Hydrogel-Based Glucose Sensors: Effects of Phenylboronic Acid Chemical Structure on Response

Phenylboronic acids (PBAs) are being considered for glucose sensing and controlled insulin release, because of their affinity for diol-containing molecules. The interaction of immobilized PBAs in a hydrogel matrix with glucose can lead to volumetric changes that have been used to monitor glucose concentration and release insulin. Although the interaction of PBAs with diol-containing molecules has been intensively studied, the response of PBA-modified hydrogels as a function of the specific PBA chemistry is not well understood. To understand the interaction of immobilized PBAs with glucose in hydrogel systems under physiological conditions, the glucose-dependent volumetric changes of a series of hydrogel sensors functionalized with different classes of PBAs were investigated. The volume change induced by PBA-glucose interactions is converted to the diffracted wavelength shift by a crystalline colloidal array embedded in the hydrogel matrix. The PBAs studied contain varying structural parameters such as the position of the boronic acid on the phenyl ring, different substituents on PBAs and different linkers to the hydrogel backbone. The volumetric change of the PBA modified hydrogels is found to be highly dependent on the chemical structure of the immobilized PBAs. The PBAs that appear to provide linear volumetric responses to glucose are found to also have slow response kinetics and significant hysteresis, while PBAs that show nonlinear responses have fast response kinetics and small hysteresis. Electron-withdrawing substituents, which reduce the p<i>K</i>_a of PBAs, either increase or decrease the magnitude of response, depending on the exact chemical structure. The response rate is increased by PBAs with electron-withdrawing substituents. Addition of a methylene bridge between the PBA and hydrogel backbone leads to a significant decrease in the response magnitude. PBAs with specific desirable features can be selected from the pool of available PBAs and other PBA derivatives with desired properties can be designed according to the findings reported here

Polymer Brushes Patterned with Micrometer-Scale Chemical Gradients Using Laminar Co-Flow

We present a facile microfluidic method for forming narrow chemical gradients in polymer brushes. Co-flow of an alkylating agent solution and a neat solvent in a microfluidic channel forms a diffusion-driven concentration gradient, and thus a gradient in reaction rate at the interface of the two flows, leading to a quaternization gradient in the underlying poly­(2-(dimethylamino)­ethyl methacrylate) polymer brush. The spatial distribution of the quaternized polymer brush is characterized by confocal Raman microscopy. The quaternization gradient length in the polymer brush can be varied with the injection flow rate and the distance from the co-flow junction. A chemical gradient in the polymer brush as narrow as 5 μm was created by controlling these parameters. The chemical gradient by laminar co-flow is compared with numerical calculations that include only one adjustable parameter: the reaction rate constant of the polymer brush quaternization. The calculated chemical gradient agrees with the experimental data, which validates the numerical procedures established in this study. Flow of multiple laminar streams of reactive agent solutions enables single-run fabrication of brush gradients with more than one chemical property. As one example, four laminar streamsneat solvent/benzyl bromide solution/propargyl bromide solution/neat solventgenerate multistep gradients of aromatic and alkyne groups. Because the alkyne functional group is a click-reaction available site, the alkyne gradient could allow small gradient formation with a wide variety of chemical properties in a polymer brush

General Method for Forming Micrometer-Scale Lateral Chemical Gradients in Polymer Brushes

We report a general diffusion based method to form micrometer-scale lateral chemical gradients in polymer brushes via selective alkylation. A quaternized brush gradient is derived from a concentration gradient of alkylating agent formed by diffusion in permeable media around a microchannel carrying the alkylating agent. Polymer brushes containing both charge and aromatic gradients are formed using the alkylating agents, methyl iodide and benzyl bromide, respectively. The gradients are quantitatively characterized by confocal Raman spectroscopy and qualitatively by fluorescence microscopy. The length and gradient strength can be controlled by varying the diffusion time, concentrations, and solvents of the alkylating agent solutions. This microfluidic brush gradient generation method enables formation of 2-D chemical potential gradients with a diversity of shapes

Hole-Mask Colloidal Nanolithography for Large-Area Low-Cost Metamaterials and Antenna-Assisted Surface-Enhanced Infrared Absorption Substrates

We use low-cost hole-mask colloidal nanolithography to manufacture large-area resonant split-ring metamaterials and measure their infrared optical properties. This novel substrate is employed for antenna-assisted surface-enhanced infrared absorption measurements using octadecanethiol (ODT) and deuterated ODT, which demonstrates easy adjustability of our material to vibrational modes. Our method has the potential to make resonant plasmon-enhanced infrared spectroscopy a standard lab tool in biology, pharmacology, and medicine

Autonomic Molecular Transport by Polymer Films Containing Programmed Chemical Potential Gradients

Materials which induce molecular motion without external input offer unique opportunities for spatial manipulation of molecules. Here, we present the use of polyacrylamide hydrogel films containing built-in chemical gradients (enthalpic gradients) to direct molecular transport. Using a cationic tertiary amine gradient, anionic molecules were directionally transported up to several millimeters. A 40-fold concentration of anionic molecules dosed in aerosol form on a substrate to a small region at the center of a radially symmetric cationic gradient was observed. The separation of mixtures of charged dye molecules was demonstrated using a boronic acid-to-cationic gradient where one molecule was attracted to the boronic acid end of the gradient, and the other to the cationic end of the gradient. Theoretical and computational analysis provides a quantitative description of such anisotropic molecular transport, and reveals that the gradient-imposed drift velocity is in the range of hundreds of nanometers per second, comparable to the transport velocities of biomolecular motors. This general concept of enthalpy gradient-directed molecular transport should enable the autonomous processing of a diversity of chemical species