Recently, single cell analysis is becoming more and more important to elucidate cellular heterogeneity. Except for nucleic acid that can be amplified by PCR, the required technical level for single cell analysis is extremely high and the appropriate design of sample preparation and a sensitive analytical system is necessary. Capillary/microchip electrophoresis (CE/MCE) can separate biomolecules in nL-scale solution with high resolution, and it is highly compatible with trace samples like a single cell. Coupled with highly sensitive detectors such as laser-induced fluorescence and nano- electrospray ionization-mass spectrometry, zmol level analytes can be detected. For further enhancing sensitivity, online sample preconcentration techniques can be employed. By integrating these high-sensitive techniques, single cell analysis of metabolites, proteins, and lipids have been achieved. This review paper highlights successful research on CE/MCE- based trace bioanalysis in recent 10 years. Firstly, an overview of basic knowledge on CE/MCE including sensitivity enhancement techniques is provided. Applications to trace bioanalysis are then introduced with discussion on current issues and future prospects.
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