Pharmaceutical Production Research Facility, Department of Chemical and Petroleum Engineering, Schulich School of Engineering, University of Calgary, 2500 University Drive N.W., Calgary, Alberta T2N 1N4, Canada.
Biomedical Engineering Graduate Program, University of Calgary, 2500 University Drive N.W., Calgary, Alberta T2N 1N4, Canada.
ACS Nano. 2021 Nov 23;15(11):17047-17079. doi: 10.1021/acsnano.1c03469. Epub 2021 Nov 1.
Exosomes are cell-derived structures packaged with lipids, proteins, and nucleic acids. They exist in diverse bodily fluids and are involved in physiological and pathological processes. Although their potential for clinical application as diagnostic and therapeutic tools has been revealed, a huge bottleneck impeding the development of applications in the rapidly burgeoning field of exosome research is an inability to efficiently isolate pure exosomes from other unwanted components present in bodily fluids. To date, several approaches have been proposed and investigated for exosome separation, with the leading candidate being microfluidic technology due to its relative simplicity, cost-effectiveness, precise and fast processing at the microscale, and amenability to automation. Notably, avoiding the need for exosome labeling represents a significant advance in terms of process simplicity, time, and cost as well as protecting the biological activities of exosomes. Despite the exciting progress in microfluidic strategies for exosome isolation and the countless benefits of label-free approaches for clinical applications, current microfluidic platforms for isolation of exosomes are still facing a series of problems and challenges that prevent their use for clinical sample processing. This review focuses on the recent microfluidic platforms developed for label-free isolation of exosomes including those based on sieving, deterministic lateral displacement, field flow, and pinched flow fractionation as well as viscoelastic, acoustic, inertial, electrical, and centrifugal forces. Further, we discuss advantages and disadvantages of these strategies with highlights of current challenges and outlook of label-free microfluidics toward the clinical utility of exosomes.
外泌体是一种由脂质、蛋白质和核酸组成的细胞衍生结构。它们存在于各种体液中，参与生理和病理过程。尽管它们作为诊断和治疗工具的临床应用潜力已经显现，但在迅速发展的外泌体研究领域，一个巨大的瓶颈阻碍了其应用的发展，即无法从体液中其他不需要的成分中有效地分离出纯外泌体。迄今为止，已经提出并研究了几种用于外泌体分离的方法，由于其相对简单、经济高效、在微尺度上精确快速处理以及易于自动化，微流控技术是最主要的候选方法。值得注意的是，避免外泌体标记在简化处理过程、节省时间和成本以及保护外泌体的生物活性方面具有重要意义。尽管在微流控策略用于外泌体分离方面取得了令人兴奋的进展，并且无标记方法在临床应用方面具有无数优势，但目前用于外泌体分离的微流控平台仍面临一系列问题和挑战，限制了其在临床样本处理中的应用。本综述重点介绍了最近开发的用于无标记外泌体分离的微流控平台，包括基于筛分、确定性侧向位移、场流和挤压流分馏以及粘弹性、声、惯性、电和离心力的微流控平台。此外，我们讨论了这些策略的优缺点，并重点介绍了当前无标记微流控技术在临床应用中外泌体方面面临的挑战和前景。
