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      Biological particle separation techniques based on microfluidics

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          Abstract

          Biological particle separation has wide applications in medical diagnosis, bioengineering, and various other domains. Traditional methods, such as filtration, density gradient centrifugation, and size exclusion chromatography, face many challenges, including low separation resolution, low purity, and the inability to be seamlessly integrated into continuous processes. The development of microfluidics has paved the way for efficient and precise biological particle separation. Microfluidic chip‐based methods can generally be performed continuously and automatically, and microfluidic chips can integrate multilevel operations, including mixing, separation, detection, and so forth, thereby achieving continuous processing of particles at various levels. This review comprehensively investigates biological particle separation techniques based on microfluidic chips. According to the different sources of force effect on the particles during the separation process, they can be divided into active separation, passive separation, and affinity separation. We introduce the principles and device design of these methods respectively, and compare their advantages and disadvantages. For the introduction of each method, we used the most classic and latest research cases as much as possible. Additionally, we discussed the differences between experimental standard particles and biological particles. Finally, we summarized the current limitations and challenges of existing microfluidic separation techniques, while exploring future trends and prospects.

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          Most cited references148

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          The origins and the future of microfluidics.

          The manipulation of fluids in channels with dimensions of tens of micrometres--microfluidics--has emerged as a distinct new field. Microfluidics has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology. But the field is still at an early stage of development. Even as the basic science and technological demonstrations develop, other problems must be addressed: choosing and focusing on initial applications, and developing strategies to complete the cycle of development, including commercialization. The solutions to these problems will require imagination and ingenuity.
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            Microfluidic large-scale integration.

            We developed high-density microfluidic chips that contain plumbing networks with thousands of micromechanical valves and hundreds of individually addressable chambers. These fluidic devices are analogous to electronic integrated circuits fabricated using large-scale integration. A key component of these networks is the fluidic multiplexor, which is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs. We used these integrated microfluidic networks to construct the microfluidic analog of a comparator array and a microfluidic memory storage device whose behavior resembles random-access memory.
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              Isolation of exosomes from whole blood by integrating acoustics and microfluidics

              We have developed a unique, integrated, on-chip technology that is capable of isolating exosomes or other types of extracellular vesicles, directly from undiluted whole-blood samples in an automated fashion. Automated exosome isolation enables biohazard containment, short processing time, reproducible results with little human intervention, and convenient integration with downstream exosome analysis units. Our method of integrating acoustics and microfluidics leads to the isolation of exosomes with high purity and yield. With its label-free, contact-free, and biocompatible nature, it offers the potential to preserve the structures, characteristics, and functions of isolated exosomes. This automated, point-of-care device can further help in advancing exosome-related biomedical research with potential applications in health monitoring, disease diagnostics, and therapeutics. Exosomes are nanoscale extracellular vesicles that play an important role in many biological processes, including intercellular communications, antigen presentation, and the transport of proteins, RNA, and other molecules. Recently there has been significant interest in exosome-related fundamental research, seeking new exosome-based biomarkers for health monitoring and disease diagnoses. Here, we report a separation method based on acoustofluidics (i.e., the integration of acoustics and microfluidics) to isolate exosomes directly from whole blood in a label-free and contact-free manner. This acoustofluidic platform consists of two modules: a microscale cell-removal module that first removes larger blood components, followed by extracellular vesicle subgroup separation in the exosome-isolation module. In the cell-removal module, we demonstrate the isolation of 110-nm particles from a mixture of micro- and nanosized particles with a yield greater than 99%. In the exosome-isolation module, we isolate exosomes from an extracellular vesicle mixture with a purity of 98.4%. Integrating the two acoustofluidic modules onto a single chip, we isolated exosomes from whole blood with a blood cell removal rate of over 99.999%. With its ability to perform rapid, biocompatible, label-free, contact-free, and continuous-flow exosome isolation, the integrated acoustofluidic device offers a unique approach to investigate the role of exosomes in the onset and progression of human diseases with potential applications in health monitoring, medical diagnosis, targeted drug delivery, and personalized medicine.

                Author and article information

                Contributors
                Journal
                Interdisciplinary Medicine
                Interdisciplinary Medicine
                Wiley
                2832-6245
                2832-6245
                April 2024
                April 20 2024
                April 2024
                : 2
                : 2
                Affiliations
                [1 ] Shenzhen Key Laboratory of Smart Healthcare Engineering Guangdong Provincial Key Laboratory of Advanced Biomaterials Department of Biomedical Engineering Southern University of Science and Technology Shenzhen Guangdong China
                [2 ] Yusuf Hamied Department of Chemistry University of Cambridge Cambridge UK
                Article
                10.1002/INMD.20240003
                a32eb3e8-2631-4ab1-9f66-fa146050e645
                © 2024

                http://creativecommons.org/licenses/by/4.0/

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