A decade of microchip electrophoresis for clinical diagnostics – A review of 2008–2017

Abstract

A core element in clinical diagnostics is the data interpretation obtained through the analysis of patient samples. To obtain relevant and reliable information, a methodological approach of sample preparation, separation, and detection is required. Traditionally, these steps are performed independently and stepwise. Microchip capillary electrophoresis (MCE) can provide rapid and high-resolution separation with the capability to integrate a streamlined and complete diagnostic workflow suitable for the point-of-care setting. Whilst standard clinical diagnostics methods normally require hours to days to retrieve specific patient data, MCE can reduce the time to minutes, hastening the delivery of treatment options for the patients. This review covers the advances in MCE for disease detection from 2008 to 2017. Miniaturised diagnostic approaches that required an electrophoretic separation step prior to the detection of the biological samples are reviewed. In the two main sections, the discussion is focused on the technical setup used to suit MCE for disease detection and on the strategies that have been applied to study various diseases. Throughout these discussions MCE is compared to other techniques to create context of the potential and challenges of MCE. A comprehensive table categorised based on the studied disease using MCE is provided. We also comment on future challenges that remain to be addressed.

Analytical techniques for multiplex analysis of protein biomarkers

“…To circumvent significant sheath liquid-mediated sample dilution and the limited sample loading capacity of CE, tapered emitters operating in the nanospray regime not only support lower flow rates of the sheath liquid, but also contribute to better desolvation, enhanced sensitivity, and better salt tolerance [122]. Miniaturization to a single microchip (MCE) with the use of an electrophoretic step prior to biomarker detection may lead to an attractive clinical diagnostic tool [123].…”

Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis

“…With regards to ME, the separation process occurring on the chip is based on the same principle as with CE, but the microfluidic separation device has unique features coming from the smaller planar format [20,33]. The typical ME design is a simple 'T' consisting of a separation channel and two side arms [34].…”

“…The very short analysis times characteristic of ME (less than a minute) make it useful for high throughput single-cell analysis and the detection of chemically labile species. Lastly, it is compatible with a number of detection platforms, including fluorescence, electrochemical, and mass spectrometric detection [20]. Additionally, the introduction of the sample-as well as its manipulation, reaction, and detection-can all be performed 'on-chip' in a very small volume (from micro-to few nanoliters).…”

Electrophoresis Applications Used in Medicine

“…Microchip electrophoresis systems are superior to other systems because they contain a large number of microchannels that allow the experiments to be carried out quickly and efficiently. It is also a fully automated system that allows minimum manuel use from sample processing to data analysis [40]. Since highly sensitive methods are required for ME, laser-induced fluorescence and electrochemical detection methods are used.…”