[Advances in microchip electrophoresis for the separation and analysis of biological samples].

Microchip electrophoresis is a separation technology that involves fluid manipulation in a microchip; the advantages of this technique include high separation efficiency, low sample consumption, and fast and easy multistep integration. Microchip electrophoresis has been widely used to rapidly separate and analyze complex samples in biology and medicine. In this paper, we review the research progress on microchip electrophoresis, explore the fabrication and separation modes of microchip materials, and discuss their applications in the detection and analysis of biological samples. Research on microchip materials can be mainly categorized into chip materials, channel modifications, electrode materials, and electrode integration methods. Microchip materials research involves the development of silicon, glass, polydimethylsiloxane and polymethyl methacrylate-based, and paper electrophoretic materials. Microchannel modification research primarily focuses on the dynamic and static modification methods of microchannels. Although chip materials and fabrication technologies have improved over the years, problems such as high manufacturing costs, long processing time, and short service lives continue to persist. These problems hinder the industrialization of microchip electrophoresis. At present, few static methods for the surface modification of polymer channels are available, and most of them involve a combination of physical adsorption and polymers. Therefore, developing efficient surface modification methods for polymer channels remains a necessary undertaking. In addition, both dynamic and static modifications require the introduction of other chemicals, which may not be conducive to the expansion of subsequent experiments. The materials commonly used in the development of electrodes and processing methods for electrode-microchip integration include gold, platinum, and silver. Microchip electrophoresis can be divided into two modes according to the uniformity of the electric field: uniform and non-uniform. The uniform electric field electrophoresis mode mainly involves micro free-flow electrophoresis and micro zone electrophoresis, including micro isoelectric focusing electrophoresis, micro isovelocity electrophoresis, and micro density gradient electrophoresis. The non-uniform electric field electrophoresis mode involves micro dielectric electrophoresis. Microchip electrophoresis is typically used in conjunction with conventional laboratory methods, such as optical, electrochemical, and mass spectrometry, to achieve the rapid and efficient separation and analysis of complex samples. However, the labeling required for most widely used laser-induced fluorescence technologies often involves a cumbersome organic synthesis process, and not all samples can be labeled, which limits the application scenarios of laser-induced fluorescence. The applications of unlabeled microchip electrophoresis-chemiluminescence/dielectrophoresis are also limited, and simplification of the experimental process to achieve simple and rapid microchip electrophoresis remains challenging. Several new models and strategies for high throughput in situ detection based on these detection methods have been developed for microchip electrophoretic systems. However, high throughput analysis by microchip electrophoresis is often dependent on complex chip structures and relatively complicated detection methods; thus, simple high throughput analytical technologies must be further explored. This paper also reviews the progress on microchip electrophoresis for the separation and analysis of complex biological samples, such as biomacromolecules, biological small molecules, and bioparticles, and forecasts the development trend of microchip electrophoresis in the separation and analysis of biomolecules. Over 250 research papers on this field are published annually, and it is gradually becoming a research focus. Most previous research has focused on biomacromolecules, including proteins and nucleic acids; biological small molecules, including amino acids, metabolites, and ions; and bioparticles, including cells and pathogens. However, several problems remain unsolved in the field of microchip electrophoresis. Overall, microchip electrophoresis requires further study to increase its suitability for the separation and analysis of complex biological samples.