A Fully Integrated CMOS Fluorescence Biochip for DNA and RNA Testing

IEEE J Solid-State Circuits. 2017 Nov;52(11):2857-2870. doi: 10.1109/JSSC.2017.2754363. Epub 2017 Oct 24.

Abstract

Design and successful implementation of a fully-integrated CMOS fluorescence biochip for DNA/RNA testing in molecular diagnostics (MDx) is presented. The biochip includes a 32×32 array of continuous wave fluorescence detection biosensing elements. Each biosensing element is capable of having unique DNA probe sequences, wavelength-selective multi-dielectric emission filter (OD of 3.6), resistive heater for thermal cycling, and a high performance and programmable photodetector. The dimension of each biosensor is 100µm×100µm with a 50µm×50µm Nwell-Psub photodiode acting as the optical transducer, and a ΣΔ modulator based photocurrent sensor. The measured photodetector performance shows ~116 dB detection dynamic range (10fA - 10nA) over the 25°C - 100°C temperature range, while being ~1 dB away from the fundamental shot-noise limit. To empirically demonstrate the compatibility of this biochip with MDx applications, we have successfully utilized the array and its thermal cycling capability to adopt a 7-plex panel for detection of 6 human upper respiratory viruses.

Keywords: Biochip; Biosensor; Fluorescence Spectroscopy; Image Sensors; Infectious Disease; Microarray; Molecular Diagnostics; Nucleic Acid; Optical Filter; Polymerase Chain Reaction.