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1.
Pathogens ; 13(5)2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38787210

ABSTRACT

This study demonstrates the capability of Raman microscopy for detecting structural differences in Giardia cells exposed to different drugs and incubation times. While metronidazole (MTZ) visibly affects the cells by inducing extracellular vesicle releases of toxic iron intermediates and modified triple-bond moieties, oseltamivir (OSM) alters the phenylalanine and lipid structures. Modifications in the heme protein environment and the transformation of iron from ferric to ferrous observed for both drug treatments are more notable for MTZ. Different contents and amounts of vesicle excretion are detected for 24 h or 48 h with MTZ incubation. At a shorter drug exposure, releases of altered proteins, glycogen, and phospholipids dominate. Agglomerates of transformed iron complexes from heme proteins and multiple-bond moieties prevail at 48 h of treatment. No such vesicle releases are present in the case of OSM usage. Drug incorporations into the cells and their impact on the plasma membrane and the dynamics of lipid raft confirmed by confocal fluorescence microscopy reveal a more destructive extent by OSM, corroborating the Raman results. Raman microscopy provides a broader understanding of the multifaceted factors and mechanisms responsible for giardiasis treatment or drug resistance by enabling a label-free, simultaneous monitoring of structural changes at the cellular and molecular levels.

2.
Dalton Trans ; 53(14): 6423-6435, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38506269

ABSTRACT

Combining the experimental techniques of high-resolution X-ray diffraction, magnetometry, specific heat measurement, and X-ray photoelectron, Raman and dielectric spectroscopy techniques, we have studied the influence of La and Cr doping on the crystal structure and magnetism of the room temperature Aurivillius multiferroic Bi5Ti3FeO15 by investigating the physical properties of (Bi4La)Ti3FeO15 and Bi5Ti3 (Fe0.5Cr0.5)O15. The parent (Bi5Ti3FeO15) and the doped ((Bi4La)Ti3FeO15 and Bi5Ti3(Fe0.5Cr0.5)O15) compounds crystallize in the A21am space group, which is confirmed through our analysis of high-resolution synchrotron X-ray diffraction data obtained on phase-pure polycrystalline powders. We determined the oxidation states of the metal atoms in the studied compounds as Fe3+, Ti4+, Cr3+, and La3+ through the analysis of X-ray photoelectron spectroscopy data. The magnetic susceptibilities of the three compounds are marked by the absence of a long-range ordered ground state, but dominated by superparamagnetic clusters with dominant antiferromagnetic interactions. This signature of short-range magnetism is also seen in specific heat as a low temperature enhancement which is suppressed upon the application of external magnetic fields up to 8 T. Our dielectric spectroscopy experiments showed that the three studied compounds display similar features in the dielectric constant measured as a function of frequency. However, upon doping La at the Bi site, the width of the ferroelectric hysteresis loop increases for (Bi4La)Ti3FeO15 compared to that of the parent compound Bi5Ti3FeO15, and with Cr doping, Bi5Ti3(Fe0.5Cr0.5)O15 becomes a leaky dielectric. The resilience of the Aurivillius crystal structure towards doping of La at the Bi site and Cr at the Fe site is clearly seen in the bulk properties of magnetic susceptibility, specific heat and the average crystal structure. The relevance of changes in the local structure is evident from our Raman spectroscopy and X-ray pair distribution function studies.

3.
Sensors (Basel) ; 22(7)2022 Mar 30.
Article in English | MEDLINE | ID: mdl-35408257

ABSTRACT

In this study, we demonstrate that Raman microscopy combined with computational analysis is a useful approach to discriminating accurately between brain tumor bio-specimens and to identifying structural changes in glioblastoma (GBM) bio-signatures after nordihydroguaiaretic acid (NDGA) administration. NDGA phenolic lignan was selected as a potential therapeutic agent because of its reported beneficial effects in alleviating and inhibiting the formation of multi-organ malignant tumors. The current analysis of NDGA's impact on GBM human cells demonstrates a reduction in the quantity of altered protein content and of reactive oxygen species (ROS)-damaged phenylalanine; results that correlate with the ROS scavenger and anti-oxidant properties of NDGA. A novel outcome presented here is the use of phenylalanine as a biomarker for differentiating between samples and assessing drug efficacy. Treatment with a low NDGA dose shows a decline in abnormal lipid-protein metabolism, which is inferred by the formation of lipid droplets and a decrease in altered protein content. A very high dose results in cell structural and membrane damage that favors transformed protein overexpression. The information gained through this work is of substantial value for understanding NDGA's beneficial as well as detrimental bio-effects as a potential therapeutic drug for brain cancer.


