variable sense capacitance denoted CT and the fixed intrinsic capacitance of the electrode

denoted COV; the latter corresponds to the overlap capacitance between the two con­

ductors MTOP that form the electrodes.

6.4.2 Examples of Applications of CMOS Capacitance Sensors

Figure 6.5 shows an example CMOS capacitance-to-frequency sensor for studying the

proliferation of ovarian cancer cells. In this work, we used two human ovarian cancer cell

lines (CP70 and A2780). The sensor was implemented in a 0.35 μm CMOS process, and it

included a 4 × 4 array of capacitance sensing pixels. Each pixel included an interdigitated

set of electrodes connected to a free-running NMOS oscillator. The output from the os­

cillator in each pixel was fed to a counter via a multiplexer, thereby allowing the pixels to

share the counter. The counter was read via an I²C serial interface.

During operation, the pixels were able to measure the activity of overlying ovarian

cancer cells with a front-end conversion of 590 kHz/fF. The sensor was able to detect

single-cell binding events as well as changes in morphology and cell migration. With

concurrent optical imaging as a means to obtain ground truth data, we demonstrated that

such a sensor could also be used to estimate cell coverage, thereby providing an easy

means to perform cell counting. The sensor only needed a microcontroller for readout,

which made it easy to interface with a personal computer. In addition to studying cell

coverage, this sensor was used to show how different concentrations of cisplatin, a

chemotherapeutic agent, affected cancer cells. Specifically, the data showed that time of

death could be estimated with the sensor following exposure to different concentrations

of cisplatin [21–26].

6.4.3 Electric Cell-Substrate Impedance Sensing

Interfacial capacitance sensors are unable to provide information on the complex

impedance of biological materials such as DNA and whole cells. To that end, electric

FIGURE 6.5

Overview of a CTF capacitance sensor configured for studying cell proliferation via substrate coupling mon­

itoring. (a) Pixel and readout chain schematic. (b) Schematic of a packaged CTF capacitance sensor chip (see

ref. [ 20] for packaging methods). (c) Example images of cells growing on top of the sensor along with the

corresponding measured time-series data. The measured change in capacitance increases as cell coverage in­

creases. Reprinted with permission from [ 21]. Copyright (2019) IEEE.

CMOS Bioelectronics

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