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

直到最近，使用思维过程控制电子设备可能还属于科幻领域。但脑机接口(BCI)的研究表明，神经植入可能会让计算机、电子设备或其他机械设备仅由思维来控制。限制脑机接口技术发展的因素之一是炎症组织反应，这会严重降低植入物的寿命。这个问题的一个解决方案可能是使用生物惰性材料，如薄膜钻石或类钻石碳(DLC)作为衬底材料，在其上生长形成生物-电子接口的神经元。这是因为钻石/类金刚石薄膜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，它们的表面化学成分可以很容易地进行修饰，允许不同类型的细胞的粘附性根据特定要求进行定制。这些材料可以被掺杂来改变它们的导电性，使电信号在钻石和连接的神经元之间传递。这一点的技术、医学、社会甚至军事意义是显而易见的。在医疗领域，BCI提出了治疗各种疾病的承诺。例如，截肢者或因脊髓损伤而瘫痪的人可能会安装BCI植入物，这种植入物将通过BCI控制一对机械腿/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。下一步将是将脑机接口与无线电链路连接起来，让安装了基于钻石的脑机接口植入物的人只需想一想就可以控制远程机器。尽管在将可靠的脑机接口应用于商业应用之前有许多不同的问题需要解决，但这个拟议项目的目标是为实现这种脑机接口设备奠定基础--即研究活的生物细胞(干细胞和神经元)与无机钻石电子设备之间的接口。我们不像以前的研究那样使用大鼠/小鼠的神经元，而是打算使用来自人类干细胞的神经元，这确保了这项研究的结果与人类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液的成分。干细胞将生长在不同的钻石和DLC表面，并对影响它们存活的因素进行识别和优化。这些因素包括表面是否被氧化、表面的粗糙度、掺杂程度等。干细胞随后将被适当的化学定义介质(CDM)处理，在几次细胞分裂过程中，这种介质会使子细胞转变为神经元。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。其目的是优化工艺条件和底物准备，使这两种类型的细胞都能在实验室培养，并能存活数周。以这种方式在钻石表面产生的神经元网络可以通过导电衬底的信号进行电刺激。最终目的是将信号从钻石/DLC衬底发送到神经元，然后再送回记录它的地方。这将演示钻石/DLC电子设备和神经元之间的双向信号处理。用激光在钻石/类金刚石细胞表面预制图案，将允许神经元沿着预先定义的“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条模拟人脑行为的途径。

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.