. Les exigences en matière de manipulation des liquides dans un laboratoire de microbiologie peuvent être différentes de celles d'autres laboratoires d'analyse. Voici quelques points à prendre en compte avant de s'engager dans l'achat d'une pipette. Points clés à considérer lors de l'achat d'une pipette pour des applications en microbiologie Volumes Les volumes de liquide à distribuer peuvent couvrir un large éventail (allant, par exemple, de l'ajout de volumes plus importants de milieux de culture jusqu'à des quantités de l'ordre du microlitre pour les essais moléculaires). Contamination Dans les laboratoires de microbiologie, il existe de BX)!1fQY ?9?!t?"CU9?B?!7!t?C7ey??@p??% s "q9'A?TC&?s?)87CW$`s4d5EW!y bactériens ou viraux, le risque de contamination croisée entre les échantillons et le matériel est bien présent. Ceci est particulièrement important lors de la réalisation de tests de stérilité ou de biocharge. Pointes Des pointes de pipette stériles, ainsi que d'autres formats comme des pointes sans endotoxines, et sans inhibiteurs de tests PCR ou avec un filtre intégré sont disponibles auprès de votre fabricant de pipettes. Des pointes à bord large peuvent être nécessaires pour pipeter des bouillons d'enrichissement contenant des débris alimentaires. Facilité d'utilisation La pipette doit être ergonomique et facile à utiliser dans l'espace confiné d'une enceinte à flux laminaire. Calendrier d'entretien et d'étalonnage Essentiel pour tous les instruments de laboratoire. Développement durable Presque tous les laboratoires s'efforcent aujourd'hui de réduire leurs déchets plastiques. Abordez cette question avec le fabricant pour comprendre comment il contribue à résoudre ce problème. 1T?P%`?P1hHe6?A?%$i)Yq Académie de formation au pipetage Pipettes mécaniques Pipettes électroniques Pointes de pipette Programmes de reprise de pipettes 3 Petit rappel - Quelle est la différence entre justesse et répétabilité ? Pour de nombreuses applications, les pipettes doivent être aussi justes ET répétables que possible, mais quelle 35?dAB?s5 A?Iy?H13?(?FY?U@?)bDA??!? 7 La justesse 7%9# CCa`&?@?C)1Y3TA??0S?h(576? la répétabilité 7%9# CCa`&?@?C)1Y3T?Qc'@t? t Ag% ?A( 67hIa6&??)bDfH?) 3?d&&EEfI??0??#` Un facteur clé de lla justesse et la répétabilité est l'utilisation de la pipette de volume approprié pour chaque étape d'un protocole, en plus de la formation au pipetage. De nombreux fabricants proposent d'excellentes ressources de formation gratuites, sous forme de vidéos ou de textes. Contamination Qu'il s'agisse d'une contamination moléculaire d'un test PCR par transfert de pointe ou d'une contamination microbienne par l'opérateur, dans un environnement BPL, le choix de votre pipette doit tenir compte de la capacité à prendre les mesures suivantes pour minimiser le risque que la pipette soit une source de contamination. Ces mesures sont notamment les %d5$@p?%$6t • Avant et après utilisation, essuyer la surface de la $7`fS?C?@%I?r • Utiliser des pointes de pipette préstérilisées. • Stocker la pipette verticalement sur un support de pipette. • Suivre les conseils du fabricant pour le nettoyage et la stérilisation de la pipette. Elle devra résister à la B7r8??P ?AVS1? V?u#e6)?r"$ Rw
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7% A? la facilité de cette opération et si des outils spéciaux sont nécessaires pour le démontage des pièces. Les pipettes mécaniques sont plus faciles à stériliser '@5s#)?r"q?3&4D?x73?? Quelle est la différence entre une pipette 6`7'87?PT#y?v ? Juste et Répétable Juste mais Pas Répétable Pas Juste mais Répétable Ni Juste Ni Répétable 4 03FU`Pointes de pipette - Sont- ?6?@??3!H??dtDt% A? (?f90
y Il existe de nombreux fournisseurs de pointes de pipette, notamment des vendeurs de marque propre proposant des prix très réduits, mais la meilleure solution consiste normalement à ce que les pointes et la pipette proviennent du même fabricant, car les performances spécifiées par un fabricant ne concernent que son dispositif utilisé avec ses pointes. La norme G? %U7??"27u$A0B?I? à piston précise que, en cas d'utilisation de pointes de pipette non fournies par le fournisseur de la pipette, la déclaration de conformité du fournisseur ne s'applique pas. Avant d'acheter la pipette, vérifiez que le fabricant propose exactement les formats de pointes dont vous 8??DC??@F? e9x'?S4?Y&xX • Faciles à mettre en place et positionnement étanche • Des pointes à filtre pour éviter la contamination de la pipette par l’échantillon • Pointes préstérilisées - emballées et conditionnées en nombre suffisant pour répondre à vos besoins • Pointes rallongées - pour atteindre le fond des longs tubes sans que la pipette ne touche le récipient • Exempt d'endotoxine/de pyrogène si vous effectuez un test d'endotoxine bactérienne (BET), un LAL ou un MAT • Sans inhibiteurs de PCR - les tests moléculaires doivent se faire avec des pointes exemptes d'inhibiteurs tels que l'endonucléase, l'exonucléase et la RNase 03FU` Facilité d'utilisation Les pipettes étant le cheval de bataille du laboratoire, le choix d'une pipette doit permettre d'accroître la productivité. Il est donc essentiel qu'elles soient fiables, faciles à utiliser, conformes aux normes ISO du laboratoire et qu'elles constituent l'outil adéquat pour la tâche à accomplir. Les pipettes électroniques sont plus ergonomiques, plus rapides à utiliser, fournissent des résultats reproductibles et peuvent être programmées. Faites une démonstration en laboratoire avant l'achat pour vous assurer que les forces d'utilisation de l'instrument sont faibles pour l'ensemble du cycle de pipetage, depuis la fixation de la pointe, jusqu'au pipetage et à l'éjection de la pointe, afin d'éviter les microtraumatismes répétés (TMS). Certains fabricants ont spécialement conçu une éjection de pointe simple. En cas d'utilisation dans une hotte à flux laminaire, tous les ajustements de volume et les tâches de manipulation devront être effectués dans l'espace restreint. D'où viennent les erreurs de A?Iuiy@Ap Une note d'application* de Sartorius indique que les erreurs les plus importantes pour les pipettes à déplacement d'air 6e26?i?v?D??@@p?%$6W • #h?%% A? 6r?m% A?4h7)G???@p?3"r`S%SyQf fuient ou sont mal ajustées •  F P s5?5ps1sXRf@p?B??S? •  C0 s5?p#C??U@p?B??S? • '?3?@p?2?h??31q?W? % A? ##xT?% A? proposent un contrat de service pour l'étalonnage régulier. Ils doivent également fournir des instructions détaillées pour la maintenance quotidienne ou hebdomadaire et un programme d'étalonnage facile à respecter par tout membre du personnel. L'autoclave peut en faire partie, surtout s'il est utilisé pour des échantillons microbiologiques. Vérifiez si les pipettes sont faciles à autoclaver. Développement durable - Comment réduire les 7XA? Poussés par la demande du marché, les fabricants de pointes de pipettes s'efforcent désormais de réduire les déchets d'emballage en plastique qui accompagnent les pointes et les supports. Ressources *$5b'?'3??193?!B?B1T?P4?Wr0!Brr 2?#?tE 1T?P!Hr8Af2I$tE Performance $5b'?'3??193?uU% for Good Laboratory Practice (cGLP) or current Good Manufacturing Practice (cGMP) Guide Sartorius pour éviter la contamination des pipettes Pour plus d'informations, consultez le site suivant www.sartorius.com Allemagne Sartorius Lab Instruments GmbH & Co. KG Otto-Brenner-Strasse 20 37079 Goettingen 1T?P?"T` États-Unis Sartorius Corporation EX??SI5P?? TPA?cX? 1T?Pa&P0 7GCCS8u@p?AQ?)p Les spécifications peuvent être modifiées sans préavis. Copyright Sartorius Lab Instruments GmbH & Co. KG. q?6erA@c@p?tW

