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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - DiaChemo (Point-of-care microfluidic device for quantification of chemotherapeutic drugs in small body fluid samples by highly selective nanoparticle extraction and liquid crystal detection)

Teaser

Summary

The aim of the project is the development of point-of-care devices for the measurement of chemotherapeutic drugs in the blood of patients in real-time. The necessity of a fast and reliable bedside measurement is that the individual metabolic modification of the drug in the patient can influence significantly the outcome for the patient in terms of overall survival (non-efficient drug concentrations are reached) and quality of life (severe side effects by intoxication). So far only analysis of the blood in specialized laboratories is performed. The labour-intensive, error-sensitive blood sampling is a major source of imprecision. With a device which allows a fast and automatic blood sampling and analysis by a technique with a sensitivity high enough to measure clinically relevant concentrations the medical doctor will be given to adjust the drug dose to every individual patient depending on his/her metabolism.

The decision-making in chemotherapy nowadays depends on standard methods that are liquid chromatography (LCMS/MS) followed by mass spectrometry or capillary electrophoresis; both are labour- and cost-intensive and can be performed only in dedicated hospitals and laboratories. This lead to a minimal therapeutic drug monitoring in patients and hence that 30-60% of drugs are administered without clinical benefits. We propose to develop a point-of-care device for quantification of chemotherapeutic drugs in small body fluid samples by highly selective nanoparticle extraction and liquid crystal detection incorporated in microfluidic lab-on-chip device (optofluidics based) allowing the real-time drug monitoring. This will improve the therapeutic outcome and reduced health care costs.

Work performed

The work was focussing to gain a better understanding of the mechanisms leading to the fast degradation of doxorubicin, which is one of the main obstacles of an efficient and handy quantification of the drug nowadays. A deeper insight in the degradation mechanism, and how the first patented approach by functionalized gold nanoparticles in combination with a liquid system was making use of it to allow the separation and quantitative transfer of Doxorubicin into a stable form, was leading to the development of a simplified approach which will be translated into a prototype for a point-of-care device early in the next reporting period. A very similar approach can be used for an even more simplified point-of-care device to measure the concentration of SN-38, the active drug of Irinotecan in blood. In both cases, the focus was on simple, cheap and easy-to-use systems with a clinically significant detection limit to measure the drugs with a minimum of preparative effort. The respective modules for a point-of-care device were either build or identified by the consortium.

Final results

A new technique to transfer the instable doxorubicin into a stable form in around 5 mins. was developed. This is the key-step for a doxorubicin detection POC device that prevents the labour-intensive, time-consuming, and error-sensitive sample handling. Moreover, this step was translated into an automatized module. Also for SN-38 a strongly metabolism dependent drug a system was developed to distinguish easily the drug from prodrug. In combination with detection system allowing for the sensitivity required for clinically relevant quantities the two key modules for a POC device were developed and identified. Both, patenting and publication of the gained knowledge is ongoing. The impact of our finding will lead to the translation in two first prototypes, which will allow the both clinical partners to compare handiness, time to result, and detection limit with the gold standard in clinical use. In the future the developed POCs will allow a tighter monitoring of actual therapeutic drug concentration in blood with a reduction of toxicity events and increase in efficiency for chemotherapeutic treatments.