Laboratory for Innovations in Micro Engineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, Canada.
Advanced Magnetic Materials Research Center, College of Engineering, University of Tehran, Tehran, Iran.
Small. 2023 Apr;19(16):e2205320. doi: 10.1002/smll.202205320. Epub 2023 Jan 31.
Capturing rare disease-associated biomarkers from body fluids can offer an early-stage diagnosis of different cancers. Circulating tumor cells (CTCs) are one of the major cancer biomarkers that provide insightful information about the cancer metastasis prognosis and disease progression. The most common clinical solutions for quantifying CTCs rely on the immunomagnetic separation of cells in whole blood. Microfluidic systems that perform magnetic particle separation have reported promising outcomes in this context, however, most of them suffer from limited efficiency due to the low magnetic force generated which is insufficient to trap cells in a defined position within microchannels. In this work, a novel method for making soft micromagnet patterns with optimized geometry and magnetic material is introduced. This technology is integrated into a bilayer microfluidic chip to localize an external magnetic field, consequently enhancing the capture efficiency (CE) of cancer cells labeled with the magnetic nano/hybrid microgels that are developed in the previous work. A combined numerical-experimental strategy is implemented to design the microfluidic device and optimize the capturing efficiency and to maximize the throughput. The proposed design enables high CE and purity of target cells and real-time time on-chip monitoring of their behavior. The strategy introduced in this paper offers a simple and low-cost yet robust opportunity for early-stage diagnosis and monitoring of cancer-associated biomarkers.
从体液中捕获罕见疾病相关的生物标志物可为不同癌症提供早期诊断。循环肿瘤细胞 (CTC) 是主要的癌症生物标志物之一，可提供有关癌症转移预后和疾病进展的深入信息。定量 CTC 的最常见临床解决方案依赖于全血中细胞的免疫磁分离。在这方面，执行磁粒子分离的微流控系统已经报告了有希望的结果，但是，由于产生的磁力低，大多数系统都受到限制，因为磁力不足以将细胞捕获到微通道中的指定位置。在这项工作中，引入了一种用于制造具有优化几何形状和磁性材料的软磁图案的新方法。这项技术被集成到双层微流控芯片中，以局部化外部磁场，从而提高在前一项工作中开发的用磁性纳米/杂化微凝胶标记的癌细胞的捕获效率 (CE)。实施了一种组合的数值-实验策略来设计微流控装置并优化捕获效率，并最大程度地提高吞吐量。所提出的设计能够实现高的目标细胞 CE 和纯度，并能够实时在芯片上监测其行为。本文介绍的策略为癌症相关生物标志物的早期诊断和监测提供了一种简单、低成本但强大的机会。
