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基于全玻璃微流控芯片的超便携式流式细胞仪。

Ultraportable Flow Cytometer Based on an All-Glass Microfluidic Chip.

作者信息

Li Jiayu, Cui Yuhan, Xie Qiucheng, Jiang Tao, Xin Siyuan, Liu Peng, Zhou Tianfeng, Li Qin

机构信息

School of Life Science, Beijing Institute of Technology, Beijing100081, China.

School of Medical Technology, Beijing Institute of Technology, Beijing100081, China.

出版信息

Anal Chem. 2023 Jan 31;95(4):2294-2302. doi: 10.1021/acs.analchem.2c03984. Epub 2023 Jan 18.

Abstract

The flow cytometer has become a powerful and widely accepted measurement device in both biological studies and clinical diagnostics. The application of the flow cytometer in emerging point-of-care scenarios, such as instant detection in remote areas and emergency diagnosis, requires a significant reduction in physical dimension, cost, and power consumption. This requirement promotes studies to develop portable flow cytometers, mostly based on the utilization of polymer microfluidic chips. However, due to the relatively poor optical performance of polymer materials, existing microfluidic flow cytometers are incapable of accurate blood analysis, such as the four-part leukocyte differential count, which is necessary to monitor the immune system and to assess the risk of allergic inflammation or viral infection. To address this issue, an ultraportable flow cytometer based on an all-glass microfluidic chip (AG-UFCM) has been developed in this study. Compared with that of a typical commercial flow cytometer (BD FACSAria III), the volume of the AG-UFCM was reduced by 90 times (from 720 to 8 L). A two-step laser processing was employed to fabricate an all-glass microfluidic chip with a surface roughness of less than 1 nm, significantly improving the optical performance of on-chip micro-lens. The signal-to-noise ratio was enhanced by 3 dB, compared with that of polymer materials. For the first time, a four-part leukocyte differential count based on single fluorescence staining was realized using a miniaturized flow cytometer, laying a foundation for the point-of-care testing of miniaturized flow cytometers.

摘要

流式细胞仪已成为生物学研究和临床诊断中一种强大且被广泛接受的测量设备。流式细胞仪在新兴的即时检测场景中的应用,如偏远地区的即时检测和急诊诊断,要求在物理尺寸、成本和功耗方面大幅降低。这一要求推动了便携式流式细胞仪的研究发展,这些研究大多基于聚合物微流控芯片的应用。然而,由于聚合物材料的光学性能相对较差,现有的微流控流式细胞仪无法进行准确的血液分析,如监测免疫系统以及评估过敏性炎症或病毒感染风险所必需的白细胞四分群计数。为了解决这个问题,本研究开发了一种基于全玻璃微流控芯片的超便携式流式细胞仪(AG-UFCM)。与典型的商用流式细胞仪(BD FACSAria III)相比,AG-UFCM的体积缩小了90倍(从720降至8升)。采用两步激光加工制造出表面粗糙度小于1纳米的全玻璃微流控芯片,显著提高了芯片上微透镜的光学性能。与聚合物材料相比,信噪比提高了3分贝。首次使用小型化流式细胞仪实现了基于单荧光染色的白细胞四分群计数,为小型化流式细胞仪的即时检测奠定了基础。

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