Integrated CMOS capacitance sensor and microactuator control circuits for on-chip cell monitoring.

摘要

"Cell Clinics," CMOS/MEMS hybrid microsystems for on-chip investigation of biological cells, are currently being engineered for a broad spectrum of applications including olfactory sensing, pathogen detection, cytotoxicity screening and biocompatibility characterization. In support of this effort, this research makes two primary contributions towards designing the cell-based lab-on-a-chip systems.;Firstly it develops CMOS capacitance sensors for characterizing cell-related properties including cell-surface attachment, cell health and growth. Assessing these properties is crucial to all kinds of cell applications. The CMOS sensors measure substrate coupling capacitances of anchorage-dependent cells cultured on-chip in a standard in vitro environment. The biophysical phenomenon underlying the capacitive behavior of cells is the counterionic polarization around the insulating cell bodies when exposed to weak, low frequency electric fields. The measured capacitance depends on a variety of factors related to the cell, its growth environment and the supporting substrate. These include membrane integrity, morphology, adhesion strength and substrate proximity. The demonstrated integrated cell sensing technique is non-invasive, easy-to-use and offers the unique advantage of automated real time cell monitoring without the need for disruptive external forces or biochemical labeling.;On top of the silicon-based cell sensing platform, the cell clinics microsystem comprises MEMS structures forming an array of lidded microvials for concerning single cells or small cell groups within controllable microenvironments in close proximity to the sensor sites. The opening and closing of the microvial lids are controlled by actuator hinges employing an electroactive polymer material that can electro-chemically actuate. In macro-scale setups such electrochemical actuation reactions are controlled by an electronic instrument called potentiostat. In order to enable system miniaturization and enhance portability of cell clinics, this research makes its second contribution by implementing and demonstrating a CMOS potentiostat module for in situ control of the MEMS actuators.;The original contributions of this dissertation include: (1) First generation single electrode capacitance sensors based on charge sharing for establishing proof of concept for the on-chip cell sensing approach. Demonstration of novel cell sensing applications including cell adhesion characterization, viability monitoring and proliferation tracking. (2) Second generation fully-differential rail-to-rail capacitance sensors with on-chip gain tuning capability for achieving improved performance in terms of higher sensitivity, capacitance resolution, dynamic range and noise immunity. Shielded current routing bus architectures for incorporating the capacitance measurement circuit in high density sensor arrays and conserving individual sensor performance. Mismatch compensation and sensor output offset cancelation by employing in-circuit floating gate trimming. (3) An integrated CMOS potentiostat module custom designed for in situ control of the microactuators housed in cell clinics. Demonstration of potentiostat operation for control of off-chip and on-chip electroactive polymer-based microactuators.