[Research progress in the application of external field separation technology and microfluidic technology in the separation of micro/nanoscales].

The micro/nanoscales concerns interactions of entities with sizes in the range of 0.1-100 μm, such as biological cells, proteins, and particles. The separation of micro/nanoscales has been of immense significance for drug development, early-stage cancer detection, and customized precision therapy. For example, in recent years, rapid advances in the field of cell therapy have necessitated the development of simple and effective cell separation techniques. The isolation technique allows the collection of the required stem cells from complex samples. With the development of materials science and precision medicine, the separation of particles is also critical. The key physicochemical properties of micro/nanoscales are highly dependent on their specific size, shape, functional group, and mobility (based on the charged characteristics), which control their performance in the separation system. The current demand has made the simultaneous innovation of a separation system and an on-line detection platform imperative. Accordingly, various analytical methods involving the use of external forces, such as the flow field, magnetic field, electric field, and acoustic field, have been used for micro/nanoscales separation. Based on the physical and chemical parameters of the separation materials, these analytical methods can select different external force fields for micro/nanoscales separation, enabling real-time, accurate, efficient, and selective separation. However, at present, most of the applied field separation technologies require complex equipment and a large sample amount. This makes it crucial to miniaturize and integrate separation technologies for low-cost, rapid, and accurate micro/nanoscales separation. Microfluidic technology is a representative micro/nanoscales separation technology. It requires only a small volume of liquid, making it cost-effective; its high throughput enables continuous separation and analysis; its fast response in a microchip can allow many reactions; and finally, the miniaturization of the device allows the coupling of multiple detectors with the microchip. With the continuous growth and progress of microfluidic technology, some microfluidic platforms are now able to achieve the non-destructive separation of cells. They also enable on-line detection, offer high separation efficiency, and allow rapid separation for different biological samples. This review primarily summarizes recent advances in microfluidic chips based on flow field, electric field, magnetic field, acoustic field, and field separation technologies to improve the micro/nanoscales separation efficiency. This review also discusses the various external force fields of micro/nanoscales, such as a microparticle, single cell separation of substances classified introduction, and summarizes the advantages and disadvantages of their application and development. Finally, the prospect of the combined application of external field separation technology and microfluidic technology in the early screening of cancer cells and for precise micro/nanoscales separation is discussed, and the advantages and potential applications of the combined technology are proposed.