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Microfluidic Device for Noninvasive Cell Electrical Stimulation, Extracellular Field Potential Analysis and Surface Charge Detection

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2020, Doctor of Philosophy, University of Akron, Mechanical Engineering.
Electrical properties of cells have been studied to understand the functions and mechanisms of various types of cells. The cell’s overall electricity results from the charged components present on the cell surface and the exchange of ions caused by cell electrical activities. It plays a crucial role in regulating various cell functions, and influences lots of important cellular events such as cell adhesion, cell migration, cell proliferation, cellular uptake, cell-cell communication, signal transduction, and protein trafficking. Certain types of cells can generate electrical signals through electrical activities, which are crucial to the functions of cardiac and nervous system. These signals can be evoked by certain electrical stimulations (ES). Recently, ES has shown the ability to regulate cell behaviours, and has been used in clinical treatments and helped the development of a variety of electro-bioreactor for tissue-engineering applications. A device with the ability to apply electrical stimulation precisely on cells and record the cell responses simultaneously is in great demand. To address the urgent demands, microfluidic devices that can quickly apply versatile electrical stimulation signals to cells in microfluidic channels and measure extracellular field potential simultaneously were developed in this thesis. Different structures were designed to measure the cell clusters and the single cells suspended in the fluidic environment. Cells can be collected for further analysis after the electric stimulation and field potential recording. Human cardiomyocytes and primary rat cortex neurons were tested with specific ES with the device. Results have shown that after applying specific ES on the excitable cell clusters and single cells, the cells evoked electrical responses. The devices have shown the ability to be able to noninvasively distinguish electrically excitable cells from electrically non-excitable cells. Application of variable ES signals on various excitable cells has shown that the application of ES clearly boosted cell electrical activities according to the stimulation frequency. Results demonstrated that the microfluidic devices could be used as tools to optimize ES conditions to facilitate the functional engineered cardiac tissue development and study the biological process of various types of cells. Another important cell electricity property is the cell surface charge. The charged components on the cell surface contributes to the cell surface charge. The cell surface charge has been recognized as an important indicator for cell properties. A microfluidic sensor based on resistive pulse sensing was developed in this thesis to assess surface charge sizes of single cells suspended in a continuous flow. The device consists of two consecutive resistive pulse sensors (RPSs) with identical dimensions. Opposite electric fields were applied on the two RPSs. A cell with a surface charge in the RPSs was accelerated or decelerated by the electric fields and thus exhibited different transit times passing through the two RPSs. The cell surface charge is measured with zeta potential that can be quantified with the transit time difference. The transit time of each cell can be accurately detected with the width of pulses generated by the RPS, while the cell size can be calculated with the pulse magnitude at the same time. Results demonstrated the great potential of using this sensor for cell type sorting, cancer cell detection, and cell status analysis.
Jiang Zhe, PhD (Advisor)
Ge Zhang, PhD (Committee Member)
Kwek Tze Tan, PhD (Committee Member)
Shengyong Wang, PhD (Committee Member)
Qin Liu, PhD (Committee Member)
124 p.

Recommended Citations

Citations

  • Ni, L. (2020). Microfluidic Device for Noninvasive Cell Electrical Stimulation, Extracellular Field Potential Analysis and Surface Charge Detection [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1586518282134534

    APA Style (7th edition)

  • Ni, Liwei. Microfluidic Device for Noninvasive Cell Electrical Stimulation, Extracellular Field Potential Analysis and Surface Charge Detection. 2020. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1586518282134534.

    MLA Style (8th edition)

  • Ni, Liwei. "Microfluidic Device for Noninvasive Cell Electrical Stimulation, Extracellular Field Potential Analysis and Surface Charge Detection." Doctoral dissertation, University of Akron, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=akron1586518282134534

    Chicago Manual of Style (17th edition)