CVD DIAMOND AS A SUBSTRATE FOR BIOLOGICAL CELL GROWTH - TOWARDS DIRECT BRAIN-COMPUTER INTERFACES

CVD 金刚石作为生物细胞生长的基质 - 迈向直接脑机接口

• 批准号: EP/K002503/1
• 负责人: Paul May
• 金额: $ 81.5万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FK002503%2F1
• 关键词: CVD; DIAMOND; SUBSTRATE; BIOLOGICAL; CELL

Controlling electronic devices using thought-processes may until recently have been in the domain of science-fiction. But brain-computer interface (BCI) research is showing that neural implants may allow computers, electronic equipment, or other mechanical devices to be controlled by thought alone. One of the limiting factors in the development of BCI technology is inflammatory tissue response, which can severely reduce the longevity of the implant. A solution to this problem may be to use bioinert materials, such as thin film diamond or diamond-like carbon (DLC) as the substrate material upon which to grow the neurons that form the biology-to-electronics interface. This is because diamond/DLC films have been shown to be bioinert, and do not produce an immune response when in contact with living cells. Moreover, their surface chemistry can be readily modified, allowing the adhesion properties of different cell types to be tailored for specific requirements. These materials can be doped to change their conductivity allowing electrical signals to pass between the diamond and attached neurons.The technological, medical, social, and even military implications for this are obvious. In the medical field, BCI holds out the promise of 'cures' for a variety of ailments. For example, amputees or people paralysed due to a damaged spinal cord may be fitted with a BCI implant which would be used to control a pair of robotic legs/arms via a BCI, enabling the patient to walk and function as normal. Recent advances such as the 'Braingate' project, the artificial cochlea and 'bionic' eye projects have demonstrated that technology similar to this may be feasible within a decade. The next step would be to link the BCI to a radio-link, allowing a person fitted with a diamond-based BCI implant to control remote machinery, all by simply thinking about it.Although there are many different problems to be solved before reliable BCIs can be achieved for commercial applications, the aim of this proposed project is to underpin the first steps towards realising such BCI devices - i.e. studying the interface between the living biological cells (stem cells and neurons) and inorganic diamond electronics. Rather than use rat/mice neurons, as in previous studies, we intend to use neurons derived from human stem cells, which ensures that the results of this study are relevant to human BCIs. Stem cells are special types of cells that can easily be converted into a specific type of neuron (or any other type of cell) depending on the method of tissue culture and the constituents of the culture media. The stem cells will be grown on different diamond & DLC surfaces, and the factors which govern their survival identified and optimised. These factors include such things as whether the surface is oxidised or not, its roughness, doping level, etc. The stem cells will then be treated with suitable chemically defined media (CDM), which over the course of several cell divisions causes the daughter cells to turn into neurons. We wish to investigate the affect of the different surfaces on the ability of the stem cells to turn into neurons. The aim is to optimise the processing conditions and substrate preparation to allow both these cell types to be cultured in the laboratory, and to allow them to survive for many weeks. The network of neurons produced on the diamond surface in this way can be stimulated electrically via signals through the conducting substrate. The ultimate aim is to send signals from the diamond/DLC substrate into a neuron, and back again where it is recorded. This would demonstrate two-way signal processing between the diamond/DLC electronics and the neuron. Prepatterning the diamond/DLC surface with lasers will allow the neurons to grow along predefined 'roadways', allowing designed neural nets to be made. Stimulating these networks using different electrical impulses provides a route to modelling the behaviour of the human brain.

直到最近，用思维过程控制电子设备可能还属于科幻小说的范畴。但脑机接口（BCI）的研究表明，神经植入物可以让计算机、电子设备或其他机械设备仅由思维控制。BCI技术发展的限制因素之一是炎症组织反应，这会严重缩短植入物的寿命。这个问题的解决方案可能是使用生物惰性材料，例如薄膜金刚石或类金刚石碳（DLC）作为基底材料，在其上生长形成生物-电子界面的神经元。这是因为金刚石/DLC薄膜已被证明具有生物惰性，并且在与活细胞接触时不会产生免疫反应。此外，它们的表面化学性质可以很容易地改变，允许不同细胞类型的粘附特性根据特定要求进行定制。这些材料可以被掺杂以改变它们的导电性，从而使电信号在钻石和附着的神经元之间传递，这在技术、医学、社会甚至军事上的意义是显而易见的。在医学领域，BCI为各种疾病提供了“治愈”的希望。例如，截肢者或因脊髓损伤而瘫痪的人可以安装BCI植入物，该植入物将用于通过BCI控制一对机器人腿/手臂，使患者能够正常行走和功能。最近的进展，如“Braingate”项目，人工耳蜗和“仿生”眼睛项目已经证明，类似的技术可能在十年内可行。下一步将是将BCI连接到无线电链路，允许安装基于金刚石的BCI植入物的人控制远程机器，所有这些都是通过简单的思考来实现的。尽管在可靠的BCI实现商业应用之前还有许多不同的问题需要解决，该项目的目标是支持实现这种脑机接口设备的第一步，即研究活生物细胞之间的界面（干细胞和神经元）和无机金刚石电子。我们不像以前的研究那样使用大鼠/小鼠神经元，而是打算使用来自人类干细胞的神经元，这确保了本研究的结果与人类BCI相关。干细胞是一种特殊类型的细胞，可以很容易地转化为特定类型的神经元（或任何其他类型的细胞），这取决于组织培养的方法和培养基的成分。干细胞将在不同的金刚石和DLC表面上生长，并确定和优化控制其存活的因素。这些因素包括表面是否被氧化，其粗糙度，掺杂水平等，然后用合适的化学成分确定的培养基（CDM）处理干细胞，在几次细胞分裂的过程中，子细胞变成神经元。我们希望研究不同表面对干细胞转化为神经元能力的影响。其目的是优化处理条件和基质制备，以允许这两种细胞类型在实验室中培养，并允许它们存活数周。以这种方式在金刚石表面产生的神经元网络可以通过导电基底的信号进行电刺激。最终目标是将信号从金刚石/DLC基底发送到神经元，并再次返回记录。这将证明钻石/DLC电子器件和神经元之间的双向信号处理。用激光对金刚石/DLC表面进行预图案化，将允许神经元沿着沿着预定义的“道路”生长，从而制造出设计好的神经网络。使用不同的电脉冲刺激这些网络提供了一种模拟人脑行为的途径。

项目成果

Spatial Control of Neuronal Adhesion on Diamond-Like Carbon

• DOI: 10.3389/fmats.2021.756055
• 发表时间: 2021-11
• 作者: J. Dugan;C. Colominas;A. García-Granada;F. Claeyssens

Diamond thin films: giving biomedical applications a new shine.

• DOI: 10.1098/rsif.2017.0382
• 发表时间: 2017-09
• 期刊: Journal of the Royal Society, Interface
• 作者: Nistor PA;May PW
• 通讯作者: May PW