To date, numerous drugs require a strict compliance of the patient and a close follow-up by the treating physician. The patients are obligated to go to the hospital frequently to have blood samples drawn and checked by the lab. This causes mild inconvenience in daily life. For example, patients have to take days off regularly to visit the hospital. Furthermore, they have to wait a few days to get the results after the blood sample is drawn, which causes a lot of discomfort and stress. And even when these blood values are determined, they are only a static measurement: They represent the values of a certain point in time, namely the time of the blood sampling, but give no information of the circumstances between sampling moments. Therefore, patients and physicians are missing valuable data on the drug concentrations in the blood in everyday life. For example, a drop of concentration below the effective threshold may go unnoticed, causing a decrease in effectiveness of the drugs. Alternatively, when a toxic concentration of the drug is not discovered, this may cause severe adverse events and side effects.
These practical issues and the disadvantages of static measurement systems 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, which influences one of the integrated ion channels. 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 patients suffering from diseases where the blood concentration of drugs are crucial for treatment.
How will our manipulated cells impact the field of medicine?
Imagine a patient suffering from severe epilepsy. Epilepsy is amongst the most common neurological disorders, affecting more than 50 million people worldwide. Patients have 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 may cause toxic side effects. With our HEKcite therapeutic drug monitoring device, these inconveniences would become something of the past.
When a drug is only monitored every few months, patients and physicians can only assume that the concentrations are on a proper level in between sampling points. Contrarily, a continuous measurement system would eliminate this guesswork from the doctor's office. This would give the patients a feeling of control and peace of mind. Furthermore, it would allow quick responses to unfavourable drug levels, which may save lives and reduce health costs. Therefore, 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 their blood values anymore but can check their blood values whenever they want, wherever they want. All these aspects will certainly have an immense positive effect on their quality of life.