Handheld Raman Device Research Articles

Quick and reagent-free monitoring of edible oil saponification values using a handheld Raman device

Saponification value, the average molecular weight of fatty acids, is a crucial parameter for detecting adulteration of edible oils. Conventionally, it is determined in a laboratory setup through a time-consuming, laborious titration process using chemical reagents. Herein, the application of Raman spectroscopy for quick SV estimation of oils is demonstrated. It was hypothesized that the SV can be predicted from Raman spectra since the spectral patterns reflect the composition of fatty acid triglycerides. Two model oil systems were studied: coconut-gingelly oil and coconut-sunflower oil. Univariate models built from Raman spectra were successful only for the specific oil system; hence, PLS-Regression was executed across the two systems. The PLSR model on the validation set returned the average error, percentage error, and root mean square error of prediction as 2.1, 0.99 %, and 2.4, respectively. This method offers several advantages of portability, little reagent use, minimal sample preparation, and reduced analysis time.

Miniaturized Raman Instruments for SERS-Based Point-of-Care Testing on Respiratory Viruses.

As surface-enhanced Raman scattering (SERS) has been used to diagnose several respiratory viruses (e.g., influenza A virus subtypes such as H1N1 and the new coronavirus SARS-CoV-2), SERS is gaining popularity as a method for diagnosing viruses at the point-of-care. Although the prior and quick diagnosis of respiratory viruses is critical in the outbreak of infectious disease, ELISA, PCR, and RT-PCR have been used to detect respiratory viruses for pandemic control that are limited for point-of-care testing. SERS provides quantitative data with high specificity and sensitivity in a real-time, label-free, and multiplex manner recognizing molecular fingerprints. Recently, the design of Raman spectroscopy system was simplified from a complicated design to a small and easily accessible form that enables point-of-care testing. We review the optical design (e.g., laser wavelength/power and detectors) of commercialized and customized handheld Raman instruments. As respiratory viruses have prominent risk on the pandemic, we review the applications of handheld Raman devices for detecting respiratory viruses. By instrumentation and commercialization advancements, the advent of the portable SERS device creates a fast, accurate, practical, and cost-effective analytical method for virus detection, and would continue to attract more attention in point-of-care testing.

A surface‐enhanced Raman sensor for trace identification and analysis of high‐priority drugs of abuse with portable and handheld Raman devices

AbstractSurface‐enhanced Raman spectroscopy (SERS) is a rapidly emerging technology that offers a fast, extremely sensitive, and quantitative approach to trace chemical detection. Such a technique incorporated into a portable device is attractive to law enforcement and emergency room personnel for rapid accurate on‐site screening of illicit and abused drugs. Toward this, we are developing an analyzer in a hand‐held unit, based on SERS that is integrated with a capillary sensor embedded with activated gold nanoparticles in a porous glass matrix. In this preliminary study, we have used this gold sol–gel capillary to measure aqueous solutions of 14 high‐priority drugs to define sensitivity (lowest measured concentration [LMC] and estimated limit of detection [LOD]), determine concentration dependence and quantification capabilities by constructing calibration curves, examine effects of pH at 3, 7, and 11 on SERS measurements, and perform multicomponent analysis of fentanyl laced drug mixtures and spectral identification on our portable and handheld units. Of particular significance, fentanyl was detected with an LMC of 1 ng/ml and estimated LOD at 0.11 ng/ml, while other representative drugs such as cocaine and phenylcyclidine produced LMCs and LODs at 5.0 and 0.77 ng/ml, and 10.0 and 0.62 ng/ml, respectively. These sub‐nanogram per milliliter detection limits are comparable or lower than previously reported and confirm that this gold sol–gel has the potential to meet the sensitivity requirements for saliva analysis. Most importantly, these sensors can be manufactured easily and cheaply and when integrated with our portable Raman units produce high‐quality spectra and accurate identification within 1.2 s.

Towards Label-free detection of viral disease agents through their cell surface proteins: Rapid screening SARS-CoV-2 in biological specimens.

Current methods for the screening of viral infections in clinical settings, such as reverse transcription polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), are expensive, time-consuming, require trained personnel and sophisticated instruments. Therefore, novel sensors that can save time and cost are required specially in remote areas and developing countries that may lack the advanced scientific infrastructure for this task. In this work, we present a sensitive, and highly specific biosensing approach for the detection of harmful viruses that have cysteine residues within the structure of their cell surface proteins. We utilized new method for the rapid screening of SARS-CoV-2 virus in biological fluids through its S1 protein by surface enhanced Raman spectroscopy (SERS). The protein is captured from aqueous solutions and biological specimens using a target-specific extractor substrate. The structure of the purified protein is then modified to convert it into a bio-thiol by breaking the disulfide bonds and freeing up the sulfhydryl (SH) groups of the cysteine residues. The formed biothiol chemisorbs favourably onto a highly sensitive plasmonic sensor and probed by a handheld Raman device in few seconds. The new method was used to screen the S1 protein in aqueous medium, spiked human blood plasma, mucus, and saliva samples down to 150 fg/L. The label-free SERS biosensing method has strong potential for the fingerprint identification many viruses (e.g. the human immunodeficiency virus, the human polyomavirus, the human papilloma virus, the adeno associated viruses, the enteroviruses) through the cysteine residues of their capsid proteins. The new method can be applied at points of care (POC) in remote areas and developing countries lacking sophisticated scientific infrastructure.

