Collaborative Research: An Enzyme-free Amplification Technique for Ultrasensitive ELISA of Disease Biomarkers

合作研究：疾病生物标志物超灵敏 ELISA 的无酶扩增技术

• 批准号: 1804742
• 负责人: Zhihong Nie
• 金额: $ 19.98万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1804742&HistoricalAwards=false
• 关键词: Collaborative; Research; Enzyme; free; Amplification

Technologies for diagnosis of diseases are essential to the improvement of our standard of living. Increasing detection sensitivity of a diagnostic technology can enable earlier diagnosis of diseases especially cancers and infectious diseases, thus improving treatment outcomes. The goal of this project is to establish a highly sensitive diagnostic platform through the development of a nanoparticle-based signal amplification technique. The broader impacts of the proposed research program include multidisciplinary training for graduate and undergraduate students particularly from underrepresented groups, as well as outreach activities such as mentoring local high-school students and student exchange between two institutes in summer.Enzyme-linked immunosorbent assay (ELISA) technology has been extensively used in research labs and clinical diagnostics for decades. However, its limit of detection has not been substantially improved in recent years. The proposed work seeks to develop a novel enzyme-free signal amplification technique that can substantially enhance the detection sensitivity of ELISA. This technique relies on the release of millions of tiny nanoparticles preloaded in gold vesicles. Each released nanoparticle can catalyze colorimetric reaction more effectively than a commonly-used enzyme in an ELISA. By substituting enzymes in a conventional ELISA with such nanoparticles-encapsulated gold vesicles, an enzyme-free ELISA with substantially enhanced sensitivity is established. To optimize the signal amplification system and thus enhance the detection sensitivity of associated enzyme-free ELISA, physicochemical properties of both nanoparticles and gold vesicles will be carefully controlled. To achieve the goal of this project, following research aims will be pursued: 1) Building the nanoparticles based signal amplification system; 2) Establishing the enzyme-free ELISA; and 3) Applying the enzyme-free ELISA to detecting human blood samples spiked with biomarker standards. The signal amplification technique is expected to impact the general field of in-vitro diagnostics and find a broad range of applications in biomedicine. This project will benefit the engagement of graduate and undergraduate students, especially women and minorities, into research. The research will also be integrated into outreach activities for K-12 students.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.

疾病诊断技术对于提高我们的生活水平至关重要。提高诊断技术的检测灵敏度可以实现疾病尤其是癌症和传染病的早期诊断，从而改善治疗结果。该项目的目标是通过开发基于纳米颗粒的信号放大技术来建立高度灵敏的诊断平台。拟议研究计划的更广泛影响包括对研究生和本科生（特别是来自代表性不足群体的学生）进行多学科培训，以及外展活动，例如指导当地高中生以及夏季两个机构之间的学生交流。酶联免疫吸附测定（ELISA） ）技术几十年来已广泛应用于研究实验室和临床诊断。然而，近年来其检出限并未得到实质性提高。这项工作旨在开发一种新型的无酶信号放大技术，可以显着提高 ELISA 的检测灵敏度。该技术依赖于金囊泡中预装的数百万个微小纳米颗粒的释放。每个释放的纳米颗粒都可以比 ELISA 中常用的酶更有效地催化比色反应。通过用这种纳米颗粒封装的金囊泡替代传统 ELISA 中的酶，建立了灵敏度大大提高的无酶 ELISA。为了优化信号放大系统，从而提高相关无酶 ELISA 的检测灵敏度，需要仔细控制纳米颗粒和金囊泡的理化性质。为实现本项目的目标，将实现以下研究目标： 1）构建基于纳米颗粒的信号放大系统； 2）建立无酶ELISA； 3) 应用无酶 ELISA 检测添加了生物标志物标准品的人体血液样本。信号放大技术预计将影响体外诊断的一般领域，并在生物医学中找到广泛的应用。该项目将有利于研究生和本科生，特别是女性和少数族裔参与研究。该研究还将纳入针对 K-12 学生的外展活动。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。