Development of an electrochemical sensor platform for diagnosis and monitoring of oesophageal cancer at the point of care

目前，大多数癌症诊断检测都是在中央实验室进行的，使用侵入性采样和昂贵的设备，需要训练有素的人员进行操作。“芯片实验室”和生物传感器技术的使用正在将这种基于实验室的测试模式转向护理点（POC）诊断。然而，有效的POC测试方法对生物传感器的开发提出了严格的要求和挑战。尽管电子学和微制造技术取得了巨大的发展，但生物传感领域的进展很少转化为改善癌症诊断。它仍然是一个挑战，开发便携式，低成本的生物传感平台，可以同时检测多种分析物从复杂的生物流体。对于该项目，将研究基于有机电化学晶体管（OECT）的生物传感器，该生物传感器能够直接从非侵入性临床样本中检测多种生物标志物，用于对有食管癌风险的患者进行分层。用于多分析物检测的非侵入性、成本有效的解决方案的开发将使得能够对患者进行周期性、纵向测试。这可以通过跟踪导致癌症的事件和监测治疗或压力的影响来更好地了解癌症的进展。目的：本项目的目的是证明一种合适的传感器平台，用于在护理点直接从非内窥镜样本中检测临床生物标志物的多分析物。因此，该项目旨在弥合临床需求与尖端技术开发之间的差距，为改善患者护理和管理提供有效的解决方案。研究方法：最初的目标是对重要的生物标志物进行分层，并获得其在临床样本中的丰度水平。了解传感器所需的检测动态范围后，将研究几种基于OECT的方法，以达到所需的灵敏度/特异性水平。还将研究OECTs的纳米颗粒功能化，以提高OECTs检测结合事件（核酸和蛋白质）的灵敏度，并探索分析物的多重检测。在优化开发的传感器平台后，将研究设计方法，以有效地应用传感器在护理点。合作：OECT阵列的制造和随后的功能化纳米材料的掺入将在Roisin Owens博士（生物电子系统技术组）的专家监督下进行。将在Rebecca Fitzgerald教授（MRC癌症部门）的指导下对生物标志物进行分层，以实现最佳治疗、样本采集和处理以及传感器验证，以确保正在开发的器械的临床实用性。最后，为了使纳米材料的生物功能化能够成功地用于不同目标物种的多重分析，与Ljiljana Fruk博士（BioNano Engineering Group）建立了合作关系。研究领域：拟议的工作属于EPSRC的“医疗技术”主题的范围，并且与EPSRC指南中规定的以下研究领域保持一致-临床技术，分析科学和传感器与仪器。

Most of diagnostic testing for cancer is currently carried out in centralized laboratories, using invasive sampling and expensive equipment that requires highly trained personnel to operate. The use of "lab-on-a-chip" and biosensor technologies is shifting this paradigm of laboratory-based testing towards point-of-care (POC) diagnostics. Effective POC testing methods however pose stringent requirements and challenges for biosensor development. Despite the vast developments in electronics and microfabrication, little of the progress in the field of biosensing has translated to improved diagnosis of cancer. It remains a challenge to develop portable, low-cost biosensing platforms that can detect multiple analytes simultaneously from complex biological fluids. For this project, an organic electrochemical transistor (OECT) based biosensor will be investigated with the ability to detect multiple species of biomarkers, directly from non-invasive clinical samples for stratification of patients at risk of developing oesophageal cancer. The development of non-invasive, cost effective solutions for multi analyte detection would enable periodic, longitudinal testing of patients. This could be used to better understand the progression of cancer by tracking the events leading up to cancer and monitoring effects due to therapy or stress. Aims:The aim of this project is to demonstrate a suitable sensor platform for multianalyte detection of clinical biomarkers directly from non-endoscopic samples, at the point of care. The project will therefore aim to bridge the gap between clinical need and cutting-edge technology development to produce an effective solution for improved patient care and management. Research Methodology:The initial objective will be the stratification of significant biomarkers, and to obtain their level of abundance in clinical samples. With an understanding of the required dynamic range of detection for the sensor, several OECT-based approaches will be investigated to achieve the required levels of sensitivity/specificity. Nanoparticle functionalisation of OECTs will also be investigated to improve the sensitivity of OECTs to detect binding events (of nucleic acid and protein), and to explore multiplexed detection of analytes. Upon optimisation of the developed sensor platform, design approaches will be investigated for the effective application of the sensor at the point of care.Collaborations:Fabrication of the OECT array and subsequent incorporation of functionalized nanomaterials will be carried out under the expert supervision of Dr. Roisin Owens (Bioelectronic Systems Technology Group). Stratification of biomarkers for optimal treatment, sample acquisition and handling, and sensor validation will be carried out under the guidance of Prof. Rebecca Fitzgerald (MRC Cancer Unit), to ensure the clinical utility of the device being developed. Finally, to enable successful biofunctionalization of nanomaterials for multiplexed analysis of different target species, a collaboration with Dr. Ljiljana Fruk (BioNano Engineering Group) has been setup.Research Area:The proposed work lies within the purview of the EPSRC's 'Healthcare Technologies' theme and it is in alignment with the following areas of research, as stated in the EPSRC guidelines - Clinical Technologies, Analytical Science, and Sensors & Instrumentation.