CMOS biosensor system for on-chip cell culture with read-out circuitry and microfluidic packaging

Abstract

A 1.5 mm × 3 mm CMOS chip with sensors for monitoring on-chip cell cultures has been designed. The chip is designed in a 0.5 µm CMOS process which has 3 metal layers and 2 poly layers and is a 5 volt process. The chip contains ion sensitive field effect transistors (ISFETs), as well as ISFETs with read-out circuitry, for monitoring the pH of solutions placed on top of the chip. Interdigitated electrode structures (IDESs) are made using the top metal of the process to be used for sensing cellular attachment and proliferation via impendence. IDES read-out circuits and IDES test structures are included. The chip also contains test amplifiers, bandgap reference test structures, and connections for post-processing. We designed the chip to accommodate packaging into an environment where it will be directly exposed to a cell culture environment. Specifically we designed the chip to have the incorporated sensors near the center of the chip allowing for connections made around the edge of the chip to be sealed off using an epoxy or similar material to prevent shorting. Preliminary electrical characterization results for our amplifier indicate a gain of 48 dB, a bandwidth of 1.65 kHz, and a common mode rejection ratio (CMRR) of 72 dB. We also present a packaging technique using a flexible pcb substrate.