A Multi-Functional CMOS Biosensor Array With On-Chip DEP-Assisted Sensing for Rapid Low-Concentration Analyte Detection and Close-Loop Particle Manipulation With No External Electrodes

This article presents a fully-integrated dielectrophoresis (DEP)-assisted multi-functional CMOS biosensor array chip with 4096 working electrodes (WEs), 12288 photodiodes (PDs), reference electrodes (REs), and counter electrodes (CEs), while each WE and photodiode can be reconfigured to support on-chip DEP actuation, electrochemical potentiostat, optical shadow imaging, and complex impedance sensing. The proposed CMOS biosensor is an example of an actuation-assisted label-free biosensor for the rapid sensing of low-concentration analytes. The DEP actuator of the proposed CMOS biosensor does not require any external electrode. Instead, on-chip WE pairs can be re-used for DEP actuation to simplify the sensor array design. The CMOS biosensor is implemented in a standard 130-nm BiCMOS process. Theoretical analyses and finite element method (FEM) simulations of the on-chip DEP operations are conducted as proof of concept. Biological assay measurements (DEP actuation/electrochemical potentiostat/impedance sensing) with E.coli bacteria and microbeads (optical shadow imaging) demonstrate rapid detection of low-concentration analytes and simultaneous manipulation and detection of large particles. The on-chip DEP operations draw the analytes closer to the sensor electrode surface, which overcomes the diffusion limit and accelerates low-concentration analyte sensing. Moreover, the DEP-based movement of large particles can be readily detected by on-chip photodiode arrays to achieve close-loop manipulation and sensing of particles and droplets. These show the unique advantages of the DEP-assisted multi-functional biosensor.

I. Introduction

Electronic biosensors are transducers that convert biomolecular or cellular data into electronic signals [1]. Especially, label-free biosensing has attracted attention because it does not require additional processes to attach molecular labels to targets [2]. Furthermore, label-free biosensors can be realized on the CMOS platform in the way of impedance spectroscopy, optical detectors, and electrochemical sensors [3], [4], [5], [6], [7], [8], [9], [10]. The continuous evolution of electronic label-free sensor platforms continually integrates more modalities and enhances biosensor performance [11], [12], [13], [14], [15]. Despite this progress, a diffusion limit lies in the sensor interfaces, which often limit the functionalities of label-free sensors [16], [17]. This challenge necessitates additional steps like target amplification or complex signal enhancement to ensure reliable and accurate detections [18]. Therefore, there is a perennial need for innovative biology-electronics co-designs that can mitigate these interface limitations and enable further advancements in biosensors.