This PDF file contains the front matter associated with SPIE Proceedings Volume 12861, including the Title Page, Copyright information, Table of Contents, and Conference Committee information.

Detecting multiple molecular markers related to immune cells in vivo can revolutionize tumor phenotyping, monitor the effects of immunotherapy, and provide personalized treatment. Raman imaging with surface enhanced Raman scattering (SERS) nanoprobes is an optical imaging technique with high sensitivity and unparalleled multiplexing capacity. Here, we present a generalized methodology for the synthesis and visualization of SERS nanoprobes to detect multiple targets in vivo after intravenous administration in mouse models of cancer. A multiplexed imaging approach allows simultaneous scanning, unmixing, quantification, and visualization of the nanoprobes. We use this method to monitor the response of tumor-bearing mice (murine breast and colon cancer) to immune checkpoint blockade therapy. We visualize 8 immunological markers simultaneously, with subsequent immunohistological verification of each target. A spatially-aware multivariate approach is used for the segmentation of the acquired spectral images, which allowed their subsequent classification into responders or non-responders using machine learning.

We report a quick and low-cost method for the fabrication of a label-free gas nanosensor for breath analysis, based on surface enhanced Raman spectroscopy (SERS), using nanowires (NWs) as a backbone. We followed a fully solution-processed method for the decoration of TiO₂ NWs with plasmonic gold (Au) nanoparticles (NPs), and their subsequent dielectrophoretic (DEP) self-assembly on predefined substrate locations. This approach produces a 3D NW mesh that maximizes the SERS-active surface of the device, while achieving signal reliability and reproducibility. The sensor’s performance was tested using 4-aminothiophenol (4-ATP) in gas phase, at concentrations as low as 0.01 parts-per-million (ppmv). These findings demonstrate the applicability of the NW mesh sensor for the development of breath analysis platforms for diagnostic and medical screening applications.

We demonstrate the capabilities of the SiPhox Home platform to measure blood biomarker concentrations such as a highsensitivity C-reactive protein (hsCRP) assay. The system consists of disposable biosensor cartridges which plug into a compact reader instrument. The reader contains a miniature low-cost swept-source laser and detection system which is designed to interrogate on-chip resonant or interferometric sensors, and we demonstrate excellent performance of manufactured readers compared to a gold-standard laboratory tunable laser. The cartridge includes a silicon photonics chip with 15 individually addressable microring resonator sensors which transduce molecular binding into a wavelength shift measured by the reader. We demonstrate both labeled and label-free ring resonator immunoassays running on our platform which can measure the relevant hsCRP concentration range of 0.2 – 10 μg/mL. In a preliminary method comparison study, 7 volunteers measured their hsCRP values at home by two methods: SiPhox Home, which displays results after only a 4-minute run time, and a commercially available mail-in blood test, which typically returns results in 3-5 business days. The results show a good correlation and demonstrate the potential for high-quality at-home measurement of blood biomarkers using manufacturable silicon photonics technology.

We experimentally demonstrated slow wave enhanced phase and spectral sensitivity in asymmetric Michelson interferometer sensors with a phase sensitivity 277,750 rad/RIU-cm and theoretical phase sensitivity as high as 461,810 rad/RIU-cm. In the context of low-cost chip integrated photonic packaged sensors, in this paper we will experimentally demonstrate a method for active tuning of interferometer fringes using phase change materials that will potentially overcome fabrication induced variation of interference fringe wavelengths, thus allowing sensor chip packaging with a fixed wavelength laser and available integrated photodetectors.

Evanescent field silicon photonics in a silicon-on-insulator or silicon-nitride-on-insulator platforms have been effectively utilized to demonstrate chemical and biosensors over the past decade with applications in the detection of nucleic acids and protein biomarkers for cancers, viruses and infectious diseases, and environmental toxins. By balancing the requirements for efficient low-loss transmission through the waveguide and enhancing light-matter interaction such as with molecules binding on the high index material surfaces in resonant microcavities, slow light and interferometer geometries, various high sensitivity biosensors have been experimentally demonstrated down to few femtograms/ml. various slotted microcavities and waveguides have been experimentally demonstrated. In recent years, subwavelength waveguides have demonstrated high bulk spectral sensitivities approaching ~500nm/RIU (RIU=refractive index unit) in periodic structures with lattice constant (Λ) <<(λ/2n_eff) where n_eff is the effective index at wavelength λ. While most experimental demonstrations have been in subwavelength ring resonator geometries, in this research, in addition to experimental demonstration of bulk spectral sensitivity ~775nm/RIU in subwavelength waveguides in interferometer configurations, we investigate optimized geometries that can reach sensitivities ~70,000nm/RIU in compact dimensions. In contrast to Mach-Zehnder interferometer (MZI) sensors of the same geometric interferometer arm lengths, the reflected path in Michelson interferometers (MI) doubles the optical path length, and thus effectively doubles the phase shift in the presence of an analyte. The interference fringe linewidths are narrowed compared to the equivalent MZI and would thus enable smaller changes in analyte concentration to be discerned from the fringe spectra.

