Microfluidic devices for glycobiomarker detection in cancer

Abstract

During oncogenesis, several alterations occur within cells, one of them being the abnormal glycosylation of proteins, resulting in the formation of glycoproteins with aberrant glycan structures, which can be secreted into the blood stream. Their specific association to tumour cells makes them useful indicators (biomarkers) of the oncogenic process and their detection in blood can be employed in different stages of tumour development for early detection, prognosis and therapeutic drug monitoring. Due to the importance of detecting cancer-associated glycoproteins with aberrant glycosylation in blood or serum, analytical methodologies with improved performance are required to ameliorate the laboratorial tests currently used for the detection of these analytes. Microfluidics was created to facilitate the implementation of simple and point-of-care analysis, away from a centralized laboratory. The massive use of microfluidic systems in clinical settings can be seen in pregnancy tests and diabetes control, for example. But what about other clinical domains, such as the detection of glycoproteins with aberrant glycans secreted by tumour cells? Are microfluidic systems helpful in this case? This review analyses the requirements of a microfluidic assay for the detection of low-abundant blood/serum cancer-associated glycoproteins with abnormal glycans and the progresses that have been made in the last years to develop integrated microfluidic devices for this particular application. The diverse microfluidic systems found in literature present, in general, the same analytical performance as the conventional assays but have additional advantages, namely a reduction in assay times, a decrease of sample and reagent consumption and lower costs. The review will also focus on the improvements that are still needed for better biosensing of this type of cancer biomarkers using microfluidic devices.

Keywords: Aberrant glycosylation; Automated assays; Cancer biomarkers; Glycoproteins; Microfluidics; Miniaturized systems; Serum.