Programmable high voltage CMOS chips for particle-based high-density combinatorial peptide synthesis

We built high voltage complementary metal oxide semiconductor (CMOS) chips that generate electrical fields on their surface, such that electrically charged microparticles (diameter 10–20μm on average) can be addressed on distinct pixel electrodes according to arbitrary field patterns. Each pixel contains a memory cell in canonical low-voltage CMOS-technology controlling a high voltage (30–100V) potential area on the top metal layer. Particle transfer with minimal contaminations in less than 10s for a complete chip was observed for pixels of 100μm×100μm down to 65μm×65μm. This allows a new way to create surface modifications on top of CMOS chips without need for additional masks or stamps. Using suitable particles, a chemically modified chip surface, and compatible chemistry, this method can be utilized for self-aligned high-density biopolymer arrays, e.g., peptide arrays. Transfer of microparticles loaded with amino acids for combinatorial peptide synthesis is demonstrated. Successful synthesis of different peptides (octamers) was proven by immunostaining. Based on results obtained by a chip containing pixel areas of different characteristics, a chip for biological applications with 16,384pixels (10,000pixel/cm2) was built. Good homogeneity of peptide synthesis over the chip area was verified by immunostaining.