Over the past decades, particle characterisation has emerged as a pivotal field, consistently demonstrating its potential through advancements in particle synthesis and the enhanced understanding of diverse applications utilising specialized particles. Shape is an important physical property of a particle and makes an impact on other properties of the particle, thus it is worth exploring. There are many techniques for measuring the shape of particles, from micrometer sized to nanometer sized. However, it is not possible to achieve accurate in situ, single-particle measurements in fluids with current methods while such measurements have great potential in areas like water quality monitoring. In this work, we demonstrated a novel technique to measure the aspect ratio of a single particle using open-access microcavities. By probing the perturbation of a rod-shaped particle in water to the optical mode formed in the microcavity, we are able to extract quantitative information about the particle, namely the aspect ratio. We apply this technique to two types of gold nanorods as well as probiotics samples to illustrate its wide applications to different materials and sizes.

π-Conjugated polymers possessing beneficial properties such as optical features are promising materials as platforms for chemical sensors by introducing appropriate molecular recognition moieties. Among π-conjugated polymers, polythiophenes are representative materials with flexible backbones that enable the functionalization of side chains at the 3- and/or 4-positions. The dynamics of the polymer behavior by analyte capture cause optical changes, which allow real-sample analysis for food analysis, environmental assessments, and clinical applications. The author has attempted to establish polymer-based chemosensors and their chips on solid-state substrates for pattern recognition. The latest results of π-conjugated polymer-based sensors will be presented.

Herein, we propose approaches of self-assembled chemosensors only using off-the-shelf reagents to easily obtain various chemosensors without organic synthesis. The concept of self-assembled chemosensors comprising off-the-shelf reagents with water solubility realizes not only the easy tuning of optical sensing properties but also chemical sensing in real samples. We summarize the comprehensive sensing applications using the facile self-assembled chemosensors and their arrays combined with pattern recognition techniques, and the usability of off-the-shelf reagents in analytical chemistry.

Both the waste of edible food and the consumption of non-edible food within the best before date are ongoing concerns in food industry. Until now, no methods are applied to access food quality of packed food without opening of packages. We demonstrate the formulation of a sensor foil comprising of a non-toxic porphyrin on an inorganic matrix in polyethylene. The sensor foil is capable of detecting amines in the gas phase over food products, which could act as spoilage indicators during the shelf life of packaged food. The foil was optimized to prevent reactions with other analytes in the gas phase of food by the alteration of the hydrophobic polymer. We performed experiments, using model packing units, to monitor the behavior of the foil and correlated the change in the fluorescence spectra to the total viable count of bacteria on the fish. The readout of the foils was performed with fluorescence spectroscopy to yield highly accurate results in contrast to less accurate the colorimetric determination.

Neglected tropical diseases, including filoviruses, constitute a class of diseases affecting some of the most impoverished and vulnerable populations worldwide. Despite their significant impact, there is a pressing need for diagnostics that can effectively and rapidly detect pathogens in field settings. Herein, we present a portable diagnostic platform leveraging plasmonic fluors and lateral flow assays for the detection of filoviruses. Plasmonic fluors are a class of engineered, ultrabright fluorescent probes whose versatility and amenability towards use in a variety of diagnostics is a major clinical strength. Our resulting assay has a rapid turnaround time and sensitivities amenable for field deployment.

Lyme disease, the most common tick-borne illness in the United States, is a significant clinical diagnostic challenge. The current approach is standard or modified two-tiered tests (STTT/MTTT), which both offer limited accuracy. A biosensing platform with nanoscale plasmonic gratings to enhance signal from antibodies was developed to resolve these issues. Human serum samples with known Lyme disease status were tested on the biosensor. These samples included patients in early and late stages of the disease, as well as healthy controls. The results were analyzed with ROC analysis to determine diagnostic thresholds. Scoring the data with these thresholds showed improved accuracy over STTT and MTTT. Further machine learning analysis on the data yielded similar results to the ROC analysis.. Based on these results, this biosensor has the potential to improve clinical outcomes for Lyme disease by enabling earlier disease diagnosis through higher sensitivity toward early stages of Lyme disease.

This work reports a 3D-printed virus sensing device that combines the functions of sample enrichment and quantification. The device consists of a nanoplasmonic biosensor surrounded by a biomimetic superhydrophobic structure. The superhydrophobic structure serves as a sample concentrator that can enrich the target analyte, which is subsequentially quantified by the nanoplasmonic biosensor. Both nanoscale sensor and microscale hydrophobic sample concentrator were fabricated using a high-resolution 3D printer through two-photon polymerization lithography (TPL). The design of the 3D-printed superhydrophobic microstructure was inspired by natural patterns found on surfaces like lotus leaves, which are known for their water-repellent properties. The TPP-based 3D printing approach enables the integration of two functions into one chip with a low-cost, high resolution, and simple fabrication process. This system was used to detect the swine influenza A virus contained in sample droplet with a starting volume of 25 μL. During a test, the droplet volume reduced due to evaporation, which was facilitated by the plasmonic heating. As a results the droplet’s diameter can shrink from 3.5 mm to 0.1 mm within 15 minutes. The volume reduction corresponds to the virus concentration increase over 4 × 10⁴ times. The implementation of superhydrophobic sample concentration around of the sensor significantly improved the immobilization of target viruses on the plasmonic sensor. The device not only achieved a higher sensitivity but also reduced the assay time.