Point-of-care microfluidic device for quantification of chemotherapeutic drugs in small body fluid samples by highly selective nanoparticle extraction and liquid crystal detection

The goal of this project is to develop a robust and reliable point-of-care sensing device to measure, in real-time and with high precision, the concentration of chemotherapeutic drugs in small samples of body fluids. The objective is to aid the decision making of clinicians on doses and dosage of such drugs in patients by providing a rapid, quantitative, and portable detection system. At present, dosage for chemotherapeutics is based almost exclusively on body surface, and doesn’t take into account the individual variability of metabolic activity and of bio-distribution. The device we propose to develop will provide a reliable and inexpensive way to adapt dosing of anticancer drugs according to patients’ individual drug pharmacokinetics. This is especially required for therapeutic drug monitoring (TDM) of antineoplastic drugs characterized by a low therapeutic index (i.e. narrow toxic-therapeutic range and effective dosage) or in very young patients.

We propose to build a microfluidics-based device, basing on two novel ideas recently developed in the laboratories of Besta and EPFL. First, innovative drug capturing nanoparticles (NPs) will be added to serum extracted from patients’ blood and deprived of the clotting factors, where they selectively bind to drug molecules. Only NPs that have bound to a specific metabolic form of the drug will then transfer into a liquid crystal (LC) phase, where we measure their concentration optically. The concentration of drug in the blood will be directly related to the concentration of the particles in the LC phase. The whole process from serum extraction to optical readout will be integrated in a single completely automated lab-on-a-chip microfluidic system. This device will be validated against current detection method on real patient samples. It will require only small sample volumes and should provide the clinician with a concentration of the drug and of its metabolites in a total time of two hours.

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pH-Mediated molecular differentiation for fluorimetric quantification of chemotherapeutic drugs in human plasma

Luis A. Serrano, Ye Yang, Elisa Salvati, Francesco Stellacci, Silke Krol and Stefan Guldin

At present, drug dosage is based on standardised approaches that disregard pharmakokinetic differences between patients and lead to non-optimal efficacy and unnecessary side effects. In this work, we demonstrate the potential of pH-mediated fluorescence spectroscopy for therapeutic drug monitoring in complex media. We apply this principle to the simultaneous quantification of the chemotherapeutic prodrug Irinotecan and its active metabolite SN-38 from human plasma across the clinically relevant concentration range, i.e. from micromolar to nanomolar at molar ratios of up to 30 : 1.