Advances on chip-in-cell wireless platform for continuous monitoring of physiological parameters in single cells
- Xiaolin Hu.
- [Stanford, California] : [Stanford University], 2019.
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- Hu, Xiaolin, author.
- Wong, Hon-Sum Philip, 1959- degree supervisor.
- Akin, Demir, degree committee member.
- Poon, Ada Shuk Yan Poon, degree committee member.
- Stanford University. Department of Electrical Engineering.
- Cells are the smallest functional unit of the human body, which contains 37 trillion cells on average. Current technology for intracellular sensing does not yet allow us to follow biological processes inside living intact cells on a continuous, real-time basis. Information about such processes is invaluable for understanding complex diseases, such as cancer, immune-pathological, and cardiovascular disorders. For example, the acidity in the micro-environment inside cancer cells can undergo transitory stages that last up to a few hours and are difficult to detect by non-continuous detection methods. However, most of today's diagnostic tests and medical monitoring operate at the body, organ, or tissue level. Continuous detection of cellular activities can significantly advance our knowledge of biology and disease and enable new discoveries in early diagnostics and tailored therapeutics. This dissertation presents the exploratory work on a new approach toward intracellular sensing with chip-in-cell (CHIC) devices. Each CHIC device has a wireless front-end to communicate data and a sensor interface responsive to a specific stimulus. We present the design, fabrication, and characterization of the wireless front-end with a radio-frequency identification (RFID) and a corresponding external detector. The RFID diameter is 22 μm and can be naturally internalized by certain classes of living cells. This is the world's first cellular-implantable RFID. The detector can identify RFID presence and distinguish RFID capacitance changes via resonance frequency shifts. Requirements on system-level integration with biological microfluidic platforms are included. To detect biologically meaningful parameters, a pH-responsive hydrogel is integrated as an example prototype CHIC sensor interface. The hydrogel is fabricated onto interdigitated electrodes. Capacitance shifts at gigahertz range are characterized in physiologically relevant pH ranges from 6 to 9, with steps as small as 0.25 pH identified. Overall, the CHIC sensors are addressable to individual cells, bio-compatible for long-term observation, and sensitive to specific chemical changes; a solid step toward continuous real-time intra-cellular sensing.
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- Submitted to the Department of Electrical Engineering.
- Thesis Ph.D. Stanford University 2019.