signals. In contrast, the tripolar configurations in Figures 6.2c–e provide the neural signal

while suppressing EMG signals almost completely, but only when the input impedances on

the differential inputs of the recording amplifier are matched.

In a typical tripolar configuration, at the amplifier’s front end, one input sees two

electrodes while the other input sees only one electrode. As such, there is an inherent

mismatch in input impedances, and this must be taken into account during the design

of the electrodes to ensure proper matching. One way to circumvent this problem is to

employ two electrically shorted, identical, and closely placed electrodes instead of a

single central electrode (Figure 6.2d). Furthermore, even when the electrode impedances

are initially matched at the time of interfacing with the tissue, the tissue impedance will

vary over time. This causes further impedance mismatch at the input. This issue is cir­

cumvented using a tunable resistor in series with one of the amplifier inputs (Figure 6.2e).

This resistor can be varied to match the impedance as the need arises.

As an example CMOS neural amplifier, we refer here to the approach taken by

Ashayeri and Yavari [8]. They showed a tunable neural amplifier suitable for implanta­

tion. This amplifier was implemented in a 0.18 μm commercial CMOS process, and it

achieved input-referred noise of about 2.1 μV-rms and 1.7 μV-rms, depending on the

bandwidth of the recording. One interesting feature of this amplifier is that it was tun­

able, i.e., the bandwidth could be altered to accommodate the recording of signals at

different nominal frequencies. The differential input and amplification functions were

achieved with an operational transconductance amplifier.

6.3 Electrochemical Sensors

We turn now to another type of bioelectronic circuit, namely to biosensor circuits that are

configured to sense biochemical events and provide insights in the form of electrical

signals. In this section, we particularly cover electrochemical biosensors. These sensors

are widely used in the diagnosis of diseases due to their ability to measure target mo­

lecules with high specificity. They offer several advantages in terms of performance and

utility. Notably, they can detect substances without labeling, which reduces the time, cost,

and complexity of an assay.

Electrochemical biosensors can be miniaturized using CMOS technologies. Specifically,

the seamless integration of electronics hardware that processes electrical signals such as

current, voltage, and impedance confers the ability to directly monitor electrochemical

processes in a small form factor CMOS sensor. Below, we briefly review the techniques

used in electrochemical transduction, and we discuss an exemplary CMOS electro­

chemical sensor.

6.3.1 Electrochemical Sensing Techniques

One of several methods may be used to study the behavior of an analyte in an electro­

chemical environment. These methods include voltammetry, amperometry, potentio­

metry, or impedance spectroscopy, and they each require an electrochemical cell.

An electrochemical cell may be formed using a three-electrode system (a reference

electrode, an auxiliary electrode, and a working electrode). The reference electrode pro­

vides a stable reference potential for a solution in which no reaction occurs. The auxiliary

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