Photonic crystal enhanced fluorescence for single-molecule biosensing and early disease detection

Xiong, Yanyu

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https://hdl.handle.net/2142/125743 Copy

Description

Title

Photonic crystal enhanced fluorescence for single-molecule biosensing and early disease detection

Author(s)

Xiong, Yanyu

Issue Date

2024-06-27

Director of Research (if dissertation) or Advisor (if thesis)

Cunningham, Brian T.

Doctoral Committee Chair(s)

Cunningham, Brian T.

Committee Member(s)

• Selvin, Paul R.
• Smith, Andrew M.
• Gruev, Viktor

Department of Study

Electrical & Computer Eng

Discipline

Electrical & Computer Engr

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Photonic Crystal
• Quantum Dots
• Single-molecule
• Fluorescence Imaging
• DNA Nanotechnology
• DNA Origami
• Biosensing
• Early Disease Detection
• Nanophotonics
• Metamaterials
• Microscopy

Abstract

This dissertation presents a comprehensive strategy for revolutionizing biosensing through Photonic Crystal Enhanced Fluorescence (PCEF) for ultrasensitive, highly selective, multiplexed biodetection. This technology offers cost-effective and accessible solutions, particularly tailored for non-invasive liquid biopsies in early disease detection and monitoring of cancers and viral infections. This ambitious objective is systematically deconstructed into three pivotal components: 1. Enhancing Sensitivity and Signal-to-Noise Ratio through Fluorescence Amplification using Nanophotonics: The foundation of this thesis lies in developing nanophotonic and plasmonic structures to amplify light-matter interactions, allowing for single-molecule detection with improved signal-to-noise ratios without complex optical systems. The first part of the thesis presents a novel all-dielectric photonic crystal (PC) surface, a cost-effective and versatile substrate for quantum dot (QD) fluorescence microscopy. The fluorescence enhancement, reaching up to 3000-fold, results from enhanced excitation, directional extraction, improved quantum efficiency, and blinking suppression through precise radiative engineering. This enables low-intensity, low-NA lens single-QD imaging and the sensitive, selective detection of prostate cancer-related microRNAs in plasma, down to 10 attomolars. Additionally, the PC significantly increases QDs' on-time, from 15% to 85%, improving signal consistency and enabling fast, single-particle motion tracking, crucial for ultrasensitive measurements. Further advancements were made through the development of a Plasmonic-Photonic Hybrid system, which synergistically combined the sub-diffraction spatial control capabilities of plasmonic nanoantennas with the high-quality factor of PCs, achieving targeted fluorescence signal amplification. 2. Achieving High Selectivity with Novel Sensing Probe Designs Using Programmable DNA Nanostructures: The second phase of this thesis addresses the need for highly selective detection by introducing innovative sensing probes made from programmable DNA nanostructures. These probes are designed with specific aptamers that trigger fluorescent signals only upon recognizing their target molecules. This method combines the precision of dynamic DNA origami structures with the signal amplification afforded by photonic crystal metasurfaces, achieving a 10,000-fold signal enhancement compared to traditional single fluorophores probe on glass. As a consequence of nearly-zero off-target signal, we achieve a limit of detection (LoD) of 100 viral genome copies/mL in human saliva solution. This approach not only improved the limit of detection by avoiding non-specific binding and off-target signal but also showcased a rapid, sensitive, and cost-effective method for SARS-CoV-2 virus detection using a designed DNA nano-machine, marking a significant advancement in the field of pandemic preparedness and response. 3. Advancing Multiplexing Sensing Capabilities with Novel Imaging Methods: The final component of this thesis addresses the critical challenge of multiplexing in robust clinical diagnostics. Traditional methods necessitate large volumes of blood samples for the detection of numerous targets in multiple tests, an impractical demand for frequent testing, especially in cancer screening and monitoring. This research presents innovative imaging and sensing methodologies that enable the simultaneous detection of multiple biomarkers within a single, minimal-volume sample reservoir. By leveraging the unique properties of PCs, this approach circumvents the reliance on spectrometry, differentiates QD wavelengths using distinct extraction angles, and aims for a breakthrough in high-throughput, highly multiplexed miRNA detection.

Graduation Semester

2024-08

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/125743

Copyright and License Information

© 2024 Yanyu Xiong

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