Encoding combinatorial libraries: A novel application of fluorescent silica colloids

Grondahl, Lisbeth, Battersby, Bronwyn J., Bryant, Darryn and Trau, Matt (2000) Encoding combinatorial libraries: A novel application of fluorescent silica colloids. Langmuir, 16 25: 9709-9715. doi:10.1021/la000995z


Author Grondahl, Lisbeth
Battersby, Bronwyn J.
Bryant, Darryn
Trau, Matt
Title Encoding combinatorial libraries: A novel application of fluorescent silica colloids
Journal name Langmuir   Check publisher's open access policy
ISSN 0743-7463
Publication date 2000-12-12
Sub-type Article (original research)
DOI 10.1021/la000995z
Volume 16
Issue 25
Start page 9709
End page 9715
Total pages 7
Editor D.G. Whitten
Place of publication Washington, DC
Publisher American Chemical Society
Language eng
Subject 02 Physical Sciences
0306 Physical Chemistry (incl. Structural)
Abstract A major challenge associated with using large chemical libraries synthesized on microscopic solid support beads is the rapid discrimination of individual compounds in these libraries. This challenge can be overcome by encoding the beads with 1 mum silica colloidal particles (reporters) that contain specific and identifiable combinations of fluorescent byes. The colored bar code generated on support beads during combinatorial library synthesis can be easily, rapidly, and inexpensively decoded through the use of fluorescence microscopy. All reporters are precoated with polyelectrolytes [poly(acrylic acid), PAA, poly(sodium 4-styrenesulfonate PSSS, polyethylenimine, PEI, and/or poly(diallyldimethylammonium chloride), PDADMAC] with the aim of enhancing surface charge, promoting electrostatic attraction to the bead, and facilitating polymer bridging between the bead and reporter for permanent adhesion. As shown in this article, reporters coated with polyelectrolytes clearly outperform uncoated reporters with regard to quantity of attached reporters per bead (54 +/- 23 in 2500 mum(2) area for PEI/PAA coated and 11 +/- 6 for uncoated reporters) and minimization of cross-contamination (1 red reporter in 2500 mum(2) area of green-labeled bead for PEI/PAA coated and 26 +/- 15 red reporters on green-labeled beads for uncoated reporters after 10 days). Examination of various polyelectrolyte systems shows that the magnitude of the xi -potential of polyelectrolyte-coated reporters (-64 mV for PDADMAC/PSSS and -42 mV for PEI/PAA-coated reporters) has no correlation with the number of reporters that adhere to the solid support beads (21 +/- 16 in 2500 mum(2) area for PDADMAC/PSSS and 54 +/- 23 for PEI/PAA-coated reporters). The contribution of polymer bridging to the adhesion has a far greater influence than electrostatic attraction and is demonstrated by modification of the polyelectrolyte multilayers using gamma irradiation of precoated reporters either in aqueous solution or in polyelectrolyte solution.
Keyword Chemistry, Physical
Drug Discovery
Chemistry
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Physical Sciences Publications
 
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Created: Mon, 13 Aug 2007, 22:05:29 EST