Raman spectroscopy: a real-time tool for identifying microcalcifications during stereotactic breast core needle biopsies

Microcalcifications are an early mammographic sign of breast cancer and a target for stereotactic breast needle biopsy. We present here a Raman spectroscopic tool for detecting microcalcifications in breast tissue based on their chemical composition. We collected ex vivo Raman spectra from 159 tissue sites in fresh stereotactic breast needle biopsies from 33 patients, including 54 normal sites, 75 lesions with microcalcifications and 30 lesions without microcalcifications. Application of our Raman technique resulted in a positive predictive value of 97% for detecting microcalcifications. This study shows that Raman spectroscopy has the potential to detect microcalcifications during stereotactic breast core biopsies and provide real-time feedback to radiologists, thus reducing non-diagnostic and false negative biopsies

Experimental and Mechanistic Study of Stabilized Dry CO2 Foam Using Polyelectrolyte Complex Nanoparticles Compatible with Produced Water To Improve Hydraulic Fracturing Performance

The amount of fresh water used in hydraulic fracturing can be significantly reduced by employing produced water-compatible supercritical CO2 (scCO2) foams. Foams generated using surfactants only have suffered from long-term stability issues resulting in low viscosity and proppant-carrying problems. In this work, foam lamella stabilization with polyelectrolyte complex nanoparticles (PECNPs) and wormlike micelles (WLMs) is investigated. Electrostatic interactions are studied as the defining factors improving the hydraulic fracturing performance using the PECNP system prepared in produced water. Two oppositely charged polyelectrolytes are investigated to generate a more stable lamellae between the aqueous phase and the scCO2 while degrading in the presence of crude oil. The generated dry foam system is used as a hydraulic fracturing fluid in a tight shale formation. The strong compatibility of the synthesized PECNPs with zwitterionic surfactants prepared in highly concentrated brine in the form of wormlike micelles above critical micelle concentration (CMC) helps develop a highly viscous, dry foam capable of using produced water as its external phase. This foam system improves fracture propagation and proppant transport fracture cleanup compared to the base case foam system with no PECNPs. The formation of PEC–surfactant nanoparticles was verified via zeta potential, particle size analysis, and transmission electron microscopy; the underlying mechanism was identified as electrostatic rearrangement of WLMs along the PECNP’s perimeter or formation of electrostatically bonded micelles with the nanoparticle to create a new enhanced nanoparticle. A Raman spectroscopic model was developed to understand the PECNP–surfactant spectra and subsequent spectroscopic and hence structural changes associated with complexation. Enhanced bulk viscosity and improved foam quality as a result of complexation at the interface was identified with rheometry in addition to sand pack experiments with PECNP–surfactant ratios of 1:9 and 4:6 in 33.3 kppm and 66.7 kppm salinity brine systems, respectively. Enhancement in the shear thinning and cleanup efficiency of the fracturing fluid was observed. Formation damage was controlled by the newly introduced mixtures as fluid loss volume decreased across the tight Kentucky sandstone cores by up to 78% and 35% for scCO2 foams made with PECNP–WLMs in 33.3 and 66.7 kppm salinity brine, respectively. The produced water compatibility and reduction of water disposal presented the prospect of environmentally friendly scCO2 foams for hydraulic fracturing of unconventional reservoirs

A robust method for automated background subtraction of tissue fluorescence

This paper introduces a new robust method for the removal of background tissue fluorescence from Raman spectra. Raman spectra consist of noise, fluorescence and Raman scattering. In order to extract the Raman scattering, both noise and background fluorescence must be removed, ideally without human intervention and preserving the original data. We describe the rationale behind our robust background subtraction method, determine the parameters of the method and validate it using a Raman phantom against other methods currently used. We also statistically compare the methods using the residual mean square (RMS) with a fluorescence-to-signal (F/S) ratio ranging from 0.1 to 1000. The method, ‘adaptive minmax’, chooses the subtraction method based on the F/S ratio. It uses multiple fits of different orders to maximize each polynomial fit. The results show that the adaptive minmax method was significantly better than any single polynomial fit across all F/S ratios. This method can be implemented as part of a modular automated real-time diagnostic in vivo Raman system. Copyright © 2007 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56132/1/1753_ftp.pd

Multivariate spectral analysis of pH SERS probes for improved sensing capabilities

