Low Concentrations Of Molecules Research Articles

Overlooked Trace Molecules in Organic Aerosol Revealed by Gas Chromatography-Orbitrap Mass Spectrometry.

Molecular characterization of organic aerosol (OA) is crucial for understanding its sources and atmospheric processes. However, the chemical components of OA remain not well constrained. This study used gas chromatography-Orbitrap mass spectrometry (GC-Orbitrap MS) and GC-Quadrupole MS (GC-qMS) to investigate the organic composition in PM2.5 from Xi'an, Northwest China. GC-Orbitrap MS identified 335 organic tracers, including overlooked isomers and low-concentration molecules, approximately 1.6 times more than GC-qMS. The "molecular corridor" assessment shows the superior capability of GC-Orbitrap MS in identifying an expansive range of compounds with higher volatility and oxidation states, such as furanoses/pyranoses, di/hydroxy/ketonic acids, di/poly alcohols, aldehydes/ketones, and amines/amides. Seasonal variations in OA composition reflect diverse sources: increased di/poly alcohols in winter are derived from indoor emissions, furanoses/pyranoses and heterocyclics in spring and summer might be from biogenic emissions and secondary formation, and amides in autumn are probably from biomass burning. Integrating partial least squares discriminant analysis (PLS-DA) and potential source contribution function (PSCF) models, the source similarities and differences are further elucidated, highlighting the role of local emissions and transport from southern cities. This study offers new insights into the OA composition aided by the high mass resolution and sensitivity of GC-Orbitrap MS.

Nanoparticle/Cellulose-Based Surface Enhanced Raman Scattering Hybrid Sensors

Surface-Enhanced Raman Scattering (SERS) sensors are versatile biosensors for detecting very low concentrations of molecules. Their molecular and chemical sensitivity crucially depends on the tailoring of their nanostructure. These sensors rely on noble metal or oxide cluster layers, with their crystallinity and nanostructure carefully tuned to enable a maximum of plasmonic hot spots and enabling charge transfer. Typically, such sensors are in thin film geometry. In order to optimize their nanostructure and optical properties of the metal or oxide clusters, cellulose nanofibrils (CNFs) as template for nanoparticle-biopolymer hybrid materials are readily employed due to their high mechanical strength and ability to establish nanoporous, scalable thin films via spray deposition.[1] In order to characterize their nanostructure during synthesis of the hybrid nanoparticle-CNF material, grazing incidence X-ray scattering (GIXS) is ideally suited due to its ability to observe the nanostructural changes during farication and optimization of the sensor materials. The resulting nanostructure is then directly correlation to the sensor capability of the hybrid materials. As a first example, we use the catalytic properties of CNF during thermal decomposition of silver nitrate as precursor for fabrication of size-tuned silver clusters on CNF to tune their optical band-gap. The correlation between hot-spot size and silver nanoparticle size for optimizing the SERS sensitivity is elucidated using GIXS, showing for the first time the optimum hot spot size.[2] In order to facilitate an equal distribution of hot-spots, we make use of the three-dimensional nanoporous structure of the CNF thin films by adding shell-free silver nanoparticles in aqueous solution, again applying spray deposition.[3] The nanoporosity allows for reducing drastically agglomerations of silver nanoparticles, detrimental to hot-spots. At the same time, the spectral position of the plasmon resonance is tuned by the amount of CNF as structural matrix. As a final example we extend these results to novel semiconductor metal oxide nanomaterial (SMON)-based sensors.[4] Here, titanium oxide is deposited via atomic layer deposition (ALD) on the nanoporous CNF network, preserving its three-dimensional morphology. We optimize the nanostructure, crystallinity and rutile-to-anatase ratio in order to obtain superior sensitivity of the hybrid titania/CNF thin films as SMON SERS substrates. The improvement of SERS activity relies on the cooperative modulation of the CNF network and the crystalline states of the deposited titania. To summarize, we present new routes for SERS sensors based on plasmonic and charge transfer properties of hybrid materials by tailoring the hybrid nanostructure.[1] Brett, C. J.; Ohm, W.; Fricke, B.; Alexakis, A. E.; Laarmann, T.; Körstgens, V.; Müller-Buschbaum, P.; Söderberg, L. D.; Roth, S. V. Nanocellulose-Assisted Thermally Induced Growth of Silver Nanoparticles for Optical Applications. ACS Appl. Mater. Interfaces 2021, 13 (23), 27696–27704. https://doi.org/10.1021/acsami.1c07544.[2] Santoro, G.; Yu, S.; Schwartzkopf, M.; Zhang, P.; Koyiloth Vayalil, S.; Risch, J. F. H.; Rübhausen, M. A.; Hernández, M.; Domingo, C.; Roth, S. V. Silver Substrates for Surface Enhanced Raman Scattering: Correlation between Nanostructure and Raman Scattering Enhancement. Appl. Phys. Lett. 2014, 104 (24), 243107. https://doi.org/10.1063/1.4884423.[3] Chen, Q.; Brett, C. J.; Chumakov, A.; Gensch, M.; Schwartzkopf, M.; Körstgens, V.; Söderberg, L. D.; Plech, A.; Zhang, P.; Müller-Buschbaum, P.; Roth, S. V. Layer-by-Layer Spray-Coating of Cellulose Nanofibrils and Silver Nanoparticles for Hydrophilic Interfaces. ACS Appl. Nano Mater. 2021, 4 (1), 503–513. https://doi.org/10.1021/acsanm.0c02819.[4] Chen, Q.; Betker, M.; Harder, C.; Brett, C. J.; Schwartzkopf, M.; Ulrich, N. M.; Toimil‐Molares, M. E.; Trautmann, C.; Söderberg, L. D.; Weindl, C. L.; Körstgens, V.; Müller‐Buschbaum, P.; Ma, M.; Roth, S. V. Biopolymer‐Templated Deposition of Ordered and Polymorph Titanium Dioxide Thin Films for Improved Surface‐Enhanced Raman Scattering Sensitivity. Adv. Funct. Mater. 2022, 32 (6), 2108556. https://doi.org/10.1002/adfm.202108556.

