Development of nanoparticle blockage based nanopore devices for biosensing and controlled chemical releasing

Solid-state nanopore devices have received extensive attention across scientific and engineering disciplines due to their applications in a variety of fields, including biological and chemical sensing, drug delivery, DNA sequencing, power generation, and water desalination. These nanoscale structures have at least one cross-sectional dimension between a few nanometers and 100 nm and their length is approximately within an order of magnitude of their diameter. The unique surface forces and physical/chemical interactions that arise from the nanoscale confinement are what make these nanopores cross the boundaries of many different disciplines. Although significant progress has been achieved over the last two decades, existing applications and studies have mainly been based on molecules/particles translocation through single nanopore. Other applications beyond translocation-based nanopore sensing and transport control have seldomly been explored. This thesis aims to develop new applications of solid-state nanopore for biosensing and controlled chemical releasing based on the blockage/trapping of nanoparticles near nanopores instead of nanopore translocation. We present three new nanoparticle blockage-enabled nanopore platforms, each of which addresses a distinct challenge for current nanopore systems. Firstly, we present a novel nanopore-based electrokinetic tweezer that can simultaneously detect, characterize, manipulate, and quantify nanoparticles in solution with single-nanoparticle resolution and high sensitivity. This technique has shared ground with both resistive pulse and optical sensing, giving it an advantage over existing characterization methods. Secondly, we report a new optical blockage-based nanopore array sensing platform for the rapid detection and quantification of ultra-low concentrations of nanoparticles. Using this platform, we demonstrate a detection limit down to 0.5 aM within 5 minutes. This concentration is within the same order of magnitude (or even lower) than many clinically relevant biomolecules such as viral nucleic acids and circulating tumor DNAs. Our detection method is significantly faster and has sensitivity 3 orders of magnitude lower than previously reported nanopore sensing platforms. In addition, we demonstrate that quantitative information about the particles concentration can be obtained by analyzing the temporal blockage of events. Thirdly, we report a new rapid and reversible nanopore gating strategy based on nanoparticle blockage that was inspired by the “ball-and-chain” inactivation mechanism in gated protein channels. This nanoparticle-blockage-enabled nanopore gating strategy offers unprecedented control of ionic/chemical transport with the transmission of chemical signals at sub-micrometer and millisecond scales which are essentially the most two important features of natural intercellular communications. The nanoparticle blockage-based nanopore devices described in this thesis can potentially be incorporated with other micro/nanofluidic components. We expect that incorporating these tools into micro/nanofluidic systems could significantly improve the capabilities of current microfluidic and nanofluidic technologies.2023-08-29T00:00:00