CAREER: Integration of photonic crystals and paper-based microfluidics for biosensing

尽管诊断技术取得了重大进展，但人们强烈要求新的检测方法以高灵敏度识别特定的生物特征，并提供定量信息。在人体体液中循环的蛋白质生物标志物在临床上具有很大的潜力来指示疾病。到目前为止，低灵敏度和高成本仍然是阻碍基于量化低丰度疾病生物标志物的实用护理点诊断测试的关键挑战。在这个项目中，研究人员的目标是建立一个基于混合传感器的低成本、高灵敏度、多路、快速和自动化的范例，并结合可以执行疾病诊断的生物标记物分析的新的读出模式。该项目的重点是研究集成了光子晶体器件和纸基微流体的纸基纳米光子学，以及如何利用光子晶体所带来的独特光学现象来进行高灵敏度和高特异度的生物标志物检测。特别是，纳米光子器件与可以过滤和传输体液样本的纸衬底的廉价集成正在得到解决。传感器的低成本和一次性功能在资源有限的环境中是非常可取的，例如床边测试、远程军事部署和发展中国家。此外，传感器已经准备好进行改装，以检测引起严重疾病的致病物种，如肝炎、结核病和艾滋病毒。该项目还包括教育和推广活动，以培养本科生对研究的热情，吸引未被充分代表的少数族裔学生，并将科学和技术带到中西部的K-12学校和农业社区。快速和准确的诊断是医疗保健的基础，无论它是用于患有癌症等疾病的个别患者，还是用于全球流行。本项目的研究目标是建立一种基于混合器件和新的读出模式的低成本、高灵敏度、多路、快速、自动化的生物传感器，可以为临床诊断提供生物标志物分析。这个项目的变革性方面是为纸-光子晶体混合系统提供基本的见解和证据，这将使新的一次性发明成为可能。这项工作的创新之处在于两个方面：一是将光子晶体和纸作为流动传感平台的集成；二是基于光声学的读出方案的应用。特别是，该项目将根据以下三个具体研究目标通过数值模型和实验相结合的方式进行：i)光子晶体和纸基微流体的集成，ii)建立用于纸基生物传感器的光子晶体增强光声检测，以及iii)用于体外疾病诊断的多重检测。该项目的成果将通过解决具有挑战性的问题来填补光流体学和护理点测试之间的重大差距，这些问题包括：光子晶体-纸张混合系统中的流体传输现象是什么？光子晶体结构如何在纸基生物传感器中实现超高灵敏度？光声检测如何提高检测灵敏度，消除纸质基材的背景噪声？

Despite significant advances in diagnostic technologies, new tests are strongly demanded to identify a specific biological signature with high sensitivity and also provide quantitative information. Protein biomarkers circulating in human body fluids have a great potential to be used in the clinic to indicate diseases. To date, the poor sensitivity and high cost are still the key challenges prohibiting a practical point-of-care diagnostic test based on quantifying low-abundance disease biomarkers. In this project, the investigator aims to establish a low-cost, high sensitivity, multiplexed, rapid, and automated paradigm based upon a hybrid sensor in conjunction with a new readout modality that can perform biomarker analysis for disease diagnostics. The project focuses on investigating the paper-based nanophotonics that integrates photonic crystal devices and paper-based microfluidics, and on how to exploit the unique optical phenomena enabled by the photonic crystal for the biomarker detection with high sensitivity and specificity. In particular, the inexpensive integration of nanophotonic devices with paper substrates that can filter and transport body fluid samples is being addressed. The low-cost and disposable feature of the sensor is highly desirable in resource-limited settings, such as bedside test, remote military deployment, and developing countries. In addition, the sensor is ready to be modified for the detection of pathogenic species that causes server diseases, such as hepatitis, tuberculosis, and HIV. The project also includes education and outreach activities to foster undergraduate students' passion for research, engage underrepresented minority students, and bring science and technology to K-12 schools and agriculture communities in the Midwest.Rapid and accurate diagnostics is fundamental to healthcare, regardless of whether it is used for an individual patient with a disease, such as cancer, or for a worldwide epidemic. The research goal of this project is to establish a low-cost, high sensitivity, multiplexed, rapid, and automated biosensor based upon a hybrid device and a new readout modality that can perform biomarker analysis for clinical diagnostics. The transformative aspect of this project is to provide fundamental insights and evidence into the paper-photonic crystal hybrid system, which would enable the invention of new disposable. The novelty of the proposed works lies in two facts: i) the integration of photonic crystal and paper as a flow-through sensor platform and ii) the application of a photoacoustics-based readout scheme. In particular, the project will be carried out by combining numerical models and experiments according to the following three specific research objectives: i) integration of photonic crystal and paper-based microfluidics, ii) establishment of photonic crystal-enhanced photoacoustic detection for paper-based biosensor, and iii) multiplexed detection for in-vitro disease diagnostics. The project outcome will fill a significant gap between optofluidics and point-of-care tests by addressing challenging questions including: What are the fluid transport phenomena in a photonic crystal-paper hybrid system? How can photonic crystal structure enable ultrahigh sensitivity in paper-based biosensors? How can the photoacoustic detection improve the detection sensitivity and eliminate background noises from paper substrates?