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MicroRNAs (miRNAs) have increasingly become an important biomarker target for applications ranging from clinical diagnostics to biofuel production monitoring. However, the current state of the art for the detection of such markers requires tedious processing and amplification techniques such as polymerase chain reaction (PCR). In an effort to create a relatively simple biosensing platform, we have developed a combined plasmonic biosensing method based on a Surface-Enhanced Raman Spectroscopy (SERS) platform called the inverse Molecular Sentinel (iMS) to directly detect in vivo miRNA such as miR858a. With Shifted Excitation Raman Difference Spectroscopy (SERDS), we can remotely detect these targets in the field in the presence of interfering background signal. The application of such technology can pave the way not just for biofuel monitoring but early and non-invasive disease detection and diagnostics.
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Wearable sensor technology is a powerful tool, but conventional wearable sensors cannot perform simultaneous chemical sensing of multiple biomarkers in biofluids such as sweat and saliva because they are typically sensitive to only one type of chemical in an analyte at a time. Here we present a wearable dual-surface substrate for in situ surface-enhanced Raman spectroscopy (SERS). The substrate is composed of a gold nanomesh structure that can be tailored into any shape and attached to virtually any surface. Notedly, SERS can be performed on both surfaces of the substrate, highly effective for multiplexed in situ chemical sensing of biofluids.
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We present the integration of a miRNA sensing probe technology with a bimetallic nanostar-based surfaced-enhanced Raman scattering (SERS) substrate for disease detection. Circulating microRNAs (miRNA) are being investigated as promising diagnostic biomarkers for many cancers, including colorectal cancer (CRC). The inverse molecular sentinel technology was used for amplification-free multiplexed detection of miRNA targets using SERS. The integration of these technologies lays the foundation for point of care device design, capable of miRNA profiling without the need for traditional sample preparation of nucleotide amplification techniques.
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Bulk optical components are conventionally used to control light. However, bulk optical components are limited by optical loss and ability for miniaturization. To address this problem, we developed soft multimaterial photonic devices. The theoretical predictions and experimental results are compared with the device characterization. Plasmonic super-resolution imaging based on this device is presented as an example. We find the result of plasmonic super-resolution imaging enabled by the compact design is comparable to commercial devices.
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Fluorescent photochromic molecules have two photocyclization states and the change between the fluorescent form and non-fluorescent form is reversible and depends on the wavelength of light. By placing these molecules in the vicinity of a silver nanowire, featuring the plasmon resonance, we can control the photoswitching properties of these emitters. In this work, we deposited a submicron droplet of molecules on one end of a nanowire and used focused laser to remotely change the photocyclization state of the molecule via surface plasmon polariton propagation. The effects observed for such a unique system can be applied for quantum optics and sensing.
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In recent years, imaging systems have increasingly become more powerful and have allowed for better spatial resolution. Such systems, however, are limited to surface level interrogation of samples. Here we have developed a general optical technique referred to as Optical Recognition of Constructs Using Hyperspectral Imaging and Detection (ORCHID) as means of obtaining a multidimensional image containing information in the three spatial (X, Y, and Z) and spectral dimensions. Spatial offsets, obtained using selected binning of radially positioned pixels on the CCD, are coupled with stage and spectral scanning to collect a hyperdimensional data cube of the sample. We demonstrate this technique on gel phantoms containing target nanoparticles such as gold nanostars and quantum dots as way to demonstrate in-depth 3D imaging.
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In this paper, we have designed and fabricated an atomically thin plasmonic sensing substrate based on two-dimensional phase change material Ge2Sb2Te5 and silver (Ag-GST). This substrate offers an ultra-low reflection in the SPR curves and a strong optical phase singularity. A custom-built SPR setup was developed here to directly measure the phase-singularity-induced lateral position shift. We have obtained a SPR sensitivity regarding the lateral position shift of 9.9577 x 10^7 μm/RIU, which is 3 orders of magnitudes higher than current position shift sensing scheme based on hyperbolic metamaterial. Due to the ultra-high SPR sensitivity, the binding processes between peptide and integrins directly from un-purified liposomes were real-time monitored. The concentrations of Mn2+ ions ranging from 1 fM to 1 mM on the binding dynamics have been systematically monitored with our developed phase-sensitive surface plasmon resonance biosensors.