Subject(s)
Glioblastoma , Antioxidants , Glioblastoma/drug therapy , Humans , Masoprocol/pharmacology , Masoprocol/therapeutic use , Phenylalanine , Reactive Oxygen Species
4.
Diagnostics (Basel) ; 10(2)2020 Jan 31.
Article in English | MEDLINE | ID: mdl-32023980

ABSTRACT

Accurate clinical evaluation of renal osteodystrophy (ROD) is currently accomplished using invasive in vivo transiliac bone biopsy, followed by in vitro histomorphometry. In this study, we demonstrate that an alternative method for ROD assessment is through a fast, label-free Raman recording of multiple biomarkers combined with computational analysis for predicting the minimally required number of spectra for sample classification at defined accuracies. Four clinically relevant biomarkers: the mineral-to-matrix ratio, the carbonate-to-matrix ratio, phenylalanine, and calcium contents were experimentally determined and simultaneously considered as input to a linear discriminant analysis (LDA). Additionally, sample evaluation was performed with a linear support vector machine (LSVM) algorithm, with a 300 variable input. The computed probabilities based on a single spectrum were only marginally different (~80% from LDA and ~87% from LSVM), both providing an unacceptable classification power for a correct sample assignment. However, the Type I and Type II assignment errors confirm that a relatively small number of independent spectra (7 spectra for Type I and 5 spectra for Type II) is necessary for a p < 0.05 error probability. This low number of spectra supports the practicality of future in vivo Raman translation for a fast and accurate ROD detection in clinical settings.

5.
Materials (Basel) ; 12(19)2019 Sep 28.
Article in English | MEDLINE | ID: mdl-31569398

ABSTRACT

The comprehensive microscopic, spectroscopic, and in vitro voltammetric analysis presented in this work, which builds on the well-studied properties of carbon-based materials, facilitates potential ways for improvement of carbon fiber microelectrodes (CFMs) for neuroscience applications. Investigations by both, scanning electron microscopy (SEM) and confocal Raman spectroscopy, confirm a higher degree of structural ordering for the fibers exposed to carbonization temperatures. An evident correlation is also identified between the extent of structural defects observed from SEM and Raman results with the CFM electrochemical performance for dopamine detection. To improve CFM physico-chemical surface stability and increase its mechanical resistance to the induced compressive stress during anticipated in vivo tissue penetration, successful coating of the carbon fiber with boron-doped diamond (BDD) is also performed and microspectroscopically analyzed here. The absence of spectral shifts of the diamond Raman vibrational signature verifies that the growth of an unstrained BDD thin film was achieved. Although more work needs to be done to identify optimal parameter values for improved BDD deposition, this study serves as a demonstration of foundational technology for the development of more sensitive electrochemical sensors, that may have been impractical previously for clinical applications, due to limitations in either safety or performance.

6.
Int J Mol Sci ; 20(19)2019 Sep 27.
Article in English | MEDLINE | ID: mdl-31569637

ABSTRACT

In this study, we designed, synthesized, and characterized ultrahigh purity single-walled carbon nanotube (SWCNT)-alginate hydrogel composites. Among the parameters of importance in the formation of an alginate-based hydrogel composite with single-walled carbon nanotubes, are their varying degrees of purity, their particulate agglomeration and their dose-dependent correlation to cell viability, all of which have an impact on the resultant composite's efficiency and effectiveness towards cell-therapy. To promote their homogenous dispersion by preventing agglomeration of the SWCNT, three different surfactants-sodium dodecyl sulfate (SDS-anionic), cetyltrimethylammonium bromide (CTAB-cationic), and Pluronic F108 (nonionic)-were utilized. After mixing of the SWCNT-surfactant with alginate, the mixtures were cross-linked using divalent calcium ions and characterized using Raman spectroscopy. Rheometric analysis showed an increase in complex viscosity, loss, and storage moduli of the SWCNT composite gels in comparison with pure alginate gels. Scanning electron microscopy revealed the presence of a well-distributed porous structure, and all SWCNT-gel composites depicted enhanced electrical conductivity with respect to alginate gels. To characterize their biocompatibility, cardiomyocytes were cultured atop these SWCNT-gels. Results comprehensively implied that Pluronic F108 was most efficient in preventing agglomeration of the SWCNTs in the alginate matrix, leading to a stable scaffold formation without posing any toxicity to the cells.


