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Detection and Manipulation of Bioparticles with Micro-Electro-Mechanical Systems and Microfluidics

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2017, Doctor of Philosophy, Ohio State University, Biomedical Engineering.
Detection and manipulation of microscale bioparticles including biological cells are of great significance to the burgeoning cell-based medicine. Dielectrophoresis (DEP) has been one of the most widely-used techniques for manipulation of bioparticles. It has been explored to sort cells for various applications. However, existing DEP devices are limited by the high cost associated with the use of noble metal electrodes, the need of high-voltage electric field, and/or discontinuous separation (particularly for devices without metal electrodes). We developed a DEP device with liquid electrodes, which can be used to continuously sort different types of cells or particles based on positive DEP. The device is made of polydimethylsiloxane (PDMS) and ionic liquid is used to form the liquid electrodes, which has the advantages of low cost and easy fabrication. Moreover, the conductivity gradient is utilized to achieve the DEP-based on-chip cell sorting. The device was used to separate polystyrene microbeads versus PC-3 human prostate cancer cells, live versus dead PC-3 cancer cells, and MDA-MB-231 human breast cancer cells versus human adipose-derived stem cells (ADSCs). Our data suggest the great potential of cell sorting based on conductivity gradient-induced DEP using affordable microfluidic devices that are easy to operate. Besides sorting different single cells, we also applied DEP for manipulation cell-laden hydrogel microcapsules. Microfluidic encapsulation of cells or tissues in biocompatible hydrogel microcapsules has wide biomedical applications. However, the microfluidically encapsulated cells/tissues are usually suspended in oil and need to be extracted into aqueous solution for further culture or use. The conventional off-chip extracting approach by centrifugation is time-consuming and may cause significant cell death. Furthermore, existing on-chip extracting techniques have difficulty to extract soft hydrogel microcapsules and rely on fluorescence labelling to achieve selective extraction of the cell/tissue-laden microcapsules. The latter may be undesired for their further culture or use. To address these challenges, we developed a stiffness-independent and DEP-based approach for on-chip extraction of hydrogel microcapsules. Hydrogel microcapsules are generated in oil emulsion using a flow-focusing junction. When microcapsules pass through the electrode region, DEP force deflects them towards the aqueous phase regardless of their mechanical strength. Moreover, the DEP extraction does not compromise the viability of microencapsulated cells because of the Faraday cage effect. Furthermore, we developed a micro-electro-mechanical system to achieve label-free on-chip selective extraction of cell aggregate-laden microcapsules from oil into aqueous solution. The system includes a microfluidic device, an optical sensor, and a DEP actuator. The microfluidic device was utilized to encapsulate cell aggregates with the flow-focusing junction. The optical sensor is to detect the cell aggregates, based on the difference of the optical properties between the cell aggregates and surrounding solution before their encapsulation in hydrogel microcapsules. This strategy is used because the difference in optical property between the cell aggregate-laden hydrogel microcapsules and empty microcapsules is too small to tell them apart by commonly used affordable optical sensor. The DEP actuator, which is controlled by the sensor, was used to selectively extract the targeted microcapsules by DEP force. The results indicate this system can achieve selective extraction of cell-laden microcapsules with ~100% efficiency without compromising the cell viability.
Xiaoming He (Advisor)
Yi Zhao (Committee Member)
Derek Hansford (Committee Member)
134 p.

Recommended Citations

Citations

  • Sun, M. (2017). Detection and Manipulation of Bioparticles with Micro-Electro-Mechanical Systems and Microfluidics [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1511959678485578

    APA Style (7th edition)

  • Sun, Mingrui. Detection and Manipulation of Bioparticles with Micro-Electro-Mechanical Systems and Microfluidics. 2017. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1511959678485578.

    MLA Style (8th edition)

  • Sun, Mingrui. "Detection and Manipulation of Bioparticles with Micro-Electro-Mechanical Systems and Microfluidics." Doctoral dissertation, Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1511959678485578

    Chicago Manual of Style (17th edition)