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Project: Enabled Heart - Anatomy and physiology-based environments for cardiac implant development.
Project description: The aim of the project is to create virtual and physical development tools that enable research and development work on medical heart implants to be tested on a realistic model before being tested in animal experiments. Thus, a reduction in development time as well as development costs should be made possible through early virtual and real testing of concepts. The virtual and physical development methods must be intertwined to enable the plausibility and continuous validation required in medical technology. While this is normally achieved through animal testing, the tools/methods should allow for visualization and testing simply by incorporating animal or human hearts.
The focus of the ICM Biofluid Mechanics Laboratory in this project is the concept development and construction of a multifunctional in vitro experimental stand for the physiological simulation of cardiac motion. In this trainer, different hearts and heart models should be able to be used, as well as the option to extend a vascular model.
Project: Novel measuring system for the quantitative determination of aerosol dispersion
Project description: Transmission of SARS-CoV-2 occurs largely via virus-laden droplets in aerosols released into the ambient air by, for example, coughing, sneezing, or talking. The spread via room or ambient air leads to great uncertainty among the population. The Aerosol Transmission Measurement System allows to determine the aerosol dispersion under real room conditions and to draw a conclusion about the transmitted aerosol amounts between dummies at certain arbitrary positions. It was developed in cooperation between the Hermann-Föttinger-Institute of the Technische Universität Berlin and the Biofluid Mechanics Laboratory of the Charité - Universitätsmedizin Berlin and is part of the project Restart 2.0 in which various venues will be investigated. Using the results obtained, it is planned to develop an evaluation system with which the indoor air technology of event venues can be effectively classified with regard to the risk of infection with e.g. SARS-CoV-2. The system has already been used independently of the Restart 2.0 project in facilities such as the Philharmonie Berlin, in various vehicles of the Berlin public transport company and in conference rooms.
Project: Proliferation of circulating tumor cells for personalized treatment of tumor patients - proCTC
Project description: The BMProbe, a medical device from Invicol GmbH, can be used to collect rare cells from the bloodstream in a minimally invasive manner. In the joint project proCTC, different methods for detaching these cells from the probe surface are being investigated. Subsequently, the expansion of the detached cells will be investigated.
The aim is to use molecular analyses to investigate to what extent the preclinical models reflect the original tumor and/or the metastasis. In addition, drug testing will be used to determine whether preclinical models derived from CTCs and/or patient-derived organoid models reflect therapy response or the presence of resistance in the patient. Thus, it will be investigated whether they are suitable for application in precision medicine of cancer patients.
Project: Influence of noble metal nanoparticles bound to titanium on thrombogenicity (NanobleVAD)
Implants like ventricular assist devices which include blood contacting surfaces always carry the risk of thrombus formation. For VAD systems, titanium is a commonly used material. In this project, a new method, which was developed by the project partner BC Berlin Catalysts GmbH, is used for the surface coating of titanium: various noble metal nanoparticles are deposited on the surface in a controlled manner (immobilization). It is being investigated to what extent the hemocompatibility of these surfaces can be improved thereby. For this purpose, the composition and particle size of the noble metal nanoparticles are varied and attachment tests of platelets are carried out in a flow chamber using a fluorescence-based evaluation method.
Project: New technical and clinical ways to realize a cost-based VAD therapy
Project description: For patients in the final stage of heart failure, heart transplantation is the last possible form of therapy. Due to the shortage of donors, the waiting period for a donor heart must be bridged by means of mechanical heart and circulation support systems, so-called VADs (Ventricular Assist Devices) or artificial hearts. These are also increasingly being used as a long-term alternative. The aim of the project is to further explore the existing functional pattern for the future development of a ventricular assist device for the chronic treatment of terminal heart failure in collaboration with Berlin Heart GmbH. With the Next Generation Pump (NGP) system, the aim is
- to improve clinical outcomes of VAD therapy in terms of life expectancy, complication rate, hemocompatibility and quality of life, and
- to reduce therapy costs as the sum of system costs, costs of implantation and follow-up treatment, and costs of aftercare.
Project: Development of antithrombogenic coatings based on polyglycerols for cardiac support systems
Project description: In cardiovascular diseases, mechanical heart and circulatory support systems, so-called VADs (Ventricular Assist Devices), are used to bridge the waiting time for a donor heart or as heart replacement. A serious complication is the formation of thrombi. If these thrombi become detached, they can block blood vessels in the bloodstream, leading to heart attacks and strokes. The aim of the project is to prevent thrombo-embolic complications by developing, testing and applying a novel coating for blood-carrying elements of cardiac assist devices. This is based on a substance made of polyglycerol (developed by the FU Berlin), which does not interact with platelets.
Project: research into a pediatric VAD system
Project description: Children who are dependent on a donor organ due to terminal heart failure often have to put up with very long waiting times, as the availability of donor organs is very limited. Accordingly, mechanical heart and circulatory support systems, so-called VADs (ventricular assist devices) or artificial hearts, bridge the waiting time. Especially for larger children there is a lack of suitable intracorporeal heart support systems. Therefore, the aim of the project is the research of a pediatric VAD system within a joint project with Berlin Heart GmbH, which enables an improved therapy for patients aged 3 - 12 years. For this purpose, starting from the clinical boundary conditions for children, the bearing and pump design, the validation of the concept and the feasibility studies for the system will be carried out. The validation in the in vivo animal model represents the conclusion of the work.
