Development of a new biosensor platform for Point-Of-Care (POC) diagnostics

该博士项目旨在开发一种新的用于床旁（POC）诊断的生物传感器平台，使样品能够用于快速核酸检测和分子诊断。将考虑抗原相关免疫测定和PCR相关分子诊断测定。基于抗原的免疫测定比分子诊断需要更多的蛋白质生物标志物。随着越来越多地采用该技术代替通过免疫测定进行的抗原检测，分子诊断学正在迅速发展。分子诊断还具有高特异性等优点，有助于检测甚至微量的生物标志物。这对于传染病的早期检测至关重要，如B肝炎病毒（HBV）、丙型肝炎病毒（HCV）、人类免疫缺陷病毒（HIV）、单纯疱疹病毒（HSV）、结核病、麻疹、登革热、南美锥虫病、霍乱、脓毒症和疟疾。该项目的灵感来自于PI博士Luigi G. Occhipinti，University of剑桥，Electrical Engineering Division，关于各种生物传感器技术，包括例如DNA Label-free Biosensors（Science of Adv. Materials 2011），关于基于石墨烯的传感器（J. of Applied Physics 2013），关于分子诊断测定（US Pat. 2014/0038193）、水栅有机晶体管（Flex.打印. Electron.2016，1，025005），以及最近与剑桥大学的临床研究团队合作，对生物相容性进行定量分析（Adv. Biosys. 2017），以及发现细胞外囊泡中的酶活性，在没有或有限副作用（如肝毒性）的新抗癌疗法中具有潜在应用（Nature Chem. Biology，2017）。在生物学、医疗保健技术和生物电子学的界面上，该项目将为剑桥大学正在进行的学术研究开辟有趣的新方向，与赞助该项目的强大行业团队合作，该项目是全球住友公司的一部分。该项目将专注于开发一种多重实时定量PCR设备，作为感染性疾病POC诊断分析的概念验证演示器，并将当前基于荧光的实时检测方法应用于基于电学，阻抗，图2示出了用于在RT-qPCR的指数期期间定量靶DNA扩增子的生物传感器阵列。他/她将接受先进的纳米纤维，传感器设计，制造和表征，包括一些印刷电子技术的全面培训。此外，还将进行护理点诊断平台培训，包括一些临床应用和验证方面，以及传感器的表征和测量。该博士项目还将研究有助于克服传统PCR终点检测方法局限性的新方法，并介绍新兴的生物传感器技术以及新的平台材料和基底，如纸、以精确的电子读出取代光学读出检测方法，为数据处理、噪声过滤和更好地提取定量信息提供了机会。所提出的平台方法的主要优点包括：成本效益，生物相容性和环境可持续性。剑桥大学的PI小组与全球领先的工业和学术合作伙伴建立了强大的合作关系，候选人还将有机会与行业主要参与者接触，并向潜在的未来雇主展示。该博士学位由住友化学集团旗下的剑桥显示技术有限公司提供支持。

This PhD project aims to develop a new biosensor platform for Point-Of-Care (POC) diagnostics that enable sample in answer out devices for rapid nucleic acid test and molecular diagnostics. Both antigen-related immunoassays and PCR-related molecular diagnostic assays will be considered. Antigen-based immunoassays require more amount of protein biomarker than molecular diagnostics. Molecular diagnostics is rapidly growing with the increasing adoption of this technology in place of antigen testing by immunoassays. Molecular diagnostics also possess advantages such as high specificity which helps detect even minute amount of biomarkers. This is of crucial importance especially in early detection of infectious diseases, such as hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), Herpes Simplex Virus (HSV), tuberculosis, measles, dengue, Chagas, cholera, Sepsis and malaria.The project is Inspired by the seminal work done and led by the academic PI Dr. Luigi G. Occhipinti, University of Cambridge, Electrical Engineering Division, on various biosensor technologies including e.g. DNA Label-free Biosensors (Science of Adv. Materials 2011), on graphene-based sensors (J. of Applied Physics 2013), on Molecular Diagnostic assays (US Pat. Appl. 2014/0038193), on water-gated organic transistors (Flex. Print. Electron. 2016, 1, 025005), and more recently, in collaboration with clinical research teams at the University of Cambridge, on quantitative analysis of biocompatibility (Adv. Biosys. 2017), and discovery of enzymatic activity in extracellular vesicles, with potential applications in new anti-cancer therapies having no or limited side effects such as liver toxicity (Nature Chem. Biology, 2017).At the interface of biology, healthcare technology and bio-electronics, this project will open interesting new directions for ongoing academic research at the University of Cambridge, in collaboration with a strong industry team sponsoring the project, which is part of the global Sumitomo company.The project will focus on developing a multiplex real-time quantitative PCR device as proof of concept demonstrator of a POC diagnostic assay for Infection Disease, and to adapt current fluorescence-based real-time detection method to an electrical, impedance-based, biosensor array for quantification of target DNA amplicons during the exponential phase of the RT-qPCR. He/She will receive full training in advanced nanofabrication, sensor design, fabrication and characterization, including some printed electronics techniques. In addition, training on point of care diagnostic platforms, including some clinical application and validation aspects will be done, as well as characterization and measurement of sensors will be provided. Working alongside other researchers and students, the candidate will integrate various sensor and diagnostic modules to demonstrate new platform capabilities.The PhD project will also look at novel approaches that help overcome the limitations of conventional PCR end-point detection methods, and introduce emerging biosensor technologies as well as new platform materials and substrates, such as paper, to possibly replace optical readout detection methods with precise electrical readout, which provides opportunities for data processing, noise filtering and better extraction of quantitative information.The main advantages of the proposed platform approach include: cost-effectiveness, biocompatibility, and environmental sustainability.The PI group at University of Cambridge has strong collaborative linkages to leading global industrial and academic partners, the candidate will also have the opportunity to engage with industrial key players and showcase to potential future employers. This PhD is supported by Cambridge Display Technology Limited, part of Sumitomo Chemical group.