Interferometry

Materials science

Scanning electron microscope

Infrared microscopy

Microscope

Palette (painting)

Physics

Infrared

Optics

Spectroscopy

Quantum mechanics

Operating system

Computer science

Optical microscope

Microscopy

Proceedings of the National Academy of Sciences

Significance This study reports the ability to provide label-free molecular information from infrared (IR) spectroscopy via the ubiquitous optical microscope. Modeling the thermal-mechanical coupling of samples, we design, build, and validate an IR-optical hybrid (IR-OH) microscope that uses optical interferometry to measure the dimensional change in materials arising from spectral absorption. We show that the seamless compatibility of IR-OH with routine optical microscopy and with emerging computational ubiquity enables all-digital pathology with applications across the spectrum of biomedical science. IR-OH microscopy provides a means to retain the ease of use and universal availability of optical microscopy, add a wide palette of IR molecular contrast, and utilize emerging computational capabilities to change how we routinely handle, image, and understand microscopic tissue structure.

All-digital histopathology by infrared-optical hybrid microscopy