Mars 2021 !Qt Test intermédiaire, poids de référence, réétalonnage, rapport d'incertitude du test (TUR), valeur conventionnelle du poids, OIML R-111 | ASTM E617 Manipulation des poids de test Sélection judicieuse et manipulation correcte des poids Dr. Ellen Hage, Axel Taube, Dr. Julian Haller, Niclas Ludolph, Sartorius Lab Instruments GmbH & Co. KG, Otto-Brenner-Strasse 20, 37079 Göttingen Correspondance ?0QX`9'?fQ?et?'y$D%@??A En résumé Des valeurs de poids correctes sont extrêmement importantes pour les processus de pesée en production, ainsi que pour l'analyse (qualité). Mais comment l'utilisateur de la balance peut-il être sûr que le poids affiché à l'écran est identique à la 9y)4R((!)?5'c?? Ce livre blanc décrit les possibilités pour l'utilisateur de contrôler et de tester une balance avec des poids de test. %0?x(8s?W(?bv#UV?c4?Y!'7??$?e?8`h??p$ft?Av9P?
R?q?)`'08% A? @`F2?5?eA226FB!y?EBtAQ((!)?!?#t5?ub?A??7?'yW?G!`?x/ pratiques pour la manipulation. En appliquant les mesures présentées ici, vous réduirez le risque d'erreur d'un processus de pesée et optimiserez les intervalles de réétalonnage. Bx7s??a1???www.sartorius.com White Paper 2 Introduction Pour une assurance qualité réussie, l'équipement de test doit être utilisé dans les plages de tolérance spécifiées. 0U ?!?Sv`wBgC4T?CB
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)?`??p?!???q3?UU@4?x?B4R Existe-t-il des règles concernant les poids de test à utiliser ??vP??t?3?VPRxS! S'il existe des procédures réglementaires d'inspection des équipements de test pour des applications spéciales, elles doivent bien entendu être suivies. Cependant, étant 5F#?WXU?DF58v?s@t? t e6YP@p?G7!
?a#R?6?3?(?H(re&e(e?(#1R?0Q être simplement suivies par les utilisateurs, ce document explique et détaille les différents aspects. Le processus qui doit être utilisé pour chaque application fait l'objet d'une décision au cas par cas. Ce livre blanc vise également à fournir une assistance en la matière. Manipulation des poids 6 `(!??p?C??&2F?B?yw Les poids de test ne sont capables de tester parfaitement, c'est-à-dire aussi précisément, que leur propre poids. 6 `(!&??10@p?"F
?1R?04@p4p7?'?Qv?i masse de leurs poids de test soit la plus connue possible ??F?? Pour cette raison, les poids de test doivent toujours être manipulés avec précaution. Ils doivent toujours être conservés à l'abri d'influences environnementales et, S$b?"7?XS1?@I!?SwX7?s?R? P surfaces propres. Toute rayure sur la surface pourrait entraîner des dépôts et une contamination ou pourrait indiquer une abrasion du matériau. Avec des poids de grande qualité, il est particulièrement important de ne les manipuler qu'avec des gants ou des pinces brucelles/dispositifs de préhension propres et non pelucheux, car même une empreinte digitale peut peser 7C3Q3"TwUvv.d sur une échelle à quatre chiffres). 9?50@7"3ts??q?@p?F$?2TX0s3?e6Dch?@t? t et, par conséquent, rendent le poids plus vulnérable aux influences environnementales. Vous trouverez d'autres recommandations et conseils pour la manipulation, la conservation et le nettoyage dans la brochure sur les poids de Sartorius (1). Même s'il est utilisé avec soin et peu souvent, chaque y4%G??Y(fq4?T??'?Sx!??2?!1g3F4?T0c??³ fournisseur spécialisé afin que l'utilisateur dispose de la valeur conventionnelle de poids mise à jour et/ou que la valeur nominale du poids soit confirmée comme se trouvant dans la plage de tolérances. Les cycles de réétalonnage doivent être définis selon la criticité des applications de pesée. Comment connaît-on exactement la masse d'un poids ?eS B?yw D'une manière générale, il faut savoir si l'on parle de la  ?C@p?v9x'?S4?Y0F?? valeur conventionnelle de poids (par exemple 8A)?@t? t déterminée par étalonnage et indiquée en conséquence YYS1@8?@w?
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WE#6?4? s 8AQ?AB?s5"a?  cette valeur correspond à la masse du poids et peut être considérée comme la valeur attendue ou réelle. Cependant, la masse (et avec elle, la force de poids sur la balance) d'un poids n'est pas constante. Avec le temps, cette valeur va évoluer (usure, dépôts, etc.). Pour s'assurer de réduire au minimum cette modification, il est important de manipuler les poids avec précaution (voir rubrique précédente). En outre, la force qu'un poids exerce sur la balance change en fonction des conditions environnementales. Par exemple, les différences de température entre le poids et le lieu d'application (poids conservé dans le bureau, testé en chambre froide) peuvent provoquer des effets de poussée aérostatique ou de convection et ainsi modifier la force de poids sur le plateau de pesée, même si la masse du poids est constante. Les différences de pression atmosphérique (pression atmosphérique différente entre le moment de l'étalonnage et le moment du test) conduisent également  t!t?"C5(?u7C3Q@p? ?PwcGPrA@c")&? différents lors des mesures sur une balance. Ces effets étant souvent difficiles à quantifier, il convient de les éliminer autant que possible en conservant les poids idéalement dans le même local (c'est-à-dire dans les mêmes conditions climatiques) que les balances et en 7C0 4Ea?'#?A?v)h#5@&r'X8??@p?(&R? acWFp ?Cvi 7ey??2'h?51R?04 v'$'08?)?c ?C#'??I7?'082??? erreurs maximales possibles (EMT) pour cette classe #ba(EG?Q?@ 2?#?)9??p4?YfA%h@?.S ?C% A? TP y????hiM $tST??4?$WS ?C#'?????@ &4?T?E?x6
?H13?7??4&??XQHb 3 Inversement, s'il existe un certificat d'étalonnage pour le poids, la valeur conventionnelle de poids (valeur attendue) qui y est spécifiée peut être utilisée. Cependant, cela reste sujet à incertitude. Celle-ci est indiquée comme une "$#Q@?#h90CXg&Ach?U et montre la plage dans laquelle se ?H13?%? ?C#'?X? ?6pSf C2
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?H13?@t? t '?e$a&y8r??= 2?uyTh0 Comme la valeur réelle d'un poids n'est connue qu'avec (?)Q60?D1ec85`U@?#h9ESgp864@'!?g( temps ou en raison de facteurs environnementaux, il est particulièrement important de garder ces facteurs à l'esprit lors du choix des tolérances pour les balances de test 2BD??@8q`E"W)(X? 3F?q?9#?6 Comment puis-je être sûr que les poids de test sont @p?1!R&A?? (?? En cas de résultats douteux d'un test intermédiaire avec APe)A)x3&W$? équipement de mesure qui ne fonctionne pas de manière optimale (par exemple, une balance mal réglée) qu'à un équipement de test non optimal (par exemple, un poids ?eS 0?3Qo Afin de connaître la vraie cause, la mesure doit être répétée et il convient de s'assurer que les conditions externes sont conformes aux niveaux normaux (les balances sont stables et de niveau, les influences environnementales telles que la température, les vibrations, le rayonnement thermique, etc. ne sont pas anormales, il n'y a pas de contamination, etc.). Si le résultat douteux se reproduit malgré des conditions normales, il se peut que le poids de test ne soit pas équivalent aux données étalonnées. Afin de confirmer cela, vous pouvez utiliser un autre poids de référence pour mesurer, puis recommencer une troisième fois avec le y???`0E??p??H??B6? Après toutes ces analyses, vous pouvez arriver à la conclusion que soit l'équipement de mesure (la balance), soit l'équipement de test (le poids de test d'origine) est défectueux. En cas de doute raisonnable sur l'exactitude de l'équipement de test, il convient d'établir une déclaration quantitative concernant la différence entre le poids et un poids de référence. Pour cela, il faudra disposer de plus de poids avec des données d'étalonnage connues et une masse aussi proche que possible de celle du poids douteux. Lors d'une mesure dite EMME, également utilisée par des laboratoires d'étalonnage spécialisés pour l'étalonnage, la valeur de poids du poids douteux (M) peut être comparée )?xQ#i&?8AQ?AB?s5"d?b2`!&(re1Vd? dans la recommandation internationale OIML R 111-1, dont '#&?@?C%? 3EFBd`# D? Ad?S% A?s74'265'08Bv?6q étalon E, dans ce cas, peut consister en plusieurs poids Z one dans laquelle \Ola valeur conventionnelle de poids doit se s\Oituer pour correspondre à la\O classe O\fML Z one possible de valeur conventionnelle d\Oe poids\b; pas connue plus en\O détail en raison \Ode l'incertitud e V aleur nominale P oids réel 200,000 05 g V aleur conventionnelle de\d \foids déterminé e Classe O\fML de poids de test E? E? F? F? 199,999 0 g 199,999 5 g200,000 0 g 200,000 5 g 200,001 0 g ?YVhW0%6w 5%`???rpp?W?A0D`r$d4?Y??15??8? ?C4)@?!A!I7C3Q@p?5Ys7 4 individuels) doivent avoir une résolution aussi bonne que possible (c'est-à-dire petit échelon d$@Tc?wa ?iU@P??&?6?X?i'qt3a 7C?8s?W##0Vv?C?@G hF`'!?g( ?Ab?H13??B
'`!IQr#° toujours être remise à zéro et les quatre valeurs d'affichage doivent être notées. Les valeurs moyennes des deux ?1QSAB?s5&e ?V%?8%?7U masses. Plus la certitude avec laquelle la masse de E est connue est grande, plus la masse de M peut être déterminée avec précision par cette méthode, et les changements possibles détectés. Choix des poids de test 3?)QH?% A?B
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0c#???B??T?!?u?7???6@t? t !t?C7ey??@p?GV@9B??6T??p?@p?62u?b"RXt6W?81@Qv" comme tous les autres équipements de mesure, les poids peuvent être vérifiés. La vérification est une confirmation souveraine que cet équipement de test est conforme à ses principales exigences et déclaré apte à l'emploi par un organisme pertinent. Jusqu'à récemment, la vérification était largement acceptée comme preuve de traçabilité 1'h?@7q")&?0`c?Dtu? &?s 5?'?Sx1R?0Q utilisés pour mesurer/étalonner/tester. Cependant, (????'?Aep?aP@p?6E??18YH?0yI0 d'accréditation) a, depuis, exigé que chaque équipement de test dispose d'un étalonnage valide comme preuve de 5???% A? 9sAA!Awv?$W?1We8"g??0??f?h9%?@p?@t? t (@??P#%8?@p?7q ?Q8i%4?0ir)1@5?%- seulement une déclaration de conformité, mais fournit également l'état réel de l'équipement de test, prenant en compte les conditions de mesure et l'incertitude, et donc beaucoup plus d'informations à l'utilisateur. Dans la recommandation internationalement reconnue 3af?d!??0?a 7C3Q@p?U9/ classes. Plus la classe est fine plus les propriétés et les tolérances sont meilleures et faibles. La classe de poids la 0i?i?UU@9vA?)A0'?uT?U9/ les plus faibles qui s'appliquent à la rugosité de la surface, 1GdS2v?F?AB7V!?s?? de la valeur de poids conventionnelle par rapport à la valeur nominale sont pertinentes. La valeur de poids déterminée d'un poids de cette classe est la plus précise, c'est-à-dire que sa vraie valeur est déterminée plus précisément qu'un poids d'une classe inférieure (incertitude de mesure plus faible). Les autres classes basées sur ces directives sont (par 8w?85??#"?7qqac?#D% -5?&%d -"YX???i2v5u2 d'informations à ce sujet, consultez le tableau en annexe. 9VCada1!Q???4UAAcw? classes de poids (000 à 7) en fonction d'exigences élevées relatives à la précision, la densité la rugosité de la surface, "?@P(?2?uT?2?401!Q?B?2R !t?CA??&w?Yg??#9x'?S4?YB70)° Pour juger de la précision de l'affichage de la balance au moyen d'un poids de référence, la masse du poids de %`??8AQ?AB?s5q?wV7?E?!?r0?b W?%M 7?5? YT4y@?78?3GT3!? 7 4?typ% A? un résultta de test, il faut déterminer la plage de tolérance au sein de laquelle l'écart est tolérable. Pour une évaluation pertinente l'incertitude du poids de référence doit évidemment être inférieure à l'écart toléré de la balance. 1????2g%2TX09 5 6 `(!1??2B!i?9?XuD@m de sorte que l'évaluation reste judicieuse et plus proche de Rapport d'incertit\sude de toléranc e échec échec tolérance inférieu\1re valeur attendue tolérance supérieu\1reIncertitude de mesu\sre 1\f:1 5:14:1 \b:1 2:1 Résultat du tes t résultat incertain\1 résultat incertain\1 réussite ?YVhW0% fqqa SA$@?h9%?@p?rA@cSDGp?uT?gsW ??@?#h9(Qw YBT?@4?f8t 5 refléter la réalité (pour plus d'informations à ce sujet, voir la ?YVhW0%$cX > Ce rapport incertitude/tolérance est également connu $sPc@p?6E??pIyA?@q?h? 2?#?(D
sX4?Y0%If 8!D?11ta?6r?m$H@S?uT?0rwhE864@0T @p?4D?d?Xu5 q?% A? 6 `(!HyB?B?P?0(?PX38w?@t? t y?t@3?`Q`'08&E?` hhHyB?$?qQ 9R"4`RY? ?C$?(i? &?b
#'?P??I? $U 88w-&?W4eb76%Q&?? ?C% A? !t?C7ey??2cH$??#'?"??) d q"F Bien sûr, dans la pratique, cela devrait se produire dans l'autre sens, c'est-à-dire que les utilisateurs devraient d'abord établir la tolérance sur l'équipement puis, à partir @F`dg4?0))P D0xiE 5?84t8AQ?AB?s5'?`?96@?gC?x6P7?E?7Tf(7 2?#?A1$bTHQ?#@1!XAA?pYU?E?U9/ déterminent les exigences de précision, c'est-à-dire la classe, du poids qui peut être utilisé pour les tests. Combien de poids sont nécessaires pour vérifier !PCG4?YGu)1`&t?q Il n'est pas possible de répondre de manière générale, car cela dépend de l'utilisation. Au sens strict, un test d'un seul point de l'étendue de pesée ne peut évaluer précisément A7Dr9vA?????@?w''7PR?%$2??0$!S (?E)39vA?????@&R?aT%) ?V )?xQ@$???'?Sxg#w1??2B? F??4??1 laboratoire modernes offrent une très bonne linéarité sur @p?@?P 2?b?Q?C?"b?d6 en un point, on peut s'attendre à ce même petit écart en tous les autres points de l'étendue de pesée. Et comme la linéarité d'une balance est une variable très stable, qui ne change pratiquement pas dans le temps 2?h&@f?T?3"TwU61??T@p???7 généralement de tester la précision avec une seule charge. Dans ce cas, il convient de choisir une charge qui correspond soit à l'étendue de charge dans laquelle les balances sont le plus fréquemment utilisées /la pesée critique réalisée, soit à une valeur proche de la charge maximale, car c'est là que les écarts possibles sont les plus importants, en termes absolus. Ce principe (test à un seul point de mesure) est également utilisé, par exemple, lors @RfsUeUi@ES?` Y` pharmacopée européenne (Ph. Eur.) ou américaine (USP) 8? 6F$YIi`xF`??T0h?GqdV?bb?= ou (7)). En cas d'exigences de précision très élevées et pour des utilisations très critiques, un test peut être effectué en plusieurs points. En raison du comportement de linéarité stable et compte tenu des aspects économiques, 9(?7ey??2'h?5`?s?4??I?#%X?d?6? poids de référence connu avec précision dans une faible &iF?02`'9x'?S4?Y'Y?&e?? TP)??&U9/ poids et, par exemple, deux tares, il est possible de tester la précision à trois points de l'étendue de charge. Pour plus d'informations, consultez également la section suivante sur les différentes possibilités de test, en particulier le point sur les tests de justesse. Utilisation de poids de test Que puis-je vérifier moi-même en tant qu'utilisateur et )t'r?115w?F7C3Q?(h?q?)`rA@c@p?62u?bBq?6 Un prestataire externe n'est pas nécessaire pour chaque test de balance. En général, l'état réel de chaque équipement doit être déterminé à intervalles réguliers via un étalonnage par des prestataires de services spécialisés et, dans le meilleur des cas, accrédités. La maintenance @p?&a?D7$)g"G!?SwXFRxS9sXVc nécessaire. Les intervalles de ces interventions externes ainsi que les avantages des organismes de service X?F?@6SQY'c( #a"?$H30 y?e? En plus des interventions réalisées par des prestataires indépendants, en tant qu'utilisateur, il est important de tester régulièrement la fonctionnalité de chaque équipement de test, c'est-à-dire de chaque balance. Il faut donc mettre sur pied une routine et documenter les tests intermédiaires. La fréquence et l'étendue de ces tests intermédiaires doivent être cohérentes avec l'utilisation !w?7ey??2'h?5e 1Ch?C`x  y4???P risques pour chaque dispositif séparément. Que dois-je garder à l'esprit concernant les balances utilisées dans des environnements réglementés par la loi/ 1C?5BAUX5`1?W@p?rA@c0X?R En plus des tests adaptés à l'utilisation et définis par l'utilisateur de l'équipement de test, il se peut que des spécifications externes nécessitent d'autres tests. De nombreuses balances sont soumises à des vérifications requises par la loi, réalisées par des personnes habilitées à des intervalles définis réglementairement, indépendamment de vos propres spécifications de vérification même si celles-ci sont plus fréquentes et utilisent des tolérances plus faibles. Pour ces balances, les scellements ne peuvent être rompus par l'utilisateur pour, par exemple, effectuer un ajustage. Dans la plupart des cas, les autres réglementations et spécifications de test sont semblables. Cependant, si certains tests peuvent être effectués par l'utilisateur, une vérification obligatoire peut généralement être considérée comme réussie si des tolérances distinctes et plus strictes sont utilisées. 6 De manière générale, les dispositions externes (légales/ réglementaires) doivent être respectées et des modifica- tions des tests intermédiaires internes peuvent en résulter. ?``0???u?BdV s0 YCa@p?3'?G7C3Q@p?U9?/ de tests intermédiaires et explique quand les utiliser. 1) Le type de test intermédiaire le plus simple consiste I25?majustage interne des balances. Presque toutes les balances de laboratoire modernes sont équipées d'un poids d'ajustage interne. Ce poids se trouve à l'intérieur 8'W?Th?W ?7@G#d1p!??0?b 1R?04 pendant le processus de production et a été enregistrée dans le logiciel de la balance. Ce poids est pesé avec le système de pesée par déclenchement soit manuel soit automatique des dispositifs d'ajustage interne (appelés BG 4xqVRI?6!F?"?6?H#%??(a être ajustée, c'est à dire ajustée à la valeur attendue. Ce type d'ajustage interne peut s'effectuer très facilement et rapidement, ne nécessite aucun matériel de test supplémentaire et garantit une bonne compensation des influences changeantes exercées sur la balance. Dans tous les cas, il doit être effectué régulièrement par l'utilisateur, BG"?'?Sx@?p"VSh 4Ea?A5IVp environnementales. 2) Un autre type de test intermédiaire consiste à tester Agf?qprécision de l'affichage, c'est-à-dire de vérifier si le l'équipement affiche correctement la masse de la substance pesée. Pour ce type de test, un poids de référence dont la masse est précisément connue est &ghwBgC"F0?(0c#7??W?h9%?@p?7?E?17$ Si possible, effectuez un ajustage interne de la balance puis, !T?S@?bS@!?0hs!?EU%PPXh '8gfA60?Dc9X%F?y7?tw bouton de tare). Placez ensuite le poids de test (un poids avec une masse connue, également appelé poids de référence) sur la balance et notez la valeur affichée. Comparez-la à la valeur de poids attendue du poids de test. Si la différence entre la valeur affichée et la valeur de poids se situe dans la plage de tolérance (déterminée par l'utilisateur), le test est considéré comme réussi et la balance peut continuer à être utilisée. Selon la criticité de l'utilisation de la balance, ce type de test peut être effectué en un point de l'étendue de pesée avec un poids de référence, ou en plusieurs points de l'étendue de pesée (c'est-à-dire avec différents poids de référence ou un poids de référence et plusieurs tares). En règle générale, même dans les applications jugées très critiques, trois points de test suffisent généralement grâce à la bonne linéarité des balances modernes. Plusieurs éléments doivent être pris en compte pour prendre cette décision. Bien entendu, la validité des tests de précision augmente lorsque les balances sont testées %087I1??2B1P?0 X?f?FH1I8@ plusieurs poids de référence très précis (ou au moins des poids de tare). L'étendue de mesure pour une pesée critique doit être considérée en conséquence. De manière générale, de nombreuses erreurs possibles peuvent être considérées comme proportionnelles à la charge et, en tant que telles, sont plus facilement détectées à des charges plus élevées. Au su de ces informations, ces considérations sont mises en pratique dans diverses situations. 'Q ?"T?c?Bb4?YGu% P SA$@1?Y?D3?F` des résultats de pesée, l'utilisateur peut également tester Agf?qrépétabilité du dispositif. Lors d'un test de répétabilité, un même poids de référence est placé sur la balance de manière répétée, et dans la mesure du possible, de la même manière. Entre chaque charge, la balance doit être mise à zéro ou vous devez attendre que l'affichage revienne à zéro. Dans des conditions environnementales optimales, un dispositif fonctionnant correctement affichera presque la même valeur à chaque mesure. Si la valeur affichée varie, il s'agit soit d'un signe de conditions ambiantes défavorables, soit d'un dysfonctionnement, qui ne peut alors être résolu que par une réparation. La fluctuation est caractérisée généralement par l'écart-type des valeurs affichées. Il n'est pas nécessaire de connaître la valeur réelle du poids de référence pour ce test complémentaire, car ce ne sont que les différences entre les différentes pesées qui sont observées. Cependant, afin de comparer les tests de répétabilité, il est important que le même poids soit toujours utilisé et que le nombre de répétitions reste le même. Pour une évaluation statistiquement significative, ?W&395#!?SwX????@7?h9? 0yE84?0RY? ?CAX?R6Qg dépasser la tolérance spécifiée. p?5?`px?Q&"p?8?`B?0@t? t3?Q Il n'y a pas qu'un seul intervalle de test qui convient pour toutes les situations. La fréquence est déterminée par l'utilisation et les différentes exigences. Le livre blanc Bg?F@p?'081?wx'?uT?(? ?x
??h9%?@p?@t? t d'importants éléments dont il faut tenir compte ainsi ve6E2H?0?5?R- Les différents types de tests intermédiaires décrits dans 7?(p?$&902?Dg@p? ??d86SU@p?5?w9Qvqa répétabilité) sont cependant utilisés différemment, !t?CR?Ar@v?F$&908?#Y 3vid 1) L'ajustage interne devrait être le type de test intermédiaire le plus fréquemment utilisé. 2) Le test de la précision devrait avoir lieu en cas de 8i?@p?'08(?xgit ?EB%% A? "x%t
Y(fqcGPrA@cB ?0%?&?)bDA??1i??s@t? t 4xX?A?&54"usPHsP 7 &???59(f"A????T0h?GqdV?@t? t )ud?'?Sx4?##'X8??4i!`q?)`'08% A? régulièrement les balances si de petites quantités doivent &4??982FxAW9?X?)bDA??!s?&1R?0Q %`??8s?WPaExP7Atst conditions environnementales ou de doutes concernant la fonctionnalité des balances. ?YVhW0%A??3?
qsT?Gd0eUi@E?#i%ws@p?G7?C?@4vx? 4(uE' 3#?@9B??t3?R En quoi consiste un contrôle réalisé 4?8@p?r?cp Voici quelques exemples du type de poids à utiliser en fonction des exigences d'analyse. !'3"R??gYbalances de précision pour échantillonnage peu fréquent d'un processus critique, vérifiées. gP?5R9Y&Q?u??f4Gv?##!rA@c&e48?$ETW??Q? " ?II`'?0D  d03FU`??Q? ??x1P'?0Db $1a)G1%??)4?? - )f?G86SU@p?(s?#%8?7?s?r(P82wiP utilisation peu fréquente) - 1T?P%3??7xB?i&5@G??uT? 6(%RX0 A wC5p??5)?Ea%5?b?Q?`7SE1?q30c??u test par rapport à cette tolérance avec le plus de certitude 3W@f!v!4)Ef?R?S. "$#Q@?#h9B??r?wBgCa(p?p%?a?P fdc)@?Le certificat d'étalonnage du poids de test exemple indique une valeur conventionnelle 300?&q?)1
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?)q@Ad?a? ?C2?0B"?Q wvT?@p?'08i?w? 9iE`'@t? t poids de test sur la balance, l'utilisateur s'attendrait donc ?#??p0?Q8?9?6?W6p$?X(i@t? t 5b6@)`YX?8AQ?AB?s5 7??&?? TPS. @p??uT?0)?3%5"#?tHc?$!6 considéré comme conforme si les valeurs affichées sont !t?C()&?P?H13?#?Vq?9?c(= - 1T?P0%?&?)bDA??52g2?H?x3T?c??P résultats de la pesée. Il est possible d'utiliser un poids p8P??`1??2B1IE#7?E?Sw?$p% A? %`??5`1?W@p?rA@c2r7"#I7b?@5?D?U@ supérieurs afin d'assurer une stabilité suffisante de la valeur de poids (inconnue). !'3"R"5balances d'analyse pour peser une substance moins critique plusieurs fois par jour. gP?8A%EBwP?q?VAy?cd?0B8?"v ??w?H?X7q?Ab1V?"S#?H13?7
x - )f?G86SU@p?rs@@???A - 1T?P%3??7xB?i&5@G??uT? 6(1!?95 bQE??9
9)?E)y&?'X8??s?w5 6DIX ?C?UU@7ey??2cH3FY2 6e26??h9%?@p??TSP@?#h9???0c??³ 1S?4D26@?gV`(p 3R7Q8?56@"w@b ?uT?6HhbA??T3% A? les tests conformément à la valeur convention nelle de poids établie sur le certificat d'étalonnage. - 1T?P0%?&?)bDA???I
$F`44v. #w?IA?a"$??9x'?S4?YA?TV !'3"R@P?$Microbalances pour analyse quotidienne 8q?`((!)?`Sb07C3Q@p?4?x$X f@p?)Iu(&R? gP?@???q?V?xYv47G(? dv? 3???s97?p $?72`VE - )f?G86SU@p?(s?#%8?7?s?r1D?R - 1T?P%3??7xB?i@?P"SYXS?uT?@t? t DE?B&'Rr?9
9)?E0g&HR 6?B??h9%?@p??TSP@?#h9Y?3? i#(. ?C?UU@7ey??2cHBAA ?'X8??1R?04 &!gcr0dD8cV39?? GV4?Yu?3yHd?s?Chv0% A? lequel la valeur conventionnelle de poids est déterminée rA@c$8??&W?B`v?qVyeyB??ev w?6Xtp'?Sx?dIQ?8w?S?Wa? fois extrêmement important de ne pas vérifier par rapport b?B??F
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)c&0 7?!riAd?a? ?C2?0yBU`@p?'08cp?d? 84R?t&q08u@Tv9iE`'p91? test sur la balance, l'utilisateur s'attendrait donc à voir $%!u?6?Hu8v?&c$?X(i4?v écarts dans les conditions de référence. ?? TP7q00??uT? #q?8(ua
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W83?9W62G?U (67?Q&????!qAt? 7 Cr9iE`'()&?P?H13????7Uuu@ ??rxE?&PQ?4#p?iA?769?5&5q?T extrêmement important d'effectuer un ajustage interne avant le test et que le poids de test se soit suffisamment adapté à l'environnement. - 1T?P0%?&?)bDA??t? 6$hGB
7% A? l'échantillon minimum au moyen de l'écart type de la mesure répétitive. 8 Bibliographie 1. Conseils pour la manipulation, la conservation et le $'F#9W%v('wg?7?4? Xx?twUg?@??0q???14DX"@Y?Yg )uw96r?m1c??B6r?me??p 2. Sartorius white paper Testing intervals and tolerances (how are testing intervals and tolerances defined %h)87? ?g? 9&Cea% A? ILAC P10 07/2020 Politique sur la traçabilité des résultats de mesure 6?4% A? % A? 'DQF@7X?46 )s?°% A? ASTM E617 Standard Specification for Laboratory ??'TI B!b#?%`??3Y?r9RHu?!PgA 6. Livre blanc Sartorius Scales in a pharmaceutically !t?C7ey???H13?q6? 3"TwU996?C?U)?qI9w??? 1&G?H026b?)QF%? y pharmacopée européenne), 2021 (à venir). 7. Livre blanc Sartorius Lowest sample weight according @p?"wi?GCy?2!yQ?UU@"Q0g??@67' . minimale de l'échantillon pour obtenir des résultats u#G? 8dq?u% A? Livre blanc Sartorius Calibration certificates from accredited providers (what advantage does our accreditation offer the user), 2021. Recommandation de Sartorius - Effectuez un ajustage interne de vos balances aussi souvent que possible, en particulier avant des pesées critiques. - Définissez des intervalles et des tolérances individuellement pour chaque balance, ainsi que pour les tests intermédiaires internes et les contrôles réalisés par des prestataires de services spécialisés. - Considérez toujours la plausibilité des résultats de pesée et vérifiez la balance en cas de doute. - Choisissez la valeur nominale et la classe de votre poids de test en fonction des spécifications de tolérance des balances. - Manipulez l'équipement de test avec soin et faites-le réétalonner à intervalles réguliers par des prestataires ??wv?cR8? r - Des vérifications intermédiaires régulières de vos poids ?eS (UY G?6H$T98AQ?AB?s5VWr?p2&3? (6Vh3" Ce livre blanc fait partie de la série de livres blancs ??DdWbP@p?G7$3V& 32 4v'082I?xp?Y?A??4`h?" manière dynamique tout en offrant aux utilisateurs le référencement le plus clair, par exemple dans leur documentation de gestion de la qualité, les livres blancs disposent d'un numéro de version. Historique des versions Version DateModifications ?11 6Ff??
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Ultrapure Water for HPLC Analysis The Role of Ultrapure Water Ms. Katrin Töppner017%, Dr. Dirk Hansen2??5, Dr. Elmar Herbig?w? 1. Sartorius Stedim Biotech GmbH, Goettingen, Germany 2. Phenomenex, Aschaffenburg, Germany 3. Sartorius Lab Instruments GmbH & Co. KG, Goettingen, Germany Introduction HPLC is an analytical procedure for separation, identification and quantification of substances using liquid chromatography. The beginnings of HPLC – High Pressure Liquid Chromatography – go back to the 60’s. Thanks to improved column materials and equipment, it has come to be known as High Performance Liquid Chromatography since the end of the 70’s.017% In HPLC, the mixture to be separated is transferred to a column with a solvent (eluting agent) or with a solvent mixture (eluant | mobile phase), by an injector and a pump. The column is a tube, in most cases of stainless steel, filled with the so-called stationary phase (see also Fig. 1). The stationary phase usually consists of porous silica gel or polymer particles with chemical ligands bound on their surface. These ligands are responsible for the selective interactions between the analytes and the stationary phase, which are necessary for effective chromatographic separation. Depending on the sample and stationary phase, the separation mechanisms involved are, for example, adsorption by Van der Waals forces, ion exchange, ion exclusion, etc. The substances of a sample are retained on the column packing material for different lengths of time and therefore exit the column after different retention times. The individual components of the sample are then registered by a detector and evaluated by a computer. The result is a chromatogram (?`#BFig. 1, 5, 6?pR?@. The number of peaks corresponds to the number of separated components in the sample, and the area is proportional to the concentration of these separated components (according to Kromidas 2000017%?pR?@. April, 2014 Keywords or phrases: Ultrapure Water for HPLC Analysis No ghost peaks – for optimal results Find out more: www.sartorius.com Application Note 2 Among the typical applications for HPLC is sugar analysis. This was performed within the scope of various tests con- ducted in order to characterize the quality of membranes. On the one hand, membranes were tested for their ability to remove sugar molecules and, on the other hand, the activity of enzyme-immobilized membranes was deter- mined. For this purpose, sugars, such as raffinose, glucose and fructose, were assayed. These types of sugar can be specifically detected by using enzymatic methods like the GOD | POD assay for glucose2??5 or spectroscopic methods, such as determination of fructose according to Dische & Borenfreund.?w? In advanced analysis, sugar is now frequently assayed by thin-layer chromatography (?`#BTLC ?pR?@, gas chromatography (?`#BGC?pR?@ and high-performance liquid chromatography (?`#BHPLC?pR?@. These methods are used especially when mixtures containing several types of sugar must be separated. ` @? In HPLC as described here, the eluant must have especially high physical and chemical purity, and may not contain sus- pended mechanical particles or any dissolved substances that can be released by the column at a delayed time and thus generate a signal. The quality of a solvent is often decisive for the reliability of an HPLC analytical run. The presence of trace contaminants during gradient elution can result in “ghost or phantom peaks”. Such trace substances accumulate in the column during an analytical run and are increasingly released when the eluting agent is subse- quently changed. Water used as an eluant must be free of microorganisms. For this purpose, substances that prevent the growth of microbes and algae in the solvent mixture, such as copper salts or sodium azide, can be added. ` @? In doing so, the column manufacturer’s recommendations need to be followed as the use of incorrect additives can result in irreversible damage to the column. Deionized or distilled water still contains considerable quantities of organic substances, which can cause ghost peaks. ` @? Contaminated solvents can lead to the buildup of deposits on the stationary phase and thus result in blockage of the column, which would be manifested by an increase in pressure and a shift in the running time for the samples. Employing Arium ® Pro VF to Purify Water for Use as an Eluant Water of the special quality required for HPLC can be purchased from various manufacturers or be produced directly on site for use on demand by employing a water purification system, such as the Arium ® Pro VF system. The following describes the tests performed for separation of sugar mixtures in which ultrapure water produced by Arium ® Pro VF was used as the mobile phase (eluant). Description of the Arium ® Pro VF Ultrapure Water System The Arium ® Pro VF system (?`#BFig. 2?pR?@ has been designed to produce ultrapure water from pretreated drinking water by removing contaminants that are still present in this potable water feed. Production of ultrapure water requires contin- uous recirculation and a constant water flow rate, which is achieved using a built-in pump system with controlled pressure. The conductivity of the water is measured at the feed water inlet and directly at the downstream port (product water outlet). The Arium ® Pro VF system used in the studies described in this paper (a predecessor model with the same technical specifications as the currently redesigned system shown next page) works with two different cartridges. These are filled with a special active carbon adsorber and mixed-bed ion exchange resins in order to deliver ultrapure water with a low TOC content. In addition, the system has an integrated UV lamp that has an oxidizing effect at wavelengths of 185 | 254 nm. Moreover, the Arium ® Pro VF ultrapure water system has a built-in ultrafilter module used as a crossflow filter. The ul- trafilter membrane incorporated in this filter retains colloids, microorganisms, endotoxins, RNA and DNA. A 0.2 µm final filter installed at the water outlet serves to remove particu- lates and bacteria during dispensing of the ultrapure water produced. The process that the unit employs to purify water is depicted in Figure 3 (?`#Bflow diagram of Arium ® Pro VF?pR?@. 3 Materials and Method The samples were analyzed using an HPLC Agilent 1200 Series system (?`#BFig. 4 and Table 1?pR?@ with a Rezex RNM Carbohydrate Na + 8 % HPLC column supplied by Phenomenex.8!&6r This column is filled with a cross-linked polystyrene- divinylbenzene-copolymer modified by sodium sulfonate groups and uses an ion exclusion mechanism. This means that analytes are separated based on different ionic inter- actions. Because of the sulfonate groups on the surface of this column packing material, the pores have a negative charge. As a result, negatively charged molecules cannot penetrate into the pores of the material, which causes them to elute earlier. This ion exclusion mechanism is based on Gibbs-Donnan equilibrium that governs the behavior of ions near a membrane. Analytes that are able to penetrate into the membrane’s pores are subsequently separated based on steric differences as well as on hydrophobic and polar interactions with the functional groups on the surface of the stationary phase. For more details on this separation mechanism, please refer to $??3X. Figure 1: Typical Setup of an HPLC System The retention times for various types of sugar are deter- mined by the absorbance of the refractive index (?`#BRI?pR?@ signal. This RI signal is expressed as a dimensionless number in nano Refractive Index Units (?`#BnRIU?pR?@ and indicates the difference between the refractive index of the sample in the sample cell and the mobile phase in the reference cell. Ultrapure water produced by the Arium ® Pro VF system was used as the mobile phase. For degassing the eluant in the HPLC system, this ultrapure water was filtered by vacuum through a Sartolab BT 500 Bottle Top disposable unit equipped with a 0.2 µm membrane (?`#BSartorius Sartolab BT 180C5?pR?@. Figure 2: The Arium ® Pro VF ultrapure water system (photo courtesy of Sartorius) Table 1: Equipment and MaterialsPC for Data Acquisition Waste Solvent Injector HPLC Column Detector Pump Equipment CompanyArticle No. Binary pump AgilentG1312A Degasser AgilentG1379B ALS autosampler AgilentG1329A Thermostatted Column Compartment (TCC) Agilent G1316A Refractive Index Detector, RID Agilent G1362A Column Phenomenex00H-0136-KO Rezex RNM Carbohydrate Na+ 8 % 4 Procedure for HPLC Analysis To prepare for the analytical runs, the Rezex column was heated to 75 °C in the column compartment (heater) and flushed overnight with Arium ® Pro VF ultrapure water at 0.6 mL/min. The optical unit of the RI detector was heated to 35 °C. Samples to be analyzed were prepared using Arium ® Pro VF ultrapure water and prefiltered through a 0.2 µm syringe filter unit (?`#BSartorius Minisart ® RC4, no. 17822?pR?@. The samples were analyzed using HPLC according to the parameters defined by an HPLC method8!&6r (?`#BTable 2?pR?@. Figure 3: Schematic flow diagram of the Arium ® Pro VF ultrapure water system (the valves and their controllers are omitted for better clarity). Flow rate [mL/min]0.6 Time [min]25 Maximum pressure [bar]70 Temperature of the Column Compartment [°C]75 Temperature of the RI detector [°C]35 Injection volume [µL]2 Sugar Retention Time [min] Raffinose Fluka 834008.96 Maltose SIGMA M588510.30 Glucose ROTH 6887.012.53 Fructose SIGMA F012713.62 Concentration [mg/mL]Retention Time [min]Peak Area [nRIU*s] 0 -- 0.015 8.96603 0.03 8.961,088 0.06 8.962.327 0.125 8.964,178 0.25 8.967,607 0.5 8.9615,097 1 8.9630,495 Table 2: HPLC method Table 3: Retention Times for Sugar Samples Passed through a Rezex RNM Carbohydrate Na + 8 % Column Table 3: Retention Times for Sugar Samples Passed through a Rezex RNM Carbohydrate Na + 8 % ColumnProduct Water UV Lamp (?`#B185 | 254 nm?pR?@ Pump Cartridge 1 Cartridge 2 Final Filter 0.2 µm Conductivity Measurement (Product Water) Reject Water Outlet Ultrafilter Inlet Water Input Conductivity Measurement (Inlet Water) Sanitization Port 5 Results To determine the retention times of the individual types of sugar (?`#BTable 3?pR?@, these were prepared and injected individually (?`#BFig. 5?pR?@. As different sugars interact with the stationary phase to a varying degree, specific retention times are recorded by the RI detector once each sugar has moved through the column. After the individual types of sugar had been determined, a sugar mixture was prepared and separated (?`#BFig. 5?pR?@. The individual sugar components were separated from one another. The peaks for the dif- ferent retention times could be allocated to the individual sugar samples assayed. The effect of contaminants, or the influence of salts, was simulated by injecting potassium phosphate buffer and tap water (?`#BFig. 6?pR?@. Injection of tap water with a conductivity of 265 µS/cm and of potassium phosphate buffer with a conductivity of 1,700 µS/cm showed clear signals and can therefore be distinctly identified as contamination. Multiply-charged ions are especially prone to binding with sulfonate groups. This alters the dissociation equilibrium and can affect the retention time for a particular sugar. For this reason, the mobile phase must be free of salts and other contaminants in order to perform reliable HPLC analysis with stable retention times and to avoid ghost peaks. The Arium ® ultrapure water used in this analysis has a conductivity of 0.055 µS/cm and is largely free of interfering contaminants, which is expressed as a flat baseline without peaks (see green baseline in Fig. 6). The column pressure during the analytical runs consistently remained at 23 bar (~334 psi). This shows that no deposits had built up in the column. Blank runs at the beginning and the end did not show any change; i.e., there were no contaminants in the mobile phase. Standard series with different concentrations were analyzed to determine the reproducibility and detection limit. Raffinose is given as an example of these series per- formed. The retention times and peak areas were recorded and are listed in the Table 4. The consistent retention times repeatedly obtained show excellent reproducibility. The raffinose standard series shows a linear curve up to a concentration of 0.015 mg/mL (?`#BFig. 7?pR?@. By generating a standard strait line based on the peak areas a quantification of the sample, in this case raffinose is possible. Figure 5: Separation of individually injected sugar samples and of a sugar mixture using a Rezex RNM Carbohydrate Na + 8 % column with ultrapure water. Black curve: sugar mixture Figure 6: Chromatograms of 2 µL of 10 mM of postassium phosphate buffer, 2 µL of tap water and 2 µL of Arium ® ultrapure water Figure 4: HPLC Agilent 1200 Series system (photo courtesy of Sartorius) Potassium phosphate buffer Tap water Arium water 3500 3000 2500 2000 1500 1000 500 0 -500 0 510 1520 25 RI signal [nRIU] Retention Time [min] 2500 2000 1500 1000 500 0 -500 0 510 1520 25 RI signal [nRIU] Retention Time [min] 3F?@0q?7??S&9w??dQ Copyright Sartorius Lab Instruments GmbH & Co. KG Status: 09 | 2020 The studies performed and the excellent experience obtained in using Arium ® Pro VF ultrapure water as a mobile phase in HPLC are to be extended in the near future to other separation technologies, such as reversed phase chroma tography, size exclusion chromatography or ultrahigh- performance liquid chromatography. References 1. Kromidas, Stavros: HPLC für Neueinsteiger, from the Internet, © by Novia GmbH, (?`#B2000?pR?@. 2. Hans Ulrich Bergmeyer, Methoden der enzymatischen Analyse Band II, Verlag Chemie, page 1179, 1180 (?`#B1970 ?pR?@. 3. Dische, Z., and Borenfreund, E.: A New Spectrophotometric Method for the Detection of Keto Sugars and Trioses, J. Biol. Chem. 192, 583-587, (?`#B1951 ?pR?@. 4. Süsswaren, issue 10, page 7, LCI-Focus, (?`#B2006?pR?@. 5. Gottwald, W.: RP-HPLC für Anwender. Reihe: Die Praxis der instrumentellen Analytik, Editor, Gruber, U., und Klein, W., VCH Verlagsgesellschaft, Weinheim, pages 7-8 (?`#B1993?pR?@. 6. Chromatography Product Guide 12/13, Phenomenex, pages 232-233, (?`#B2012?pR?@. 7. Weiß, Joachim: Ionenchromatographie, Wiley-VCH Verlag, Weinheim, Chapter 5, pp. 349 ff. (?`#B2001?pR?@. Acknowledgements The authors would like to take this opportunity to thank Phenomenex based in Aschaffenburg, Germany, for providing the Rezex RNM Carbohydrate column for their use. First version in English published in G.I.T. Laboratory Journal Europe 3-4, Volume 17, April 2014 Germany Sartorius Lab Instruments GmbH & Co. KG Otto-Brenner-Strasse 20 37079 Goettingen Phone +49 551 308 0 USA Sartorius Corporation 565 Johnson Avenue Bohemia, NY 11716 Phone +1 631 254 4249 Toll-free +1 800 635 2906 For further contacts, visit www.sartorius.com Conclusion The results show that ultrapure water produced by Arium ® Pro VF can be readily used as the mobile phase for HPLC analysis of the water-soluble saccharides described in this paper. The interactions of the sample with the stationary phase are not affected by the mobile phase as the ultrapure water that is produced with a conductivity of 0.055 µS/cm can be considered virtually free of contaminants. As a result, there are no salts present that would otherwise cause ghost or phantom peaks. ` @? In addition, the results of the trials lead to the conclusion that no deposits occur on the stationary phase, which would otherwise be manifested by an increase in pressure and a shift in the running times of the samples. Therefore, Arium ® Pro VF ultrapure water, which can be pre- pared on demand at any time, offers an affordable alternative to commercially sold ultrapure water to prepare high- purity eluants for HPLC analysis, as used in food analysis, environmental analysis, as well as in medical, chemical and biochemical research and during in-process quality control testing in the pharmaceutical and biotech industries. 35000 30000 25000 20000 15000 10000 5000 0 0 0.2 0.4 0.6 0.8 1.01.2 Peak area [nRIU*s] Concentration [mg/mL] Figure 7: Standard series for raffinose (values from Table 4) passed through a Rezex RNM Carbohydrate Na + 8 % column with Arium ® ultrapure water

