POC-TDM · Development of a point-of-care microfluidic device for Therapeutic Drug Monitoring in cancer treatment (POC-TDM)

Cancer claims almost 10 million lives annually, making it one of the major causes of death around the world. Despite the development of novel drugs and treatment options, the 5-years survival of the most common cancers are still strikingly low. Chemotherapy (CT) is a widely used option to treat malignancies, however CT protocols are established on a “one size fits all” basis and ignore inter-patient differences in drug pharmacokinetics which influence the blood levels of anticancer drugs, therefore leading to improper dosing in 50% of patients. Missing target blood concentration will lead to drug resistance and/or unwanted side effects. Therapeutic Drug Monitoring (TDM) could be the key to improve and personalize CT, however the lack of an affordable point-of-care (POC) method is preventing its introduction to oncology. Mass spectrometry (MS) is the golden standard analytical approach to determine blood drug levels, but the instrument and specialized expertise to operate it are rarely available in the clinical environment. The high volume of blood required for MS analysis is also a challenge, because cancer patients are regularly weakened. Exploiting the strong and specific fluorescence of anthracyclines, the most used CT agents, we propose a radically new microfluidic chip-based approach to rapidly determine plasma concentrations of several widely applied anticancer drugs. Microvolume plasma separation and collection from a drop of blood (>50 ul) will be done with a specifically designed chip, then plasma anthracycline concentration will be measured using a compatible spectrophotometer. The approach will be validated using clinically relevant mouse tumour models and with samples from veterinary cancer patients. This interdisciplinary project, combining microfluidic engineering with cancer research, will introduce a novel POC-TDM system which could change CT treatments and improve survival through patient-tailored therapy.