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A 20-year journey on the invention of vibrational photothermal microscopy

Vibrational microscopy opens a new window onto understanding life at the molecular level. Yet the vibrational signals from chemical bonds are weaker than the fluorescence signal from a dye by many orders of magnitude. Detecting such weak signal from a tight focus under a microscope is extremely challenging. I have devoted my career to overcoming such a daunting barrier through the development of advanced chemical microscopes over the past 25 years. In this historical Comment, I am honored to share my journey of serendipity-driven innovation and entrepreneurship in the growing field of chemical imaging, with a focus on the invention of vibrational photothermal microscopy.

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Fig. 1: Raman resonance-enhanced photodamage in CARS microscopy.
Fig. 2: The 2014 MIP microscope in the Cheng lab based on a loaned quantum cascade laser.
Fig. 3: Number of publications per year.

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Acknowledgements

I am grateful for the hard work by dedicated postdoctoral fellows and graduate students in my group over the past years. Many thanks to collaborators and industrial partners. I acknowledge the NIH, NSF, DoD, DoE, Veterans Affairs, Kech Foundation, American Heart Association, Chan-Zuckerburg Initiative and DRS Daylight Solutions for their financial support.

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Correspondence to Ji-Xin Cheng.

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J.-X.C. claims financial interests with Vibronix Inc and Photothermal Spectroscopy Corp, which did not fund this work.

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Cheng, JX. A 20-year journey on the invention of vibrational photothermal microscopy. Nat Methods 22, 883–885 (2025). https://doi.org/10.1038/s41592-025-02619-0

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