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

PI: Lee, Jeunghoon

Proposal 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.