Every year, about 500,000 people in Germany are diagnosed with cancer. Diagnostics and treatment are constantly developing. Currently, surgery, chemotherapy and radiotherapy are used as standard treatment options. Immunotherapy using therapeutic antibodies and genetically modified, endogenous immune cells (CAR-T cells) has recently moved into focus.
The distinction between healthy tissue and tumor tissue is often not easy. The aim of tumor surgery is to maintain tumor-free resection margins while at the same time increasing the preservation of surrounding healthy tissue. Possible problems are the following:
Development of an easy-to-use optical method, that:
Acquisition of optical sectional images using confocal MEMS-based laser fluorescence microscopy in vivo.
Within the project, a laboratory demonstrator of a miniaturized confocal laser scanning microscope is to be developed. The advantages of the development should be the use of a MEMS device (Micro-Electro-Mechanical System) developed at the Fraunhofer IPMS and thus the miniaturization and the cheaper production compared to competing technologies. The proof-of-concept for a robust MEMS-based fluorescence laser scanning microscope has already been provided2,3 and is protected by patent (DE102013222349B3 of Febr 15, 2015).
The further development of the demonstrator should allow its application in surgically accessible tumors (e.g. brain or skin tumors). To this end, a method for the specific staining of tumor cells using fluorescence-labeled antibodies at the cell culture level was established at Fraunhofer IZI. In a next step, patient material will be used and the specific staining of tumor cells will be visualized on 2D sections of patient material. Subsequently, the possibility of using the demonstrator on 3D tissue samples from patients outside the body (ex vivo) will be investigated in order to work out an intraoperative application on the patient (in vivo).
Research Fraunhofer IZI, fluorescent dyes - approved for use in humans:
485 nm (pH 9)
514 nm (pH 9)
|indocyanine green (ICG)||excitation maximum:
600 – 900nm
750 – 950 nm
1. Falco, J. et al. Fluorescein Application in Cranial and Spinal Tumors Enhancing at Preoperative MRI and Operated With a Dedicated Filter on the Surgical Microscope: Preliminary Results in 279 Patients Enrolled in the FLUOCERTUM Prospective Study. Frontiers in surgery 6, 49; 10.3389/fsurg.2019.00049 (2019).
2. Bechtel, C., Knobbe, J., Grüger, H. & Lakner, H. Large field of view MEMS-based confocal laser scanning microscope for fluorescence imaging. Optik 125, 876–882; 10.1016/j.ijleo.2013.07.091 (2014).
3. Bechtel, C. Development of a MEMS-based confocal laser scanning microscope for fluorescence imaging. Zugl.: Dresden, Techn. Univ., Diss., 2014 (TUDpress Verl. der Wiss, Dresden, 2015).
4. Cavallo, C. et al. The utilization of fluorescein in brain tumor surgery: a systematic review. Journal of neurosurgical sciences 62, 690–703; 10.23736/S0390-5616.18.04480-6 (2018).
5. Yannuzzi, L. A. Indocyanine green angiography: a perspective on use in the clinical setting. American journal of ophthalmology 151, 745-751.e1; 10.1016/j.ajo.2011.01.043. (2011).
6. Porcu, E. P. et al. Indocyanine green delivery systems for tumour detection and treatments. Biotechnology advances 34, 768–789; 10.1016/j.biotechadv.2016.04.001. (2016).