Multilayer carbon hybrid based electrodes for direct electrochemical detection of analgesics and biomolecules - Development of an electrochemical sensor for determination of analgesics in blood samples

There is increasing interest in point-of-care (POC) determination of drugs and biomolecules, as well as real-time monitoring of these analytes, with wearable and in vivo sensors. Rapid response POC tests can improve patient safety in situations like poisoning and enable personalized treatments whereas real time detection of physiological processes such as neurotransmission events can improve our understanding of neurophysiology and enable novel treatments for neurological disorders. Electrochemical detection is an attractive technology for both POC in vitro diagnostics and wearable sensors alike, due to its low price, simple instrumentation and small required sample volume. Many analgesic drugs show highly individual dose response and thus a dose that causes dangerous side effects in one patient may lack analgesic effect in another. Analgesics are also some of the most abused prescription drugs. Opioid overdoses kill tens of thousands of people annually in the United states alone. Both intentional and unintentional poisoning of over-the-counter analgesics, such as paracetamol, also regularly occur. Therefore, a quantitative POC test for determination of analgesics in capillary blood samples, could be a powerful diagnostic tool for poisoning. However, the POC determination of small drug and biomolecules in unprocessed blood samples has proven to be difficult. In this thesis, we have investigated the use of tetrahedral amorphous carbon (ta-C) and single-walled carbon nanotube (SWCNT) thin films in electrochemical sensing. We have carried out extensive physicochemical characterization of these electrode materials. We combine synchrotron based x-ray spectroscopy with electron microscopy, diffraction and conventional spectroscopic techniques. Both the studied materials were found to support facile electron transfer and show low background currents enabling highly sensitive detection of dopamine and morphine. They, however, lack the fouling resistance and selectivity required for detection of dopamine and analgesics in complex biological samples. Modification with carbon nanomaterials or polymer membranes significantly improved the selectivity as well as reduced the electrode fouling, allowing for detection of dopamine and analgesics in blood samples without precipitation of proteins. We show that such multilayer electrodes can be tailored for the requirements of detection of neurotransmitters and analgesic drugs. Finally, we demonstrate a process for mass production of electrochemical test strips. These sensor strips were shown to be capable of detecting clinically meaningful concentrations of paracetamol from a 20 µL blood sample in less than 5 min. Based on these results we propose an electrochemical assay for quantitative detection of paracetamol.