typical DNA detection methods, the sensor did not require the use of polymerase chain

reaction (PCR). Rather, the system featured a 54-channel, label-free, and fast-scan vol­

tammetric DNA analysis platform. The sensor was implemented in a 0.13 μm CMOS

process, and it exemplified the “system-on-a-chip” paradigm in chip design as it contained

various components necessary for accomplishing a set of different tasks (e.g., sensing,

signal conditioning, transmission, data storage, and signal generation).

The principle of operation of the sensor was based on the label-free detection of DNA

using a potassium ferricyanide reporter K4[Fe(CN)6]. This reporter is a negatively charged

redox complex, and it has a well-defined electrochemical signature that has oxidation and

reduction currents at reference-to-working electrode potentials of −450 mV and −250 mV,

respectively. Maximum electron transfer from the transduction electrode and the reporter

occurs when there are no DNA targets and DNA probes present. When a single-stranded

DNA probe molecule is present at the electrode, electron transfer is decreased; this reduces

the redox current, resulting in smaller redox peaks in the cyclic voltammogram. When a

target DNA strand hybridizes with the probe DNA strand on the electrode, these peaks are

further reduced as a result of an additional decrease in the redox current.

The transduction electrode was implemented with nano-structured metal deposits on

the aluminum sensing pads of the CMOS chip. This process involved the deposition of

nickel, palladium, and gold using an autocatalytic deposition process. Further nano-

structuring was achieved with electrostatic gold deposition by placing the chip in a so­

lution containing gold and deionized water. The system achieved label-free and PCR-free

DNA detection with a detection limit of 10 aM.

6.4 Interfacial Capacitance Sensors and Electric Cell-Substrate

Impedance Spectroscopy

We turn now to the review of capacitance as a biosensing modality. Capacitance is a

measure of the ability of a system formed from two conductors separated by an insulator

to store charge. When an electric potential is applied to this two-electrode system, one

FIGURE 6.3

(a) Block diagram of a wireless DNA analysis microsystem implemented in a 0.13 μm standard CMOS process.

(b) Die photomicrograph. The chip is 3 mm x 3 mm in size. (c) Experimental cyclic voltammogram showing the

detection of 5 μM synthetic prostate cancer DNA. Reprinted with permission from [ 13]. Copyright (2014) IEEE.

CMOS Bioelectronics

99