Silicon Nanowire Arrays for Viral Infection Markers

用于病毒感染标记的硅纳米线阵列

• 批准号: EP/G061696/1
• 负责人: Peter Ashburn
• 金额: $ 141.15万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FG061696%2F1
• 关键词: Silicon; Nanowire; Arrays; Viral; Infection

Laboratory analysis of a clinical sample such as blood serum is a powerful diagnostic tool. It establishes the presence and concentration of a specific biomolecule that correlates with the risk or progression of a particular disease, or with the susceptibility of the disease to a given treatment. Regular screening for a large number of such biomarkers, the discovery of which is a major biomedical research activity, would make the large-scale application of predictive, preventive and personalized medicine a reality. This emphasis on prevention and individualization of healthcare is highly desirable from a socio-economical perspective, but the required increase in the number of laboratory tests (already about a billion per annum in the UK) will be huge and cannot be met with the biochemical analysis methods that are currently employed.The aim of this Grand Challenge project is to develop silicon nanowire arrays, the only technology that has been shown to enable highly specific and ultrasensitive analysis of protein biomarkers with electronic rather than costly optical detection, into a robust user platform for the simultaneous analysis of a large number of biomarkers in the same clinical sample. We will optimize a unique method to fabricate extensive arrays of silicon nanowires with a cost-effective mass-production technology that is similar to that used by the microelectronics industry. The silicon nanowires will be incorporated in an advanced microfluidic matrix that will not only allow the sample volume to be very small (a blood droplet obtained with a simple finger prick could be sufficient), but will also provide the means to divide the nanowire array, which can consist of up to a thousand parallel nanowires, into many individually addressable sets of nanowires. Through appropriate functionalization chemistry, each nanowire set can be made to recognize and quantify a different biomarker, enabling a maximum amount of information to be extracted from a minimal amount of sample.The nanowire devices, including the microfluidics for sample handling, will be developed as a single disposable chip, suitable for the mass production of commercial diagnostic kits. Our industrial partners, one manufacturer and two different end-users, will provide a pronounced commercial perspective to the development of the nanowire platform. For clinically relevant pre-commercialization proof of principle, the project will focus on the analysis of six different protein markers of viral infection and treatment. The project will have unique access to clinical samples -serum and induced sputum- obtained from patients admitted to the Acute Medical Unit at the Southampton General Hospital suffering from acute asthma exacerbations. It will also have access to serum samples from asthmatic volunteers undergoing Phase I clinical trials using inhaled beta-interferon which is being developed for treatment of virus-induced asthma exacerbations.The silicon nanowire technology will enable routine and economical high-throughput biomarker analysis outside the clinical laboratory, providing the technological means for a transition to a healthcare system in which regular screening for complex diseases facilitates prevention and early intervention. Throughout the project we will explore practical questions of implementation during scientific and technological development rather than, as is more commonly the case, after scientific and technological phases have been completed. To achieve this we will engage with the public, healthcare professionals, healthcare managers and policy makers to explore key questions of risk and regulation as well as exploring how this technology might be brought into effective use within established systems of healthcare work and organization.

临床样品如血清的实验室分析是一种强大的诊断工具。它确定了与特定疾病的风险或进展相关的特定生物分子的存在和浓度，或与疾病对给定治疗的易感性相关。定期筛选大量此类生物标志物（发现此类生物标志物是一项重要的生物医学研究活动）将使预测性、预防性和个性化医学的大规模应用成为现实。从社会经济的角度来看，这种对预防和个性化医疗保健的强调是非常可取的，但实验室检查数量的增加（在英国每年已经有大约10亿）将是巨大的，并且不能用目前采用的生化分析方法来满足。这个大挑战项目的目的是开发硅纳米线阵列，这是唯一一种已被证明能够通过电子检测而不是昂贵的光学检测对蛋白质生物标志物进行高度特异性和超灵敏度分析的技术，该技术被整合到一个强大的用户平台中，用于同时分析同一临床样本中的大量生物标志物。我们将优化一种独特的方法来制造广泛的硅纳米线阵列，并采用与微电子行业类似的具有成本效益的大规模生产技术。硅纳米线将被纳入一个先进的微流控矩阵，这不仅允许样品体积非常小（用简单的手指刺破获得的血滴可能就足够了），而且还将提供将纳米线阵列（可以由多达一千个平行纳米线组成）划分为许多可单独寻址的纳米线组的方法。通过适当的功能化化学，每个纳米线组可以识别和量化不同的生物标志物，从而能够从最少量的样品中提取最大量的信息。纳米线设备，包括用于样品处理的微流体，将被开发为单个一次性芯片，适用于商业诊断试剂盒的大规模生产。我们的工业合作伙伴，一个制造商和两个不同的最终用户，将为纳米线平台的开发提供明显的商业前景。对于临床相关的预商业化原理证明，该项目将重点分析病毒感染和治疗的六种不同蛋白质标志物。该项目将有独特的机会获得临床样本-血清和诱导痰-从南安普顿总医院急性医疗单位收治的急性哮喘加重患者中获得。它还将获得哮喘志愿者的血清样本，这些志愿者正在接受使用吸入性β-干扰素的I期临床试验，该试验正在开发用于治疗病毒引起的哮喘急性发作。硅纳米线技术将使临床实验室之外的常规和经济的高通量生物标志物分析成为可能，提供技术手段，以过渡到一个保健系统，在该系统中，定期筛查复杂疾病有助于预防和早期干预。在整个项目中，我们将探讨在科学和技术发展期间而不是象通常情况那样在科学和技术阶段完成之后执行的实际问题。为了实现这一目标，我们将与公众、医疗保健专业人员、医疗保健管理人员和政策制定者合作，探讨风险和监管的关键问题，并探索如何在现有的医疗保健工作和组织系统中有效利用这项技术。

项目成果

Effect of Fluorine on the Lateral Crystallization of Amorphous Silicon Nanowires

氟对非晶硅纳米线横向结晶的影响

• DOI: 10.1149/2.023202jss
• 发表时间: 2012
• 期刊: ECS Journal of Solid State Science and Technology
• 影响因子: 2.2
• 作者: Sun K

Inflammatory biomarker sensing using rectangular polycrystalline silicon nanowires made by dry etching

使用干法蚀刻制成的矩形多晶硅纳米线进行炎症生物标志物传感

• 作者: M. Lombardini (Author)

Comparison of etches for top-down fabrication of polycrystalline silicon nanowires

自上而下制造多晶硅纳米线的蚀刻比较

• 作者: K. Sun (Author)

Effect of an Oxide Cap Layer and Fluorine Implantation on the Metal-Induced Lateral Crystallization of Amorphous Silicon

氧化物盖层和氟注入对非晶硅金属诱导横向结晶的影响

• DOI: 10.1149/2.038301jss
• 发表时间: 2012
• 期刊: ECS Journal of Solid State Science and Technology
• 影响因子: 2.2
• 作者: Sun K

Rectangular Polysilicon Nanowires by Top-Down Lithography, Dry Etch and Metal-Induced Lateral Crystallization

• DOI: 10.1149/2.011203esl
• 发表时间: 2012-03
• 期刊: Electrochemical and Solid State Letters
• 作者: K. Sun;M. Hakim;P. Ashburn