High Precision Ping-pong Auto-zeroed Lock-in Fluorescence Photometry Sensor.

This paper presents a high-precision CMOS fluorescence photometry sensor using a novel lock-in amplification scheme based on switched-biasing and ping-pong auto-zeroing techniques. The CMOS sensor includes two photodiodes and a lock-in amplifier (LIA) operating at 1 kHz. The LIA comprises a differential low-noise amplifier using a novel switched-biasing ping-pong auto-zeroed scheme, an automatic phase aligner, a programmable gain amplifier, a band-pass filter, a mixer, and an output low-pass filter. The design is fabricated in 0.18-µm CMOS process, and the measurement shows that the LIA can retrieve noisy input signals with a dynamic reserve of 42 dB, while consuming only 0.7 mW from a 1.8 V supply voltage. The measured results show that the LIA can detect a wide range of incident light power from 8 nW to 24 µW. The proposed design is encapsulated in a 3D-printed housing allowing for real-time in vitro biomarker detection. This ambulatory platform uses an LED and a fiber optic to convey the excitation light to the sample and retrieve the fluorescence signal. Experiments with a beads solution diluted in PBS demonstrate that the sensor has a sensitivity of 1:100 k. Experimental results obtained in vitro with NIH3T3 mouse cells tagged with membrane dye show the ability of the prototype to detect different densities of cell culture. The portable prototype, which includes optical filters and a small 30 mm × 36 mm × 30 mm printed circuit board enclosed inside the 3D-printed housing, consumes 36.7 mW and weighs 120 g.

A Wireless Fiber Photometry System Based on a High-Precision CMOS Biosensor With Embedded Continuous-Time Modulation.

Fluorescence biophotometry measurements require wide dynamic range (DR) and high-sensitivity laboratory apparatus. Indeed, it is often very challenging to accurately resolve the small fluorescence variations in presence of noise and high-background tissue autofluorescence. There is a great need for smaller detectors combining high linearity, high sensitivity, and high-energy efficiency. This paper presents a new biophotometry sensor merging two individual building blocks, namely a low-noise sensing front-end and a order continuous-time modulator (CTSDM), into a single module for enabling high-sensitivity and high energy-efficiency photo-sensing. In particular, a differential CMOS photodetector associated with a differential capacitive transimpedance amplifier-based sensing front-end is merged with an incremental order 1-bit CTSDM to achieve a large DR, low hardware complexity, and high-energy efficiency. The sensor leverages a hardware sharing strategy to simplify the implementation and reduce power consumption. The proposed CMOS biosensor is integrated within a miniature wireless head mountable prototype for enabling biophotometry with a single implantable fiber in the brain of live mice. The proposed biophotometry sensor is implemented in a 0.18- CMOS technology, consuming from a 1.8- supply voltage, while achieving a peak dynamic range of over a 50- input bandwidth, a sensitivity of 24 mV/nW, and a minimum detectable current of 2.46- at a 20- sampling rate.