Nanofluidics Drives Point-of-care Technology for on the Spot Protein Marker Analysis with Rapid Actionable Results

Protein sensing in a nanofluidic environment dramatically shortens immunoassay time-to-result through the combined action of efficient mass transfer and short diffusion distances. Here, we report on a fully automated point-of-care in vitro diagnostic platform based on disposable capsule containing nanofluidic sensors in which fluorescent immunoassays are performed. Performances of the system were established with three model assays for ferritin, immunoglobulin E (IgE) and pancreatic stone protein (PSP). The described system has the typical high capture efficiency of nano-confined spaces combined with forced-flow, which induce a constant maximal concentration gradient on the sensor. Remarkably, analytes are detected in zeptomole quantities from a drop of blood. Dose-response curves show that high precision and accuracy are achieved in the clinically relevant assay ranges. Moreover, accuracy of the system is excellent agreement with laboratory reference method, as illustrated in a method comparison with total IgE as a model. While several academic proof-of-concepts have already described the possibility to exploit the properties of fluids at the nanoscale to develop immunoassay, the transition of these models to a product fulfilling requirements for use at the point-of-care in terms of operability, affordability, reliability and analytic performances remains a challenging endeavor. This study demonstrates that nanofluidic-based immunoassays can efficiently quantify protein biomarkers in the femto- and picomolar range within ultra-short assay time, high precision and accuracy on a closed, small, easyto- operate platform.