Locational enrichment of low-abundance analytes through force-environment-modulation microsystem with ion concentration polarization

Ion concentration polarization (ICP) effect in micro-nanofluidic devices can concentrate low-concentration molecules. In this paper, we proposed a novel ICP-based enrichment system with horizontal barriers that adjust the force environment of charged particles, to achieve specific locational analytes enrichment. Mechanism of analyte enrichment through force modulation is revealed through numerical simulation using microchannels with varied channels widths, which is further validated through physical experiment. Overall, a specific target-oriented structure and load regulation method was proposed, under which the low-abundance analytes could be locationally concentrated by ∼ 4000 times. This study is expected to develop an innovative method for specifically locational ion enrichment in terms of scientific principles, providing theoretical and technical support for concentration and detection of charged substances in both research and industry such as biology, environment, chemistry studies, etc.

A Three-Dimensional Hydrophobic Surface-Enhanced Raman Scattering Sensor via a Silver-Coated Polytetrafluoroethylene Membrane for the Direct Trace Detection of Molecules in Water.

We report a three-dimensional (3D) SERS substrate consisting of a silver nanoparticle (AgNP) coating on the skeleton-fiber surfaces of a polytetrafluoroethylene (PTFE) membrane. Simple thermal evaporation was employed to deposit Ag onto the PTFE membrane to produce grape-shaped AgNPs. The 3D-distributed AgNPs exhibit not only strong localized surface plasmon resonance (LSPR) but also strong hydrophobic performance. High-density hotspots via silver nano-grape structures and nanogaps, the large 3D interaction volume, and the large total surface area, in combination with the hydrophobic enrichment of the specimen, facilitate high-sensitivity sensing performance of such a SERS substrate for the direct detection of low-concentration molecules in water. An enhancement factor of up to 1.97 × 1010 was achieved in the direct detection of R6G molecules in water with a concentration of 10-13 mol/L. The lowest detection limit of 100 ppt was reached in the detection of melamine in water. Such a SERS sensor may have potential applications in food-safety control, environmental water pollution monitoring, and biomedical analysis.

