Team:KU Leuven/Applied Design
Applied Design
To date, numerous drugs require a strict compliance of the patient and a close follow-up of the treating physician. The patients are obligated to go to the hospital frequently and have their blood samples drawn and checked by the lab, causing mild inconvenience in daily life. In practice, this means they have to take the day off regularly to visit the hospital. After the blood sample is drawn, the patients have to wait a few days to get the results, which causes a lot of discomfort and stress. These results are a static measurement, which means they represent only a certain point in time, namely the time of the blood sampling. With this method, they are missing valuable information of the drug concentration in their blood. For example, when the drug reaches a concentration below the effective threshold unknowingly (thus in between two measurements), the drug will not be able to have a therapeutic effect in the body. The opposite effect can also occur when the drug unintentionally reaches a toxic concentration, the patient can experience severe adverse events and side effects. It needs no explanation that these serious practical issues and lack of information are associated with increased health costs, morbidity and mortality.
To tackle these difficulties, we propose a continuous therapeutic drug monitoring device. Our HEKcite device consists of manipulated human embryonic kidney (HEK) cells, containing three key ion channels that enable these cells to oscillate intrinsically at a stable rate. Specific drugs can have an agonistic or antagonistic effect on the specific receptors present on our manipulated HEK cells, causing a change in frequency of the rhythm. In practice, this means that we can easily correlate the concentration difference of one drug in particular to the frequency change of the oscillations, enabling a continuous therapeutic drug monitoring system. But the versatility of our device can go even further. Not only can our device detect drugs that directly affect these three ion channels, but also drugs affecting different GPCR receptors. This is possible because of a signal transduction pathway activates the secondary messenger, cAMP. In our results, we showed that the rhythm is indeed affected. This multifunctionality ensures a broad application in the field of medicine, simplifying the life of numerous of patients suffering from diseases that need drugs.
How will our manipulated cells impact the field of medicine?
Imagine a patient suffering from severe epilepsy. Epilepsy is amongst one of the most common neurological disorders, affecting more than 50 million people worldwide. This patient has to maintain a stable plasma concentration of the anti-epileptic drug in order to control the amount of seizures, meaning that drug compliance is of key importance. If the patient accidentally forgets to take a pill, the drug concentration in the plasma decreases below a threshold, which hinders the treatment. On the opposite, if the patient takes double the dose needed, the drug concentration increases. This can cause toxic side effects. With our HEKcite therapeutic drug monitoring device, these inconveniences can become something of the past.
All of this can happen when the drug is only measured every few months, meaning that the concentration is not known in between measurements at the fixed time points during doctor appointments. To facilitate this process, we propose our HEKcite therapeutic drug monitoring device.
How will our measuring device operate in practice?
Firstly, our manipulated HEK cells are encapsulated in a biocompatible capsule, as a monolayer on top of a multielectrode array (MEA). This MEA measures the intrinsic oscillations in a sensitive manner and is the main part of the sensing device, enabling easy data transfer to the bracelet (see further) by Bluetooth. Next, this capsule should be implanted in the forearm, which enables simple read-out and data collection, as well as easy surgery and the least discomfort in daily life for these patients. Because we are implanting a foreign object in the human body, natural immunological reactions will occur. First, fibrosis around the capsule will strengthen the capsule and make sure that it stays in place. Besides fibrosis, neovascularization can develop, ensuring that the necessary nutrients, oxygen and the drug molecules reach our oscillating cells. This process of neovascularization increases the survival of our cells, and thus the continuous measurement of the drug molecules. Since the MEA can only sense the frequency change of the oscillating cells, a transfer of this data is necessary to have a proper read out. Thus, the MEA sends all the data to a bracelet, which can be placed around the arm at the level of the implanted capsule. Next, this bracelet sends the information to a smartphone, which can process the data and show it on an user-friendly interface. This app allows the patients to have real-time and continuous information about the drug concentration. Furthermore, the treating physician also gets an notification when the drug concentrations is not within optimal range, enabling fast and accurate treatment.
The patients will have more control over their disease and the medicine they take, they will not have to wait for his blood values anymore but can check their blood values whenever he wants, wherever they want. All these aspects will certainly have an immense positive effect on their quality of life.
