Engineering a point-of-care paper-microfluidic electrochemical device applied to the multiplexed quantitative detection of biomarkers in sputum

Health initiatives worldwide demand affordable point- of-care devices to aid in the reduction of morbidity and mortality rates of high-incidence infectious and noncommunicable diseases. However, the production of robust and reliable easy-to-use diagnostic platforms showing the ability to quantitatively measure several biomarkers in physiological fluids and that could in turn be decentralized to reach any relevant environment remains a challenge. Here, we show the particular combination of paper-microfluidic technology, electro- chemical transduction, and magnetic nanoparticle-based immunoassay approaches to produce a unique, compact, and easily deployable multiplex device to simultaneously measure interleukin-8, tumor necrosis factor-a, and myeloperoxidase biomarkers in sputum, developed with the aim of facilitating the timely detection of acute exacerbations of chronic obstructive pulmonary disease. The device incorporates an on-chip electrochemical cell array and a multichannel paper component, engineered to be easily aligned into a polymeric cartridge and exchanged if necessary. Calibration curves at clinically relevant biomarker concentration ranges are produced in buffer and artificial sputum. The analysis of sputum samples of healthy individuals and acutely exacerbated patients produces statistically significant biomarker concentration differences between the two studied groups. The device can be mass-produced at a low cost, being an easily adaptable platform for measuring other disease-related target biomarkers.
This research was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) grants PCIN-2016-052 and PCIN-2016-134 and by Portuguese Fundação para a Ciência e a Technologia grant ENMed/0049/2016, through the ERA-NET EuroNanoMed II initiative (LungCheck project). This research was also funded by the European Commision-NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI). This work used the Spanish ICTS Network MICRONANOFABS and was partly supported by the Spanish Ministry of Science and Innovation.
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Postprint (published version)