This PDF file contains the front matter associated with SPIE Proceedings Volume 11661, including the Title Page, Copyright information, and Table of Contents.

Surface-enhanced Raman scattering (SERS) is emerging as an alternative non-invasive detection method in many applications. We recently show the use of SERS nanoprobes to detect tumors in vivo in mice, as well as the use of SERS sensors in vivo in plants for the detection of mIRNA. In spite of these advancements, the translation of SERS to real-world settings has been limited due to issues with observing Raman signal over complex background. For example, it remains challenging to observe SERS under sunlight or under strong illumination (e.g., operating room), using a conventional Raman setup. To this end, we combined a Raman setup with a newly developed dual-wavelength laser to perform shifted-excitation Raman difference spectroscopy (SERDS). Using SERDS, we demonstrate that the use of SERS sensors to detect miRNA in live plants inside a growth chamber, under full illumination. Additionally, we show that SERDS can be used to accurately identify tumors in mice, under ambient light. In both these applications, we demonstrate that the combination of SERS with SERDS improves the sensitivity and accuracy. This work will aid the translation of Raman and SERS to real-world settings.

This study shows unique capability of deep-subwavelength metal-insulator-metal (MIM) width-graded nano-gratings in offering high intensity electromagnetic field. The plasmonic field is underpinned by the strong coupling of the surface plasmon polaritons on the sidewalls of the nanogrooves. We present quantitative SERS detection of various biomolecule species at an ultra-low concentration corresponding to detection of single molecule. We report limit of detection of a gold coated bullseye width-graded plasmonic nano-grating as a SERS platform in detecting small molecule (such as propylene glycol) or sepsis biomarkers (such as protein c) at multiple wavelengths of light.

There are many ways to deliver biomolecules to cells past their cell membrane barrier, but the field of laser-activated materials have helped further the drug delivery field. When nanostructure and materials are irradiated by pulsed laser in an aqueous environment, thermoplasmonic effects and localized heating occur. There are also pressure waves being generated, with the quantity of impulse varying due to laser-parameter and surface type. We demonstrate the relationship between the magnitude of impulse, generated from gold thermoplasmonic nanostructure and bulk polymer substrates, and cargo delivery in cells.

In this proceeding, we study very low birefringence changes in microscopic sites from the spatial frequency response of focused surface plasmon. For the feasibility test, we consider thin films of photo-addressable azo-polymers as potential samples. We confirmed the proposition with the help of various concentrations of thin films of azo-polymers resulting in various orders of photo-induced birefringence even as low as 0.01. Further, we test human dermal fibroblasts (HDFs) birefringence changes in various environments towards label free detection of hotspots of dermatoheliosis.

LHCII — the main light-harvesting complex of plants and green algae — is the most abundant membrane protein on earth. Here, we investigate theoretically the effect of exciton-plasmon coupling on LHCII’s fluorescence quantum yield and compare our modelling results to experimental data where plasmon-enhanced fluorescence has been reported in an LHCII–gold nanorod system. One of the models relies on the modified Gersten-Nitzan approach; the other is based on classical plexcitonics. We show that the latter is more robust and leads to more realistic enhancement factors.

Laser generated bubbles surrounding plasmonic nanoparticles (known as plasmonic nanobubbles) are an attractive candidate approach for imaging and therapy, especially for cancer research. Nanobubbles are typically small in size (in microns), have a short lifetime (microseconds), and require complex instrumentation to characterize. Current approaches measure the bubble size using flash photography or an ultrafast camera and the bubble lifetime indirectly with a light scattering of a probe beam. Here, we demonstrate swept-source (1310+/-70 nm, 100 Khz scan rate) optical coherence tomography (OCT) as a new approach to monitoring plasmonic nanobubbles' dynamics. We recorded a one-dimensional (A-scan) analysis on a thin Au-nanoparticle-embedded gelatin layer and monitored the phase offset of the gelatin/air interface where nanobubbles were generated in response to a high energy single 10-ns 1064nm Nd: YAG laser pulse. We observed the gel/air interface movement reflecting the formation and collapse of nanobubbles with radius in the range of 200 – 600 nm and lifetime up to 100 microseconds corresponding to an incident laser fluence of 0.9 – 2.4J/cm². We observed interface oscillations following nanobubble collapse. In conclusion, OCT may provide a simple technique to characterize both nanobubble's size and lifetime in response to pulsed laser irradiation of plasmonic nanoparticles.