Plasmonic nanogrooves for SERS sensing by 3D printing

Surface enhanced Raman scattering (SERS) spectroscopy is a widely used analytical technique for detecting chemicals or biological molecules with high sensitivity and high specificity. Enhancing the sensitivity and lowering the detection limits are always the working direction of this research field. Furthermore, direct detection of low-concentration molecules in liquids remains a big challenge. In this work, we construct a SERS device consisting of periodically arranged polylactic acid (PLA) lines that are coated with silver, where the PLA line array is produced by 3D printing technique. The plasmonic nanogroove within the gap between the two adjacent PLA lines is found to be the dominant mechanism for SERS detection. A maximum enhancement factor of 2.26 × 106 has been achieved for the plasmonic nanogroove, with respect to a pure planar glass substrate. A detection limit of lower than 0.5 ppm has been research for such a sensor device in the direct detection of melamine in its aqueous solution. Furthermore, the PLA lines have advantages of biodegradability, biocompatibility, low costs, and thermo-plasticity, making the device environmentally friendly in potential applications in food safety inspection and pollutant detection in water.

Low-toxicity PEG-coated SERS silver nanocubes for diagnosing esophageal cancer

The early detection of esophageal cancer is crucial for enhancing patient survival. Surface-enhanced Raman scattering (SERS), renowned for its precise detection capabilities of low-concentration molecules and organisms, holds immense promise for early diagnosis. However, the use of silver nanoparticles to enhance the Raman signal can disrupt the detection process. To address this problem in this study, we synthesized polyethylene glycol (PEG)-coated silver nanocubes (PEG-AgNCs) as stable, label-free, and low-toxicity nanoprobes for detecting esophageal cancer. AgNCs with sharp corners and edges are selected as the SERS substrate to increase the strength of the Raman signal. To minimize the toxicity of AgNCs, the surface is coated with PEG, which exhibits outstanding biocompatibility. The SERS effectiveness of PEG-AgNCs was evaluated using 4-mercaptobenzoic acid as a Raman probe molecule, and the toxicity of PEG-AgNCs at different concentrations was investigated using human keratinocytes (HaCaT) and human esophageal carcinoma cells (TE-1). Results showed that PEG-AgNCs can effectively reduce the toxicity of AgNCs while maintaining a strong SERS signal. Remarkable differences in Raman spectra were observed between HaCat and TE-1 cells within the spectral range of 588–768 cm−1, indicating the potential of PEG-AgNCs in the early detection of esophageal cancer using Raman detection. Our study highlights the potential of developing low-toxicity SERS biosensors for biological and chemical analyses.

Faraday effect sensing of single-molecules by graphene-based layered structures

To investigate the sensing properties of the Faraday effect in graphene in terahertz (THz), we consider the modulations of Dirac gaps in graphene when gas molecules are adsorbed to its surface. Here, the effect of the associated bandgap opening in graphene’s spectrum on the sensing properties of the Faraday rotation (FR) in a 1D photonic graphene-based sensor with a microcavity defect channel covered by two graphene layers. Our proposed model introduces an optical contact-free mechanism for detecting low-concentration molecules attached to graphene’s surface. We also show that FR angles could reveal reversal signs for a different amount of surface transfer doping. Finally, the effect of increasing the temperature on the Faraday effect at a certain opening gap in graphene’s spectrum is investigated. Interestingly, stronger FR effect it was observed at higher temperatures. Our results could open the path for development of contact-free sensing applications in THz region.

Ultrasensitive and Reliable SERS Chip Based on Facile Assembly of AgNPs on Porous LIG to Enhance the Local Electromagnetic Field

Low-concentration molecular detection is of great value in chemical analysis, environmental monitoring, biological analysis, and other trace detection fields. Surface-enhanced Raman scattering (SERS) is widely used in the analysis of low-concentration molecules with great potential for biological detection due to nondestructive measurement. However, detection uniformity and repeatability are challenges in the application of SERS, especially as regards ultrasensitive detection. Here, a AgNPs@LIG SERS chip with excellent sensitivity and uniformity was fabricated by electroplating Ag nanoparticles (AgNPs) on a laser-induced graphene (LIG) surface prepared on a polyimide (PI) film, which realized large-scale production with controllable shape and area. Such an SERS chip features a limit of detection (LOD) of 10–14 M, an enhancement factor (EF) of 3 × 1010, and fine uniformity (∼9.6% relative standard deviation) for rhodamine 6G, benefiting from excellent local electromagnetic field enhancement generated by the gap of AgNPs and excellent performance of porous LIG. Finally, the chip was applied to the detection of melamine with the LOD of 10–9 M, which confirmed the potential application value of the SERS chip for pollutant analysis. In addition, the preparation of the composite SERS chip is simple for mass production, which provides great potential for the development of ultrasensitive SERS biosensors for various biological and chemical analyses.

Toward Plasmon-Controlled Generation of the Activating Ag Hotspot Nanospheres for Quantitative SERS Analysis

Introduction: Surface-enhanced Raman scattering (SERS) has attracted enormous concern as a robust vibrational spectroscopy technique with widespread applications, primarily for the ultrasensitive detection of low-concentration molecules and selective identification. Nevertheless, the optimization of SERS efficiency has been impeded by limitations in controlling the size of nanoparticles utilized in this technique. Method: In this study, the morphology, structure, chemical components, and optical properties of the as-synthesized Ag nanoparticles (Ag NPs) via a hydrothermal method were thoroughly investigated by sophisticated analyses. The synthesized Ag NPs were characterized for its morphological characteristics using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), X-ray diffraction (XRD), UV-Vis absorption spectroscopy, Raman spectroscopy, and assessed for their SERS performance in detecting organic substances including Crystal Violet (CV) and Rhodamine B (RhB). Results: The results showed that Ag NPs with different sizes could be obtained from 10 to 30 nm. These sizes corresponded to the duration of the hydrothermal method, which was 15, 20, and 25 hours, respectively. The optimal sample exhibited the capability to detect dye molecule solutions at diluted-low concentrations as low as 10-8 M. Conclusion: Through these results, we contribute to advancing the understanding of tailored nanoparticle synthesis for superior SERS performance, thus opening avenues for enhanced molecular detection in various applied analytical fields.

Direct Laser Writing of SERS Hollow Fibers.

We report the direct laser writing (DLW) of surface-enhanced Raman scattering (SERS) structures on the inner wall of a hollow fiber. Colloidal gold–silver alloy nanoparticles (Au–Ag ANPs) are firstly coated onto the inner wall of a hollow fiber. A green laser beam is focused through the outer surface of the hollow fiber to interact with colloidal Au–Ag ANPs so that they become melted and aggregated on the surface of the inner wall with strong adhesion. Such randomly distributed plasmonic nanostructures with high density and small gaps favor the SERS detection of low-concentration molecules in liquids flowing through the hollow fiber. Such a SERS device also supplies a three-dimensional microcavity for the interaction between excitation laser and the target molecules. The DLW system consists mainly of the flexible connection between the motor shaft and the hollow fiber, the program-controlled translation of the hollow fiber along its symmetric axis and rotation about the axis, as well as the mechanical design and the computer control system. This DLW technique enables high production, high stability, high reproducibility, high precision, and a high-flexibility fabrication of the hollow fiber SERS device. The resultant microcavity SERS scheme enables the high-sensitivity detection of R6G molecules in ethanol with a concentration of 10−7 mol/L.

Theory of chemical exchange saturation transfer MRI in the context of different magnetic fields.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a versatile MRI method that provides contrast based on the level of molecular and metabolic activity. This contrast arises from indirect measurement of protons in low concentration molecules that are exchanging with the abundant water proton pool. The indirect measurement is based on magnetization transfer of radio frequency (rf)-prepared magnetization from the small pool to the water pool. The signal can be modeled by the Bloch-McConnell equations combining standard magnetization dynamics and chemical exchange processes. In this article, we review analytical solutions of the Bloch-McConnell equations and especially the derived CEST signal equations and their implications. The analytical solutions give direct insight into the dependency of measurable CEST effects on underlying parameters such as the exchange rate and concentration of the solute pools, but also on the system parameters such as the rf irradiation field B1 , as well as the static magnetic field B0 . These theoretical field-strength dependencies and their influence on sequence design are highlighted herein. In vivo results of different groups making use of these field-strength benefits/dependencies are reviewed and discussed.

Optical Feedback for Sensitivity Enhancement in Direct Raman Detection of Liquids

Detection of low-concentration molecules in liquids has been a challenge in sensing technologies. Raman spectroscopy is an effective approach for trace detection, which is in fact a “volume-excitation” and “volume-collection” technique in the analysis of liquid samples. However, for the commonly employed one-pass excitation and back-scattering detection scheme, a large portion of both the excitation laser energy and the Raman-scattering light energy is wasted without efficient reuse or collection. In this consideration, we demonstrate a broadband optical feedback scheme by a curved high-reflection mirror for both the excitation and the Raman-scattering light, so that the excitation and the forward-propagating Raman signal can be back-reflected and collected with a high efficiency. Using the “F+2f” design, where F and f are the focal lengths of the focusing lens and curved reflection mirror, respectively, we were able to not only produce two focuses of the excitation laser beam but also extend the Raman interaction by a doubled distance. For the detection of pure ethanol molecules and the R6G molecules in water with a concentration of 10−3 M, the Raman signal was enhanced by a factor of about 5.6. The optical feedback scheme and discovered optical mechanisms supply effective improvements to the Raman spectroscopic measurements on liquid samples.

Micron-Scale NV-NMR Spectroscopy with Signal Amplification by Reversible Exchange

Optically-probed nitrogen-vacancy (NV) quantum defects in diamond can detect nuclear magnetic resonance (NMR) signals with high-spectral resolution from micron-scale sample volumes of about 10 picoliters. However, a key challenge for NV-NMR is detecting samples at millimolar concentrations. Here, we demonstrate an improvement in NV-NMR proton concentration sensitivity of about $10^5$ over thermal polarization by hyperpolarizing sample proton spins through signal amplification by reversible exchange (SABRE), enabling micron-scale NMR of small molecule sample concentrations as low as 1 millimolar in picoliter volumes. The SABRE-enhanced NV-NMR technique may enable detection and chemical analysis of low concentration molecules and their dynamics in complex micron-scale systems such as single-cells.

Acceleration of Biomolecule Enrichment and Detection with Rotationally Motorized Opto-Plasmonic Microsensors and the Working Mechanism.

Vigorous research efforts have advanced the state-of-the-art nanosensors with ultrahigh sensitivity for bioanalysis. However, a dilemmatic challenge remains: it is extremely difficult to obtain nanosensors that are both sensitive and high-speed for the detection of low-concentration molecules in aqueous samples. Herein, we report how the controlled mechanical rotation (or rotary motorization) of designed opto-plasmonic microsensors can substantially and robustly accelerate the enrichment and detection speed of deoxyribonucleic acid (DNA) with retained high sensitivity. At least 4-fold augmentation of the capture speed of DNA molecules is obtained from a microsensor rotating at 1200 rpm. Theoretical analysis and modeling shed light on the underlying working mechanism, governed by the molecule-motor-flow interaction as well as its application range and limitation. This work provides a device scheme that alleviates the dilemmatic challenge in biomolecule sensing and offers the understanding of the complex interactions of molecules and moving microobjects in suspension. The results may assist the rational design of efficient microrobotic systems for the capture, translocation, sensing, and release of biocargoes.

Quantitative Drug Dynamics Visualized by Alkyne-Tagged Plasmonic-Enhanced Raman Microscopy.

Visualizing live-cell uptake of small-molecule drugs is paramount for drug development and pharmaceutical sciences. Bioorthogonal imaging with click chemistry has made significant contributions to the field, visualizing small molecules in cells. Furthermore, recent developments in Raman microscopy, including stimulated Raman scattering (SRS) microscopy, have realized direct visualization of alkyne-tagged small-molecule drugs in live cells. However, Raman and SRS microscopy still suffer from limited detection sensitivity with low concentration molecules for observing temporal dynamics of drug uptake. Here, we demonstrate the combination of alkyne-tag and surface-enhanced Raman scattering (SERS) microscopy for the real-time monitoring of drug uptake in live cells. Gold nanoparticles are introduced into lysosomes of live cells by endocytosis and work as SERS probes. Raman signals of alkynes can be boosted by enhanced electric fields generated by plasmon resonance of gold nanoparticles when alkyne-tagged small molecules are colocalized with the nanoparticles. With time-lapse 3D SERS imaging, this technique allows us to investigate drug uptake by live cells with different chemical and physical conditions. We also perform quantitative evaluation of the uptake speed at the single-cell level using digital SERS counting under different quantities of drug molecules and temperature conditions. Our results illustrate that alkyne-tag SERS microscopy has a potential to be an alternative bioorthogonal imaging technique to investigate temporal dynamics of small-molecule uptake of live cells for pharmaceutical research.

On the interference from agar in chemical exchange saturation transfer MRI parameter optimization in model solutions.

Chemical exchange saturation transfer (CEST) MRI is currently set to become part of clinical routine as it enables indirect detection of low concentrated molecules and proteins. Recently, intermediate to fast exchanging functional groups of glucose and its derivatives, glutamate and dextran, have gained attention as promising CEST contrast agents. To increase the specificity of CEST MRI for certain functional groups, the presaturation module is commonly optimized. At an early stage, this is performed in well-defined model solutions, in which, for instance, the relaxation times are adjusted to mimic in vivo conditions. This often involves agar, assuming the substance would not yield significant CEST effects by itself, which the current study proves to be an invalid assumption. Model solutions at different pH values and concentrations of agar were investigated at different temperatures at a 9.4 T human whole body MR scanner. High power presaturation of around 4 μT, optimal for investigating intermediate to fast exchanging groups, was applied. Postprocessing included spatiotemporal corrections for B0 and spatial corrections for B1+ . CEST effects of up to 3 % of the bulk water signal were observed. From pH, concentration and temperature dependency, it was concluded that the observed behavior reflects a CEST effect of agar. It was also shown how to remove this undesirable contribution from CEST MRI data. It was concluded that if agar is involved in the CEST MRI parameter optimization process, its contribution to the observed effects has to be taken into account. CEST agent concentration must be sufficiently high to be able to neglect the contribution of agar, or a control sample at matched pH is necessary for correction. Experiments on pure agarose showed reduced CEST effects compared with agar but did not provide a neutral baseline either.

Review of the Application and Mechanism of Surface Enhanced Raman Spectroscopy (SERS) as Biosensor for the Study of Biological and Chemical Analyzes

Raman spectroscopy is an important method for the identification of molecules that is widely used to determine the chemical and structural properties of various materials. Many materials have special Raman spectra so that this phenomenon can it has become an effective tool for studying the structural and chemical properties of molecules. Since Raman spectroscopy can provide accurate information on the chemical and structural properties of biological compounds, this method is used in the field of science. Vital and especially in biological and medical studies is rapidly expanding. Amman is inherently weak and sometimes masked by noise and fluorescence. As a result, the study of low-concentration molecules is not feasible and the need to amplify the Raman scattering signal is clearly felt. . One of the efficient methods for studying low and even single molecular concentrations is the Surface Enhanced Raman Scattering (SERS) method. It uses gold, silver, copper and noble metal nanoparticles to enhance the Raman scattering signal. . SERS has been rapidly expanding over the past four decades, as applications for recognition in the fields of chemistry, materials sciences, biochemistry and biosciences are rapidly expanding. Advances in the manufacture of SERS-based biosensors are a major breakthrough in the detection of biological materials in which the electromagnetic field (effect) molecule is affected by the external field, this larger substitute field due to electromagnetic resonance near the metal surface is formed. Mechanisms of electromagnetic field (field effect) amplifiers mainly contribute to the development of SERS, which includes the study of detection performance, direct and indirect fabrication methods for the identification of biological and chemical analytes, Applications of biosensors, amplifiers, and SERS-based biosensor structures to detect biomolecules are briefly described.

Magnetic assembled 3D SERS substrate for sensitive detection of pesticide residue in soil

Three-dimensional (3D) surface enhanced Raman scattering (SERS) substrates were produced by magnetic force assisting self-assembled nanoparticles in arrayed holes. Compared to ‘2D’ plasmonic structures used in conventional SERS substrates, the ‘hot spots’ existed on whole depth of the 3D SERS substrates, which greatly enhanced the sensitivity. The prepared 3D SERS substrate was able to detect 4-aminothiophenol with a concentration down to 1 pM. Furthermore, the substrate was applied to detect hexachlorobenzene residue in soil, indicating its great potential for rapid and sensitive detection of extreme low concentrated molecules, especially pollutants residues in foods and environments.

Approximated analytical characterization of the steady-state chemical exchange saturation transfer (CEST) signals.

CEST MRI can indirectly detect low-concentrated molecules via their proton exchange with the bulk water and is widely measured by a sensitivity index, the asymmetry of magnetization transfer ratio (MTRasym ). Because CEST applications are often limited by their low sensitivity or specificity, it is important to characterize MTRasym analytically to optimize its sensitivity or specifity. Approximated analytical solutions of the MTRasym spectrum were derived based on a 2-pool chemical exchange model for slow-to-intermediate exchanges. The optimal saturation pulse power for maximizing the MTRasym or tuning MTRasym to a specific exchange rate and the peak position and linewidth of a MTRasym spectrum were also derived. These approximated analytical solutions were compared with the solutions from the Bloch-McConnell equations using computer simulations. The approximated analytical solutions of the MTRasym spectra, the optimizing parameters, and the peak and linewidth of MTRasym matched well with the solutions of Bloch-McConnell equations in the slow or slow-to-intermediate exchange regimes. These approximate analytical solutions can provide insights to the understanding of CEST signal property and help the optimization of saturation parameters and the interpretation of CEST data.

Large-Area, Reproducible Ag-Film-Functionalized Mixed Polystyrene Spheres on Silicon for Surface-Enhanced Raman Spectroscopy

Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical tool which presents high sensitivity in detection of the low concentration molecules and analytes. Its physical mechanism is based on strong confined electric fields in the tiny gaps between metallic nanostructures. In this work, two different sizes of polystyrene (PS) spheres were mixed to fabricate large-area quasi-random nanoarray on silicon decorated with Ag film for SERS. With the tuning of the volume ratio of two different sizes of spheres and the thickness of Ag film, it will always exhibit higher SERS intensity than periodic nanoarray with only one size. The Finite-Difference Time-Domain (FDTD) simulation shows that this hybrid structure provides high density of hot spots around the hybrid nanostructure due to surface plasmons, and the produced long decay length of the enhanced electric field makes the SERS substrate a zero-gap system for sensitive detection of large biomolecules. And this SERS system achieved an enhancement factor of the order of 105-106 in the detection of R6G molecules. The hybrid nanostructure is reproducible with a relative standard deviation of 10% .And the SERS substrates also produced sensitive Raman signals on long Aβ and hIAPP fibrils, which is potential for sensitive detection of amyloid aggregates that are related to Alzheimer's disease and type 2 diabetes (T2D). Our study demonstrates that the Ag-Film-Functionalized mixed PS spheres substrates may serve as good SERS substrates in the detection for biomedical and chemical analytes.