Mid-Infrared Photothermal Mesoscopy with Millimeter Field of View and Sub-micron Spatial Resolution.

Area of Science:

• Biomedical Optics
• Chemical Imaging
• Microscopy

Background:

• Mid-infrared photothermal (MIP) microscopy provides sensitive chemical imaging with submicron resolution.
• Current widefield MIP systems have limited fields of view (FOV), restricting applications in large tissue samples.
• Enhanced imaging speed was achieved with spatially multiplexed camera-based widefield detection.

Purpose of the Study:

• To develop a Mid-infrared photothermal (MIP) mesoscope with a significantly larger field of view (FOV) while maintaining submicron resolution.
• To overcome the FOV limitations of existing MIP systems for large-area tissue analysis.
• To demonstrate the capability of the MIP mesoscope for in vivo and ex vivo chemical imaging applications.

Main Methods:

• Utilized an all-reflective laser scanning architecture for MIP mesoscope construction.
• Employed low-magnification, medium numerical-aperture objectives for broad image capture.
• Implemented a defocused signal collection scheme to achieve a large FOV and high resolution.

Main Results:

• Achieved a 1.2 × 1.2 mm² field of view (FOV) with 650 nm lateral resolution.
• Enabled microsecond-scale pixel dwell time for rapid imaging.
• Successfully performed in vivo chemical imaging of Caenorhabditis elegans.
• Demonstrated high-throughput detection of beta-amyloids in mouse and human Alzheimer's disease brain tissues.

Conclusions:

• The developed laser-scan MIP mesoscope significantly expands the FOV for chemical imaging applications.
• This technology preserves submicron resolution, enabling detailed analysis of large biological samples.
• The MIP mesoscope shows promise for in vivo imaging and high-throughput screening of disease biomarkers like beta-amyloids.