William Olds

Spatially offset Raman spectroscopy (SORS) for the analysis and detection of packaged pharmaceuticals and concealed drugs

Spatially offset Raman spectroscopy (SORS) is a powerful new technique for the non-invasive detection and identification of concealed substances and drugs. Here, we demonstrate the SORS technique in several scenarios that are relevant to customs screening, postal screening, drug detection and forensics applications. The examples include analysis of a multi-layered postal package to identify a concealed substance; identification of an antibiotic capsule inside its plastic blister pack; analysis of an envelope containing a powder; and identification of a drug dissolved in a clear solvent, contained in a non-transparent plastic bottle. As well as providing practical examples of SORS, the results highlight several considerations regarding the use of SORS in the field, including the advantages of different analysis geometries and the ability to tailor instrument parameters and optics to suit different types of packages and samples. We also discuss the features and benefits of SORS in relation to existing Raman techniques, including confocal microscopy, wide area illumination and the conventional backscattered Raman spectroscopy. The results will contribute to the recognition of SORS as a promising method for the rapid, chemically specific analysis and detection of drugs and pharmaceuticals.

In vitro model of vitamin D3 (Cholecalciferol) synthesis by UV radiation : Dose-response relationships

Vitamin D deficiency is a major health concern worldwide. Very little is understood regarding its production in the human body by exposure to UV radiation. In particular, we have no means of predicting how much vitamin D (cholecalciferol) will be produced in the skin after exposure to sunlight. Using a refined in vitro model, we found that there is a nonlinear relationship between UV dose and cholecalciferol synthesis. Two minimal erythemal doses (MED) of UV radiation produced 1.84 microg/mL of cholecalciferol whereas 4 MED produced 2.81 microg/mL. We also found that the production of cholecalciferol is restricted by the initial concentration of its precursor (7-dehydrocholesterol, 7-DHC). For example, using an initial concentration of 7-DHC of 102 microg/mL, the resultant cholecalciferol production was 1.05 microg/mL after receiving 4 MED exposure. Under the same exposure conditions, an initial concentration of 305 microg/mL yielded 2.81 g/mL of cholecalciferol. The data presented in this paper has important implications for humans, including: (1) increasing UV exposure does not result in a proportionate increase in the amount of cholecalciferol that is produced; and (2) the initial concentration of 7-DHC in the skin may impact the amount of cholecalciferol that can be synthesized. When translating these results to population groups, we will discuss how the sun exposure message needs to be carefully formulated to account for such considerations.

Noninvasive, Quantitative Analysis of Drug Mixtures in Containers Using Spatially Offset Raman Spectroscopy (SORS) and Multivariate Statistical Analysis

In this paper, spatially offset Raman spectroscopy (SORS) is demonstrated for noninvasively investigating the composition of drug mixtures inside an opaque plastic container. The mixtures consisted of three components including a target drug (acetaminophen or phenylephrine hydrochloride) and two diluents (glucose and caffeine). The target drug concentrations ranged from 5% to 100%. After conducting SORS analysis to ascertain the Raman spectra of the concealed mixtures, principal component analysis (PCA) was performed on the SORS spectra to reveal trends within the data. Partial least squares (PLS) regression was used to construct models that predicted the concentration of each target drug, in the presence of the other two diluents. The PLS models were able to predict the concentration of acetaminophen in the validation samples with a root-mean-square error of prediction (RMSEP) of 3.8% and the concentration of phenylephrine hydrochloride with an RMSEP of 4.6%. This work demonstrates the potential of SORS, used in conjunction with multivariate statistical techniques, to perform noninvasive, quantitative analysis on mixtures inside opaque containers. This has applications for pharmaceutical analysis, such as monitoring the degradation of pharmaceutical products on the shelf, in forensic investigations of counterfeit drugs, and for the analysis of illicit drug mixtures which may contain multiple components.

