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Microfluidic compartmentalization to identify gene biomarkers of infection
Ahmad Ismat Kathrada1, Shih-Chung Wei, Ying Xu2
1Department of Biomedical Engineering, National University of Singapore, 4 Engineering Drive 3, Block 4, #04-08, Singapore 117583.
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.
Insights
Microfluidic technologies offer advanced gene biomarker detection for infectious diseases, improving accuracy and enabling point-of-care diagnostics. These innovations move testing from labs to the field, enhancing pandemic prevention efforts.
Area of Science:
- Biomedical Engineering
- Molecular Diagnostics
- Infectious Disease Research
Background:
- Infectious diseases pose significant global health threats, often presenting with similar symptoms that complicate diagnosis and treatment.
- Current polymerase chain reaction (PCR) methods for gene biomarker detection are sensitive but resource-intensive, limiting point-of-care applications.
- Accurate and rapid identification of specific pathogens is crucial for effective therapeutic intervention and pandemic prevention.
Purpose of the Study:
- To review microfluidic approaches for gene biomarker compartmentalization in infectious disease detection.
- To highlight advancements in microfluidic technologies for sensitive and precise gene biomarker quantification.
- To discuss the potential of these technologies for point-of-care diagnostics and decentralized infectious disease surveillance.
Main Methods:
- Review of three microfluidic platforms for gene biomarker detection: microwell-based PCR, droplet-based PCR, and integrated point-of-care devices.
- Discussion of sample volume minimization techniques, from microliters (μl) in microwells to picoliters (pl) in droplets.
- Analysis of technological improvements including cost, automation, usability, and portability.
Main Results:
- Microwell-based platforms enhance sensitivity by capturing target genes in small sample volumes.
- Droplet-based PCR enables precise gene quantification through significant sample volume minimization.
- Integrated microfluidic devices facilitate the development of portable, low-cost point-of-care diagnostic tools.
Conclusions:
- Microfluidic technologies significantly advance infectious disease diagnostics by enabling sensitive and precise gene biomarker detection.
- These platforms overcome the limitations of traditional PCR, offering improved cost-effectiveness, automation, and portability.
- The development of microfluidic point-of-care devices is critical for decentralizing testing and improving global response to infectious disease outbreaks.