How to Set Up a Pipetting Quality Control Program for Your Lab Improve the Quality of Pipetting and Reliability of Results Abstract Calibration, maintenance, and regular control of tools are essential to ensure the highest quality standards of laboratory work. For pipettes, the best practice would be to do cali bration and maintenance according to the manufacturer’s recommendations at least annually or biannually, as well as implement a program for regular testing of pipette performance during use and between calibration intervals. This practical guide outlines the requirements for in-lab testing program, as well as for professional calibration and maintenance services. September 2018 Keywords or phrases: Pipette Calibration, Pipette Maintenance, Pipette Service, Pipette Control Find out more: www. sartorius.com Application Guide 2 Introduction Many quality systems and standards, such as Good Laboratory Practice (GLP), Good Manufacturing Practice (GMP), and the ISO 9000 series require that a regular, documented maintenance and calibration procedure must be in place for all instruments. Some labs, especially accredited laboratories, also require regular calibration of pipettes in ISO 17025 certified accredited calibration facility due to the security and traceability of results it brings. The good quality program of pipettes is a combination of regular day-to-day in-house checks and regular professional calibration and maintenance. Pipette Quality Control Program To meet the regulatory and quality system requirements, laboratories should have in place a documented program for pipette quality control during use. A suggested program based on best industry practices consists of the following elements: e DIn-lab testing routine, with pipette performance checked in-lab regularly, such as daily, weekly or monthly e DRegular calibration and maintenance of pipettes performed at an accredited service laboratory, annually, biannually or every 3 – 4 months. In-Lab Testing Routine In-lab testing routine includes a regular checking of all pipettes in the laboratory for their systematic and random error. 1. What Should Be Done? The pipettes are checked using a balance or a photometer and the systematic and random errors are calculated from the results, compared against acceptance limits, and recorded. This testing can be done by the actual users of the pipettes, but the results should be checked and documented by an independent party, such as quality management personnel. 2. How Often? The testing frequency is based on the risks associated with the use of the pipettes—the testing interval should be in ratio with the amount of work you can afford to lose if you find the pipettes are out of specifications. Practices used in various labs differ greatly, but a common testing routine is monthly or weekly, sometimes even daily. Pipettes should also be checked each time after autoclaving pipettes or pipette parts. Performance check is also needed if a pipette is dropped or if physical damage is suspected. 3. What is Needed? For In-lab testing, you will need the following items: e D4- or 5-decimal balance with pipette calibration setup such as evaporation trap, or a photometer system e DSoftware for calculating and recording results e DDisposable tips, the same type as used with the pipettes when in use e DDe-ionized water or dye solutions if photometric measurement is used e DThermometer and barometer e DStandard Operating Procedure document describing the in-lab testing routine and the procedure for dealing with pipettes that do not meet the acceptance criteria 4. What Acceptance Criteria Should Be Used? The pipettes should be checked at 1–2 volumes, with 4–10 measurements each. The systematic and random error should be compared against the limits defined either by pipette manufacturer or ISO 8655. 5. What are the Outcomes of the Testing? The in-house testing routine should provide the following deliverables: e DDocumented history of all the pipettes showing their testing interval, testing dates, and at minimum the result if they met the acceptance criteria or not e DThe pipettes not meeting acceptance criteria should be clearly marked and removed from use, and forwarded to maintenance and calibration to resolve the issue 3 Calibration and Maintenance Program Most laboratory quality systems require a regular calibration and maintenance program for pipettes. Today, laboratories commonly use an external service provider for this labor- intensive work that requires highly sophisticated quality systems. 1. What Should Be Done? The pipettes should be maintained according to the manufacturer’s instructions regularly. The maintenance consists of the cleaning and greasing of pipettes, as well as replacement of wearable parts. Alongside maintenance, the pipettes should have their performance verified by calibration—measurement of systematic and random error along with any necessary adjustments. 2. How Often? The testing frequency is based on the risks associated with the use of the pipettes. The maintenance interval is affected by such factors as pipetting frequency, liquids used, and the age and model of pipette. A minimum maintenance interval of one year is suggested, with calibration done annually or more often, such as every 3–6 months. If, for example, volatile liquids or solvents are used, maintenance should be done more often. 3. What is Needed? For a full maintenance and calibration of pipettes, the calibration laboratory used should have at minimum: e DFull ISO 8655 compliance, including controlled environment in terms of temperature, vibration, and humidity e DAccreditation according to ISO 17025 standard with traceability of measurements to international standards e DBalances with a minimum of 5- and 6-decimals along with evaporation traps or draft shields e DSoftware for recording results e DProfessionally trained technicians | engineers who understand pipette technology and good pipetting practices, as well as requirements set by regulatory and quality systems 4. What Acceptance Criteria Should Be Used? The pipettes should be measured at 2–3 volumes, with 4–10 measurements each, with systematic and random error calculated and compared against the acceptance limits. The limits defined in ISO 8655 or by the manufacturer of the pipettes are suggested. 5. What Are the Outcomes of the Calibration? The calibration and maintenance program should provide at minimum: e DDocumented records of all maintenance and repair activities done to the pipettes e D6 `(!?x705?ub?@??e@p?)%?`9?2P"q pipettes, such as serial numbers and time of calibration, tips used, measurement conditions, measurement equipment and personnel e DRandom error and systematic error should be calculated and documented, along with acceptance criteria such as pass | fail limits Specifications subject to change without notice. Copyright Sartorius Lab Instruments GmbH & Co. KG. All Rights Reserved. Printed in the EU or US on paper bleached without chlorine. Version 1 | 06 | 2021 Germany Sartorius Lab Instruments GmbH & Co. KG Otto-Brenner-Strasse 20 37079 Goettingen Phone +49 551 308 0 USA Sartorius Corporation 565 Johnson Avenue Bohemia, NY 11716 Phone +1 631 254 4249 Toll-free +1 800 635 2906 For further contacts, visit www.sartorius.com Best Practices for Setting up the Pipetting Quality Control Program To work according to Good Laboratory Practice, a Standard Operating Procedure (SOP) for Pipette Quality Control should be defined. Below are areas that should be described at minimum in the SOP to guide laboratory personnel through the process: 1. For in-lab testing routine, define: a. Testing frequency b. Testing equipment and environment c. Personnel qualifications to conduct testing d. Measured volumes and aliquot quantities e. Acceptance criteria f. How to record and store the results g. Actions of isolating and marking pipettes not meeting acceptance criteria h. Procedures for evaluating the effect of failure on the work performed with the pipette in question 2. For maintenance and calibration program, define: a. Requirements for a calibration laboratory, ISO 8655 and ISO 17205 at minimum i. Testing equipment, environment, and procedures ii. Qualifications for maintenance and calibration personnel b. Calibration and maintenance frequency c. Decontamination procedures for the pipettes before maintenance d. Volumes tested and number of measurements e. Acceptance criteria f. Recording and documentation systems g. Actions of isolating and marking pipettes not meeting acceptance criteria h. Procedures for evaluating the effect of failure on the work performed with the pipette in question 3. For continuous education of laboratory personnel, define: a. Training program for personnel on correct pipetting techniques and ergonomics b. Training on quality systems and standards related to pipettes and pipetting c. Documentation and qualification plans for personnel training Summary Pipettes are precision tools that have significant influence on results of scientific experiments. All laboratories working with pipettes should have in place a regular program for not only calibration and maintenance but also regular in-lab testing of pipettes, using qualified personnel and correct equipment for all work. To implement this quality program, the program should be documented and controlled with Standard Operating Procedures for laboratory personnel. The SOP should cover all aspects of the program, including the continuous training of personnel on pipettes and pipetting. Do you need support in pipette service and maintenance? Contact Sartorius for a Pipetting Academy training at www.sartorius.com/pipetting-academy

