Tailoring Surface Properties To Build Colloidal Diagnostic Devices: Controlling Interparticle Associations Gwendolyn Lawrie, ² Lisbeth Grøndahl, ‡ Bronwyn Battersby, ² Imelda Keen, ² Michael Lorentzen, ² Peter Surawski, ² and Matt Trau* ,² Centre for Nanotechnology and Biomaterials, Department of Chemistry, The UniVersity of Queensland, QLD 4072, Australia ReceiVed July 7, 2005. In Final Form: October 18, 2005 The ability to control the surface properties and subsequent colloidal stability of dispersed particles has widespread applicability in many fields. Sub-micrometer fluorescent silica particles (reporters) can be used to actively encode the combinatorial synthesis of peptide libraries through interparticle association. To achieve these associations, the surface chemistry of the small fluorescent silica reporters is tailored to encourage robust adhesion to large silica microparticles onto which the peptides are synthesized. The interparticle association must withstand a harsh solvent environment, multiple synthetic and washing procedures, and biological screening buffers. The encoded support beads were exposed to different solvents used for peptide synthesis, and different solutions used for biological screening including phosphate buffered saline (PBS), 2-[N-morpholino]ethane sulfonic acid (MES) and a mixture of MES and N-(3-dimethyl-aminopropyl)-N′-ethylcarbodiimide (EDC). The number of reporters remaining adhered to the support bead was quantified after each step. The nature of the associations were explored and tested to optimize the efficiency of these phenomena. Results presented illustrate the influence of the surface functionality and polyelectrolyte modification of the reporters. These parameters were investigated through zeta potential and X-ray photoelectron spectroscopy. Introduction The manipulation of the surface of a particle to alter its physical properties, either through chemical modification of the surface functionalities or by surface adsorption of molecules, has emerged as a powerful strategy in colloidal science. A common goal has been to increase the stability of a dispersion of colloidal particles with reduced flocculation. Another strategy is to produce tailored surfaces for biological applications such as drug delivery. In the majority of applications the particles are required to remain discrete; however, there are instances where an increased attraction between particles in suspension is in fact a desirable outcome. A novel approach to encoding combinatorial libraries syn- thesized on solid supports is to use sub-micrometer colloidal silica particles (reporters) to tag each synthetic step. 1-4 These reporters possess unique fluorescent signatures and once attached to the support microbead (Figure 1) they must remain adhered throughout subsequent synthetic and screening procedures. This robust adhesion will ensure accurate decoding of the identity of the compound synthesized on each support bead. This colloidal encoding approach offers significant advantages over molecular tagging of combinatorial libraries (Figure 1). 1 In the latter case the identity of the molecular tag must be complementary to the structure of the probe molecule so as not to interfere with the synthesis and decoding processes. Typical molecular tags for peptide libraries are oligonucleotide sequences 5 and decoding of the molecular tag involves cleavage of the tag from the support bead followed by spectroscopic characterization. The use of fluorescent silica reporters adhered to the surface of the microbead as a tag overcomes several limitations as decoding can take place in situ. Each support bead possesses a unique combination of fluorescent reporters forming a barcode which can be read by a fluorescence microscope and which reveals the identity of the probe. In a combinatorial library of probes there will be millions of support beads each possessing a different probe and a unique barcode; the development of this strategy has been described in detail elsewhere. 1-3,6,7 The attachment of the small reporters to larger support microbeads is achieved through modification of the surface properties of the reporters (Figure 2). The controlled assembly of polyelectrolyte layers of opposing charge onto small particles has been established as a successful strategy to modify surface charge and is known as the “layer by layer” or LbL approach. 8,9 To date, this strategy has been implemented to design particles with carefully nanoarchitectured structures. The application of * Corresponding author. E-mail: m.trau@uq.edu.au. Phone: + 61 7 3365 3816. Fax: +61 7 3365 4299. ² Centre for Nanotechnology and Biomaterials. ‡ School of Molecular and Microbial Sciences. (1) Lawrie, G. A.; Battersby, B. J.; Grøndahl, L.; Trau, M. Curr. Pharm. Biotechnol. 2003, 4, 439-449. (2) Battersby, B. J.; Bryant, D.; Meutermans, W.; Matthews, D.; Smythe, M. L.; Trau, M. J. Am. Chem. Soc. 2000, 122, 2138-2139. (3) Grøndahl, L.; Battersby, B. J.; Bryant, D.; Trau, M. Langmuir 2000, 16, 9709-9715. (4) Battersby, B. J.; Lawrie, G. A.; Trau, M. Drug DiscoVery Today: HTS Supplement 2001, 6, S19-26. (5) Liu, R.; Enstrom, A. M.; Lam, K. S. Exp. Hematology 2003, 31, 11-30. (6) Battersby, B. J.; Lawrie, G. A.; Johnston, A. P. R.; Trau, M. Chem. Commun. 2002, 14, 1435-1441. (7) Matthews, D. C.; Grøndahl, L.; Battersby, B. J.; Trau, M. Aust. J. Chem. 2001, 54, 649-656. (8) Decher G. Science 1997, 277, 1232-1237. (9) Caruso, F.; Caruso, R. A.; Mo ¨hwald, H. Science 1998, 282, 1111. Figure 1. Options for active encoding of combinatorial synthesis supports. 497 Langmuir 2006, 22, 497-505 10.1021/la051833b CCC: $33.50 © 2006 American Chemical Society Published on Web 11/19/2005