A Low-Cost Time-Correlated Single Photon Counting Portable DNA Analyzer

Abstract

Photon-counting analysis of nucleic acids plays a key role in many diagnostics applications for its accurate and non-invasive nature. However, conventional photon-counting instrumentations are bulky and expensive due to the use of conventional optics and a lack of optimization of electronics. In this paper, we present a portable, low-cost time-correlated single photon-counting (TCSPC) analysis system for DNA detection. Both optical and electronic subsystems are carefully designed to provide effective emission filtering and size reduction, delivering good DNA detection and fluorescence lifetime extraction performance. DNA detection has been verified by fluorescence lifetime measurements of a V-carbazole conjugated fluorophore lifetime bioassay. The time-to-digital module of the proposed TCSPC system achieves a full width at half maximum (FWHM) timing resolution from 121 to 145 ps and a differential non-linearity (DNL) between −8.5% and +9.7% of the least significant bit (LSB) within the 500 ns full-scale range (FSR). With a detection limit of 6.25 nM and a dynamic range of 6.8 ns, the proposed TCSPC system demonstrates the enabling technology for rapid, point-of-care DNA diagnostics.

Geiger Mode Single Photon Counting: A Laboratory Experiment Exploring Delayed Fluorescence in Plants

“…Photon counting is the time-dependent quantification of extremely low intensity light through the use of highly sensitive photodetectors and ultrafast electronics with up to nanosecond resolution. − Over the past few decades, photon counting has been applied to a wide variety of scientific fields including time-resolved fluorescence, , Raman spectroscopy, particle physics, astronomy, DNA/RNA sequencing, , in vivo CT imaging, − single cell function, cancer therapy evaluation and discovery of mechanisms, − and single-molecule fluorescence microscopy . Photon counting has also become essential to communications technologies, as fiber-optic communication rates are now in the range of tens of gigabits per second.…”