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Highly selective, specific, and non-invasive diagnostic markers are urgently needed for early cancer detection. Extracellular vesicles (EVs) are cell-derived sub-micron vesicles comprising surface proteins. With recent improved methods for EV characterization and isolation, new opportunities have emerged to study EVs as biomarkers and mediators of human diseases, including cancer. This work discusses the development of a pan-cancer multiplex surface plasmon resonance (SPR)-based platform to detect and quantify EV protein biomarkers for early-stage cancer screening with high sensitivity and specificity. Our optical biosensor has the potential to be applied as a pan-cancer panel for patient selection and early management of cancer.
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Surface-enhanced Raman scattering (SERS) has extended its biomedical application to in vivo preclinical imaging. However, the in vivo SERS imaging requires non-clearable large gold nanoparticles, limiting their translation in humans.
Here, we address this problem by creating SERS supraparticles composed of small-sized nanoclusters. First, we performed the FDTD simulation of the supraparticle design, and the maximum enhancement factor of 10^6 was achieved. Second, we chemically synthesized bright supraparticles that enabled in vivo Raman imaging of rodent models. Furthermore, the supraparticles were highly excretable, offering great potential for clinical application of in vivo Raman imaging by replacing non-excretable SERS nanotags.
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This paper presents a widefield label-free plasmonic method for imaging electrical activity of pancreatic beta cells. MIN6 insulinoma cells were grown on gold surfaces modified with poly-L-lysine to promote adhesion. The results presented show synchronised electrical signals upon extracellular exposure to 10mM glucose solution. Spatiotemporal patterns of electrical activity are recorded with a sampling frequency of 100Hz and the microscopic technique offers a signal-to-noise ratio that enables measurements from an area as small as 1µm2.
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Photon avalanche is one of the anti-Stokes upconversion processes characterized by highly nonlinear response of the emission intensity to excitation power density changes. By exceeding the critical pumping power threshold, even minute increase of this power results in a steep increase (by 2-3 orders of magnitude) of the emission intensity. While photon avalanche has been observed in bulk materials since 80-ties, it was reported in thulium-doped nanocrystals only recently, enabling to use them for single excitation beam super-resolution imaging. In current work we explore new perspectives for nanoscale avalanche phenomenon by combining the avalanching materials with plasmonically active metallic nanostructures.
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Detection of biologically relevant substances is an important aspect of interdisciplinary research with aim to specifically, selectively and efficiently determine the presence of various analytes. In our research, we test the concept of applying patterned silver nanostructures featuring plasmon resonance for efficient fluorescence – based detection of photoactive proteins. We will describe the recent results about controlling spatial position of plasmonic paths made of silver islands, as well as of silver nanowires. Detection protocol is based on real-time imagining using wide-field fluorescence microscopy, which allows for observing emission of individual proteins. The approach is universal and applicable for variety of analytes.
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MicroRNAs (miRNAs) are an emerging biotarget for clinical applications such as non-invasive detection of diseases such as cancer. However, current methods of miRNA quantification require tedious processing and amplification with highly trained specialists. Herein we show a simple and rapid colorimetric smartphone system that takes advantage of plasmonic nanoparticle-based assays to easily quantify miR-21 biomarker as a representative target for cancer disease detection. To achieve this, we use a unique assay known as Plasmonic Coupling Interference (PCI) to optically quantify the amount of biomarkers present. In addition, we utilize a specialized colorimetric processing method paired with accessible and cheap 3D printed parts to obviate the need for specialists to analyze and interpret the data. Our smart phone sensing system offers a practical miRNA diagnostic platform for the point-of-care applications as an alternative to more expensive lab-based methods.
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