Analysis of pressure-driven membrane preconcentration for point-of-care assays

Point-of-care diagnostic devices for both physicians and patients themselves are now ubiquitous, but often not sensitive enough for highly dilute analytes (e.g., pre-symptomatic viral detection). Two primary methods to address this challenge include (1) increasing the sensitivity of molecular recognition elements with greater binding affinity to the analyte or (2) increasing the concentration of the analyte being detected in the sample itself (preconcentration). The latter approach, preconcentration, is arguably more attractive if it can be made universally applicable to a wide range of analytes. In this study, pressure-driven membrane preconcentration devices were developed, and their performance was analyzed for detecting target analytes in biofluids in the form of point-of-care lateral-flow assays (LFAs). The demonstrated prototypes utilize negative or positive pressure gradients to move both water and small interferents (salt, pH) through a membrane filter, thereby concentrating the analyte of interest in the remaining sample fluid. Preconcentration up to 33× is demonstrated for influenza A nucleoprotein with a 5 kDa pore polyethersulfone membrane filter. LFA results are obtained within as short as several minutes and device operation is simple (very few user steps), suggesting that membrane preconcentration can be preferable to more complex and slow conventional preconcentration techniques used in laboratory practice.