Jaqueline S. Soares

Modulating the electronic properties along carbon nanotubes via tube-substrate interaction.

We study single wall carbon nanotubes (SWNTs) deposited on quartz. Their Raman spectrum depends on the tube-substrate morphology, and in some cases, it shows that the same SWNT-on-quartz system exhibits a mixture of semiconductor and metal behavior, depending on the orientation between the tube and the substrate. We also address the problem using electric force microscopy and ab initio calculations, both showing that the electronic properties along a single SWNT are being modulated via tube-substrate interaction.

Investigation of noise-induced instabilities in quantitative biological spectroscopy and its implications for noninvasive glucose monitoring.

Over the past decade, optical spectroscopy has been employed in combination with multivariate chemometric models to investigate a wide variety of diseases and pathological conditions, primarily due to its excellent chemical specificity and lack of sample preparation requirements. Despite promising results in several proof-of-concept studies, its translation to the clinical setting has often been hindered by inadequate accuracy of the conventional spectroscopic models. To address this issue and the possibility of curved (nonlinear) effects in the relationship between the concentrations of the analyte of interest and the mixture spectra (due to fluctuations in sample and environmental conditions), support vector machine-based least-squares nonlinear regression (LS-SVR) has been recently proposed. In this paper, we investigate the robustness of this methodology to noise-induced instabilities and present an analytical formula for estimating modeling precision as a function of measurement noise and model parameters. This formalism can be readily used to evaluate uncertainty in information extracted from spectroscopic measurements, particularly important for rapid-acquisition biomedical applications. Subsequently, using field data (Raman spectra) acquired from a glucose clamping study on an animal model subject, we perform the first systematic investigation of the relative effect of additive interference components (namely, noise in prediction spectra, calibration spectra, and calibration concentrations) on the prediction error of nonlinear spectroscopic models. Our results show that the LS-SVR method gives more accurate results and is substantially more robust to additive noise when compared with conventional regression methods such as partial least-squares regression (PLS), when careful selection of the LS-SVR model parameters are performed. We anticipate that these results will be useful for uncertainty estimation in similar biomedical applications where the precision of measurements and its response to noise in the data set is as important, if not more so, than the generic accuracy level.

Spectroscopic approach for dynamic bioanalyte tracking with minimal concentration information

Vibrational spectroscopy has emerged as a promising tool for non-invasive, multiplexed measurement of blood constituents - an outstanding problem in biophotonics. Here, we propose a novel analytical framework that enables spectroscopy-based longitudinal tracking of chemical concentration without necessitating extensive a priori concentration information. The principal idea is to employ a concentration space transformation acquired from the spectral information, where these estimates are used together with the concentration profiles generated from the system kinetic model. Using blood glucose monitoring by Raman spectroscopy as an illustrative example, we demonstrate the efficacy of the proposed approach as compared to conventional calibration methods. Specifically, our approach exhibits a 35% reduction in error over partial least squares regression when applied to a dataset acquired from human subjects undergoing glucose tolerance tests. This method offers a new route at screening gestational diabetes and opens doors for continuous process monitoring without sample perturbation at intermediate time points.

Label-free route to rapid, nanoscale characterization of cellular structure and dynamics through opaque media.

We report a novel technique for label-free, rapid visualization of structure and dynamics of live cells with nanoscale sensitivity through traditionally opaque media. Specifically, by combining principles of near-infrared (NIR) spectroscopy and quantitative phase imaging, functional characterization of cellular structure and dynamics through silicon substrates is realized in our study. We demonstrate the efficacy of the new approach by full-field imaging of erythrocyte morphology in their native states with a nm path length sensitivity. Additionally, we observe dynamic variations of human embryonic kidney cells, through a silicon substrate, in response to hypotonic stimulation with ms temporal resolution that also provides unique insight into the underlying biophysical changes. The proposed technology is fundamentally suited for high-performance investigations of biological specimens and significantly expands the options for visualization in complex microfluidic devices fabricated on silicon.

In Situ Atomic Force Microscopy Tip-Induced Deformations and Raman Spectroscopy Characterization of Single-Wall Carbon Nanotubes

In this work, an atomic force microscope (AFM) is combined with a confocal Raman spectroscopy setup to follow in situ the evolution of the G-band feature of isolated single-wall carbon nanotubes (SWNTs) under transverse deformation. The SWNTs are pressed by a gold AFM tip against the substrate where they are sitting. From eight deformed SWNTs, five exhibit an overall decrease in the Raman signal intensity, while three exhibit vibrational changes related to the circumferential symmetry breaking. Our results reveal chirality dependent effects, which are averaged out in SWNT bundle measurements, including a previously elusive mode symmetry breaking that is here explored using molecular dynamics calculations.

