Shen L.,University of Texas at Austin |
Guo A.,Microsurfaces, Inc. |
Zhu X.,University of Texas at Austin
Surface Science | Year: 2011
Tween surfactants, each containing hydrophilic ethylene glycol head groups and a hydrophobic alkyl tail, are being actively explored as protein-resistant surface coatings, but little is known about how they adsorb on surfaces. We carry out a comparative study of the adsorption of two Tween molecules (same hydrophilic head group, but a shorter dodecyl tail for Tween 20 and a longer octadecyl tail for Tween 40) on Au and polystyrene surfaces. Despite the similarity between these two molecules, there is a drastic difference in their protein resistance: a monolayer of Tween 20 on a hydrophobic surface is repulsive against protein adsorption but that of Tween 40 is not. The difference in protein resistance can be attributed to two distinctly different adsorption mechanisms. While the adsorption of Tween 40 is described by a simple first-order mechanism, that of Tween 20 consists of a fast adsorption step and a slower reorganization process at a high surface coverage. The latter leads to the formation of a high-density and self-organized monolayer, which is responsible for the enhanced stability and resistance against non-specific protein adsorption. © 2010 Elsevier B.V. All rights reserved.
Microsurfaces, Inc. | Date: 2008-07-08
Protein arrays and nucleotide arrays for scientific and medical research. Plates, glass slides or chips having multi-well arrays that can be used in chemical analysis, biological analysis or patterning for scientific, laboratory or medical research use.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 746.99K | Year: 2011
DESCRIPTION (provided by applicant): This research project aims to develop fluidic glycan microarrays for the quantitative profiling and characterization of pathogens, and for the screening of pathogen inhibitors and the development of vaccines. The approach targets a common mechanism at the initial stage of pathogen attack: the recognition of and attachment onto host cells via multivalent interaction between receptor proteins and glycan molecules. The tremendous variation in glycans and the complexity inmultivalent interaction have necessitated the use of large-scale profiling and analysis techniques, particularly glycan microarrays. The proposed fluidic approach overcomes two major limitations of current glycan microarray technology: the lack of mobilityand the difficulty in quantitatively controlling glycan density. Multivalent cell surface interactions often require mobility of the fluidic cell membrane environment and are strong functions of surface glycan density. In order to quantitatively apply theglycan microarray in profiling and characterization, one must ensure mobility and control of glycan density over a broad range. The specific aims during phase-II are: Aim 1: using haemagglutinin, a predominant antigen on influenza viruses, and the dendritic cell receptor DC-SIGN, a binding receptor for mannose moieties on HIV-1 virus, as model systems and establish the roles of secondary interactions in binding affinity, avidity, and specificity. These experiments will establish the general applicability of the fluidic microarrays in profiling and characterizing complex pathogen-cell surface interactions; Aim 2: using several strains of E. coli with varying affinity and selectivity towards mannose as model systems and establishing that the fluidic and density gradient glycan microarray can be used to quantitatively profile the variability in binding affinity and multivalency among strains of the same species. Quantifying such variability is essential to the understanding and surveillance of how random mutations can lead to new pathogen threats, as exemplified by the recent outbreaks of avian flu and swine flu; Aim 3: To establish chemical procedures for the optimization of the fluidic glycan microarray, including spatial confinement of the supported lipid bilayer spots, efficient blocking of surfaces outside the spotted areas, recoverability in drying and rehydration of the microarrays, and long term stability of content glycan microarrays. These practical issues must be addressed in developing the fluidic glycan microarray as a viable product. The long-term goal of this RandD plan is to develop an effective high-throughput tool in the combat against pathogen threats. PUBLIC HEALTH RELEVANCE: This research project aims to develop cell-membrane mimickingmicroarrays of sugar molecules for the profiling and characterization of pathogens, and for the screening of vaccines and inhibitors against pathogens. )
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2008
This Small Business Innovation Research Phase I project develops cell membrane mimetic-microarrays for high-throughput screening and analysis of multivalent drug candidates, particularly nanomedicine. Traditional drugs based on mono-valent and high-affinity interactions can lead to non-specific side effects and toxicity. Advances in synthetic and processing techniques for nanoparticles (inorganic, organic, dendrimer, polymer, liposomes, and etc.) have made available an increasing library of drug candidates that incorporate multivalent surface functionalities for targeting specific cells. The proposed cell membrane mimicking microarrays will be based on an air-stable and fluidic supported lipid bilayer system; the robustness of the proposed membrane microarrays greatly simplifies manufacturing, product distribution, and usage. This product will be of high value to pharmaceutical companies and research institutions that are involved in multivalent and nanomedicine development as well as fundamental research on cell-cell interactions. The broader impacts of this research are contributions to drug development and human health. Nanomedicine is a $7 billion market today and growing at double digits annually. While pharmaceutical companies, biotech startups, and academic laboratories are actively developing nanoparticle-based therapies, there are no products that provide high-throughput analysis of these potential drug candidates. The proposed research will allow development of a superior product to meet the needs for large-scale screening of multivalent drug candidates and, in return, accelerate the development of nanomedicine.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2008
DESCRIPTION (provided by applicant): This research project aims to develop cell mimic microarrays for the profiling, characterization, and detection of pathogens. The proposed approach exploits a common mechanism at the initial stage of pathogen attack, na mely the recognition of and attachment onto host cells via multivalent interaction between receptor proteins on pathogens and carbohydrate (glycan) molecules on cell surfaces. Unlike the highly specific protein-protein interaction, the low and varying affi nity between a protein receptor and a single glycan molecule is compensated for by the presence of multiple interactions. It has been argued that the display of a high density of glycan molecules on the surface of a microarray can facilitate such multivale nt interaction. Carbohydrate microarrays have been successfully demonstrated in multivalent binding, including the detection of pathogens. Despite the initial successes, a significant limitation remains: most carbohydrate microarrays demonstrated to date u se carbohydrate molecules covalently attached to solid surfaces. The lack of mobility does not mimic cell surface processes in vivo where glycan groups associated with glycolipids and glycoproteins are in a fluidic lipid bilayer environment. Indeed, mobili ty is believed to be a significant factor in mediating multivalent interactions, e.g., in the dynamic clustering of glycan ligands on the host cell surface. It is the purpose of this SBIR proposal to develop a platform for carbohydrate microarrays based on a proprietary air-stable supported lipid bilayer possessing a high level of fluidity. Compared to other carbohydrate microarrays, the proposed fluidic array more closely mimics the cell surface environment and can be applied more efficiently in the study of pathogen adsorption. The specific aims are to fabricate fluidic carbohydrate microarrays based on glycol lipids incorporated into the air-stable supported lipid bilayers and to use plant lectin ConA and cholera toxin B-subunits (CTB) in proof-of-concept experiments. A long-term outcome will be the development of effective tools for the understanding and detection of pathogens, as well as for the development of treatment and prevention. This research project aims to develop cell mimic microarrays f or the understanding and detection of pathogens, as well as for the development of prevention and treatment of pathogen attack.