A Fully Integrated CMOS Fluorescence Biochip for DNA and RNA Testing

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.

Nano-plasmonics and electronics co-integration in CMOS enabling a pill-sized multiplexed fluorescence microarray system

“…In a classical fluorescence set-up, both fluorescence signal and laser excitation are collimated to allow the usage of a high-performance multi-layer fluorescence emission filter which typically works within a very small range of angles (≈ ±5 • ) [35,36]. In this miniaturized sensor platform without optical collimation, the radiation from the fluorescent dipoles on the surface interacts with the integrated filters in a complex fashion for a wide range of incident angles [58][59][60].…”

“…For fluorescence assays, while CMOS can enable highdensity multiplexed photo-detection and readout with sensitivity comparable to CCDs, it does not have the capability to manipulate optical fields to emulate the functions of the external optical components in a traditional fluorescence reader. This typically requires a similar approach as before with external filtering and collimating optics and post-fabrication [35][36][37], or by allowing fluorescence lifetime detection with complex laser synchronization with picosecond levels of accuracy [38,39] and significantly sacrificing sensitivity (∼nM).…”

Towards Fully Integrated Portable Sensing Devices for COVID-19 and Future Global Hazards: Recent Advances, Challenges, and Prospects

“…Recent decades have witnessed unprecedented advances in CMOS sensors using optical [ 26 ], electrochemical [ 27 , 28 , 29 ], and magnetic [ 30 , 31 ] techniques alike for a variety of applications such as for the detection of different viruses (such as human respiratory viruses [ 32 , 33 ], Zika virus [ 27 ], and dengue virus [ 30 ]), as well as monitoring various bacteria (e.g., Streptococcus pneumoniae [ 34 ], bacillus globigii [ 35 ], Staphylococcus epidermidis [ 26 ], and Escherichia coli [ 28 ]) and detecting parasites (such as Plasmodium falciparum malaria diagnosis [ 29 ]). There are other opportunities for reconfiguring these devices for the diagnosis of similar diseases.…”

A novel CIS pixel structure design and simulation for DNA fluorescence sequencing

“…The differential output is used to satisfy the differential input requirement of the counting circuit, while reducing the sensitivity to common mode and power noise. A. Manickam et al [27,28,29,30] presents an integrated biochip with a specific DNA probe sequence in each biosensing unit, a wavelength-selective multimedia emission filter, and a high-performance programmable photoelectric detector for a resistance heater. Biochemical reactions occur on the surface of the photosensitive area, which enables continuous wave fluorescence detection to improve the dynamic range and reduce the noise.…”