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Printing Peptide Arrays with a Complementary Metal Oxide Semiconductor Chip

  • Felix F. Loeffler
  • Yun-Chien Cheng
  • Bastian Muenster
  • Jakob Striffler
  • Fanny C. Liu
  • F. Ralf Bischoff
  • Edgar Doersam
  • Frank Breitling
  • Alexander Nesterov-Mueller
Chapter
Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE, volume 137)

Abstract

In this chapter, we discuss the state-of-the-art peptide array technologies, comparing the spot technique, lithographical methods, and microelectronic chip-based approaches. Based on this analysis, we describe a novel peptide array synthesis method with a microelectronic chip printer. By means of a complementary metal oxide semiconductor chip, charged bioparticles can be patterned on its surface. The bioparticles serve as vehicles to transfer molecule monomers to specific synthesis spots. Our chip offers 16,384 pixel electrodes on its surface with a spot-to-spot pitch of 100 μm. By switching the voltage of each pixel between 0 and 100 V separately, it is possible to generate arbitrary particle patterns for combinatorial molecule synthesis. Afterwards, the patterned chip surface serves as a printing head to transfer the particle pattern from its surface to a synthesis substrate. We conducted a series of proof-of-principle experiments to synthesize high-density peptide arrays. Our solid phase synthesis approach is based on the 9-fluorenylmethoxycarbonyl protection group strategy. After melting the particles, embedded monomers diffuse to the surface and participate in the coupling reaction to the surface. The method demonstrated herein can be easily extended to the synthesis of more complicated artificial molecules by using bioparticles with artificial molecular building blocks. The possibility of synthesizing artificial peptides was also shown in an experiment in which we patterned biotin particles in a high-density array format. These results open the road to the development of peptide-based functional modules for diverse applications in biotechnology.

Graphical Abstract

Keywords

Functional particle deposition High-throughput screening Peptide microarray Solid-phase synthesis 

Abbreviations

Ac2O

Acetic anhydride

CMOS

Complementary metal oxide semiconductor

DIPEA

Diisopropylethylamine

DMF

Dimethylformamide

Fmoc

9-Fluorenylmethoxycarbonyl

MMA

Methyl methacrylate

mol

Mole(s)

OPfp

Pentafluorophenyl

PEGMA

Poly(ethylene glycol) methacrylate

PTFE

Polytetrafluoroethylene

Boc

tert-butyloxycarbonyl

TFA

Trifluoroacetic acid

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Felix F. Loeffler
    • 1
  • Yun-Chien Cheng
    • 3
  • Bastian Muenster
    • 1
  • Jakob Striffler
    • 1
  • Fanny C. Liu
    • 1
  • F. Ralf Bischoff
    • 2
  • Edgar Doersam
    • 3
  • Frank Breitling
    • 1
  • Alexander Nesterov-Mueller
    • 1
  1. 1.Karlsruhe Institute of Technology, Institute of Microstructure TechnologyEggenstein-LeopoldshafenGermany
  2. 2.German Cancer Research CenterChip Based Peptide LibrariesHeidelbergGermany
  3. 3.Institute of Printing Science and TechnologyDarmstadtGermany

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