Nanometer-scale pores have demonstrated potential for the electrical detection, quantification, and characterization of molecules for biomedical applications and the chemical analysis of polymers. Despite extensive research in the nanopore sensing field, there is a paucity of theoretical models that incorporate the interactions between chemicals (i.e., solute, solvent, analyte, and nanopore). Here, we develop a model that simultaneously describes both the current blockade depth and residence times caused by individual poly(ethylene glycol) (PEG) molecules in a single α-hemolysin ion channel. Modeling polymer-cation binding leads to a description of two significant effects: a reduction in the mobile cation concentration inside the pore and an increase in the affinity between the polymer and the pore. The model was used to estimate the free energy of formation for K þ -PEG inside the nanopore (≈ − 49.7 meV) and the free energy of PEG partitioning into the nanopore (≈0.76 meV per ethylene glycol monomer). The results suggest that rational, physical models for the analysis of analyte-nanopore interactions will develop the full potential of nanopore-based sensing for chemical and biological applications.alpha-hemolysin | nanopore-based sensing | polymer confinement | polymer analysis P olymers play a fundamental role in life (1) and are central to many emerging technologies (2). Many of these applications require a detailed understanding of the structure, morphology, and chemical interactions of polymers under confinement in either 2-dimensional films (3) or narrow tubes (4). The ability to isolate and study single molecules has shown promise in overcoming the limitations of measurements with ensemble averages and permits probing the inter-and intra-molecular forces, structural changes, and dynamics of polymers (for a detailed review of single-molecule polymer analysis see refs. 5 and 6).Molecules partition into a nanopore and alter the flow of ions resulting in distinct current blockades that can be used to detect, characterize, and quantify a wide range of polymer types (7). These include single-stranded RNA and DNA (8-10), proteins (11-14), biowarfare agents (15), therapeutic agents against anthrax toxins (15, 16), and chemically synthesized molecules (14,(17)(18)(19)(20). More recently, single nanopores were used to determine the size distribution of polymers in a manner akin to mass spectrometry (19).To fully realize the potential of nanopore-based sensors, it is important to develop a detailed understanding of the physical and chemical interactions of polymers with the nanopore, solvent, electrolyte, and other components. In this work, the interaction between poly(ethylene glycol) (PEG) and the α-hemolysin (αHL) channel in a high ionic strength electrolyte was used to develop a unique model of polymers confined within single nanopores.Previous attempts to describe the magnitude of PEG-induced nanopore current blockades focused on volume exclusion (21) and/or microviscosity (22), which required adjustable ad hoc...

Nitric oxide (NO)-releasing sol-gel materials are synthesized by combining aminefunctionalized alkoxysilanes (aminosilanes) with alkyltrimethoxysilanes (alkylsilanes). Upon hydrolysis and condensation, the amine-functionalized silanes are covalently bound to the alkyltrimethoxysilane backbone and easily converted to diazeniumdiolate NO donors via exposure to high pressures of NO. Immersion of the sol-gel into solution is not required to initiate NO release. The NO-release characteristics of the sol-gels are easily controlled by varying the type and amount of the aminosilane precursor in the sol. The sol-gel coatings release NO for up to 20 d with average fluxes between 8.0 × 10 -12 and 5.6 × 10 -11 mol‚s -1 ‚cm -2 (coating thickness of 50 µm) over the first 10 h. These materials exhibit reduced platelet and bacterial adhesion. The results indicate that sol-gel chemistry may be an effective strategy for preparing coatings that release NO both controllably and locally for a range of applications including blood-and tissue-based devices.

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The antibacterial characteristics of nitric oxide (NO)-releasing sol-gel coatings are described. The NO release from these surfaces is steady over short periods (approximately 1 h) and measurable over several days. The ability of NO to prevent bacterial adhesion is evaluated by exposing controls and NO-releasing sol-gels to approximately 10(8) colony-forming units (cfu)/mL saline suspensions of Pseudomonas aeruginosa. Pseudomonas aeruginosa adhesion to sol-gel controls varies depending on the sol-gel formulation. Sol-gel surfaces capable of NO release decrease bacterial adhesion by 30% to 95% relative to controls. The contact angle measurements of control and NO-releasing surfaces are similar, supporting NO's action as an antibacterial agent against bacterial adhesion.

Nitric oxide (NO) releasing sol-gel materials coated with poly(vinyl chloride) (PVC) films exhibit increased stability at ambient and physiological temperatures. The polymer overcoat, however, reduces the NO fluxes by 5-35% over the initial week of release. The variation in NO fluxes between unmodified and PVC-coated sol-gels is negligible after 7 days. The PVC polymeric layer provides controlled surface chemistry for systematic studies of the effects of NO release on bacterial adhesion. As an example, the adhesion of Pseudomonas aeruginosa and Proteus mirabilis at PVC-coated NO-releasing sol-gels is investigated. A direct NO dependence on the reduction of P. aeruginosa adhesion is observed for NO fluxes up to 20 pmol cm(-2) s(-1). Although decreased by 50% in the presence of NO release, P. mirabilis adhesion does not appear to correlate to the flux of NO release. PVC-coated NO-releasing sol-gels may prove useful for studying the effects of localized NO release on other biological and chemical systems.

Nonelectrolyte polymers of poly(ethylene glycol) (PEG) were used to estimate the diameter of the ion channel formed by the Bacillus anthracis protective antigen 63 (PA(63)). Based on the ability of different molecular weight PEGs to partition into the pore and reduce channel conductance, the pore appears to be narrower than the one formed by Staphylococcus aureus alpha-hemolysin. Numerical integration of the PEG sample mass spectra and the channel conductance data were used to refine the estimate of the pore's PEG molecular mass cutoff (approximately 1400 g/mol). The results suggest that the limiting diameter of the PA(63) pore is<2 nm, which is consistent with an all-atom model of the PA(63) channel and previous experiments using large ions.