Microarrays have become one of the most convenient tools for high throughput screening, supporting major advances in genomics and proteomics. Other important applications can be found in medical diagnostics, detection of biothreats, drug discovery, etc. Integration of microarrays with microfluidic devices can be highly advantageous in terms of portability, shorter analysis time and lower consumption of expensive biological analytes. Since fabrication of microfluidic devices using traditional materials such as glass is rather expensive, there is a high interest in employing polymeric materials as a low cost alternative that is suitable for mass production. A number of commercially available plastic materials were reviewed for this purpose and poly(methylmethacrylate) and Zeonor™ 1060R were identified as promising candidates, for which methods for surface modification and covalent immobilization of DNA oligonucleotide were developed. In addition, we present proof-of-concept plastic-based microarrays with and without integration with microfluidics.

Mussel adhesive protein analogs are biologically-derived materials that possess unique adhesion properties. We have demonstrated thin film growth of DOPA modified- PEG block copolymer mussel adhesive protein analogs using a novel laser processing technique known as matrix assisted pulsed laser evaporation (MAPLE). The main functional groups of the mussel adhesive protein analog are present in the MAPLE-transferred film. These novel polymer thin films have numerous medical, electronic, and marine applications.

Adhesion between swollen hydrogels was studied using a simple tack-evaluation technique by a point contact in air at room temperature. The hydrogel used here was poly(sodium acrylate) (PSA) gel physically cross-linked by aluminum ions. The adhesion force and the separation energy showed a power-law increase with separation velocity, normal force, and waiting period　prior to separate. Effects of the degrees of protonation in PSA as well as of dehydration on the adhesive properties are also presented. The results are discussed in terms of the surface molecular interaction and the bulk elastic and viscous properties.

This paper describes studies of surface-patterned nanohydrogels and their use as possible substrates for high-density and high-sensitivity protein arrays. Nanohydrogels, approximately 200 nm in diameter, were created by locally crosslinking dry amine-terminated poly(ethylene glycol) [PEG] (5000 Da) thin films using a focused electron beam. These gels then had a dry height of 50 nm and a swell ratio of about five. They were patterned into arrays with approximately 1 μm inter-gel spacing. These arrayed gels were functionalized with Zinc Finger 9 (ZNF9), a nucleic-acid binding protein. As part of ongoing research, we are interested in how the performance of the functionalized gels compares to that of current commercial substrates. We show, using an assay that binds α-GST antibody to mediate attachment of GST-tagged ZNF9, that nanohydrogels have a consistently higher combination of fluorescent signal and signal-to-noise (SNR) ratio than the comparable commercial substrates. We further show that the SNR characteristic of our assay degrades slower on the nanohydrogel array than on a comparable microarray printed on an epoxide substrate, and we speculate that the difference is in part attributable to the fact that the nanohydrogel array presents a softer and more hydrophilic surface.

Melt processing of binary immiscible polymer systems has been a focus of our group as an economical and scalable route to achieve synergistic or superior mechanical properties at and around the co-continuous region without the need of compatibilization. System of poly(L-lactide) (PLLA) and poly(methyl methacrylate) (PMMA) was selected to target bio-related applications, including bone fillers and scaffolds, where the biodegradability of PLLA will enable the integration of native tissue into the material over time. Tunable properties such as morphology, interconnectivity, resorbability and interfacial bonding control the long-term integrity of the new material and influence the interaction and integration of new tissue. Binary blends of PLLA and PMMA has been prepared and characterized over a large range of compositions in which regions of co-continuity are of special interest. Such regions exhibit a well interconnected structure that ensures controlled release of resorbable PLLA. Modulated differential scanning calorimetry (MDSC) detected a broad and unexpected transition between 70 °C and 100 °C. The magnitude of this transition is greatest within co-continuous regions, suggesting the presence of a complex or other derivative of the two primary phases. This complex appears to provide a degree of compatibilization between the phases, thus inducing mechanical property synergism which has been confirmed by flexural and nano-indentation analyses.

Enhanced drug partitioning in hydrogels can be achieved by configurational biomimetic imprinting (CBIP) techniques which involve the formation of pre-polymerization complexes between template molecules and functional monomers with specific chemical structures designed to interact with the template via non-covalent chemistry. This new class of recognitive intelligent materials is designed by incorporating motifs with structural and molecular homology to biological receptors and has a strong potential to impact the administration of a number of ocular therapies.

