Microfluidic system for near-patient extraction and detection of miR-122 microRNA biomarker for drug-induced liver injury diagnostics

Maïwenn Kersaudy-Kerhoas, Antonio Liga, Appan Roychoudhury, Marilena Stamouli, Rhiannon Grant, Damaso Sanchez Carrera, Holger Schulze, Witold Mielczarek, Wilna Oosthuyzen, Juan F. Quintana, Paul Dickinson, Amy H. Buck, Nicholas R. Leslie, Jurgen Haas, Till T. Bachmann, James W. Dear

Research output: Contribution to journalArticlepeer-review

Abstract

Drug-induced liver injury (DILI) results in over 100 000 hospital attendances per year in the UK alone and is a leading cause for the post-marketing withdrawal of new drugs, leading to significant financial losses. MicroRNA-122 (miR-122) has been proposed as a sensitive DILI marker although no commercial applications are available yet. Extracellular blood microRNAs (miRNAs) are promising clinical biomarkers but their measurement at point of care remains time-consuming, technically challenging, and expensive. For circulating miRNA to have an impact on healthcare, a key challenge to overcome is the development of rapid and reliable low-cost sample preparation. There is an acknowledged issue with miRNA stability in the presence of hemolysis and platelet activation, and no solution has been demonstrated for fast and robust extraction at the site of blood draw. Here, we report a novel microfluidic platform for the extraction of circulating miR-122 from blood enabled by a vertical approach and gravity-based bubble mixing. The performance of this disposable cartridge was verified by standard quantitative polymerase chain reaction analysis on extracted miR-122. The cartridge performed equivalently or better than standard bench extraction kits. The extraction cartridge was combined with electrochemical impedance spectroscopy to detect miR-122 as an initial proof-of-concept toward an application in point-of-care detection. This platform enables the standardization of sample preparation and the detection of miRNAs at the point of blood draw and in resource limited settings and could aid the introduction of miRNA-based assays into routine clinical practice.
Original languageEnglish
Article number024108
Number of pages13
JournalBiomicrofluidics
Volume16
Issue number2
Early online date18 Apr 2022
DOIs
Publication statusE-pub ahead of print - 18 Apr 2022

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