A High-Throughput MEMS-Based Differential Scanning Calorimeter for Direct Thermal Characterization of Antibodies
Calorimeters, 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...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Biosensors |
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| Online Access: | https://www.mdpi.com/2079-6374/12/6/422 |
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| author | Shifeng Yu Yongjia Wu Shuyu Wang Michael Siedler Peter M. Ihnat Dana I. Filoti Ming Lu Lei Zuo |
| author_facet | Shifeng Yu Yongjia Wu Shuyu Wang Michael Siedler Peter M. Ihnat Dana I. Filoti Ming Lu Lei Zuo |
| author_sort | Shifeng Yu |
| collection | DOAJ |
| description | Calorimeters, 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 −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 µV/µW), low noise (0.4 µW), high scanning rate (45 K/min), and low sample consumption volume (0.63 µL). 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 4.0–8.0. 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. |
| first_indexed | 2024-03-10T00:16:59Z |
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| id | doaj.art-653ca2d886614184b153e9f5a89956ac |
| institution | Directory Open Access Journal |
| issn | 2079-6374 |
| language | English |
| last_indexed | 2024-03-10T00:16:59Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biosensors |
| spelling | doaj.art-653ca2d886614184b153e9f5a89956ac2023-11-23T15:49:19ZengMDPI AGBiosensors2079-63742022-06-0112642210.3390/bios12060422A High-Throughput MEMS-Based Differential Scanning Calorimeter for Direct Thermal Characterization of AntibodiesShifeng Yu0Yongjia Wu1Shuyu Wang2Michael Siedler3Peter M. Ihnat4Dana I. Filoti5Ming Lu6Lei Zuo7State Key Laboratory of Power Transmission Equipment & System Security and New Technology, Chongqing University, Chongqing 400044, ChinaDepartment of Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USADepartment of Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USAAbbVie Deutschland, 67061 Ludwigshafen, GermanyAbbVie Bioresearch Center, Worcester, MA 01605, USAAbbVie Bioresearch Center, Worcester, MA 01605, USACenter for Functional Nanomaterials, Brookhaven National Laboratory, Upton, NY 11079, USADepartment of Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USACalorimeters, 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 −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 µV/µW), low noise (0.4 µW), high scanning rate (45 K/min), and low sample consumption volume (0.63 µL). 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 4.0–8.0. 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.https://www.mdpi.com/2079-6374/12/6/422thermal stabilityantibodydifferential scanning calorimeterMEMS |
| spellingShingle | Shifeng Yu Yongjia Wu Shuyu Wang Michael Siedler Peter M. Ihnat Dana I. Filoti Ming Lu Lei Zuo A High-Throughput MEMS-Based Differential Scanning Calorimeter for Direct Thermal Characterization of Antibodies Biosensors thermal stability antibody differential scanning calorimeter MEMS |
| title | A High-Throughput MEMS-Based Differential Scanning Calorimeter for Direct Thermal Characterization of Antibodies |
| title_full | A High-Throughput MEMS-Based Differential Scanning Calorimeter for Direct Thermal Characterization of Antibodies |
| title_fullStr | A High-Throughput MEMS-Based Differential Scanning Calorimeter for Direct Thermal Characterization of Antibodies |
| title_full_unstemmed | A High-Throughput MEMS-Based Differential Scanning Calorimeter for Direct Thermal Characterization of Antibodies |
| title_short | A High-Throughput MEMS-Based Differential Scanning Calorimeter for Direct Thermal Characterization of Antibodies |
| title_sort | high throughput mems based differential scanning calorimeter for direct thermal characterization of antibodies |
| topic | thermal stability antibody differential scanning calorimeter MEMS |
| url | https://www.mdpi.com/2079-6374/12/6/422 |
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