Protein-crystal detection with a compact multimodal multiphoton microscope

Qing di Cheng, Hsiang Yu Chung, Robin Schubert, Shih Hsuan Chia, Sven Falke, Celestin Nzanzu Mudogo, Franz X. Kärtner, Guoqing Chang, Christian Betzel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


There is an increasing demand for rapid, effective methods to identify and detect protein micro- and nano-crystal suspensions for serial diffraction data collection at X-ray free-electron lasers or high-intensity micro-focus synchrotron radiation sources. Here, we demonstrate a compact multimodal, multiphoton microscope, driven by a fiber-based ultrafast laser, enabling excitation wavelengths at 775 nm and 1300 nm for nonlinear optical imaging, which simultaneously records second-harmonic generation, third-harmonic generation and three-photon excited ultraviolet fluorescence to identify and detect protein crystals with high sensitivity. The instrument serves as a valuable and important tool supporting sample scoring and sample optimization in biomolecular crystallography, which we hope will increase the capabilities and productivity of serial diffraction data collection in the future.

Original languageEnglish
Article number569
JournalCommunications Biology
Issue number1
StatePublished - 1 Dec 2020


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