Lee Dohwan, Lee Jee Won, Kim Cheonjung, Lee Dongho, Chung Seok, Yoon Dae Sung, Lee Jeong Hoon
Department of Electrical Engineering, Kwangwoon University, Seoul, 01897, Republic of Korea.
CALTH. Inc. Changeop-ro 54, Seongnam, Gyeonggi, 13449, Republic of Korea.
Biosens Bioelectron. 2021 Mar 15;176:112904. doi: 10.1016/j.bios.2020.112904. Epub 2020 Dec 16.
Micro/nanofluidics are excellent candidates for biological sample preparation. However, the limited process volume in micro/nanofluidics is the main hurdle limiting their practical applications. To date, most micro/nanofluidics have processed sample volumes of several microliters and have rarely been used to handle large-volume samples. Herein, we propose a microfluidic paper-based large-volume preconcentrator (u-LVP) for enrichment and purification of biomarkers (e.g., miRNA) using ion concentration polarization. A Nafion (ion-selective nanoporous membrane)-functionalized multilayer cellulose paper enables microscale division of milliliter-scale samples, thus electrokinetically separating and preconcentrating the biomarker in different locations within the u-LVP. By inserting collecting discs at optimal positions in the u-LVP, the enriched biomarker is simply recovered with high efficiency. With this approach, as an exemplary biomarker, miRNA-21 in human serum was separated from proteins and preconcentrated with an effective preconcentration factor exceeding 6.63 and a recovery rate above 84%. Thus, our platform offers new opportunities and benefits for biomarker, diagnostic, prognostic, and therapeutic research.
微纳流体技术是生物样品制备的理想选择。然而，微纳流体中有限的处理体积是限制其实际应用的主要障碍。迄今为止，大多数微纳流体技术处理的样品体积为几微升，很少用于处理大体积样品。在此，我们提出了一种基于微流控纸的大体积预浓缩器（u-LVP），用于利用离子浓度极化富集和纯化生物标志物（如miRNA）。一种经Nafion（离子选择性纳米多孔膜）功能化的多层纤维素纸能够对毫升级样品进行微尺度划分，从而在u-LVP内的不同位置通过电动方式分离和预浓缩生物标志物。通过在u-LVP的最佳位置插入收集盘，可高效简便地回收富集的生物标志物。采用这种方法，作为示例性生物标志物，人血清中的miRNA-21被分离并预浓缩，有效预浓缩因子超过6.63，回收率高于84%。因此，我们的平台为生物标志物、诊断、预后和治疗研究提供了新的机遇和优势。
