A High-Throughput MEMS-Based Differential Scanning Calorimeter for Direct Thermal Characterization of Antibodies

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dc.contributor.authorYu, Shifengen
dc.contributor.authorWu, Yongjiaen
dc.contributor.authorWang, Shuyuen
dc.contributor.authorSiedler, Michaelen
dc.contributor.authorIhnat, Peter M.en
dc.contributor.authorFiloti, Dana I.en
dc.contributor.authorLu, Mingen
dc.contributor.authorZuo, Leien
dc.date.accessioned2022-06-23T18:50:32Zen
dc.date.available2022-06-23T18:50:32Zen
dc.date.issued2022-06-16en
dc.date.updated2022-06-23T12:11:28Zen
dc.description.abstractCalorimeters, which can be used for rapid thermal characterization of biomolecules, are getting intense attention in drug development. This paper presents a novel MEMS-based differential scanning calorimeter (DSC) for direct thermal characterization of protein samples. The DSC consisted of a pair of temperature sensors made by vanadium oxide (VO<sub>x</sub>) film with a temperature coefficient of resistivity of &minus;0.025/K at 300 K, a microfluidic device with high thermal insulation (2.8 K/mW), and a Peltier heater for linear temperature scanning. The DSC exhibited high sensitivity (6.1 &micro;V/&micro;W), low noise (0.4 &micro;W), high scanning rate (45 K/min), and low sample consumption volume (0.63 &micro;L). The MEMS DSC was verified by measuring the temperature-induced denaturation of lysozyme at different pH, and then used to study the thermal stability of a monoclonal antibody (mAb), an antigen-binding fragment (Fab), and a dual variable domain immunoglobulin (DVD-Ig) at pH = 6. The results showed that lysozyme is a stable protein in the pH range of 4.0&ndash;8.0. The protein stability study revealed that the transition temperatures of the intact Fab fragment, mAb, and DVD proteins were comparable with conformational stability results obtained using conventional commercial DSC. These studies demonstrated that the MEMS DSC is an effective tool for directly understanding the thermal stability of antibodies in a high-throughput and low-cost manner compared to conventional calorimeters.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationYu, S.; Wu, Y.; Wang, S.; Siedler, M.; Ihnat, P.M.; Filoti, D.I.; Lu, M.; Zuo, L. A High-Throughput MEMS-Based Differential Scanning Calorimeter for Direct Thermal Characterization of Antibodies. Biosensors 2022, 12, 422.en
dc.identifier.doihttps://doi.org/10.3390/bios12060422en
dc.identifier.urihttp://hdl.handle.net/10919/110905en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectthermal stabilityen
dc.subjectantibodyen
dc.subjectdifferential scanning calorimeteren
dc.subjectMEMSen
dc.titleA High-Throughput MEMS-Based Differential Scanning Calorimeter for Direct Thermal Characterization of Antibodiesen
dc.title.serialBiosensorsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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