Abstract

Drug Quantification in Whole Blood within Microstructures for Point-Of-Care Therapeutic Drug Monitoring

Jean-Manuel Segura, Professor, Institute of Life Technologies, University of Applied Sciences and Arts Western Switzerland Valais

Therapeutic Drug Monitoring (TDM) allows for personalized dosage during therapeutic treatments and is often mandatory for modern potent drugs against cancer, infections or in organ transplantation cases. A prototypical example is the antibiotics tobramycin, which is often prescribed to neonates in case of bacterial infection and requires TDM to ensure efficacy while avoiding oto- and nephrotoxicity. Currently, the process of TDM is demanding for the patient as several milliliters of blood are required, is slow and costly due to the transfer of sample to a central laboratory, and suffers of limited efficacy owing to the difficulty to interpret the results for a non-specialist. In order to circumvent these problems, we aim at developing a point-of-care device enabling the quantification of therapeutic drugs in blood. Our strategy is based on the use of homogeneous assays, in particular fluorescence-polarization immunoassays (FPIA), that require less handling steps, but may suffer from interferences caused by the micro-environment. Here, we show that FPIA can be downsized with reduced requirements in blood sample (only 1 µL) and number of steps, without compromising assay reliability, and can be successfully integrated within microfluidic channels as well as paper-like microstructures. For Tobramycin, the integrated assay enabled quantification in serum with satisfactory performance in terms of precision and recoveries. Furthermore, whole-blood measurements were made possible by jointly using the same paper-like microchamber as a filtering device and a measurement chamber. The final TDM point-of-care test requires minute amounts of blood and minimal handling steps.