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Combinatorial Patterning of Particles for High Density Peptide Arrays (CombiPatterning)
Date du début: 1 nov. 2011, Date de fin: 31 oct. 2016 PROJET  TERMINÉ 

We want to use selective laser melting to pattern a substrate with different solid micro particles at a density of 1 million spots per cm2. First, a homogeneous particle layer is deposited on a substrate and a pattern of micro spots of melted matrix is generated by laser radiation. Then, non-melted particles are blown away. Embedded within the particles are different chemically reactive amino acid derivatives that will start coupling to very small synthesis sites upon melting the particle pattern in an oven. This is done once all of the 20 different amino acid particles have been glued by laser patterning to the surface. Washing away uncoupled material, removing Fmoc protecting group, and repeating the patterning steps according to standard Merrifield synthesis, leads to the combinatorial synthesis of very high-density peptide arrays. The main objective of this proposal is to develop this method up to the level of a semi-automated synthesis machine. In addition, we will use the manufactured very high-density peptide arrays to readout the information that is deposited in the immune system, i.e. find a peptide binder for every one of the 200-500 antibody species that patrol the serum of an individual in elevated levels. These experiments might lead to novel tools to find out the causes of hitherto enigmatic diseases because then we might be able to correlate antibody patterns with disease status without knowing in advance the disease-specific antibodies. Beyond the life sciences, we want to embed 10.000 peptides per cm2 within an insulating layer of alkane thiols, each on a different gold pad of a specially designed screening chip. Then, we could readout I/V characteristics of individual peptide species, and eventually find peptide-based diodes. These could be modified in their sequence and screened again for better performance. This evolution-inspired screening approach might lead to novel materials that could be used in fuel cells.

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