15 December 2021

One million euros for histology in 3D

Scientists at the Berlin Institute of Health at Charité (BIH) and Charité – Universitätsmedizin Berlin have developed an automatable method for the histological examination of three-dimensional tissue preparations. Their idea could revolutionize microscopic tissue examinations and ease the burden on pathologists. The three founders of the project 3D-HistoPATH have now won a grant of over one million euros from the EXIST Transfer of Research aid program run by the German economics ministry. This will enable the scientists to develop their prototype into an end-to-end histopathology platform over the next two years.

Dr. René Hägerling’s main field of research is blood and lymphatic vessels: “I’m interested in how they grow, how they branch, and the role they play in various diseases,” explains the physician and chemist, who works at the BIH Center for Regenerative Therapies. “Because blood vessels in the body grow in all directions, I was becoming increasingly dissatisfied with two-dimensional microscopy images. Over time, this evolved into the 3D-HistoPATH project.”

Analysis of the entire tissue

Currently, clinical tissue samples – taken, for example, from a tumor or a suspicious lymph node in a cancer patient – are cut into fine slices, stained with antibodies targeted against specific markers, and evaluated under the microscope in a pathology lab. “Pathologists can look at a maximum of five sections per biopsy, so if they don’t find any tumor cells in these samples, that doesn’t mean there aren’t any,” explains Hägerling. “We wanted to create a way to analyze all the material.”

Hägerling and his two colleagues Dr. Fabian Mohr and Dr. Nils Hansmeier from the Institute of Medical and Human Genetics at Charité were excited about the possibilities provided by computed tomography, in which tissue is optically sliced into many thousands of sections, analyzed, and then reassembled three-dimensionally on a computer. “We figured that light sheet fluorescence microscopy, where the tissue is scanned by an entire plane of light rather than a single beam, would lend itself to a three-dimensional analysis of this kind,” reports Hägerling.

Fully automated workflow

Supported by the Berliner Startup Stipendium funding program and the BIH Digital Health Accelerator, the colleagues then developed a fully automated workflow – from sample preparation and microscopy to image analysis and diagnosis. For the staining, they used particularly small antibodies called nanobodies, which can easily penetrate the tissue due to their small size, paired with fluorescent dyes. “We can even combine our image analyses with molecular genetic methods,” says Mohr enthusiastically. “These methods now play an important role in determining the appropriate therapy for more and more tumor types.”

The goal of the future company is to make its service available for clinical studies, where many hundreds of samples often need to be analyzed relatively quickly. But the platform should also be able to be integrated into the everyday work carried out in pathology labs. “We are certainly not putting pathologists out of work, because they still have to make the final diagnosis and recommend treatment,” explains Hägerling. “But a growing elderly population will unfortunately also result in a greater demand for clinical analysis with increasingly sophisticated means of doing so. This is where we want to help.”