Abstract
Since the birth of the first plasmonic-based sensor in 1990, the plasmonic detection field has witnessed decades of development and continuous improvement. Gold (Au) and silver (Ag) have first been investigated in many aspects because of their excellent plasmonic behavior and efficient structure control methods. However, poor abrasion-resistance of Au and readily oxidization of Ag made these sensor chips not durable. Thus, one major challenge in the widespread use of plasmonic materials lies in the sustainability of the constructed sensors, namely, using a solid plasmonic material as sensor chips, both physically and chemically. Therefore, there is an incentive for researchers to keep finding emerging plasmonic substrate materials. Titanium compounds, e.g., titanium nitride (TiN) and titanium dioxide (TiO2), can be excellent candidates in this respect.Firstly, three different TiN nanostructures, i.e., TiN film on glass (f-TiN), TiN film onto a roughened glass (R-TiN), and TiN film with nanoholes (NH-TiN), with different surface roughness were successfully synthesized and evaluated as plasmonic biosensing substrates. TiN, as an alternative plasmonic ceramic material with superb properties including high hardness, outstanding corrosion resistance, and excellent biocompatibility, has exhibited great potential for optical biochemical sensing applications. Based on these synthesized TiN based sensor chips, the surface plasmon resonance (SPR) and localized surface plasmon resonance (LSPR) sensing properties were systematically compared. It was found that the constructed surface roughness and localized plasmonic field can directly improve the sensing performance. In detail, the calculated refractive index resolution (RIR) of the optimal NH-TiN sensors for NaCl was found to be 9.5×10-8 refractive index unit (RIU), which had outperformed the f-TiN and R-TiN sensors. For biosensing, the optimized NH-TiN sensor was found to be capable of detecting both small and large biomolecules, i.e., biotin (molecular weight of 244.3 g/mol) and human IgG (160,000 g/mol), in a label-free manner. Especially, the NH-TiN sensor significantly improved sensitivity in detecting small molecules due to the localized plasmonic confinement of the electromagnetic field.
To further investigate the biosensing capacity of the NH-TiN sensor, a sensitive non-invasive titanium nitride-nanoholes-localized surface plasmon resonance (TiN-NH-LSPR) biosensor was developed to detect parent glioma cells (GMs)’ malignant migration. Glioma is the fatal tumors in the brain whose malignant progression is highly related to a cluster of differentiation 44 (CD44). It was found that enhanced CD44 in exosomes from malignant GMs could be quantitatively detected by the proposed sensitive TiN-NH-LSPR biosensor. The limit of detection (LOD) for exosomal CD44 with TiN-NH-LSPR is 3.46 × 10-3 g mL−1, which could be a promising technique in detecting parent GMs’ malignant migration, thus supporting its potential use in the diagnosis and prognosis of glioma as a liquid biopsy.
For another important titanium compound, it was found that TiO2 columnar thin film (CTF), coupled with conventional gold nanoislands (AuNIs), can significantly enhance the performance of plasmonic sensing within the visible range by amplifying the localized plasmonic effect. In detail, the TiO2-CTF enhanced-gold nanoislands (TiO2-CTFE-AuNIs) plasmonic biosensor was developed for the detection of GMs-derived exosomes. The TiO2-CTFE-AuNIs sensor chip was fabricated with a secure two-step anodization-annealing method, which could quantitatively detect GMs-derived exosomes via CD63 with the LOD of 4.24 × 10−3 µg mL−1. The sensitivity of this plasmonic biosensor was enhanced by 152% as compared with a conventional self-assembled monolayer-gold nanoislands (SAM-AuNIs) plasmonic biosensor. Furthermore, it was employed to detect BIGH3 in GMs-derived exosomes for tracking GMs' malignant progression and temozolomide (TMZ)'s anti-glioma effects. Notably, the proposed plasmonic biosensor could quantitatively detect the dynamic change of exosomal BIGH3 in response to hypoxia and TMZ treatment with LOD of 3.84 × 10-3 μg mL-1, thus enabling tracking of the proliferation level of parent GMs.
Therefore, with excellent plasmonic sensing performance, the proposed titanium compounds based LSPR biosensors showed great potential for their applications to real-time detection of biomolecules.
| Date of Award | 31 Jul 2020 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Lawrence WU (Supervisor) |