Self-assembly of Vesicle Nanoarrays on Si: A Potential Route to
High-density Functional Protein Arrays


Chandra S. Ramanujan1, Koji Sumitomo2, Maurits R. R. de Planque1, Hiroki Hibino2,
Keiichi Torimitsu2, and John F. Ryan1
1University of Oxford, 2Materials Science Laboratory

   DNA arrays have played a critical role in developing our understanding of genomics. However, whilst they can measure the expression levels of large numbers of genes simultaneously, they cannot be used to further characterize the protein products of such genes and their activity. An important objective of current research is to extend the use of array technology to both directly study the function of the proteins to aid drug discovery. Whereas DNA microarray technology is well-developed, the protein equivalent is still at the early stages of development. Protein microarrays have been recognized as a valuable tool since they require only a nanolitre-scale sample volume with a few picograms of the target protein or drug.
 We show that 100 nm unilamellar thiol-tagged vesicles bind discretely and specifically to Au nanodots formed on a Si surface (See Fig.1). An array of such dots, consisting of 20 nm Au-Si three-dimensional islands, is formed by self-assembly on terraces of small-angle-miscut Si(111) after Au deposition [1]. Consequently, both the formation of the nano-pattern as well as the subsequent attachment of the vesicles are self-organized and occur without the need for any ‘top-down’ lithographic processes. This approach has the potential to provide the basis of a low-cost, high-density nanoarray for use in proteomics and drug discovery.
 Today’s DNA microarray technology has the potential of screening up to 105 ~106 probes in a 300 ml solution volume. In our nanodot arrays about 109 nanodots are covered by a 10 ml droplet [2]. The next steps towards producing a protein chip will include reconstituting proteins into the vesicles and determining a reliable way of labeling and reading the array, possibly using scanned probe techniques such as AFM or a combination of AFM and Scanning Near-field Optical Microscopy (SNOM). The AFM-SNOM has a resolution of about 100 nm. The gold-silicon combination provides an ideal substrate with a low background for fluorescence detection techniques. One way of producing a protein nanoarray would be to first scan and locate each nanodot, and then repeatedly expose to different protein-vesicle solutions and re-scan, until the chip is fully loaded. The deposition of a number of different protein-vesicles can be achieved by optimizing exposure time and vesicle density. The interaction of these mapped vesicle-proteins with fluorescent-labeled antibodies could be detected using the AFM-SNOM.

[1] H. Hibino and Y. Watanabe, Surf. Sci. 588 (2005) L233.
[2] C. S. Ramanujan, et al., App. Phys. Lett. 90 (2007) 033901.

Fig.1. AFM image of nanodot rows with vesicles that are modified to specifically attach to the gold nanodots formed by an earlier self-assembly process.

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