Development of photoelectrochemical DNA biosensors based on plasmonic/photoelectrochemcial interactions

生物传感器是用于检测和/或量化生物分析物（例如核酸、蛋白质和代谢物）以管理疾病和监测健康的装置。手持式生物传感器将这种分析能力带到患者的床边、患者的家中、当地诊所以及一般的护理点，被设想为通过实现预防性的、加速的和以患者为中心的临床决策来显著提高医疗保健的质量，同时降低其成本。核酸如DNA和RNA是重要的预测、早期诊断和治疗选择以及监测生物标志物，并且正在努力创建手持式核酸生物传感器。尽管有这些努力，目前还没有用于疾病管理的在功能上类似于电化学葡萄糖监测器的市售手持式核酸生物传感器。创建手持式核酸生物传感器的困难在于，一方面，它们需要满足临床决策所需的灵敏度、特异性和多重性;另一方面，它们需要通过便携式、快速、易于使用和廉价的平台提供这些，这些平台适用于非实验室环境。开发光电化学信号转导领域的新知识，以满足手持式核酸生物传感器的要求，是本研究计划的中心。光电化学核酸生物传感器使用光活性材料将核酸杂交转化为电流的变化。与使用电信号进行激发和测量的广泛开发的电化学对应物相比，这些设备提供了更大的信噪比。此外，考虑到信号读出是电完成的，光电化学传感器仍然受益于多路复用的容易性和电化学装置可用的廉价读出仪器。我们提出了一种新的光电化学生物传感器的基础上发现的光电化学和等离子体材料之间的短程（<20 nm）的相互作用。在该感测策略中，核酸杂交导致等离子体纳米颗粒从光电化学材料附近移除，这将产生所产生的光电化学电流的增加。此外，基于DNA自组装的内置信号放大策略将首次被纳入此类生物传感器中，以增强所产生的电流和设备的分析灵敏度。拟议的研究将使我们能够产生新的知识，用于开发基于光电化学/等离子体相互作用的第一个多路复用核酸生物传感器，以满足即时护理生物传感器的要求。

Biosensors are devices used to detect and/or quantify biological analytes such as nucleic acids, proteins, and metabolites for managing diseases and monitoring health. Handheld biosensors that bring this analytical capability to the patients' bedsides, patients' homes, local clinics, and in general, the point-of-care, are envisioned to significantly improve the quality of healthcare while reducing its cost by enabling preventive, expedited, and patient-centered clinical decision making. Nucleic acids such as DNA and RNA are important predictive, early diagnosis, and treatment selection and monitoring biomarkers, and there is an ongoing effort towards creating handheld nucleic acid biosensors. In spite of these efforts, there are currently no commercially-available handheld nucleic acid biosensors, similar in functionality to electrochemical glucose monitors, for disease management. The difficulty in creating handheld nucleic acid biosensors is that on one hand, they are required to meet the sensitivity, specificity and multiplexing required for clinical decision making; and, on the other hand, they need to offer these through portable, rapid, easy-to-use, and inexpensive platforms that are suitable for use in non-laboratory settings. Developing new knowledge in the field of photoelectrochemical signal transduction for addressing the requirements of handheld nucleic acid biosensors is at the center of this research program.***Photoelectrochemical nucleic acid biosensors use photo-active materials to translate nucleic acid hybridization into changes in electrical currents. These devices offer a larger signal-to-noise ratio compared to their widely-explored electrochemical counterparts that use electrical signals for excitation and measurement. Furthermore, given that signal readout is done electrically, photoelectrochemical sensors still benefit from the ease of multiplexing and the inexpensive readout instrumentation available to electrochemical devices. We propose to develop a novel photoelectrochemical biosensor based on the newly discovered short range (<20 nm) interactions between photoelectrochemical and plasmonic materials. In this sensing strategy, nucleic acid hybridization causes a plasmonic nanoparticle to be removed from the vicinity of the photoelectrochemical material, which will generate an increase in the generated photoelectrochemical current. Furthermore, built-in signal amplification strategies, based on DNA self-assembly, will be incorporated for the first time within this class of biosensors to enhance the generated current and the analytical sensitivity of the device. The proposed research will allow us to generate new knowledge for developing the first multiplexed nucleic acid biosensor based on photoelectrochemical/plasmonic interactions, for meeting the requirements of point-of-care biosensors.