Department of Materials Science and Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon 999077, Hong Kong, China.
Sensors (Basel). 2019 Jun 26;19(13):2838. doi: 10.3390/s19132838.
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.
光子计数分析在许多诊断应用中起着关键作用，因为它具有准确和非侵入性的特点。然而，由于传统光学的使用和电子学缺乏优化，传统的光子计数仪器体积庞大且昂贵。在本文中，我们提出了一种用于 DNA 检测的便携式、低成本的时间相关单光子计数（TCSPC）分析系统。光学和电子子系统都经过精心设计，提供有效的发射滤波和尺寸减小，实现了良好的 DNA 检测和荧光寿命提取性能。通过 V-咔唑共轭荧光团寿命生物测定的荧光寿命测量验证了 DNA 检测。所提出的 TCSPC 系统的时间数字模块在 500ns 满量程范围内实现了从 121 到 145ps 的全宽半最大值（FWHM）定时分辨率和最小有效位（LSB）的-8.5%至+9.7%的差分非线性（DNL）。该 TCSPC 系统的检测限为 6.25nm，动态范围为 6.8ns，为快速、即时的 DNA 诊断提供了实现技术。
