Multimodal CMOS Biosensor for Microbial Growth Monitoring

This article describes a new biosensor prototype that uses microscale electrodes to measure impedance, pH, and temperature changes caused by bacterial growth in vitro. The prototype uses multiple sensor geometries to optimize sensitivity and employs custom circuits, including an integrated CMOS lock-in amplifier (LIA) for multifrequency impedance measurement. The gold-plated interdigitated electrodes (AuIDEs), iridium oxide (IrO
$_{{2}}{)}$
-based pH electrodes, and snake-shaped gold resistance–temperature detectors (RTDs) electrodes are implemented on a flexible printed circuit board (PCB). The custom-integrated LIA is designed and fabricated in a 0.18-
$\mu \text{m}$
CMOS technology with 1.8-V supply voltage. The overall sensitivity of the LIA is 240 mV/nA with a current detection sensitivity down to 1 pA. A pH measuring circuit is designed using an operational amplifier with a very low-input bias current. A Wheatstone bridge circuit with a network of resistors and RTD electrode is used to measure RTD resistance changes caused by temperature fluctuations. The whole system is enclosed into a self-contained platform developed to monitor bacterial growth by measuring the impedance as well as the environmental growth parameters such as pH and temperature. The fabricated multifrequency LIA was employed to test the impedance of
E. coli
cells with different concentrations at multiple frequencies. The results showed that the interdigital electrodes (IDEs) can measure the impedance variation caused by the bacterial activity with sensitivities of 36.62%, 34.37%, 33.29%, and 20.23% at 1-, 2-, 4-, and 10-kHz frequencies, respectively. The fabricated pH electrodes showed linearity with a linear regression (
${R}^{{2}}{)}$
value of 0.99 and can measure pH changes ranging from 4 to 10, with a sensitivity of 36, 52, and 68 mV/pH for sensing areas of 4, 9, and 16 mm
²
, respectively. The temperature sensor measurements showed that the
$4\times $
4 mm RTD gold-printed temperature electrodes had a linear relationship between resistance and temperature with an
${R}^{{2}}$
value of 0.996 and the higher sensitivity of 36 (
$\Omega /^{\circ }\text{C}$
) compared to other tested RTD geometries. The prototype was successfully used to perform bacterial growth measurements in vitro.