Lehrstuhl für Physikalische Chemie II (Prof. Dr. Dr. Jürgen Popp)
Die Forschung der Arbeitsgruppe konzentriert sich hauptsächlich auf die Entwicklung und Anwendung innovativer Raman-basierter Methoden zur Beantwortung biomedizinischer Fragen. Raman-Spektroskopie und die verschiedenartigen Raman-basierten Technologien wie zum Beispiel die Raman-Mikroskopie, SERS oder CARS sind leistungsfähige Werkzeuge zur Bearbeitung eines breiten Spektrums bioanalytischer und biomedizinischer Probleme wie der schnellen Identifizierung von Pathogenen, der sensitiven Überwachung geringkonzentrierter Moleküle (beispielsweise Drogen oder Metabolite) oder der objektiven klinischen Beurteilung von Zell- und Gewebeproben zur Krebsfrüherkennung.
Raman imaging of molecular groups in the wavenumber silent region
Autoren
C. Schultz, J. Popp
Erscheinungsjahr
Erschienen in:
Analytical & bioanalytical chemistry
Raman imaging in the wavenumber silent region emerged around 15 years ago as a powerful tool for visualizing biomolecules and synthetic compounds in complex environments with minimal spectral and biological interference. Since then, the field has advanced from simple proof-of-concept studies using available tags to the rational design of highly efficient Raman labels with sharp silent region signatures, now applied to real biological and biomedical questions. This review traces the evolution from the versatility of label-free Raman to the increasing relevance of labeled strategies, emphasizing how tag design influences functionality, application, and impact. We highlight recent progress in both the synthesis and deployment of tags tailored for specific cellular targets and processes and discuss the emerging need for labeled strategies to meet the demands of sensitivity, multiplexing, and biocompatibility in complex systems. Through this design-to-application perspective, the review provides a comprehensive overview of the current capabilities and significant applications, and identifies key future directions to fully exploit the potential of silent region Raman imaging.
Pathway to versatile, point of care, and wearable photonics in the mid-infrared and fingerprint region based on quantum-cascade lasers and analytical and computational advances [Invited]
Autoren
S. Taccheo, T. Mayerhöfer, M. Doron, M. Lepage, R. Douté, A. Manca, A. Hobl, S. Messaoudene, M. Volpert, C. Constancias, R. Ballarini, K. Jourde, J. Coutard, B. Bourlon, A. D’Avolio, B. Bakir, J. Popp
Erscheinungsjahr
Erschienen in:
Optical Materials Express
This paper aims to propose and discuss a pathway to versatile, portable, and wearable photonics devices in the mid-infrared region. We address the benefits and challenges of mid-infrared spectroscopy in the fingerprint region and the development of low-cost mass production devices for real-world applications in the near future. Firstly, the paper briefly introduces the mid-infrared and fingerprint region and discusses the importance of the detection of mid-infrared biomarkers for point-of-care medical applications, stressing the importance of multi-wavelength probing systems. We also discuss the challenge of long-wavelength signals through the matter and the benefits of photo-acoustic detection. The pathway we envisage is twofold: the first is to improve and predict deviation from the standard Bouguer–Beer–Lambert approximation for light propagation in tissue and matter. This approach requires calibrated and wavelength-specific sources. Secondly, to address these requirements, the paper presents the potential for future low-cost personalized devices based on an array of quantum cascade lasers developed on low-cost C-MOS technology and using photo-acoustic detection. The technology was first developed for gas analyses, but we report on a recent successful wearable device for glucose monitoring, which passed clinical trials. This technology will allow the development of future widespread portable mid-infrared devices with potential application not only in healthcare, addressed here, but also in precise gas and environmental chemical monitoring. The ability to record mid-infrared biomarkers at the point of care will be fundamental for the personalized optical digital twin, which will be the cornerstone of future healthcare systems.
Label-free in vivo molecular profiling of the human retina by non-resonant Raman spectroscopy
Autoren
R. Sentosa, M. Kendrisic, M. Salas, M. Eibl, M. Schmitt, V. Shynkar, W. de Jong, H. Stino, A. Pollreisz, M. Kempe, J. Popp, T. Schmoll, M. Andreana, A. Unterhuber, W. Drexler, R. Leitgeb
Erscheinungsjahr
Erschienen in:
Communications Biology
Early detection of retinal molecular biomarkers is crucial for addressing the unmet clinical need to prevent irreversible neural tissue damage in ophthalmic and neurodegenerative diseases. Among emerging molecular sensing techniques, non-resonant Raman spectroscopy stands out as a naturally label-free and noninvasive method, offering rich biochemical information. However, in vivo detection of non-resonant Raman spectra from retinal tissue has proven to be challenging so far. Previous studies have reported conflicting results, likely due to overwhelming pigment autofluorescence. In this study, we identified the optic nerve head as the optimal retinal location for acquiring non-resonant Raman spectra in the molecular fingerprint region. Through longitudinal intra-subject measurements, we revealed dynamic changes in the molecular composition. Furthermore, a comparative study across age groups enabled the identification of molecular alterations associated with aging. These findings establish a critical foundation for utilizing non-resonant Raman spectroscopy as an early diagnostic tool for the detection of molecular biomarkers associated with ophthalmic and neurodegenerative diseases.
