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: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=588505
• 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提高世界人口的生活质量。另一方面，新的疾病正在出现，影响到65岁以上的人口。这些健康问题大多与神经退行性疾病有关，这些疾病主要与大脑中的神经递质（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，到2025年，全球患有这种疾病的患者人数将达到3400万，到2031年，加拿大的患者总数将达到75万。到目前为止，还没有治疗阿尔茨海默病的方法，但有几种替代方法可以减少其影响和影响。我们的发现提案将通过控制大脑局部区域的神经递质（NT）浓度，为患有这种疾病的患者提供希望，以便使用小型化和可植入的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。几乎所有的人类行为和身体功能都受到NTs的监控，任何由于这些分子引起的疾病都会影响我们的生活质量和健康状况。 我们最近发表的研究结果表明，脑脊液（CSF）的电特性受NTs浓度的影响。我们已经确定了CSF阻抗，电导率和NTs浓度之间的关系。最后，我们已经证明了与谷氨酸NT和γ-氨基丁酸（GABA）NT的CSF的阻抗和电导率的影响的NTs浓度的变化。作为一个例子，阿尔茨海默氏病与乙酰胆碱NT的显著减少有关，乙酰胆碱NT影响CSF的性质，这是基于我们以前的研究。此外，由于NT的浓度可以在亚纳升的范围内，我们需要具有0.001 S/m和10欧姆的精度的极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性贡献是建立了一个新的角度来分析大脑神经元的活动，其中一个假设NT（乙酰胆碱，多巴胺和GABA）可以区分基于其浓度，阻抗和/或电导率。如果成功的话，这将为目前治疗阿尔茨海默氏症等神经退行性疾病的患者提供一种重要的替代方案。 我们正在提出新一代的大脑植入式设备，这些设备可以感知大脑的化学和分子活动，也可以实现神经递质的局部传递，以阻止大脑紊乱。 为了实现这一目标，我们提出了一个医疗仪器芯片（MIOC）的传感和调制NT浓度在有限的区域。这一发现涵盖了MIOC设计的以下方面： 1-开发了一种新的用于纳米管传感和操作的微电极的制备工艺，以及基于碳纳米管的纳米管生物传感技术。 2-检测NT浓度变化的高灵敏度微电子电路的设计与实现 3-开发一种新的通道内和气泡液体取样技术，对几纳升的NT进行取样。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制造工艺。 所提出的MIOC还可以推广用于血液化学和分子疾病，例如胆固醇、镰状细胞性贫血等，因为传感和液体操作架构是相同的，而生物界面从一个应用到另一个应用是不同的。