Microfluidic compartmentalization to identify gene biomarkers of infection.

Abstract

Infectious diseases caused by pathogens, such as SARS-COV, H7N9, severe fever with thrombocytopenia syndrome virus, and human immunodeficiency virus, have fatal outcomes with common features of severe fever and subsequent bacterial invasion progressing to multiorgan failure. Gene biomarkers are promising to distinguish specific infections from others with similar presenting symptoms for the prescription of correct therapeutics, preventing pandemics. While routine laboratory methods based on polymerase chain reaction (PCR) to measure gene biomarkers have provided highly sensitive and specific viral detection techniques over the years, they are still hampered by their precision and resource intensity precluding their point-of-care use. Recently, there has been growing interest in employing microfluidic technologies to advance current methods for infectious disease determination via gene biomarker measurements. Here, based on the requirement of infection detection, we will review three microfluidic approaches to compartmentalize gene biomarkers: (1) microwell-based PCR platforms; (2) droplet-based PCR; and (3) point-of-care devices including centrifugal chip, SlipChip, and self-powered integrated microfluidic point-of-care low-cost enabling chip. By capturing target genes in microwells with a small sample volume (∼μl), sensitivity can be enhanced. Additionally, with the advance of significant sample volume minimization (∼pl) using droplet technology, gene quantification is possible. These improvements in cost, automation, usability, and portability have thereby allowed point-of-care applications to decentralize testing platforms from laboratory-based settings to field use against infections.