We present a method to trap nanoscale analytes in double nanohole (DNH) nanoapertures integrated on top of solid-state nanopores (ssNPs). The analytes are propelled by an electrophoretic force from the cis towards the trans side of the nanopore but are trapped in the process when they have reached the vicinity of the DNH-ssNP interface. The self-induced back action (SIBA) force, created by the plasmonic field between the tips of the DNH, opposes the electrophoretic force and enables simultaneous optical and electrical sensing of a single nanoparticle for many seconds. The SIBA actuated nanopore electrophoresis (SANE) sensor was fabricated using two-beam gas field ion source (GFIS) focused ion beam (FIB). Firstly, Ne FIB milling was used to create the DNH features and was combined with end pointing to stop milling at the metal-dielectric interface. Subsequently, He FIB was used to drill a 25 nm nanopore through the center of the DNH. The capabilities of the device are demonstrated using a series of three experiments involving nanoparticles, high-affinity protein ligand interactions and low-affinity protein-ligand interactions. The presence of optical trapping in the SANE sensor extended electrical sensing and translocation times by up to four orders of magnitude over classical nanopores. In addition, SANE sensor measurements enabled quantification of bimodal optical-electrical parameters that were quantified concurrently for each trapping event, which enabled distinguishing analytes from each other, specific from non-specific binding events, and protein complex formation. Importantly, the SANE sensor enabled ultra-high sensitivity in protein-ligand interaction detection. Electrically driven focusing of reactants into the sensor’s nanoscopic optical trap volume enabled formation of significant bound fractions (30–50% range) at reactant concentrations up to three orders of magnitude lower than the free solution equilibrium binding constant. Furthermore, the SANE sensor could measure the off-binding rate of low-affinity (micromolar) protein-ligand interactions that are challenging to measure with current label-free commercial assays.
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We thank Mr. Soeren Eyhusen and Mr. Chuong Huynh for permitting us with the access and providing technical guidance on focused ion beam milling at the Zeiss ORION NanoFab facility in Peabody, MA. We are also thankful to all the engineers and staff at the Shimadzu Institute Nanotechnology Research Center at the University of Texas at Arlington for their support and guidance. The authors acknowledge the financial support from the National Cancer Institute (1R21CA240220-01A1) and the National Science Foundation (CBET#2022398 and CBET#2022374).
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Renkes, S., Peri, S.S.S., Raza, M.U., Weidanz, J., Kim, M.J., Alexandrakis, G. (2022). Self-induced Back-Action Actuated Nanopore Electrophoresis (SANE) Sensing. In: Bowen, W., Vollmer, F., Gordon, R. (eds) Single Molecule Sensing Beyond Fluorescence . Nanostructure Science and Technology. Springer, Cham. https://doi.org/10.1007/978-3-030-90339-8_13
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