Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, 113-8654, Japan.
Anal Bioanal Chem. 2022 May;414(11):3419-3428. doi: 10.1007/s00216-022-03963-2. Epub 2022 Feb 15.
Microfluidic immunoassay devices are a promising technology that can quickly detect biomarkers with high sensitivity. Recently, many studies implementing this technology on paper substrates have been proposed for improving cost and user-friendliness. However, these studies have identified problems with the large volume of sample required, low sensitivity, and a lack of quantitative accuracy and precision. In this paper, we report a novel structure implemented as a cellulosic material-based microchannel device capable of quantitative immunoassay using small sample volumes. We fabricated microfluidic channels between a transparent cellophane film and water-resistant paper to facilitate loading of small-volume samples and reagents, with a 40-μm-wide immunoreaction matrix constructed in the center of the microchannel using highly precise photolithography. A fluorescence sandwich immunoassay for C-reactive protein (CRP) was successfully implemented that required only a 1-μL sample volume and a 20-min reaction time. We confirmed that the limit of detection of the device was 10-20 ng/mL with a coefficient of variation under 5.6%, which is a performance level comparable to conventional plastic-based human CRP enzyme-linked immunosorbent assay (ELISA) kits. We expect that such devices will lead to the elimination of large amounts of medical waste from the use of ubiquitous diagnostics, a result that is consistent with environmental sustainability goals.
微流控免疫分析装置是一种很有前途的技术,可以快速、高灵敏度地检测生物标志物。最近,许多在纸基上实现这一技术的研究被提出来以提高成本效益和用户友好性。然而,这些研究已经发现了一些问题,例如需要大量样本、灵敏度低、定量准确性和精密度差。在本文中,我们报告了一种新颖的结构,它是一种基于纤维素材料的微通道装置,能够使用小体积的样本进行定量免疫分析。我们在透明玻璃纸薄膜和防水纸之间制造微流道,以方便小体积样本和试剂的加载,在微通道的中心使用高度精确的光刻技术构建了 40μm 宽的免疫反应矩阵。成功实现了用于 C 反应蛋白 (CRP) 的荧光夹心免疫分析,仅需 1μL 样本体积和 20 分钟的反应时间。我们确认该设备的检测限为 10-20ng/mL,变异系数在 5.6%以下,这与传统的基于塑料的人 CRP 酶联免疫吸附测定 (ELISA) 试剂盒的性能相当。我们预计,这种设备将消除无处不在的诊断设备使用带来的大量医疗废物,这与环境可持续性目标是一致的。