Subject(s)
Alginates/chemistry , Carbon Monoxide/chemistry , Hydrogels/chemistry , Nanotubes, Carbon/chemistry , Biocompatible Materials/chemistry , Cell Line , Cell Survival , Electric Conductivity , Humans , Nanotubes, Carbon/ultrastructure , Pressure , Rheology , Spectrum Analysis
7.
Biosensors (Basel) ; 9(1)2018 Dec 26.
Article in English | MEDLINE | ID: mdl-30587770

ABSTRACT

With the goal of accurately detecting and quantifying the amounts of dopamine (DA) and serotonin (5-HT) in mixtures of these neurotransmitters without using any labelling, we present a detailed, comparative computational and Raman experimental study. Although discrimination between these two analytes is achievable in such mixtures for concentrations in the millimolar range, their accurate quantification remains unattainable. As shown for the first time in this work, the formation of a new composite resulting from their interactions with each other is the main reason for this lack of quantification. While this new hydrogen-bonded complex further complicates potential analyte discrimination and quantification at concentrations characteristic of physiological levels (i.e., nanomolar concentrations), it can also open new avenues for its use in drug delivery and pharmaceutical research. This remark is based not only on chemical interactions analyzed here from both theoretical and experimental approaches, but also on biological relationship, with consideration of both functional and neural proximity perspectives. Thus, this research constitutes an important contribution toward better understanding of neural processes, as well as toward possible future development of label-free biosensors.


Subject(s)
Biosensing Techniques , Dopamine/analysis , Neurotransmitter Agents/analysis , Serotonin/analysis , Density Functional Theory , Humans , Spectrum Analysis, Raman
8.
Sensors (Basel) ; 18(8)2018 Aug 16.
Article in English | MEDLINE | ID: mdl-30115871

ABSTRACT

To better understand detection and monitoring of the important neurotransmitter adenosine at physiological levels, this study combines quantum chemical density functional modeling and ultrasensitive surface-enhanced Raman spectroscopic (SERS) measurements. Combined simulation results and experimental data for an analyte concentration of about 10-11 molar indicate the presence of all known molecular forms resulting from adenosine's complex redox-reaction. Detailed analysis presented here, besides assessing potential Raman signatures of these adenosinic forms, also sheds light on the analytic redox process and voltammetric detection. Examples of adenosine Raman fingerprints for different molecular orientations with respect to the SERS substrate are the vibrational line around 920 ± 10 cm-1 for analyte physisorption through the carbinol moiety and around 1600 ± 20 cm-1 for its fully oxidized form. However, both hydroxyl/oxygen sites and NH2/nitrogen sites contribute to molecule's interaction with the SERS environment. Our results also reveal that contributions of partially oxidized adenosine forms and of the standard form are more likely to be detected with the first recorded voltammetric oxidation peak. The fully oxidized adenosine form contributes mostly to the second peak. Thus, this comparative theoretical⁻experimental investigation of adenosine's vibrational signatures provides significant insights for advancing its detection, and for future development of opto-voltammetric biosensors.

