Fabricating Cost-Effective Nanostructures for Biomedical Applications

In this thesis we described inexpensive alternatives to fabricate nanostructures on planar substrates and provided example applications to discuss the efficiency of fabricated nanostructures. The first method we described is forming large area systematically changing multi-shape nanoscale structures on a chip by laser interference lithography. We analyzed the fabricated structures at different substrate positions with respect to exposure time, exposure angle and associated light intensity profile. We presented experimental details related to the fabrication of symmetric and biaxial periodic nanostructures on photoresist, silicon surfaces, and ion-milled glass substrates. Behavior of osteoblasts and osteoclasts on the nanostructures was investigated. These results suggest that laser interference lithography is an easy and inexpensive method to fabricate systematically changing nanostructures for cell adhesion studies. We also used laser interference lithography to fabricate plasmonic structures. Fabrication details of gold nanodisk arrays were described. Experimental and simulation results show that those structures are suitable to develop highly sensitive plasmonic sensors. As a second fabrication method we described the growth of surface immobilized gold nanoparticles with organometallic chemical vapor deposition (OMCVD) on amine terminated surfaces. Samples fabricated using different deposition times were characterized by UV-Vis spectroscopy and scanning electron microscopy. Particle stability on the samples was tested by washing and rinsing treatments with various organic solvents. The size, interparticle distance, and shape of the gold nanoparticles demonstrated that OMCVD is a simple, economical, and fast way to fabricate surface-bonded and stable gold nanoparticles. The plasmonic properties, the stability of the particles and the biotin-streptavidin test showed that these OMCVD-grown gold nanoparticles are suitable for reproducible, low noise and highly sensitive biosensing applications. We further investigated the similar-to-real-life biosensing capabilities of the OMCVD-grown nanoparticles. Conventional antibody immobilization methods using biotin-streptavidin affinity, introduces additional chemistry and distance between the surface and the recognition sites and decreases the sensitivity. With the new recognition chemistry, epidermal growth factor receptor (EGFR) antibody recognition sites were directly immobilized on AuNP surfaces to decrease the distance between the sensor surface and the recognition sites for detecting EGFR antigens. In comparison with the literature, we obtained increased signal response with further optimization possibilities

Laser Nano-Filament Explosion for Enabling Open-Grating Sensing in Optical Fibre

Embedding strong photonic stopbands into traditional optical fibre that can directly access and sense the outside environment is challenging, relying on tedious nanoprocessing steps that result in fragile thinned fibre. Ultrashort pulsed laser filaments have recently provided a non contact means of opening high aspect ratio nanoholes inside of bulk transparent glasses. This method has been extended here to optical fibre, resulting in high density arrays of laser filamented holes penetrating transversely through the silica cladding and guiding core to provide high refractive index contrast Bragg gratings in the telecommunication band. The point by point fabrication was combined with post-chemical etching to engineer strong photonic stopbands directly inside of the compact and flexible fibre. Fibre Bragg gratings with sharply resolved pi-shifts are presented for high resolution refractive index sensing from n = 1 to 1.67 as the nano-holes were readily wetted and filled with various solvents and oils through an intact fibre cladding.Comment: 21 pages, 12 figure

Surface Plasmon Resonance Sensing Properties of a 3D Nanostructure Consisting of Aligned Nanohole and Nanocone Arrays

Molecular surface plasmon resonance (SPR) sensing is one of the most common applications of an array of periodic nanoholes in a metal film. However, metallic nanohole arrays (NHAs) with low-hole count have lower resolution and SPR sensing performance compared to NHAs with high-hole count. In this paper, we present a compact three-dimensional (3D) plasmonic nanostructure with extraordinary optical transmission properties benefiting from surface plasmon matching and enhanced localized surface plasmon coupling. The 3D nanostructure consisted of a gold film containing a NHA with an underlying cavity and a gold nanocone array (NCA) at the bottom of the cavity. Each nanocone was aligned with the nanohole above and the truncated apex of each nanocone was in close proximity (100 nm) to the gold film. The NHA-NCA structures outperformed conventional NHA structures in terms of bulk sensitivity and Figure of Merit (FOM). Furthermore, the NHA-NCA structure with 525-nm periodicity was capable of sensing streptavidin down to 2 nM exhibiting a 10-fold increase in streptavidin sensitivity compared to conventional NHA structures. The sensitivity and performance of the 3D nanostructure can be further improved by exploiting multiplexing methods in combination with stable light sources and detection systems

A Biosensor based on Periodic Arrays of Gold Nanodisks under Normal Transmission

We present a biosensor based on periodic arrays of gold nanodisks patterned on top of a glass substrate. The sensor’s resonance wavelength, peak linewidth and figure of merit were studied both in experiments and in simulations. We analyzed the dependence of the sensor’s resolution on the inherent figure of merit of the sensor structure and the signal to noise ratio of the detection system. The best achieved refractive index resolution is 1.5×10-4 RIU and the detection limit on and antigen-antibody binding is better than 1 ng/mL

Large area periodic, systematically changing, multishape nanostructures by laser interference lithography and cell response to these topographies

The fabrication details to form large area systematically changing multishape nanoscale structures on a chip by laser interference lithography (LIL) are described. The feasibility of fabricating different geometries including dots, ellipses, holes, and elliptical holes in both x- and y- directions on a single substrate is shown by implementing a Lloyd\u27s interferometer. The fabricated structures at different substrate positions with respect to exposure time, exposure angle and associated light intensity profile are analyzed. Experimental details related to the fabrication of symmetric and biaxial periodic nanostructures on photoresist, silicon surfaces, and ion milled glass substrates are presented. Primary rat calvarial osteoblasts were grown on ion-milled glass substrates with nanotopography with a periodicity of 1200 nm. Fluorescent microscopy revealed that cells formed adhesions sites coincident with the nanotopography after 24 h of growth on the substrates. The results suggest that laser LIL is an easy and inexpensive method to fabricate systematically changing nanostructures for cell adhesion studies. The effect of the different periodicities and transition structures can be studied on a single substrate to reduce the number of samples significantly

Femtosecond laser filaments for rapid and flexible writing of fiber Bragg grating

A new beam delivery method is introduced for controlling filament formation in optical fiber that enables point-by-point writing of 1st order fiber Bragg gratings (FBGs) with single femtosecond laser pulses. Uniform filament tracks with azimuthal symmetry were formed fully through the 9.3 µm core waveguide by a modified immersion focusing method to eliminate astigmatism by the cylindrical fiber shape. Filament arrays were precisely assembled inside of single-mode fiber, generating strong FBG resonances in the telecommunication band. Laser exposure control within this unique thin-grating geometry were key to manipulating the relative strength of the Bragg and cladding mode resonances while also independently tailoring their spectral resolution and features. This filament-by-filament writing rapidly forms gratings with highly flexible pattern control to tune wavelength, or introduce optical defects, demonstrated by a π-shifted FBG having a sharp 25 pm resonance embedded within a broader Bragg peak.NSERC Strategic Partnerships Project 447284