All-digital histopathology by infrared-optical hybrid microscopy

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.