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一种通量自适应、无泵的基于微流控的自容式多癌症生物标志物检测平台。

A flux-adaptable pump-free microfluidics-based self-contained platform for multiplex cancer biomarker detection.

机构信息

Engineering Research Center of Optical Instrument and System, The Ministry of Education, Shanghai Key Laboratory of Modern Optical System, University of Shanghai for Science and Technology, Shanghai, 200093, China.

出版信息

Lab Chip. 2021 Jan 7;21(1):143-153. doi: 10.1039/d0lc00944j. Epub 2020 Nov 13.

DOI:10.1039/d0lc00944j
PMID:33185235
Abstract

Microfluidics drives technological advancement in point-of-care (POC) bioanalytical diagnostics towards portability, fast response and low cost. In most microfluidic bioanalytical applications, flowing antigen/antibody reacts with immobilized antibody/antigen at a constant flux; it is difficult to reach a compromise to simultaneously realize sufficient time for the antigen-antibody interaction and short time for the entire assay. Here, we present a pump-free microfluidic chip, in which flow is self-initialized by capillary pumping and continued by imbibition of a filter paper. Microfluidic units in teardrop shape ensure that flow passes through the reaction areas at a reduced flux to facilitate the association between antigen and antibody and speeds up after the reaction areas. By spotting different antibodies into the reaction area, four types of biomarkers can be measured simultaneously in one microfluidic chip. Moreover, a small-sized instrument was developed for chemiluminescence detection and signal analysis. The system was validated by testing four biomarkers of colorectal cancer using plasma samples from patients. The assay took about 20 minutes. The limit of detection is 0.89 ng mL, 1.72 ng mL, 3.62 U mL and 1.05 U mL for the assays of carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 125 and carbohydrate antigen 19-9, respectively. This flux-adaptable and self-contained microfluidic platform is expected to be useful in various POC disease-monitoring applications.

摘要

微流控技术推动了即时诊断(POC)生物分析诊断技术的发展,使其具有便携性、快速响应和低成本的特点。在大多数微流控生物分析应用中,流动的抗原/抗体以恒定的流速与固定化的抗体/抗原反应;很难同时实现足够的抗原-抗体相互作用时间和整个检测的短时间。在这里,我们提出了一种无泵微流控芯片,其中流动通过毛细泵送自初始化,并通过滤纸的吸液继续。泪滴形状的微流控单元确保流动以降低的流速通过反应区域,以促进抗原和抗体的结合,并在反应区域之后加速。通过将不同的抗体点入反应区域,可以同时在一个微流控芯片上测量四种类型的生物标志物。此外,还开发了一种用于化学发光检测和信号分析的小型仪器。该系统通过使用来自患者的血浆样本测试四种结直肠癌生物标志物进行了验证。该测定大约需要 20 分钟。该检测系统对癌胚抗原、甲胎蛋白、糖链抗原 125 和糖链抗原 19-9 的检测限分别为 0.89ng/mL、1.72ng/mL、3.62U/mL 和 1.05U/mL。这种适应流量的自包含微流控平台有望在各种即时疾病监测应用中发挥作用。

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