9.
Biosensors (Basel) ; 8(2)2018 Apr 08.
Article in English | MEDLINE | ID: mdl-29642494

ABSTRACT

Defining the pathogenesis of renal osteodystrophy (ROD) and its treatment efficacy are difficult, since many factors potentially affect bone quality. In this study, confocal Raman microscopy and parallel statistical analysis were used to identify differences in bone composition between healthy and ROD bone tissues through direct visualization of three main compositional parametric ratios, namely, calcium content, mineral-to-matrix, and carbonate-to-matrix. Besides the substantially lower values found in ROD specimens for these representative ratios, an obvious accumulation of phenylalanine is Raman spectroscopically observed for the first time in ROD samples and reported here. Thus, elevated phenylalanine could also be considered as an indicator of the disease. Since the image results are based on tens of thousands of spectra per sample, not only are the average ratios statistically significantly different for normal and ROD bone, but the method is clearly powerful in distinguishing between the two types of samples. Furthermore, the statistical outcomes demonstrate that only a relatively small number of spectra need to be recorded in order to classify the samples. This work thus opens the possibility of future development of in vivo Raman sensors for assessment of bone structure, remodeling, and mineralization, where different biomarkers are simultaneously detected with unprecedented accuracy.


Subject(s)
Chronic Kidney Disease-Mineral and Bone Disorder/diagnostic imaging , Microscopy/methods , Spectrum Analysis, Raman/methods , Aged , Chronic Kidney Disease-Mineral and Bone Disorder/pathology , Humans
10.
Materials (Basel) ; 10(11)2017 Nov 11.
Article in English | MEDLINE | ID: mdl-29137133

ABSTRACT

The focus of this paper is the investigation of reduced graphene oxide (GO)/nickel foam (RGON) samples for use as supercapacitor electrodes. Nickel foam samples were soaked in a GO suspension and dried before being subjected to two different methods to remove oxygen. Atmospheric pressure annealed (APA) samples were treated with a varying number (10-18) of nitrogen plasma jet scans, where sample temperatures did not exceed 280 °C. Furnace annealed (FA) samples were processed in an atmosphere of hydrogen and argon, at temperatures ranging from 600 °C to 900 °C. Environmental Scanning Electron Microscope (ESEM) data indicated that the carbon to oxygen (C:O) ratio for APA samples was minimized at an intermediate number of plasma scans. Fourier Transform Infrared Spectroscopic (FTIR) and Raman spectroscopic data supported this finding. ESEM analysis from FA samples showed that with increasing temperatures of annealing, GO is transformed to reduced graphene oxide (RGO), with C:O ratios exceeding 35:1. X-ray Photoelectron Spectroscopy (XPS) and X-ray diffraction (XRD) data indicated the formation of RGO with an increasing annealing temperature until 800 °C, when oxygen reincorporation in the surface atomic layers becomes an issue. Supercapacitors, constructed using the FA samples, demonstrated performances that correlated with surface atomic layer optimization of the C:O ratio.

11.
Biosensors (Basel) ; 7(4)2017 Sep 28.
Article in English | MEDLINE | ID: mdl-28956820

ABSTRACT

A combined theoretical and experimental analysis of dopamine (DA) is presented in this work with the objective of achieving more accurate detection and monitoring of this neurotransmitter at very low concentrations, specific to physiological levels. Surface-enhanced Raman spectroscopy on silver nanoparticles was employed for recording DA concentrations as low as 10-11 molar. Quantum chemical density functional calculations were carried out using Gaussian-09 analytical suite software. Relatively good agreement between the simulated and experimentally determined results indicates the presence of different DA molecular forms, such as uncharged DA±, anionic DA-, and dopaminequinone. Disappearance of the strongest bands of dopamine around 750 cm-1 and 790 cm-1, which suggests its adsorption onto the metallic surface, is not only consistent with all of these DA configurations, but also provides additional information about the analyte's redox process and voltammetric detection. On the other hand, occurrence of the abovementioned Raman lines could indicate the formation of multilayers of DA or its presence in a cationic DA⁺ form. Thus, through coordinated experiment and theory, valuable insights into changes observed in the vibrational signatures of this important neurotransmitter can be achieved for a better understanding of its detection at physiological levels, which is crucial if further optovoltammetric medical device development is envisioned.


