CMOS-Chip Based Printing System for Combinatorial Synthesis

Peptide arrays, produced through combinatorial synthesis from amino-acid monomers, are an important tool for proteomic research. The arrays enable high throughput screening by exposing a large number of different peptide spots to a solution of target molecules. In particle based synthesis, the monomers are encapsulated into solid particles and deposited on the synthesis spots. The resulting spot density can be much higher than that of liquid based on-spot peptide synthesis. This dissertation presents the construction of a CMOS-chip based “printing system” that automatically prints monomer particles onto a glass slide for combinatorial synthesis of high-density arrays. The monomer particles (~4 μm) are addressed onto the electrode pixels of a CMOS chip, and then printed onto a glass slide by using an electrical field. Afterwards, the particles are melted to release monomers for peptide synthesis. The printing system should print particles onto the slide with high reproducibility and homogeneity. This is achieved with high precision (μm) motors, a slide holder and 3 electrical contact sensors. For ideal printing result, the parameters including particle size, printing voltage, and printing distance are discussed. With printed particles, a peptide synthesis is performed, resulting in an array with 10,000 spots per cm2, which is 100 times more than with conventional method. Additionally, the advantage of the printing system is that the synthesis is not performed on the CMOS chip but on the regular glass slide, which is more chemically robust and suitable for biological applications