Appropriate functional groups adsorbed to the surface of plasmonic nanoparticles provides a platform for localised optical sensing. For example, intracellular pH nanosensors based on surface enhanced Raman spectroscopy (SERS) have been developed. However, the measurement methods and analysis of pH-SERS can greatly impact the precision and accuracy of pH calibration. This paper provides several key improvements to the performance and analysis pH nanosensors which thus transforms the performance into a useable intracellular pH sensor. We report the plasmon-induced decarboxylation of para-mercaptobenzoic acid (pMBA) pH-reporters which are bound to the gold nanoparticles, and attribute this to the laser power. This detrimental decarboxylation of pMBA has significant implications for accurate reporting and analysis due to the sensitivity and reliability of the pH sensor. The greatest implication of decarboxylation of pH sensors is inaccurate or false pH reporting, because the decarboxylation spectral signatures map directly onto those that are typically used to record pH changes. Here a unique application of the multivariate statistical technique, principal components analysis (PCA) is presented along with an optimal spectral region for pH calibration. By direct comparisons between the PCA method with the typically employed ratio-metric analysis a significant improvement in generating accurate pH sensing is demonstrated. An application of intracellular pH sensing in macrophage cells using these nanosensors promotes these step-changes in pH measurement methodology

Raman spectroscopy: elucidation of biochemical changes in carcinogenesis of oesophagus

Several techniques are under development to diagnose oesophageal adenocarcinoma at an earlier stage. We have demonstrated the potential of Raman spectroscopy, an optical diagnostic technique, for the identification and classification of malignant changes. However, there is no clear recognition of the biochemical changes that distinguish between the different stages of disease. Our aim is to understand these changes through Raman mapping studies. Raman spectral mapping was used to analyse 20-μm sections of tissue from 29 snap-frozen oesophageal biopsies. Contiguous haematoxylin and eosin sections were reviewed by a consultant pathologist. Principal component analysis was used to identify the major differences between the spectra across each map. Pseudocolour score maps were generated and the peaks of corresponding loads identified enabling visualisation of the biochemical changes associated with malignancy. Changes were noted in the distribution of DNA, glycogen, lipids and proteins. The mean spectra obtained from selected regions demonstrate increased levels of glycogen in the squamous area compared with increased DNA levels in the abnormal region. Raman spectroscopy is a highly sensitive and specific technique for demonstration of biochemical changes in the carcinogenesis of Barrett's oesophagus. There is potential for in vivo application for real-time endoscopic optical diagnosis

Challenges and perspectives in continuous glucose monitoring

Diabetes is a global epidemic that threatens the health and well-being of hundreds of millions of people. The first step in patient treatment is to monitor glucose levels. Currently this is most commonly done using enzymatic strips. This approach suffers from several limitations, namely it requires a blood sample and is therefore invasive, the quality and the stability of the enzymatic strips vary widely, and the patient is burdened by performing the measurement themselves. This results in dangerous fluctuations in glucose levels often going undetected. There is currently intense research towards new approaches in glucose detection that would enable non-invasive continuous glucose monitoring (CGM). In this review, we explore the state-of-the-art in glucose detection technologies. In particular, we focus on the physical mechanisms behind different approaches, and how these influence and determine the accuracy and reliability of glucose detection. We begin by reviewing the basic physical and chemical properties of the glucose molecule. Although these play a central role in detection, especially the anomeric ratio, they are surprisingly often overlooked in the literature. We then review state-of-the art and emerging detection methods. Finally, we survey the current market for glucometers. Recent results show that past challenges in glucose detection are now being overcome, thereby enabling the development of smart wearable devices for non-invasive continuous glucose monitoring. These new directions in glucose detection have enormous potential to improve the quality of life of millions of diabetics, as well as offer insight into the development, treatment and even prevention of the disease

Noble Metal Nanoparticles for Biosensing Applications

In the last decade the use of nanomaterials has been having a great impact in biosensing. In particular, the unique properties of noble metal nanoparticles have allowed for the development of new biosensing platforms with enhanced capabilities in the specific detection of bioanalytes. Noble metal nanoparticles show unique physicochemical properties (such as ease of functionalization via simple chemistry and high surface-to-volume ratios) that allied with their unique spectral and optical properties have prompted the development of a plethora of biosensing platforms. Additionally, they also provide an additional or enhanced layer of application for commonly used techniques, such as fluorescence, infrared and Raman spectroscopy. Herein we review the use of noble metal nanoparticles for biosensing strategies—from synthesis and functionalization to integration in molecular diagnostics platforms, with special focus on those that have made their way into the diagnostics laboratory