Bimodiag
Bimodal micro-fluidic platforms for the diagnosis and monitoring of therapeutic agents
Abstract
The goal of this project is to develop a bimodal sensor to simultaneously determine blood plasma concentrations of a therapeutic agent and a disease marker. It will integrate an electrochemical sensor (to detect markers of the target pathology) and an optofluidic sensor (to monitor the concentration of the therapeutic agent) on the same platform, using the same surface chemistry. This simple and rapid device ensuring these two detections at the same time could lead to the monitoring of various pathologies in hospitals or in medical offices.
In the biomedical field, diagnostic and monitoring methods require the simultaneous detection of the progression of the disease as well as the presence of therapeutic agents. This double detection is in great demand for the surveillance of certain pathologies or the appearance of side effects during prolonged treatment (cancer). The difficulty of this detection by the same device is linked to the fact that the chemical structures and the concentrations of the biomarker and of the therapeutic agent present in the biological fluids are very different.
Thus, monitoring the evolution of therapeutic agents in serum makes it possible to determine their pharmacokinetics and their elimination from the body. For example, monitoring doxorubicin, considered to be the most widely used anticancer agent, concerns plasma concentrations between 10ng / ml and 100ng / ml depending on the patient's condition. However, this monitoring is done with conventional analysis methods such as HPLC, mass spectrometry, etc., and requires time to give a reliable response.
In this context, we wish to develop a multimodal platform operating in a microfluidic regime, integrating an opto-fluidic sensor and an electrochemical sensor and implementing the same controlled surface chemistry, in order to follow the evolution of therapeutic agents present in biological fluids with very high concentrations at the start of therapy and in parallel to detect one of the biomarkers of the disease, the concentration of which must decrease significantly during treatment until very low concentrations. The figure below gives the general architecture.
Opto-fluidic sensors can detect molecules of low molecular weight (therapeutic agents) with sensitivities on the order of ng to µg / mL; electrochemical sensors make it possible to reach very low biomarker concentration detection thresholds, on the order of the attomolar. Their integration in the fluidic platforms will allow the detection of DNA or RNA without amplification, thanks to a surface chemistry using the same material SU8 for the two sensors, so as to obtain a high surface density in biomolecules and to prevent non-specific interactions.
This approach can be generalized to other diagnostic and therapeutic follow-ups. These biochemical analyses could lead to biomedical applications usable in medical offices and hospitals, and bring adequate solutions to different problems, such as double detection which is still a major issue in the therapeutic approach.
In the biomedical field, diagnostic and monitoring methods require the simultaneous detection of the progression of the disease as well as the presence of therapeutic agents. This double detection is in great demand for the surveillance of certain pathologies or the appearance of side effects during prolonged treatment (cancer). The difficulty of this detection by the same device is linked to the fact that the chemical structures and the concentrations of the biomarker and of the therapeutic agent present in the biological fluids are very different.
Thus, monitoring the evolution of therapeutic agents in serum makes it possible to determine their pharmacokinetics and their elimination from the body. For example, monitoring doxorubicin, considered to be the most widely used anticancer agent, concerns plasma concentrations between 10ng / ml and 100ng / ml depending on the patient's condition. However, this monitoring is done with conventional analysis methods such as HPLC, mass spectrometry, etc., and requires time to give a reliable response.
In this context, we wish to develop a multimodal platform operating in a microfluidic regime, integrating an opto-fluidic sensor and an electrochemical sensor and implementing the same controlled surface chemistry, in order to follow the evolution of therapeutic agents present in biological fluids with very high concentrations at the start of therapy and in parallel to detect one of the biomarkers of the disease, the concentration of which must decrease significantly during treatment until very low concentrations. The figure below gives the general architecture.
Opto-fluidic sensors can detect molecules of low molecular weight (therapeutic agents) with sensitivities on the order of ng to µg / mL; electrochemical sensors make it possible to reach very low biomarker concentration detection thresholds, on the order of the attomolar. Their integration in the fluidic platforms will allow the detection of DNA or RNA without amplification, thanks to a surface chemistry using the same material SU8 for the two sensors, so as to obtain a high surface density in biomolecules and to prevent non-specific interactions.
This approach can be generalized to other diagnostic and therapeutic follow-ups. These biochemical analyses could lead to biomedical applications usable in medical offices and hospitals, and bring adequate solutions to different problems, such as double detection which is still a major issue in the therapeutic approach.