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智能手机内结合单波长比色法和数字锁定放大器的 DNA 生物传感器。

DNA biosensor combining single-wavelength colorimetry and a digital lock-in amplifier within a smartphone.

机构信息

Institute of Bio-informatics and Bioelectronics, National Taiwan University, Taiwan, Republic of China.

Institute of Biomedical Engineering, National Taiwan University, Taiwan, Republic of China.

出版信息

Lab Chip. 2016 Nov 15;16(23):4527-4533. doi: 10.1039/c6lc01170e.

DOI:10.1039/c6lc01170e
PMID:27778010
Abstract

Smartphone camera based gold nanoparticle colorimetry (SCB-AuNP colorimetry) has shown good potential for point-of-care applications. However, due to the use of a camera as a photo-detector, there are major limitations to this technique such as a low bit resolution (∼8 bits mainstream) and a low data acquisition rate. These issues have limited the ultimate sensitivity of smartphone based colorimetry as well as the possibility to integrate efficiently a more sensitive approach such as detection based on a lock-in amplifier (LIA). In this paper, we improve the metrological performance of the smartphone to overcome existing issues by adding the LIA capability to AuNP sensing. In this work, instead of using the camera as a photo-detector, the audio jack is used as a photo-detector reader and function generator for driving a laser diode in order to achieve a smartphone based digital lock-in amplifier AuNP colorimetric (SBLIA-AuNP colorimetry) system. A full investigation on the SBLIA design, parameters and performance is comprehensively provided. It is found that the SBLIA can reduce most of the noise and provides a detection noise-to-signal ratio down to -63 dB, which is much better than the -49 dB of the state-of-the-art SCB based method. A DNA detection experiment is demonstrated to reveal the efficacy of the proposed metrological method. The results are compared to UV-visible spectrometry, which is the gold standard for colorimetric measurement. Based on our results, the SBLIA-AuNP colorimetric system has a detection limit of 0.77 nM on short strand DNA detection, which is 5.7 times better than the 4.36 nM limit of a commercial UV-visible spectrometer. Judging from the results, we believe that the sensitive SBLIA would be further extended to other optical diagnostic tools in the near future.

摘要

基于智能手机摄像头的金纳米粒子比色法(SCB-AuNP 比色法)在即时检测应用中显示出良好的潜力。然而,由于使用相机作为光电探测器,该技术存在主要局限性,例如低比特分辨率(主流约 8 位)和低数据采集率。这些问题限制了基于智能手机的比色法的最终灵敏度,以及有效地集成更灵敏方法(例如基于锁相放大器(LIA)的检测)的可能性。在本文中,我们通过在 AuNP 传感中添加 LIA 功能来改善智能手机的计量性能,以克服现有问题。在这项工作中,我们不是使用相机作为光电探测器,而是使用音频插孔作为光电探测器读取器和函数发生器,以驱动激光二极管,从而实现基于智能手机的数字锁相放大器 AuNP 比色(SBLIA-AuNP 比色)系统。本文全面提供了对 SBLIA 设计、参数和性能的全面研究。结果表明,SBLIA 可以减少大部分噪声,并提供低至-63 dB 的检测噪声与信号比,这比最先进的基于 SCB 的方法的-49 dB 要好得多。进行了 DNA 检测实验以揭示所提出的计量方法的效果。将结果与比色测量的金标准——紫外可见光谱法进行了比较。根据我们的结果,SBLIA-AuNP 比色系统在短链 DNA 检测中的检测限为 0.77 nM,比商用紫外可见光谱仪的 4.36 nM 检测限好 5.7 倍。从结果来看,我们相信敏感的 SBLIA 将在不久的将来进一步扩展到其他光学诊断工具。

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