From Vision to Application: How Researchers at Leibniz IPHT Are Collaborating on a Breakthrough in Diagnosing Life-Threatening Infections

A laser-based rapid test from Leibniz IPHT could be a game-changer in the fight against resistant germs. The technology works – now the researchers face the challenge of implementing the method in medical practice.

When Dr. Walter Hauswald’s systems technology team visited Dr. Anja Silge, Dr. Richard Grohs and Dr. Cornelia Reuter in the microbiology laboratory in December 2023 with the portable miniature spectrometer, they simply gave it a try. They placed the newly developed chip under the laser in the small gray box, filled the 40 small wells with bacterial samples and antibiotics, connected the rainbow-colored cables – and sure enough, it worked. “To the great delight of everyone involved, we were able to measure real bacteria with the new chip in the newly developed spectrometer,” reports Anja Silge, deputy head of the Spectroscopy and Imaging research department at Leibniz IPHT. “For us, it was like a new rocket really landing on the moon.

A Chip That Could Save Lives

The gray box and the quartz glass chip with the colorful cables contain more than two decades of research work by various teams and groups at Leibniz IPHT and the University Hospital Jena. Technologists and chemists, data scientists and microbiologists, physicians and physicists have worked together to develop an optical method that could revolutionize the diagnosis of infectious diseases: the RamanBioAssay®, a laser-based rapid test that identifies pathogens and the appropriate antibiotic from a single sample – in less than three hours. Current microbiology methods take up to three days. This could be life-saving in cases of serious infections that can develop into sepsis. In the case of aggressive, resistant pathogens, a patient’s chance of survival decreases by several percent every hour. Instead of prescribing a broad-spectrum antibiotic on suspicion, physicians could use antibiotics in a targeted manner – and thus make a decisive contribution to combating the growing number of resistant germs.

From Idea to Instrument

The gray box is a miniaturized Raman spectrometer for point-of-care diagnostics, fully functional with light source and detector – a handy mobile device that can be used in the future where there is no specialized laboratory nearby, for example in doctors’ offices in structurally weak rural regions. Instead of lenses and mirrors, a cleverly structured optical grating the size of a fingernail directs the light. It was developed and manufactured by the micro- and nanotechnology team in the clean room of Leibniz IPHT.

Teamwork Is the Key to Success

The second generation of the mobile spectrometer – the successor to the Raman2Go – and the latest version of the RamanBioAssay® chip were developed by interdisciplinary research teams at the newly established Leibniz Center for Photonics in Infection Research (LPI). The latest chip, which is about the length of a stick of chewing gum, can now test twelve instead of four different antibiotics at the same time – in different concentrations, so that doctors can immediately see how high the correct dose of the drug needs to be. This allows multiple samples to be tested three times faster, one after the other. The bacteria from a patient sample – blood or urine – are sealed behind laser-transparent quartz glass, sterile and hygienically covered.

When Prof. Dr. Jürgen Popp first came to the Friedrich Schiller University in Jena in 2002 and then to Leibniz IPHT as scientific director in 2006, he brought with him the idea of using Raman spectroscopy to study bacteria in order to make their molecular fingerprints visible. With the help of laser technology, researchers are now able to detect differences between different bacteria. Since the first BMBF-funded research project, research teams have been working on the implementation of a portable device for the rapid detection of infectious pathogens using Raman spectroscopy. Since 2010, they have been investigating how bacteria react to antibiotics; four years later, high-ranking publications followed, then the first patents and a spin-off. The method has received numerous awards, including the Thuringian Research Prize and the Berthold Leibinger Innovation Prize. Prof. Dr. Ute Neugebauer, who did her doctorate on this topic under Jürgen Popp, is now deputy scientific director of the Leibniz IPHT and heads her own research department of clinical spectroscopic diagnostics. Young researcher Dr. Johanna Kirchhoff received the German Academic Award for one of the most important dissertations in Germany for her work on the method.

Artificial Intelligence Speeds Up the Process

As the mobile spectrometer became more compact, the team grew larger. “We have left our laboratory and are continuing to develop the method and the devices together with our partners in clinical microbiology,” says Jürgen Popp. Leibniz IPHT has established its own group for system technology and instrument development. Over the past 15 years, the institute has increasingly focused on the evaluation of spectroscopic data, which is the key to the speed and accuracy of the method. Since 2019, an entire research department for photonic data science, headed by Prof. Dr. Thomas Bocklitz, has been working on the further development of AI-based methods. In total, Popp estimates that more than 40 people are working on the research and development of the method.

The Challenge: Regulatory Hurdles

The project is now facing its biggest challenge: the transfer to clinical practice. Proof of concept has been achieved. “We have provided extensive evidence that the technology works,” says Popp. Now it’s all about marketing – specifically technical and regulatory issues. Feasibility studies for clinical validation are underway with the University Hospital of Jena. Leibniz IPHT is initiating a cooperation with the University of California Davis to further develop the technology for the American market.

At the same time, the teams at Leibniz IPHT are working on automating the procedure to make it easier for doctors to use. The devices must also be cost-effective to compete with existing diagnostic methods. “A test should not cost more than three or four euros,” explains Jürgen Popp.

The increased requirements for the approval of medical devices under the EU Medical Device Directive and the associated documentation pose a challenge, especially since the handy miniature Raman device works with self-learning AI algorithms to quickly evaluate the pathogens.

Looking to the ­Future: The LPI

The Leibniz Center for Infection Research (LPI) is being established in Jena to exploit the potential of light-based technology for diagnostics (see page 41). The further development of the RamanBioAssay® with a compact Raman spectrometer for use directly at the point of care is being funded as the basic technology for the LPI. The unique translational infrastructure will bring together researchers with a proven concept and experts from industry on the way to market. “It is intended to become a one-stop agency for light-based infection research,” explains Popp. “So that good ideas from the laboratory reach people faster.”