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用于即时检测的带集成自设计微流控芯片的疾病生物标志物同时检测,具有可调检测范围。

Tape integrated self-designed microfluidic chip for point-of-care immunoassays simultaneous detection of disease biomarkers with tunable detection range.

机构信息

School of Mechanical Engineering, Yangzhou University, Yangzhou, 225127, China.

School of Mechanical Engineering, Yangzhou University, Yangzhou, 225127, China.

出版信息

Biosens Bioelectron. 2022 Sep 15;212:114429. doi: 10.1016/j.bios.2022.114429. Epub 2022 May 27.

Abstract

Multiple biomarkers to diagnose the combined manifestations of a patient's disease are an indispensable guide in point-of-care testing (POCT) and clinical applications. Currently, multiplex determination of molecules at different concentrations usually requires assays with adjustable detection ranges. Here, for the first time, commercially available 3M tapes, Tape 610, Tape 810, Tape 600, are integrated into a self-designed key valve microfluidic chip (KVMC) to construct a Tape-based KVMC. Interestingly, 3M tapes with different absorption tunability for the encapsulated antibodies have been used in KVMC as substrate to enable detection of diseases biomarkers in serum ranging from pg mL to μg mL. The Tapes antibody layer in the chip has been successfully developed without sophisticated modifications, and the detection probe can be used for a wide range of detection of three biomarkers without multiple modifications and amplification. Automated, multiplexed, simultaneous bioassays of clinically relevant inflammatory biomarkers are performed in the Tape-based KVMC POCT system, with a limit of detection (LOD) of 0.23 μg mL for C-reactive protein (CRP), 0.14 ng mL for procalcitonin (PCT), and 12.53 pg mL for interleukin-6 (IL-6), respectively, which offers a desirable strategy for the early clinical diagnosis of sepsis. The developed Tape-based KVMC possesses high sensitivity and excellent selectivity for three biomarkers in undiluted human serum samples, providing the foundation for the application of chip POCT in clinical and field precision diagnostics.

摘要

用于诊断患者疾病综合表现的多种生物标志物是即时检测(POCT)和临床应用中不可或缺的指导。目前,通常需要具有可调检测范围的分析方法来对不同浓度的分子进行多重测定。在这里,首次将市售的 3M 胶带(Tape 610、Tape 810 和 Tape 600)集成到自行设计的键控微流控芯片(KVMC)中,构建基于胶带的 KVMC。有趣的是,已经将具有不同吸收可调性的 3M 胶带用于 KVMC 作为基底,以实现对 pg mL 至 μg mL 血清中疾病生物标志物的检测。该芯片中的 Tape 抗体层无需复杂修饰即可成功开发,并且检测探针可用于广泛检测三种生物标志物,无需多次修饰和放大。在基于胶带的 KVMC POCT 系统中,可自动、多重、同时进行临床相关炎症生物标志物的生物分析,对 C-反应蛋白(CRP)的检测限(LOD)为 0.23μg mL,降钙素原(PCT)为 0.14ng mL,白细胞介素-6(IL-6)为 12.53pg mL,为脓毒症的早期临床诊断提供了一种理想的策略。该基于胶带的 KVMC 对未稀释的人血清样本中的三种生物标志物具有高灵敏度和优异的选择性,为芯片 POCT 在临床和现场精准诊断中的应用奠定了基础。

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