Raman spectroscopy is a non-invasive vibrational technique that yields the biochemical signature of bone, and this can be done transcutaneously using spatially offset Raman spectroscopy. The percentage of bone signal detected will increase with further source-detector offsets, but the overall signal will be decreased. In recent work, our work suggests that 3 mm is an optimal offset for detecting bone signal for phalanges and 5 mm for measuring metacarpals. The objective of this work is to create and validate a SORS instrument that collects offsets at 0, 3, and 6 mm offsets simultaneously. By conducting simulations with an optical design software, we were able to optimize the imaging throughput for each offset location. Preliminary data from a cadaver specimen suggests we collect good quality data from offsets 0, 3, and 6 mm from both metacarpals and phalanges. Future work will work on validating this instrument as a valid tool to perform bone quality assessment.
We investigate spatially offset Raman spectroscopy’s varying sensitivity to subsurface bone features in different regions of human cadaver hands and in subjects with different body mass index values.
Fracture toughness, a bone’s resistance to breaking, is typically measured via invasive mechanical tests. In this ex vivo study on mouse femurs, four Raman spectral features associated with bone properties were significantly correlated to fracture toughness using a partial least squares regression model. By including parameters measured from dual-energy absorptiometry and micro-computed tomography in the model, fracture toughness predictions on ovariectomized mice were significantly lower than a control cohort’s. This shows that meaningful estimates of fracture toughness can be estimated using input parameters obtained non-destructively.
Using transcutaneous spatially offset Raman spectroscopy (SORS) and partial least squares regression (PLSR), we recently predicted the areal bone mineral density (aBMD), volumetric bone mineralization density (vBMD) and maximum torque (MT) of tibiae in living mice. Despite the spatial offset geometry, the accuracy of the predictions was still affected by the signal from the overlying soft tissue that, like bone, contains large amounts of Type I collagen. Here we report a way to use SOLD (simultaneous, overconstrained, library-based decomposition) to improve the PLSR accuracy. The SOLD processing generates one bone spectrum estimate, one soft tissue spectrum estimate, and a residual. We combine the bone and residual spectra together for submission to PLSR, discarding only the soft tissue contribution. With the implementation of this soft-tissue-subtracted SOLD processing, we demonstrate that we can predict vBMD and MT more accurately than our previous transcutaneous measurements.
The biomarkers of many diseases such as malaria can be found in intradermal measurements. We will present two surface enhanced Raman spectroscopy (SERS) based methods for the detection of malaria biomarkers in blood, which are comparable to or outperform the standard clinical method. To eliminate the need of drawing blood, we will also report a stainless-steel microneedle based probe for direct intradermal SERS measurements. Moreover, we developed a deformable agarose needle to reduce the risk of sharp injury and cross contamination due to needle reuse. Tests in skin phantoms for glucose measurements demonstrated accuracy comparable to those traditional methods requiring blood drawing.
In this work, we report a novel substrate for surface enhanced Raman spectroscopy (SERS) composed of silver nanoparticles protected by small nitrogen-doped Graphene Quantum Dots, i.e. Ag NPs-N-GQDs, synthesized under mild experimental conditions, which can preserve the SERS performance in normal indoor environment for up to 30 days. The field emission scanning electronic microscope (FESEM) images confirm that the N-GQDs play a significant role in the control of metallic nanoparticles morphology. The X-ray photoelectron spectroscopy (XPS) result clearly indicates the N-GQDs was successfully immobilized on the surface of silver nanoparticles (Ag NPs). Ag NPs-N-GQDs demonstrated Raman enhancement stronger than pure Ag NPs likely due to an increase in the number of the “hotspots” formed by coupled nanostructures. N-GQD protected Ag NPs were evaluated in SERS measurements of R6G when they were made fresh and have been stored in normal indoors condition for up to 30 days. Then Ag NPs-N-GQDs were used as a SERS substrate for glucose detection. The linearity range of glucose was found to be ranged from 1 μM to 1 M with a detection limit of 0.1 μM in glucose solutions. It was also applied successfully for glucose detection in rat blood samples. The present study demonstrates that the novel Ag NPs−N-GQDs nanostructure has great potential to be used as a cost effective sustained SERS substrate, which can be extremely useful in the wide adoption of SERS based sensors.
