A Self-Contained Optical Heterodyned Second Harmonic Sensor

在化学系化学测量和成像项目的支持下，以及CBET生物传感器项目的部分共同资助下，犹他大学的John Conboy教授和他的研究小组正在开发一种新型光学生物传感器，能够检测和定量各种生物分子。拟议的研究寻求一种可靠、高灵敏度、多路复用、无标记的生物传感器，用于分析血液、血清、尿液或其他液体中的生物标志物。该方法可提高生物制剂的临床诊断和现场检测。与研究相结合的是对研究生和本科生进行生物分析/生物物理方法和技术的教育。该团队还参与了地区学校的外展活动，旨在吸引学生，包括来自代表性不足群体的学生，从事STEM（科学、技术、工程和数学）职业。对能够检测和定量生物标志物的分析方法的需求是明确的。抗体具有优良的化学特异性和高亲和力，非常适合生物特异性检测和定量。然而，由于难以感知捕获事件，在非竞争性免疫分析中利用抗体直接无标记检测低分子量生物标志物是一个主要的技术挑战。Conboy小组正在使用非线性光学二次谐波生成（SHG）技术开发一种高灵敏度、无标记的生物标志物生物传感器。这种生物传感器的一个关键方面是一种独特的光学外差检测系统，它显著增强了其他微弱的SHG响应。这种新颖的传感器方法能够用pi电子检测大多数目标，这使得它对许多感兴趣的生物标志物敏感，创造了一种高度通用的，无标签的检测方式。该项目正在开发的方法有望提供一种独特的分析方法，既不影响灵敏度，又提供一种具有成本效益和灵活的无标签非竞争性生物标志物免疫测定。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, and partial co-funding from the Biosensors Program in CBET, Professor John Conboy and his research group at the University of Utah are developing a novel optical biosensor capable of detecting and quantitating a wide range of biological molecules. The proposed research seeks a reliable, highly sensitive, multiplexed, label-free biosensor for analytes such as biomarkers found in blood, serum, urine, or other fluids. The approach can enhance clinical diagnostics and field detection of biological agents. Integrated with the research is education of both graduate and undergraduate students in bioanalytical/biophysical methods and techniques. The team is also engaged in outreach to regional schools, aiming to attract students, including students from underrepresented groups, to STEM (science, technology, engineering and mathematics) careers.The need for analytical methods capable of biomarker detection and quantification is clear. Antibodies, with their exquisite chemical specificity and high affinity, are exceptionally well-suited for bio-specific detection and quantification. However, utilizing antibodies for the direct label-free detection of low molecular weight biomarkers in a noncompetitive immunoassay represents a major technical challenge due to the difficulty of sensing the capture event. The Conboy group is using the nonlinear optical Second Harmonic Generation (SHG) technique to develop a highly sensitive, label-free biomarker biosensor. A key aspect of this biosensor is a unique optical heterodyned detection system which significantly enhances the otherwise weak SHG response. This novel sensor approach is capable of detecting most targets with pi-electrons, which makes it sensitive to many biomarkers of interest, creating a highly versatile, label-free detection modality. The methodology under development in this project is expected to provide a unique analytical approach that does not compromise sensitivity, yet provides a cost-effective and flexible label-free noncompetitive biomarker immunoassay.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.