Metrohm lands distribution deal for handheld Raman devices in security markets

Metrohm lands distribution deal for handheld Raman devices in security markets

Identification of Pre-1950 Synthetic Organic Pigments in Artists’ Paints. A Non-Invasive Approach Using Handheld Raman Spectroscopy

There is little information on the actual use of early synthetic organic pigments (SOPs) in art objects, especially those from before 1950. Their presence can, however, pose a challenge to conservation because their chemical composition, as well as their lightfastness and sensitivity to solvents, are often unknown. Here, a study on the non-invasive identification of SOPs in historic pre-1950 varnished paint-outs from artists’ materials manufacturer Royal Talens is presented. The paints were analysed using a handheld Raman device. Spectra were evaluated by recording the spectra of the same samples with a benchtop instrument. This study demonstrated that the identification of SOPs in varnished oil paints with a non-invasive approach is possible and rather straightforward. The handheld Raman device allowed us to identify fourteen SOPs from eight pigment classes. Besides the occurrence of expected and the known SOPs of this time period, there were also some surprising results, like the detection of the triarylcarbonium pigments PG2 and PB8, and the monoazo Mordant Yellow 1.

Evaluation of Suspected Counterfeit Pharmaceutical Tablets Declared to Contain Controlled Substances Using Handheld Raman Spectrometers.

This study describes the performance of handheld Raman devices for determining whether suspect pharmaceutical tablets declared to contain controlled substances were consistent with authentic (CWA) or not consistent with authentic (NCWA) tablets using a simple, rapid, field-friendly method capable of being used by nonexperts. Twenty-five authentic products and 84 known NCWA tablets were examined using three "parent" devices for a total of 327 analyses. On average, the parent devices yielded a true pass rate of 100%, a true fail rate of 98.4%, a false pass rate of 1.6%, and a false fail rate of 0%. The methods/libraries were then transferred to 13 identical "daughter" devices, which were used to examine 10 suspect finished dosage forms in duplicate (six known NCWA tablets and four authentic tablets) for a total of 260 measurements. On average, the daughter devices had a true pass rate of 100%, a true fail rate of 95.5%, a false pass rate of 4.5%, and a false fail rate of 0.0%. These data demonstrate that the parent-daughter electronic transfer method was successful, which permits the ability to develop methods in the laboratory that can be seamlessly pushed out to field devices. The methods can then be used to (i) prioritize samples for additional testing using other more time-consuming laboratory-based techniques needed to detect and quantify active ingredients and (ii) help support the interdiction of dangerous tablets at ports of entry, thereby preventing them from reaching the supply chain.

Evaluating Low-Cost Optical Spectrometers for the Detection of Simulated Substandard and Falsified Medicines.

Distribution of substandard and falsified (SF) medicines is on the rise, and its impact on public health, particularly in low-resource countries, is becoming increasingly significant. Portable, nondestructive screening devices can support regulatory authorities in their defense against the spread of SF medicines. Vibrational spectroscopy is an ideal candidate due to its sampling ease and speed. In this work, five portable, among which four are considered low-cost, spectroscopic devices based on near-infrared (NIR), Raman, and mid-infrared (MIR) were evaluated to quantify active pharmaceutical ingredients (APIs) and formulation accuracy within simulated authentic, falsified, and substandard medicines. Binary sample mixtures containing a typical API in antimalarial, antiretroviral, or anti-tuberculosis medicines were assessed. In both univariate and multivariate analyses, the API quantification performance of the digital light processing (DLP) NIR spectrometer and a handheld Raman device consistently matched or exceeded that of the other NIR spectrometers and a scientific grade MIR spectrometer. In the formulation accuracy tests, data from all devices, other than the silicon photodiode array NIR spectrometer, were able to create regression models with less than 6% error. From this exploratory study, we conclude that certain portable NIR devices hold significant promise as cost-effective screening tools for falsified and potentially substandard medicines, and they warrant further investigation and development.

Identification of Opioids and Related Substances using Handheld Raman Spectrometers.

