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Work Group Molecular Imaging

Scientific Profile

The working group molecular imaging investigates new chemically sensitive linear and non-linear spectroscopic contrast mechanisms, laser technologies and detection techniques for multi-contrast and multi-parameter imaging of biological and biomedical target structures (e.g. pathogens and their antibiotic resistance, tumor cells, tissue samples, cell organelles, marker molecules such as drugs, organs, etc.). The application focus is on molecular and functional diagnostics in medicine and the life sciences. In addition, the working group molecular imaging focuses on the integration of the investigated multimodal approaches into compact clinically usable automated systems with high TRL levels for preclinical and prospective clinical studies. The clinical focus is on infectious diseases and tumor diseases, as these diseases have a high medical need for early diagnosis and therapy.

Fig. 1: Multimodal nonlinear microscopy for labelfree intraoperative frozen section diagnostics
Fig. 2: Compact multimodal nonlinear microscope for intraoperative frozen section analysis
Fig. 3: Endoscopic probe concepts for multimodal nonlinear imaging

Research Topics

  • Automated nonlinear multimodal CARS/SRS/SHG/TPEF/FLIM imaging for labelfree intraoperative frozen section analysis
  • Multimodal (Raman, CARS, SRS, SHG, TPEF, FLIM) microscopy and intravital microscopy for (I) label-free imaging of biomolecules (lipids, proteins, endogenous chromophores/autofluorophores such as NAD(P)H and FAD, elastin, as well as SHG-active macromolecules such as collagen, etc.)), (II) for the specific observation of the localization of active substances and their release dynamics and (III) for displaying small Raman labels (alkyne tags, stable isotope markings) in cells, tissues and organs.
  • Research of in vivo suitable multimodal nonlinear (CARS, SRS, SHG, TPEF) spectroscopic probe concepts (imaging fibers, rigid endoscopes with gradient index lenses, transport fibers)
  • Investigation of new concepts for (coherent) Raman microscopy with high spatial resolution
  • Establishment of new nonlinear contrast mechanisms in multimodal imaging approaches
  • Research and realization of miniaturized low-cost Raman systems
  • Realisation of chip-based concepts and microfluidic systems for drop, particle and cell diagnostics using linear and non-linear multimodal microspectroscopic methods
  • Raman spectroscopic characterization and identification of pathogens and their antibiotic resistance (RamanBioAssay)
  • Implementation of concepts for combined laser-based therapy and diagnostics (fs laser ablation and multimodal imaging)
  • Research of fiber laser concepts for fast spectral tuning with extremely low noise (RIN), high robustness and compact design especially for clinical applications
  • Robust and fast methods for statistical and multiparametric online data analysis in close cooperation with AG Bocklitz

Innovative multimodal molecular imaging approaches will be explored with a focus on nonlinear contrast phenomena with the aim to visualize biomolecules in cells, tissues and organs. Furthermore, the research work focuses on the realization of linear Raman spectroscopic assays for pathogen diagnostics and their resistance determination, with the aim of covering the entire workflow from sample preparation to result in the shortest possible time. In addition to the realization of compact setups for clinical use, the technological research focus is on the optimization and improvement of key parameters such as: spatial and spectral resolution, acquisition time, spectral bandwidth of detection, sensitivity (single photon counting method), molecular specificity or penetration depth.

Fig. 4: Dielectrophoretic chip with 20 cavities for Raman-based pathogen diagnosis and resistance determination
Fig. 5: Design of a miniaturized Raman system

Addressed application fields

  • Medical pathological diagnostics: Optical biopsy / spectral histopathology
  • Oncology: Tumor diagnostics and therapy
  • Infection diagnostics 
  • Cytometry
  • Mechanisms of action of drugs
  • Live cell microscopy
  • Therapy monitoring

The application focus of the researched multimodal imaging approaches and linear Raman spectroscopic assays are an improved disease diagnosis and therapy as well as new insights into dynamic life processes. Furthermore, in close cooperation with physicians and life scientists, new fields of application for molecular imaging are constantly being developed.

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