Anatomy of noise in quantitative biological Raman spectroscopy

Raman spectroscopy is a fundamental form of molecular spectroscopy that is widely used to investigate structures and properties of molecules using their vibrational transitions. It relies on inelastic scattering of monochromatic laser light irradiating the specimen. After appropriate filtering the scattered light is dispersed onto a detector to determine the shift from the excitation wavelength, which appears in the form of characteristic spectral patterns. The technique can investigate biological samples and provide real-time diagnosis of diseases. However, despite its intrinsic advantages of specificity and minimal perturbation, the Raman scattered light is typically very weak and limits applications of Raman spectroscopy due to measurement (im)precision, driven by inherent noise in the acquired spectra. In this article, we review the principal noise sources that impact quantitative biological Raman spectroscopy. Further, we discuss how such noise effects can be reduced by innovative changes in the constructed Raman system and appropriate signal processing methods.

Study of Carbon Nanotube-Substrate Interaction

Environmental effects are very important in nanoscience and nanotechnology. This work reviews the importance of the substrate in single-wall carbon nanotube properties. Contact with a substrate can modify the nanotube properties, and such interactions have been broadly studied as either a negative aspect or a solution for developing carbon nanotube-based nanotechnologies. This paper discusses both theoretical and experimental studies where the interaction between the carbon nanotubes and the substrate affects the structural, electronic, and vibrational properties of the tubes.

Efficient delivery of DNA into bovine preimplantation embryos by multiwall carbon nanotubes.

The pellucid zone (PZ) is a protective embryonic cells barrier against chemical, physical or biological substances. This put, usual transfection methods are not efficient for mammal oocytes and embryos as they are exclusively for somatic cells. Carbon nanotubes have emerged as a new method for gene delivery, and they can be an alternative for embryos transfection, however its ability to cross the PZ and mediated gene transfer is unknown. Our data confirm that multiwall carbon nanotubes (MWNTs) can cross the PZ and delivery of pDNA into in vitro-fertilized bovine embryos. The degeneration rate and the expression of genes associated to cell viability were not affected in embryos exposed to MWNTs. Those embryos, however, had lower cell number and higher apoptotic cell index, but this did not impair the embryonic development. This study shows the potential utility of the MWNT for the development of new method for delivery of DNA into bovine embryos.

Raman spectroscopic sensing of carbonate intercalation in breast microcalcifications at stereotactic biopsy

Microcalcifications are an early mammographic sign of breast cancer and frequent target for stereotactic biopsy. Despite their indisputable value, microcalcifications, particularly of the type II variety that are comprised of calcium hydroxyapatite deposits, remain one of the least understood disease markers. Here we employed Raman spectroscopy to elucidate the relationship between pathogenicity of breast lesions in fresh biopsy cores and composition of type II microcalcifications. Using a chemometric model of chemical-morphological constituents, acquired Raman spectra were translated to characterize chemical makeup of the lesions. We find that increase in carbonate intercalation in the hydroxyapatite lattice can be reliably employed to differentiate benign from malignant lesions, with algorithms based only on carbonate and cytoplasmic protein content exhibiting excellent negative predictive value (93–98%). Our findings highlight the importance of calcium carbonate, an underrated constituent of microcalcifications, as a spectroscopic marker in breast pathology evaluation and pave the way for improved biopsy guidance.

Strain Discontinuity, Avalanche, and Memory in Carbon Nanotube Serpentine Systems.

This work addresses the problem of how a nano-object adheres to a supporting media. The case of study are the serpentine-like structures of single-wall carbon nanotubes (SWNTs) grown on vicinal crystalline quartz. We develop in situ nanomanipulation and confocal Raman spectroscopy in such systems, and to explain the results, we propose a dynamical equation in which static friction is treated phenomenologically and implemented as cutoff for velocities, via Heaviside step function and an adhesion force tensor. We demonstrate that the strain profiles observed along the SWNTs are due to anisotropic adhesion, adhesion discontinuities, strain avalanches, and memory effects. The equation is general enough to make predictions for various one- and two-dimensional nanosystems adhered to a supporting media.