Project: Development of a low-strain blood pump
Project description: Blood pumps for mechanical cardiac support are already successfully used in the clinic for the therapy of myocardial diseases. However, the traumatization of blood in the pump flow often leads to disruption of the coagulation system and thus to bleeding complications in patients. There is a proven link between the high shear stress on the blood in the pump and damage to a protein important for the clotting process - the Von Willebrand factor. This is observed, for example, in stenoses of the aortic valve, where a pressure gradient of about 30 mmHg already leads to a reduction in the long-chain components of this coagulation factor. This led to the project to implement the pressure increase of the pump with the help of novel approaches in such a way that the pressure gradient remains below this threshold value.
In the course of the project, a two-stage semi-axial cardiac support pump (Careflow) was developed and manufactured together with Dualis MedTech (see picture).
Project: Platelet adhesion
Project description: When blood flows onto an implant, it is briefly stressed by shear and can then come into repeated contact with a foreign material in a flow separation. This combination of high and low shear favors thrombus formation, which has been modeled in this project. The aim is to gain a better understanding of Virchow's triad, in particular of thrombus formation. For this purpose, a special plate-plate shear apparatus was developed. The whole apparatus is mounted on an inverted microscope to observe and record the formation of a thrombus. Thrombus formation could be observed after only 20 s.
Project: Low-stress determination of vital parameters based on flow measurement in the wrist artery
Project description: About 10-15% of operations performed in Germany are high-risk procedures and about 10% of all patients develop serious complications postoperatively. To avoid complications, an indiviualized therapy already during surgery is necessary. So far, measures like determination of cardiac output and hemodynamic parameters and the associated optimized fluid administration have proven to be useful. For hemodynamic optimization, two variables are crucial: Blood pressure and blood flow. Therefore, a novel system (RadialisPeriOP) for non-invasive determination of blood pressure and other vital parameters is being developed within the project. The basis for this is the measurement of blood flow in the wrist artery using ultrasound Doppler measurement technology. From the blood flow, volumetric hemodynamic parameters are determined on the one hand and the blood pressure is measured non-invasively via a control circuit on the other.
Project: GlobalResist – Forecasting antibiotic resistance evolution – a new approach to address a major issue in global health
Project description: The development of antimicrobial resistance is one of the major challenges in the fight against infectious diseases. GlobalResist is developing a multi progned approach to predicting antibiotic resistance befor it occurs, closely linking different disciplines. The aim is to make it possible in future to assess the risks of resistance development before use, in order to ideally avoid the resistance problem and use antibiotics more sustainably.
Project: Research of a novel blood pressure measurement method at the facial artery
Project description: In the "FacialisPressure" project, research is being conducted on a novel method for non-invasive blood pressure measurement in the facial artery. The measurement is based on volume changes in the facial artery, which are detected photometrically. For this purpose, a brace is inserted into the mouth, see figure. A pressure pad with a light-emitting diode is attached to the outer leg of the brace. With the help of the pressure pad, the blood flow in the artery is cut off. The LED continuously emits light through the artery, while a photodiode in the opposite leg records the light intensity. Together with the pressure curve, the arterial blood pressure can be determined from the light signal.
Project: Method for long-term measurement of blood pressure
Project description: For the treatment and prevention of cardiovascular diseases, knowledge of the patient's blood pressure over the course of the day is very important. The state of the art is automatic devices that obtain a blood pressure profile over 24 hours from individual measurements taken at 15-minute intervals. This measurement by means of an arm cuff still has some disadvantages (measurement only possible at rest, uncomfortable) and is very susceptible to artifacts. Therefore, long-term blood pressure measurement is not used as often as it should be. The novel measurement of blood pressure of this project is also based on the principle of Riva-Rocci like the method just described, but it does not occlude the whole vascular system of the arm or hand, but only one single artery: the radial artery or the temporal artery. This is occluded by a small pressure pad on the skin until no more blood flows and finally the pressure in the pad is gradually released. The imposed pressure is then equal to the systolic blood pressure. As the pressure in the cushion continues to be released, the time during which there is no blood flow becomes shorter and shorter. The diastolic blood pressure is reached when this time approaches zero.
Project: Novel probe for in vivo isolation of circulating endothelial cells for diagnosis and follow-up of cardiovascular disease
Project description: Cardiovascular disease is the leading cause of death and disability worldwide. The identification of rare circulating endothelial cells (CEC) is a novel, reliable biomarker associated with endothelial damage. From a clinical point of view, these endothelial cells are important indicators of pathological processes in the body and can therefore be used for diagnosis and follow-up of various cardiovascular diseases. The aim of the project is therefore to explore a probe that allows the isolation of CEC in vivo directly from the patient's blood, thus circumventing the problem of ensuring sufficient cell yield.
Project: Novel probe for in vivo isolation of circulating tumor cells for diagnosis and follow-up of cancer
Project description: The number of documented cancer cases is increasing worldwide. To diagnose or rule out cancer, a tissue sample is usually taken (biopsy) and examined histologically. However, virtually all tumors release circulating tumor cells (CTC) into the bloodstream and are therefore always available for detection. These circulating tumor cells in the blood are a new, reliable biomarker associated with cancer and can therefore be used to diagnose and/or monitor the progression of various forms of cancer (liquid biopsy). However, these CTC consistently occur at very low concentrations and are therefore difficult to detect. Therefore, the aim of this project is to investigate a probe that allows the in vivo detection of CTC directly in sufficient numbers from the patient's bloodstream, thus addressing the problem of lack of sensitivity of existing diagnostic systems.