Editorial Feature

The Hybrid Microscope and the Future of Cancer Diagnosis


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A new hybrid microscope has been developed by a team of researchers working at the Cancer Center at the University of Illinois that promises to create digital biopsies that could transform the field of cancer biopsies.

In a research paper published in the Proceedings of the National Academy of Sciences, the team describes how their innovation that pairs an infrared capability with the standard optical microscope generates digital biopsies that are comparable to those created by traditional pathology techniques and were better than those produced by state-of-the-art infrared microscopes.

The team believes that its hybrid microscope will enhance diagnostic methods by speeding up the time it takes to process test results, bringing down the costs due to eliminating the need to use reagents and dedicate valuable staff time to stain tissue and introduce an 'all-digital' solution for cancer pathology.

Staining Methods are Limited in their Use in Cancer Diagnosis

Currently, immunohistochemistry is considered the gold standard in terms of imaging methods used in pathology. Immunohistochemistry is the most popular immunostaining technique that involves the identifications of proteins (antigens) present in a sample by staining antibodies that bind to these specific antigens. In an alternative indirect process, an antibody is used against the target antigen and a second, labeled antibody is used against the first.

Staining allows shapes and patterns within cells to be visualized under a microscope. It allows scientists to see the organelles, proteins, and other molecules that may exist within a tissue. The idea is that it can identify markers of disease to help distinguish between health and diseased tissue. However, cancer is not always easy to distinguish from healthy tissue. In addition, segregating the boundaries of a tumor can also prove difficult, leaving diagnosis to the opinion of the health professional and therefore leaving it vulnerable to human error.

Dyes have been added to tissue biopsies for over 100 years as a method of tumor diagnosis, but the technique is limited in its ability to reveal the molecular changes related to cancer progression. Therefore, there is a strong need for a new, improved imaging method.

This is what drove the scientists at the University of Illinois to establish a new technique that can better visualize tumors. They looked to infrared microscopy due to its ability to measure the tissues molecular composition, quantitatively measuring features associated with cancerous cells. Infrared on its own, however, is not suitable for use in cancer diagnosis because it requires specialized handling and preparation making it impractical and expensive.

Combining High-Resolution Microscope Technology with Infrared Microscopy

To overcome the limitations of both methods and to create a new diagnostic technique, the team added an infrared laser as well as an interference objective (a specialized microscope lens), to an optical camera. The method was developed to measure high-resolution optical image data along with infrared data with a light microscope.

The hybrid microscope was constructed with off-the-shelf components, making it accessible to a wide range of labs who can simply build their own microscope.

Click here to find out more about various optical microscopes

The combination of the two imaging techniques resulted in incorporating the strengths of both methods, establishing a technique that has a high-resolution, a large field-of-view, and the accessibility of a common piece of lab equipment, the optical microscope.

In addition, the technique works without the requirement of staining tissues, meaning that damage to the samples is limited, and time is not needed to carry out this step of the process.

Success in Imaging Breast Cancer Tissues

The team tested the efficacy of their new technique by imaging breast tissue samples taken from patients with and without cancer. The results of the digital biopsy were found to be closely correlated with those obtained by traditional methods.

The infrared-optical hybrid microscope was also shown to outperform infrared microscopes in terms of coverage, consistency, and resolution.

An 'All-Digital' Solution for Cancer Pathology

Overall, the team was successful in developing an enhanced technique for investigating cancerous tissues by combining infrared measurements, high-resolution optical images, and machine learning algorithms. The technique will allow scientists to more accurately measure the chemistry of tumor cells which will help to improve both diagnostic methods and our understanding of the disease.

The team hopes that due to the ease of access to the approach, given that the microscope can be built in the lab from conventional pieces of equipment, infrared-optical hybrid microscopy will be widely adopted by the scientific community and will result in a shift in how tissue samples are handled and investigated.

It is promising that the new technique could benefit the diagnosis of cancer, helping to speed up the time it takes to make a diagnosis, as well as reducing the costs of the process and the overall accuracy of the method. The infrared-optical hybrid microscope will be an 'all-digital' solution for cancer pathology.

References and Further Reading

Freudiger, C., Min, W., Saar, B., Lu, S., Holtom, G., He, C., Tsai, J., Kang, J. and Xie, X., 2008. Label-Free Biomedical Imaging with High Sensitivity by Stimulated Raman Scattering Microscopy. Science, 322(5909), pp.1857-1861. https://pubmed.ncbi.nlm.nih.gov/19095943/

Ghaznavi, F., Evans, A., Madabhushi, A. and Feldman, M., 2013. Digital Imaging in Pathology: Whole-Slide Imaging and Beyond. Annual Review of Pathology: Mechanisms of Disease, 8(1), pp.331-359. https://pubmed.ncbi.nlm.nih.gov/23157334/

Schnell, M., Mittal, S., Falahkheirkhah, K., Mittal, A., Yeh, K., Kenkel, S., Kajdacsy-Balla, A., Carney, P. and Bhargava, R., 2020. All-digital histopathology by infrared-optical hybrid microscopy. Proceedings of the National Academy of Sciences, 117(7), pp.3388-3396. https://www.pnas.org/content/117/7/3388

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Sarah Moore

Written by

Sarah Moore

After studying Psychology and then Neuroscience, Sarah quickly found her enjoyment for researching and writing research papers; turning to a passion to connect ideas with people through writing.


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