This work addresses the unmet need for the controlled release of histamine antagonists such as ketotifen fumarate on the surface of the eye to treat allergic conjunctivitis. Mast cell and eosinophil degranulation occurs due to the IL-4 driven TH2 cell response to allergens and the subsequent IgE secretion. This prompts the release of inflammatory mediators such as histamine, which binds to the H1-receptors. Pharmacological downregulation is possible by the local delivery of H1-antihistamines, resulting in decreased vascular permeability, bronchodilation, and exudation of effector cells.

Treatment options for seasonal and perennial allergic conjunctivitis primarily consist of oral antihistamines (which provide only partial and delayed relief with potential systemic side effects) and topical treatments. Since ocular bioavailability of topical drugs is very poor (typically less than 7% is absorbed by the eye), a high dosage is needed which prohibits contact lens use. Controlling and tailoring the release of anti-histamines via novel recognitive contact lenses with significantly enhanced partitioning can solve these problems with increased bioavailability, less irritation to ocular tissue, and reduced ocular and systemic side effects. Controlled release by conventional soft contact lenses typically does not work due to a lack of sufficient drug loading.

Inspired by Nature, we have successfully synthesized and characterized recognitive networks for H1 antihistamines by choosing monomers on the basis of the non-covalent interactions found in histamine docking sites. This leads to significantly enhanced drug loading and tailorable controlled release of a therapeutically viable dosage of drug.

Environmentally friendly organic-inorganic hybrid materials with repellent activity against marine fouling organisms, such as blue mussel, have been developed using interpenetrating polymer networks (IPNs), composed of a 3-dimensional siloxane matrix of tetraethoxysilane (TEOS) and poly(vinylacetate) (PVAc). Facile bioassay using blue mussels allowed screening the adequate proportions of those components. The repellent activity of IPN with PVAc/silica reached approximately 90% at a specific fraction, relative to that of tributyl tin oxide (TBTO). On the other hand, poly(methylmethacrylate)(PMMA) /silica composite did not show marked repellent activity against blue mussel, even though chemical structure of MMA is similar to that of vinylacetate.

Polyethylene imine hydrogel complexes with various salts of ferric and ferrous iron and also with complex salts of iron as well as insoluble ternary complexes of various composition: low cross-linked polyethylene imine hydrogel - copper (II) nitrate - sodium dodecylbenzylsulfate have been received. Their biocatalytic properties in the reaction of hydrogen peroxide decomposition (catalase activity) have been investigated. It was shown that catalase activity of complexes depends on the salts type and valence state of iron ions. The complexes of ferric iron as well as ternary complexes are most active in the reaction of hydrogen peroxide decomposition.

The aim of this work is the development of controlled delivery system immobilized by antimicrobial drug rifampicine on the basis of microparticles of alginate calcium gel, modified by natural polymer chitosan. Modified microparticles were obtained by syringed dropwise a solution of rifampicine in solution of sodium alginate was into a mixed solution of chitosan in calcium chloride. The obtained modified alginate microparticles were contained immobilized rifampicine and a surface layer of chitosan. Effects of chithosan concentration and exposure duration on the thickness of polymer coating were determined. For the determination of surface thickness a red congo dye has been used able to form a complex with chitosan. It has been established that with an increase in the concentration of a polymer from 0,3 up to 1,5 mass % the thickness of the modified layer increases from 5 up to 60 mcm, and an increase of the time of gel exposition in a 2,5% solution of chitosan from 30 min to 24 h results in an increase in thickness of a layer from 5 up to 20 mcm respectively. When studying an influence of pH of the medium upon an interaction of alginate and chitosan it was been observed a formation of a polyelectrolyte complex between a chitosan polycation and an alginate polyanion stabilized by ionic bonds. The release of rifampicine from the modified alginate gel particles into a physiological solution with different thickness of a chitosan coating were studied. It was shown that the characteristic maximums on the curve of release observe after 10, 30, 90 and 120 min for the samples without the coating and with the coating thickness of 55, 100 and 150 mcm respectively. The data obtained shown a possibility of the regulation of the rate of rifampicine relase from the modified alginate particles by way of alternation of thickness of the chitosan coating.

