Best known for his research on Raman spectroscopy, Prof. Dr. Jürgen Popp is the scientific director of the Leibniz Institute of Photonic Technology in Jena, Germany, and chairman of the department of physical chemistry at the Friedrich-Schiller University of Jena. After receiving his doctorate degree in chemistry from the University of Würzburg in Germany, Popp continued his postgraduate studies at Yale University and eventually made his way back to Würzburg for habilitation. He has been published in more than 450 peer-reviewed journals. Since 2002, he has been speaker of BioPhotonik, a funding initiative of the German Ministry of Education and Research meant to highlight the importance of photonics and the need for continued research in light science. In addition to being a fellow of SAS and SPIE, Popp recently received the Robert-Kellner Lecture award and an honorary doctorate degree from Babes-Bolyai University in Cluj-Napoca, Romania. He is also editor-in-chief and founding editor of Journal of Biophotonics. Popp is set to speak at the Photonics4Life Interdisciplinary School on Clinical Biophotonics this month on the topic of Raman microscopy. Photonics Spectra recently asked Popp three questions about his work with microbial analysis and early disease detection through Raman-based approaches. Q: What are you working on right now? A: Our research interests are concerned with biophotonics and the development and application of enabling technologies, like custom-made light sources or optical fibers, to address important questions within the areas of health, life sciences, safety, energy and the environment. In doing so, one major focus lies on the development and application of Raman-based approaches for medical diagnosis as well as environmental and food safety monitoring. Raman-based methods are label-free, noninvasive [and] provide molecular fingerprint information, [making them] ideal tools for medical and life science research. [Our research utilizes] the unique potential of Raman microspectroscopy for microbial analysis with online, on-site identification of single microorganisms. We were able to show that Raman microscopy, in combination with statistical methods, allows for rapid and direct identification of sepsis pathogens in urine samples of real patients, of anthrax endospores embedded in complex matrices, and of food pathogens in milk and meat without any precultivation steps. Despite prokaryotic cells, we also use Raman spectroscopy to characterize eukaryotic cells like tumor cells. [We] are working on Raman-activated cell sorting (RACS) by coupling Raman spectroscopy with microfluidics and micromanipulation approaches. Besides single cells, we are also characterizing whole tissue sections like biopsy specimens through Raman microspectroscopy. The processing of specific Raman maps via mathematical approaches enables an objective evaluation of the tissue samples for an early disease diagnosis like cancer. Besides these ex vivo Raman studies on excised tissue, we are taking the first steps towards in vivo Raman spectroscopy by using novel Raman fiber probes for intravascular monitoring of the arteriosclerotic plaque in living rabbits. The low-Raman-scattering cross section often results in long acquisition times. However, the acquisition times can be reduced by utilizing nonlinear Raman approaches like coherent anti-Stokes Raman scattering (CARS) that allows recording images of single-characteristic Raman bands in real time. In order to further improve the diagnostic result, CARS microscopy can be easily extended by the two other nonlinear contrast phenomena second-harmonic generation (SHG) and two-photon fluorescence (TPF). We developed a compact CARS/SHG/TPF multimodal nonlinear microscope in combination with novel fiber laser sources for clinical use. The diagnostic potential of this compact multimodal microscope as compared to conventional histopathological images has been demonstrated in atherosclerosis and cancer. Q: What are the implications of Raman approaches? A: The microbial Raman analysis approach, which does not require any time-consuming cultivation step, is of great relevance to quickly diagnosing infectious diseases. The fast detection of disease-causing microorganisms is important for many invasive infections. In cases of sepsis, a rapid detection and identification of the inducing pathogens is crucial for choosing a proper initial antibiotic therapy. Furthermore, the fast identification of microorganisms is extremely important for efficient water, air, soil or food monitoring. The work on ex vivo and in vivo optical tissue Raman imaging allows for an identification and characterization of pathological alterations in tissue, and therefore offers the unique possibility for an objective medical diagnosis towards optical pathology. Overall, linear and nonlinear Raman approaches show an enormous potential for clinical applications. Q: What’s the next step? A: We are planning to transfer our Raman approaches into clinical settings [and focus] on in vivo Raman spectroscopy to monitor pathophysiological processes within organs. These efforts involve the development of portable and easy-to-use inclusive laser and Raman systems. In doing so, we particularly focus on the development of novel linear and nonlinear Raman fiber probes for Raman endospectroscopy. Furthermore, we are planning to concentrate more on chip-based Raman analytics – that is, lab-on-a-chip Raman spectroscopy for point-of-care biomedical Raman diagnostics.