Division of Biology, Office of Science and Engineering, FDA, Silver Spring, MD 20993, United States; University of Maryland, College Park, MD 20742, United States.
Biosens Bioelectron. 2014 Jan 15;51:1-7. doi: 10.1016/j.bios.2013.06.053. Epub 2013 Jul 17.
The low sensitivity of Mobile Health (mHealth) optical detectors, such as those found on mobile phones, is a limiting factor for many mHealth clinical applications. To improve sensitivity, we have combined two approaches for optical signal amplification: (1) a computational approach based on an image stacking algorithm to decrease the image noise and enhance weak signals, and (2) an optical signal amplifier utilizing a capillary tube array. These approaches were used in a detection system which includes multi-wavelength LEDs capable of exciting many fluorophores in multiple wavelengths, a mobile phone or a webcam as a detector, and capillary tube array configured with 36 capillary tubes for signal enhancement. The capillary array enables a ~100× increase in signal sensitivity for fluorescein, reducing the limit of detection (LOD) for mobile phones and webcams from 1000 nM to 10nM. Computational image stacking enables another ~10× increase in signal sensitivity, further reducing the LOD for webcam from 10nM to 1 nM. To demonstrate the feasibility of the device for the detection of disease-related biomarkers, adenovirus DNA labeled with SYBR green or fluorescein was analyzed by both our capillary array and a commercial plate reader. The LOD for the capillary array was 5 ug/mL, and that of the plate reader was 1 ug/mL. Similar results were obtained using DNA stained with fluorescein. The combination of the two signal amplification approaches enables a ~1000× increase in LOD for the webcam platform. This brings it into the range of a conventional plate reader while using a smaller sample volume (10 ul) than the plate reader requires (100 ul). This suggests that such a device could be suitable for biosensing applications where up to 10 fold smaller sample sizes are needed. The simple optical configuration for mHealth described in this paper employing the combined capillary and image processing signal amplification is capable of measuring weak fluorescent signals without the need of dedicated laboratories. It has the potential to be used to increase sensitivity of other optically based mHealth technologies, and may increase mHealth's clinical utility, especially for telemedicine and for resource-poor settings and global health applications.
移动医疗（mHealth）光学探测器的低灵敏度是许多 mHealth 临床应用的一个限制因素。为了提高灵敏度，我们结合了两种光学信号放大方法：（1）基于图像堆叠算法的计算方法，用于降低图像噪声并增强弱信号；（2）利用毛细管阵列的光学信号放大器。这些方法用于检测系统中，该系统包括多波长 LED，能够在多个波长下激发多种荧光团、移动电话或网络摄像头作为探测器，以及配置有 36 个毛细管用于信号增强的毛细管阵列。毛细管阵列使荧光素的信号灵敏度提高了约 100 倍，将手机和网络摄像头的检测限（LOD）从 1000 nM 降低到 10 nM。计算图像堆叠使信号灵敏度再提高约 10 倍，将网络摄像头的 LOD 从 10 nM 进一步降低到 1 nM。为了证明该设备用于检测与疾病相关的生物标志物的可行性，用我们的毛细管阵列和商业平板读数器分析了用 SYBR 绿色或荧光素标记的腺病毒 DNA。毛细管阵列的 LOD 为 5ug/mL，平板读数器的 LOD 为 1ug/mL。用荧光素染色的 DNA 得到了类似的结果。两种信号放大方法的结合使网络摄像头平台的 LOD 提高了约 1000 倍。这使其进入了传统平板读数器的范围，同时使用的样本量比平板读数器（100 ul）要求的小（10 ul）。这表明，这种设备可能适用于生物传感应用，在这些应用中需要的样本量减少了 10 倍。本文描述的用于 mHealth 的简单光学配置采用组合的毛细管和图像处理信号放大，能够测量弱荧光信号，而无需专用实验室。它有可能用于提高其他基于光学的 mHealth 技术的灵敏度，并且可能增加 mHealth 的临床实用性，特别是对于远程医疗以及资源匮乏的环境和全球健康应用。
