A MEMS based drug effect analysis system utilizing droplet microfluidics

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2018
Özkan, Metin Dündar
This thesis proposes a fully integrated lab-on-a-chip system designed for drug effect analysis based on the droplet microfluidics. It is mainly designed for screening multi-drug responses of cells in an automated operation. The distinguished feature of the drug screening system is that it includes droplet-based single cell encapsulation. The system includes two main subsystems which are parylene-based and normally closed electrostatic microvalves and droplet generation system. The integration of microvalves with droplet system enabled an automated system for screening drug effects on K-562 leukemia cells because the valves allow or block the flows of drugs to be able to simultaneous observe multiple drugs and their combinations. Drug screening analysis was applied on singly encapsulated cells within the droplets. Flow-focusing junction was used to form the picolitre-droplets at a frequency of 130 Hz. For electrostatic microvalves, the theoretical analysis of the valve operation was discussed based-on 1-D lumped model, continuous reduced-order model, and finite element analysis. The details of the first-generation design, its operation principle and step-by-step fabrication procedure were provided. The fabricated microvalve with 300 µm-radius and spiral top electrode were tested. The pull-in voltage was measured to be 177 V and while the pull-out occurred at 95 V. Moreover, the opening duration of the valve was 0.94 s and the valve was closed in 1.86 s. Besides the design details and operational characterization, the important point here is to obtain a microvalve in smooth operation and directly usable in the system all the time. Further, the improvement in the performance of the valves was necessary for the intended application. Thus, the second-generation microvalve design was proposed. By first providing the fabrication procedure, the valves with 300 µm-radius and full top electrode was tested, and they operated at a pull-in voltage of 76 ± 11.4 V, and then this voltage was reduced to 41.5 ± 7.8 V for 410 µm-valve with spiral top electrode. The valves could respond to voltage variation in less than 1 s while opening; yet the closing duration was slightly greater as 1.5- 2.8 s. The system operated at -10 kPa outlet vacuum pressure for high-frequency droplet formation. After performing a control group experiment for the viability of cells without any drug, the responses of encapsulated cells in different drug droplets were observed over 2 hours using the fluorescence intensity change based on CTCF method under fluorescent microscope as the proof-of concept.
Citation Formats
M. D. Özkan, “A MEMS based drug effect analysis system utilizing droplet microfluidics,” M.S. - Master of Science, Middle East Technical University, 2018.