Pipette Calibration and Standards Emilia Varhimo, PhD* Sartorius Biohit Liquid Handling Oy * Correspondence E-Mail: emilia.varhimo@sartorius.com Abstract Pipetting results are critically depending on the maintenance and calibration of the pipette. The most import International Stardardization Organization (ISO) standards related to pipetting are ISO8655 and ISO17025 and these standards set the guidelines how and in which conditions calibration should be performed. Regular cleaning and maintenance according to guidelines also prolongs the lifetime of the pipette. August 01, 2018 Keywords or phrases: Pipetting, Calibration, ISO standard, Service, Maintenance Find out more: www.sartorius.com/en/products/pipetting-and-dispensing Application Note 2 Pipette calibration consists of: - Checking the accuracy and precision of the pipette using 4 – 10 measurements per volume at 1 – 4 different volumes (usually selected from minimum or 10%, 50%, and 100% of the nominal volume of the pipette) - Calculation of results and comparison against pass/fail limits - Issuing of a calibration certificate. For maintenance a maximum interval of one year is recom - mended, with calibration being performed a minimum of once per year, but ideally every 3 – 6 months. Accreditation and Quality Systems: Different quality systems and industry requirements pose different demands for the control of work quality. Most laboratory work is done under various standards such as ISO 9000-series, ISO 17025 accreditation and Good Laboratory Practice (GLP) guidelines. All have a central theme of controlling the performance of instruments in use with a regular and documented program. A reference often used in the laboratory work is GLP guidelines which dictate that precision tools like pipettes must be maintained and calibrated at regular intervals by a competent body: “Apparatus used in a study should be periodically inspected, cleaned, maintained, and calibrated according to Standard Operating Procedures. Records of these activities should be maintained. Calibration should, where appropriate, be traceable to national or international standards of measurement.” Good Laboratory Practice (OECD 2005) What is ISO 8655? The International Standard ISO 8655 specifies the require- ments for pipettes and pipette calibration laboratories, pro- viding detailed guidance for the respective environmental conditions, procedures, and equipment. For example pipette calibration in accordance with ISO 8655 is performed using a reliable measurement equipment, such as a high-quality balance, in a carefully controlled environment without any drafts or vibrations. ISO 8655 sets guidelines for: - Characteristics, features, and marking of pipettes - Responsibilities of pipette users and manufacturers - Pipette testing equipment, conditions, and procedures Introduction Taking proper care of your pipettes is one of the most critical factors affecting the quality of your work. Pipette performance can deteriorate over time due to drift of calibration, leakage, part wear or contamination. Although cleaning and maintenance help to eliminate these sources of incorrect dispensing, the accuracy and precision of pipettes must be checked at regular intervals. This application note outlines what is involved in calibration and maintenance and the various standards and concepts associated with these procedures. What is Calibration and Preventive Maintenance? All pipette manufacturers recommend preventive mainte- nance and calibration programs to maintain reliable pipetting results and to maximize the lifetime of the pipette. Pipette calibration is a fundamental part of Good Laboratory Practice (GLP) and quality systems, and must be considered as a vital part of any laboratory workflows where precise volumes of fluids need to be transferred. Pipette performance is measured as accuracy and precision, meaning how close the dispensed volumes are to the target and how close the results are to each other. Calibration is predominantly undertaken by gravimetric analysis of the dispensed volumes and the results are compared against specifications provided by manufacturer or defined by ISO 8655 standard. Calibration should always be done for the pipette-tip combination used in the actual lab work and it is important to keep in mind that pipette manufacturer’s specifications are valid only in combination with the manufacturer’s tips. Preventive maintenance consists of cleaning and greasing the piston and tip cone of the pipette and replacement of worn parts to guarantee long lifetime and accurate and precise results. Just like any other devices, pipettes may need repairing from time to time. It is usually worth investing in repairs rather than simply disposing of pipettes. Professional service teams can supply spare parts and repair services for any make and model, or an offer for replacements if repairing the pipettes is deemed uneconomical. Pipette maintenance consists of: - Cleaning and decontamination - Opening, cleaning and greasing pistons, tip cones and any associated seals - Checking the operation of the pipette for any jams, leakages or other faults 3 What is ISO 17025? The ISO 17025 standard specifies the general require- ments for the competence of calibration laboratories to carry out tests and calibrations. A pipette calibration laboratory with ISO 17025 accreditation provides the highest level of reliability and confidence in pipette calibration, as proven by the uncertainty of measure- ment provided for each calibration when required. Achieving and maintaining ISO 17025 accreditation requires extensive testing of personnel, procedures, and facilities, with the accreditation reviewed in an annual audit by the relevant body. Using an ISO17025 accredited calibration laboratory is essential for all laboratories where quality and reliability of results are important as it guarantees the following: - All measurements are traceable to national and inter- national methods and standards - The uncertainty of both the pipette and the measuring process are taken into account - You can be sure exactly which part of the uncertainty is due to pipette performance and which is due to the uncertainty of measuring process, for example the balance used - The laboratory issuing the certificate has been approved by independent experts and authorities (e.g. DaKKs, UKAS, A-Class, COFRAC, UKAS, JCSS, FINAS, or Rosstandart). All European accreditation bodies are members of the European Cooperation for Accreditation (EA) and signa- tories to the Multilateral Recognition Agreements (MRA). European Cooperation for Accreditation (EA) is recognized body of International Laboratory Accreditation Coopera- tion (ILAC), linking the European accreditation bodies to Inter American Accreditation Cooperation (IAAC), Asia Pacific Laboratory Accreditation Coopertion Inc (APLAC), Arab Accreditation Cooperation (ARAC), and African Accreditation Cooperation (AFRAC). This means that accredited pipette calibration certificate from one of the calibration laboratory part of the Multilateral Recog- nition Agreement (MRA) is widely accepted around the world. Conclusion Laboratories using pipettes should be familiar with the relevant standards as well as maintenance & calibration tasks associated with pipettes. Pipette calibration and maintenance should be performed regularly, at minimum annually or more often. The basic requirement for all laboratories to follow is the ISO 8655 standard, which outlines the calibration of pipettes and other piston- operated liquid handling instruments. For accredited laboratories and laboratories requiring traceability of measurement, the golden standard is ISO 17025, which provides the best possible confidence in results and quality of work. Do you need support in pipette service and maintenance? Contact Sartorius for a Pipetting Academy training, go to www.sartorius.com/pipetting-academy References 1. Good Laboratory Practice. OECD Principles and Guidance for Compliance Monitoring, 2005 2. ISO 8655:2002 Piston-operated volumetric apparatus Part 6: Gravimetric methods for the determination of measurement error, International Organization for Standardization, Geneva, Switzerland 3. ISO 17025:2005 General requirements for the competence of testing and calibration laboratories, International Organization for Standardization, Geneva, Switzerland Specifications subject to change without notice. Copyright Sartorius Lab Instruments GmbH & Co. KG. Status: 09 | 2020 Germany Sartorius Lab Instruments GmbH & Co. KG Otto-Brenner-Strasse 20 37079 Goettingen Phone +49 551 308 0 USA Sartorius Corporation 565 Johnson Avenue Bohemia, NY 11716 Phone +1 631 254 4249 Toll-free +1 800 635 2906 For further contacts, visit www.sartorius.com Finland & Baltics Sartorius Biohit Liquid Handling Oy Laippatie 1 00880 Helsinki Phone +358.9.755.951

The Importance of Accurately Measuring the Moisture Content of Plastic Resin in the Molding Process of Medical Devices King Snyder017%, Dennis Acord017%, Evelyn Marschall2??5 1. Sales Specialist, Moisture Products, Sartorius USA, 2. Product Manager, Moisture Analysis, Sartorius Lab Instruments, Germany Abstract Moisture content is an important variable that must be monitored for and controlled during the production of plastic medical device parts. ASTM standard D6869 is the benchmark for measuring the moisture content of plastic resin, and stipulates the use of Karl Fischer (KF) titration as the applicable standard method. However, a KF titrator is expensive, and testing for moisture requires the use of toxic chemicals so that it can only be used by a trained chemist. A loss-on-drying (LOD) moisture analyzer can be an alternate method for testing moisture in plastic resin, but must be correlated to the KF titration as the measurement principles of both differ. Herein, we show that the Sartorius Mark 3 High Performance Moisture Analyzer cor- relates well with KF titration standards for a number of plastic resins commonly used in medical device manufacture. The Mark 3 is a recognized ASTM 6980 standard method for testing the moisture content of plastic resin that is a good return on investment for medical device manufacturers because it is easy to use, has low maintenance costs, reduces the risk of rejected parts and customer dissatisfaction, and reduces energy consumption. October, 2019 Keywords: Omnimark, Mark 3, Moisture analyzer for medical devices, plastic moisture analysis, ASTM Moisture Plastic resins standard, Moisture testing plastic resin Find out more: www.sartorius.com Application Note 2 Introduction One important variable to monitor and control for during the production of plastic medical device parts is moisture content. Resin manufacturers provide material specification sheets detailing the maximum moisture specification, or the maximum allowable ratio of water in the resin before molding or extrusion. Depending on the resin, maximum moisture specification can vary from 0.20 % to as low as 0.005 % moisture. The manufacturer’s data sheet also provides general guidelines on drying temperature and time for the resin before molding. For instance, a typical drying specification is drying the resin at 180 °F for 4 hours before molding. However, these general recommendations do not take into consideration the environment where the resin is stored, or the efficiency of the drying system being used. When following the recommendations for drying temperature and time, the result is likely to be satisfactory – if the resin is within anticipated moisture levels before loading into the dryer. If the resin is wetter than anticipated, however, the recom- mended drying time may not be enough to drive off the moisture required to meet the maximum moisture speci- fication. Molding wet resin can result in splay marks, streak- ing, fogging, burrs, and poor mechanical properties. Many medical device parts, such as syringes, medical tubing, and even eyeglass lenses, must be totally transparent and without visual defects. Other medical parts are molded to very precise specifications, and excess moisture can affect the flow properties of the resin, causing imperfections that make the final part useless for its intended purpose. Over-drying a resin, on the other hand, can actually be more problematic than under-drying. An over-dried part may look perfect, yet, over-drying may burn off technically important plasticizers and additives that are critical for the durability, elasticity, and corrosion resistance of the part. Accurate measurement of the moisture content in plastic resin ASTM standard D6869 is the benchmark for measuring the moisture content of plastic resin, and stipulates the use of Karl Fischer (KF) titration as the applicable standard method. However, a KF titrator is both expensive to purchase and to maintain. Also, testing moisture with a KF titrator requires the use of toxic chemicals, so the test can only be Generic Specific GradeKF TitrationMark 3 ResultsTest Times (min.)Std. Dev. Polypropylene RTP 199 X 991670.014 %0.01 %4.0 0.001 Polystyrene Styron 4780.021 %0.021 %5.0 0.001 Polycarbonate Lexan 5000.015 %0.016 %4.0 0.002 Peek Victrex 381G 0.015 %0.015 %4.3 0.002 ABS Lustran LK 2790.061 %0.060 %10 0.001 Polysulfone Udel P-17000.020 %0.019 %5.0 0.001 Polyethylene Borstar HE3490-LS0.017 %0.016 %5.0 0.001 Polyamide Durethan BG30X0.071 %0.072 %5.0 0.004 PET Rynite 5300.020 %0.019 %3.5 0.003 Polyvinyl Choride Apex 910-R40.033 %0.032 %5.0 0.002 TPC Hytrel 82380.040 %0.040 %6.3 0.001 PBT Valox 3250.010 %0.010 %4.0 0.001 Table 1: Correlation results between Karl Fischer coulometric titration and the Mark 3 moisture analyzer. 3 Conclusions Manufacturers of medical parts recognize the necessity of accurately monitoring the moisture content of their plastic resin throughout the manufacturing process. The high cost of resins used in making these parts, the stringent specifi- cation these parts must meet, and the potential liability should a part fail, all make the purchase of an LOD moisture analyzer a good investment. The Mark 3 High Performance Moisture Analyzer is a good choice for such manufacturers. The Mark 3 can be programmed with methods for all the resins manufacturers commonly process, and is recognized as an ASTM 6980 standard method for testing the moisture content of plastic resin. The Mark 3 is easy to use and has low maintenance costs. In addition, the cost savings associ- ated with reducing the risk of rejected parts and customer dissatisfaction as well as energy reductions by cutting dry- ing time makes the purchase of a Mark 3 High Performance Moisture Analyzer a good return on investment. For more information on the Mark 3, including a quote, please visit www.sartorius.com performed by a trained chemist, using appropriate safety precautions. Therefore, most manufacturers prefer to use alternative methods for moisture testing. Fortunately, ASTM 6980 states that a loss-on-drying (LOD) moisture analyzer can be an alternate method for testing moisture in plastic resin. LOD moisture analyzers measure weight loss to determine the moisture content of a sample. Because they cannot distinguish between weight loss from water and weight loss from other volatiles being driven off by heating the sample, ASTM 6980 requires that test meth- ods on an LOD analyzer are developed to correlate to the ASTM 6980 KF titration standard. One such LOD analyzer is the Sartorius Mark 3 High Perfor- mance Moisture Analyzer, which is recognized as an ASTM 6980 standard method for testing the moisture content of plastic resin. We undertook this study to demonstrate the calibration of the Mark 3 to the KF titration standard for a number of different resins. Methods & Results Our Sartorius Moisture Application labs, based in the US (Bohemia, New York) and Göttingen (Germany) offer pro- gram development for all kinds of plastic resins, including correlation to the reference method (usually KF titration). To make sure that the final program provides traceable and reproducible results for samples of different moisture con- tent, dry and wet samples are used during program devel- opment to make sure the resulting program is sufficient in any case. Specific programs are developed for each resin to guarantee both a correlation between KF titration and the Mark 3 and to ensure ASTM 6980 requirements of are met. To date, Sartorius has developed programs for over 7,000 resins. The table below lists some commonly used plastic resins in the molding and extruding of medical parts, along with data showing the correlation between the Mark 3 and KF titration standard. Of particular note, the standard deviation between the moisture content as determined by the KF titration standard and the Mark 3 never reaches statistical significance, indicating that the Mark 3 gives comparable results to the KF titration standard. For further contacts, visit www.sartorius.com Specifications subject to change without notice. Copyright Sartorius Lab Instruments GmbH & Co. KG. Status: 09 | 2020 Germany Sartorius Lab Instruments GmbH & Co. KG Otto-Brenner-Strasse 20 37079 Goettingen Phone +49 551 308 0 USA Sartorius Corporation 565 Johnson Avenue Bohemia, NY 11716 Phone +1 631 254 4249 Toll-free +1 800 635 2906