Standoff Raman spectrometry for the non-invasive detection of explosives precursors in highly fluorescing packaging.

Noninvasive standoff deep Raman spectroscopy has been utilised for the detection of explosives precursors in highly fluorescing packaging from 15m. To our knowledge this is the first time standoff deep Raman spectroscopy of concealed substances in highly fluorescing coloured packaging is demonstrated. Time-resolved Raman spectroscopy, spatially offset Raman spectroscopy and time-resolved spatially offset Raman spectroscopy have been compared to identify their selectivity towards the deep layers of a sample. The selectivity of time-resolved Raman spectroscopy towards the concealed chemical substances was found to be comparable to that of spatially offset Raman spectroscopy. However, time-resolved Raman spectroscopy did not require precise translation of the laser excitation beam onto the surface of the interrogated packaging as in the case of spatially offset Raman spectroscopy. Our results confirm that standoff time-resolved spatially offset Raman spectroscopy has significantly higher selectivity towards the deep layers of a sample when compared to the other deep Raman spectroscopy modes. The developed spectrometer was capable of detecting the concealed substances within 5s of data acquisition. By using time-resolved spatially Raman spectroscopy, a Raman spectrum that is representative of the content alone was acquired without the use of sophisticated algorithms to eliminate the spectral contributions of the packaging material within the acquired spectrum as in the case of time-resolved Raman spectroscopy and spatially offset Raman spectroscopy.

Toward non-invasive detection of concealed energetic materials in-field under ambient light conditions

Spatially offset Raman spectroscopy (SORS) is demonstrated for the non-contact detection of energetic materials concealed within non-transparent, diffusely scattering containers. A modified design of an inverse SORS probe has been developed and tested. The SORS probe has been successfully used for the detection of various energetic substances inside different types of plastic containers. The tests have been successfully conducted under incandescent and fluorescent background lights as well as under daylight conditions, using a non-contact working distance of 6 cm. The interrogation times for the detection of the substances were less than 1 minute in each case, highlighting the suitability of the device for near real-time detection of concealed hazards in the field. The device has potential applications in forensic analysis and homeland security investigations.

Real-time detection of concealed chemical hazards under ambient light conditions using Raman spectroscopy

Current concerns regarding terrorism and international crime highlight the need for new techniques for detecting unknown and hazardous substances. A novel Raman spectroscopy‐based technique, spatially offset Raman spectroscopy (SORS), was recently devised for noninvasively probing the contents of diffusely scattering and opaque containers. Here, we demonstrate a modified portable SORS sensor for detecting concealed substances in‐field under different background lighting conditions. Samples including explosive precursors, drugs, and an organophosphate insecticide (chemical warfare agent surrogate) were concealed inside diffusely scattering packaging including plastic, paper, and cloth. Measurements were carried out under incandescent and fluorescent light as well as under daylight to assess the suitability of the probe for different real‐life conditions. In each case, it was possible to identify the substances against their reference Raman spectra in less than 1 min. The developed sensor has potential for rapid detection of concealed hazardous substances in airports, mail distribution centers, and customs checkpoints.

Enhancing Raman Signal Sufficiently for Practical Sensing Applications

Techniques are presented for enhancing weak Raman scattering signals for rapid yet accurate substance detection. Novel surfaces that allow signal enhancement quantification are described as are eye-safe methodologies that maximize the stand-off Raman detection range.

Concealed substance identification using a defocused inverse Spatially Offset Raman Spectrometer

We report an inverse Spatially Offset Raman Spectrometer capable of non-invasively identifying packaged substances from a distance. Usual inverse SORS spectrometer has a non-contact distance that is equivalent to the focal distance of the collection system. In this work we demonstrate the defocused geometry with a modified data analysis method capable of making inverse SORS measurements from a distance greater than the focal distance of the collection lenses. With the defocused geometry we were able to detect acetaminophen, concealed inside a 2 mm thick plastic bottle, at a non-contact distance of 30 cm.