Document Type



Doctor of Philosophy (PhD)



First Advisor's Name

Jin He

First Advisor's Committee Title

committee chair

Second Advisor's Name

Xuewen Wang

Second Advisor's Committee Title

committee member

Third Advisor's Name

Hebin Li

Third Advisor's Committee Title

committee member

Fourth Advisor's Name

Yuan Liu

Fourth Advisor's Committee Title

committee member


SERS, Raman, single molecule, biological, single cell

Date of Defense



Surface-enhanced Raman spectroscopy (SERS) is a surface analytical technique, which enhances the Raman signal based on the localized surface plasmon resonance (LSPR) phenomenon. It has been successfully used for single molecule (SM) detection and has extended SERS to numerous applications in biomolecular detection. However, SM detection by SERS is still challenging especially with traditional SERS substrates and detection methods. In addition, the fundamental understanding of the SERS enhancement mechanism is still elusive. Furthermore, the application of SERS in biological field is still in the early stage. To address these challenges, there are two main aspects of SERS studied in my dissertation: (a) fundamental aspects through systematic experimental studies combined with simulations, which focus on SM detection, Raman enhancement mechanisms, and (b) the development and optimization of the SERS-based nanoprobe for biomarkers detection from fluidic devices to a single cell.

In my dissertation, the following studies have been investigated. First, the sensitivity of a home-made SERS instrument was tested. SM detection was realized by utilizing a highly curved nanoelectrode (NE) to limit the number of attached nanoparticle (NP), which will allow us to have even a single NP on NE (NPoNE) junction in the SERS detection area. The molecule number in a single NPoNE junction which contributes to SERS can be hundreds or even SM. In this first study, we also conducted a correlation study between electrochemical current and SERS to monitor the dynamic formation of the plasmonic junctions. Second, we investigate electromagnetic and chemical enhancement factor tuning by the electrode potential with the assistant of Au@Ag core-shell NPs. The electrode potential induced electromagnetic enhancement (EME) tuning in the Au@Ag NPoNE structure has been confirmed by 3D Finite-difference time-domain (FDTD) simulations. Last is the design of a SERS-based nanoprobe for biomarkers detection and the effort towards single cell analysis. Finally, several SERS-active substrates were examined for biomarkers (H+, glucose, and H2O2) detection, including gold NPs (AuNPs) colloid and AuNPs decorated glass nanopipette.

In summary, my dissertation presents the fabrication and development of gold tip nanoelectrode for chemical detection, which can achieve SM sensitivity. SM SERS can be used to improve the fundamental understanding and provide more in-depth insight into mechanisms of SERS and the chemical behaviors of SM on surfaces and in plasmonic cavities. Second, the fabrication and optimization of SERS-active, flexible nanopipette for biological applications. The flexible nanopipette probe provides a platform for reliable detection and quantitative analysis of biomarkers at a single cell level, which is critical and vital for detecting diseases earlier and understanding the fundamental biological process better.



Previously Published In

1. J. Guo, J. Pan, S. Chang, X. Wang, J. He (2018) “Monitoring the Dynamic Process of Formation of Plasmonic Molecular Junctions during Single Nanoparticle Collisions.” Small 14(15): 1704164.

2. J. Guo, A. Rubfiaro, Y. Lai, J. Moscoso, F. Chen, Y. Liu, X. Wang, J. He (2020) “The Dynamic Single-Cell Intracellular pH Sensing by a SERS-Active Nanopipette” Analyst 145(14): 4852-4859.

Included in

Physics Commons



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