2022 Guide to Medical Devices Quality Control and Testing Introduction To remain competitive in the medical device market, you need to be able to reduce costs while improving quality. q4??Icb0$pG1
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Are You Compliant When it Comes to Pipetting? Guidelines to Ensure Compliance with Good Laboratory and Manufacturing Practices Paulus Artimo 1*, Joni Åke 1, Emilia Varhimo 1 1. Sartorius Biohit Liquid Handling Oy, Laippate 1, 00880 Helsinki, Finland * Correspondence E-Mail: paulus.artimo@sartorius.com Introduction When developing or testing your medical device, there is always the question: are you following methods for current Good Lab- oratory Practice (cGLP) or current Good Manufacturing Practice (cGMP)? In this practical guide, we’ve compiled a list that you can follow to give you peace-of-mind on the topic of compliance. 03FU` Quality systems and standards regulating product development and manufacturing of pharmaceuticals, medical devices, and the way clinical studies are conducted, such as GLP, GMP and ISO 9000 series, require that appropriate and technically valid standard operating procedures (SOPs) are followed and a regular, documented maintenance and calibration process is in place for all instruments. In this guide, we’ll look into some tools and principles that can help with these demanding requirements, especially when it comes to your pipetting practices. March 11, 2020 Keywords or phrases: GMP, Good Manufacturing Practice, GLP, Good Laboratory Practice, Quality system, compliance, pipetting Application Note 23 Ensure That Standard Operating Procedures Are Followed Ensuring that appropriate and technically valid SOPs are followed is a core requirement for GLP and GMP compliance. In practice in the laboratory, this means repeating the set work instructions, without deviations. Many other processes at the workplace are already fully or semi-automated, and this kind of assistance is also available for laboratory work. Electronic pipettes, such as the Sartorius Picus® NxT, can be used to simplify and speed up workflows by allowing integration of SOPs to programmable pipetting protocols. Once activated, the program automatically adjusts the parameters after each completed step. This reduces the possibility of human error that is apparent when manually adjusting the pipette parameters. The programs can be password protected (Fig. 1) to add an extra layer of security to ensure proper protocol is followed. The use of electronic pipettes has ergonomic benefits, and also raises the pipetting performance and repeatability of dispensing of inexperienced and moderately experienced personnel to the level of experts (Fig. 2). User-dependent sources of pipetting errors can accumulate up to a 2% increase in the standard deviation, according to ISO8655. So, use of electronic pipettes eliminates these errors, because the electronic piston movement ensures consistency. Fig 2. The random error of dispensing 1000 µl, 500 µl and 100 µl using a 1000 µl m\?echanical or electronic pipette by inexperienced, moderately experienced, and expert users from testing conducted by Sartorius. The standard ISO 8655 recognizes the major error sources and sources of variation to be operator derived. Dispensing with mechanical pipettes is more likely to have operator derived variance compared to electronic pipettes, where the system operates the piston consistently. Uneven piston movement and rhythm when manually operating the piston of the mechanical pipette is known as the pipetting “handwriting”. Lab personnel may feel like an expert in pipetting, but when working according to GLP, an electronic pipette is the best tool to eliminate these differences between users. Fig 1. Picus® NxT password protection option on display How to Ensure That Instruments Are Calibrated? Has someone in your lab ever forgotten to calibrate their pipettes before the calibration due date set in your SOPs? Most laboratories use sticker labels on pipettes, but they are far inferior in helping you remember than the calendar notifications you use for your other important dates. Some electronic pipettes, such as Sartorius Picus® NxT, can be set to enforce proper calibration interval by using the calibration reminder option (Fig. 3). With the help of the reminder, you will be aware of pipettes in the lab with expired calibration, thus saving you from frustration you experience when your work must be delayed to find a calibrated pipette. The last calibration date can be set into the pipette software by trained service personnel and you can set a calibration interval, after which the pipette notifies you of an upcoming calibration. Forget about the sticker labels, as there is a more reliable way to make sure calibrations are performed on time What is the Correct Calibration and Maintenance Interval? This is one of the most frequently asked questions, but is not all there is to it. Laboratories need a documented pipette quality control program to meet regulatory and quality system requirements. The user is responsible for setting up the program, according to ISO 8655, a standard for piston-operated volumetric apparatuses.. The program should describe an in-lab cleaning and testing routine, the calibration and maintenance interval, and how to ensure continuous education of your lab personnel. Our suggestion for a two-tier program, that will ensure continuous monitoring of pipetting deviations, is created by adhering to the following guidelines: e D In-lab cleaning and testing routines, with pipette performance checked in-lab regularly, for instance, daily, weekly, or monthly e D Regular calibration and maintenance of pipettes performed at an accredited service laboratory, annually, biannually, or even every 3 – 4 months. Anyone who has set up a Quality Program knows that the first steps can be challenging, but to get you started, we have added guidance in the supplemental material. 500 µl 100 µl 1000 µl Random error % 3.5 3 2.5 2 1.5 1 0.5 0 Inexperienced Moderately experienced Experts 500 µl 100 µl 1000 µl Random error % 3.5 3 2.5 2 1.5 1 0.5 0 Inexperienced Moderately experienced Experts Mechanical Pipette Electronic Pipette ENV/MC/Chem(98)17 Section II Good Laboratory Practuice Principles 1. Test Facility Organisation and Personnel 1.1 Test Facility Management’s Responsibilities 1. At a minimum it should: (e) Ensure that appropriate and technically valid standard operating procedures are established and followed, - - Fig 3. Picus® NxT calibration reminder on display. ENV/MC/Chem(98)17 Section II Good Laboratory Practuice Principles 4. Apparatus, Material, and Reagents 2. Apparatus used in a study should be periodically inspected, cleaned, maintained, and calibrated according to Standard Operating Procedures. Records of these activities should be maintained. Calibration should, where appropriate, be traceable to national or international standards of measurement 45 Supplement 1 In-Lab Testing Routine An in-lab testing routine includes a regular check of all pipettes in the laboratory for systematic and random error.. 1. What Should Be Done? Pipettes are checked using a balance or a photometer, the systematic and random errors are calculated from the results, compared against acceptance limits, and recorded. This testing can be done by the actual users of the pipettes, but the results should be checked and documented by an independent party, such as quality management personnel. 2. How Often? The testing frequency is based on the risks associated with the use of the pipettes – the testing interval should be in proportion with the amount of work you can afford to lose if you find the pipettes are out of specifications. Practices used in various labs differ greatly, but a common testing routine is monthly or weekly, sometimes even daily. Pipettes should also be checked each time after autoclaving pipettes or pipette parts. A performance check is also needed if pipette is dropped or if physical damage is suspected. 3. What Is Needed? For In-lab testing you will need the following items: e D 4- or 5-decimal balance with pipette calibration setup, such as evaporation trap, or a photometer system e D Software for calculating and recording results e D Disposable tips, the same type as used with the pipettes when in use e D De-ionized water or dye solutions if photometric measurement is used e D Thermometer and barometer e D Standard Operating Procedure document describing the in-lab testing routine and the procedure for dealing with pipettes that do not meet the acceptance criteria 4. What Acceptance Criteria Should Be Used? The pipettes should be checked at 1 – 2 volumes, with 4 – 10 measurements each. The systematic and random error should be compared against the limits defined either by pipette manufacturer or ISO 8655. 5. What Are the Outcomes of the Testing? The In-house testing routine should provide the following deliverables: e D Documented history of all your lab’s pipettes, showing their testing interval, testing dates, and at minimum, the result if they met the acceptance criteria or not. e D The pipettes not meeting acceptance criteria should be clearly marked and removed from use and forwarded to maintenance and calibration for resolving the issue. Are You Sure About the Volume? – a Human Factor To be certain that your measurements are in accordance with the study plan and relevant SOPs, your pipette should have a simple and unambiguous volume display with clear digits (Fig. 4). This way, volume setting is effortless and a quick glance is all it takes to affirm that you are using the intended volume setting, thus keeping your mind on your experiment. If you choose a mechanical pipette, make sure that the volume display clearly shows all digits to ensure that volume setting and checking doesn’t take your mind off of your work. Fig 4. From left to right: Sartorius Picus® NxT electronic pipette display, Sartorius Tacta mechanical pipette four digit volume display, Manufacturer A mechanical pipette three digit volume display and Manufacturer B three digit volume display. The Sartorius pipettes unambiguously display the selected volume. The Manufacturer A and B pipettes’ volume display use a red-black color code to indicate the decimal separator and an analog line indicator for the last value. Summary A pipette is a precision measuring apparatus that has a significant influence on your lab results, but it can also be your companion in ensuring compliance. Compliant pipetting can be achieved easily by creating a Pipetting Quality Control Program, according to industry best practices and by equipping laboratories with Picus® NxT electronic pipettes that can be programmed according to SOPs and work instructions and remind users to perform periodical maintenance and calibration. To implement, the quality program should be documented and controlled with SOPs for laboratory personnel. SOPs should cover all aspects of the program, including the continuous training of personnel to pipettes and pipetting. 67 Supplement 2 Calbration and Maintenance Program Most laboratory quality systems require a regular calibration and maintenance program for pipettes. Today, laboratories commonly use external service providers for this labor-intensive work that require highly sophisticated quality systems. 1. What Should Be Done? The pipettes should regularly be maintained according to the manufacturer’s instructions. The maintenance consists of cleaning and greasing of pipettes, as well as replacement of wearable parts. Alongside maintenance, the pipettes should have their performance verified by calibration – measurement of systematic and random error along with any necessary adjustments. 2. How Often? The testing frequency is based on the risks associated with the use of the pipettes. The maintenance interval is affected by such factors as pipetting frequency, liquids dispensed, and the age and model of pipette. A minimum maintenance interval of one year is suggested, with calibration done annually or more often, such as every 3 – 6 months. If, for example, volatile liquids or solvents are dispensed, maintenance should be done more often. 3. What Is Needed? For a full maintenance and calibration of pipettes, the used calibration laboratory should have at minimum: e D Full ISO 8655 compliance, including controlled environment in terms of temperature, vibration, and humidity e D Accreditation according to ISO 17025 standard with traceability of measurements to international standards e D Balances with a minimum of 5- and 6-decimals, along with evaporation traps or draft shields e D Software for recording results e D Professionally trained technicians | engineers understanding pipette technology and good pipetting practices, as well as requirements set by regulatory and quality systems. 4. What Acceptance Criteria Should Be Used: The pipettes should be measured at 2 – 3 volumes, with 4 – 10 measurements each, with systematic and random error calculated and compared against the acceptance limits. Use of limits defined in ISO 8655 or by the manufacturer of the pipettes are suggested. 5. What Are the Outcomes of the Calibration? The Maintenance and Calibration program should provide at minimum e D Documented records of all maintenance and repair activities done to the pipettes e D Calibration certificates showing the identification of pipettes, such as serial numbers and time of calibration, tips used, measurement conditions, measurement equipment, and personnel e D Random error and systematic error should be calculated and documented, along with acceptance criteria, such as pass | fail limits. Supplement 3 Best Practices for Setting up The Pipetting Quality Control Program To work according to Good Laboratory Practice, a Standard Operating Procedure (SOP) for Pipette Quality Control should be defined. Below are areas that should be described at minimum in the SOP to guide laboratory personnel through the process: 1. For In-Lab Testing Routine, Define: a. Testing frequency b. Testing equipment and environment c. Personnel qualifications to conduct testing d. Measured volumes and aliquot quantities e. Acceptance criteria f. How to record and store the results g. Actions of isolating and marking pipettes not meeting acceptance criteria h. Procedures for evaluating the effect of failure on the work performed with the pipette in question 2. For Maintenance and Calibration Program, Define: a. Requirements for a calibration laboratory, ISO 8655 and ISO 17205 at minimum i. Testing equipment, environment and procedures ii. Qualifications for maintenance and calibration personnel b. Maintenance and Calibration frequency c. Decontamination procedures for the pipettes before maintenance d. Volumes tested and number of measurements e. Acceptance criteria f. Recording and documentation systems g. Actions of isolating and marking pipettes not meeting acceptance criteria h. Procedures for evaluating the effect of failure on the work performed with the pipette in question 3. For Continuous Education of Laboratory Personnel, Define: a. Training program for personnel on correct pipetting techniques and ergonomics b. Training on quality systems and standards related to pipettes and pipetting c. Documentation and qualification plans for personnel training Sales and Ser C F www \251 2020 Sart design ar St German Sart GmbH & C Ott 3 P F Sart Liquid Handling Oy Laippa 00880 Helsinki, F P lhinfo.finland@sart USA Sart North America 565 Johnson A Bohemia, NY T

How to Select a Mechanical Pipette Points to consider when choosing a Mechanical Pipette Joni Åke Sartorius Biohit Liquid Handling Oy, Laippatie 1, 00880 Helsinki Finland Contact E-Mail: lhinfo.finland@sartorius.com Introduction Widely used in laboratories of all kinds, mechanical pipettes are long-lasting tools. Because they are used for several hours a day, ergonomics and personal preferences – such as handling comfort – are important selection criteria. Other factors such as the application, laboratory workflow, required volume ranges, physical properties of the sample, and requirements for accuracy and precision also need to be considered when searching for the right pipette for the job. Find out more: www.sartorius.com Practical Selection Guide 2 Accuracy and Precision Accuracy and precision are two of the most critical aspects when choosing a pipette. Accuracy means that the delivered volume equals the set volume. Precision expresses the proximity of multiple pipetting results. Here are some examples: The terms accuracy and precision are expressed in the technical specifications of the pipette as systematic error % (inaccuracy %) and random error % (imprecision %). It is worth noting that the specifications are typically valid only when using the manufacturer’s own pipette tips. The best accuracy can be obtained by using a high quality, professionally maintained and calibrated pipette with appropriate high quality tips. Precision, on the other hand, is largely affected by pipetting experience and good laboratory practices, such as correct pipetting angles, optimal pipetting speed, and a consistent pipetting rhythm. To achieve the highest level of accuracy, you should choose the smallest volume pipette capable of handling the volume in question. This is important because pipetting accuracy decreases when the dispensed volume approaches the pipette’s minimum capacity. For example, when dispensing bgW@t? t"&T"a!Wc?qB(? WD?!)Fc%54"Ug0?Gp@t? t&! '08BI8" pipette ideal. Moreover, to achieve good pipetting results, it is important to select a pipette with low pipetting, tip-loading, and tip-ejection forces. High forces exhaust the arm and hand muscles more quickly, resulting in poorer results, especially in long pipetting series. We recommend that you also look for the following features, all of which affect the reliability of pipetting results: - Easy calibration for various types of liquids. It is also advantageous if settings can be saved for later use. - Volume adjustment locking – this feature helps to prevent accidental volume changes during pipetting. Pay special attention to the reliability, ergonomics, and intuitiveness of the mechanism. - Color coding of the pipette or pipette caps – this helps you select the correct tip for the pipette. The result is accurate, but not precise: The mean volume matches the set volume, but the individual pipetting results deviate from each other. Accurate, but not precise Result is precise, but not accurate: There is only minor variation between pipetting results; however, the mean volume differs from the set volume. Precise, but not accurate Result is accurate and precise: The mean volume equals the set volume; there is only minor variation between pipetting results. Precise and accurate 3 Ergonomics Pipetting is one of the most common tasks performed in a laboratory on a daily basis. Studies have associated pipetting with increased risk of upper body musculo- skeletal disorder, and even more than 40% of lab professionals can suffer pipetting related disorders.* In addition to causing discomfort, hand or arm injuries limit working performance and may therefore impact accuracy, precision, and the reliability of results. For the best possible ergonomics, it is important to pay attention to the following qualities when choosing a pipette: - Required pipetting force: High pipetting force increases the risk of RSI. Moreover, it lowers accuracy and precision in long pipetting series. The typical force required to move the plunger to the first stop is between 3 and 15 N. The force required to press the plunger to the second stop can be as high as 40 N. You can carry out a simple test to compare the pipetting forces of two pipettes by pressing the plungers against each other. The plunger with the lower pipetting force will move first. - Tip ejection forces: Tip ejection typically requires more force than pipetting. The high tip ejection forces of mechanical pipettes present an injury risk, especially in conjunction with repetitious pipetting. Typical tip ejection forces range from 15 to 30 N. - Tip loading: Next to tip ejection, tip loading requires the most force during pipetting. The tip loading force is the force required to attach the tip firmly to the pipette. Poorly fitting tips require tapping, rocking, or even tightening by hand to ensure proper sealing. The force can be reduced by using properly fitting tips. - Grip design and balance: The pipette should fit com- fortably in the hand, and the finger support should make holding the pipette effortless. Moreover, a well- balanced pipette with the mass center close to palm provides stability that considerably reduces hand muscle strain and wrist torque. - Weight and length: The lighter and shorter the pipette, the more ergonomic it is. - Volume adjustment: Adjusting the pipetting volume should be convenient and ergonomic. To avoid unnecessary strain on the thumb, it should be possible to adjust the volume with two hands – one holding the pipette while the other rotates the adjustment wheel. - Volume display: To avoid having to hold the pipette in an awkward position, the volume should be easily readable during normal pipetting. Also, larger the numbers are the easier they are to read. - Suitability for right and left-handed users: The pipette should be comfortable to use for both right and left-handed users. All operations should be equally functional from both directions. Moreover, the display should be easy to read regardless of direction. *Bjorksten, M. G., B. Almby, and E., S. Jansson. 1994, Fredriksson, K. 1995 Preventing Contamination To avoid aerosols or drops of a sample from being spread around when ejecting the tip, be sure to select a pipette with gentle tip ejection. When the tip is gently ejected, the remaining liquid droplets or aerosols are much less likely to disperse over a wide area. For fast and convenient decon- tamination procedures, choose a mechanical pipette that is fully autoclavable without disassembly. This also applies to multichannel models. You should choose a pipette that offers the possibility to use a filter on the tip cone. Tip-cone filters prevent aerosols and fluids from contaminating the internal components of the pipette. They are also an eco- nomical and effective way to prevent sample contamination. Alternatively, filtered pipette tips can be used. Single or Multichannel Pipette? Single-channel pipettes are the workhorses of liquid handling. They are available in adjustable and fixed-volume models. Adjustable-volume pipettes allow the dispensed volume to be changed as needed, whereas fixed-volume pipettes always dispense the same quantity of liquid. Fixed-volume pipettes prevent dispensing errors caused by incorrect volume selection. They are suitable for applications with a constant liquid transfer volume as well as being ideal for beginners and non-certified technicians. Here are the most important points to consider when selecting a multichannel pipette: - Check that the position of the lower part of the pipette can be adjusted 360 degrees to ensure that pipetting can be performed ergonomically. - Make sure that the pipette provides fast, secure, and simultaneous tip-loading for all tips. It should be possible to mount the tips evenly without excessive force. - Check that the tips can be easily ejected. 4 Calibration and Maintenance All pipettes need regular maintenance to ensure reliable results and maximum instrument lifetime. When choosing a pipette, it is important to consider the service aspects. Do you want the user to be able to perform calibration? If yes, ensure that this is possible and that it is easy to do. If the user will clean the pipette, it should be easy to disassemble and have as few removable parts as possible. The easiest pipettes to clean have only three removable parts and can be disassembled without tools. If you plan to use external calibration and maintenance services, check the location of the closest service center, as well as the quality, cost, and speed of their services. To learn more about Sartorius pipettes, visit https://www.sartorius.com/en/products/pipetting A disassembled mechanical pipette Lubricating a mechanical pipette Air or Positive Displacement Pipette? There are two types of mechanical, piston-operated pipettes: air displacement and positive displacement pipettes. Air displacement pipettes, which are intended for general laboratory work and aqueous samples, have an air column between the piston and the liquid. Most pipetting work in laboratories is performed using this type of pipette. How an air displacement pipette works Positive displacement pipettes are intended for demanding samples such as highly viscous, volatile, radioactive, or corrosive liquids. In this type of pipette the piston is in direct contact with the liquid, ensuring there is no risk of contamination. Because these pipettes require special tips, positive displacement pipetting is more costly than air displacement pipetting. How a positive displacement pipette works Specifications subject to change without notice. Copyright Sartorius Lab Instruments GmbH & Co. KG. Status: 06 | 2021 Germany Sartorius Lab Instruments GmbH & Co. KG Otto-Brenner-Straße 20 37079 Göttingen Phone +49 551 308 0 USA Sartorius Corporation 565 Johnson Avenue Bohemia, NY 11716 Phone +1 631 254 4249 Toll-free +1 800 635 2906 For further information, visit www.sartorius.com Finland Sartorius Biohit Liquid Handling Oy Laippatie 1 00880 Helsinki, Finland Phone +358.9.755.951

