Static and Dynamic Permeability Assay for Hydrophilic Small Molecules Using a Planar Droplet Interface Bilayer

Because numerous drugs are administered through an oral route and primarily absorbed at the intestine, the prediction of drug permeability across an intestinal epithelial cell membrane has been a crucial issue in drug discovery. Thus, various <i>in vitro</i> permeability assays have been developed such as the Caco-2 assay, the parallel artificial membrane permeability assay (PAMPA), the phospholipid vesicle-based permeation assays (PVPA) and Permeapad. However, because of the time-consuming and quite expensive process for culturing cells in the Caco-2 assay and the unknown microscopic membrane structures of the other assays, a simpler yet more accurate and versatile technique is still required. Accordingly, we developed a new platform to measure the permeability of small molecules across a planar freestanding lipid bilayer with a well-defined area and structure. The lipid bilayer was constructed within a conventional UV spectrometer cell, and the transport of drug molecules across the bilayer was recorded by UV absorbance over time. We then computed the permeability from the time-dependent diffusion equation. We tested this assay for five exemplary hydrophilic drugs and compared their values with previously reported ones. We found that our assay has a much higher permeability compared to the other techniques, and this higher permeability is related to the thickness of the lipid bilayer. Also we were able to measure the dynamic permeability upon the addition of a membrane-disrupting surfactant demonstrating that our assay has the capability to detect real-time changes in permeability across the lipid bilayer

Structural Determinants of Chirally Selective Transport of Amino Acids through the α‑Hemolysin Protein Nanopores of Free-Standing Planar Lipid Membranes

Despite the importance of the enantioselective transport of amino acids through transmembrane protein nanopores from fundamental and practical perspectives, little has been explored to date. Here, we study the transport of amino acids through α-hemolysin (αHL) protein pores incorporated into a free-standing lipid membrane. By measuring the transport of 13 different amino acids through the αHL pores, we discover that the molecular size of the amino acids and their capability to form hydrogen bonds with the pore surface determine the chiral selectivity. Molecular dynamics simulations corroborate our findings by revealing the enantioselective molecular-level interactions between the amino acid enantiomers and the αHL pore. Our work is the first to present the determinants for chiral selectivity using αHL protein as a molecular filter

Fluorescence Recovery after Merging a Surfactant-Covered Droplet: A Novel Technique to Measure the Diffusion of Phospholipid Monolayers at Fluid/Fluid Interfaces

We present a novel technique to measure diffusion coefficients of insoluble surfactant monolayers. We merge a surfactant-coated droplet with a fluorescently labeled planar monolayer. During the merging process, a monolayer on a droplet displaces the existing planar monolayer, leaving a dark area when viewed under a fluorescence microscope. We measure fractional intensities as the dyes recover, which allows diffusion coefficients to be computed. We validate this technique with the two most common phospholipid monolayers (DPPC and DOPC) and study the diffusion of their mixtures. The proposed technique has several advantages over the FRAP technique and is potentially capable of measuring the diffusion of any soluble/insoluble surfactant monolayers

Removal Analysis of Residual Photoresist Particles Based on Surface Topography Affected by Exposure Times of Ultraviolet and Developer Solution

Particle removal from the surface of a substrate has been an issue in numerous fields for a long time. In semiconductor processes, for instance, the formation of clean surfaces by removing photoresist (PR) must be followed in order to create neat patterns. Although PR removal has been intensively investigated recently, little is known about how ultraviolet (UV) and developer solutions alter the PR resin (and in what manner) near the surface. While varying the exposure times of UV and developer solution, we investigated the topographic changes on the surfaces of PR resin films and particles. The measured surface properties were then correlated with the detachment force determined using films, and eventually with the residual PR particle removal percentages obtained in a microchannel. Using a positive PR and a base developer solution, we demonstrated that UV causes the surface of PR resin to become hydrophilic and wavy, whereas the developer solution produces a surface with a larger degree of roughness by swelling and partially dissolving the resin. Ultimately, the increased roughness decreased the effective contact area between PR resins, hence decreasing the detachment force and increasing the particle removal percentages. We anticipate that our findings will help understand residual particle issues, particularly on the removal mechanism of PR resins based on surface topography

Thermally Fast-Curable, “Sticky” Nanoadhesive for Strong Adhesion on Arbitrary Substrates

Demand of adhesives that are strong but ultrathin with high flexibility, optical transparency, and long-term stability has been rapidly growing recently. Here, we suggest a thermally curable, “sticky” nanoadhesive with outstanding adhesion strength accomplished by single-side deposition of the nanoadhesive on arbitrary substrates. The sticky nanoadhesive is composed of an ionic copolymer film generated from two acrylate monomers with tertiary amine and alkyl halide functionalities, formed by a solvent-free method, initiated chemical vapor deposition (iCVD). Because of the low glass transition temperature (<i>T</i>_g) of the copolymer (−9 °C), the ionic copolymer shows a viscoelastic behavior that makes the adhesive attachable to various substrates, regardless of the substrate materials. Moreover, the copolymer film is thermally curable via a cross-linking reaction between the alkyl halide and tertiary amine functionalities, which substantially increased the adhesion strength of the 500 nm thick nanoadhesive greater than 25 N/25 mm within 5 min of curing at 120 °C. The adhesive thickness can further be reduced to 50 nm to achieve greater than 35 N/25 mm within 30 min at 120 °C. The nanoadhesive layer can form uniform adhesion in a large area substrate (up to 130 × 100 mm²) with the deposition of the adhesive only on one side of the substrates to be laminated. Because of its ultrathin nature, the nanoadhesive is also optically transparent as well as highly flexible, which will play a critical role in fabrication and the lamination of future flexible/wearable devices

Thermally Fast-Curable, “Sticky” Nanoadhesive for Strong Adhesion on Arbitrary Substrates

Demand of adhesives that are strong but ultrathin with high flexibility, optical transparency, and long-term stability has been rapidly growing recently. Here, we suggest a thermally curable, “sticky” nanoadhesive with outstanding adhesion strength accomplished by single-side deposition of the nanoadhesive on arbitrary substrates. The sticky nanoadhesive is composed of an ionic copolymer film generated from two acrylate monomers with tertiary amine and alkyl halide functionalities, formed by a solvent-free method, initiated chemical vapor deposition (iCVD). Because of the low glass transition temperature (<i>T</i>_g) of the copolymer (−9 °C), the ionic copolymer shows a viscoelastic behavior that makes the adhesive attachable to various substrates, regardless of the substrate materials. Moreover, the copolymer film is thermally curable via a cross-linking reaction between the alkyl halide and tertiary amine functionalities, which substantially increased the adhesion strength of the 500 nm thick nanoadhesive greater than 25 N/25 mm within 5 min of curing at 120 °C. The adhesive thickness can further be reduced to 50 nm to achieve greater than 35 N/25 mm within 30 min at 120 °C. The nanoadhesive layer can form uniform adhesion in a large area substrate (up to 130 × 100 mm²) with the deposition of the adhesive only on one side of the substrates to be laminated. Because of its ultrathin nature, the nanoadhesive is also optically transparent as well as highly flexible, which will play a critical role in fabrication and the lamination of future flexible/wearable devices