Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China.
Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Hong Kong, China.
Sci Rep. 2022 Sep 14;12(1):15461. doi: 10.1038/s41598-022-19844-8.
Human host-associated microbial communities in body sites can reflect health status based on the population distribution and specific microbial properties in the heterogeneous community. Bacteria identification at the single-cell level provides a reliable biomarker and pathological information for clinical diagnosis. Nevertheless, biosamples obtained from some body sites cannot offer sufficient sample volume and number of target cells as required by most of the existing single-cell isolation methods such as flow cytometry. Herein we report a novel integrated microfluidic system, which consists of a microemulsion module for single-bacteria encapsulation and a sequential microdroplet capture and release module for selectively extracting only the single-bacteria encapsulated in microdroplets. We optimize the system for a success rate of the single-cell extraction to be > 38%. We further verify applicability of the system with prepared cell mixtures (Methylorubrum extorquens AM1 and Methylomicrobium album BG8) and biosamples collected from human skin, to quantify the population distribution of multiple key species in a heterogeneous microbial community. Results indicate perfect viability of the single-cell extracts and compatibility with downstream analyses such as PCR. Together, this research demonstrates that the reported single-bacteria extraction system can be applied in microbiome and pathology research and clinical diagnosis as a clinical or point-of-care device.
人体不同部位的宿主相关微生物群落可根据其群落中种群分布和特定微生物特性反映健康状况。单细胞水平的细菌鉴定为临床诊断提供了可靠的生物标志物和病理信息。然而,从某些部位获得的生物样本不能提供足够的样本量和目标细胞数量,而大多数现有的单细胞分离方法(如流式细胞术)都需要这些数量。本文报道了一种新型的集成微流控系统,该系统由微乳液模块组成,用于单细胞封装,以及顺序微滴捕获和释放模块,用于选择性地仅提取封装在微滴中的单细胞。我们对该系统进行了优化,以实现单细胞提取成功率>38%。我们进一步通过使用从人类皮肤收集的制备细胞混合物(Methylorubrum extorquens AM1 和 Methylomicrobium album BG8)和生物样本验证了该系统的适用性,以定量异质微生物群落中多个关键物种的种群分布。结果表明单细胞提取物具有完美的生存能力,并且与下游分析(如 PCR)兼容。总之,这项研究表明,所报道的单细胞提取系统可作为临床或即时诊断设备,应用于微生物组和病理学研究以及临床诊断中。