Developing an On-Chip Reagentless Cancer screen

开发具有低处理要求的便携式诊断方法有可能在更广泛的社区中改进诊断测试。基于电化学阻抗和电容的无标签生物传感方法被证明是高度敏感的，并且专注于易于小型化和更快的结果，这些设备是对目前可用的多步骤标记（三明治）分析的实际改进。此外，这些技术的电化学性质导致了将方法集成到微电子和微流体细胞中，并且总体上降低了进行最终生物测定所需程序的复杂性。生物传感中的电化学阻抗谱（EIS）以Randles等效电路为模型，允许通过溶液中氧化还原探针的电荷转移电阻（RCT）和电容（CDL）的变化来检测界面的变化。通过修改这些过程与特定受体发生的界面，阻抗和电容可以作为目标捕获的函数来测量迄今为止，已将一系列生物受体固定在界面上，通常使用金和碳电极，取得了不同程度的成功。例如，Q. Xu等人先前创建了一种与帕金森病相关的α -突触核蛋白的阻抗测定法，其临床意义范围和灵敏度为3.1 ng mL-1，然而在许多其他项目中，由生物液体中物种的非特异性结合引起的污染仍然存在问题。目前，临床使用的癌症生物标志物相对较少，而且大部分可用的检测方法都是针对治疗选择而不是诊断。该项目旨在通过将抗原和抗原模拟受体整合到电极表面，建立一个检测早期癌症自身抗体的平台。具体来说，将重点关注在电极功能化中使用无污垢聚合物薄膜，以便进行具有高特异性的测试。未来的工作将集中于利用阻抗和电容光谱将这些电极开发成电化学生物传感器，其灵敏度水平适合临床使用。研究方法的新颖性：利用新的肽受体捕获抗体表位；新型电极约束聚合物支架的设计、制备和表征基于功能分析的分析方法优化。该项目属于EPSRC物理科学和医疗保健技术主题，特别是优化治疗研究领域。该项目还与EPSRC的未来制造战略主题（临床技术、聚合物开发、超分子化学）和分析科学直接相关。此外，新的高灵敏度分析检测平台与全球不确定性主题相关。该项目将与英国牛津的奥斯勒诊断公司合作进行。

The development of portable diagnostics with low processing requirements has the potential to improve diagnostic testing in the wider community. Label-free biosensing methods based on electrochemical impedance and capacitance are proven to be highly sensitive, and with a focus on easy miniaturisation and quicker results, these devices are a practical improvement on the multi-step, labelled (sandwich) assays currently available. Additionally, the electrochemical nature of these techniques results in ready integration of methods into microelectronic and microfluidic cells, and an overall reduced complexity in the procedures required for conducting the eventual bioassay. Electrochemical impedance spectroscopy (EIS) in biosensing, as modelled on a Randles equivalent circuit, allows changes at an interface to be detected via variance in the charge transfer resistance (RCT) and capacitance (CDL) of the redox probe in solution. By modifying the interface across which these processes occur with specific receptors, impedance and capacitance may be measured as a function of target capture.3 To date, a range of bioreceptors have been immobilized onto interfaces, commonly utilising gold and carbon electrodes, with varying success. For example, Q. Xu et al. have previously created an impedimetric assay for alpha-synuclein associated with Parkinson's disease, with a clinically significant range and a sensitivity of 3.1 ng mL-1, however in many other projects fouling caused by the non-specific binding of species in biological fluids remains problematic. Currently there are relatively few cancer biomarkers in clinical use and a significant proportion of available assays are directed at treatment selection rather than diagnosis. This project will look to create a platform for the detection of auto-antibodies indicated in early-stage cancer by integrating antigen and antigen-mimic receptors into an electrode surface. Specifically there will be a focus on the use of non-fouling polymer films in the functionalisation of the electrode in order to result in a test with high specificity. Future work will then concentrate on the development of these electrodes into an electrochemical biosensor using impedance and capacitance spectroscopy, with levels of sensitivity suitable for clinical use. Novelty of the research methodology: the use of new peptide receptors to capture antibody epitopes; the design, generation and characterisation of new electrode confined polymer supports; the optimisation of analytical methodologies based on function analysis. This project falls within the EPSRC Physical sciences and Healthcare technologies themes, and specifically the optimising treatments research area. The project also relates directly to the EPSRC strategic themes of Manufacturing the Future (clinical technology, polymer developments, supramolecular chemistry), and Analytical Science. New, highly sensitive, analytical detection platforms are, additionally, of relevance to the Global Uncertainties theme.This project will be conducted in collaboration with Osler Diagnostics, Oxford, UK.