While solid-state nanopores show promise as single-molecule sensors for biomedical applications, in order to improve their resolution and efficiency, analyte molecules must be probed more frequently and must remain longer in the nanopore sensing volume. This proposal describes a novel, simple, and versatile method to improve nanopore sensitivity and temporal resolution by slowing translocation speed and increasing capture efficiency via interactions outside the nanopore, while still leaving the nanopore itself available for further functionalization. This will be achieved by applying a chemically tunable nanofiber polymeric mesh (NFM) directly to a solid-state nanopore chip, where its fibers (hydrophobic, cationic, or anionic) may interact with analyte molecules during sensing from outside the nanopore, guiding them into the sensing volume and slowing their movement through it. The NFM is composed of a network of fibers (100-1000 nm diameter) formed from poly(?-caprolactone) (PCL) doped with poly(glycerol-co-?-caprolactone) (PGC), deposited onto a surface by electrospinning. The PGC component of this polymer may be modified to include a range of side groups which confer hydrophobic, anionic, or cationic properties to the NFM. The fiber size and mesh density may be controlled by adjusting the electrospinning parameters. Thus, adjustment of the polymer NFM parameters will be completely independent of alterations to the nanopore surface itself. A broad range of designer translocation properties will be accessible for any solid-state nanopore application through simple selection of an appropriate NFM. We will first construct nanopore-nanofiber mesh (NP-NFM) hybrid devices with different charge and mesh characteristics, then screen these devices to determine which combinations are suitable for nanopore sensing. Candidate devices will be tested using a range of ssDNA and dsDNA lengths to determine how each type of NFM affects translocation and capture. The application of an external, chemically tunable coating that can improve sensing efficiency and resolution without requiring intrinsic modification of the nanopore will directly support efforts t develop viable nanopore-based sequencing and diagnostic platforms by enabling slower translocation speeds and increased threading probability.

Public Health Relevance

Solid-state nanopores show potential as single-molecule biosensors, but to date they lack the sensitivity required for diagnostic and sequencing applications because molecules move too infrequently and too quickly through the nanopore. We propose a simple process to layer a chemically tunable polymeric nanofiber mesh (NFM) coating immediately outside the nanopore. The NFM will interact with long analyte biopolymers, such as DNA, as they enter and translocate through the nanopore, guiding them more efficiently into the nanopore and slowing down their movement through it to improve nanopore sensing efficiency and resolution.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Exploratory/Developmental Grants (R21)
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Nanotechnology Study Section (NANO)
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Hunziker, Rosemarie
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Boston University
Engineering (All Types)
Biomed Engr/Col Engr/Engr Sta
United States
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Falde, Eric J; Freedman, Jonathan D; Herrera, Victoria L M et al. (2015) Layered superhydrophobic meshes for controlled drug release. J Control Release 214:23-9
Hersey, Joseph S; Meller, Amit; Grinstaff, Mark W (2015) Functionalized Nanofiber Meshes Enhance Immunosorbent Assays. Anal Chem 87:11863-70
Squires, Allison H; Hersey, Joseph S; Grinstaff, Mark W et al. (2013) A nanopore-nanofiber mesh biosensor to control DNA translocation. J Am Chem Soc 135:16304-7