Recent years have witnessed many breakthroughs in research on graphene (the first two-dimensional atomic crystal) as well as a significant advance in the mass production of this material. This one-atom-thick fabric of carbon uniquely combines extreme mechanical strength, exceptionally high electronic and thermal conductivities, impermeability to gases, as well as many other supreme properties, all of which make it highly attractive for numerous applications. Here we review recent progress in graphene research and in the development of production methods, and critically analyse the feasibility of various graphene applications.

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A roadmap for graphene

A review of reported tissue optical properties summarizes the wavelength-dependent behavior of scattering and absorption. Formulae are presented for generating the optical properties of a generic tissue with variable amounts of absorbing chromophores (blood, water, melanin, fat, yellow pigments) and a variable balance between small-scale scatterers and large-scale scatterers in the ultrastructures of cells and tissues.

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Optical properties of biological tissues: a review.

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

The somatic genomic landscape of glioblastoma

We review the field of femtosecond pulse shaping, in which Fourier synthesis methods are used to generate nearly arbitrarily shaped ultrafast optical wave forms according to user specification. An emphasis is placed on programmable pulse shaping methods based on the use of spatial light modulators. After outlining the fundamental principles of pulse shaping, we then present a detailed discussion of pulse shaping using several different types of spatial light modulators. Finally, new research directions in pulse shaping, and applications of pulse shaping to optical communications, biomedical optical imaging, high power laser amplifiers, quantum control, and laser-electron beam interactions are reviewed.

Femtosecond pulse shaping using spatial light modulators

Optical sensing of specific molecular targets and pathways deep inside living mice has become possible as a result of a number of advances. These include design of biocompatible near-infrared fluorochromes, development of targeted and activatable 'smart' imaging probes, engineered photoproteins and advances in photon migration theory and reconstruction. Together, these advances will provide new tools making it possible to understand more fully the functioning of protein networks, diagnose disease earlier and speed along drug discovery.

Shedding light onto live molecular targets

Urinary tract infection diagnosis and antibiogram require a 48 hour waiting period using conventional methods. This results in ineffective treatments, increased costs and most importantly in increased resistance to antibiotics. In this work, a novel method for classifying bacteria and determining their sensitivity to an antibiotic using Raman spectroscopy is described. Raman spectra of three species of gram negative Enterobacteria, most commonly responsible for urinary tract infections, were collected. The study included 25 samples each of E.coli, Klebsiella p. and Proteus spp. A novel algorithm based on spectral ratios followed by discriminant analysis resulted in classification with over 94% accuracy. Sensitivity and specificity for the three types of bacteria ranged from 88–100%. For the development of an antibiogram, bacterial samples were treated with the antibiotic ciprofloxacin to which they were all sensitive. Sensitivity to the antibiotic was evident after analysis of the Raman signatures of bacteria treated or not treated with this antibiotic as early as two hours after exposure. This technique can lead to the development of new technology for urinary tract infection diagnosis and antibiogram with same day results, bypassing urine cultures and avoiding all undesirable consequences of current practice.

Raman spectroscopy for UTI diagnosis and antibiogram

The high water content of meat, combined with all the nutrients it contains, make it vulnerable to spoilage at all stages of production and storage even when refrigerated at 5 °C. A non-destructive and in situ tool for meat sample testing, which could provide an accurate indication of the storage time of meat, would be very useful for the control of meat quality as well as for consumer safety. The proposed solution is based on Raman spectroscopy which is non-invasive and can be applied in situ. For the purposes of this project, 42 meat samples from 14 animals were obtained and three Raman spectra per sample were collected every two days for two weeks. The spectra were subsequently processed and the sample age was calculated using a set of linear differential equations. In addition, the samples were classified in categories corresponding to the age in 2-day steps (i.e., 0, 2, 4, 6, 8, 10, 12 or 14 days old), using linear discriminant analysis and cross-validation. Contrary to other studies, where the samples were simply grouped into two categories (higher or lower quality, suitable or unsuitable for human consumption, etc.), in this study, the age was predicted with a mean error of ~ 1 day (20%) or classified, in 2-day steps, with 100% accuracy. Although Raman spectroscopy has been used in the past for the analysis of meat samples, the proposed methodology has resulted in a prediction of the sample age far more accurately than any report in the literature.

Raman spectroscopy for highly accurate estimation of the age of refrigerated porcine muscle

The unique optical properties of noble metal nanostructures have led to an increased interest into their potential uses for various biological applications. For many medical investigations, it would be beneficial to use near infrared (NIR) excitation as well as small gold nanospheres, which can easily reach the cytoplasm and cell nucleus. To fulfil both requirements simultaneously, this paper proposes a novel nanostructure, the "shell aggregate", which consists of small nanospheres aggregate around a core such as an intracellular organelle. The extinction efficiency of such monolayer and bilayer shell aggregates is thoroughly investigated with appropriate simulations. The extinction spectra appear to depend heavily on the distance between the small nanospheres. The monolayer shell aggregate could be a good candidate for use in various biological, intracellular, applications since it provides a reasonably tunable plasmon resonance wavelength while the small size of its components can be exploited for intracellular distribution.

Investigation of shell aggregate gold nanostructures

In vivo high resolution imaging of gastrointestinal tissue using optical coherence tomography

Colorectal cancer (CRC) is one of the top causes of malignancy in both men and women. Although screening has significantly reduced CRC mortality, colonoscopy suffers from inadequate inspection and sampling of the tissue, a limitation that can be addressed by Optical Coherence Tomography (OCT). The use of fractal analysis, which has been shown to estimate the scatterer size from OCT data, could help improve the classification of colon polyps as compared to using morphological information alone. For this study, thirty polyps were imaged immediately post excision, histologically processed, and both the OCT and H&E images annotated by an expert. Multi-step segmentation was used to segment the crypt regions. Fractal analysis of those areas was employed to estimate the nuclear size and classify the polyps as normal or tubular adenoma. This process resulted in an accuracy of 81% (92% sensitivity, 40% specificity) as confirmed by histology. The poor specificity can be partially attributed to the small number (only 5) of normal polyps and, more importantly, to the confirmed presence of other histological features which might influence the fractal analysis. The proposed approach must be expanded to include more polyps and further enhanced to improve its specificity. However, these preliminary results provide evidence that this method has the potential to perform scatterer size estimation and tissue classification from en face images, thus, providing a robust approach for the improvement of the accuracy of endoscopic OCT and, in the future, the effectiveness of colonoscopy.

Costas Pitris

Papers

Raman spectroscopy for UTI diagnosis and antibiogram

Raman spectroscopy for highly accurate estimation of the age of refrigerated porcine muscle

Investigation of shell aggregate gold nanostructures

In vivo high resolution imaging of gastrointestinal tissue using optical coherence tomography

Morphological segmentation and fractal analysis for the classification of colon polyps from en face optical coherence tomography (OCT) images