Liu Yaoping, Xu Han, Li Tingyu, Wang Wei
Institute of Microelectronics, Peking University, Beijing, 100871, China.
Lab Chip. 2021 Mar 21;21(6):994-1015. doi: 10.1039/d0lc01101k. Epub 2021 Mar 12.
Liquid biopsy, an important enabling technology for early diagnosis and dynamic monitoring of cancer, has drawn extensive attention in the past decade. With the rapid developments of microtechnology, it has been possible to manipulate cells at the single-cell level, which dramatically improves the liquid biopsy capability. As the microtechnology-enabled liquid biopsy matures from proof-of-concept demonstrations towards practical applications, a main challenge it is facing now is to process clinical samples which are usually of a large volume while containing very rare targeted cells in complex backgrounds. Therefore, a high-throughput liquid biopsy which is capable of processing liquid samples with a large volume in a reasonable time along with a high recovery rate of rare targeted cells from complex clinical liquids is in high demand. Moreover, the purity, viability and release feasibility of recovered targeted cells are the other three key impact factors requiring careful considerations. To date, among the developed techniques, micropore-type filtration has been acknowledged as the most promising solution to address the aforementioned challenges in practical applications. However, the presently reported studies about micropore-type filtration are mostly based on trial and error for device designs aiming at different cancer types, which requires lots of efforts. Therefore, there is an urgent need to investigate and elaborate the fundamental theories of micropore-type filtration and key features that influence the working performances in the liquid biopsy of real clinical samples to promote the application efficacy in practical applications. In this review, the state of the art of microtechnology-enabled filtration is systematically and comprehensively summarized. Four key features of the filtration, including throughput, purity, viability and release feasibility of the captured targeted cells, are elaborated to provide the guidelines for filter designs. The recent progress in the filtration mode modulation and sample standardization to improve the filtration performance of real clinical samples is also discussed. Finally, this review concludes with prospective views for future developments of filtration-based liquid biopsy to promote its application efficacy in clinical practice.
液体活检作为癌症早期诊断和动态监测的一项重要支撑技术，在过去十年中受到了广泛关注。随着微技术的快速发展，已能够在单细胞水平上操控细胞，这极大地提升了液体活检能力。随着基于微技术的液体活检从概念验证演示向实际应用成熟发展，它目前面临的一个主要挑战是处理临床样本，这些样本通常体积庞大，同时在复杂背景中含有非常罕见的目标细胞。因此，迫切需要一种高通量液体活检技术，能够在合理时间内处理大量液体样本，并从复杂临床液体中高回收率地获取罕见目标细胞。此外，回收的目标细胞的纯度、活力和释放可行性是另外三个需要仔细考虑的关键影响因素。迄今为止，在已开发的技术中，微孔型过滤被认为是在实际应用中解决上述挑战最有前景的解决方案。然而，目前报道的关于微孔型过滤的研究大多基于针对不同癌症类型的设备设计的反复试验，这需要大量努力。因此，迫切需要研究和阐述微孔型过滤的基本理论以及影响实际临床样本液体活检工作性能的关键特性，以提高其在实际应用中的效能。在本综述中，系统且全面地总结了基于微技术的过滤的现状。详细阐述了过滤的四个关键特性，包括捕获的目标细胞的通量、纯度、活力和释放可行性，为过滤器设计提供指导。还讨论了在过滤模式调制和样本标准化方面的最新进展，以提高实际临床样本的过滤性能。最后，本综述对基于过滤的液体活检的未来发展进行了前瞻性展望，以促进其在临床实践中的应用效能。
