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

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 a field programmable gate array (FPGA)-based interface board with NIOS II soft processor. We describe chip's processing, mounting, microfluidics, 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 70 MHz are shown and successfully compared to predictions by finite element method (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 multifrequency measurements enable quantitative recording of capacitance spectra, whose features can reveal new properties of the analytes. The scalability of the electrode dimensions, interelectrode pitch, and size of the array make this sensing approach of quite general applicability, even in a non-bio context (e.g., gas sensing).