We have performed for the first time a complete structural characterization of PLA-PEO-PLA in the solution and hydrogel states. Previous studies on hydrogels of these polymers have shown that these gels have excellent mechanical properties suitable for possible application in tissue engineering and drug delivery. We have performed SANS, USAXS and confocal microscopy to relate the change in micro to nano scale self-assembled structure of these polymers in aqueous solution with changes in the block length and stereospecificity of the PLA block. A significant difference in structure and association behavior was seen between the polymers made from amorphous D/L-lactide as compared to those with crystalline L lactide blocks. In the former case spherical micelles were seen to form whereas the latter forms nonspherical polydisperse micellar assemblies. Both polymers form an associative network structure at higher concentrations, leading to gelation. USAXS and confocal microscopy show the presence of large-scale fractal aggregates in the hydrogels of these polymers. The fractal structure was denser for the L lactide series polymers as compared to the D/L-lactide series polymers. These results show that we can tune the microstructure and thereby the mechanical strength of these gels depending upon the specific application we need it for. We also show profiles for release of hydrophobic drug sulindac from 5 weight% solutions of these polymers in phosphate buffer saline. The profiles follows an almost zero order release behavior that continues slowly and steadily over several days and is again found to be strongly dependent on the crystallinity and molecular weight of the PLA block.

The polymer/bioceramic composite materials attract much attention for the development of bioresorbable implants and tissue engineering scaffolds. Hydroxyapatite (HA) is the most commonly used bioceramic material due to its similarity to the major mineral component of the hard tissue. We synthesized carbonated and Mg-substituted HA nanocrystals with various concentrations of CO3 2− and Mg2+ ions by chemical precipitation in the range of the process temperatures from 25 °C to 100 °C.

The HA nanocrystals were mixed with several polymeric materials (PCL, PLA, PVA, collagen) to fabricate bulk and nanofiber polymer/HA nanoparticle composites with the HA loading up to 80 % by weight. The HA nanocrystals and polymer/HA composites were characterized by X-ray diffraction, FT-IR spectroscopy, scanning electron and atomic force microscopy. Mechanical properties of the composites were investigated using nanoindentation technique.

In the present study the preparation of biomedical devices and some biomedical application of implantable devices based on segmented polyurethane (SPU)/collagen blends have been described. SPU with different content of hard and soft segments were synthesised by a two-step polymerization using a number of polyethylene and propylene glycols and tolylene diisocyanate.

The successful biomedical application of SPU/collagen blends as biomaterials at some fields of medicine has been shown. These blends were used for the fabrication of artificial esophageal prostheses for treatment of injures and diseases of esophagus such as chemical burns, cicatrical structures, total stenosis in children when standard technique of surgical bypass of the nonfunctioning esophagus can not be used. The SPU/collagen blends containing anticancer agents were used for treatment of sarcoma of the orbit. It was established that the anticancer effect against Rhabdomiosarcoma of implanted blends prolongs 17-20 days and the toxic effects decrease due to reduce a total therapeutic dose from 2,0 mg/kg to 1,4 mg/kg.

Microparticles of SPU with diameter 200-500 microns were prepared with water-toluene interface emulsion polycondensation of toluene-2,4-diisocyanate and poly(ethylene glycol) of various molecular weight 400-2000. The current procedure allows to develop a series of microcapsulated drug delivery forms for respiratory therapeutic use. A method of exterior nose correction using a biocompatible SPU/collagen blend has been developed. The successful application of polyurethane films for reconstruction of the bridge and septum of nose in 15 patients was described.

Soft polymer networks with large mesh size, not flat rigid surfaces, are the normal environment for most animal cells. Cell structure and function depend on the stiffness of the surfaces on which cells adhere as well as on the type of adhesion complex by which the cell binds its extracellular ligand. Many cell types, including fibroblasts and endothelial cells, switch from a round to spread morphology as stiffness is increased between 1000 and 10,000 Pa. Coincident with the change in morphology are a host of differences in protein phosphorylation levels, expression of integrins, and changes in cytoskeletal protein expression and assembly. In contrast, other cells types such as neutrophils and platelets do not require rigid substrates in order to spread, and neurons extend processes better on soft (50 Pa) materials than on stiffer gels. We compare the stiffness sensing of four cell types: platelets, neurons and astrocytes, a glial cell type derived from embryonic rat brain, and melanoma cells. Astrocytes switch from a round to spread morphology as substrate stiffness increases, but do so over a stiffness range 10 times softer than that over which fibroblasts alter morphology. Stiffness-dependent morphologic changes observed from studies of cells grown on surfaces of protein-laminated polyacrylamide gels that have linear elasticity are also seen when cells are on matrices of natural biopolymers such as fibrin. Biopolymer gels like fibrin can be formed with appropriate stiffness to optimize for neuronal cell survival and patterning, and may have utility for repair of damaged neural tissues. The complex non-linear rheology of fibrin and other gels formed by semi-flexible biopolymers that exhibit strain-stiffening provide additional mechanisms by which cells can respond to and actively remodel the mechanical features of their environment.

