Diamond devices for bioelectronic applications - invited resubmission

现代微电子设备传感器与生物之间的接口是一个不断发展的领域，其中产生的电子信号被用来提供有关生物中发生的化学和电子过程的信息。应用出现在生物和医药领域，以及生物技术和食品工业等行业。目前一个有趣的领域是神经元接口。神经元是神经系统的细胞--人类大脑大约有1000亿个神经元--它们通过电化学过程传递信息。神经元的行为可以通过检测神经元发出信号时产生的电信号来跟踪，或者通过对神经递质的化学检测来跟踪，神经递质是在一个神经元和另一个神经元之间传递信息的特定化学物质。神经元接口需要生物介质与电子或电化学设备之间的密切接触，这些设备通常可能是硅基电子设备或石墨碳/金属电极或电极阵列。研究进展有限，要么是因为监测设备没有足够的灵敏度，要么是因为对培养细胞怀有敌意，要么是因为生物介质中发生了化学变化和显著降解。同样的情况是，传统设备往往只执行一项功能，如测量动作电位。理想情况下，这些设备应该能够刺激细胞，并在设备-培养界面控制纳米级的化学环境，同时监测神经递质和动作电位的释放。最近，由碳氢化合物和氢在固体表面的等离子体状态下发生低压反应而形成的人造钻石，已经可以以经济的价格获得，其性能与天然钻石相似或超过天然钻石。这种材料可以在电绝缘、半导体或金属状态下制备，这取决于所采用的确切生长条件，并且非常适合在恶劣环境中的电子和电化学应用，部分原因是由于钻石具有非常高的化学稳定性。这种新材料的特性使其非常适合于神经元接口领域的开发，而且应该有可能开发出多功能器件，利用钻石的电学和电化学性质，产生比现有器件更可靠和更灵敏的信号。尽管先前已经证实了薄膜金刚石的生物相容性，但开发它的尝试主要涉及被动应用，如耐磨或耐化学屏障。在这里，我们将探索使用钻石来制造用于神经元应用的有源多功能传感器的潜力。该项目将涉及培育项目所需的特殊形式的薄膜钻石，用其制造FET和电化学传感器，在钻石和生物介质之间的界面培养神经细胞，并测试这些生物电子设备测量动作电位和神经递质释放。为此，我们组建了一个由钻石电子工程、钻石电化学和神经细胞生物学专业知识组成的多学科团队。如果取得了有希望的结果，该项目将为开发应用程序铺平道路，这些应用程序显然可能对生物医学技术产生巨大影响。

The interfacing between modern microelectronic device sensors and living organisms is a growing field, in which the electronic signals produced are used to provide information concerning the chemical and electrical processes occurring in the organisms concerned. Applications arise in the fields of biology and medicine, and in industries such as the biotechnology and food industries. An interesting field at present is neuron interfacing. Neurons are cells of the nervous system - the human brain has around 100 billion neurons - which carry messages through an electrochemical process. The behaviour of neurons can be followed by detecting electrical signals arising when a neuron sends a signal, or by chemical detection of neurotransmitters, which are specific chemicals that transmit information between one neuron and the next. Neuron interfacing requires intimate contact between the biological media and electronic or electrochemical devices, which typically might be silicon-based electronic devices or graphitic carbon/metal electrodes or electrode arrays. Progress in the research has been limited, either because the monitoring devices do not possess sufficient sensitivity, are hostile to the cultured cells, or undergo chemical change and significant degradation in the biological media. It is also the case that the traditional devices tend to carry out one function only, such as measurement of action potential. Ideally the devices should be able to stimulate the cells and control the chemical environment on the nanoscale at the device-culture interface, whilst monitoring the release of neurotransmitters and action potentials. Recently synthetic diamond, formed by the low pressure reactions of hydrocarbons and hydrogen in an energised plasma state at a solid surface, has become available at an economic price, with properties similar or surpassing those of natural diamond. The material can be prepared in an electrically insulating, semi-conducting or metallic state, depending on the exact growth conditions employed, and is ideally suited for electronic and electrochemical applications in harsh environments, in part because of the very high chemical stability of diamond. The properties of this new material make it ideal for exploitation in the field of neuron interfacing, and it should be possible to formulate multifunctional devices, which exploit both the electronic and electrochemical properties of diamond, and which yield more reliable and sensitive signals than the present devices.Although the biocompatibility of thin film diamond has been identified previously attempts to exploit it have mainly been concerned with passive applications, such as a wear- or chemically- resistant barriers. Here we will explore the potential of using diamond to fabricate active multifunctional sensors for neuronal applications. The project will involve growing the special forms of thin film diamond needed for the project, making FET and electrochemical sensors from it, culturing neuronal cells at the interface between the diamond and the biological media, and testing these biolectronic devices in the measurement of action potential and neurotransmitter release.To do this, we have assembled a multidisciplinary team comprising expertise in diamond electronic engineering, diamond electrochemistry and neuronal cell biology. If promising results are obtained, the project will pave the way for developing applications which could clearly have a huge impact in biomedical technology.