This PDF file contains the front matter associated with SPIE Proceedings Volume 12654, including the Title Page, Copyright information, Table of Contents, and Conference Committee information.

Lateral flow immunoassays are paper-based tests that can be used to detect different pathogenic biomarkers at the point-of-use. Conventionally, detection antibodies labelled with gold nanoparticles form sandwich immunoassays between the target antigen and capture antibody on the test line/spot when the biomarker is present in a sample. They provide rapid, visual and yes/no answers based on the appearance of the gold nanoparticles on the strip. However, lateral flow tests suffer from poor sensitivity which can lead to false negative results when the biomarker concentration is below the visual threshold of the test, especially at early infection stages. They also can’t accurately quantify the biomarker concentration which is important in monitoring the progression of an infection or the effectiveness of a treatment. Accordingly, lateral flow test should be combined with a read-out system that is convenient for points of use and could enable the accurate, sensitive and rapid quantification of the test results. In this work, we discuss the integration of surface enhanced Raman scattering technique with the lateral flow test in one platform to improve the test sensitivity and quantification capability, while maintaining the user-friendly and point-of-use features the lateral flow test provides. We have applied this approach for the detection of Clostridioides difficile and SARS-COV-2, as demonstrators for pathogenic infections, using new recognition elements in the test as a proof-of-concept.

While tip-enhanced Raman spectroscopy (TERS) has enabled vibrational spectroscopy with single molecule sensitivity and even atomic-scale spatial resolution, a counterpart for infrared spectroscopy has remained elusive regardless of advantages in terms of its versatility and compatibility with unique sets of the ultrafast and nonlinear spectroscopy. Here, we apply nano-FTIR spectroscopy, based on infrared scattering scanning near-field optical microscopy (IR s-SNOM), to detect amide-I vibration modes from a single protein consisting of ~500 amide groups. A protein with an effective radius of a few nm was deposited on an atomically flat gold substrate in the air. By lock-in demodulating the tip-scattered field with harmonics (n = 2 ~ 7) of the tip-tapping frequency, we identify a strong enhancement of the vibrational amplitude for higher harmonics associated with the increasingly localized tip-sample near-field interactions confined below < 10 nm. We then regard the protein as an infrared-resonant dielectric sphere and calculate complex-valued scattering spectra from a tip-protein-substrate hybrid system based on a few analytical models under quasi-static approximation. Such a calculation semi-quantitatively reproduces key features in the observed vibrational response from single protein particles, including the magnitude of the vibrational response in the optical phase and its dependence on the demodulation harmonics. This work bridges the currently established application of nano-FTIR to a relatively large protein complex or molecular monolayer to studies of objects significantly smaller than the tip radius at a few-nm level, paving a path toward single-molecule and atomic-scale infrared vibrational spectroscopy.

Label-free and nondestructive mid-infrared (MIR) vibrational hyperspectral imaging has emerged as a valuable ex-vivo tool for biomedical tissue analysis. However, due to the chemically complex and heterogeneous composition of tissue specimens, the analytical performance of conventional MIR spectral histopathology is limited. We introduce an innovative MIR spectrochemical tissue imaging modality that uses plasmonic metasurfaces to support strong surface-localized electromagnetic fields, enabling the capture of quantitative molecular maps of large-area brain tissue sections. Our surface-enhanced chemical imaging method has broad potential applications in both translational biomedical research and diagnostic clinical histopathology.

