LAUSR

Although resistive pulse sensing using solid state nanopores is capable of single molecule sensitivity, previous work has shown that measurements can often significantly deviate from theoretically predicted current amplitudes and event frequencies, because most nanoparticles pass through the pore too quickly for accurate detection or resolution by typical measurement apparatus. Here, we show that a hydrogel placed on the distal side of a nanopore can increase the residence time of nanoparticles within the nanopore, significantly increasing the detection rate and allowing improved resolution of blockage currents. The method is simple and inexpensive to implement while being label-free and applicable to a wide range of nanoparticle targets. Using hydrogel-backed nanopores, we detected the protein IgG with event frequencies several orders of magnitude higher than in the absence of the hydrogel, and with larger measured currents that agree well with theoretical models. We also show that the improved measurement also enables discrimination of IgG and BSA in a mixed solution. Lastly, we show that measurements of IgG with the hydrogel-backed nanopores can also yield current amplitude distributions that can be analyzed to infer its approximate shape.