A close-up of the intelligent multi-well plate showing the reaction chambers with sensors

Sensor-Driven Diagnostics: Immediate, Reliable, and Quick

Bioelectronic sensors play an increasingly central role in patient treatment

Each person’s metabolism is different, and thus the effect of a medicine on patients depends on the individual. In the future, it will be possible to identify the ideal combination of active ingredients to include in a medicine – and quickly and easily adapt it to individual patients. In fact, bioelectronic sensors are already capable of providing the information we require to predict the success of therapy. They can be used to monitor how a broken bone is healing or to spot if a tumor has suddenly started to grow. They also offer us the opportunity to avoid animal testing when trying out new medicines. Experts at Medical Electronic and Lab on Chip Systems, the Munich-based Steinbeis Transfer Center, have specialized in bioelectronic sensors and are now using them to develop intelligent systems for use in medical applications.

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At the heart of these systems lies a special electronic sensor chip that was developed and perfected through years of research carried out by Professor Dr. Bernhard Wolf and his colleagues. They have called their technology the multi-parameter sensor chip. This chip is capable of detecting several parameters at the same time – such as pH values, absolute temperature, oxygen concentration, impedance, and ion concentrations – by lining up several sensors within a single chip. The sensor chip has been continuously miniaturized and now measures no more than a couple of millimeters. This is a decisive factor for many medical applications, such as electronic implants.

The information provided by the multi-parameter sensor chip can be evaluated by a computer and cross-correlated. For example, the chip can quickly observe the condition of living cells and tissue, offering crucial benefits in a whole host of medical areas.

Quick medicine testing, fewer side effects, lower costs

 The Steinbeis experts are using a microtiter plate with 24 reaction chambers to carry out drug tests. The chambers can be filled by a pipetting robot. In each chamber there is a multi-parameter sensor array, turning each reaction chamber into a kind of tiny bioelectronic laboratory. Animal or human cells are cultivated directly on top of the sensors on an intelligent multi-well plate. The result is a biohybrid system of living cells combined with an electronic sensor. Whenever a substance (in liquid form) is added to the reaction chambers, the sensors measure metabolism responses in the cells, such as changes in pH values or the concentration of oxygen around the cells. This information is forwarded to a computer by the electronic system.

The scientists’ process makes it possible to carry out large batches of tests – crucial when testing medicines. For example, the system can ascertain which combination of active ingredients would be best for treating a patient’s tumor. To do this, a doctor conducts a biopsy on a patient and removes tumor cells, which are then cultivated in the lab on the sensors of the intelligent multi-well plate. Next, an ultra-precise robot pipettes 24 different combinations and concentrations of active ingredients into the reaction chambers so that the sensors can measure the responses of the tumor cells. The computer then uses these measurements to come up with the ideal active ingredients and dosage levels. This allows physicians treating the patient to gain important information on the drug most likely to offer successful therapy options – or to highlight drugs that do not come into question. This kind of information can be crucial when treating patients, especially in cancer treatment. In this way, from the very beginning patients can be treated with the right mixture of drugs and the ideal dose, also making it possible to reduce side effects and save money.

The intelligent microplate reader (IMR) developed by the team of Steinbeis experts from Munich can be adapted to a variety of testing requirements. It is particularly well suited to testing drugs for efficacy and tolerability prior to approvals. In the future, this could make it possible to avoid a large number of experiments currently carried out on animals. The Steinbeis experts have also been working with Domatec, a medium-sized specialist in water hygiene and environmental analysis. Together, they intend to modify the IMR system to allow quick and reliable measurements to be taken of bacteria in air conditioning systems and drinking water.

Reacting quickly by taking measurements directly in the body using electronic implants

Personalized medicine is currently one of the most important trends in medicine. Electronic implants can be used in this area for capturing physiological information directly inside the human body for individual medical diagnostic purposes and personalized treatment. In fact this is another area where the future is just around the corner: The Steinbeis experts have developed intelligent implants about the size of a 2 cent coin.These implants can be used in minimal invasive procedures directly on tumors that cannot be removed surgically. If a tumor grows, the sensor measures decreasing oxygen concentrations on the surface of the implant in combination with lower pH values in the surrounding tissues, and transmits this data to a receiver outside the body. The physician can then initiate therapy. Alternatively, the implant can act automatically and change the transmembrane potential of the tumor cells electronically with the aim of inhibiting tumor growth. The cancer is, so to speak, “deactivated electronically.” This kind of closed-loop system makes it possible to react extremely quickly to changes in the tumor. Aside from avoiding serious side effects, this also protects the human body, with a much less detrimental impact on the quality of life for patients than conventional treatment.

The implants make it possible to take long-term in vivo measurements. In the future, it may be possible to use these devices to monitor the healing of broken bones, the condition of orthopedic implants, or the performance of transplanted organs. This is because even in such situations, the oxygen saturation of tissue is an important indicator of the condition of affected areas of the body, and the sensors on the electronic implants provide crucial information. The Steinbeis researchers have been working with the electronics company Texas Instruments as part of a project aimed at optimizing their sensors and implants – and ideally miniaturizing them.

Electronic dental splints used to stop people grinding their teeth

The intelligent dental splint works along the same lines as a closed-loop system. The splint is used to diagnose and treat bruxism (teeth-grinding), although in this case different kinds of sensors are used. The system is based on a dental splint made individually for each patient. The splint is fitted with a piezoelectric sensor, a radio transmitter, and its own power supply. The sensor’s job is to measure chewing (mainly at night). Data is transmitted wirelessly to a receiver next to the bed or under the pillow. Stored data can then be transferred to a physician’s PC via USB. By examining the timing and intensity of teeth-grinding, doctors can identify what might be causing the behavior. In addition to using the system for diagnostic purposes, it can also give immediate physical (vibrations) or acoustic biofeedback through a receiver unit. In the long term, stimulating the patient eventually helps them to stop grinding their teeth.

