IEEE Trans Biomed Eng. 2020 May;67(5):1517-1527. doi: 10.1109/TBME.2019.2939419. Epub 2019 Sep 4.
Clostridium difficile (C. diff) infection leads to hundreds of nosocomial infections, and early diagnosis of this toxin-mediated disease is important. This paper aims to develop a microrobotic system and related methods that enable the automated and rapid detection of toxins secreted by C. diff that exist in patient's stool.
We utilize the fluorescent magnetic spore-based microrobot (FMSM), a microscale mobile sensing tool, to efficiently detect C. diff toxins by utilizing its property of selective fluorescence responses to C. diff toxins. A plug-and-play (PnP) electromagnetic coil system integrated with fluorescence microscopy is developed for actuation, control and observation of FMSMs. In order to track in real time and accurately obtain the fluorescence parameters of a FMSM under varied background noise in fluorescence signal, an image gradient-based method is proposed. For accelerating the FMSM-toxin interaction in different samples, an automated navigation control scheme for the FMSM is proposed and implemented. Moreover, data post-processing methods that can optimally extract the fluorescence decay trend from the dense and fluctuated fluorescence data are developed.
This automated mobile detection process finishes within only 20 minutes, and the toxin detection result is immediately given by adopting the proposed system and methods. Experimental results on different biological samples confirm the qualitative detection capability. And, C. diff toxins are automatically detected from the clinical stool of infectious patients and the relationship between the fluorescence decay and the toxin concentration is calibrated for semi-quantitative detection purpose.
The proposed automated microrobotic platform provides a rapid and low-cost detection technique for C. diff toxins, and it has good competency for future clinical use.
艰难梭菌（C. diff）感染导致了数百例医院获得性感染，早期诊断这种毒素介导的疾病非常重要。本文旨在开发一种微机器人系统和相关方法，使我们能够自动且快速地检测存在于患者粪便中的 C. diff 分泌的毒素。
我们利用荧光磁孢子微机器人（FMSM），一种微型移动传感工具，通过其对 C. diff 毒素的选择性荧光响应特性来高效检测 C. diff 毒素。开发了一个带有荧光显微镜的即插即用（PnP）电磁线圈系统，用于 FMSM 的驱动、控制和观察。为了实时跟踪并在荧光信号中的背景噪声变化下准确获得 FMSM 的荧光参数，提出了一种基于图像梯度的方法。为了在不同的样本中加速 FMSM-毒素相互作用，提出并实现了一种 FMSM 的自动导航控制方案。此外，还开发了数据后处理方法，可从密集且波动的荧光数据中最佳地提取荧光衰减趋势。
这个自动化的移动检测过程仅需 20 分钟即可完成，采用提出的系统和方法可立即给出毒素检测结果。在不同的生物样本上的实验结果证实了定性检测能力。此外，还从感染患者的临床粪便中自动检测到了 C. diff 毒素，并对荧光衰减与毒素浓度之间的关系进行了校准，以实现半定量检测目的。
所提出的自动化微机器人平台为 C. diff 毒素提供了一种快速且低成本的检测技术，对于未来的临床应用具有良好的竞争力。