Fluorescence super-resolution imaging relies on fluorophores as contrast agents. As a result of the inevitable photobleaching and thus a limited photon budget, they put fundamental limitations on the temporal resolution. We propose non-bleaching, plasmonic nanoparticles as non-bleaching contrast agents with an unlimited photon budget such that both the temporal and spatial resolution can be pursued at the same time. We demonstrated a continuous observation of fine structural features in resolved actin networks. We believe the non-bleaching nanoscale imaging will open new doors for observing biological processes on a much longer timescales with higher spatial and temporal details.

Surface plasmon resonance (SPR) biosensors are optical materials that measure changes in the refractive index as they monitor non-covalent molecular interactions in real time. These utilise a label free analytical approach, which does not require dyes to produce a visible signal. In this study SPR was assessed for the detection of DNA hybridization between complementary DNA sequences within the pol gene of the human immunodeficiency virus (HIV) genome. HIV mutates rapidly due to its error prone reverse transcriptase enzyme. Some of these mutations make the virus to be resistant to antiretroviral drugs used to treat HIV infected individuals, rendering the drugs ineffective. In order to assess whether an infected individual expresses any drug resistant mutations, different bio-assays must be performed. However, these tests are expensive and require sophisticated equipment, which might be unavailable in resource limited settings. In a quest to simplify these tests so that they can be used in resource limited settings and reduce costs associated with HIV drug resistance testing, SPR capabilities were explored in this study. This was achieved by amplifying a 174 bp region of the HIV-1 pol gene using polymerase chain reaction (PCR). The detection was based on the hybridization between the PCR amplified DNA sequence and a biotinylated oligonucleotide probe immobilized onto an SPR sensor chip made of a gold coated slide. The acquired results indicated that the SPR-sensor-chip used was able to recognize changes in different wells and thereby able to differentiate between a sample with DNA hybridization and the one without. Based on these findings, this approach has potential to detect HIV drug resistance mutations with high efficiency in less time, at lower cost.

Gold nanoparticles are ideal tools for cargo transportation. However, injection of nanoparticles into cells remains difficult. Current method utilizes laser light to heat up the particles and the surrounding media to create shock wave or air bubble to push the particle into the cells. However, high temperatures may result in cell and/or cargo damage. To solve this issue, we propose a new mechanism that utilizes mechanical force without causing high temperature. We carefully tune the geometry of gold nanoparticles to maximize the applied force on the membrane while minimizing the particle temperature. This work paves the way for further applications in cargo transportation.

The proliferation of multiresistant bacteria is having an increasing and profound impact on the world. A credible alternative to antibiotics is bacteriophage therapy, which are expected in the near future to form the basis of an entirely new treatment paradigm for infectious diseases. In order to facilitate such an epochal transition, new tools are needed for the rapid and multiplexed screening of large libraries of candidate bacteriophages in order to provide a personalized bacteriophage cocktail for each patient. This talk presents recent progress towards the development of a SPR-based screening method, wherein immobilized bacteriophages form a biosensing layer which produces a measurable surface plasmon resonance signal as a result of the specific interaction between the bacteriophages and their host bacterial cells in a microfluidic flow above the sensor surface.

In this work, we explore a way to design meta-plasmonic structure-based biosensors using machine learning methods. Plasmonic biosensing is a label-free detection method that is widely used to measure various biomolecular interactions. One of the main challenges has been how to improve the sensitivity and detection limit to detect very small molecules at low concentrations. Here, metamaterial was employed to address these issues using machine learning for the design. Transfer matrix algorithm was used to calculate optical characteristics of meta-plasmonic structure to generate training data. The multilayer perceptron was then applied to predict the optical characteristics of the meta-plasmonic structure. The performance was compared with conventional interpolation methods. Multilayer perceptron was shown to achieve mean squared error lower by about 1.5 times. Autoencoder and t-Stochastic Neighbor Embedding were also used to cluster the optical characteristics. Structural parameters which provide resonance in reflection can be found through clustering of optical characteristics. It was shown that meta-plasmonic structure improves sensitivity by more than ten times over conventional plasmonic biosensors. We expect that machine learning methods can be further extended to other biosensing modalities.