www.sartorius.com Pipette Cleaning Your pipette and samples are precious Cleaning the the lower part of the pipette Set the cleaning and decontamination interval according to the application. Recommendation is to clean every 3 months. 1. Check the cleaning or decontamination protocol and chemical compatibility of the selected cleaning solution for your pipette in the pipette user manual. 2. Wearing gloves, disassemble the pipette lower parts. As a matter of routine, inspect the parts for wear and tear. Replace the broken and worn parts with new ones or send the pipette to a service provider. 3. Thoroughly clean the lower parts of the pipette with the selected cleaning agent, and wipe the outer parts of pipette handle. Don’t use tools to clean as that might scratch the surface of the lower parts. 4. After cleaning, remove residual detergent, bleach, or radioactivity cleaning agents from the pipette thoroughly with pure (Type 3) water or distilled water. Wipe the pipette dry or allow to dry. 5. Re-grease the pipette. Use only the grease recommended by the pipette manufacturer. Check the performance of the pipette gravimetrically or with a balance. 6. Pipette maintenance and performance test can be outsourced to service providers. Make sure that provided service is fulfilling the level and quality of your needs. Daily cleaning of pipettes Cleaning & Decontamination Quick Guide Autoclaving 1. Remove the Safe-Cone filter if attached. Clean the pipette with ethanol and allow it to dry. 2. Check the autoclaving protocol in the pipette user manual to determine if the pipette is fully autoclavable, or if only specific parts must be disassembled and autoclaved. 3. Put the pipette or autoclavable pipette parts into the sterilization bag, and place the bag into the autoclave. 4. Sterilize at 121 °C and 1 bar overpressure for 20 minutes. (252 °F, 1 atm). 5. After autoclaving, cool down and dry the pipette before reassembly. Drying can be done overnight at room temperature or at 60 °C for 3 hours. 6. Insert new Safe-Cone filter onto the pipette. 7. Reassemble the pipette, or check if the lower parts have become loose during autoclaving, and tighten them if necessary. 8. It is recommended to check the performance of the pipette after every autoclaving. It is also recommended to grease the piston or seal of the pipette after every 10 autoclavings. Cleaning the outer surface of the pipette. 1. Remove Safe-Cone filter from the pipette. 2. Gently clean the surface of the pipette with a moistened cloth using a disinfectant liquid for example 70 % ethanol, or mild detergent, and a soft, lint-free cloth. Pay special attention to cleaning the tip cone. 3. After cleaning, allow ethanol to dry, or remove detergent from the pipette thoroughly with moistened cloth using pure (Type 3) water or distilled water, then wipe it dry. 4. Insert new Safe-Cone filter onto the pipette. Interested to know more about pipette maintenance? Contact Sartorius and request for a Pipetting Academy. ? www.sartorius.com/en/knowledge/trainings/pipetting-academy Contaminant Cleaning reagent Proteins Detergents DNA, RNA Bleach, Nucleic acid removing agents, UV RNase Nuclease removal agents, DEPC Acids/Alkali Water Contaminant Cleaning reagent Organic Solvents Detergents Radioactive Radioactivity removing agents Bacteria Autoclave, Bleach, Ethanol, Hydrogen peroxide, Quartenary ammonium agents, VHP Contaminant Cleaning reagent Viruses Autoclave, Bleach, Ethanol, Hydrogen Fungi Autoclave, Bleach, Hydrogen peroxide, VHP Biological Sample (blood serum, urine, tissue) Detergents & Autoclave

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Minimize Risks in Endotoxin Testing Smart Pipetting Solutions Are You Testing Your Medical Devices with Endotoxin-Free Pipette Tips? Guarantee Consistently Reliable Endotoxin Testing Results with Purity- Certified Pipette Tips Endotoxins can be a risk to patient safety. Even a low endotoxin concentration in the blood stream can produce inflammation in the human body; therefore, preventing endotoxin exposure to your patients is important. To prevent patient exposure to endotoxins, frequent and reliable testing for endotoxin levels on medical devices is required. The LAL method, is one such reliable test method used to guarantee patient safety and the risk-free use of medical devices. An alternative method is the recombinant Factor C (rFC) assay that is completely animal-free. Depending on the intended use, US Pharmacopeia (USP) chapter 161 states that all final sterilized products, such as medical devices, must be tested for endotoxin levels, usually by batch, and describes endotoxin release limits as follows for products that come into contact with: e D the cardiovascular system or they lymphatic system -- 0.5 EU/mL or 20 EU/ device e D the cerebrospinal fluid - 0.06 EU/mL or 2.15 EU/device New Application Note: Are You GLP/GMP Compliant When it Comes to pipetting Are you following methods for current Good Laboratory Practice (cGLP) or current Good Manufacturing Practice (cGMP)? Our new application note introduces tools and principles that can help you with these demanding requirements, especially when it comes to your pipetting practices. A pipette is a precision measuring apparatus that has a significant influence on your lab results, but it can also be your companion in ensuring compliance. View Application Note Endotoxin Facts - What You Need To Know What Are Endotoxins and Where Do They Enter the Life- Cycle? Endotoxins are lipopolysaccharide complexes natively located on the outer membrane of Gram-negative bacteria. They can cause several clinical conditions, of which the most severe example is septic shock. Endotoxins, as a product of bacterial death, can be found wherever bacterial growth is possible. Inactivation and destabilization of endotoxins is difficult because they have high heat- tolerance and the ability to tolerate extreme pH values. Also, their removal is tedious as the lipopolysaccharides contain a hydrophobic lipid moiety and a hydrophilic phosphate group. Therefore, the most effective way to achieve an endotoxin- free level for products is to avoid exposure to the possible sources of endotoxins in the first place Laboratory consumables as a source of endotoxin contamination should be taken seriously, as it has been shown endotoxin contaminated test tubes can compromise the reliability of clinical biomarker assay measurement. (Newhall et al. (2010). Evidence for Endotoxin Contamination in Plastic Na+-Heparin Blood Collection Tube Lots. Clinical Chemistry 56; 1483-- 1491)Five Vital Questions to Ask Yourself about Endotoxin Testing Before Buying Pipettes and Consumables? e D iDP@t? t")AIi"E8?G6?1
1q?)`8q?2R)?WG?('9?9!5?G?% A? low endotoxin-free limits? e D Does the packaging of tips protect the purity of tips through transportation to your lab bench? e D Do you have clear standard operating procedures (SOPs), for example, for pipetting protocols and maintenance? e D Do your instruments support the avoidance of errors in pipetting? e D Are the users trained in correct pipetting technique, and Rpr?p3e???e39?0?
R?"5?Qa% A? results? The Effects of Endotoxin Contamination Did you know that endotoxin contamination of lab consumables can influence your assay results? Pipetting is an integral part of the endotoxin testing workflow for medical devices. To minimize potential sources of endotoxin contamination, use endotoxin-free consumables, such as pipette tips, within the testing workflow. Pipette tips that are not manufactured in an automated process can contain endotoxins that cause false endotoxin test results and contaminate samples. Highly automated processes minimize human contact with the raw materials and the final product during the entire manufacturing process, thus minimize endotoxin contamination risk. Sartorius pipette tips are manufactured in a highly automated process and in a clean room environment, and go through a lot-specific testing with an endotoxin test limit of <0.005 EU/ml, which is 100 times lower than the regulatory requirement. All Sartorius endotoxin-free tips are supplied with purity certificates. Before purchasing endotoxin-free pipette tips, check the test limits for endotoxin-free certification of pipette tips to ensure they are low enough to match your test needs. The Effects of Pipetting Technique Pipetting errors are a common source of variance in testing procedures. For example, variance in endotoxin testing standard curves can have a deleterious effect on the reliability of test results. The pre-programmable protocols of electronic pipettes can reduce user error in pipetting steps. Using the same manufacturer’s pipette tips with your pipettes ensures the perfect fit, thus reducing leakage, accuracy, and precision performance promised for the pipette. To ensure the most reliable results, take care of your pipettes and calibrate them regularly. Sartorius also offers certified and accredited pipette calibration services. View Poster Pipetting in Endotoxin Testing View Application Note Endotoxin-free Pipette Tips Sartorius pipette tips are tested and certified to be endotoxin free, so they fit into workflows of medical device QC labs. Sartorius manufactures pipette tips according to ISO 14644-1 in a certified ISO 8 cleanroom environment to maintain the highest quality and purity standards. Only the best plastic materials are selected, and our automated manufacturing process is strictly controlled from beginning to end in line with GMP to reliably prevent contamination by human contact. An independent laboratory checks every tip lot to ensure the absence of DNase, RNase, and endotoxins with a test limit of 100 times lower than the regulatory requirement. Optifit Pipette Tips Sartorius Optifit tips ensure perfect fitting and leak-tight sealing on Sartorius pipettes for maximum pipetting accuracy and reproducibility. The color coding of the tip trays enable you to easily match them to their color-coded Sartorius pipette. e D Tips are packed in single tray racks with an air-tight wrapping to protect the tips from endotoxins e D DNase-, RNase-, and endotoxin-free production processes reliably protect your sample from contamination e D The highest quality pure polypropylene is used as raw material to ensure material purity e D "x%t
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i ??UU@@??e@p?Gs Purity Certified Pipette Tips Accurate and Precise Pipettes Sartorius pipettes are a perfect choice for endotoxin testing of medical devices, as they have been designed with cleanliness, accuracy, and ease-of-use in mind. The pipettes are easy to clean with the lower parts of the pipette being easy to remove. They are also easy to calibrate and are equipped with a volume lock to ensure that your dispensing volume is as intended. In addition, the Picus ® Nxt has a calibration reminder feature so that you don’t forget your next calibration expiry date. Tacta ® Mechanical Pipette – Perfectly Balanced Tacta ® is the new premium mechanical pipette with superb comfort and reliability. Tacta ® makes pipetting effortless and safe, while producing accurate and reliable results time after time. Experience the benefits of Tacta ®: e D Fully autoclavable pipette for best contamination control e D Reliable results, even over lengthy pipetting periods e D Controlled and smooth tip ejection with the new Sartorius Optiject technology e D Comfortable to hold due to the ergonomically designed handle e D The unique Sartorius Optilock system provides flexibility for volume adjustment and locking e D Calibration adjustment to provide accurate results for various liquid types e D Easy to clean, with only three parts to disassemble Picus ® Nxt Electronic Pipette – Highly Sophisticated and Ergonomic Picus ® Nxt is the lightest and smallest electronic pipette on the market. Its ergonomic design, fully electronic operation, and advanced functionalities ensure an easy and comfortable pipetting experience. Experience the benefits of Picus ® Nxt: e D e D Fully electronic operations guarantee accurate and precise pipetting results, regardless of user skill level e D The extensive range of pipetting modes, from diluting and titrating to serial dispensing, makes pipetting tasks quick and easy e D 7G?$HV`(re%d9G?!p
)s sequences and add reliability on standard curve pipetting e D 6 `(!@??e@p?c%?s6SQYUI?!3a6
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WS?uiI? and ISO 8655) conforms to the strictest regulations e D Maintenance and calibration reminders alert you when service is required e D Possibility to lock the pipette and prevent the use, for instance, in case of contamination e D Uniquely lightweight (weighs only 100 grams) and 76??@9??619u?? Additional Resources View these resources to help you find information-rich solutions. Cleaning and Decontamination Guide for Sartorius Pipettes Application Note: Pipette Calibration and Standards Practical Selection Guide: Set up Pipetting Quality Control Program for Your Lab Poster: Get the most out of your electronic pipette Poster: Pipette cleaning - your pipette and samples are precious Poster: ABC of the pipette tip purity Brochure: High Quality Pipette Tips for Consistent and Reliable Results Brochure: Tacta ® Mechanical Pipettes — Perfectly Balanced Brochure: Picus ® and Picus ® NxT Electronic Pipettes View Guide View Application Note View Guide View Poster View Poster View Poster View Brochure View Brochure View Brochure For further contacts, visit www.sartorius.com Specifications subject to change without notice. Copyright Sartorius Lab Instruments GmbH & Co. KG. Status: 08 | 2022 Germany Sartorius Lab Instruments GmbH & Co. KG Otto-Brenner-Strasse 20 37079 Goettingen Phone +49 551 308 0 USA Sartorius Corporation 565 Johnson Avenue Bohemia, NY 11716 Phone +1 631 254 4249 Toll-free +1 800 635 2906

Get the most out of your electronic pipette Work faster, smarter & improve reproducibility in cellular and molecular biology www.sartorius.com 96-well or 384-well plate assays - PCR - Enzyme assays - Cell culture – drug or reagent additions Cell culture: Mixing and seeding cells Use Pipetting with Mixing mode: Adjustable pipetting speed for sensitive cell types. Number of mixings can be varied to ensure even distribution of cells. Avoiding bubbles Use Reverse Pipetting mode: Adjust the excess volume to save on expensive reagents. Used for fluorescence-, absorbance-, or cell-based assays, proteins, foamy or viscious liquids. Standard curves and calibration curves Use “Sequential Pipetting” mode: Ensures faster preparation of curves in spectrometric or colorimetric assays and immunoassays. Checking protein yield, sample or reagent volumes Use manual mode: Manually controlled aspiration for accurate and rapid checking of volume. Sample pooling (Ce?G&aet% A? % A? HvCdd9 sample pooling. Used for NGS, PCR, protein assays and changing media on cell cultures in 96-well plates. PCR, cell assays, immunoassays, fluorescence assays, ELISA Use Multi-Dispensing mode: Used for long pipetting series. Ensures fast and reproducible pipetting. Can be combined with Plate tracker. Use “Plate Tracker” For keeping track of one’s position when pipetting on micro-well plates. Never accidentally pipette into the wrong well again.

Preparation of Standards – Easier than Ever with the Sartorius Cubis ® MSA Dosing System Holger Densow* Sartorius Lab Instruments GmbH & Co. KG, Otto-Brenner Str. 20, 37079 Göttingen, Germany * Correspondence E-Mail: holger.densow@sartorius.com Abstract Preparation of standards, also called reference samples, of known concentrations is a common routine procedure in analytical laboratories. Internal or external standards with very low concentrations are used in these laboratories for highly sensitive quantitative analytical methods to exactly determine the concentration of chemical components in samples using highly sensitive quantitative analytical procedures. June, 2017 Keywords or phrases: Preparation of standards or solutions of defined concentration for analytical procedures Find out more: https://www.sartorius.com/en/applications/life-science-research/sample-preparation/hplc-sample-prep Application Note 2 Preparation of standards of known concentrations is a com- mon routine procedure in analytical laboratories. Internal or external standards with very low concentrations are used in these laboratories for highly sensitive quantitative analytical methods to exactly determine the concentration of chemi- cal compounds in samples. External standards are separate samples used for comparison to test samples, whereas in- ternal standards are added to the samples to be analyzed. Therefore, the concentration of such standards must be as accurate as possible to prevent subsequent errors in the determination of unknown concentrations of compounds in samples. Two problems can occur when standards are manually prepared from soluble solids: 1. The solvent volume required and the compound concen- tration desired are both used to calculate the amount of a soluble compound to be weighed. The essential prob- lem does not lie in the calculation itself, but rather in the accuracy with which the amount of the solid is weighed according to the calculated target quantity. On high- resolution laboratory balances, it is next to impossible to 3!??(Ye?i1?a(?@p?(?Bq?
R???4B7?u?p 2. If the amount actually weighed does not precisely match the target amount calculated, the solvent quantity has to be adjusted to reach the desired final concentration. Recalculation of the required liquid volume takes up valuable time and is a potential source of error. Depend- ing on the type of concentration specified, various para- meters need to be taken into account, such as the desired concentration, purity of the substance, amount actually weighed and possibly even the molecular weight. For inexperienced users, recalculation of the compound weight is usually takes considerable time, whereas expe- rienced users commonly find this a boring task so inad- vertent errors can easily creep in. The Cubis ® MSA dosing system simplifies workflows in the preparation of standards. Once the user enters the desired concentration and volume of a standard solution, the sys- tem automatically calculates the required amount of the compound to weigh in and shows the target weight as a bar graph with the minimum and maximum tolerances: Although the user hardly ever ends up weighing the exact amount in this case as well, the system software uses the actual weight of the compound to recalculate the volume of the solvent and transmits this value to the automatic dispenser. As a result, any variations in the amount weighed from the desired target weight will not require the user to recalculate the volume of solvent when using the Cubis ® MSA dosing system. Instead, the entire workflow can prog- ress without any interruptions and the solvent can be auto- matically dispensed. After the solvent is added, the weight of the sample is de- termined again. In this way, the Cubis ® balance verifies how much solvent was actually added. This gravimetric monitor- ing step is considerably more accurate than any volumetric measurement of a solvent. Volumetric measurement proce- dures are disadvantageous in that they do not sufficiently allow for the effects on accuracy, such as evaporation of highly volatile solvents, hold-up volume in tubing or pipettes, differences in the density of solvents, etc. By contrast, gravi- metric measurement methods deliver absolute values and achieve the highest accuracy. At the end of the workflow, the dosing system software calculates the exact concentra- tion of the standard solution. 3 of standards, the semi-automatic system introduced in this Application Note offers higher flexibility and saves considerable time. Compelling reasons in favor of an open- design system are the lower purchase costs and, by virtue of the system’s simplicity, much lower operating and main- tenance costs. Although the software of the Cubis ® MSA dosing system offers the option of managing data sets of up to 100 differ- ent compounds, solvents and standards, this number may be too low for analytical laboratories that routinely prepare standards. In addition, preparation of standards is only one step in the entire analytical procedure so centralized data management that represents the entire process chain is recommended. For this purpose, the software of the Cubis ® MSA dosing system has an interface for the ThermoFisher Chromeleon™* 7.2 SR4 chromatography data system that is designed to manage chromatographic systems and per- form data analysis. Compared with known, fully automatic dispensing systems on the market, the product presented in this Application Note offers a number of decisive advantages. Fully auto- matic systems, which take care of dispensing fine powder, granules and homogeneous or heterogeneous mixtures, require exact knowledge of the dispensing properties of these substances. For example, the flowability, size, shape, compactness, density, tendency to aggregate and electro- static properties of the particles must either be known or visually evaluated. Choosing the right dispensing head is not always easy given the many different dosing parameters that have often been only qualitatively assessed. Beyond this, changing the equipment accessories of such a dosing system to dispense a different compound each time is time-consuming and expensive as various dispens- ing heads have to be purchased. It makes sense to use such systems only if a very high number of standards have to be prepared. For preparation of a low or medium number When the command “Send weighing input to scale” is activated, data, such as the name of the standard and the desired concentration, is transmitted to the Cubis ® MSA dosing system. The software application installed on the balance uses this desired concentration to calculate the amounts to be weighed, shows these values to the user for verification and then starts the weighing and dispensing procedure. This process is repeated until all standard samples transmit- ted by Chromeleon have been processed. The data saved for the standards is retrieved from the balance using the function “Retrieve weighing result from scale” and trans- mitted to Chromeleon. The verified concentrations of the standards and the unit are saved by Chromeleon and used for later evaluation. This direct communication interface ensures the highest data integrity as there is no need for any manual inputs, or such inputs are not possible in the first place, in order to exchange data. In the Chromeleon component table, the user defines the desired concentration of standard samples: For further information, visit www.sartorius.com Chromeleon* 7.2 SR4 enables fully automated data manage- ment of any number of standards. Connection of the Cubis ® MSA dosing system to Chromeleon is recommended for extending analytical laboratories’ capabilities for automation of workflows. Ultimately, automation signifies considerable time savings compared with manual data exchange while increasing process reliability. * Dionex™ Chromeleon™ 7.2 Chromatography Data System (CDS) software is a trade mark of company Thermo Scientific™ Germany Sartorius Lab Instruments GmbH & Co. KG Otto-Brenner-Strasse 20 37079 Goettingen Phone +49 551 308 0 USA Sartorius Corporation 565 Johnson Avenue Bohemia, NY 11716 Phone +1 631 254 4249 Toll-free +1 800 635 2906 Specifications subject to change without notice. Copyright Sartorius Lab Instruments GmbH & Co. KG. Status: 11 | 2020

