When soft tissue is transplanted, for example in a patient undergoing tumour surgery, care must be taken to ensure that the new tissue is connected to the blood system in the area where the tumour has been removed. How well this works is difficult to find out, especially in the case of deep-seated defects. Partially implantable microsensor probes called FlexiTel have the potential to improve this situation by monitoring success during the first few days after transplantation.
After the removal of tumours in the mouth, jaw, face or breasts, tissue from other body regions often needs to be transplanted to the area where the diseased tissue has been removed. The blood vessels in the transplanted tissue need to be connected to the body's blood vessels in order to ensure supply of oxygen and nutrients. However, this is associated with a certain risk. Blood clots can form in the blood vessels, especially in the first days after transplantation, preventing the supply of nutrients and oxygen and leading to the death of the transplanted tissue. Dr. Martin Stelzle, head of bioMEMS and Sensor Systems at the NMI in Reutlingen, explains the extent of the problem: “Surgical removal of tumours and transplantation of replacement tissue can take ten hours or more. Moreover, the procedure is not infinitely repeatable, for the simple reason that the amount of tissue that can be removed from a different body part is limited. In order to replace mouth, jaw and facial tissue, tissue from the shoulder blade is often used, which is not that big an area." Monitoring of tissue function after transplantation is therefore highly essential in order to be able to intervene when a blood clot starts forming and save the transplanted tissue. However, this can be difficult for deep transplants with little skin. “We cannot use touch and visual inspection,” says Stelzle. Partially implantable tissue monitoring sensors have the potential to improve this situation.
In cooperation with five partners from industry and research, a team from the NMI in Reutlingen has commenced a project aimed at developing a flexible microsensor probe for continuous tissue monitoring. The project began in January 2016 and will be funded by the German Federal Ministry of Education and Research (BMBF) with around 1.45 million euros for a period of three years.
The probe is approximately seven millimetres wide and around one centimetre long and will contain not just one but several sensors that will provide the physician with information about whether all is as it should be. The optical sensors are located on the upper side of the probe: a laser determines the oxygen saturation of the blood and laser-Doppler anemometry is used to determine the speed of the blood cells. This is done by directing laser light into the bloodstream, which is then scattered by the blood components that move past the measurement point. The frequency of the scattered light changes in relation to the speed of the blood cells. This change in frequency is detected and provides information about the speed of blood flow.
Electrochemical sensors will be placed on the underside of the probe. “We plan to use a pH sensor to obtain information on potential inflammatory reactions, which would result in a pH change. We will also integrate an oxygen electrode in the sensor,” says Simon Werner from the NMI, project manager. The blood oxygen is measured in two ways, optically and electrochemically. This redundancy is intentional in terms of operational reliability. Werner explains: “The use of two different sensors will contribute to the robustness of the information as we want to ensure reliable measurements over a period of several days.”
The measurement system will be coupled with a flexible polyimide (PI) substrate in order to ensure that the probe adapts well to different tissue geometries. “PI is ideal for the probe. Like Scotch Tape, it does not stretch, but is nevertheless flexible,” says Werner. FlexiTel will be implanted into the patient along with the replacement tissue graft, and connected to a so-called bedside box by way of a fibre optic cable. The box will contain a transmitter and the evaluation unit. “This box will be constructed so that it can be placed directly at the patient's bedside,” says Stelzle. The rest is telemetry: the bedside box will continuously send the data to a receiver, i.e. a computer, which can be placed outside the bed area. Telemetric analysis avoids computer cables getting tangled around the bed, and also meets the high hygiene requirements of intensive care units.
The risk of losing the tissue graft decreases a few days after surgery and the probe can be removed. Although this requires another surgical intervention, Stelzle believes that the strain for the patient is absolutely justifiable, especially when the consequences of a potential transplant loss are taken into account. Together, Werner and Stelzle are orchestrating the project. This means that the NMI’s sensor developments are combined with other probe components and integrated into a functioning system by competent project partners on whom the NMI relies.
LEA Medizintechnik GmbH from Giessen has developed optical surface sensors and will be in charge of assembling the system. Multi Channel Systems MCS GmbH from Reutlingen will provide the telemetry electronics and the software for reading the sensor data. 2E mechatronic from Kirchheim unter Teck will be providing the plug-in connections for the probes. NMI TT GmbH develops processes for the cost-effective manufacture of electrochemical microsensors that will be produced and distributed in small quantities in order to test FlexiTel in a range of applications.
The clinical partners will be advising the development team throughout the duration of the project, and will also be involved in clinical studies at a later stage. The Department of Oral Medicine and Maxillofacial Surgery at Tübingen University Hospital will be the first hospital to carry out relevant clinical trials involving patients who need to undergo surgery to remove a tumour in the mouth, jaw or facial area. The department’s medical director, Prof. Dr. Dr. Siegmar Reinert, and his colleague Prof. Dr. Dr. Joachim Polligheit are involved in the FlexiTel project. “Continuous exchange with clinicians is important for the success of the project and the practical application of the FlexiTel probe. They will be providing us with information about clinical practice, about what is possible and what a good probe should look like,” says Werner.
The developers also take into account the expected costs. Due to the high cost pressure hospitals are facing, the developers are working hard to enable the best possible use of the FlexiTel probe. In this respect, another area of application appears to benefit rather well from the system, i.e. anastomosis monitoring following colon surgery. “One to ten percent of patients who have had a piece of colon removed experience post-operative leaks in the anastomosis area where the two remaining pieces of colon are connected to one another. Leaks that are detected too late or not at all can lead to severe infections and even death, therefore preventing them is crucial. Monitoring using FlexiTel can make an important contribution here,” says Stelzle.