A pocket-held doctor 

The researchers working under Bernhard Wolf have also used their sensor expertise to develop a handy all-in-one medical device, a kind of doctor in the pocket. Patients insert a finger once a day into an integrated sleeve equipped with sensors, which only need to take a single measurement to assess blood pressure, body temperature, pulse rate, oxygen in the blood, and hydration levels. Blood sugar levels can also be measured with a drop of blood and a measurement band. If patients give their permission, the all-in-one medical device will automatically send all measurements via radio signal to a database. This is done by a telemedicine system called COMES®, which was launched a couple of years ago. The physician treating the patient has instant access to patient data, so that the alarm can be raised and interventions can be made if abnormal values are detected. COMES® can also automatically alert patients and suggest appropriate action.

As we have seen recently under the current pandemic, it would be useful to lighten the load on doctors’ offices. To a certain degree, future medical practice will therefore also involve telemedicine methods. One day patients will take their own measurements, but still stay in touch with the doctor’s offices using digital technology. One major benefit offered by the all-in-one medical device is that it’s hand-size and easy to use. It can be used at home or while out and about, not only by patients but also by nursing staff. It also goes a long way toward lightening the load on nursing staff in hospitals if they can take a whole range of measurements in a single step. The device also helps by sending information directly to digital patient files. This simplifies the often time-consuming task of documenting readings. The Steinbeis experts are currently working on a new generation of the all-in-one device, which will be even easier to handle and offer a particularly intuitive design.

“Digital medicine makes it possible to offer treatment over space and time”

An interview with Professor Dr. Bernhard Wolf, Steinbeis Entrepreneur, from Medical Electronic and Lab on Chip Systems, the Steinbeis Transfer Center

Hello Professor Wolf. How far have we come on the digital transformation journey in health services – are things going quickly enough?

No, they’re not. I think things are going much too slowly. Compared to the Scandinavian countries, we’re about 15 years behind. Even southern European countries have made huge leaps forward compared to Germany. This is partly to do with the different technology standards that need to be introduced to the market, but also partly to do with the financial interests of the different institutions involved in public health services. Germany could have had a medical data network a long time ago, comparable with the German network for science and academia. But the fragmentation we’ve had until now will continue to hold things back over the next century and prevent digital solutions – that would benefit patients in this country – being expanded in the healthcare industry.

Which problems could rapid digitalization solve in medicine? And how would digital solutions be received by patients and physicians?

Digital medicine makes it possible to offer treatment over space and time. If it’s applied responsibly and judiciously, it is very well received by patients, which is something I know from my own experience and contacts with digital service providers – such as the Medgate healthcare network in Switzerland. But many doctors are still skeptical about digital medicine because they’re worried about losing patients. Also, some physicians are worried about being prosecuted for neglect of duty if they fail to intervene quickly enough or provide their patients with telehealth support in an emergency. Yet the Scandinavian countries have been successful in improving their standards compared to Germany, raising quality by up to 75% – depending on the illness – and they achieved that through a much more thinned out network of hospitals.

Bioelectronic sensors can be used to gather data directly from human beings. What are the data privacy issues with such sensors?

It’s already possible to gather extremely precise health information on people without using invasive technology, but that doesn’t seem to be a threat to data privacy. This issue only becomes critical if personal data “goes astray.” But in principle, there are already encryption technologies that allow us to set up secure and interference-free data networks – as we’ve seen recently in the field of space travel, where even highly critical processes can be controlled over huge distances using sensors. Naturally, this level of security is also possible with medical data networks.

Do electronic sensors really have what it takes to make medicine less expensive?

Many medical conditions take a while to develop, so they don’t just turn up like that; they could be detected early. Good examples of this are heart failure and strokes. This is where data recorded by sensors have an important role to play. If you measure blood pressure regularly and observe people’s weight, and data can be collected periodically using a simple ECG implant in combination with pulse oxymetry, in roughly four out of five cases physicians are able to spot and react in advance to their patients’ disorders, and that can save a huge amount of money. The devices for doing this, and the required sensors, have already been available for a long time – such as the all-in-one medical device we developed, which measures vital data through the patient’s finger and sends it to the physician.

Won’t the human factor get lost if medicine goes digital?

No, quite the opposite. Digital medicine always plays a supportive role – it makes it easier for doctors to get on with their everyday work and concentrate more closely on their patients, and that makes things more human. We also know from practical experience with telemedicine centers that in many cases they’re able to help patients quickly because they get them to stop panicking and offer a more calm assessment of the acute situation. This also avoids many patients being unnecessarily admitted to emergency, and immediate treatment can be started based on what’s really happening. It has to be advantageous to patients to have data immediately available in an emergency, so the attending physician can access information digitally and gain a direct impression of the patient’s general condition. This also makes it possible to avoid complications caused by drug intolerances. That’s the positive thing about individualized and personalized medicine.


Prof. Dr. Bernhard Wolf (author)
Steinbeis Entrepreneur
Steinbeis Transfer Center Medical Electronic and Lab on Chip Systems (Munich)

Christian Scholze (author)
Project coordinator and head of administration
Steinbeis Transfer Center Medical Electronic and Lab on Chip Systems (Munich)