How to Achieve Optimal Weighing Performance with Cubis ® II High-resolution Balances How to Achieve Optimal Weighing Performance Scientists in R&D or analytical laboratories need the most reliable lab weighing results. The Cubis ® II platform from Sartorius provides a completely configurable, high- performance portfolio of both lab weighing hardware and software to meet the customers expectation on the highest level. The Cubis ® II modularity allows to choose from a range of 45 different weighing modules that fit your prefer- ences. This portfolio also includes balances with very high-resolution, e.g. ultramicro, microbalances, semi-micro and analytical balances. These highly sensitive balances require a little closer inspection of their site and a slightly deeper understanding of external influences caused by the user or the environment, to achieve always the highest performance. Very often, the application requires weighing of very small amounts of sam- ples into large flasks or containers. The smaller the sample quantities used, the greater the relative measuring errors become, and the larger the tare container size employed, the higher the influence of environmental conditions will be on weighing accuracy. External environ- mental influences or improper handling can lead to inaccurate results or poor weighing performance, which are not caused by the balance. To ensure high accuracy during weight measurements and excellent repeat- ability of the results you need to observe certain basic rules and requirements. When following the instructions and recommendations below, your balance will always provide the best weighing performance and highly reliable results. 1. Choose a Stable Weighing Table in a Quiet Place to Set Up Your Balance. 1. The table should be solid-built and, whenever possible, be made of stone or synthetic stone. 2. Avoid causing the tabletop to sag or deflect even slightly; for example, never use it to prop up your arm. 3. Set up the balance in a vibration-free location. Ensure that there are no machines or engines that generate vibrations or electromagnetic fields near the balance. Magnetism must be ruled out (e.g., tables may not be made of stainless steel). 4. Do not position the table in the middle of the room, but near a wall or, even better, in the corner of a room, as this is where the vibration amplitudes are generally at their lowest. 5. Avoid exposing your balance to sunlight and infrared radiation emitted by lamps or heaters. 6. The location may only be slightly ventilated. Exposure to drafts needs to be avoided, and the air flow rate should be below 0.2 m/s. 7. Cold air currents from air conditioners may not pass directly across or over the draft shield, as this can result in an in- version layer of air inside the draft shield. This, in turn, can cause unstable weight readouts. 2. Work in the Lab under Consistently Constant Climate Conditions. 1. Avoid significant temperature changes or spikes. 2. Keep the relative humidity as constant as possible. Prevent the relative humidity from dropping below 40%, as this will significantly in- crease interference by static electricity. 3. Use the Cubis ® II climate sensor option (temperature, baro- metric pressure and relative humidity) to monitor climate conditions. > 40% 4. Use the Cubis ® II ionizer option to eliminate electrostatic influences. Electrostatic charges on glass vessels dissipate only very slowly, particu- larly when these vessels have very clean surfaces, especially when they are used freshly from a labo- ratory glassware washer. Electrostatic influences are easy to detect by the continuous drift of weight readouts. Increase the air humidity to levels up to 60%, and use an ionizer to reduce these effects on the re- sulting weight readings. 3. Ensure That the Balance Is Leveled and Calibrated. 1. All Cubis ® II balances will support you in using the calibration | adjustment function isoCAL, and the Q-Level function implemented in the balance for leveling continuously maintains the accuracy of the weighing results within a narrow tolerance range. 2. Moreover, routinely check the balance using an external, certified weight. 3. The Cubis ® II Status Center shows all information about your balance and environmental conditions, e.g. calibration, leveling, temperature, humidity, air pressure and service, centralized in a dashboard. In case of warnings or errors, you get detailed help and support. 4. During the Measuring Sequence, Ensure That … 1. … the vessels used are acclimatized next to your balance; i.e., have adapted to the tem- perature conditions in the same room. 2. … you do not touch the container with your hands when positioning it on the weighing pan or in a sample holder. Touching the sample vessel with your hand usually increases the temperature of the vessel. Buoyancy and air current effects influ- ence weighing results. Remember that it takes ten minutes for these effects to subside. Use a pair of tweezers or forceps to position the vessel. 3. Avoid placing your hand inside the draft shield to ensure that no unnecessary inter- change of air outside and inside the draft shield takes place and that no heat is trans- ferred into the draft shield. 4. Avoid touching a vessel with your bare fingers at all times, as a single fingerprint can weigh ?He?hTXGV- fore have a major impact on the accuracy of your weight measurement result. 5. When weighing, en- sure that no powder falls onto the weighing pan next to the vessel, as this will mean that the displayed sample weight is not what is actually in the vessel. Specifications subject to change without notice. Copyright Sartorius Lab Instruments GmbH & Co. KG. Status: 09 | 2020 6. Avoid the complete interchange of air when opening the draft shield by opening only one door, where possible. Optimal to use the draft shield learning capability to open the door only as far as actually necessary. 7. Carefully place the tare container on the weighing pan or in the sample holder. Avoid applying any excessive force. Germany Sartorius Lab Instruments GmbH & Co. KG Otto-Brenner-Strasse 20 37079 Goettingen Phone +49 551 308 0 USA Sartorius Corporation 565 Johnson Avenue Bohemia, NY 11716 Phone +1 631 254 4249 Toll-free +1 800 635 2906 For further contacts, visit www.sartorius.com 8. Do not lean on or against the weighing table or rest your arm on it during the weigh- ing procedure.

Continuous Microbial Air Monitoring in Clean Room Environments Claudia Scherwing017%, Jasmin Bunke2??5 1. Product Development Lab Consumables Microbiology, Sartorius Stedim Biotech, Göttingen, Germany 2. Product Management Lab Essentials Microbiology, Sartorius Lab Instruments, Göttingen, Germany * Correspondence E-Mail: kai.nesemann@sartorius.com Abstract Environmental monitoring is an important part of quality assurance for the production environments of sterile pharma­ ceutical products. Especially for aseptic filling lines where products are filled without a terminal sterilization step it is of utmost importance for product safety and thus an essential part of the quality control strategy. Such ISO 5 graded manufacturing environments are required to have < 1 colony­forming unit (?`#BCFU?pR?@ per m³ of air. A typical method for monitoring contamination of air is to actively draw air and filter it through special gelatin filters. According to Annex 1 to the EU GMP guide a minimum sample volume of 1 m³ of air should be taken per sample location. Considering an 8 hours work shift 1 m?w? is a too low sample volume to reliably judge the air quality of the manufacturing environ­ ment. One approach to improve product safety would be the implementation of a continuous air monitoring covering the complete production process (at multiple sampling points). Unlike agar plates, which would dry out during long­term sampling, the Gelatin membrane filters can be used for the whole 8 h period. Human intervention, such as change of agar plates, could then be avoided, thus lowering the risk of secondary contaminations to nearly zero. February 2019 Keywords: continuous air monitoring, clean room, gelatin filter, MD8 Airscan ®, EU GMP Guideline Annex 1 Find out more: www.sartorius.com Application Note 2 Introduction The following study aimed to establish whether a continu­ ous sampling (and multisampling point assay) provides effective monitoring for the entire production process (?`#B8 h?pR?@ by determining whether trapped organisms can withstand long­term drying stress with unaltered recovery. This study examined the recovery and viability of micro organisms captured on gelatin filters during 8 h of filtration with HEPA­filtered air from a laminar flow hood, using the MD8 Airscan ® system. Stressed and unstressed filters were compared with parallel­run reference filters as controls. The CFU were counted and the genus of the identified micro­ organism populations determined to examine any changes in microbiological flora occurring during continuous long­ term sampling. Compared to the unstressed reference filters, neither total recovery nor recovered bacterial diversity changed. No sta­ tistically significant differences in CFU/m?w? were found be­ tween test filters and reference filters, and no differences in the microbiological flora between test filters and reference filters. CFU populations were comparable. 8 h continuous air sampling on gelatin filters with the MD8 Airscan ® system did not affect total recovery or change the diversity of recovered microorganisms when comparing test filters to reference filters. Monitoring microbiological contamination of air in pro­ duction areas is of major importance because aseptic filling is the step in the production process of the pharmaceuti cal industry that harbors one of the highest risks for contami­ nation2??5 . Aseptic filling lines are increasingly used in the phar­ maceutical industry because increasing numbers of bio­ technology products cannot be sterilized after production without the sterilization process affecting their quality. Fill­ ing lines are defined as ISO 5017%, and air actively sampled in these environments must have less than one colony forming units per cubic meter (?`#BCFU/m?w??pR?@, with a minimum sample volume of one m?w? of air taken per sample location, according to Annex 1 to the EU GMP guide. Considering an 8 hour work shift, one m?w? may be too low a sample volume to reli­ ably judge the air quality of the manufacturing environment. Thus, the development of a continuous production­moni­ toring tool to minimize risks for contamination and increase the overall standard of quality control is required. A method is needed, which continually surveys all cycles of the pro­ duction process and allows sampling at multiple points. To determine if continuous air sampling using gelatin mem­ branes can effectively monitor the entire production pro­ cess over an eight hour shift, the viability of microorganisms on gelatin filters during sterile air long­term filtration, i.e. whether trapped organisms can withstand long­term drying stress and yield unaltered recovery, was examined. Former tests showed that gelatin filters with an inlet velocity of 0.25 m/s had average retention rates of 99.9995 % for Bacillus subtilis varniger spores and 99.94 % for T3 coliphages ` @?. Figure 1: Comparison of mean CFU on test and reference gelatin filters.Comparison of mean CFU on test and reference gelatin filters n = 26 0 130 120 110 100 90 80 70 60 50 40 30 20 10 Ref Test CFU 3 Materials and Methods The study examined whether the viability of microorgan­ isms on gelatin filters was maintained during the long­term filtration of filtered air. The expression “filtered air” describes the ISO 5 HEPA­filtered air of the used Class 2 biological safety cabinet. Test and reference gelatin filters were first exposed to non­ sterile air for 30 minutes. The MD8 Airscan ® air samplers (?`#Bset at an air flow rate of 2.0 m?w?/h (?`#B0,144 m/s?e$? had been located in a non­controlled laboratory environment (auto­ clave room) approx. 30–40 cm apart from each other. This sampling location had been chosen in order to build up special environmental conditions. There, a higher relative humidity (?`#B~ 57 ± 6 % and temperature: ~ 21 ± 1 °C?pR?@ was ex­ pected (thus increased amount of drying stress sensitive, waterborne microorganisms (e.g. gram­, generating a “worst case” scenario). Further, a general higher content of airborne microorganisms per cubic meter was expected than in the “normal” laboratory. Because of that, it was pos­ tulated that the following 8 hours of drying stress would show a clearly visible and statistical detectable effect. Following, the test filters were used to sample filtered air for a further 8 hour period. For the filtration of ISO 5 graded air, the MD8 Airscan ® sampling heads were placed under a laminar flow hood (?`#B relative humidity: ~ 43 ± 3 % and temperature: ~ 23 ± 1 °C?pR?@, thus, there was no additional high relative humidity while the 8 hour stressing. The reference filters were subjected to only 30 minutes filtration of non­sterile air without further aeration. They were placed on soybean­casein­digest agar medium directly after sampling. At the end of the 8 h filtration period under the laminar flow hood, the test filters also were placed on soybean­casein­ digest agar medium plates and incubated at 32 °C for 4 days. The colonies that developed were counted and recorded as CFU/m?w? a total of 26 times. Then, the CFU/m?w? were compared for the test and reference filters. Additionally, the genus of each colony was identified to determine if the microbiological flora had changed during continuous long­ term sampling. Results Figure 1 shows the mean CFU/m?w? on test (gold bar, mean = 69 colonies, sd = 51 colonies) and reference filters (grey bar, mean = 64 colonies, sd = 32 colonies). A mean difference of 5 CFU/m?w? (not statistically significant according to the paired T ­test) was found, but observed no general trend upon comparison of test and reference filters (?`#Bsee Fig. 2?pR?@. In 12 cases, there were more CFU/m?w? on test filters than on reference filters, but the opposite was examined in 13 cases (?`#Bsee Fig. 2?pR?@. The standard deviation in test and reference filters can be attributed to the broad fluctuation of micro­ organisms naturally occurring in the ambient air of non­con ­ trolled environments. CFU 26 25 24 23 22 21 20 Figure 2: Comparison of CFU on the paired test and reference gelatin filters. Comparison of CFU on the paired test and reference gelatin filters 1 19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 0 260 240 220 200 180 160 140 120 100 80 60 40 20 Test Ref 4 No statistically significant difference in the growth of micro­ organisms on test versus reference filters could be observed. Figures 3 and 4 show a representative soybean­casein­ digest agar medium plate with microbiological flora grown on the paired test (left) and reference filters (right). This visual impression shows that the microbiological population found on the test and reference filters is comparable. The genus identification data from a macroscopic comparison of the microbiological flora shown in Figure 5A and 5B con­ firms the visual impression that the microbiological popula­ tion on the test and reference filters is comparable. No statistically significant difference in mean CFU/m?w? be­ tween test and reference gelatin filters. The gold bar shows a mean CFU/m?w? of 69 colonies, with a standard deviation (sd) of 51 colonies for the test filters (counted 26 separate times). The grey bar shows a mean CFU/m?w? of 64 colonies, with an sd of 51 colonies for the reference filters (counted 26 separate times). The mean difference of 5 CFU/m?w? be­ tween test and reference gelatin filters was not statistically significant. No general trend of CFU/m?w? upon comparison of test and reference filters. The gold bar shows CFU/m?w? for 26 repli­ cates of the test filters, and the grey bar shows CFU/m?w? for the reference filters. Figure 3: Comparison of the microbiological flora grown on a test filter (left) and its corresponding reference filter (right). The composition of the microbiological population found on the test and reference filters is comparable. Representative soybean-casein-digest agar medium plates showing the microbiological flora grown on a test filter (left) and its corresponding reference filter (right). Figure 4: Comparison of the microbiological flora grown on a test filter (left) and its corresponding reference filter (right). The composition of the microbiological population found on the test and reference filters is comparable. Representative soybean-casein-digest agar medium plates showing the microbiological flora grown on a test filter (left) and its corresponding reference filter (right). Cocci 91 % Cocci 90 % Gram - 3 % Gram - 3 % Yeast 3 % Yeast 4 % Sporeforming 0 % Sporeforming 1 % Mold 3 % Mold 1 % Staphylococci 0 % Staphylococci 1 % A B 5 Conclusion This study aimed to examine if gelatin filters manufactured by Sartorius Stedim Biotech GmbH are qualified for long­term (eight hours [8 h]) air sampling in production environments in the pharmaceutical industry. Specifically, if microorgan­ isms collected on gelatin membranes can survive long­term filtration with filtered air. The 8­hour filtration period is rep­ resentative of a typical work shift on an aseptic filling line. The focus of the study aimed to establish whether long­ term air filtration decreased the number of CFU/m?w? on filters. Therefore, a non­sterile air sampling on test filters for 30 minutes, followed by a filtration of ISO 5 graded air for 8 h. The experiment provided no statistically significant differ­ ences between test (stressed) and reference (unstressed) filters. The test filters had the same number of CFU/m?w? as the reference filters (i.e., no microorganisms died during long­term filtration). The standard deviations in test and reference filters were attributable to the broad fluctuation of microorganisms naturally occurring in the ambient air of non­controlled environments. Moreover, no difference between the bacterial flora grown on the test and reference filters in either visual comparison or macroscopic com­ parison could be detected. Even gram­negative bacteria were found on stressed test filters. No statistical difference between stressed and unstressed gelatin filters. In conclusion, this study showed that there was no statis­ tical difference between stressed and unstressed gelatin filters, thus proving that gelatin membranes manufactured by Sartorius Stedim Biotech GmbH are qualified for contin­ uous air monitoring in industrial pharmaceutical production environments covering a whole 8 h work shift without the need for human intervention. References ­ (?`#BDraft of the Revision of?pR?@ Annex 1 of the EU Guidelines to Good Manufacturing Practice, November 2008 (?`#BDecember 2017?pR?@ ­ USP, Chapter 1116 – Microbiological Evaluation of Cleanrooms ­ C. Scherwing, F. Golin, O. Guenec, K. Pflanz, G. Dalmaso, M. Bini, F. Andone, Continuous microbiological air moni­ toring for aseptic filling lines, PDA J Pharm Sci Technol, March | April 2007 61: 102–109 ­ CAMR Report 1993 “An assessment of the Sartorius MD­8 Microbial Air Sampler” Figure 5: A. Composition of the microbiological population grown on the test gelatin filters. Almost all microbes grown on test filters is Cocci. This figure shows a breakdown of microbes grown on soybean-casein- digest agar medium plates from test filters. B. Composition of the micro- biological population grown on the reference gelatin filters. Almost all microbes grown on reference filters are Cocci. This figure shows a break- down of microbes grown on soybean-casein-digest agar medium plates from reference filters. For further contacts, visit www.sartorius.com Specifications subject to change without notice. Copyright Sartorius Lab Instruments GmbH & Co. KG. Status: 10 | 2020 Germany Sartorius Lab Instruments GmbH & Co. KG Otto-Brenner-Strasse 20 37079 Goettingen Phone +49 551 308 0 USA Sartorius Corporation 565 Johnson Avenue Bohemia, NY 11716 Phone +1 631 254 4249 Toll-free +1 800 635 2906

