Electrochemical ELISA systems for the rapid, low cost and point of need analysis of clinical samples

电化学生物传感器系统是一种很有前途的低成本和简单易用的疾病诊断解决方案。及时诊断癌症是一个特别具有挑战性的领域。这是因为症状通常是模糊和非特异性的，直到疾病发展到治疗选择更有限和预后较差的阶段。一种越来越受欢迎的想法是“液体活检”，即对容易获得的体液进行检查，以寻找癌症的早期迹象。这包括使用血液、血清、血浆、尿液和唾液来寻找临床相关的生物标志物。这些生物标志物可以包括特定的蛋白质，例如前列腺癌中的前列腺特异性抗原（PSA），或多种炎症生物标志物的组合，例如肿瘤坏死因子α、IL-6和c反应蛋白。除了蛋白质外，血液中自由循环的核酸序列，特别是含有癌变突变的DNA序列，也是越来越重要的癌症生物标志物。目前，诸如上述的癌症生物标志物是使用大型、高通量系统进行分析的，例如最近引入的GRAIL系统。这些技术很昂贵，而且仍然不能达到很高的诊断准确性。该项目的目标是开发简单易用的护理点技术，该技术可用于初级卫生保健环境，以极低的成本筛查癌症，并改善患者向专科肿瘤单位的分流。为了实现这一目标，将追求以下技术目标：1)开发低成本传感器阵列-理想情况下在PCB基板上2)筛选一组胰腺癌样本的生物标志物信号3)使用先进的信号处理技术建立胰腺癌的生物标志物面板4)开发电化学ELISA系统来测量胰腺癌的蛋白质标志物5)开发循环肿瘤DNA系统来测量胰腺癌的突变DNA指示物6)将以上几个方面结合起来，形成一个低成本系统的原型

Electrochemical biosensor systems are a promising route to low cost and simple to use diagnostic solutions for a range of diseases. One particularly challenging area for timely diagnosis is cancer. This is because symptoms are often vague and non-specific until the disease has reached a stage where treatment options are more limited and the prognosis is poor. An idea that is gaining increasing traction is that of the "liquid biopsy" where easy to access bodily fluids are investigated for early signs of cancer. This includes the use of blood, serum, plasma, urine and saliva to look for clinically relevant biomarkers. Such biomarkers can include specific proteins, e.g. Prostate Specific Antigen (PSA) in prostate cancer, or combinations of multiple inflammatory biomarkers such as tumour necrosis factor alpha, IL-6 and C-reactive protein. In addition to proteins, nucleic acid sequences and specifically DNA sequences circulating freely in the blood which contain cancerous mutations are also an increasingly important biomarker for cancer.Currently, cancerous biomarkers such as those mentioned are assayed using large, high throughput systems such as the recently introduced GRAIL system. These techniques are expensive and still do not achieve high diagnostic accuracy.The goal of this project is to develop simple to use point of care technologies which can be used in the primary healthcare environment to screen for cancer at extremely low cost and improve the triage of patients towards specialist oncology units. To achieve this the following technical goals will be pursued:1) Development of a low cost sensor array - ideally on a PCB substrate2) Screening a set of pancreatic cancer samples for biomarker signals3) Using advanced signal processing techniques to establish a panel of biomarkers for pancreatic cancer4) Developing an electrochemical ELISA system to measure protein markers of pancreatic cancer5) Developing a circulating tumour DNA system to measure mutated DNA indicative of pancreatic cancer6) Combine the above aspects into a prototype low cost system