Abstract
Laser writing is used to structure surfaces in many different ways in materials and life sciences. However, combinatorial patterning applications are still limited. Here we present a method for cost-efficient combinatorial synthesis of very-high-density peptide arrays with natural and synthetic monomers. A laser automatically transfers nanometre-thin solid material spots from different donor slides to an acceptor. Each donor bears a thin polymer film, embedding one type of monomer. Coupling occurs in a separate heating step, where the matrix becomes viscous and building blocks diffuse and couple to the acceptor surface. Furthermore, we can consecutively deposit two material layers of activation reagents and amino acids. Subsequent heat-induced mixing facilitates an in situ activation and coupling of the monomers. This allows us to incorporate building blocks with click chemistry compatibility or a large variety of commercially available non-activated, for example, posttranslationally modified building blocks into the array's peptides with >17,000 spots per cm2.
Highlights
Laser writing is used to structure surfaces in many different ways in materials and life sciences
At 90 °C, the solid matrix material becomes viscous and the spots are transformed into gel-like droplets that serve as spatially confined reaction vessels, without evaporation or spreading on the surface
Our goal was to overcome the aforementioned problems with a combinatorial Laser-induced forward transfer (LIFT) method, which allows us to synthesize affordable, very high-density (417,000 spots per cm2) and high-quality peptide arrays
Summary
Laser writing is used to structure surfaces in many different ways in materials and life sciences. The lightdirected lithographic synthesis uses light patterns to remove photolabile protecting groups from the growing peptides or photogenerated acids cleaving the acid-labile protecting groups at selected areas with a digital micromirror device These methods have severe drawbacks: liquid solvents in the SPOT synthesis tend to evaporate or spread on the surface, which limits the spot density of arrays to some 25 peptides per cm[2]. The particle-based variant of the Merrifield synthesis method uses, for example, a laser printer or a microelectronic chip to structure a surface with 20 different types of solid polymer particles, each embedding a different type of amino-acid building block This approach overcomes most of the mentioned drawbacks: structuring is achieved by electrical fields to precisely deposit patterns of the 20 different amino acid particle types, before the coupling reaction is induced for the whole pattern at once by heating. Each material spot can comprise a different amino-acid building block or the chemicals that are needed for an in situ activation of a non-activated amino-acid building block
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