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有前途的低成本和简单易用的诊断解决方案，用于一系列疾病的路线。及时诊断的一个特别具有挑战性的领域是癌症。这是因为症状通常是模糊和非特异性的，直到疾病达到治疗选择更加有限且预后不良的阶段。一个越来越受关注的想法是“液体活检”，在这种方法中，可以容易地获得体液来研究癌症的早期迹象。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。这样的生物标志物可以包括特定蛋白质，例如前列腺癌中的前列腺特异性抗原（PSA），或多种炎性生物标志物的组合，例如肿瘤坏死因子α、IL-6和C反应蛋白。除了蛋白质之外，在血液中自由循环的含有癌性突变的核酸序列，特别是DNA序列也是越来越重要的癌症生物标志物。这些技术都是昂贵的，仍然没有达到高的诊断准确性。该项目的目标是开发简单易用的护理点技术，可用于初级医疗保健环境中，以极低的成本筛查癌症，并改善病人的分流到专科肿瘤单位。为了实现这一点，将追求以下技术目标：1）开发低成本传感器阵列-理想地在PCB基板上2）针对生物标志物信号筛选一组胰腺癌样品3）使用先进的信号处理技术来建立胰腺癌的生物标志物组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系统来测量指示胰腺癌的突变DNA 6）将上述方面联合收割机组合成原型低成本系统

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