FBH has been contributing its expertise in laser light sources to the Research AllianceLeibniz Health Technologies since 2014. This association of 15 research institutes develops technological solutions for urgent medical issues and unites expertise in multiple scientific fields, from photonics and medicine to microelectronics and materials research, to economic research and applied mathematics. Innovative health technologies can thus be brought to market maturity along a gapless innovation chain of industry, clinics, insurance companies, and politics. Leibniz Health Technologies takes a comprehensive approach that includes researching the economic, social, and ethical consequences of new technologies. FBH is currently involved in the two Research Alliance projects EXASENS and HYPERAM.
Since January 2016, FBH and eight other partners from the Research Alliance Leibniz Health Technologies have been collaborating in the EXASENS project to research point-of-care (POC) technology for predicting and diagnosing chronic inflammatory respiratory diseases such as asthma or chronic obstructive pulmonary disease, COPD. According to the journal “Pneumologie”, there are nearly 12 million suffers of these diseases in Germany alone. The Alliance is backed by 6.25 million Euros from the German Federal Ministry of Education and Research (BMBF).
Prediction or early detection of acute, attack-like exacerbations by telemedicine-capable POC diagnosis systems could reduce the necessity for intensive medical measures and also improve prognoses. The ultimate goal is to have POC systems readily available for rapid intervention in acute situations, for individualized treatment, and for closely networked monitoring of disease progression and treatment, thereby significantly helping to improve quality of life.
FBH is developing the necessary compact light sources, and thus a key component, for the POC system which, among other things, employs Shifted Excitation Resonance Raman Difference Spectroscopy (SERRDS). The diode laser modules, which emit at 532 nm wavelength, deliver two excitation lines at a close spectral distance of about 10 cm-1. When measuring two Raman spectra with excitation wavelengths at this distance, Raman signals can be separated from interfering signals such as fluorescence or ambient light. A particular requirement for the light source, which is only about half the size of a box of matches, is rapid spectral switching capability for the excitation wavelength. This, in turn, allows for much shorter measuring times and thus faster diagnoses than ever before.
SERRDS requires precise adjustment of the properties of two active components in the system: the diode laser as pump light source, and the crystal for non-linear frequency conversion. Because such SHG crystals are third-party components, the diode laser must be precisely adjustable to accommodate any manufacturers’ tolerances in the crystals. This demands utmost precision in the manufacture of the wavelength-stabilizing grating and in the lateral design of the waveguide in the semiconductor chip. Heating elements are also installed to allow precise adjustment of the wavelength by altering the temperature of the grating section. Switching between the two wavelengths is done directly via the active gain section.
In the Leibniz Research Network HYPERAM, three Leibniz institutes have joined forces from the fields of biosciences, astrophysics, electronics, and medicine. They are combining their interdisciplinary knowledge in order to develop rapid, label-free and non-invasive tissue diagnosis methods based on wide-field Raman imaging. This will open up new possibilities for clinically evaluating tissue already during surgery using functional Raman images to reveal tumor margins. This would make for shorter and more precise surgical operations in oncology, for example. Among other things, the project aims to translate the method of integral field spectroscopy, which was born from astrophysics and is normally used to study large areas of the night sky, to biomedical imaging applications. The overall project started in 2016 and is planned to run for three years with approximately one million Euros in funding from the Leibniz competition.
In this project, FBH is again developing the Raman-based diode lasers optimized for tissue diagnosis, as an important centerpiece of the system. The challenge lies in combining the high laser powers required for imaging with the spectral characteristics needed for spectroscopy and SERRDS. At the same time, the maximum permissible radiation doses must not be exceeded. FBH is therefore taking two approaches: it is developing a light source of 785 nm wavelength and up to 4 watt output power, plus a second beam source in the blue-green spectral range of 457 nm wavelength – a frequency range in which strong fluorescence occurs. This light source should be suitable for the SERRDS method and thus allow the separation of Raman signals and fluorescence for the imaging method as well.