Pipette Essentials Make Your Choice Check These Features to Choose Your Perfect Pipette Test the Pipette in Your Lab —Ask for a Demo Pipette from Sartorius! www.sartorius.com Sartorius Biohit Liquid Handling Oy Laippatie 1 00880 Helsinki, Finland 5?U6?7P'Y?.`dAp(?x)C?@?CSQ%"H`5?UrA@cp?C(`b?%YTf&rA@c%`??@p?8w-'Y??!45?!%YTf&SQ%!t?"C%@??A 4p??94h)GV!t?"C'Y??A%0G?!t?"CrA@c@p?'Y??&?@?C`dAp8?"3!45?!A00PgC ?GV!t?"C!?v?v'??ed6?7PrA@c`dApAG)?E7?'Y??@p?6?7P&?@?C!45?!(7&?@?C@p?'Y??!t?"CGV2$R??&?@?C94h)1
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How to Avoid Contamination in Pipetting Joni Ake 1 * 1. Sartorius Biohit Liquid Handling Oy, Laippatie 1, 00880 Helsinki * Correspondence E-Mail: Joni.Ake@sartorius.com Introduction Preventing contamination in pipetting is paramount to achieving reliable results. It requires identification of the potential contamination mechanisms in order that they can all be addressed. Aerosols, suspensions of solid or liquid particles in a gas, are formed in many laboratory activities such as pipetting with air displacement pipettes, and aerosols are the major contamination source in pipetting. They may transfer into the pipette body when unfiltered pipette tips are used and consequently contaminate subsequent samples. A slow and careful pipetting rhythm helps minimize aerosol formation. This paper addresses the three contamination types that originate from pipetting: pipette-to-sample contamination, sample-topipette contamination, and sample-to-sample contamination. April 27, 2018 Keywords or phrases: Pipetting, contamination, cross-contamination, sample preparation, filter tips, sterile tips Find out more: www.sartorius.com Application Note 2 Pipette-to-Sample Contamination This type of contamination occurs when a contaminated pipette or pipette tip contaminates the sample. Pipette tips are available in multiple purity grades from most manufacturers. Purity grades can be divided into three categories: - no purity certification - certified free of contaminants like DNase, RNase, and endotoxins - sterilized to be free of microbial life Contaminants such as DNase, RNase, and endotoxins are difficult to remove by any sterilization method, so it is very important to prevent contamination during manufacturing. The absence of these contaminants is separately tested, usually by a third-party laboratory. Sterilization after manu- facturing ensures that the tips do not contain any microbial life (bacteria, viruses etc.) when delivered to customers. Pipette tips can also be a potential source of leachables – trace amounts of chemicals originating from materials or process equipment that can contaminate the samples. Examples of potential leachables are heavy metals, UV stabilizers, antioxidants, pigments, release agents, bio- cides, and surfactants. High quality tips manufactured from 100% virgin polypropylene in a high quality manufacturing facility do not contain leachables. It is recommended that you confirm this with the tip manufacturer. In daily laboratory work, pipette-to-sample contamination can be avoided by following these simple guidelines: - Select a tip with the relevant purity class for your application. - Use (sterilized) filter tips. Alternatively, you may be able to use tip-cone filters with some manufacturers’ pipettes. The filters prevent aerosols from reaching the pipette body and potentially contami- nating subsequent samples. - Always change the pipette tip after each sample. - Regularly autoclave, or disinfect, the pipette or the components that may come into contact with the sample. 3 Sample-to-Pipette Contamination This type of contamination takes place when the pipetted liquid or aerosol particles from it enter the pipette body. To minimize the risk of sample-to-pipette contamination, the following precautions are recommended: - Always release the pipette’s push button slowly to prevent aerosol formation and uncontrolled liquid splashing within the pipette tip. - Hold the pipette in a vertical position during pipetting and store the pipette in an upright position. This prevents liquids from running into the pipette body. - Use filter tips to prevent aerosol transfer from the sample into the pipette body. Alternatively, filters can be used on pipette tip cones. Sample-to-Sample Contamination Sample-to-sample contamination (or carry-over contamina- tion) occurs when aerosol or liquid residue from one sample is carried over to the next sample. This may take place, for example, when the same pipette tips are used multiple times. To avoid carry-over contamination: - Use filter tips to prevent aerosol transfer from the sample into the pipette body, and again to the next sample. Alternatively, filters can be used on pipette tip cones. - Always change the pipette tip after each sample. - If you suspect pipette contamination, autoclave or disinfect the pipette according to the manufacturer’s instructions. Definitions: Decontamination Any activity that reduces microbial load to prevent contamination. Includes methods for sterilization, disinfection, and antisepsis. Sterilization The destruction of all microbial life, including bacterial endospores. Can be accomplished e.g. using steam, heating, chemicals, or radiation. Autoclaving Autoclaving (moist heat) is an efficient sterilization method for laboratories. A hot, pressurized, and saturated steam is applied to destroy microorgan- isms and decontaminate e.g. laboratory plastic and glassware. Exposure time and temperature are critical. Moreover, the steam needs to penetrate through the entire load to be efficient. Disinfection The elimination of virtually all pathogenic microor- ganisms (excluding bacterial endospores) and reduction of the microbial contamination to an acceptable level. A practical method for surface decontamination. The disinfectant (e.g. alcohols, phenolic compounds, halogens), concentration, and exposure time should be selected according to the assumed contamination type. Antisepsis The application of an antimicrobial chemical to living tissue to destroy microorganisms. DNase Powerful enzymes (nucleases) that degrade DNA by hydrolyzing it into short fragments. Even trace amounts of DNases can lead to low or no yields in DNA techniques such as PCR, or to degradation during DNA purification. Contamination sources: human contact, saliva, bacteria. RNase Powerful enzymes (nucleases) that catalyze the degradation of RNA into short fragments. Very stable enzymes that are difficult to remove. Contamination sources: oils from skin, as well as hair, tears, bacteria. Endotoxins Lipopolysaccharides, large molecules that are part of the outer membrane of Gram-negative bacteria such as E. coli, Salmonella, Shigella, Pseudomonas, and Haemophilus. Cause fever in humans and impair the growth of cell cultures. Are released into the environment when bacteria die and the cell wall is destroyed. Contamination sources: endotoxins are present wherever bacteria are able to grow, i.e. air, water, soil, skin, raw materials, any non-sterile environment. For further contacts, visit www.sartorius.com Specifications subject to change without notice. Copyright Sartorius Lab Instruments GmbH & Co. KG. Order No.: 85037-550-68 Publication No.: SUL1002-e Status 07 | 2020 Germany Sartorius Lab Instruments GmbH & Co. KG Otto-Brenner-Strasse 20 37079 Goettingen Phone +49 551 308 0 USA Sartorius Corporation 565 Johnson Avenue Bohemia, NY 11716 Phone +1 631 254 4249 Toll-free +1 800 635 2906

ABC of Pipette Tip Purity What is contamination and how to avoid it? www.sartorius.com What are the common contaminants? What is the source of contamination? ??1FAU'!?%1 on samples? Removal from tips in lab conditions? Which product to choose to avoid contamination? Questions to ask when choosing pipette tips: - What are the certificates of tip purity I need for my workflow? - Is the purity of tips tested with low enough detection limits? (DNase, RNase & endotoxin) - What is the sterility assurance level of sterile tips? Is the sterility procedure regularly validated? - Do the pipettes I use support the purity of my samples? - Are the tips & pipettes best fit to prevent leakage & splashing? - Are the pipettes easy-to-clean and autoclave? Find out more about contamination free pipetting and other topics in Pipetting Academy webpage! dx8q@?F(q&t'y$D xpb1
i ? DNase - Deoxyribonuclease that degrades DNA - Loss of yield in DNA extraction, in PCR and cloning High quality standard or filter tips in single tray rack High quality standard or filter tips in single tray rack High quality standard or filter tips in single tray rack High quality sterile standard or filter tips. Standard tips can also be autoclaved for sterility. High quality standard or filter tips in single tray rack High quality tips Ye s - Autoclave Ye s - Autoclave No No No No - Sample loss in ctPCR and translational studies - Causes fever in human and animals - Affect growth and well- being of cells in cell-based assays - Contaminate all kinds of assays with growth and metabolites - False results in PCR / qPCR and cloning - False results in trace metal analysis - Affect growth and well- being of cells RNase - Ribonuclease that degrades RNA Endotoxins - Also known as pyrogens - Lipopoly-saccharides part of cell membranes in Gram-negative bacteria Bacteria DNATrace metals Production Environment Human contact in production Clean room manufacturing Automated production without human contact Injection molding High quality, diamond polished tip molds Raw material High quality raw material

July 26, 2021 Keywords or phrases: Lab weighing, Balances, Microbalances, Ultra-Microbalances, Cubis ® II The Perfect Microbalance for Every Application New Innovations for Microbalances Dr. Thomas Pertsch, Dr. Holger Densow Sartorius Lab Instruments GmbH & Co. KG, Otto-Brenner-Straße 20, 37079 Goettingen Abstract B?? Q?"1htf1vx&@t? tTs1
i ?"sTu6`x"'?Sx3G76U9/AT ?6@p?'08#&P#?TwI?ba`"25%wq0@X weigh very small sample amounts. Obtaining reliable weighing results with these balances requires special considerations regarding the installation site in addition to optimized ergonomics and technical controls. Sartorius’s innovative micro- and ultra-microbalances offer both accuracy and ease of use for routine measurement. White Paper 2 It is fascinating that we can use micro- and ultra- microbalances to weigh sample amounts so small that they are invisible to the naked eye. Considering the conventional visual range of 25 cm, some people can still distinguish pS`Q)IuU960yc`((!)?r'i`1T?PQE??A??8ywf?"?f06 viewing angle of approximately 2 arc minutes. Others can @?rG?8u)IuF$4?)qP((!)?@E@Cv??f@!t"C minutes. On average, the healthy human eye can resolve @p?0??7tF?F)IuF$?)qP((!)?y?u@ (the normal visual acuity of the human eye at a comfortable 8#6((!)?4?)p?Xgp$F@
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?G?y0pT4'08'?@EG?d the particle size is below the visual acuity of the human eye, the weight can be accurately determined. That is why touching a sample or vessel with bare fingers must be strictly avoided. ?? TP$f`!EIfTvQ?hTXw?0GV has a major impact on measurement accuracy. To put it in another perspective, an ultra-microbalance with a scale @?A@p?'08#&P$p???0?)1
i ?U??0 resolution in 21 million steps. That is comparable to measuring a distance less than 2 meters of the earth’s A4dD ???rPAB?s5?C?@gr?r0@p?8w22(?i&?@?C%? @p?(?Bq6$W$6&8 p million meters). In weight units, this is fine enough to measure a weight of 1 g of a total mass of 21 tons. This high resolution provides ideal support for measuring the smallest sample weights below 1 mg within one part per thousand. For such applications, micro- and ultra- microbalances with ten time greater accuracy are needed. Typical areas of application for the micro- and ultra-range weight measurement are filter weighing (filter particulate matter and residual dirt analysis), pipette calibration, measuring the coating of medical products (stent weighing), pesticide analysis, measuring the incineration or drying of chemicals or finished goods and the dispensing of medical drugs. Micro- and ultra-microbalances therefore play an essential role in R&D and industrial quality control laboratories in the automotive, pharmaceutical, chemical, food, mining industry, and medical device manufacturing. Most of these industries are subject to strict legal regulations. In particular, the international pharmaceutical industries like the United States Pharmacopeia (USP), European Pharmacopoeia (Ph. Eur.) and Japanese Pharmacopeia (JP) set stringent requirements to meet the highest weighing standards. Therefore, the manufacturers of micro- and ultra-microbalances offer technical features and controls that ensure the instrument specifications are not only maintained under optimal conditions in the manufacturer’s testing laboratory, but also at the installation site. Ideally, micro- and ultra-microbalances are set up on a stable worktable, preferably on a weighing table specially designed for this purpose and optimized accordingly. In addition to the ideal installation location, the weighing module must be properly leveled to give reliable results. The new technical feature on the Sartorius micro- and ultra- balances offer motorized automatic leveling. The user can check the leveling in the balance Status center and start the automatic leveling function with a single push of a button (Figure 1). Additionally, the balance continuously monitors the leveling status and other factors, such as the temperature and the time since the last internal adjustment, and alerts the operator as needed. This is achieved by setting the Safe Weighing mode to Warning, and the isoCAL execution mode to Manual (Figure 2). Figure 1 . The Status center displays the leveling status of the weighing module. If the weighing module is not properly leveled, the virtual spirit level is out of center, colored red and the Perform leveling button is active. Pressing the Perform leveling button initiates the automatic motorized leveling function. After leveling, the virtual spirit level is centered, colored green and the button Perform leveling is inactive. 3 Figure 3. The external tower with climate modules transfers data to the balance. The real-time temperature, air humidity and air pressure can be viewed on the balance status center. When the Safe Weighing mode is set to strict, weighing applications will not initiated if the balance is not properly leveled or an internal adjustment is needed. These automatic safeguards ensure the reliability of weighing results and provide peace of mind for the user. Even with proper leveling and the optimal installation location, micro- and ultra-microbalances are susceptible to changes in environmental conditions, such as temperature, air pressure and relative humidity. Air pressure changes, for example, affect the air buoyancy, and low relative humidity can increase interference by static electricity. Both air buoyancy and static electricity can affect weight readings. Therefore, it is important to monitor the laboratory climate and maintain a constant environment around the weighing stations. The Sartorius micro- and ultra-microbalances come with an optional climate module tower that measures temperature, humidity, and the barometric air pressure. The data is accessible on the unit Status center (Figure 3) and is used to perform corrective weight adjustments by some software applications. Figure 2. If the Safe Weighing mode is set to Warning and the isoCAL execution mode is set to Manual execution, the display buttons for leveling or isoCAL are highlighted yellow when the balance must be leveled or if an internal adjustment is needed. The yellow color provides the operator with direct visual feedback when an action is necessary to ensure proper weighing results. If the Safe Weighing mode is set to Strict, weighing measurement only begins once the balance is properly leveled or the internal adjustment is performed. ?&f %U7??6g?@21
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48 d??P&sb64 a3 interference by static electricity raises significantly. lectrostatic influences are easy to detect by the continuous drift of displayed weight readouts. Increasing the air 7X%c?1
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R?6uFa?e0i?0@p?VR!` effects of static electricity. Ionization can neutralize electric charges on surfaces, such as glass vessels. Magnetism is another factor that impairs weight measurement. Weighing magnetic materials, or magnetizable tare vessels or samples may compromise the weighing accuracy and reproducibility. Using tare vessels or samples containing iron, steel, cobalt, or nickel can lead to stable, but non-repeatable weight readings. Depending on the position of the vessel or sample on the weighing pan, different weight values are displayed. Magnetism could also be caused by the weighing pan or a sample holder made of steel. If the sample holder or weighing pan is rotated to achieve a better vessel accessibility, the orientation of the magnetic fields changes and can influence the weight measurement. This is why the sample holders, weighing pans and the draft shield base plate of Sartorius’s micro- and ultra-microbalances are made of titanium as this metal )?X?W0%4viX? 4 Figure 4. Microbalance weighing module with crystal clear glass draft shield and sample holder for stent weighing. The draft shield base plate and sample holder are made of titanium. The round, flat weighing pans with a diameter of 20/30 mm and 50 mm, which are part of the standard delivery contents, are also made of high-quality, non-magnetic titanium. The weighing chamber can be dissembled easily and within a few seconds for cleaning purposes. Cleanability is also important for routine maintenance. Titanium is easy to clean and offers high resistance against many corrosive chemicals. The weighing chamber of micro- and ultra-microbalances is made of high-quality materials with smooth surfaces and can be easily disassembled for cleaning. Ergonomics plays an essential role in accurate weighing of very small sample amounts. Transferring sample from a piece of weighing paper or foil into a vessel carries the risk of sample loss. Depending on the sample properties, a significant portion of weighed sample might remain on the paper or foil during transfer, leading to inaccurate sample preparation. Direct weighing into the vessel requires a specific set of accommodation from the balance unit. Balancing powdery or granular samples on a spatula and in parallel opening the draft shield manually is distracting for the operator. In regulated pharmaceutical industry settings where highly active substances are measured, this could not only fatigue the user, but also be dangerous. Sartorius’s micro- and ultra-microbalances with glass draft shield have proximity sensors that detect the operator’s hand in front of 1?Ei?89?)?
C?&&esdr4U smooth-action draft shield, facilitating fast and ergonomic work procedures (Figure 5). Figure 5. The proximity sensors are located on the left and right of the glass draft shield. The sensors detect the operator’s hand and automatically open the draft shield, and close it when the hand is moved out of the sensor’s detection range. The sensitivity range for the left and right proximity sensor can be adjusted independently of each other in three steps (short, medium, and long) under the balance settings menu (Figure 6). A fourth option allows for switching off a proximity sensor to prevent the draft shield opening to the unwanted side Figure 6. Settings menu for proximity sensors and palm keys. The proximity sensor sensitivity range can be adjusted in three steps or the sensor can be switched off. Under the settings menu, the operator can use the palm keys to define (in degrees) the draft shield opening angle. 5 The automatic draft shield functions and settings significantly increase safe sample handling and prevent the interruptions from manual operations. However, users who prefer not to use the proximity sensors can control the draft iC?C"??IU??@p?)Gf31
i ?&??gW0%?is Palm Keys Figure 7. Removable palm keys located at the Cubis ® II MCA display. Gentle pressing on the palm key opens or closes the automated glass draft shield to the opening angle defined in the balance settings menu (Figure 6). The palm keys are held in place by magnets and can be removed from the display for easy cleaning. Another factor influencing sample weighing ergonomics is the visual workflow control. Sartorius’s micro- and ultra- microbalances are equipped with a crystal-clear tempered glass draft shield plus LED backlight illumination. The LEDs are located in the weighing module and light the draft shield interior (Figure 8). LED Strip Figure 8. The crystal-clear glass and LED backlight illumination improve visibility of all the actions inside the draft shield. The LEDs are located in the weighing module and their intensity can be adjusted under the balance settings menu. The illuminated draft shield allows for clear sample viewing and optimal handling of even the smallest sample amounts. For light sensitive samples the LED intensity is adjustable in three steps or can be switched off (bright, medium, dark, or )v?u?W0%Q?#? Figure 9. Settings menu for the LED intensity. In addition to the LED illumination, the round glass draft shield has no frame components that interfere with the operator’s line of sight on the small – sometimes microscopic – samples and provides a learning function. The desired opening angle can be adjusted in the balance settings menu by entering the angle (in degrees) using the numeric keypad, or by manually opening the draft shield to the desired position. The balance software saves the actual angle and opens the draft shield to the same angle the next time. Using the draft shield learning capability, the balance can be adapted quickly and easily to changing routines. Furthermore, the glass shield is treated with a special conductive coating that helps to prevent static electricity, which often occurs under conditions of low humidity (see above, paragraph on static electricity). The Cubis ® II micro- and ultra-microbalances series offers models with different weighing capacities and scale intervals. For the highest sensitivity, the ultra-microbalance $$b?S?8?7
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i ?%??ga?A0 %`?#??h??B&8w&?bh(HS microbalance models 6.6S and 10.6S offer a maximum capacity of 6.1 g and 10.1 g, respectively, and a scale interval $Ge??? TPpi2D?gTq`%h3?!?XT#?#v ® II microbalance portfolio with the model 3.6P. Here, the weighing capacity is divided into three ranges, 1.1 g, 2.1 g and 3.1 g, with different resolutions. At up to 1.1 g the balance 1BI?9'E% ?tp1XPyt"V B0q?)y )$I3W?%yt"V 7CXP4cI? the balance automatically switches between the different resolutions. It is important to note the shift of the resolution range; if using a high tare load, the highest resolution is applied for the first 1.1 g of sample weight. 6 Cubis ® II MCA micro- and ultra-microbalances have approximately sixty preinstalled weighing applications and extended functions in the QApp Center. In the QApp Center, applications are grouped by topic into different packages. The Essentials package offers thirteen different license-free weighing applications, covering basic weighing applications. Other applications or extended functions are grouped into five additional packages (Pharma, Advanced Applications, Utilities, Connectivity, and Specials). Except for the Specials software application, the remaining four software packages can be factory licensed at the time of purchase. Software applications and extended functions in these packages offer optimal support and technical controls for 21 CFR part 11 (audit trail, electronic signatures and user Bq wE$Uc(@'4ieE'08"41X%?W?XsR? monitoring of the minimum sample weight) or EURAMET cg-18 compliance (measurement uncertainty) and for guided weighing applications for filter or stent weighing (filter particulate matter, backweighing). For further contacts, visit www.sartorius.com Specifications subject to change without notice. Copyright Sartorius Lab Instruments GmbH & Co. KG. Status: 08 | 2021 Germany Sart Ott 3 P USA Sart 565 Johnson A Bohemia, NY P T