Smart Medical Instrumentation On Chips For Early Detection and Treatment of Brain Molecular Disorder

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Major advances in medicine, drug discovery and new treatments can considerably improve the quality of life of the world population. On the other hand, new diseases are surfacing and affecting the 65 years and plus population. Most of these health problems are associated with neurodegenerative diseases, which are mainly related to a neurotransmitter (NT) concentration disorder in the brain. Alzheimer’s is one of neurodegenerative diseases that affect the largest portion of the world’s elderly population. The Alzheimer’s society of Montreal estimates that the number of patient suffering from this disease will be 34 million worldwide in 2025 and will reach a total of 750 000 patients in Canada in 2031. Up to now, there is no treatment for Alzheimer’s disease, but there are several alternatives to reduce its impact and effects. Our discovery proposal will offer hope for patients suffering from this disease by controlling the neurotransmitters (NTs) concentration in a local area of the brain in order to stop the disorder caused by Alzheimer’s using miniaturized and implantable microsystems. Indeed, NTs are among the most important information vehicles in the brain. Almost all human behavior and body functions are monitored by NTs and any disorder due to these molecules will affect our quality of life and health conditions. Our recently published results show that the electrical properties of cerebrospinal fluid (CSF) are affected by the NTs concentration. We have identified a relation between CSF impedance, conductivity and NTs concentration. Finally, we have proven with glutamate NT and gamma amino butyric acid (GABA) NT that the CSF impedance and conductivity are affected by the change of NTs concentration. As an example, Alzheimer’s disease is related to a considerable decrease of acetylcholine NT which affects CSF properties based on our previous research. Furthermore, as the concentration of NTs can be in the range of sub-nano liters, we need an extremely highly sensitive device with an accuracy of 0.001 S/m and 10 ohm to measure the conductivity and resistivity of the CSF, respectively. An innovative contribution of this work is the establishment of a new perspective for the analysis of brain neuronal activities where one assumes that NTs (acetylcholine, dopamine and GABA) can be differentiated based on their concentration, impedance and/or conductivity. If successful, this could provide an important alternative to the current treatment of patients with neurodegenerative diseases such as Alzheimer’s. We are proposing a new generation of brain implantable devices that are sensing the chemical and molecular brain activity and can also achieve neurotransmitter local delivery in order to stop brain disorder. In order to achieve this objective, we propose a medical instrumentation on-chip (MIOC) to sense and modulate NT concentration in limited area. This discovery covers the following aspects of MIOC design: 1- Development of a new fabrication process to design microelectrode for NTs sensing and manipulation and biosensing techniques for NTs based on carbon nanotubes. 2- Design and Implementation of highly sensitive microelectronics circuit to detect NT concentration change 3- Development of a new in-channel and air bubble liquid sampling technique to sample a few nano-liters of NT. Such a technique, will certainly open other alternatives to replace conventional micro pumps as it does not require any dedicated microfabrication process. The proposed MIOC can also be generalized for blood chemical and molecular disorders such as for cholesterol, sickle-cell anemia, etc. as the sensing and liquid manipulation architecture are the same while the bio-interface differs from one application to another.