Bioinspired Nanostructures for Biomedical Applications

Nature boasts a myriad examples of coloration achieved purely through the physical interaction of light with nano-scale features also known as biophotonic nanostructures. From reptiles to insects, birds to flora, structural coloration has been achieved through a variety of fascinating nano-architectures that leverage different physics. Beyond structural coloration, these nanostructures are often truly multifunctional. For instance, biophotonic nanostructures can also serve as self-cleaning and bactericidal surfaces, gas and thermal sensors, waveguides and beam splitters. With the growing need for robust and compact biomedical devices, the requirement to embed multiple functionalities towards sensing, monitoring, diagnostics and therapeutics within a diminutive device footprint becomes crucial. In this regard, inspiration from the multifunctionality of biophotonic nanostructures can prove to be greatly beneficial for medical applications. Consequently, this work attempts to showcase various examples of the utilization of nanostructures inspired from biophotonic nanostructures for biomedical applications under various overlapping themes such as ophthalmic sensors, bioinspired optics and plasmonic biosensing. This thesis is summarized in two parts. The first part (Chapters 2--4) introduces a proof-of-concept optical intraocular pressure (IOP) sensor implant and various challenges faced during its in vivo implementation. In Chapter 3, nanostructures inspired by light-trapping epidermal micro-/nanostructures on flower petals are proposed and embedded onto the sensor platform to improve its in vivo optical signal-to-noise ratio and biocompatibility. Chapter 4 covers nanostructures inspired by biophotonic nanostructures on longtail glasswing butterfly wings that improve the in vivo angle of acceptance and biocompatibility of the sensor. The second part (Chapters 5 and 6) presents the use of bioinspired nanostructures in plasmonic biosensors. Chapter 5 discusses an on-chip platform consisting of bioinspired plasmonic nanostructures to detect various nucleic acid sequences of relevance in the pathogenesis of HIV-1 via plasmon-enhanced fluorescence. Chapter 6 describes the employment of bioinspired quasi-ordered nanostructuring on flexible substrates for broadband surface-enhanced Raman spectroscopy (SERS). Here, SERS-based biosensing enabled by quasi-ordering is used to detect uric acid -- a biomarker of various pathologies in human tears.</p

Bioinspired Disordered Flexible Metasurfaces for Human Tear Analysis Using Broadband Surface-Enhanced Raman Scattering

Flexible surface-enhanced Raman scattering (SERS) has received attention as a means to move SERS-based broadband biosensing from bench to bedside. However, traditional flexible periodic nano-arrangements with sharp plasmonic resonances or their random counterparts with spatially varying uncontrollable enhancements are not reliable for practical broadband biosensing. Here, we report bioinspired quasi-(dis)ordered nanostructures presenting a broadband yet tunable application-specific SERS enhancement profile. Using simple, scalable biomimetic fabrication, we create a flexible metasurface (flex-MS) of quasi-(dis)ordered metal–insulator–metal (MIM) nanostructures with spectrally variable, yet spatially controlled electromagnetic hotspots. The MIM is designed to simultaneously localize the electromagnetic signal and block background Raman signals from the underlying polymeric substrate—an inherent problem of flexible SERS. We elucidate the effect of quasi-(dis)ordering on broadband tunable SERS enhancement and employ the flex-MS in a practical broadband SERS demonstration to detect human tear uric acid within its physiological concentration range (25–150 μM). The performance of the flex-MS toward noninvasively detecting whole human tear uric acid levels ex vivo is in good agreement with a commercial enzyme-based assay

Bioinspired Disordered Flexible Metasurfaces for Human Tear Analysis Using Broadband Surface-Enhanced Raman Scattering

Flexible surface-enhanced Raman scattering (SERS) has received attention as a means to move SERS-based broadband biosensing from bench to bedside. However, traditional flexible periodic nano-arrangements with sharp plasmonic resonances or their random counterparts with spatially varying uncontrollable enhancements are not reliable for practical broadband biosensing. Here, we report bioinspired quasi-(dis)ordered nanostructures presenting a broadband yet tunable application-specific SERS enhancement profile. Using simple, scalable biomimetic fabrication, we create a flexible metasurface (flex-MS) of quasi-(dis)ordered metal–insulator–metal (MIM) nanostructures with spectrally variable, yet spatially controlled electromagnetic hotspots. The MIM is designed to simultaneously localize the electromagnetic signal and block background Raman signals from the underlying polymeric substrate—an inherent problem of flexible SERS. We elucidate the effect of quasi-(dis)ordering on broadband tunable SERS enhancement and employ the flex-MS in a practical broadband SERS demonstration to detect human tear uric acid within its physiological concentration range (25–150 μM). The performance of the flex-MS toward noninvasively detecting whole human tear uric acid levels ex vivo is in good agreement with a commercial enzyme-based assay

Aluminum Metasurface with Hybrid Multipolar Plasmons for 1000-Fold Broadband Visible Fluorescence Enhancement and Multiplexed Biosensing

Aluminum (Al)-based nanoantennae traditionally suffer from weak plasmonic performance in the visible range, necessitating the application of more expensive noble metal substrates for rapidly expanding biosensing opportunities. We introduce a metasurface comprising Al nanoantennae of nanodisks-in-cavities that generate hybrid multipolar lossless plasmonic modes to strongly enhance local electromagnetic fields and increase the coupled emitter’s local density of states throughout the visible regime. This results in highly efficient electromagnetic field confinement in visible wavelengths by these nanoantennae, favoring real-world plasmonic applications of Al over other noble metals. Additionally, we demonstrate spontaneous localization and concentration of target molecules at metasurface hotspots, leading to further improved on-chip detection sensitivity and a broadband fluorescence-enhancement factor above 1000 for visible wavelengths with respect to glass chips commonly used in bioassays. Using the metasurface and a multiplexing technique involving three visible wavelengths, we successfully detected three biomarkers, insulin, vascular endothelial growth factor, and thrombin relevant to diabetes, ocular and cardiovascular diseases, respectively, in a single 10 μL droplet containing only 1 fmol of each biomarker

