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

用于早期检测和治疗脑分子疾病的芯片上的智能医疗仪器

• 批准号: RGPIN-2014-05603
• 负责人: Miled, Amine
• 金额: $ 1.6万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=678880
• 关键词: Smart; Medical; Instrumentation; Chips; Early

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.

医学、药物发现和新疗法的重大进步可以大大改善世界人口的生活质量。另一方面，新的疾病正在出现并影响 65 岁及以上人群。这些健康问题大多与神经退行性疾病有关，而神经退行性疾病主要与大脑中神经递质（NT）浓度紊乱有关。阿尔茨海默氏症是影响世界上最大部分老年人口的神经退行性疾病之一。蒙特利尔阿尔茨海默氏症协会估计，2025年全球患有这种疾病的患者人数将达到3400万，2031年加拿大患者总数将达到75万。迄今为止，阿尔茨海默氏症尚无治疗方法，但有有几种减少其影响和影响的替代方案。我们的发现提案将为患有这种疾病的患者带来希望，通过控制大脑局部区域的神经递质（NT）浓度，以使用微型和可植入微系统来阻止阿尔茨海默氏症引起的疾病。事实上，NT 是大脑中最重要的信息载体之一。几乎所有人类行为和身体功能都受到 NT 的监控，由这些分子引起的任何疾病都会影响我们的生活质量和健康状况。 **我们最近发表的结果表明，脑脊液 (CSF) 的电特性受到 NT 浓度的影响。我们已经确定了 CSF 阻抗、电导率和 NT 浓度之间的关系。最后，我们用谷氨酸NT和γ氨基丁酸（GABA）NT证明了脑脊液阻抗和电导率受到NT浓度变化的影响。例如，根据我们之前的研究，阿尔茨海默病与乙酰胆碱 NT 的显着降低有关，乙酰胆碱 NT 会影响脑脊液特性。此外，由于NT的浓度可以在亚纳升范围内，因此我们需要精度为0.001 S/m和10欧姆的极其高灵敏度的设备来分别测量CSF的电导率和电阻率。这项工作的一个创新贡献是为分析大脑神经元活动建立了一个新的视角，其中人们假设 NT（乙酰胆碱、多巴胺和 GABA）可以根据其浓度、阻抗和/或电导率来区分。如果成功，这可能为当前治疗阿尔茨海默氏症等神经退行性疾病患者提供一种重要的替代方案。**我们正在提出新一代脑植入设备，该设备可以感知大脑化学和分子活动，还可以实现神经递质局部输送为了阻止大脑紊乱。**为了实现这一目标，我们提出了一种片上医疗仪器（MIOC）来感测和调节有限区域内的 NT 浓度。这一发现涵盖了 MIOC 设计的以下方面： * 1- 开发一种新的制造工艺来设计用于 NT 传感和操纵的微电极以及基于碳纳米管的 NT 生物传感技术。 * 2- 设计和实现高灵敏度微电子电路来检测NT 浓度变化* 3- 开发一种新的通道内和气泡液体采样技术，可对几纳升的 NT 进行采样。这种技术肯定会开辟其他替代方案来取代传统的微型泵，因为它不需要任何专用的微加工工艺。**所提出的 MIOC 也可以推广到血液化学和分子疾病，例如胆固醇、镰状细胞性贫血等因为传感和液体操纵架构是相同的，而生物接口则因应用而异。