Monitoring of the concentration of drugs in the blood on-line
A miniature device developed by researchers at the University of California at Santa Barbara will soon allow doctors to prescribe the dosage of drugs not at random, but based on the biological characteristics of the patient's body.
Traditionally, specialists of pharmaceutical companies determine the recommended dosages of medicines based on the results of many laboratory tests and clinical studies. However, the effectiveness of drug treatment depends on maintaining a stable therapeutic concentration of the drug in the body. Unfortunately, it is not so easy to achieve this.
According to one of the developers, Professor Kevin Plaxco, today the principles of selecting treatment protocols are quite primitive. They are based on the age and body weight of the patient and do not take into account any specific reactions of the body. The concentration of the drug in the body depends on the characteristics of the patient's metabolism, other medications he takes, and even on the food he eats. In combination with the primitive nature of modern dosing protocols, this variability can be quite dangerous when taking medications with narrow ranges of therapeutic concentrations, especially antitumor chemotherapy drugs. As a result, both doctors and patients are forced to balance on a fine line between effectiveness and toxicity.
The device developed by the authors, called MEDIC (from the English Microfluidic Electrochemical Detector for In vivo Continuous monitoring – microfluidic electrochemical detector for continuous monitoring in vivo), significantly brings to reality the possibility of registering the patient's biological reactions to the drugs he takes.
It allows you to continuously determine the concentrations of certain molecules in a small amount of blood in real time. The availability of such information in the future can literally personalize medicine.
MEDIC consists of a microfluidic chamber, on the surface of which gold electrodes are applied, covered with artificial DNA chains – aptamers that perform the recognition function. When the target molecule interacts with the corresponding aptamer, the DNA chain wraps around it. As a result, electrons from the end of the chain are transferred to the base of the aptamer. The resulting weak electrical pulse signals the presence of a target molecule.
Earlier versions of the device quickly lost functionality due to the protein components of the blood sticking to the sensors. This problem was solved by creating a second flow in the chamber from a liquid buffer that washes the sensors and does not mix with the blood flow. The buffer acts as a filter that traps large components of blood and passes small molecules to the sensors.
MEDIC measures the concentrations of certain compounds in the blood (diagram from an article in Science Translational Medicine).(A) The MEDIC chip connects to the patient's bloodstream to evaluate the pharmacokinetics of the drug.
(C) An aptamer probe attached to a gold electrode. Binding of the target (green) induces a reversible change in the conformation of the probe molecule, which increases the intensity of electron transfer between the electrochemical redox generator (blue) and the microelectrode, which ensures the occurrence of a recorded electric charge showing a change in the concentration of the drug in real time (top right).
(C) A diffusion filter formed by superimposed laminar buffer flows (blue) and blood (red) provides access of target molecules to probe molecules and eliminates interference from large protein molecules.
(D) The presence of a signal (red) and the absence of a signal (blue) provide a significant bias in response to the impact of the target (purple). Kinetic differential measurement (green) improves the accuracy of the real-time current estimation by minimizing bias and increasing the signal-to-noise ratio.Testing of the new device in the laboratory has demonstrated its high efficiency.
It provided accurate data on the concentration of target molecules in the blood for several hours. Moreover, its exceptional selectivity ensured the registration of the concentration of target molecules only, even when using a complex of drugs.
To date, MEDIC is in the early stages of clinical research and its approval for practical use may not be obtained earlier than in a few years. However, the developers are confident in its great future. In addition to improving the efficiency of using existing medicines, MEDIC can also be useful for the pharmaceutical industry. The fact is that many experimental drugs do not pass phase 3 of clinical trials, the purpose of which is to test the effect of the drug on the general population of patients. Continuous monitoring in real time will improve the effectiveness of drugs by individually selecting the dosage.
Moreover, aptamer-based biosensors are relatively easy to manufacture and can be used to monitor proteins that are indicators of diseases. And several layers of such biosensors in one device can be used for simultaneous monitoring of several target molecules.
The next stage of the work is to supplement MEDIC with a feedback mechanism and a device for automatic administration of drugs in the optimal dosage determined based on monitoring results. An example of such a system, in the development of which the authors participated, is an artificial pancreas, currently undergoing clinical trials with patients with type 1 diabetes mellitus.
Article by B. S. Ferguson et al. Real-Time, Aptamer-Based Tracking of Circulating Therapeutic Agents in Living Animals is published in the journal Science Translational Medicine.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on UC Santa Barbara: Live Feed into Our Bodies.
24.01.2014