Free-electron laser-based extended wide-field mid-infrared photothermal imaging for biomedical and microplastic analysis

TL;DR

This paper introduces a wide-field mid-infrared photothermal imaging system using a high-power free-electron laser, significantly expanding the imaging field of view for biomedical and microplastic analysis with high resolution.

Contribution

It demonstrates the use of a free-electron laser as a pump source to achieve a much larger FOV in wide-field MIP imaging compared to traditional quantum cascade lasers.

Findings

FOV increased by nearly 20 times with FEL pulses

Achieved sub-micrometer resolution in imaging

Successfully imaged biological tissues and microplastics

Abstract

Wide-field mid-infrared photothermal (MIP) imaging offers rapid labelfree chemical contrast for biomedical and polymer analysis. However, its field of view (FOV) is limited by the pulse intensity of conventional infrared lasers. Here, we present a wide-field MIP microscope that uses a high-power free-electron laser (FEL) rather than a quantum cascade laser (QCL) as the pump source to achieve a substantially larger FOV. Both implementations use counter-propagating beam paths with a 450 nm LED as the probe source and a CMOS camera that records images using a virtual lock-in detection scheme. QCL nanojoule pulse energies enables FOV of around 45 micrometers for widefield MIP imaging with a sub-micrometer resolution for polystyrene beads, Mycobacterium tuberculosis infected fixed tissues, and laryngeal cancer cryosections. IR spectra in the range of 1000-1800 wavenumbers can be reconstructed by tuning the QCL. FEL pulse energies of up to microjoules expand the FOV by a factor of nearly 20 as demonstrated by wide-field MIP imaging of polystyrene beads, single cells, and murine brain tissue. We discuss current challenges and further improvements to implement high-power IR lasers for wide-field MIP imaging with even larger FOVs in the context of biomedical research and diagnostics.