A portable microfluidic electrochemical sensing platform for the real-time detection of clinical neurochemical markers
File(s)
Author(s)
Cicatiello, Chiara
Type
Thesis
Abstract
The regulation of the brain biochemistry is intricate and complex. Ions fluxes play an important role in the regulation of neuronal signalling. Probing the tissue neurochemistry is a valuable tool to understand the fundamental mechanisms of brain injury and optimise the critical care of brain injury patients.
The primary focus of this thesis was the development of a portable microfluidic electrochemical platform for the real-time and simultaneous detection of potassium, sodium and pH. The electrochemical device consisted of a fully integrated ion-sensitive field-effect transistor (ISFET) array based on complementary metal-oxide-semiconductor (CMOS) technology. The sensing surface of the chip was coated with drop-cast ion selective membranes (ISMs). For the real-time detection of ion concentration changes in vivo, the chip was coupled with microdialysis (MD) and integrated into a 3D printed microfluidic flow cell. The microfluidic development was necessary for the analysis of small volume MD streams and optimisation of the sensor response time. Post-processing clustering algorithms enabled the discernment of the data generated by different ions on the surface of the same chip.
Following on from the optimisation work of the experimental setup, the multi-ion sensing device was combined with microelectrode-based biosensors for the detection of several other analytes, mainly glucose and lactate. This multi-analyte monitoring system was employed to monitor the brain during an evaluation study of cardiopulmonary resuscitation strategies in a multimodal neuromonitoring porcine model. The continuous monitoring device was capable of resolving the dynamic changes in the chemical analytes associated with ischaemia. It also provided crucial insight into the effects of transient ischaemic events on neuronal metabolism and activity. The results of this proof-of-concept study demonstrated the feasibility of using MD for sampling extracellular ionic changes and using the optimised electrochemical device for their detection.
The primary focus of this thesis was the development of a portable microfluidic electrochemical platform for the real-time and simultaneous detection of potassium, sodium and pH. The electrochemical device consisted of a fully integrated ion-sensitive field-effect transistor (ISFET) array based on complementary metal-oxide-semiconductor (CMOS) technology. The sensing surface of the chip was coated with drop-cast ion selective membranes (ISMs). For the real-time detection of ion concentration changes in vivo, the chip was coupled with microdialysis (MD) and integrated into a 3D printed microfluidic flow cell. The microfluidic development was necessary for the analysis of small volume MD streams and optimisation of the sensor response time. Post-processing clustering algorithms enabled the discernment of the data generated by different ions on the surface of the same chip.
Following on from the optimisation work of the experimental setup, the multi-ion sensing device was combined with microelectrode-based biosensors for the detection of several other analytes, mainly glucose and lactate. This multi-analyte monitoring system was employed to monitor the brain during an evaluation study of cardiopulmonary resuscitation strategies in a multimodal neuromonitoring porcine model. The continuous monitoring device was capable of resolving the dynamic changes in the chemical analytes associated with ischaemia. It also provided crucial insight into the effects of transient ischaemic events on neuronal metabolism and activity. The results of this proof-of-concept study demonstrated the feasibility of using MD for sampling extracellular ionic changes and using the optimised electrochemical device for their detection.
Version
Open Access
Date Issued
2023-12-20
Date Awarded
01/03/2024
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Boutelle, Martyn Gordon
Georgiou, Pantelis
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)