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

Abstract

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.

Opportunities and limitations of membrane-based preconcentration for rapid and continuous diagnostic applications

“…In conclusion, when considering the work of others 15,17,19–21,27,28 and our groups work, 29,32 membrane preconcentration remains attractive due to its simplicity compared other preconcentration techniques. 13,14,16,18 However, the applied value of membrane-based preconcentration is limited by the alternative of being able to use a more sensitive laboratory or clinic-based test.…”

“…Many rapid influenza tests use a nasopharyngeal swab and extraction buffer to release the nucleoprotein, and therefore test sensitivities could be improved with preconcentration. Multiple membranes were tested in the lab to determine their flux (see original publication for membrane characterization procedure detail 32 ), and plotted as seen in Fig. 4b.…”

“…For example, some methods include osmotic pressure, 29 electrokinetics, 20,21 and pneumatic pressure. 32…”

“…In our work, methods of fluid removal included osmosis, 29 vacuum, 32 wicking, and pneumatic pressure. 32 Our goal was to find a method which is rapid, reliable, and cost effective to create a device which could easily be integrated into rapid diagnostic tests or continuous diagnostics which require rapid preconcentration to enable ‘real time’ data.…”

“…In our work, methods of fluid removal included osmosis, 29 vacuum, 32 wicking, and pneumatic pressure. 32 Our goal was to find a method which is rapid, reliable, and cost effective to create a device which could easily be integrated into rapid diagnostic tests or continuous diagnostics which require rapid preconcentration to enable ‘real time’ data. Based on our cumulative findings, in this article we will discuss the major challenges facing membrane-based concentration and important elements that must be considered for such a device to be successful.…”