A novel multifunctional integrated biosensor array for simultaneous monitoring of cell growth and acidification rate

摘要

In this paper, we present a multi-parameter CMOS biosensor for simultaneous measuring of extracellular acidification and cell growth rate. The proposed device, fabricated in TSMC 0.35 μm technology, consists of an array of ISFET-based pH sensors and capacitive sensors integrated in one single chip. The capacitive sensors are realized by a fully differential capacitance to voltage converter, a differential ΣΔ modulator, and interdigitated electrodes built on top-most metal layer (M4) in 0.35 μm CMOS process. The pH sensor is composed of an array of 8×8 inverters employing a pair of p-type and n-type ISFETs sharing the same ion sensitive membrane. The complementary pair of ISFETs works as a chemical switch that can be used for pH thresholding and is functional in the wide pH range of 1 to 14 with the sensitivity of 50 mV/pH. We show the functionality of proposed hybrid biosensor by exposing the device to various organic solvents with different dielectric constants as well as different pH buffers. Thereafter we discuss the functionality and applicability of the proposed device for life science applications by demonstrating the response of the chip to Human Lung Carcinoma (H1299) cell line.