Rapid colorimetric detection of biomarkers via catalytic disassembly of gold nanoparticle aggregates

通过金纳米粒子聚集体的催化分解快速比色检测生物标志物

• 批准号: 1706065
• 负责人: Jeunghoon Lee
• 金额: $ 30.34万
• 依托单位: Boise State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1706065&HistoricalAwards=false
• 关键词: Rapid; colorimetric; detection; biomarkers; via

PI: Lee, JeunghoonProposal No: 1706065 One of the challenges for medical science is to develop low-cost, point-of-care diagnostic tools for diseases. This research project involves developing new, high sensitivity approaches to detect key biological molecules that are markers for disease states. The mechanism for sensing is based upon the disassembly of gold nanoparticle (particles that have diameters on the order of nanometers) aggregates held together by DNA strands. The proposed approach provides key advantages to overcome the challenges of conventional color-based sensing technologies that utilize nanoparticle aggregation. One advantage is that the disassembly mechanism should be less prone to false positives. Another is the fact that the surfaces of the nanoparticles can be functionalized with different special recognition molecules that can target different types of diseases.  If successful, the proposed method will result in an easy-to-read color change, similar to a pregnancy test, for low-cost point-of-care cancer diagnostics, among many other diseases. The proposed research focuses on creating a colorimetric sensing system driven by disassembly of gold nanoparticle (AuNP) aggregates that can significantly increase the speed and the sensitivity of biosensing compared to those based on AuNP aggregation. While colorimetric sensing based on AuNP aggregation is very promising as a low-cost, point-of-care diagnostic tool, adoption of this approach has been hindered by slow speed and limited sensitivity due to the inherently slow diffusion of AuNP-bound DNA strands and the size of aggregates required for visible changes in optical properties. A colorimetric sensing system based on the disassembly of AuNP aggregates is a potential solution to address both speed and sensitivity. A DNA reaction network, which is a mixture of DNA strands programmed to undergo cascading strand displacement reactions, is capable of signal amplification. The proposed effort will integrate DNA reaction networks with AuNP disassembly to achieve high sensitivity in biosensing. The proposed research consists of developing and optimizing AuNP disassembly process, maximizing sensitivity and specificity by minimizing DNA reaction network leakage, and designing and testing aptamer transducer for detecting a wider variety of biomolecules. This research will significantly improve the performance and broaden the utility of AuNP-based colorimetric sensing systems in biomedical applications. The proposed research will make DNA reaction networks competitive with immunoassays, and promote interdisciplinary research between physical sciences and engineering that involves underrepresented populations, such as women, minority, first-generation, and non-traditional students.

PI：Lee，JeunghoonProposal No：1706065医学科学面临的挑战之一是开发针对疾病的低成本、定点诊断工具。这项研究项目涉及开发新的、高灵敏度的方法来检测作为疾病状态标志的关键生物分子。传感的机制是基于由DNA链结合在一起的金纳米颗粒(直径在纳米量级的颗粒)的分解。提出的方法提供了关键的优势，以克服传统的基于颜色的传感技术的挑战，利用纳米颗粒聚集。一个优点是，拆卸机制应该不太容易出现误报。另一个事实是，纳米颗粒的表面可以用不同的特殊识别分子来功能化，这些分子可以针对不同类型的疾病。如果成功，建议的方法将导致易于阅读的颜色变化，类似于怀孕测试，用于低成本的医疗保健点癌症诊断，以及许多其他疾病。这项研究的重点是建立一种基于金纳米粒子聚集体分解的比色传感系统，与基于金纳米微粒聚集体的生物传感系统相比，该系统可以显著提高生物传感的速度和灵敏度。虽然基于AuNP聚集的比色传感作为一种低成本的护理点诊断工具非常有前途，但由于AuNP结合的DNA链固有的缓慢扩散和可见光学性质变化所需的聚集体的大小，这种方法的采用受到了速度慢和灵敏度有限的阻碍。基于AuNP聚集体分解的比色传感系统是一种解决速度和灵敏度问题的潜在解决方案。DNA反应网络是一种DNA链的混合物，它被编程为经历级联链置换反应，能够进行信号放大。这项拟议的工作将把DNA反应网络与AuNP分解结合起来，以实现生物传感的高灵敏度。建议的研究包括开发和优化AuNP拆解过程，通过最小化DNA反应网络泄漏来最大化灵敏度和特异度，以及设计和测试适体换能器以检测更多种类的生物分子。本研究将显著提高基于AuNP的比色传感系统的性能，拓宽其在生物医学应用中的应用。这项拟议的研究将使DNA反应网络与免疫分析竞争，并促进物理科学和工程学之间的跨学科研究，涉及女性、少数族裔、第一代和非传统学生等代表性不足的人群。

项目成果

Availability-Driven Design of Hairpin Fuels and Small Interfering Strands for Leakage Reduction in Autocatalytic Networks

• DOI: 10.1021/acs.jpcb.0c01229
• 发表时间: 2020-04-23
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY B
• 影响因子: 3.3
• 作者: Lysne, Drew;Jones, Kailee;Graugnard, Elton
• 通讯作者: Graugnard, Elton