期刊
IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS
卷 13, 期 2, 页码 343-351出版社
IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
DOI: 10.1109/TBCAS.2019.2892825
关键词
Analog counting pixel; biosensor; CMOS; molecular diagnosis; on-chip histogramming; SPAD; time-resolved fluorescence
资金
- Catalan government through ACCIA via the project 'Portable Device for Molecular Diagnosis' [VALTEC13-1-0020-00]
- AGAUR [2014LLAVOR00003]
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 mu m 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 mu m x 50 mu m. 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.
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