This doctoral project will be carried out in the frame of a multidisciplinary research project, where expertise in soft-matter physics, nanobiosensing and neurotechnologies is combined with advanced expertise in neurophysiology, and in mechanisms of psychiatric and neurological disorders. While the main part of the work concerns sensor development and validation in vitro in the Nanobiophysics team of the Soft Matter and Biophysics unit of the Department of Physics and Astronomy, under the supervision of Prof Carmen Bartic (Department of Physics and Astronomy), the devices will be customized and tested in vivo in collaboration the neuroscience teams under the supervision of Prof. Myles McLaughlin (Department of Neurosciences) and Prof. Rudi D’Hooge and Dr. Laura Luyten (Faculty of Psychology).
The Nanobiophysics team has expertise in biosensors, nanotechnologies and neuroengineering methods. Our main research teams are artificial extracellular matrices and implantable biosensors based on hybrid nano-biomaterials that preserve implant functionality (by reducing inflammation and foreign body response) and add biosensing functionalities to neural prostheses.
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Neurons in the brain communicate via complex electrochemical signalling processes that underpin the functioning of the nervous system. Electrochemical signaling allows neurons to form simple local circuits that in turn form vast neural networks to facilitate complex functions such as learning, memory, emotions, and cognition. Recent advances in silicon probe technology allow in vivo electrical recordings with unprecedented throughput and spatio-temporal resolution. However, an equivalent technology for monitoring chemical signalling in a similar way is still missing.
A large variety of electrochemical sensors have been demonstrated in vitro, with proof-of-concept neurotransmitter sensitivities down to nanomole concentrations and millisecond time resolution. However, the huge potential of these methods remains essentially unexploited in vivo, mainly because of: (1) inflammation and foreign body reactions (FBR) that lead to sensor fouling and loss of sensing functionality in chronic settings; (2) instability of conventional Ag/AgCl reference electrodes in vivo; (3) poor sensor selectivity in a complex biochemical environment.
The main goal of the project is to tackle these challenges and develop electrochemical biosensors with high sensitivity and selectivity for fast and multiplexed in vivo neurochemical monitoring and integrate these into in vivo probes. The sensors should provide stable (for several weeks) in vivo chemical readout of dopamine (DA) and glutamate (Glu). The sensors will be based on nanocomposite sensing layers incorporating biocompatible metal nanoparticles in combination with enzymatic biorecognition elements encapsulated into thin cell/protein resistant layers (to prevent in vivo biofouling). Different electrochemical sensing schemes will be explored different scanning methods (e.g. square wave potentiometry to identify neurotransmitter-specific peaks, followed by chronoamperometry for millisecond chemical readout), while deep learning methods will be applied to realize multiplexed sensing (i.e. deconvolute individual neurotransmitter release patterns).
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