High-porosity nanoporous silica was prepared by nanocasting method using N-isopropylacrylamide (NIPAm) cross-linked by N, N’-methelenbisacrylamide (BIS) as the templating agent. The obtained silica was a bulk silica with good transparency indicating that the characteristic length-scale of the obtained silica is in the nanoscopic scale being much smaller than that of the wave length of visible light. Nitrogen adsorption/desorption measurements revealed that the nano porosity increases up to 80% with the weight ratio of NIPAm to silica. The mean pore size (radius) also increased with the weight ratio in the region smaller than 10nm. TEM observation revealed that the nanoscopic network structure was replicated into tube-like nanopores randomly distributed in the silica matrix. The whole nanoscopic morphology of these tube-like nanopores was much like as the predicted for the cross-linked polymer.

We investigate the role of particle potential symmetry on self-assembly by Monte Carlo simulation with the particular view towards synthetically creating structures of prescribed form and function. First, we establish a general tendency for the rotational potential symmetries of the particles to be locally preserved upon self-assembly. Specifically, we find that a dipolar particle potential, having a continuous rotational symmetry about the dipolar axis, gives rise to chain formation, while particles with multipolar potentials (e.g., square quadrupole) having discrete rotational symmetries led to the self-assembly of random surface polymers preserving the rotational symmetries of the particles within these sheet structures. Surprisingly, these changes in self-assembly geometry with the particle potential symmetry are also accompanied by significant changes in the thermodynamic character and in the kinetics of the self-assembly process. Linear chain growth involves a continuous chain growth process in which the chains break and reform readily, while the growth of the two-dimensional polymers only occurs after an ‘initiation’ or ‘nucleation’ time that fluctuates from run to run. We show that the introduction of artificial seeds provides an effective method for controlling the structure and growth kinetics of sheet-like polymers. The significance of these distinct modes of polymerization on the functional character of self-assembly growth is illustrated by constructing an artificial centrosome structure derived from particles having continuous and discrete rotational potential symmetries.

It is now well accepted that the mechanical properties and cell adhesion profile of 2D and 3D extracellular matrix molecules combine to dictate cellular fate processes, such as differentiation, migration, proliferation, and apoptosis, through a process generally known as 'mechanotransduction', or the conversion of mechanical signals into a cellular response. The stiffness and adhesion density combine to affect the force balance that exists between an adherent cell and the surrounding substrate. We have established BioMEMS, microfluidic technology to alter the mechanical properties and cell adhesion profile of collagen scaffolds. Using soft lithography, we fabricate elastomeric networks that serve as conduits for the controlled mixing of type I collagen solutions. Our technology enables us to generate reproducible, controlled homogeneous and inhomogeneous microenvironments for 3D cell culture, assays of cell behavior in 3D, and the development of bioartificial tissue equivalents for regenerative and reparative therapies. The adhesivity of collagen is modulated by covalently grafting peptides (such as RGD) or proteins (such as albumin) to soluble collagen molecules with 1- ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC), a hetero-bifunctional coupling agent. EDC activates the carboxylic group of collagen and forms an amine bond with the grafting molecule. The grafted collagen self-assembles into a fibrillar gel at physiological temperature and pH with no measurable changes in rheological properties compared to controls. A solution of peptide-grafted collagen is then mixed in microfluidic networks with unaltered collagen to form controlled gradients or other patterns of the two solutions, which immobilize upon self-assembly. Separately or in the same network, the mechanical properties of the collagen gel can be altered regionally by the microfluidic delivery a solution of a cell-tolerated crosslinking agent. We use genipin, which has the unique property of generating crosslinks that autofluoresce. The intensity of the fluorescence correlates with the degree of crosslinking (and thus the mechanical properties) enabling us to monitor and measure changes in mechanical properties dynamically and non-invasively. Lastly, though it requires constant delivery or recirculation, the same networks can be used to impose gradients of soluble factors, such as growth factors and cytokines. Thus, we have developed a platform to examine the response of cells to simultaneous chemotactic, haptotactic, and durotactic gradients in a 3D environment. We are employing this technology to examine the response of neural cells to gradients of biomaterial properties to optimize cues for spinal cord regeneration.

