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Automated laser-transfer synthesis of high-density microarrays for infectious disease screening

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Paris,  Grigori
Felix Löffler, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Heidepriem,  Jasmin
Felix Löffler, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Tsouka,  Alexandra
Felix Löffler, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Liu,  Yuxin       
Felix Löffler, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Pinzón Martín,  Sandra
Daniel Varón Silva, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Dallabernardina,  Pietro
Felix Löffler, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Mende,  Marco
Felix Löffler, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Wawrzinek,  Robert
Christoph Rademacher, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Seeberger,  Peter H.
Peter H. Seeberger - Automated Systems, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Löffler,  Felix F.
Felix Löffler, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Citation

Paris, G., Heidepriem, J., Tsouka, A., Liu, Y., Mattes, D. S., Pinzón Martín, S., et al. (2022). Automated laser-transfer synthesis of high-density microarrays for infectious disease screening. Advanced Materials, 34(12): 2200359. doi:10.1002/adma.202200359.


Cite as: https://hdl.handle.net/21.11116/0000-000A-59D7-0
Abstract
Abstract Laser-induced forward transfer (LIFT) is a rapid laser-patterning technique for high-throughput combinatorial synthesis directly on glass slides. A lack of automation and precision limited LIFT applications to simple proof-of-concept syntheses of fewer than 100 compounds. Here, we report an automated synthesis instrument that combines laser transfer and robotics for parallel synthesis in a microarray format with up to 10000 individual reactions/cm2. An optimized pipeline for amide bond formation is the basis for preparing complex peptide microarrays with thousands of different sequences in high yield with high reproducibility. The resulting peptide arrays are of higher quality than commercial peptide arrays. More than 4800 15-residue peptides resembling the entire Ebola virus proteome on a microarray were synthesized to study the antibody response of an Ebola virus infection survivor. We identified known and unknown epitopes that serve now as a basis for Ebola diagnostic development. The versatility and precision of the synthesizer is demonstrated by in situ synthesis of fluorescent molecules via Schiff base reaction and multi-step patterning of precisely definable amounts of fluorophores. This automated laser transfer synthesis approach opens new avenues for high-throughput chemical synthesis and biological screening.