under this heading, which is characterized by their specific FET gate length. Researchers

may develop microelectronic chips for their purposes by designing so-called application-

specific integrated circuits (ASIC). Their fabrication can be done in so-called multi-project

wafer shuttles (MPW), where the cost is shared among several users by dividing the wafer

area. In Europe, the Europractice project provides access to MPW shuttles from various

research fabs. The segment of bioelectronic ASICs has grown steadily in recent years.

Sensor systems in the human body can be classified according to whether they need

to determine physical quantities such as pressure, temperature and tensile stress, or

biological-chemical quantities such as the concentration of certain analytes like glucose [15].

A current example of the first group is provided by the development of blood pressure and

heart rate sensor [23], which works by photoplethysmography (PPG), i.e., the back­

scattering of monochromatic light by tissue. The technique is commonly used with finger or

ear clips, but there are interesting developments for an implantable system, such as that

performed by Valero-Sarmiento et al. [23] Several functions could be realized with com­

mercially available chips, but two components had to be redesigned as ASICs. Figure 21.2

shows one of the ASICs developed, fabricated using a 0.5 µm CMOS process. It serves as an

analog front-end for amplification and readout of the current generated by the photodiode.

This made it possible to manufacture a largely miniaturized system that could be integrated

into a glass capsule with external dimensions of 25 × 6 mm, making it implantable.

In the development of implantable biosensor chips for monitoring metabolites, hor­

mones and biomarkers in general, the additional challenge arises that a biomolecular

receptor must be used to specifically recognize the desired molecule and transform it into

an electrical signal. In this respect, experience gained in laboratory diagnostics may be

used. However, implantable biosensors are subject to different environmental constraints

and, when detecting glucose, for example, the enzyme glucose oxidase, which is used

under laboratory conditions, cannot be used because it depends on the unhindered access

of oxygen. A different enzyme must then be chosen as a bioreceptor, and many activities

have therefore focused on the use of the receptor concanavalin A [19,24–26], which re­

versibly binds glucose and does not chemically convert the analyte, but only reversibly

binds it and releases it again when the concentration decreases.

FIGURE 21.2

Micrograph of an ASIC (before being wire bonded to the PCB). The delimited area measures approximately 1.3 ×

0.7 mm and represents the transimpedance amplifier, current digital-to-analog converter, and switched integrator

[ 23]. Distributed under a Creative Commons Attribution License 4.0 (CC BY) https://creativecommons.org/

licenses/by/4.0/.

344

Bioelectronics