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Cluster Report Photonics in the Capital Region Berlin-Brandenburg

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5.1.4 Optical Technology

5.1.4 Optical Technology in Biomedicine and Pharmaceuticals Optical methods for diagnostics, therapy and analytics Uwe Netz, Joachim Mertens, Gerrit Rössler, Kai Kolwitz Whether in diagnostics, therapy or analytics: many biomedical processes are based on optical methods. And optics continually opens up new applications in the medical field. The Berlin-Brandenburg region proves competence also in this area, both in development of new processes and products, as well as in providing high quality equipment and components, through close collaboration of local institutions and companies. laser angioplasty for dilating blood vessels were developed at LMTB in Berlin. This begins with fundamental questions: whoever wants to develop new processes, first needs to know how light propagates in different types of biological tissue, how it is absorbed, scattered and re-radiated. The detailed questions depend on what is to be achieved. If you want to treat with light, you need to know how much of which wavelength is absorbed in the target tissue and the effects it causes there. The scattering influences the spatial extent of the reachable target volume. For diagnostics and sensors, in turn, in addition to the absorption, mainly scattering processes such as fluorescence or Raman scattering are important: What proportion of the incident light can pass through the tissue, and how far has it been deflected? And can one make statements that way about whether a tumor is degenerated or not? Quartz light guide with millions of scattering centers by ultra-short laser pulses as scattered light applicator for laser therapy © Laser- und Medizin- Technologie GmbH, Berlin The advantage of such methods is that they allow an immediate diagnosis without the need to take samples which need to be analyzed in a laboratory. One can determine the concentration of diagnostically relevant biomolecules from the spectra. Spectroscopic diagnoses and optical scalpels It's even better when models can be developed from experiments that allow general predictions for the behavior of radiation in the body. That means that the characteristics of new devices for diagnosis and treatment can be determined theoretically, even before the first prototype is built. The determination of such sizes and models is among the core competencies of the Berlin Laser- und Medizin-Technologie (LMTB), just like the development of applications based on the knowledge acquired. Current standard therapies such as laserinduced thermotherapy for the treatment of liver tumors or Blood bag sensor, project SenTiss © Laser- und Medizin-Technologie GmbH, Berlin With this expertise, the institution is a sought after partner for research and development projects. For example, LMTB works in the Berlin group project “SenTiss” to develop a set of new optical sensors for use in biological tissues. The technology is available, for example, to determine if stored blood is still usable, to monitor the oxygen supply in heart-lung machines, and to determine the concentration of substances such as hemoglobin and water in the skin. The cooperation partners are the Berlin photometer manufacturer Robert Riele, the Berlin manufacturer of optical systems opTricon, Berliner Glas, a specialist in optical components, and the Sorin Group Germany. The question if medical instruments are really sterilized after cleaning is at the heart of the project “Optical Cleaning Control.” Here, various spectroscopic techniques of fluorescence detection are used to detect contamination via intrinsic fluorescence of protein buildup with high sensitivity. Project partners, aside from LMTB, are the TU Berlin, Berlin's Vanguard AG, which specializes in the preparation of instruments and sterile services for hospitals, as well as other industry partners. Another research focus of LMTB is minimally invasive surgery using lasers. Because of their thermal effects, laser radiation can selectively destroy tumors, e.g., in the liver. On this topic, LMTB cooperates most intensively with the Charité. Jointly with World of Medicine, LMTB has developed the FREDDY laser technology, which is mainly applied in order to eliminate gall and kidney stones. However, also other applications are possiple such as the cleansing of surfaces or artwork. 66

5.1.4 Optical Technology in Biomedicine and Pharmaceuticals Prototype LIMES 16-P diagnostic device for early detection of melanoma © LTB Lasertechnik Berlin GmbH The principle was developed as part of the research project Fluo- TOM, which was funded by the Federal Ministry of Science and Research. Partners involved were World of Medicine in Berlin, LTB Lasertechnik Berlin, and the Institute of Physics of the University of Potsdam, in collaboration with the Elizabeth Hospital in Berlin and the University Hospital in Magdeburg. The project partners hope that this technology will be useful even for endoscopic examinations. Laserfragmentation of body concretions (here, a gall stone) with the FREDDY technology © Laser- und Medizin-Technologie GmbH, Berlin Research at LMTB is also conducted on medical laser scanning microscopy, and one is looking for alternatives to the difficult to handle CO2 laser in surgery. Whether skin cancer or rheumatism – light helps to detect it early Another example of the application of optical methods is the “Limes 16-P” manufactured by Lasertechnik Berlin (LTB). The device is able to detect the dreaded black skin cancer, melanoma, even at a very early stage. The diagnosis work with nearly 100% reliability; no tissue samples have to be taken. The method was developed at the Max Born Institute for Nonlinear Optics and Short Pulse Spectroscopy. There it was discovered that in the near-infrared region at about 800 nm, an absorption of incident light can be detected which could distinguish a tumor from normal tissue. Researchers and companies cooperated, and the collaboration resulted in a marketable product. White skin cancers, basalioma, can be diagnosed in a similar fashion: Using two-photon fluorescence microscopy layered images of the skin are generated with the aid of which a tumor can be quickly and accurately evaluated by a doctor as far as extent, location and aggressiveness are concerned. The principle can also be used to appraise how locally applied therapeutic substances will distribute in the body. Increasingly, such non-invasive diagnostic techniques are used in everyday medical practice – and often are research institutions and companies from Berlin-Brandenburg involved in their development. Another example is the diagnosis of rheumatoid arthritis. In inflammation spurts, it destroys articular cartilage and bones in a painful manner and affects the entire body. The Physikalisch-Technische Bundesanstalt (PTB), together with the Berlin mivenion GmbH, developed a fluorescence-based method for the early enough detection of pathological changes in the finger joints in order to allow effective therapy. Mivenion markets the developed rheumatism scanner under the name xiralite. This approach not only allows to diagnose this ailment more easily than before, but also to specify the necessary medication more individually than previously. In the new procedure, the contrast agent indocyanine green (ICG) is administered to the patient; the fluorescent light allows the observation of finger blood flow. Another focus of the PTB is the diagnosis of breast cancer that could be improved by using a similar method. After administration of the same fluorescent contrast agent, a malicious breast tumor can be distinguished from a benign one in the optical mammography. Pinpoint tumor removal – medical optics makes it possible Also for surgeons, imaging is of great importance because it helps them to get oriented in the surgical area and to unambiguously identify pathological areas. The molecular imaging can bring to light what previously was only possible with the aid of biopsies: the combination of contrast and near-infrared fluorescence makes pathological tissue areas visible, and thus the surgeon knows exactly what needs to be removed during a surgery. 67

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