Subject(s)
Dopamine/chemistry , Silver/chemistry , Spectrum Analysis, Raman/methods
12.
Sensors (Basel) ; 17(7)2017 Jun 22.
Article in English | MEDLINE | ID: mdl-28640186

ABSTRACT

Combined theoretical and experimental analysis of serotonin by quantum chemical density functional calculations and surface-enhanced Raman spectroscopy, respectively, is presented in this work to better understand phenomena related to this neurotransmitter's detection and monitoring at very low concentrations specific to physiological levels. In addition to the successful ultrasensitive analyte detection on silver nanoparticles for concentrations as low as 10-11 molar, the relatively good agreement between the simulated and experimentally determined results indicates the presence of all serotonin molecular forms, such as neutral, ionic, and those oxidized through redox reactions. Obvious structural molecular deformations such as bending of lateral amino chains are observed for both ionic and oxidized forms. Not only does this combined approach reveal more probable adsorption of serotonin into the silver surface through hydroxyl/oxygen sites than through NH/nitrogen sites, but also that it does so predominantly in its neutral (reduced) form, somewhat less so in its ionic forms, and much less in its oxidized forms. If the development of opto-voltammetric biosensors and their effective implementation is envisioned for the future, this study provides some needed scientific background for comprehending changes in the vibrational signatures of this important neurotransmitter.


Subject(s)
Metal Nanoparticles , Adsorption , Colloids , Serotonin , Silver , Spectrum Analysis, Raman
13.
Adv Colloid Interface Sci ; 244: 90-99, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27337997

ABSTRACT

The distribution of ions in the vicinity of the air/water interface is still a matter of strong debate, with numerous calculations and experiments providing contradictory results, even regarding the preference of simple ions (such as H+ and OH-) for interfacial or bulk water. When short range interactions between ions and the interface are assumed independent of bulk concentrations, if they are compatible with the surface tension data, they underpredict the experimental Zeta potentials by orders of magnitude. If they are compatible with Zeta potential data, they are in strong disagreement with surface tension experiments. It is suggested that these observations might be a result of the relatively low number of interfacial water molecules available to hydrate the ions and the competition between various ions for adsorption sites. Therefore, whereas at low bulk concentrations, the Structure-Breaking ions prefer the interface, at sufficiently large bulk concentrations the surface adsorptions of these ions become saturated, and their interfacial concentrations may become lower than in the bulk. Consequently, the total interactions of ions with the interface can be strongly attractive at low bulk concentrations, and less attractive (or even repulsive), at high concentrations. To model this effect, the interactions between ions and interface are taken into account via modified Langmuir adsorption expressions for OH- and Cl-, while the H+ ions are considered to be attached to any interfacial water molecule, even if the latter participate in the hydration of anions. The simple model of adsorption employed here is in agreement with both experiments on Zeta potential and on surface tension, and might reveal the conditions under which a given ion exhibits propensity for either the air/water interface, or for bulk water.

14.
Technol Cancer Res Treat ; 16(4): 461-469, 2017 08.
Article in English | MEDLINE | ID: mdl-27381847

ABSTRACT

Although not yet ready for clinical application, methods based on Raman spectroscopy have shown significant potential in identifying, characterizing, and discriminating between noncancerous and cancerous specimens. Real-time and accurate medical diagnosis achievable through this vibrational optical method largely benefits from improvements in current technological and software capabilities. Not only is the acquisition of spectral information now possible in milliseconds and analysis of hundreds of thousands of data points achieved in minutes, but Raman spectroscopy also allows simultaneous detection and monitoring of several biological components. Besides demonstrating a significant Raman signature distinction between nontumorigenic (MCF-10A) and tumorigenic (MCF-7) breast epithelial cells, our study demonstrates that Raman can be used as a label-free method to evaluate epidermal growth factor activity in tumor cells. Comparative Raman profiles and images of specimens in the presence or absence of epidermal growth factor show important differences in regions attributed to lipid, protein, and nucleic acid vibrations. The occurrence, which is dependent on the presence of epidermal growth factor, of new Raman features associated with the appearance of phosphothreonine and phosphoserine residues reflects a signal transduction from the membrane to the nucleus, with concomitant modification of DNA/RNA structural characteristics. Parallel Western blotting analysis reveals an epidermal growth factor induction of phosphorylated Akt protein, corroborating the Raman results. The analysis presented in this work is an important step toward Raman-based evaluation of biological activity of epidermal growth factor receptors on the surfaces of breast cancer cells. With the ultimate future goal of clinically implementing Raman-guided techniques for the diagnosis of breast tumors (e.g., with regard to specific receptor activity), the current results just lay the foundation for further label-free optical tools to diagnose the disease.


