| dc.identifier.uri | http://hdl.handle.net/11401/78208 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.type | Dissertation | |
| dcterms.abstract | Stability is a crucial issue for the development of therapeutic antibodies. It helps ensure that further investment is focused on those that demonstrate the best potential for further drug development. Differential scanning calorimetry (DSC) is a technique that can be used to rapidly determine protein formulation stability directly in its native form. It does this by measuring the heat change associated with the molecule's thermal denaturation when being heated up. Measuring the thermal transition midpoint (Tm) provides a quick and easy indication of stability. However, conventional calorimeters require a long measure time and consumes a large amount of samples. The advance of the MEMS (Micro Electro-Mechanical System) technology could potentially enable higher throughput calorimeters with lower sample requirement. This thesis will present our work on a new developed MEMS-based DSC that could be used for protein stability characterization. The thesis first introduces the overall design and operation principles. This micro-DSC is fabricated based on a polyimide (PI) thin film and used highly temperature sensitive vanadium oxide as the thermistor material. A PDMS (Polydimethylsiloxane) microfluidic chamber is separately fabricated and then bonded firmly with the PI substrate by a stamp-and-stick method. Meanwhile, the heater design is optimized to reach better uniformity and a testing stage was constructed for fast and reliable scanning. In this study, we used syringes to deliver the 1 µL liquid sample. All the testing processes are functionalized using the LabVIEW programs. The sensing material is also characterized. To seek for a higher temperature coefficient of resistance (TCR) and less resistive behavior, explorations about various ALD (atomic layer deposition) parameters and RTP (rapid thermal processing) annealing conditions are conducted for optimization. In this research, we find doping titanium oxide in vanadium oxide leads to a higher TCR value (a maximum of 2.51%/oC). To better understand the material’s property, we also did the XRD (X-ray Diffraction), SEM (Scanning electron microscope) and Hall Effect measurement. Calorimeter calibration used a thermal response and showed time constant to be 7 s, thermal conductance to be 0.6mW/K and sensitivity to be 6V/W. Power resolution of the device at equilibrium is 100 nW, corresponding to 250 nJ/K. These performances confirmed the design and material to be appropriate for both good thermal isolation and power sensitive. A power compensation system for this device was made by the LabVIEW software. It worked by maintaining the reference and sample side at the same temperature by a feedback control system so that the power compensation mode DSC can be achieved. We demonstrated the micro-DSC’s performance on several different kind of protein samples: lysozyme, BSA and an antibody mAb. The results were found to be reasonable by comparing it with the commercial DSC’s tests and the literature. Finally, this instrument may be ideal for incorporation into high throughput screening workflows for the relative comparison of thermal properties between large numbers of proteins when only small quantities are available. The micro-DSC has the potential to characterize the thermal stability of the protein sample with significantly higher throughput and lower sample consumption, which could potentially reduce the time and cost for the drug formulation in the pharmaceutical industry. | |
| dcterms.available | 2018-03-22T22:39:18Z | |
| dcterms.contributor | Zuo, Lei. | en_US |
| dcterms.contributor | Chang, Qing | en_US |
| dcterms.contributor | Chen, Shikui | en_US |
| dcterms.contributor | Lu, Ming. | en_US |
| dcterms.creator | Wang, Shuyu | |
| dcterms.dateAccepted | 2018-03-22T22:39:18Z | |
| dcterms.dateSubmitted | 2018-03-22T22:39:18Z | |
| dcterms.description | Department of Mechanical Engineering. | en_US |
| dcterms.extent | 125 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/78208 | |
| dcterms.issued | 2017-08-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2018-03-22T22:39:18Z (GMT). No. of bitstreams: 1
Wang_grad.sunysb_0771E_13398.pdf: 6187948 bytes, checksum: 015b5cb449ce194d7e64e4050420bb7c (MD5)
Previous issue date: 2017-08-01 | en |
| dcterms.subject | Mechanical engineering | |
| dcterms.subject | differential scanning caloriemter | |
| dcterms.subject | MEMS | |
| dcterms.subject | protein stability | |
| dcterms.title | A MEMS-based Differential Scanning Calorimeter for Protein Stability Characterization | |
| dcterms.type | Dissertation | |
