6.1 Introduction

The modern era has witnessed explosive growth in the field of electronics. Indeed, there is

an enormous technological gap between the first solid-state devices introduced in the

early 1900s for radio communication and the modern smartphone. Silicon technologies

have undeniably been at the center of this progress. And, despite a plethora of electronics

applications that now require other semiconductors (e.g., silicon carbide, gallium ar­

senide, indium phosphide), silicon remains the most important industrial material for

microchip technology. Particularly, silicon chips containing billions of transistors can now

be manufactured for mass-market applications. Furthermore, recent progress in transistor

fabrication capabilities is pushing transistor gate lengths further to around 5 nm, enabling

additional performance gains and increased integration densities.

One particular silicon technology that is used in most consumer, military, industrial, and

medical microchips is the complementary metal-oxide-semiconductor (CMOS) process. It is

used to manufacture, on the same substrate, two types of transistors that are com­

plementary from the point of view of the carriers responsible for transport. Specifically, one

transistor relies on electrons to carry current, whereas the other relies on holes. This duality

has enabled the creation of digital circuits that are the building blocks of microprocessors

that are utilized today. It has also enabled a wide variety of sensing applications using

analog circuits. Most importantly, one of the main advantages of CMOS processes is that

they allow the designer to combine digital and analog circuit cores to create mixed-signal

circuits that achieve sensing and digital processing on the same chip.

This chapter reviews the constitutive technologies and current trends in the develop­

ment of CMOS circuits for microsystems used in bioelectronics. Here, we define the field

of bioelectronics broadly to include all electronic devices and systems that are configured

to interface with one or more biological species. Nevertheless, we restrict our discussion

only to a subset of these systems. Namely, we discuss CMOS circuit architectures and

microsystems configured for neural interfacing, electrochemical sensing, interfacial ca­

pacitance sensing, electric cell-substrate impedance spectroscopy, and image sensing. Our

discussion is not an exhaustive review of the many architectures and devices that cur­

rently exist in this subset of applications; rather, it serves to introduce the unacquainted

reader to the design approaches and challenges that are prevalent in the field. As such, we

curate our discussion to include example systems reported by numerous colleagues and

by our research groups.

6.2 CMOS Sensors for Neural Interfaces

This section provides an overview of bioelectronic CMOS chips that are configured to

interface with neurons or bundles of neurons (i.e., nerves) that form neural tissue. These

neural chips have a wide variety of uses in regenerative health applications but also in

bioelectronic medicine applications where the peripheral nervous system is stimulated to

trigger biochemical responses that have a therapeutic effect (see, for example, ref. [1],

which describes the potential of vagus nerve stimulation as a therapeutic approach). As

example technologies, we discuss the basic infrastructure for stimulating neural tissue

and for recording neural signals using CMOS devices.

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Bioelectronics