Next-generation surface-enhanced Raman scattering (SERS) nanoparticles for biodiagnostics and intraoperative imaging

My Ph.D. research focuses on the design of novel SERS nanotags with superior brightness, signal stability and mono-dispersibility for biomedical applications. Chapter 1 starts with a systematic introduction of SERS nanotags, including fundamental theories of SERS (Chapter 1.1), labeled and label-free SERS detection (Chapter 1.2), the design principles of SERS nanotags (Chapter 1.3), and their applications in bio-diagnostics, bioimaging and spectroscopy-guided surgery (Chapter 1.4). Chapter 2 to Chapter 6 discuss five of my research projects. In Chapter 2, aiming at improving signal robustness of dye-encoded SERS nanoparticles (NPs) in biological fluids, I introduced a hydrophobic inner layer on gold nanoparticle surface using an amphiphilic PEG. The hydrophobic domain brought a 5-10 times SERS intensity improvement compared with its PEG counterpart. The main mechanism behind was hypothesized to be a dielectric medium change at the plasmonic surface leading to electromagnetic enhancement. The rigid hydrophobic shell also provided better resistance to electric field coupling between nanoparticles in high-ionic-strength biological buffers, and prevented severe protein corona formation on SERS NPs, which consequently stabilized SERS signal in serum. In Chapter 3, to realize non-invasive metastatic sentinel lymph node detection by SERS, the hydrophobic locked Au nanostars (AuNS) were applied as the detection agents using a dual-tracer strategy to minimize the influence of non-specific binding. Good signal linearity and signal independency were achieved. The paired SERS agents show similar surface properties, hydrodynamic size and in-vivo lymph node binding kinetics. A whole spectrum identification algorithm was applied to identify the SERS signal of the paired SERS NPs respectively from the detected mixed signal. The presence of tumor cells at breast cancer metastatic sentinel lymph node was detected based on statistically significant different ratio of the target and non-target SERS NPs in health and tumor mice model. In Chapter 4, natural derived membranes from red blood cells (RBC) were employed as a novel type of biocompatible layer for SERS NPs. RBC membrane (RBCM) coating offered enhanced SERS intensity with the dyes embedded in the hydrophobic environment of the lipid bilayer. Good cryo-protection ability of the RBCM was observed against harsh storage conditions such as lyophilization and freezing of the colloids. With lipid-insertion strategy, RBCM coated SERS NPs can be further functionalized with target ligands, and an increased cellular uptake was demonstrated compared with the non-target controls. In Chapter 5, RBCM coated AuNSs are being used as a dual-modality imaging agent for both preoperative photoacoustic (PA) imaging and intraoperative SERS detection for tumor resection. Star-shaped AuNPs were chosen as the core of the imaging agents due to its superior SERS enhancement as well as energy conversion efficiency for PA compared with spherical nanostructures. A bovine tissue phantom experiment have proved excellent PA and SERS performance demonstrated by these NPs. Natural red-blood-cell membrane was shown to provide better biocompatibility by reducing macrophage uptake, and to realize target ligand conjugation by lipid-insertion strategy. An ex-vivo tissue tumor detection phantom study was then conducted to show the potential of RBCM-coated AuNSs as imaging agents for SERS-PA dual-modality. In Chapter 6, a quantitative evaluation of near-infrared (NIR) tissue penetration ex vivo with the use of SERS was first presented. A preliminary experiment to compare the spectral and tissue scattering properties of SERS in the first and second NIR windows was first performed. Tissue penetration depths were evaluated to be much improved in NIR-II window compared to that at of the first near-infrared (NIR-I) window, as well as a dramatically lower auto-fluorescence background. Aiming at developing SERS NPs excited at the second near-infrared (NIR-II) region for ‘bio-transparent’ in-vivo imaging, I successfully synthesized SERS nanostars with strong resonance in NIR-II range as well as small size around 60 nm for in-vivo purpose. The synthesized NIR-II AuNS with long and sharp tips exhibited strong SERS intensity with NIR-II resonant dye attached, and the high NIR-II absorbance was well preserved after 14 days with the inner hydrophobic layer. The NIR-II SERS AuNSs show great potential for a variety of biomedical applications such as intraoperative imaging, wearable spectroscopic devices development, etc.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Materials Science & Engr

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Xue, Ruiyang

Contributors dc:contributor

• Nie, Shuming
• Braun, Paul
• Leal, Cecilia Das Neves Barbosa
• Wang, Hua

• Surface-enhanced Raman scattering (SERS)
• Plasmonic nanoparticles
• Protection coating
• Cancer diagnostics
• Raman spectroscopy
• Bio-detection
• Image-guided surgery

Statement dc:rights

• Copyright 2022 Ruiyang Xue

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/115897

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F115897