Subject(s)
Breast Neoplasms/diagnostic imaging , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , ErbB Receptors/metabolism , Female , Humans , MCF-7 Cells , Microscopy, Confocal , Spectrum Analysis, Raman , Staining and Labeling
15.
Front Hum Neurosci ; 10: 102, 2016.
Article in English | MEDLINE | ID: mdl-27014033

ABSTRACT

Deep brain stimulation (DBS), a surgical technique to treat certain neurologic and psychiatric conditions, relies on pre-determined stimulation parameters in an open-loop configuration. The major advancement in DBS devices is a closed-loop system that uses neurophysiologic feedback to dynamically adjust stimulation frequency and amplitude. Stimulation-driven neurochemical release can be measured by fast-scan cyclic voltammetry (FSCV), but existing FSCV electrodes rely on carbon fiber, which degrades quickly during use and is therefore unsuitable for chronic neurochemical recording. To address this issue, we developed durable, synthetic boron-doped diamond-based electrodes capable of measuring neurochemical release in humans. Compared to carbon fiber electrodes, they were more than two orders-of-magnitude more physically-robust and demonstrated longevity in vitro without deterioration. Applied for the first time in humans, diamond electrode recordings from thalamic targets in patients (n = 4) undergoing DBS for tremor produced signals consistent with adenosine release at a sensitivity comparable to carbon fiber electrodes. (Clinical trials # NCT01705301).

16.
Materials (Basel) ; 9(11)2016 Nov 04.
Article in English | MEDLINE | ID: mdl-28774016

ABSTRACT

In this study, we present a comprehensive investigation of graphene's optical and conductive properties using confocal Raman and a Drude model. A comparative analysis between experimental findings and theoretical predictions of the material's changes and improvements as it transitioned from three-dimensional graphite is also presented and discussed. Besides spectral recording by Raman, which reveals whether there is a single, a few, or multi-layers of graphene, the confocal Raman mapping allows for distinction of such domains and a direct visualization of material inhomogeneity. Drude model employment in the analysis of the far-infrared transmittance measurements demonstrates a distinct increase of the material's conductivity with dimensionality reduction. Other particularly important material characteristics, including carrier concentration and time constant, were also determined using this model and presented here. Furthermore, the detection of micromolar concentration of dopamine on graphene surfaces not only proves that the Raman technique facilitates ultrasensitive chemical detection of analytes, besides offering high information content about the biomaterial under study, but also that carbon-based materials are biocompatible and favorable micro-environments for such detection. Such information is valuable for the development of bio-medical sensors, which is the main application envisioned for this analysis.

17.
Med Eng Phys ; 37(10): 1020-6, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26318799

ABSTRACT

This paper presents the development of an energy harvesting circuit for use with a head-mountable deep brain stimulation (DBS) device. It consists of a circular planar inverted-F antenna (PIFA) and a Schottky diode-based Cockcroft-Walton 4-voltage rectifier. The PIFA has the volume of π × 10(2) × 1.5 mm(3), resonance frequency of 915 MHz, and bandwidth of 16 MHz (909-925 MHz) at a return loss of -10 dB. The rectifier offers maximum efficiency of 78% for the input power of -5 dBm at a 5 kΩ load resistance. The developed rectenna operates efficiently at 915 MHz for the input power within -15 dBm to +5 dBm. For operating a DBS device, the DC voltage of 2 V is recorded from the rectenna terminal at a distance of 55 cm away from a 26.77 dBm transmitter in free space. An in-vitro test of the DBS device is presented.


Subject(s)
Deep Brain Stimulation/instrumentation , Electrical Equipment and Supplies , Radio Waves , Animals , Equipment Design , Head , Mice , Models, Animal
18.
J Mater Sci ; 49(16): 5782-5789, 2014 Aug 01.
Article in English | MEDLINE | ID: mdl-25328245

