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.
Optical digital twins for disease prevention, diagnosis, therapy, and intervention
Autoren
A. Ozcan, M. Skala, B. Pogue, J. Popp, L. Marcu, C. Clancy
Erscheinungsjahr
Erschienen in:
Journal of Biomedical Optics
Significance: Digital twins are transitioning from conceptual models to operational frameworks that link measurement, prediction, and intervention in biomedicine. However, most biomedical digital twin efforts remain fragmented, with limited integration across biological scales, sensing modalities, and clinical decision points. Biophotonics provides a uniquely suited measurement foundation for biomedical digital twins by enabling quantitative, physics-grounded, and longitudinal noninvasive measurements spanning molecular, cellular, tissue, organ, and whole-body scales. These capabilities position photonics as a foundational measurement layer for next-generation biomedical digital twins. Aim: To synthesize current advances and future opportunities in optical digital twins and to establish a unifying framework for how photonic sensing can support digital twin architectures for disease diagnosis, therapy guidance, prevention, continuous monitoring, and interventional healthcare. Approach: This white paper summarizes perspectives presented at the annual meeting of the international society for optics and photonics (SPIE Photonics West), in the session "Digital Twins as New Approach Methodologies (NAMs) in Biophotonics." We review five complementary implementations of the digital twin paradigm: (i) virtual tissue staining for histopathology, which combines label-free optical imaging with machine learning-based inference to generate clinically interpretable representations with uncertainty quantification and validation; (ii) cell-level metabolic digital twins that use autofluorescence and redox imaging to predict patient-specific therapeutic responses in tumor organoids and immune cells under controlled perturbations; (iii) therapeutic digital twin frameworks for radiation therapy, in which Cherenkov imaging and radiation chemistry sensing verify treatment delivery and enable biophysical model correction and personalization; (iv) personalized optical digital twins for continuous monitoring that integrate longitudinal photonic sensing with physiological and contextual data to support early detection, prevention, and adaptive care; and (v) personalized digital twins for interventional healthcare. Results: Across these diverse applications, a common digital twin architecture emerges. Optical measurements define patient state, inference models translate measurements into predictions, therapeutic interventions perturb the system, verification measurements constrain and validate execution, and longitudinal sensing continuously updates the twin over time. The reviewed examples demonstrate that optical measurements can serve as a scalable and biologically relevant data layer linking prediction and intervention across multiple levels of biological organization. Conclusions: Optical digital twins are no longer merely a conceptual aspiration but are emerging as a practical, measurement-driven infrastructure for precision medicine. The primary challenge is no longer feasibility, but rather the integration, interoperability, validation, and uncertainty quantification of digital twin systems capable of operating safely and at scale. Advances in photonic sensing, computational modeling, and clinical translation position optical digital twins to support real-time, patient-specific clinical decision-making across diagnosis, treatment, monitoring, and prevention.
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.
Bioanalysis Using Surface-Enhanced Raman Spectroscopy: From the Perspective of Single Molecules
Autoren
X. Yao, J. Popp, J. Huang
Erscheinungsjahr
Erschienen in:
ACS Nano
Single-molecule surface-enhanced Raman spectroscopy (SM-SERS), with single-molecule sensitivity and fingerprint-like specificity, has become a rising tool for probing the physicochemical properties of biomolecules at a single-molecule level. Notably, SM-SERS is generally achieved by complex methodologies with the assistance of rationally designed substrates and single-molecule techniques, often accompanied by significant technical challenges. Given the persistent issues of reproducibility and reliability, this critical perspective does not aim to provide a comprehensive review but instead progresses from a selective overview of representative SM-SERS methods and features to a detailed discussion of its intrinsic and often overlooked limitations, including the long-existing signal intensity fluctuations (SIFs), sample degradation, and the emerging challenge of big data processing and analysis. It is aimed to provide a conceptual framework that advances both the fundamental understanding and practical application of SM-SERS in future research.
Reducing Non-Linearity in Spectral Evaluation via a Modified Lorentz–Lorenz Relation
Autoren
T. Mayerhöfer, I. Noda, J. Popp
Erscheinungsjahr
Erschienen in:
Applied spectroscopy: an international journal of spectroscopy
Quantitative infrared spectroscopy of liquids often assumes linear Beer–Lambert behavior, although local-field interactions and dipole–dipole coupling introduce intrinsic nonlinearities. We investigate whether a modified Lorentz–Lorenz relation, motivated by electromagnetic theory, can reduce these deviations and restore approximate linearity in binary mixtures. Using benzene–toluene and benzene–cyclohexane as model systems, we evaluate linearity through RMSE metrics, hybrid 2D-correlation analysis, asynchronous residual sums of squares, and complex-valued classical least squares (CLS) regression. While correlation-based measures provide qualitative insights, they fail to reliably identify optimal linearization parameters. In contrast, CLS in the Lorentz–Lorenz–transformed domain, particularly with systematic-error correction, yields clear minima and substantially improves prediction accuracy, reducing mean absolute errors by more than a factor of three relative to the Beer–Lambert domain. These results demonstrate that the modified Lorentz–Lorenz transformation provides a physics-informed chemometric domain in which spectral mixing becomes more linear. The approach suggests extending inverse least square regression, principal component regression, and partial least squares regression into this domain to further enhance quantitative mixture analysis.