Spontaneous and stimulated Raman spectroscopies provide label-free, diffraction and sub-diffraction limited imaging capabilities, particularly valuable for biomedical applications. Plasmonically enhanced (PE) nonlinear versions of these spectroscopies can potentially provide even higher sensitivities enabling more rapid chemical imaging of a wider range of analytes for “real time” applications. A unifying density matrix framework for treating all plasmon-enhanced molecular spectroscopies is presented. The temporal description of PE optical electric fields of any pulse duration is an essential first step. The effects of the complex plasmonic enhancement factor on ultrafast, picosecond and cw pulses based on an idealized Lorentz oscillator model and observed dielectric properties of metal nanoparticle structures is shown. In particular, plasmonic enhancement effects on the optical phase, carrier frequency and pulse duration of incident ultrafast pulses are described. Unlike spontaneous PE Raman (SERS), the locally generated signal field of plasmon-enhanced stimulated Raman spectroscopies is also itself enhanced by a plasmonic response. A density matrix framework formulism is used to describe plasmonically enhanced femtosecond stimulated Raman scattering (FSRS), stimulated Raman gain/loss (SRG/L), impulsive stimulated Raman, CARS and spontaneous Raman. Plasmonic enhanced ultrafast pulses result in Raman spectroscopies that display dispersive vibrational line shapes (FSRS) or mixed dichroic and birefringent nuclear coherences (pump-probe) in agreement with experimental observations.

We fabricate SERS sensors by inkjet printing and demonstrate that their SERS response correlates with their diffuse reflectance characteristics. Using a modified commercial inkjet-printer, SERS sensors are prepared with multiple printing passes. Performances of the printed sensors only become noticeable after five printing passes as observed in both SERS and diffuse reflectance measurements. This suggests that the simpler diffuse reflectance measurement can be used as an alternative method to characterize and optimize the SERS performance of the printed sensors. Although sensors with a very high number of printing passes exhibit a much stronger SERS response from the benzenethiol reporter molecule, we also noticed a significant increase in the background from blank sensors. This may not be a desirable feature particularly for the detection of weakly bound molecules. Controlling SERS background and attaining a desirable SERS enhancement would need to be balanced in the design of sensors for the end-user’s specific need.

Near-field microscopy has emerged as a powerful tool for investigating the optoelectronic properties of van der Waals crystals on deeply subwavelength length scales. Complementary information may be obtained by interrogating the layered materials with electromagnetic radiation oscillating at vastly different frequencies: In the terahertz spectral range, for example, the polarizability of excitons in transition metal dichalcogenide (TMDC) heterostructures can be recorded on subcycle timescales–granting access to ultrafast formation dynamics or the exciton Mott transition with nanometer precision. In contrast, visible or near-infrared light propagates through thin van der Waals slabs in the form of waveguide modes (WMs). By resolving interference patterns in maps of the scattered electric field, the anisotropic dielectric tensor of layered materials is retrieved and signatures of strong light-matter coupling in the dispersion of the WMs are revealed. This approach also allows for boosting the potential of 3R-stacked TMDCs for applications in nonlinear optics by quantifying their birefringence, thus providing essential parameters for future phase-matched waveguide second harmonic generation and compact on-chip optical devices in general.

Raman spectroscopy is a technique that can visualize various molecular information noninvasively without the need for invasive pretreatment of samples such as staining. However, Raman scattering light is very weak, and thus Raman spectroscopy has limitations in terms of molecular sensitivity and measurement time. One solution to overcome the problem of weak signal intensity is optical enhancement based on the plasmon resonance effect. Surface-enhanced Raman scattering (SERS) spectroscopy enables highly sensitive Raman spectroscopy owing to the enhancing near-field produced by plasmon resonance. This enhancing field is formed in an area of about 10 nm around the metallic nanostructures. However, the direct contact between the metallic nanostructures and the analyte molecules causes denaturation of the metallic nanostructures and the analyte molecules themselves, limiting the Raman spectroscopic analysis and its applications. In the present study, we developed a remote plasmonic enhancement (RPE) method, which is expected to provide a high enhancement by plasmon-molecule remote coupling via a silica columnar structure of several tens nm in size to a metallic nanostructure. We demonstrated that the RPE could be applied to Raman spectroscopy (RPERS, remote plasmonic-enhanced Raman spectroscopy). We have confirmed the high enhancement of more than 104 by RPERS and clarified the fundamental characteristics of the RPERS.