ABSTRACT

Boron-doped diamond (BDD) has seen a substantial increase in interest for use as electrode coating material for electrochemistry and studies of deep brain stimulation mechanism. In this study, we present an alternative method for determining important characteristics, including conductivity, carrier concentration, and time constant, of such material by the signature of Drude-like metallic behavior in the far-infrared (IR) spectral range. Unlike the direct determination of conductivity from the four-point probe method, using far-IR transmittance provides additional information, such as whether the incorporation of boron results in a large concentration of carriers or in inducing defects in the diamond lattice. The slightly doped to medium-doped BDD samples that were produced using chemical vapor deposition and analyzed in this work show conductivities ranging between 5.5 and 11 (Ω cm)-1. Different growth conditions demonstrate that increasing boron concentration results in an increase in the carrier concentration, with values between 7.2 × 1016 and 2.5 × 1017 carriers/cm3. Addition of boron, besides leading to a decrease in the resistivity, also resulted in a decrease in the time constant, limiting BDD conductivity. Investigations, by confocal Raman mapping, of the induced stress in the material due to interaction with the substrate or to the amount of doping are also presented and discussed. The induced tensile stress, which was distributed closer to the film-substrate interface decreased slightly with doping.

19.
Neuromodulation ; 16(3): 192-9; discussion 198-9, 2013.
Article in English | MEDLINE | ID: mdl-22989218

ABSTRACT

OBJECTIVES: We demonstrate that confocal Raman mapping spectroscopy provides rapid, detailed, and accurate neurotransmitter analysis, enabling millisecond time resolution monitoring of biochemical dynamics. As a prototypical demonstration of the power of the method, we present real-time in vitro serotonin, adenosine, and dopamine detection, and dopamine diffusion in an inhomogeneous organic gel, which was used as a substitute for neurologic tissue. MATERIALS AND METHODS: Dopamine, adenosine, and serotonin were used to prepare neurotransmitter solutions in distilled water. The solutions were applied to the surfaces of glass slides, where they interdiffused. Raman mapping was achieved by detecting nonoverlapping spectral signatures characteristic of the neurotransmitters with an alpha 300 WITec confocal Raman system, using 532 nm neodymium-doped yttrium aluminum garnet laser excitation. Every local Raman spectrum was recorded in milliseconds and complete Raman mapping in a few seconds. RESULTS: Without damage, dyeing, or preferential sample preparation, confocal Raman mapping provided positive detection of each neurotransmitter, allowing association of the high-resolution spectra with specific microscale image regions. Such information is particularly important for complex, heterogeneous samples, where changes in composition can influence neurotransmission processes. We also report an estimated dopamine diffusion coefficient two orders of magnitude smaller than that calculated by the flow-injection method. CONCLUSIONS: Accurate nondestructive characterization for real-time detection of neurotransmitters in inhomogeneous environments without the requirement of sample labeling is a key issue in neuroscience. Our work demonstrates the capabilities of Raman spectroscopy in biological applications, possibly providing a new tool for elucidating the mechanism and kinetics of deep brain stimulation.


Subject(s)
Microscopy, Confocal , Neurotransmitter Agents/analysis , Spectrum Analysis, Raman/methods , Animals , Humans
20.
Materials (Basel) ; 6(12): 5726-5741, 2013 Dec 06.
Article in English | MEDLINE | ID: mdl-28788420

ABSTRACT

Building on diamond characteristics such as hardness, chemical inertness and low electron emission threshold voltage, the current microscopic, spectroscopic and voltammetric investigations are directed towards improving the properties of electrode coating materials for their future use in clinical studies of deep brain stimulation via fast-scan cyclic voltammetry (FSCV). In this study we combine the capabilities of confocal Raman mapping in providing detailed and accurate analysis of local distributions of material constituents in a series of boron-doped polycrystalline diamond films grown by chemical vapor deposition, with information from the more conventional techniques of scanning electron microscopy (SEM) and infrared absorption spectroscopy. Although SEM images show a uniform distribution of film crystallites, they have the limitation of being unable to differentiate the distribution of boron in the diamond. Values of 1018-1021 atoms/cm³ of boron content have been estimated from the absorption coefficient of the 1290 cm-1 infrared absorption band and from the 500 cm-1 Raman vibration. The observed accumulation of boron atoms and carbon sp² impurities at the grain boundaries suggests that very high doping levels do not necessarily contribute to improvement of the material's conductivity, corroborating with voltammetric data. FSCV results also indicate an enhanced stability of analyte detection.

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