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

PI：Lee，Jeunhoon提案编号：1706065医学科学面临的挑战之一是开发低成本的疾病即时诊断工具。 该研究项目涉及开发新的高灵敏度方法来检测作为疾病状态标志物的关键生物分子。 传感的机制是基于金纳米颗粒（直径为纳米级的颗粒）聚集体的分解，这些聚集体由DNA链保持在一起。 所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，利用纳米粒子聚集的挑战。 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功能化，这些分子可以针对不同类型的疾病。 如果成功，该方法将导致易于阅读的颜色变化，类似于怀孕测试，用于低成本的护理点癌症诊断，以及许多其他疾病。拟议的研究重点是创建一个由金纳米粒子（AuNP）聚集体的分解驱动的比色传感系统，与基于AuNP聚集的系统相比，该系统可以显着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低成本的即时诊断工具是非常有前途的，但是由于AuNP结合的DNA链的固有缓慢扩散和光学性质的可见变化所需的聚集体的大小，这种方法的采用受到缓慢速度和有限灵敏度的阻碍。基于AuNP聚集体分解的比色传感系统是解决速度和灵敏度的潜在解决方案。DNA反应网络是被编程以经历级联链置换反应的DNA链的混合物，其能够进行信号放大。拟议的努力将整合DNA反应网络与AuNP拆卸，以实现生物传感的高灵敏度。拟议的研究包括开发和优化AuNP拆卸过程，通过最大限度地减少DNA反应网络泄漏来最大限度地提高灵敏度和特异性，以及设计和测试用于检测更广泛生物分子的适体传感器。这项研究将显着提高基于AuNP的比色传感系统的性能并拓宽其在生物医学应用中的实用性。拟议的研究将使DNA反应网络与免疫测定竞争，并促进物理科学和工程之间的跨学科研究，涉及代表性不足的人群，如妇女，少数民族，第一代和非传统学生。

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.