Document Detail


The use of glass substrates with bi-functional silanes for designing micropatterned cell-secreted cytokine immunoassays.
MedLine Citation:
PMID:  21550110     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It is often desirable to sequester cells in specific locations on the surface and to integrate sensing elements next to the cells. In the present study, surfaces were fabricated so as to position cytokine sensing domains inside non-fouling poly(ethylene glycol) (PEG) hydrogel microwells. Our aim was to increase sensitivity of micropatterned cytokine immunoassays through covalent attachment of biorecognition molecules. To achieve this, glass substrates were functionalized with a binary mixture of acrylate- and thiol-terminated methoxysilanes. During subsequent hydrogel photopatterning steps, acrylate moieties served to anchor hydrogel microwells to glass substrates. Importantly, glass attachment sites within the microwells contained thiol groups that could be activated with a hetero-bifunctional cross-linker for covalent immobilization of proteins. After incubation with fluorescently-labeled avidin, microwells fabricated on a mixed acryl/thiol silane layer emitted ∼ 6 times more fluorescence compared to microwells fabricated on an acryl silane alone. This result highlighted the advantages of covalent attachment of avidin inside the microwells. To create cytokine immunoassays, micropatterned surfaces were incubated with biotinylated IFN-γ or TNF-α antibodies (Abs). Micropatterned immunoassays prepared in this manner were sensitive down to 1 ng/ml or 60 pM IFN-γ. To further prove utility of this biointerface design, macrophages were seeded into 30 μm diameter microwells fabricated on either bi-functional (acryl/thiol) or mono-functional silane layers. Both types of microwells were coated with avidin and biotin-anti-TNF-α prior to cell seeding. Short mitogenic activation followed by immunostaining for TNF-α revealed that microwells created on bi-functional silane layer had 3 times higher signal due to macrophage-secreted TNF-α compared to microwells fabricated on mono-functional silane. The rational design of cytokine-sensing surfaces described here, will be leveraged in the future for rapid detection of multiple cytokines secreted by individual immune cells.
Authors:
Jeong Hyun Seo; Li-Jung Chen; Stanislav V Verkhoturov; Emile A Schweikert; Alexander Revzin
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-05-07
Journal Detail:
Title:  Biomaterials     Volume:  32     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-05-30     Completed Date:  2011-09-19     Revised Date:  2012-01-30    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  5478-88     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
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MeSH Terms
Descriptor/Qualifier:
Acrylates / chemistry
Animals
Antibodies / chemistry,  immunology
Avidin / chemistry
Biotin / chemistry
Cell Line, Tumor
Cytokines / analysis*,  secretion
Eukaryotic Cells / drug effects,  secretion*
Fluorescent Dyes / chemistry
Glass / chemistry*
Humans
Hydrogels / chemistry
Immunoassay / methods
Interferon-gamma / analysis,  immunology
Macrophages / drug effects,  secretion
Maleimides / chemistry
Mice
Microscopy, Atomic Force
Microscopy, Fluorescence
Microtechnology / methods
Photochemical Processes
Polyethylene Glycols / chemistry
Silanes / chemistry*
Spectrometry, Mass, Secondary Ion
Streptavidin / chemistry
Surface Properties
Tetradecanoylphorbol Acetate / pharmacology
Tumor Necrosis Factor-alpha / analysis,  immunology
Grant Support
ID/Acronym/Agency:
R01 DK079977-01A2/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Acrylates; 0/Antibodies; 0/Cytokines; 0/Fluorescent Dyes; 0/Hydrogels; 0/Maleimides; 0/Polyethylene Glycols; 0/Silanes; 0/Tumor Necrosis Factor-alpha; 0/neutravidin; 1405-69-2/Avidin; 16561-29-8/Tetradecanoylphorbol Acetate; 4369-14-6/3-acryloxypropyltrimethoxysilane; 4420-74-0/(3-mercaptopropyl)trimethoxysilane; 58-85-5/Biotin; 82115-62-6/Interferon-gamma; 9013-20-1/Streptavidin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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