A Compact Analog Histogramming SPAD-Based CMOS Chip for Time-Resolved Fluorescence

• Published in: IEEE transactions on biomedical circuits and systems Vol. 13; no. 2; pp. 343 - 351
• Main Authors: Dieguez, Angel, Canals, Joan, Franch, Nil, Dieguez, Joel, Alonso, Oscar, Vila, Anna
• Format: Journal Article
• Language: English
• Published: United States IEEE 01-04-2019; The Institute of Electrical and Electronics Engineers, Inc. (IEEE)
• Subjects: Analog counting pixel; Biomedical measurement; biosensor; Capacitors; CMOS; Data processing; Decay; Decay rate; Digital cameras; Electricity; Fluorescence; Histograms; Microfluidics; molecular diagnosis; on-chip histogramming; Photonics; Photons; Pixels; Quantum dots; Semiconductor device measurement; Semiconductors; Signal Processing, Computer-Assisted; SPAD; Time Factors; time-resolved fluorescence; Timing
• ISSN: 1932-4545; 1940-9990
• DOI: 10.1109/TBCAS.2019.2892825

Time-resolved fluorescence measurement is extraordinarily powerful in the analysis of substances due to its effectiveness in eliminating measurement artifacts. Some fluorescence measurements are still conducted on CMOS chips with the decay times determined after reading the data off the chip and fitting the fluorescence decay histogram. We present a novel approach in which an analog CMOS chip divides the fluorescence decay time into slices and classifies the photons according to their arrival times at a CMOS SPAD sensor. The chip was fabricated in a 1P6M 0.18 μm HV-CMOS process. The slice timings can be tailored from 168 ps to 4.9 ns, covering most fluorescence decay times. 9 timing windows are generated per pixel that count up to 13 b each, with a resolution of 0.16 mV/photon, for a maximum output voltage of 1.3 V, in an area of 150 μm × 50 μm. Here, we report on the first practical application of this circuit, which integrates an array of 5 pixels in a single chip and has an excitation light and a microfluidic chip of up to 3 channels. This system could determine the decay time of quantum dots in 20 nl of solution. Thus, this paper could help in the development of a point-of-care device based on time-resolved fluorescence.