The proof-of-principle particle based peptide synthesis (Nesterov-Mueller A et al. Science, 2007)  and its successful adaptation for printing peptide arrays xerographically (Stadler et al. Ang. Chem. 2008) have opened persepctives for novel arrays with a very high density. Prerequisits for such development are (a) particles as compact carriers of amino acids without spreading as by droplets; (b) parallel coupling of all amino acids in contrast to the lithographyc peptide synthesis which requires signle coupling steps for each amino acids.
Peptide arrays with combinatorial laser fusing
Fig. 1 shows a pattern of fused amino acids particles for the peptide synthesis. With this method, we demostrated the proof-of-principle peptide arrays with a density of 40000 spots per cm2 [4,5].
Fig. 1: Laser fusing of amino acid particles. Spot pitch is 50 µm.
Combinatorial synthesis with laser transfer of particles between microcavities
The principle of the method is shown in Fig. 2. The micro cavities prohibit the spreading the particles by transfer. The molecular arrays with a density of 1 million spots per cm2 have been demonstrated .
Fig. 2: Particle patterning with microstructured supports.
Stochastic Arrays – novel combinatorial chemistry
The stochastic arrays recently invented in our group are based on the self-organization of monomers in the microcavities. Both random and stochastically directed synthetic peptide libraries can be generated where peptide spots are located in the microcavities on a microscope slide. The stochastic combinatorial synthesis doesn’t have principle limitations of the array spot size and allow for up to 1012 different synthetic peptides per cm2.
Parameters of the current version of stochastic arrays: