An antigen-targeting assay for Lyme disease: Combining aptamers and SERS to detect the OspA protein.

Lyme disease is the fastest growing vector-borne disease in the United States. However, current testing modalities are ill suited to detection of Lyme disease, leading to the diagnosis of many cases after treatment is effective. We present an improved, direct method Lyme disease diagnosis, where the Lyme specific biomarker Outer Surface Protein A (OspA) in clinical serum samples is identified using a diagnostic platform combining surface enhanced Raman scattering (SERS) and aptamers. Employing orthogonal projections to latent structures discriminant analysis, the system accurately identified 91% of serum samples from Lyme patients, and 96% of serum samples from symptomatic controls. In addition, the OspA limit-of-detection, determined to be 1 × 10-4 ng/mL, is greater than four orders of magnitude lower than that found in serum samples from early Lyme disease patients. The application of this platform to detect this difficult-to-diagnose disease suggests its potential for detecting other diseases that present similar difficulties.

Modeling research universities: Predicting probable futures of public vs. private and large vs. small research universities.

The future of the American academic research enterprise is considered. Data are presented that characterize the resources available for the 160 best-resourced research universities, a small subset of the 2,285 4-year, nonprofit, higher education institutions. A computational model of research universities was extended and used to simulate three strategic scenarios: status quo, steady decline in foreign graduate student enrollments, and downward tuition pressures from high-quality, online professional master's programs. Four specific universities are modeled: large public and private, and small public and private. The former are at the top of the 160 in terms of resources, while the latter are at the bottom of the 160. The model's projections suggest how universities might address these competitive forces. In some situations, it would be in the economic interests of these universities to restrict research activities to avoid the inherent subsidies these activities require. The computational projections portend the need for fundamental change of approaches to business for universities without large institutional resources.

Relative contributions of Franck-Condon to Herzberg-Teller terms in charge transfer surface-enhanced Raman scattering spectroscopy.

We have theoretically modeled charge transfer (CT) surface enhanced raman scattering (SERS) spectroscopy using pyridine bound to a planar Ag6 metal nanocluster. CT states were determined by natural transition orbital hole-particle plots and CT distance DCT and the amount of charge transferred qCT indices. We first consider a resonance Raman (RR) model based on the Albrecht approach and calculate the ratio of the Herzberg-Teller (HT) B or C term to the Franck-Condon (FC) A term for a totally symmetric a1 vibrational mode exciting in the lowest energy CT state. Using a dimensionless upper limit to the displacement factor ∆ = 0.05 in the FC term based on the examination of overtones in experimental spectra and a calculated HT coupling constant hCT = 0.439 eV/Å(amu)1/2 in the HT term, we calculated the scattering ratio of the HT to FC intensities as 147. This example indicated that for totally symmetric modes, the scattering intensity would all come from HT scattering. To further verify this result, we used the general time-dependent-RR formulation of Baiardi, Bloino, and Barone with the adiabatic Hessian model to calculate the FC, the Frank-Condon and Herzberg-Teller (FCHT), and the HT terms for pyridine in the C2v Ag6-pyridine complexes. For all cases we studied with pyridine in two orientations either parallel or perpendicular to the planar Ag6 cluster, the HT terms, FCHT + HT, dominate the FC term in the CT RR spectrum. These results indicate that for CT SERS, the intensity of all the totally and non-totally symmetric vibrational modes should come from the HT effect.

Retrospective analysis of cardiac index and lactate production on cardiopulmonary bypass for a congenital cardiac patient population.

BACKGROUND: Providing adequate metabolic support is the principal concern during cardiopulmonary bypass (CPB) with different strategies utilized to enhance oxygen delivery to the patient. Modifying temperature, hematocrit (Hct) and cardiac index (CI) during CPB are primary techniques which aid in this effort. Based upon surgeon preference, the study institution employs differing perfusion strategies (PS) during congenital cardiac surgery requiring CPB. One method utilizes a 2.4 L/min/m2 CI and nadir Hct of 28% (PS1) and the other a 3.0 L/min/m2 CI with a nadir Hct of 25% (PS2). METHODS: Cardiopulmonary bypass cases during which the PS1 or PS2 strategies were applied were retrospectively examined, finding no significant difference in pre-CPB lactate, maximum lactate on CPB or maximum change in lactate on CPB. RESULTS: While the post-CPB lactate was statistically significantly higher in the PS2 group (p=0.024), the magnitude of difference (0.15 mmol/L) was small. CONCLUSIONS: This study illustrates that, when oxygen delivery or tissue perfusion is suspected as the primary cause of lactate production during CPB, increasing the CI to a 3.0 rather than a 2.4 CI may be more advantageous than packed red blood cell administration.

Detection and Quantitation of Trace Fentanyl in Heroin by Surface-Enhanced Raman Spectroscopy.

The identification of fentanyl, a main culprit in opioid overdose deaths, has become critical. Whereas Raman spectroscopy is an effective tool for detecting illicit drugs, the weak intensity of Raman scattering can make it difficult to distinguish trace materials. This shortcoming is addressed by surface-enhanced Raman spectroscopy (SERS), which produces strong signal enhancements when target compounds are near metal nanoparticles. This work examines the use of a paper-based substrate impregnated with silver nanoparticles for the detection of trace quantities of fentanyl alone and as an adulterant in heroin. In addition, intensity ratios of diagnostic peaks associated with each substance were fitted to a Langmuir isotherm calibration model and used for the quantitative analysis of fentanyl in heroin mixtures. Linearity was observed at <6% fentanyl, a significant finding that is consistent with concentrations found in drugs seized during law enforcement efforts. In addition, swabbing with these paper-based SERS substrates facilitated the recovery of fentanyl from surfaces, showing this to be applicable for crime scene investigations. However, assessment using the calibration model proved difficult for swabbed samples. Overall, this work demonstrates a potentially simple and sensitive technique for the forensic analysis and quantitation of fentanyl in trace amounts.

Enhanced Raman Scattering with Dielectrics.

Dielectrics represent a new frontier for surface-enhanced Raman scattering. They can serve as either a complement or an alternative to conventional, metal-based SERS, offering key advantages in terms of low invasiveness, reproducibility, versatility, and recyclability. In comparison to metals, dielectric systems and, in particular, semiconductors are characterized by a much greater variety of parameters and properties that can be tailored to achieve enhanced Raman scattering or related effects. Light-trapping and subwavelength-focusing capabilities, morphology-dependent resonances, control of band gap and stoichiometry, size-dependent plasmons and excitons, and charge transfer from semiconductors to molecules and vice versa are a few examples of the manifold opportunities associated with the use of semiconductors as SERS-active materials. This review provides a broad analysis of SERS with dielectrics, encompassing different optical phenomena at the basis of the Raman scattering enhancement and introducing future challenges for light harvesting, vibrational spectroscopy, imaging, and sensing.

The theory of surface-enhanced Raman scattering on semiconductor nanoparticles; toward the optimization of SERS sensors.

We present an expression for the lowest order nonzero contribution to the surface-enhanced Raman spectrum obtained from a system of a molecule adsorbed on a semiconductor nanoparticle. Herzberg-Teller vibronic coupling of the zero-order Born-Oppenheimer states results in an expression which may be regarded as an extension of the Albrecht A-, B-, and C-terms to SERS substrates. We show that the SERS enhancement is caused by combinations of several types of resonances in the combined system, namely, surface, exciton, charge-transfer, and molecular resonances. These resonances are coupled by terms in the numerator, which provide selection rules that enable various tests of the theory and predict the relative intensities of the Raman lines. Furthermore, by considering interactions of the various contributions to the SERS enhancement, we are able to develop ways to optimize the enhancement factor by tailoring the semiconductor nanostructure, thereby adjusting the locations of the various contributing resonances. This provides a procedure by which molecular sensors can be constructed and optimized. We provide several experimental examples on substrates such as monolayer MoS2 and GaN nanorods.

Accuracy of the Spectrum Medical M4 and Terumo CDI 500 compared to the Radiometer ABL90 FLEX benchtop blood analyzer.

The benchtop blood analyzer is the gold standard for blood oxygen saturation (SO2) and hemoglobin (Hb) analysis. However, the benchtop analyzer only provides values at a given point in time. In the field of cardiovascular perfusion and the practice of cardiopulmonary bypass (CPB), continuous measurement of SvO2 and hemoglobin values have become commonplace. Two devices currently available which monitor these values are the Terumo CDI 500 and Spectrum Medical M4. A retrospective study was conducted to examine the accuracy of the M4 technology and the CDI 500 as they compare to each other and the ABL90 FLEX, a benchtop blood gas analyzer. The data revealed the magnitude of mean differences were small, even when significant. However, the 95% Limits of Agreement were too large for either device to allow substitution of the CDI 500 and M4 hemoglobin or SvO2 values for ABL90 values. As recommended by the manufacturers, the CDI 500 and M4 should only be used as a trending device.

Enhancement of surface phonon modes in the Raman spectrum of ZnSe nanoparticles on adsorption of 4-mercaptopyridine.

By chemically etching a thin film of crystalline ZnSe with acid, we observe a strong Raman enhancement of the surface phonon modes of ZnSe on adsorption of a molecule (4-mercaptopyridine). The surface is composed of oblate hemi-ellipsoids, which has a large surface-to-bulk ratio. The assignment of the observed modes (at 248 and 492 cm(-1)) to a fundamental and first overtone of the surface optical mode is consistent with observations from high-resolution electron energy loss spectroscopy as well as calculations.

Detection of organic colorants in historical painting layers using UV laser ablation surface-enhanced Raman microspectroscopy.

Surface-enhanced Raman spectroscopy (SERS) has been increasingly used in the study of works of art to identify organic pigments and dyes in paintings, which (depending on the material) are difficult or not possible to detect by other current methods. The application of SERS to the study of paintings has been limited, however, by the lack of a sampling approach with sufficient sensitivity and spatial resolution. We show that ultraviolet laser ablation (LA) sampling coupled with SERS detection can be successfully used to study paint layers. LA-SERS permitted the isolation of signals from colorants in individual thin paint layers in sample cross-sections, avoiding contamination from adjacent layers. These results expand the range of analytical applications of SERS demonstrating how the technique can be used to sensitively detect minor organic components in complex matrices. While this is fundamental for the study of cultural heritage, it is also relevant in other fields such as forensic analysis, food science, and pharmacology.

Laser ablation surface-enhanced Raman microspectroscopy.

Improved identification of trace organic compounds in complex matrixes is critical for a variety of fields such as material science, heritage science, and forensics. Surface-enhanced Raman scattering (SERS) is a vibrational spectroscopy technique that can attain single-molecule sensitivity and has been shown to complement mass spectrometry, but lacks widespread application without a robust method that utilizes the effect. We demonstrate a new, highly sensitive, and widely applicable approach to SERS analysis based on laser ablation in the presence of a tailored plasmonic substrate. We analyze several challenging compounds, including non-water-soluble pigments and dyed leather from an ancient Egyptian chariot, achieving sensitivity as high as 120 amol for a 1:1 signal-to-noise ratio and 5 µm spatial resolution. This represents orders of magnitude improvement in spatial resolution and sensitivity compared to those of other SERS approaches intended for widespread application, greatly increasing the applicability of SERS.

Highly efficient construction of oriented sandwich structures for surface-enhanced Raman scattering.

The purpose of this study is to solve the problem of low achievement in fabricating sandwich surface-enhanced Raman scattering (SERS) substrates. We demonstrated a highly efficient sandwich structure by the oriented assembly of metal nanoparticles (NPs) on a periodic hexagonal array of metal nanoprisms with 1,4-benzenedithiol (1,4-BDT) as linkers. The metal nanoprism array was prepared by vacuum deposition of metal on a close-packed polystyrene nanosphere pre-patterned substrate. The metal nanoprism array presents different surface properties from the pits left from the removal of polystyrene nanospheres, which causes linkers to selectively adsorb on the metal nanoprism array and sequentially leads to the oriented immobilization of the second-layer metal NPs, avoiding mismatched orientation. These sandwich SERS substrates were characterized by extinction spectroscopy and atomic force microscopy and their enhancement activity was evaluated under different excitation wavelengths. The sandwich structure greatly increases the achievement of 'hot spots' to almost 100% of all the metal nanoprisms and enables a large amplification of SERS signals by a factor of ten. This method has the advantages of simplicity, high efficiency, high throughput, controllability and high reproducibility. It has significance in both the study of SERS substrates and the development of plasmonic devices.

Sample treatment considerations in the analysis of organic colorants by surface-enhanced Raman scattering.

The introduction of surface-enhanced Raman spectroscopy (SERS) in the field of cultural heritage has significantly improved the analysis of the organic dyes and their complexes that have been used as textile dyes and pigments in paintings and other polychrome works of art since antiquity. Over the last five years, a number of different procedures have been developed by various research groups. In this Article, we evaluate the effect of pretreating samples by exposing them to hydrofluoric acid (HF) vapor prior to SERS analysis, a step designed to hydrolyze the dye-metal complexes and increase analyte adsorption on the nanosized metallic support, thus enhancing the SERS signal. Materials studied include pure colorants, commercial lake pigments, and fibers from dyed textiles, as well as actual aged samples, such as microscopic fragments of lakes on paper and ancient pigments and glazes from several works of art, covering a wide range of time, from the second century B.C. to the early 20th century. In each case, SERS spectra obtained with or without HF hydrolysis were critically evaluated. The pretreatment with HF vapor resulted in faster analysis and increased sensitivity in most cases, with the exception of dyed silk fibers, where silk protein hydrolyzates were found to interfere with SERS analysis. As a final point, a two-step procedure including SERS on untreated and treated samples is proposed as a standard approach: by analyzing a sample first without hydrolysis, and then, following removal of the colloid, upon HF treatment, the best and most reliable results for a great number of dyes and substrates are assured.

The theory of surface-enhanced Raman scattering.

By considering the molecule and metal to form a conjoined system, we derive an expression for the observed Raman spectrum in surface-enhanced Raman scattering. The metal levels are considered to consist of a continuum with levels filled up to the Fermi level, and empty above, while the molecule has discrete levels filled up to the highest occupied orbital, and empty above that. It is presumed that the Fermi level of the metal lies between the highest filled and the lowest unfilled level of the molecule. The molecule levels are then coupled to the metal continuum both in the filled and unfilled levels, and using the solutions to this problem provided by Fano, we derive an expression for the transition amplitude between the ground stationary state and some excited stationary state of the molecule-metal system. It is shown that three resonances contribute to the overall enhancement; namely, the surface plasmon resonance, the molecular resonances, as well as charge-transfer resonances between the molecule and metal. Furthermore, these resonances are linked by terms in the numerator, which result in SERS selection rules. These linked resonances cannot be separated, accounting for many of the observed SERS phenomena. The molecule-metal coupling is interpreted in terms of a deformation potential which is compared to the Herzberg-Teller vibronic coupling constant. We show that one term in the sum involves coupling between the surface plasmon transition dipole and the molecular transition dipole. They are coupled through the deformation potential connecting to charge-transfer states. Another term is shown to involve coupling between the charge-transfer transition and the molecular transition dipoles. These are coupled by the deformation potential connecting to plasmon resonance states. By applying the selection rules to the cases of dimer and trimer nanoparticles we show that the SERS spectrum can vary considerably with excitation wavelength, depending on which plasmon and/or charge-transfer resonance is excited.

Left ventricular noncompaction cardiomyopathy in Barth syndrome: an example of an undulating cardiac phenotype necessitating mechanical circulatory support as a bridge to transplantation.

Barth syndrome (BTHS) is associated with myocardial disease, frequently left ventricular noncompaction cardiomyopathy, which may necessitate cardiac transplantation or lead to death in some patients. We report a child with BTHS who had an "undulating cardiac phenotype" and ultimately developed decompensated heart failure requiring mechanical circulatory support with a ventricular assist device as a bridge to transplantation. His course was complicated by acute lung injury requiring placement of an in-line oxygenator to maintain end-organ function. Not only was his course complicated by cardiac and respiratory failure but his BTHS associated comorbidities complicated the management of his therapy using mechanical assist device support. He was successfully supported and subsequently was transplanted. Here we discuss the management of a child with BTHS using mechanical circulatory support and describe the use of an in-line oxygenator, Quadrox, with the Berlin Excor device.

The Theory of Surface-Enhanced Raman Spectroscopy on Organic Semiconductors: Graphene.

Drawing on a theoretical expression previously derived for general semiconductor substrates, we examine the surface-enhancement of the Raman signal (SERS) when the substrate is chosen to be monolayer graphene. The underlying theory involves vibronic coupling, originally proposed by Herzberg and Teller. Vibronic coupling of the allowed molecular transitions with the charge-transfer transitions between the molecule and the substrate has been shown to be responsible for the SERS enhancement in semiconductor substrates. We then examine such an expression for the Raman enhancement in monolayer graphene, which is dependent on the square of the derivative of the density of states of the graphene. On integration, we find that the discontinuity of the density-of-states function leads to a singularity in the SERS intensity. Knowledge of the location of this resonance allows us to maximize the Raman intensity by careful alignment of the doping level of the graphene substrate with the charge-transfer transition.