Theophylline (THO) is a drug that is effective for the treatment of respiratory illnesses and inflammation. However, it is toxic, if administered above specified limits. Therefore, there is a demand for rapid and accurate sensing instruments that can carefully track THO levels in patients.
Researchers from Shibaura Institute of Technology (SIT) Japan have currently engineered a paper-based THO sensor with a 3-second response time. This unique sensor is extremely sensitive and selective. It has also been effectively verified using whole bovine blood.
THO is a natural organic compound whose molecular structure is quite similar to that of caffeine present in cacao and coffee. Through the years, because of its therapeutic features, THO has become one of the most extensively analyzed xanthine group derivatives.
THO is employed for the dilation of respiratory passages in people who have trouble breathing, and as an anti-asthmatic, muscle relaxant and diuretic (drugs used to boost urine production and lower blood pressure). It is also said to possess anti-tumor and anti-inflammatory properties and can control the immune responses as well.
While THO is advantageous in the treatment process of many conditions, the drug has a highly narrow therapeutic window. This means it can produce contrary effects if administered over a specific limit (and that limit can be reached quite easily). An inadvertent or deliberate overdose can be very toxic and result in issues such as seizures, excitation of the nervous system, rapid heartbeats or even death. This makes careful tracking of THO levels during therapy very critical.
In a recent revolutionary article, published in Volume 27, Issue 8 of the journal Molecules, made available online on April 11th, 2022 — a group of scientists from SIT Japan illustrate how they created an inexpensive and fast electrochemical sensor for the detection of THO.
This article is a part of the journal’s special issue titled “Molecularly Imprinted Polymers: Impactful Technology vs. Academic Exercise.”
Elaborating on their motivation for the study, Prof. Yasuo Yoshimi (who is the corresponding author of the article) says, “Conventional drug monitoring relies on laboratories outside the hospital to analyze the molecular levels of drugs in blood. Our reagentless sensing tool can easily detect THO directly from whole blood in less than 3 seconds, just like a glucose sensor.”
Therapeutic drug tracking is vital for enhancing the effects of treatments like chemotherapy, which necessitate stringent control over the concentration of the drug in the patient’s blood to avoid severe side effects. Nevertheless, most monitoring methods are frequently time-consuming and mandate complicated procedures that can be performed only by skilled personnel. The same applies to THO detection approaches.
To lessen these difficulties, scientists through the years have formulated inexpensive electrochemical approaches that are basic, sensitive and fast. One of these, a collection of electrochemical tools that has gained momentum of late, is molecularly imprinted polymers (MIPs).
These tools have customized molecular cavities that can identify and adhere to particular target molecules, similar to how receptors in the human body would. Their capability to do so is being extensively used in a number of applications, such as drug detection.
In this research, the researchers engineered a disposable, paper-based THO sensor consisting of an electrode composed of molecularly imprinted graphite. Since MIPs are developed using the target molecule as a template, the researchers used THO as a template when creating the carbon-based electrode paste of the sensor. The synthesized paste was then placed onto a printed sensor chip and its THO detection capabilities were assessed.
The sensor was verified to be very sensitive (meaning it could identify even tiny amounts of THO) and exhibited great selectivity toward the drug. The sensor could detect THO even in samples with very low THO concentrations — 2.5 µg/ml ( µg=microgram, i.e., 1/1,000 of a milligram). Furthermore, this sensor only needs 3 seconds to identify THO. It could achieve this even in whole bovine blood.
This handy, cost-effective, dependable and rapid sensor has longstanding stability and can be used for immediate detection of drugs such as THO without having to rely on advanced equipment. Moreover, the fabrication strategy offered in this study can be applied to create efficient electrochemical sensors for several other medical interventions.
Existing methods for the analysis of the drugs in blood are expensive and need specialized equipment. This can be a problem for developing countries dealing with a lack of resources and technicians. The paper-based sensor that we have developed is not only easy to use but also economical and can reduce the burden of drug analysis in developing countries.
Assistant Prof. Aaryashree, Study First Author, SIT
“Further, its prototype can be used to develop a bedside therapeutic drug monitoring system, which will alert us of any overdose, avoiding side effects in patients taking these drugs,” Assistant Prof. Aaryashree added
This is certainly a beneficial innovation.
Aaryashree, et al. (2022) A Disposable Sensor Chip Using a Paste Electrode with Surface-Imprinted Graphite Particles for Rapid and Reagentless Monitoring of Theophylline. Molecules. doi.org/10.3390/molecules27082456.