Ocular infection is a serious eye disease that could lead to blindness without prompt and proper treatment. In pathology, ocular infection is caused by microorganisms such as bacteria, fungi or viruses. The essential prerequisite for the optimal treatment of ocular infection is to identify the microorganism causing infection early as each type of microorganism requires a different therapeutic approach. The clinical procedure for identifying the microorganism species causing ocular infection includes Gram staining (for bacteria)/microscopy (for fungi) and the culture of corneal surface scraping, or aqueous and vitreous smear samples taken from the surface of infected eyes. The culture procedure is labor intensive and expensive. Moreover, culturing is time consuming, which usually takes a few days or even weeks. Such a long delay in diagnosis could result in the exacerbation of patients’ symptoms, the missing of the optimal time frame for initiating treatment and subsequently the rising cost for disease management. Raman spectroscopy has been shown highly effective for non-invasive identification of both fungi and bacteria qualitatively. In this study, we investigate the feasibility of identifying the microorganisms of ocular infection and quantifying the concentrations using Raman spectroscopy by measuring not only gram negative and gram positive bacteria but also infected cornea. By applying a modified orthogonal projection approach, the relative concentration of each bacteria species could be quantified. Our results indicate the great potential of Raman spectroscopy as an alternative tool for non-invasive diagnosis of ocular infection and could play a significantly role in future ophthalmology.
Neurological diseases are one of the leading causes of adult disability and they are estimated to cause more deaths than cancer in the elderly population by 2040. Stem cell therapy has shown great potential in treating neurological diseases. However, before cell therapy can be widely adopted in the long term, a number of challenges need to be addressed, including the fundamental research about cellular development of neural progenitor cells. To facilitate the fundamental research of neural progenitor cells, many methods have been developed to identify neural progenitor cells. Although great progress has been made, there is still lack of an effective method to achieve fast, label-free and noninvasive differentiation of neural progenitor cells and their lineages. As a fast, label-free and noninvasive technique, spontaneous Raman spectroscopy has been conducted to characterize many types of stem cells including neural stem cells. However, to our best knowledge, it has not been studied for the discrimination of neural progenitor cells from specific lineages. Here we report the differentiation of neural progenitor cell from their lineages including astrocytes, oligodendrocytes and neurons using spontaneous Raman spectroscopy. Moreover, we also evaluate the influence of system parameters during spectral acquisition on the quality of measured Raman spectra and the accuracy of classification using the spectra, which yield a set of optimal system parameters facilitating future studies.
We report three strategies of surface enhanced Raman spectroscopy (SERS) for β-hematin and hemozoin detection in malaria infected human blood, which can be potentially developed for field malaria diagnosis. In the first strategy, we used silver coated magnetic nanoparticles (Fe3O4@Ag) in combination with an external magnetic field to enhance the Raman signal of β-hematin. Then we developed two SERS methods without the requirement of magnetic field for malaria infection diagnosis. In Method 1, silver nanoparticles were synthesized separately and then mixed with lysed blood just like in traditional SERS measurements; while in Method 2, we developed an ultrasensitive SERS method by synthesizing silver nanoparticles directly inside the parasites of Plasmodium falciparum. Method 2 can be also used to detect single parasites in the ring stage.
We report two methods of surface enhanced Raman spectroscopy (SERS) for hemozoin detection in malaria infected human blood. In the first method, silver nanoparticles were synthesized separately and then mixed with lysed blood; while in the second method, silver nanoparticles were synthesized directly inside the parasites of Plasmodium falciparum.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.