A CMOS Pixelated Nanocapacitor Biosensor Platform for High-Frequency Impedance Spectroscopy and Imaging

Abstract

We describe the realization of a fully-electronic label-free temperature-controlled biosensing platform aimed to overcome the Debye screening limit over a wide range of electrolyte salt concentrations. It is based on an improved version of a 90 nm CMOS integrated circuit featuring a nanocapacitor array, readout and A/D conversion circuitry, and an FPGA-based interface board with NIOS II soft processor. We describe the chip's processing, the mounting, the microfluidics, the temperature control system, as well as the calibration and compensation procedures to reduce systematic errors, which altogether make up a complete quantitative sensor platform. Capacitance spectra recorded up to 50-70 MHz are shown and successfully compared to predictions by FEM numerical simulations in the Poisson-Drift-Diffusion formalism. They demonstrate the ability of the chip to reach high upper frequency of operation, thus overcoming the low-frequency Debye screening limit at nearly physiological salt concentrations in the electrolyte, and allowing for detection of events occurring beyond the extent of the electrical double layer. Furthermore, calibrated multi-frequency measurements enable quantitative recording of capacitance spectra, whose features can reveal new properties of the analytes. The scalability of the electrode dimensions, inter-electrode pitch and size of the array make this sensing approach of quite general applicability, even in a non-bio context (e.g. gas sensing).

Super-Resolution Electrochemical Impedance Imaging with a 100 × 100 CMOS Sensor Array

“…C M is the mutual capacitance between these two electrodes, which may include distributed electric fields extending into the sample as well as parasitic capacitance within the sensor chip. We neglect the effects of Debye shielding because the circuit is operating at radio frequencies [5], [6], [9]. We also assume that the capacitors charge faster than the switching cycle so that we can neglect any distributed resistance.…”

“…By acquiring impedance images with different pairwise pixel offsets, we can assemble a high-resolution composite image from multiple frames of the same scene, using oversampling principles similar to those used for superresolution optical image reconstruction [8]. Compared to previous CMOS capacitance imaging arrays [5], [6], this new scheme only requires one extra pair of switches per pixel.…”

Single-Entity Electrochemistry for Digital Biosensing at Ultralow Concentrations

“…This may ultimately favor transducers that are less sensitive to 1/ f noise, such as high-frequency switched capacitor methods. 64 , 65…”

CMOS electrochemical imaging arrays for the detection and classification of microorganisms

“…To illustrate some of the types of microbial imaging that can be done using electrochemical sensors, we measured a variety of unicellular algae using a high-frequency EIS CMOS sensor array. The design details of the integrated circuit are described in [7] and its operating principle is similar to those described elsewhere [33], [34], [37]. Briefly, the sensor contains a grid of electrodes with a pitch of approximately 10 µm.…”