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Free-Electron Laser-Based Extended Wide-Field Mid-Infrared Photothermal Imaging for Biomedical and Microplastic Analysis

ACS Omega 2026
Anooj Thayyil-Raveendran, Subham Adak, Artem Shydliukh, Natalja Redinger, Matthias Hauptmann, Ulrich E. Schaible, Anna Mühlig, J. Michael Klopf, Orlando Guntinas‐Lichius, Jürgen Popp, Christoph Krafft

Summary

Scientists have developed a faster, more powerful microscope technique that uses infrared light to spot tiny details in cells, tissue samples, and even microplastic particles—without needing to add dyes or stains. By using a stronger laser source, they were able to scan an area about 20 times larger than previous methods while still seeing fine details, which could speed up medical diagnoses (like detecting cancer or infections in tissue samples) and make it easier to screen for microplastic contamination in the environment or human body.

Polymers
Body Systems
Models

High Resolution Image Download MS PowerPoint Slide Wide-field mid-infrared photothermal (MIP) imaging offers rapid label-free chemical contrast for biomedical and polymer analysis. Its field of view (FOV) depends on the mid-infrared pump power of infrared lasers. Here, a wide-field MIP microscope is presented using up to 150 nJ pulse energies of a free-electron laser (FEL) as the pump source to achieve a larger FOV compared to a quantum cascade laser (QCL) excitation with typically 1 nJ pulses. Both implementations use counter-propagating beam paths with a microsecond pulsed 450 nm LED as the probe source and a CMOS camera that records images using a virtual lock-in detection scheme. FEL’s higher pulse power expands the FOV by approximately a factor of 20, enabling submicron-resolution wide-field MIP imaging of polystyrene beads, single cells, and a murine brain tissue section. QCL systems with less intense pump pulses achieve only 45 μm FOV for samples including polystyrene beads, Mycobacterium tuberculosis -infected fixed tissue sections, and laryngeal cancer cryosections. IR spectra are reconstructed by tuning FEL and QCL wavelengths and collecting a series of wide-field images. We discuss current challenges and further improvements to implement high-power mid-IR pump lasers and shorter pulse probe sources for wide-field MIP imaging with even larger FOVs in the context of biomedical diagnostics and microplastic screening.

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