Fully Integrated Microfluidic Device for Magnetic Bead Manipulation to Assist Rapid Reaction and Cleaning
Zhen Yang, Miaoning Ren, Ya Li, Mingxing Zhou, Jingyi Peng, Si Lin, Kang Du, and Xian Huang*
Cite this: Anal. Chem. 2023, 95, 40, 14934–14943
Publication Date:September 26, 2023
https://doi.org/10.1021/acs.analchem.3c02285


Abstract


Methods to manipulate magnetic beads are essential factors to determine the efficiency and dimension of an in vitro diagnostic system. Currently, using movable permanent magnets and planar electromagnets is still the major approach to achieve magnetic bead control, causing significant constraint in the miniaturization of in vitro diagnostic systems. Here, we propose techniques to construct a fully integrated microfluidic device that can conduct automatic magnetic bead manipulation as well as rapid chemical reaction and cleaning in a minimized dimension similar to a USB disk. The device combines the precision control of multiple electromagnetic coils with the compactness of microfluidic channels, leading to one of the smallest automatic magnetic bead manipulation systems that can complete several major magnetic bead-based operation steps such as sample injection, reaction, cleaning, and collection. The influencing factors such as coil driving parameters, surface treatment of the microchannels, and properties of magnetic particles have also been investigated to optimize the device performance. The device can drive mixtures of Fe3O4 microparticles and polymer magnetic beads (PMBs) with a weight ratio of 1:1 at a maximum speed of 0.5 cm·s–1 and reduce the time for DNA binding and dissociation reactions from 20 min to only 48 s. This device has significantly advanced the conventional manipulation methods of magnetic beads and has demonstrated the possibility to construct an automatic and ultraminiaturized in vitro diagnostic system that may facilitate portable or even wearable chemical analysis.

操纵磁珠的方法是决定体外诊断系统的效率和尺寸的重要因素。目前，使用可移动永磁体和平面电磁铁仍然是实现磁珠控制的主要方法，这对体外诊断系统的小型化造成了重大制约。在这里，我们提出了构建一种完全集成的微流体设备的技术，该设备可以进行自动磁珠操作，并以类似于U盘的最小尺寸进行快速化学反应和清洁。该设备将多个电磁线圈的精确控制与微流体通道的紧凑性相结合，成为最小的自动磁珠操作系统之一，可以完成几个主要的基于磁珠的操作步骤，如样品注入、反应、清洁和收集。还研究了线圈驱动参数、微通道的表面处理和磁性粒子的性质等影响因素，以优化器件性能。该设备可以以0.5 cm·s–1的最大速度驱动重量比为1:1的Fe3O4微粒和聚合物磁珠（PMBs）的混合物，并将DNA结合和解离反应的时间从20分钟缩短到仅48秒。该设备显著改进了磁珠的传统操作方法，并证明了构建自动超小型体外诊断系统的可能性，该系统可以促进便携式甚至可穿戴的化学分析。