Hybrid Infrared-Optical Microscope For Pathology Studies

When imaging tissues microscopically, pathology labs have to stain the samples to see the cellular shapes and structures within. This is not trivial and requires expertise, time, and related costs.

Infrared light has the capability to help visualize biomedical samples without staining, but the wavelengths of such light make it incompatible with optical microscopes and require samples to be prepared in a special way. Now, researchers at the University of Illinois at Urbana-Champaign are reporting in Proceedings of the National Academy of Sciences on a hybrid infrared-optical hybrid microscope that can see the cellular details of tissues without having to rely on any staining or special prep. The technology may revolutionize histopathology both in the clinic and for research, allowing for faster diagnoses, wider availability, and lower cost.

“The advantage is that no stains are required, and both the organization of cells and their chemistry can be measured,” said Rohit Bhargava, one of the researchers involved in the study. “Measuring the chemistry of tumor cells and their microenvironment can lead to better cancer diagnoses and better understanding of the disease.”



The team converted a conventional optical microscope to include an infrared laser and an interference objective, a special microscopy lens. The optical and infrared components work together to produce a complex set of data for the sample, which is reconstructed using a computer into an intuitive image that looks similar to conventional stained samples. Moreover, the software can reproduce how conventional stains would look if imaging the sample the traditional way, helping users to quickly adapt to the new technology.

To make sure the technology is providing accurate results, the team compared results when imaging using conventional techniques and their hybrid microscope. They discovered that the two approaches had a strong correlation, paving the way for this technology to be further tested and hopefully widely adopted.

“Infrared-optical hybrid microscopy is widely compatible with conventional microscopy in biomedical applications,” said Martin Schnell, the first author of the study. “We combine the ease of use and universal availability of optical microscopy with the wide palette of infrared molecular contrast and machine learning. And by doing so, we hope to change how we routinely handle, image and understand microscopic tissue structure.”

Study in Proceedings of the National Academy of Sciences: All-digital histopathology by infrared-optical hybrid microscopy

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Left: tissue sample dyed by traditional methods. Center: a computed stain created from infrared-optical hybrid imaging. Right: tissue types identified with infrared data. The pink in this image signifies malignant cancer. Images courtesy of Rohit Bhargava