ULTRA-SENSITIVE GRAPHENE NANO-BIOSENSORS

癌症、心血管疾病、阿尔茨海默病、帕金森病和糖尿病等疾病对患者、社会和保险系统都有负面影响。日益老龄化的人口迫切需要更高效、负担得起的医疗保健。纳米技术正在为电子和医疗应用制造纳米大小的设备，这提高了人们对更好的诊断和“智能”治疗的期望。纳米传感器可以在尽可能早的阶段识别疾病生物标志物，从而有可能拦截更严重的疾病。通过早期发现，现有的治疗选择大大增加，例如前列腺癌是男性癌症患者的第二大杀手，如果早期发现，成功治疗的机会超过70%。生物标记物通常以非常低的浓度存在。监测生物标记物，如前列腺特异性抗原、葡萄糖或其他临床浓度的血液标记物——可能使用纳米传感器阵列——可以为患者提供真正的好处。使用尿液或呼吸样本的非侵入性智能测试将对慢性患者和治疗后监测生物标志物水平产生巨大的有益影响。目前疾病生物标志物的诊断是基于检测荧光标记的探针分子，这些探针分子与特定的底物结合受体相互作用。这种方法既昂贵又耗时，而且灵敏度有限。纳米级电化学生物传感器可以实现更高的灵敏度，使用无标记的生物标志物。我们将利用我们在石墨烯生长和半导体表面功能化方面的最新进展，开发基于晶圆的石墨烯/碳化硅（SiC）技术，用于新型生物传感器的应用。石墨烯是一种单原子石墨层，具有一些特殊的电子特性，如零带隙和室温下非常高的载流子迁移率——类似于碳纳米管。石墨烯可以通过硅升华在SiC衬底上生长。石墨烯/SiC相对于传统石墨烯的主要优势——从石墨衬底上剥离石墨烯薄片——是石墨烯在平坦、大面积晶圆（直径达100毫米）上生长的能力，随后可以使用标准半导体加工在其上制造器件。纳米通道石墨烯电子器件将在SiC衬底上制造。我们已经证明石墨烯可以被生物功能化，并将使用表面功能化化学将生物受体连接到纳米通道石墨烯器件上。由于其高表面/体积比和量子约束特性，石墨烯纳米通道的电学特性增加了信号/噪声比，并且受到轻微扰动的强烈影响，从而能够在超敏感（fM）分析物水平上检测生物标志物。通过纳米传感器的电流传输应该对其局部环境表现出极高的敏感性。一种概念验证的纳米通道生物传感器将使用抗体功能化的石墨烯，能够与目标前列腺癌生物标志物8-羟基脱氧鸟苷（8-OHdG）特异性和选择性相互作用。当生物分子与功能化表面结合时，它会产生可以被检测到的电信号。有效的生物传感器的关键是只有特定的生物分子才能与受体结合并产生反应。选择性可以通过选择正确的生物受体来控制。提出的功能化化学允许附着各种抗体，酶或氨基酸生物受体。我们的石墨烯/碳化硅生物芯片最终可以为许多疾病生物标志物提供超灵敏、快速诊断、成本效益高的测试——通过将诊断和监测带到护理点，有可能彻底改变医疗保健。一旦试验成功，将信号传输到手持读数显示器的移动监控系统，就可以将医疗保健从医院传递到患者家中。

Illnesses like cancer, cardiovascular diseases, Alzheimer's, Parkinson's, and diabetes have negative effects on patients, society and insurance systems. The ever-ageing population has a critical demand for more efficient, affordable healthcare.Nanotechnology is building nanometre sized devices for electronics and medical applications, raising expectations for better diagnostics and 'smart' treatments. Nanosensors could identify disease biomarkers at the earliest possible stage, potentially intercepting more serious illness. Available therapeutic options informed by early detection are greatly enhanced e.g. prostate cancer, the 2nd largest killer of male cancer patients, better than 70% chance of successful treatment if detected early. Biomarkers are often present at very low concentrations. Monitoring of biomarkers like prostate-specific-antigen, glucose or other blood-based markers at clinical concentrations - possible using nano-sensor arrays - could provide genuine benefits to patients. Non-invasive smart-testing using urine or breath samples would have a hugely beneficial impact on chronic patients and for monitoring biomarker levels after treatment. Current diagnosis of disease biomarkers is based on detection of fluorescently labeled probe molecules which interact with specific substrate-bound receptors. This is expensive and time-consuming, with limited sensitivity. Nanoscale electrochemical biosensors can achieve much higher sensitivities, using label-free biomarkers. We will exploit our recent advances in graphene growth and semiconductor surface functionalisation, to develop wafer-based, graphene/Silicon Carbide (SiC) technology for novel biosensor applications. Graphene, a single atomic layer of graphite, has some exceptional electronic properties such as its zero bandgap and very high carrier mobilities at room temperature - similar to carbon nanotubes. Graphene can be grown on SiC substrates using silicon sublimation. The principal advantage of graphene/SiC over conventional graphene - from exfoliation of graphene flakes from graphite substrates - is the capacity for graphene growth on flat, large-area wafers (up to 100mm in diameter), on which devices can subsequently be fabricated using standard semiconductor processing. Nano-channel graphene electronic devices will be fabricated on SiC substrates. We have shown that graphene can be bio-functionalized and will use surface functionalisation chemistry to attach bio-receptors to nano-channel graphene devices. Because of their high surface/volume ratio and quantum confinement properties, the electrical properties of graphene nano-channels have increased signal/noise ratios and are strongly influenced by minor perturbations, enabling biomarker detection at ultra-sensitive (fM) analyte levels. Current transport through the nanosensor should show extreme sensitivity to its local environment.A proof-of-concept nano-channel bio-sensor will be developed using antibody-functionalized graphene, capable of specific and selective interaction with the target prostate cancer biomarker, 8-hydroxydeoxyguanosine (8-OHdG). When the bio-molecule binds to the functionalised surface, it produces an electrical signal, which can be detected. The key to an effective biosensor is that only specific bio-molecules will bind to the receptor and produce a response. Selectivity can be controlled by choosing the correct bio-receptor.The functionalisation chemistry proposed allows for attachment of a variety of antibody, enzyme, or aminoacid bio-receptors. Our graphene/SiC biochip could eventually provide an ultra-sensitive, fast-diagnosis, cost-effective test for numerous disease biomarkers - potentially revolutionizing healthcare by bringing diagnosis and monitoring to the point-of-care. Once trialed, mobile monitoring systems, transmitting a signal to a hand held readout display, could allow translation of healthcare from hospitals to patients in their own homes.