New approaches for molecular typing in Gram-positive pathogens
Autor
I. Osadare
Erscheinungsjahr
Antimicrobial resistance (AMR) represents one of the most severe global health threats of the 21st century. Vancomycin-resistant enterococci (VRE), primarily Enterococcus faecium and E. faecalis, are significant nosocomial pathogens that cause difficult-to-treat infections with high mortality rates in immunocompromised patients. Precise and rapid diagnostics are essential for infection control and targeted therapy. This dissertation addresses these challenges through the development and evaluation of innovative molecular methods for the detection and high-resolution typing of VRE. The first part of the study involved the design and optimization of a DNA microarray assay. Based on bioinformatic analyses using the ConsensusPrime pipeline, three generations of microarrays were developed, covering up to 327 target genes including resistance, virulence, and species-specific markers. In tests involving over 180 clinical isolates and 220 strains from Germany and Romania, the system demonstrated significantly higher discriminatory power than traditional Multilocus Sequence Typing (MLST). By combining microarray data with Next-Generation Sequencing (Illumina, Nanopore) and implementing a novel, image-based hexadecimal nomenclature system, regional differences in VRE populations were accurately identified. The second part of the work focused on rapid clinical diagnostics using a multiplex real-time PCR and recombinase polymerase amplification assays. These assays allow for the simultaneous identification of species and key resistance genes (vanA, vanB) directly from clinical colonies without extensive sample preparation. With a sensitivity of up to 100% and high cost-efficiency, the method offers significant potential for routine clinical diagnostics. In summary, this work provides critical advancements for the epidemiological monitoring and rapid identification of VRE. The developed tools contribute significantly to global strategies against the spread of AMR.
Cardiac Microanatomy Imaging Using Forward-viewing Optical Coherence Tomography Endoscope
Autoren
D. Vasquez, F. Einmuller, I. Latka, K. Kulkarni, N. Pallares-Lupon, M. Constantin, J. Marchant, V. Loyer, S. Bloquet, D. Hamrani, J. Naulin, W. Drexler, J. Popp, A. Unterhuber, M. Andreana, R. Walton, I. Schie
Erscheinungsjahr
Erschienen in:
IEEE Transactions on Biomedical Engineering
Objective: Due to limitations in current imaging technologies detecting subtle cardiac microstructural changes that can lead to sudden cardiac death is a significant clinical challenge. To address this problem, we developed a forward-viewing optical coherence tomography (OCT) endoscope for the detection of relevant cardiac microstructures in the subendocardium, including Purkinje fibers, scar tissue, surviving myocytes, and adipose tissue. Methods: An endoscopic probe based on the scanning fiber principle was developed for OCT measurements in contact. The probe was evaluated in freshly excised ovine hearts exhibiting chronic myocardial infarction. Relevant regions within the cardiac chamber were measured, and distinctive microstructures were identified, characterized, and subsequently corroborated using Masson's trichrome staining. The volumetric imaging data were used to train a convolutional neural network (CNN) to detect Purkinje fibers, enabling the reconstruction of their 3D morphology. Results: We were able to distinguish between healthy myocardium, fibrotic remodeling, and critical elements of the cardiac conduction system. Our findings demonstrate the capability of this technology to provide detailed images of cardiac microstructures in large mammal hearts. Conclusion: A novel application of forward-viewing endoscopic OCT in cardiology is demonstrated by visualizing cardiac microstructures within the subendocardium at depths accessible by optical imaging modalities. Significance: By enhancing visualization at the cellular level, this method may contribute to a better understanding of cardiac physiology and pathology, potentially extending future diagnostic and therapeutic strategies.
Mimicking a Light-Harvesting Complex to Accelerate Photooxidation in Asymmetric Lipid Membrane Nanoreactors
Autoren
J. Bösking, R. Nau, N. Alleva, R. Jacobi, T. Meyer-Zedler, H. Voßhenrich, F. Mazotta, I. Lieberwirth, D. Ng, M. Schmitt, J. Popp, L. González, T. Weil, A. Pannwitz
Erscheinungsjahr
Erschienen in:
Angewandte Chemie: international edition
In nature, photosynthesis is driven by solar light and a large proportion of the visible spectrum is absorbed by the light harvesting complexes (LHCs), which then transfer the energy to the reaction center. Inspired by nature, we implemented a light harvesting energy transfer cascade within biomimetic lipid bilayers of liposomes built with DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), using membrane-anchored fluorescein, 2-(3,6-dihydroxy-9H-xanthen-9-yl)-5-dodecanamidobenzoic acid (FlC ₁₂ ) as primary absorber and membrane anchored eosin Y, hexadecyl 2-(2,4,5,7-tetrabromo-3,6-dihydroxy-9H-xanthen-9-yl)benzoate (EYC ₁₆ ), as energy acceptor to sensitize oxygen and generate the reactive oxygen species ¹ O ₂ . Finally, the model substrate nicotinamide adenine dinucleotide (NADH) is oxidized by ¹ O ₂ within the compartmentalizing liposome nanoreactors. It was observed that our metal-free LHC system has only a minor effect on the photooxidation rate of NADH when the nanoreactor membrane is functionalized symmetrically. By contrast, asymmetric membrane functionalization of the liposome nanoreactor membranes leads to acceleration by 16% to 27% when using multi-colored light emitting diodes (LED) or simulated solar light, respectively.
