| Author: | Ho, Kwun Hei Willis |
| Title: | Pathological biomarker detection via SERS based sensing platform |
| Advisors: | Yang, Mo (BME) |
| Degree: | Ph.D. |
| Year: | 2023 |
| Subject: | Biosensors Surface plasmon resonance Raman effect, Surface enhanced Nanotechnology Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Biomedical Engineering |
| Pages: | xvi, 141 pages : color illustrations |
| Language: | English |
| Abstract: | Accurate and sensitive biosensors are designed for reporting a specific biomolecule or a particular biological event through chemical/physical signal transduction. The target analytes are usually from biological origin, ranging from small molecules such as nucleotides and metabolic substances to pathological proteins. Those biosensing methods are of paramount importance for various applications such as clinical disease diagnosis, drug discovery and environment toxin monitoring. In order to develop an efficient biosensor, instrumentation designs and sensing strategies remain as a major research direction for scientists. Benefited from the small-size, manipulatable surface and enhanced light-matter interactions. Nanophotonic technologies are regarded as a promising strategy for advanced biosensor development. While SERS emerges as an exciting biomolecular probing tool which is strongly favoured by chemist and biologists, since the “fingerprint” SERS signal is highly specific, and it could be substantially enhanced by plasmonic nanostructure. In this thesis, the plasmonic biosensing methods will be briefly discussed and it is followed by summarization of three SERS-based studies for pathological biomarker detection. 1.Buoyant Plasmonic MB platform for protein detection via matched frequency SERS Buoyant plasmonic substrate with PVA based microbubble (MB) was synthesized by in-suit reduction of Au nanoclusters on MB surface (Au/MB). Benefited with buoyant and infrared plasmonic features, Au/MB can serve as an ideal substrate for biomolecular study via SERS. We demonstrated nano-stress sensing method to detect Aβ 1-40 detection with the Cu2+/4-MBA functionalized Au/MB platform. Our results stressed that the Aβ 1-40 protein size is of high importance to cause signal changes on 4- MBA SERS spectrum due to coordination complex formation between Aβ protein and Cu2+ ion causing the deformation on the 4-MBA molecules. These spectroscopic changes allow us to detect Aβ1-40 down to 1x10-9 M. We also studied the conformation change of the SERS reporter (4-MBA), as evidenced by spectroscopic changes the 4-MBA molecules adopted different orientation when Cu2+/4-MBA is incubated with the Aβ1-40. This work shows the prepared Au/MB is a novel SERS platform for biomolecular sensing but also provide fundamental spectroscopic insight for constructing nano-stress sensing platform interaction. 2.Magnetic-Responsive Surface-Enhanced Raman Scattering Platform with adjustable Hot Spot for Ultrasensitive Virus Nucleic Acid Detection Sandwiched strategy for sensitivity long-chain nucleic acid remains inaccessible for SERS based biosensor such that the large size molecules or long oligonucleotide limit the Raman signal enhancement through optical coupling strategy. In this study, we demonstrated a long-chain N-cDNA gene nucleic acid detection via a magnetic-responsive SERS substrate. This sandwiched assay is constructed with a superparamagnetic iron oxide nanoparticle (SPIONs) and it allows us to reduce the coupling distance between the Raman reporter Au nanoparticle (AuNPs) and the plasmonic substrate. With the magnetic modulation, this SERS sensing platform achieved a 10 times detection N-cDNA sensitivity improvement with limit of detection (LOD) down to 100 aM. Also, the SERS signal showed a high detection selectivity towards the N-cDNA. To further support the result, we conducted a numerical electrodynamic simulation and nucleotide length dependent study to show that the reduced coupling distance plays a key role in improving detection sensitivity of this magnetic modulated SERS platform. 3.Her-2 Positive Exosome detection via dual mode dual mode microfluidic based aptamer sensor. In the project, we proposed an aptamer based dual module sensing for Her-2 positive exosome detection. Our design relies on GNP aggregation due the salting process. The aggregation leads to the observable bulk colour change of the GNP solution, and this colorimetric module allows us to have an exosome concentration signal readout either by naked eyes and UV-vis spectra, and the detection sensitivity for Her 2 positive SKBR 3 exosome is around log10 concentration 5.5 particles/mL. On the other hand, the aggregation of GNP also allows the exosome detection though SERS signal. In comparing to colorimetric module, The SERS detection module had improved the detection sensitivity for more than 1 order of magnitude (~log10 concentration 4 particles/mL). This improvement can be explained by the FDTD simulation that the aggregated provided a remarkable SERS signal enhancement (E/Eo)2 on the surface of the GNP. We also demonstrated that both colorimetric and SERS module has a great sensing specificity. With Her 2 aptamers, the SKBR 3 exosomes induce a much stronger signal than the other exosome derived from MCF-7 and NP 460 cell lines. More importantly, we realized a high throughput, automated Her 2-exosome detection by integrating SERS module into the droplet based microfluidic chip and it demonstrated that this chip is capable for continuous Her-2 exosome screening by measuring the SERS signal of the microdroplet. |
| Rights: | All rights reserved |
| Access: | open access |
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