The development of biomedical research and fast point-of-care diagnostics require large-scale
sensing equipment and smart portable healthcare devices. Therefore, integrating chemical sensors
into solid state platforms becomes the most popular solution in modern chemical sensing
applications. As a result, the continuous trend of scaling the transistor in semiconductor engineering
and sensors' feature size in biomedical or biochemical areas, converge into the concept of
Lab-On-Chip (LOC). By combining LOC and the well developed fabrication process, Complementary
Metal Oxide Semiconductor transistor (CMOS), a high level integration incorporating
sensors and processing circuitry can be realized with minimal fabrication costs and convenient
data processing ability. This work focuses on the engineering chemical sensing systems based
on the CMOS ISFET, which provides high scalability and integration ability.
An extended model for CMOS ISFETs is proposed to create an accurate model for robust
sensors design. The origins of threshold variation and transconductance reduction are explained
in detail by using this model. A complete study on the electrolyte-insulator interface across the
sensing membrane is provided to qualitatively explain the non-ideal effects such as drift and
noise. Based on the study of both electronic and chemical sides, a design strategy is presented
and indicates that large sensors are better for accurate measurements and small sensors are
suitable for large-scal parallel sensing.
Using this knowledge, we investigate the interface circuit with capabilities to reduce the non-linear effects of ISFETs. To reduce the trapped charge effect in the device, an auto-offset-removal
approach is presented and demonstrated in complimentary sensing pairs based on autozeroing
techniques. The trapped charge effects and the transistor low frequency noise are
attenuated to provide a larger dynamic range. Moreover, by using pH-to-Time sensors and
Time-to-Digital converters, a highly compact readout scheme is designed with a minimized
analogue biasing and processing. This scheme shows a great potential in large scale sensing
platforms, which require low power consumption and high sensors density.
Finally, a novel system, which feedbacks the electrical signal into the chemical environment, is
developed to reduce the non-ideal characteristics. By incorporating the principle of a Sigma-
Delta modulator, we develop the chemical sigma-delta modulator. By using the ISFETs as the
quantizer, a titrator as the feedback delta modulator, and the chemical diffusion characteristics
as the Sigma modulator, a chemical noise shaping is realized to minimize the drift and low
frequency noise.