Progress in Microfluidics-Based Exosome Separation and Detection Technologies for Diagnostic Applications.

Exosomes are secreted by most cell types and circulate in body fluids. Recent studies have revealed that exosomes play a significant role in intercellular communication and are closely associated with the pathogenesis of disease. Therefore, exosomes are considered promising biomarkers for disease diagnosis. However, exosomes are always mixed with other components of body fluids. Consequently, separation methods for exosomes that allow high-purity and high-throughput separation with a high recovery rate and detection techniques for exosomes that are rapid, highly sensitive, highly specific, and have a low detection limit are indispensable for diagnostic applications. For decades, many exosome separation and detection techniques have been developed to achieve the aforementioned goals. However, in most cases, these two techniques are performed separately, which increases operation complexity, time consumption, and cost. The emergence of microfluidics offers a promising way to integrate exosome separation and detection functions into a single chip. Herein, an overview of conventional and microfluidics-based techniques for exosome separation and detection is presented. Moreover, the advantages and drawbacks of these techniques are compared.

Lin S ，Yu Z ，Chen D ，Wang Z ，Miao J ，Li Q ，Zhang D ，Song J ，Cui D ... -  《-》

Exosome separation using microfluidic systems: size-based, immunoaffinity-based and dynamic methodologies.

Exosomes, nanovesicles secreted by most types of cells, exist in virtually all bodily fluids. Their rich nucleic acid and protein content make them potentially valuable biomarkers for noninvasive molecular diagnostics. They also show promise, after further development, to serve as a drug delivery system. Unfortunately, existing exosome separation technologies, such as ultracentrifugation and methods incorporating magnetic beads, are time-consuming, laborious and separate only exosomes of low purity. Thus, a more effective separation method is highly desirable. Microfluidic platforms are ideal tools for exosome separation, since they enable fast, cost-efficient, portable and precise processing of nanoparticles and small volumes of liquid samples. Recently, several microfluidic-based exosome separation technologies have been studied. In this article, the advantages of the most recent technologies, as well as their limitations, challenges and potential uses in novel microfluidic exosome separation and collection applications is reviewed. This review outlines the uses of new powerful microfluidic exosome detection tools for biologists and clinicians, as well as exosome separation tools for microfluidic engineers. Current challenges of exosome separation methodologies are also described, in order to highlight areas for future research and development.

Yang F ，Liao X ，Tian Y ，Li G ... -  《-》

[Microfluidic strategies for separation and analysis of circulating exosomes].

Chen W ，Gan Z ，Qin J 《-》

Microfluidic-Based Exosome Analysis for Liquid Biopsy.

Liquid biopsy offers non-invasive and real-time molecular profiling of individual patients, and is thus considered a revolutionary technology in precision medicine. Exosomes have been acknowledged as significant biomarkers in liquid biopsy, as they play a central role in cell-cell communication and are closely related to the pathogenesis of most human malignancies. Nevertheless, in biofluids exosomes always co-exist with other particles, and the cargo components of exosomes are highly heterogeneous. Thus, the isolation and molecular characterization of exosomes are still technically challenging. Microfluidics technology effectively addresses this challenge by virtue of its inherent advantages, such as precise manipulation of fluids, low consumption of samples and reagents, and a high level of integration. Recent advances in microfluidics allow in situ exosome capture and molecular detection with unprecedented selectivity and sensitivity. In this review, the state-of-the-art developments in microfluidics-based exosome research, including exosome isolation approaches and molecular detection strategies, with highlights of the characterization of exosomal biomarkers in cancer liquid biopsy is summarized. The major challenges are also discussed and some perspectives for the future directions of exosome-based liquid biopsy in microfluidic systems are presented.

Lin B ，Lei Y ，Wang J ，Zhu L ，Wu Y ，Zhang H ，Wu L ，Zhang P ，Yang C ... -  《Small Methods》

The Yin and Yang of exosome isolation methods: conventional practice, microfluidics, and commercial kits.

Exosomes are a subset of extracellular vesicles released from various cells, and they can be found in different bodily fluids. Exosomes have been utilized as biomarkers to diagnose many diseases and to monitor therapy efficiency as they represent the status and origin of the cell, which they are released from. Considering that they co-exist in bodily fluids with other types of particles, their isolation still remains challenging since conventional methods are time-consuming, user-dependent, and result in low isolation yield. This review summarizes the conventional strategies and microfluidic-based methods for exosome isolation along with their strengths and limitations. In particular, microfluidic devices emerge as a promising approach to tackle the existing limitations of conventional methods, and they provide unique features, such as operating with minute volume of samples and rapid process, in order to isolate exosomes with the high yield and the high purity, which make them unprecedented tools for molecular biology and clinical applications in exosome research. This review further elaborates on the existing microfluidic-based exosome isolation methods and denotes their benefits and drawbacks. Herein, we also introduce various commercially available platforms and kits for exosome isolation along with their working principles.

Shirejini SZ ，Inci F 《-》