Aluminum Metasurface with Hybrid Multipolar Plasmons for 1000-Fold Broadband Visible Fluorescence Enhancement and Multiplexed Biosensing

Aluminum (Al)-based nanoantennae traditionally suffer from weak plasmonic performance in the visible range, necessitating the application of more expensive noble metal substrates for rapidly expanding biosensing opportunities. We introduce a metasurface comprising Al nanoantennae of nanodisks-in-cavities that generate hybrid multipolar lossless plasmonic modes to strongly enhance local electromagnetic fields and increase the coupled emitter’s local density of states throughout the visible regime. This results in highly efficient electromagnetic field confinement in visible wavelengths by these nanoantennae, favoring real-world plasmonic applications of Al over other noble metals. Additionally, we demonstrate spontaneous localization and concentration of target molecules at metasurface hotspots, leading to further improved on-chip detection sensitivity and a broadband fluorescence-enhancement factor above 1000 for visible wavelengths with respect to glass chips commonly used in bioassays. Using the metasurface and a multiplexing technique involving three visible wavelengths, we successfully detected three biomarkers, insulin, vascular endothelial growth factor, and thrombin relevant to diabetes, ocular and cardiovascular diseases, respectively, in a single 10 μL droplet containing only 1 fmol of each biomarker

Overcoming evanescent field decay using 3D-tapered nanocavities for on-chip targeted molecular analysis

Enhancement of optical emission on plasmonic nanostructures is intrinsically limited by the distance between the emitter and nanostructure surface, owing to a tightly-confined and exponentially-decaying electromagnetic field. This fundamental limitation prevents efficient application of plasmonic fluorescence enhancement for diversely-sized molecular assemblies. We demonstrate a three-dimensionally-tapered gap plasmon nanocavity that overcomes this fundamental limitation through near-homogeneous yet powerful volumetric confinement of electromagnetic field inside an open-access nanotip. The 3D-tapered device provides fluorescence enhancement factors close to 2200 uniformly for various molecular assemblies ranging from few angstroms to 20 nanometers in size. Furthermore, our nanostructure allows detection of low concentration (10 pM) biomarkers as well as specific capture of single antibody molecules at the nanocavity tip for high resolution molecular binding analysis. Overcoming molecule position-derived large variations in plasmonic enhancement can propel widespread application of this technique for sensitive detection and analysis of complex molecular assemblies at or near single molecule resolution

High-performance flexible metal-on-silicon thermocouple

We have demonstrated metal-on-silicon thermocouples with a noticeably high Seebeck coefficient and an excellent temperature-sensing resolution. Fabrication of the thermocouples involved only simple photolithography and metal-liftoff procedures on a silicon substrate. The experimentally measured Seebeck coefficient of our thermocouple was 9.17 × 10^(−4) V/°K, which is 30 times larger than those reported for standard metal thin-film thermocouples and comparable to the values of alloy-based thin-film thermocouples that require sophisticated and costly fabrication processes. The temperature-voltage measurements between 20 to 80 °C were highly linear with a linearity coefficient of 1, and the experimentally demonstrated temperature-sensing resolution was 0.01 °K which could be further improved up to a theoretical limit of 0.00055 °K. Finally, we applied this approach to demonstrate a flexible metal-on-silicon thermocouple with enhanced thermal sensitivity. The outstanding performance of our thermocouple combined with an extremely thin profile, bending flexibility, and simple, highly-compatible fabrication will proliferate its use in diverse applications such as micro-/nanoscale biometrics, energy management, and nanoscale thermography

Enhanced broadband fluorescence detection of nucleic acids using multipolar gap-plasmons on biomimetic Au metasurfaces

Recent studies on metal–insulator–metal-based plasmonic antennas have shown that emitters could couple with higher-order gap-plasmon modes in sub-10-nm gaps to overcome quenching. However, these gaps are often physically inaccessible for functionalization and are not scalably manufacturable. Here, using a simple biomimetic batch-fabrication, a plasmonic metasurface is created consisting of closely-coupled nanodisks and nanoholes in a metal–insulator–metal arrangement. The quadrupolar mode of this system exhibits strong broadband resonance in the visible-near-infrared regime with minimal absorptive losses and effectively supresses quenching, making it highly suitable for broadband plasmon-enhanced fluorescence. Functionalizing the accessible insulator nanogap, analytes are selectively immobilized onto the plasmonic hotspot enabling highly-localized detection. Sensing the streptavidin–biotin complex, a 91-, 288-, 403- and 501-fold fluorescence enhancement is observed for Alexa Fluor 555, 647, 750 and 790, respectively. Finally, the detection of single-stranded DNA (gag, CD4 and CCR5) analogues of genes studied in the pathogenesis of HIV-1 between 10 pM–10 μM concentrations and then CD4 mRNA in the lysate of transiently-transfected cells with a 5.4-fold increase in fluorescence intensity relative to an untransfected control is demonstrated. This outcome promises the use of biomimetic Au metasurfaces as platforms for robust detection of low-abundance nucleic acids

Biocompatible Multifunctional Black-Silicon for Implantable Intraocular Sensor

Multifunctional black-silicon (b-Si) integrated on the surface of an implantable intraocular pressure sensor significantly improves sensor performance and reliability in six-month in vivo studies. The antireflective properties of b-Si triples the signal-to-noise ratio and increases the optical readout distance to a clinically viable 12 cm. Tissue growth and inflammation response on the sensor is suppressed demonstrating desirable anti-biofouling properties