Diagnostics and Sensors

Label-free detection methods - i.e. without additional reagents for molecular characterisation - have a high development potential as they can provide simpler diagnostic tools that can be used outside the laboratory and thus become accessible to non-specialist users. Fraunhofer IPMS is developing photonic label-free biosensors based on silicon nitride microring resonators in silicon technology. They are used for the selective detection of biomarkers or microbial substances and offer, for example, a suitable detection method for the early detection of diseases. 

For this purpose, Fraunhofer IPMS and Fraunhofer IZI are developing a highly sensitive integrated photonic biosensor platform.

Deep vein thrombosis (DVT) and its fatal complication pulmonary embolism afflict millions of people worldwide and are responsible for a large percentage of acute hospitalizations. Deep vein thrombosis (DVT) is the formation of a blood clot within the deep veins, most commonly those of the lower limbs, causing obstruction of blood flow. In 50% of people with DVT, the clot is at some point detached from the vein wall and travels to the lung to cause pulmonary embolism. About 25% of people experiencing pulmonary embolism will die from it, making it the 3 leading cause of cardiovascular death worldwide after stroke and heart attack. Clinical assessment of DVT is notoriously unreliable because up to 2/3 of DVT episodes are clinically silent and patients are symptom free even when pulmonary embolism has developed.

Early diagnosis of DVT is crucial and has been proven to prevent life-threatening complications (pulmonary embolism), minimize the risk of long-term disability (post-thrombotic syndrome, recurrent DVT), improve treatment outcomes, and reduce healthcare costs. ThrombUS+ brings together an interdisciplinary team of industrial, technology, social science and clinical trial experts to develop a novel wearable device for continuous, operator free continuous monitoring in patients with high DVT risk.

Fraunhofer IPMS is developing the ultrasound transducer array for wearable, point of care DVT continuous monitoring together with VERMON. We are focusing on our CMUTs (Capacitive Micromachined Ultrasonic Transducers), which are MEMS-based transducers considered the next generation of medical ultrasound devices. CMUTs can be manufactured at low cost due to high-volume production. Additionally, advantages like miniaturization with high channel numbers, high bandwidth in combination with high sensitivity will help to develop a completely new device. 

The Corona pandemic poses a challenge for medical diagnostics: In addition to severe symptoms, the SARS-CoV-2 virus also causes mild symptoms that can worsen very quickly. However, continuous patient monitoring has so far only been available in intensive care units. As a result, sudden deterioration in health is often only recognised with a time delay and those affected are brought to hospital too late. This is exactly where the cluster project M3Infekt comes in. By mobile recording, analysis and fusion of relevant biosignals with the help of different technologies, valid diagnoses can be made about the condition and course of the disease.

In the long term, the system under development will address decentralised patient monitoring on normal wards and in non-clinical environments using multimodal parameters of the cardiovascular system (including heart rate, ECG, oxygen saturation, blood flow situation) and respiration (including respiratory rate/volume, respiratory air analysis). Machine learning methods will be used as the basis for evaluation, which facilitates diagnostics and ensures that the system can be easily integrated and deployed in various application scenarios.

Diseases can be detected by analysing the air we breathe. For example, traces of specific gases in the breath are an early sign of various diseases, including cancer. Spectroscopic breath analysis can detect these gases and thus enable early diagnosis and thus prompt therapy. Corresponding chemical sensor systems that can be used in everyday life are based on a MEMS ion mobility spectrometer, which can be used to provide procedures for rapid tests.

Lab-on-chip (LOC) diagnostics is now the state of the art in various laboratory diagnostic procedures. It enables the automated processing and evaluation of samples. Diagnostic results can thus be provided faster, earlier, and more cost-effectively than with conventional analysis in a medical laboratory. However, lab-on-chip systems are not available for all applications. Together with partners, the Fraunhofer IPMS is therefore developing new components and modules for LOC diagnostics in cytokine release syndrome.

Cytokine release syndrome (CRS) can occur with various diseases and therapies (e.g., immunotherapy, sepsis, and infectious diseases such as COVID-19). In a CRS, cytokines are produced as part of the body’s immune response, thereby activating more immune cells. These migrate to the site of inflammation and produce cytokines that trigger an excessive immune response. This does not subside automatically – as is usually the case – but rather continues to intensify. Because this serious side effect can be fatal, it must be diagnosed and treated as soon as possible.

Cell-based therapies are usually personalized to the patient and are often still very expensive due to the sometimes very complex manufacturing processes. For people with a critical stage of the disease, timely production is often vital. As part of MIC-PreCell, modern methods of integrated quality assurance will therefore be established, with which the manufacturing processes can be shortened and any production errors can be detected considerably earlier.

The project team is focusing on the broad use of innovative quality assurance methods in cell production, such as optomechanical profiling, which can be used to determine mechanical cell properties immediately and without marking. The Fraunhofer researchers also want to use a gas chromatograph-ion mobility spectrometer to analyze VOCs, volatile organic compounds, which are released into the outside air by cell cultures. In addition, devices for the micromanipulation of cells and cell clusters or organoids will be used to provide direct and detailed real-time information on the condition of therapeutic cell products.

A sensor for measuring the oxygen concentration in gases using a specially developed sensor layer or commercial sensor spots. A blue OLED excites the dye layer and the response phosphorescence signal is detected and evaluated in the CMOS backplane chip. Using a calibration curve, the oxygen concentration is calculated from the decay time of the dye response.