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

直到最近，利用思维过程控制电子设备可能还只存在于科幻小说中。但脑机接口（BCI）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通过思想来控制。BCI技术发展的限制因素之一是炎症组织反应，这可能严重降低种植体的使用寿命。这个问题的解决方案可能是使用生物惰性材料，如薄膜金刚石或类金刚石（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薄膜已被证明是生物惰性的，当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修改，允许根据特定要求定制不同细胞类型的粘附特性。这些材料可以通过掺杂来改变其导电性，从而使电信号在金刚石和附着的神经元之间传递。这对技术、医学、社会甚至军事的影响是显而易见的。在医学领域，脑机接口有望“治愈”各种疾病。例如，截肢者或因脊髓受损而瘫痪的人可以安装脑机接口植入物，通过脑机接口控制一对机械腿/手臂，使患者能够正常行走和运作。最近的一些进展，如“脑门”项目、人工耳蜗和“仿生眼”项目，已经证明了类似的技术在十年内是可行的。下一步是将脑机接口连接到无线电链路上，这样一个装有钻石脑机接口植入物的人就可以通过简单的思考来控制远程机器。虽然在实现可靠的脑机接口商业应用之前，还有许多不同的问题需要解决，但这个项目的目标是为实现这种脑机接口设备奠定基础，即研究活生物细胞（干细胞和神经元）和无机金刚石电子之间的界面。与以往研究中使用大鼠/小鼠神经元不同，我们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脑接口相关。干细胞是一种特殊类型的细胞，根据组织培养的方法和培养基的成分，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）。干细胞将在不同的金刚石和DLC表面生长，并确定和优化控制其存活的因素。这些因素包括表面是否氧化、表面粗糙度、掺杂程度等。然后，干细胞将被适当的化学定义介质（CDM）处理，经过几次细胞分裂，使子细胞变成神经元。我们希望研究不同表面对干细胞转变为神经元的能力的影响。目的是优化处理条件和底物制备，使这两种细胞类型都能在实验室中培养，并使它们存活数周。以这种方式在金刚石表面产生的神经元网络可以通过传导衬底的信号受到电刺激。最终目标是将钻石/DLC衬底的信号发送到神经元中，然后再返回到被记录的地方。这将展示钻石/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表面进行预模式化，将允许神经元沿着预定义的“道路”生长，从而可以制作设计好的神经网络。使用不同的电脉冲刺激这些网络为模拟人类大脑的行为提供了一条途径。

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.