Hemoglobinopathies are the most common genetic disorders caused by a mutation in the genes encoding for one of the globin chains and leading to structural (hemoglobin [Hb] variants) or quantitative defects (thalassemias) in hemoglobin. Early diagnosis and characterization of hemoglobinopathies are essential to avoid severe hematological consequences in the offspring of healthy carriers of a mutation. Despite being extensively studied, hemoglobinopathies continue to provide a diagnostic challenge. Sickle-cell hemoglobin (HbS) is the most common and clinically significant hemoglobin variant among all Hb variants. To overcome the challenge of diagnosing Hb variants, we propose the use of Surface-Enhanced Raman Spectroscopy (SERS). SERS is a powerful label-free tool for providing fingerprint structural information of analyses. It can rapidly generate the spectral signature of samples. This study investigates the structural differences between HbS and normal Hb using gold nanopillar SERS substrates with a leaning effect. The SERS spectra of Hb variants showed subtle spectral differences between HbS and normal Hb located in the valine (975 cm^-1) and glutamic acid (1547 cm^-1) band, reflecting the amino acid substitution in the HbS β-globin chain. We also automated the identification of HbS and normal Hb with principal component analysis (PCA) combined with support vector machine (SVM) and linear discriminant analysis (LDA) classifiers, leading to an accuracy of 98% and 96%, respectively. This study demonstrated that SERS can provide a fast, highly sensitive, noninvasive, and accurate detection module for the diagnosis of Sickle-cell disease and potentially other hemoglobinopathies.

Thermochemical degradation of thermal barrier coatings generated by the infiltration of siliceous debris at high temperatures is considered a serious threat by aircraft industry due to phase destabilization of the thermal barrier material induces changes on its properties. Most materials-based strategies to mitigate the infiltration aim to promote the reactive crystallization of phases such as apatite. In this work, 2D Raman spectroscopy was carried out over the cross sections of lanthanum-gadolinium zirconate ceramic samples infiltrated by Colima and Popocatepetl volcanic ashes at 1250 °C for 10 h to identify the phases reprecipitated after infiltration. Raman mappings showed the characteristic peaks and the distribution of reprecipitated phases such as rare-earth apatite, monoclic and tetragonal zirconia. Additionally, rare-earth zirconate ceramics were identified by the characteristic F_2g band of the pyrochlore structure. At the reaction layer, two zones were observed. Zirconia phases reprecipitating right at the upper zone while rare-earth apatite reprecipitating at the lower zone. For apatite, the peak corresponding to stretching vibrations of Si-O tetrahedra shows shifting to higher wavenumber values as gadolinium content increases in the rare-earth zirconate infiltrated. The 2D Raman spectroscopy was very effective to observe the distribution of the reprecipitated phases in addition to correlate the influence of gadolinium in the formed apatite. A correlation between infiltration depth and bands were confirmed.

Bifunctional nanoparticle of combining magnetic and plasmonic nanomaterials retain both unique properties, contributing to the high photothermal performance, excellent biocompatibility, physiological stability, low cytotoxicity and easy separation. Herein, we report a core-shell plasmonic magnetic nanostructure (PMNs), then introduce the plasmonic photothermal polymerase chain reaction (PPT-PCR) platform for fast, sensitive, cheap, and simple nucleic acid detection based on PMNs. Magnetic nanoparticles can be synthesized by solvothermal reaction. PMNs can be prepared after Au coating on the magnetic core, which can act as nanoheater and heat solution to 95°C in several seconds upon infra-red (IR) light irradiation, and can be collected by magnet easily. Furthermore, our platforms utilize ultrafast PCR amplification based on the photothermal effect of plasmonic magnetic nanoparticles for molecular diagnostics through two modes, including in-situ end-point quantitative fluorescence detection (PPT-qPCR) and colorimetric assay (PPT-cPCR), having comparable limit of detection (LOD) on DNA targets.