Mechanical properties of a class of self-assembling hydrogels based on DNA hybridization were studied using rigid, embedded inclusions. Because inclusions can be deflected without direct contact with a manipulator (e.g., magnet) once they are embedded within the subject material, the measurement technique is well suited for monitoring instantaneous and time-varying changes in the mechanical properties of active materials as they respond to external stimuli. In gels crosslinked with complementary strands of oligonucleotides, hybridization chemistry and strand displacement mechanisms allow reversible assembly, shape change, and large changes in compliance through the application of particular strands of DNA. In earlier work using large (diameter ∼0.8 mm) magnetic beads, the scaling behavior of the global elastic modulus with crosslink density was determined. More recently, it was shown that a threefold increase in stiffness was possible by generating prestress in the DNA-crosslinked gel network. Currently, the gels are functionalized to support cell attachment and embedded with micro-fabricated nickel bars. Through the measurement of local elastic and shear moduli as well as Poisson’s ratios, cell-substrate interactions can be used as a means of evaluating the potential of DNA-crosslinked gels as active cellular engineering substrates and tissue engineering scaffolds.

Bone is a composite material consisting of aqueous gel and mineral phases. The aqueous gel phase gives bone its form and contributes to its ability to resist tension, while the mineral component resists compression. The combination of a hard inorganic phase and an elastic gel network provides bone with unique mechanical properties as well as a medium for diffusion and release of biologically active agents and it also facilitates communication with the cellular environment. A tissue engineered synthetic biomaterial as a scaffold for bone regeneration should provide temporary structural support to the reconstructed region and a medium for solubilization, diffusion, release of nutrients and growth factors, and their interactions with cells. In this work, the material and biologic properties of a novel synthetic matrix metalloproteinase (MMP) degradable hydrogel/apatite nanocomposite is investigated for its usefulness as a model matrix to mimic the gel and mineral components of the bone matrix and to fabricate aqueous-based scaffolds for bone regeneration. The gel phase is made from poly(lactide-ethylene oxide-fumarate), hereafter designated as PLEOF, terpolymer in which the water content can be adjusted by changing the ratio of the hydrophobic (lactide) to hydrophilic (ethylene oxide) oligomers. The hydrogel and apatite phases are crosslinked using an MMP degradable peptide crosslinker to modulate the matrix degradation kinetics with the migration of bone marrow stromal (BMS) cells. The results demonstrate that MMP degradable scaffolds fabricated from the PLEOF hydrogel and apatite nanoparticles are biocompatible and support cell attachment and migration.

We discuss the mechanism by which gastric mucin forms a gel at low pH, which serves to protect the stomach from being damaged by the acidic gastric juice that it secretes. Frequency dependence of viscoelastic moduli of pig gastric mucin gels obtained by microscopic dynamic light scattering is presented. Atomic Force Microscopy provides direct visual evidence to indicate that mucin broken into its subunits does not gel at low pH.

The small volume of sample and fast response time are the primary features of micro fluidic system. It is essential for expensive samples. Microvalve is a key to regulate the flow movement component in an integrated microfluidic system. The working principle of conventional microvalves relies on its mechanical or electromagnetic properties. These valves are neither biocompatible nor are suitable for bioassays. Stimuli-response hydrogels whose properties of efficient mode of energy conversion (chemical to mechanical), excellent biocompatibility and the combination of multiple function (sensing and actuation) have become the leading candidate as engineered microscale components. In this paper, we study the feasibility of thermo-sensitive hydrogel as a valve on the microchip. A metal resistor was used as the temperature regulator. The results show that the miniaturization fabrication of the hydrogel depends on many factors like the volume of the hydrogel (the size of the valve), the vacuum condition (the evaporation rate) and the deposition substrate. The degree of swelling and deswelling of the hydrogel valve depends on the size of the hydrogel. This micro fluidic system is regulated by temperature change of the aqueous solution. The integration with other fluidic component is crucial for practical application.