This study describes the performance of handheld Raman devices for detecting one hundred opioids and related substances including fentanyl and several analogs. Using a single "parent" device, signatures (spectra) with excellent signal-to-noise ratios were generated using <5mg of most compounds. The signatures were added to a method (library), which was electronically transferred to three "daughter" devices. The devices were able to discriminate different salt forms and isomers. On average, the daughter devices yielded a true-positive rate of 97.3% for generating an alarm for opioids and were 93.3% effective for correctly identifying the opioid. The devices yielded true-negative, false-positive and false-negative rates of 100%, 0%, and 2.7%, respectively, where false negatives were due to weak signal and fluorescence. These data demonstrate that the parent-daughter electronic transfer method was successful and effective, which permits the ability to develop methods in the laboratory that can be seamlessly pushed out to field devices.

Mineral fibres and environmental monitoring: A comparison of different analytical strategies in New Caledonia

Covered by ultrabasic units for more than a third of its surface, the New Caledonia (South West Pacific) is one of the largest world producers of Ni-ore from lateritic deposits. Almost all outcrops of geological units and open mines contain serpentine and amphibole, also as asbestos varieties. In this geological context, in which weathering processes had a great contribution in the production and dispersion of mineral fibres into the environment, the development of a routinely analytical strategy, able to discriminate an asbestiform fibre from a non-harmful particle, is a pivotal requisite. However, the acquisition of all these parameters is necessary for determining the risk associated to fibres exposition. A multidisciplinary routinely approach, based on the use of complementary simply-to-use but reliable analytical methods is the only possible strategy. In addition, the instrumental apparatus must be easily transportable on the field, directly on the mining site. The employment of specialized tools such as Polarized Light Microscopy associated to Dispersion Staining method (PLM/DS) and portable Raman spectroscopy for identification of environmental asbestos, are proved extremely effective in the improvement of the performance and rapidity of data acquisition and interpretation. Both PLM/DS and handheld Raman devices confirmed to be discriminant in the detection and characterization of asbestos fibres for both serpentine and amphibole. Furthermore, these techniques proved extremely effective even in the presence of strongly fibrous and altered samples.

First use of handheld Raman spectroscopic devices and on-board chemometric analysis for the detection of milk powder adulteration

Two handheld Raman spectroscopic devices in combination with chemometrics were explored as rapid, non-targeted screening tools for the detection of milk powder (MP) adulteration using melamine as an example contaminant. The first device (device 1) employs a unique laser setup and data processing software that decreases the spectral interference from background fluorescence which could allow for improved detection capabilities. The second instrument (device 2) is the first of its kind to combine advanced chemometric data processing directly on-board the portable device which could allow for more rapid analysis of complex samples through “pass/fail” results. In this work, the performance of these two devices were evaluated and compared to each other and to that of a benchtop Raman spectrometer for the detection of melamine-spiked MP samples. The portable devices had similar levels of performance as the benchtop Raman spectrometer in terms of sensitivity and specificity for classifying test samples as genuine MP or MP-melamine blends. High specificity (100%) for melamine adulterated MPs at concentrations ≥1.0% (w/w) for dry-blends and ≥0.30% for wet-blends in the validation set was found for the non-targeted, soft independent modeling of class analogy (SIMCA) model developed for portable device 2. A similar level of specificity was observed when the non-targeted model was tested using a blind set of test samples and on-board chemometrics. Additionally, SIMCA models for devices 1 and 2 correctly classified genuine MPs with 97 and 100% correct classifications, respectively. Device 1 had comparatively lower specificity for MP blends. These results indicate that the developed screening methods using the handheld Raman devices are potentially well-suited for rapid, routine field analysis of MP samples for detection of economically motivated adulteration.

Survey to Identify Substandard and Falsified Tablets in Several Asian Countries with Pharmacopeial Quality Control Tests and Principal Component Analysis of Handheld Raman Spectroscopy.

The World Health Organization has warned that substandard and falsified medical products (SFs) can harm patients and fail to treat the diseases for which they were intended, and they affect every region of the world, leading to loss of confidence in medicines, health-care providers, and health systems. Therefore, development of analytical procedures to detect SFs is extremely important. In this study, we investigated the quality of pharmaceutical tablets containing the antihypertensive candesartan cilexetil, collected in China, Indonesia, Japan, and Myanmar, using the Japanese pharmacopeial analytical procedures for quality control, together with principal component analysis (PCA) of Raman spectrum obtained with handheld Raman spectrometer. Some samples showed delayed dissolution and failed to meet the pharmacopeial specification, whereas others failed the assay test. These products appeared to be substandard. Principal component analysis showed that all Raman spectra could be explained in terms of two components: the amount of the active pharmaceutical ingredient and the kinds of excipients. Principal component analysis score plot indicated one substandard, and the falsified tablets have similar principal components in Raman spectra, in contrast to authentic products. The locations of samples within the PCA score plot varied according to the source country, suggesting that manufacturers in different countries use different excipients. Our results indicate that the handheld Raman device will be useful for detection of SFs in the field. Principal component analysis of that Raman data clarify the difference in chemical properties between good quality products and SFs that circulate in the Asian market.

Molecular recognition and detection of Pb(II) ions in water by aminobenzo-18-crown-6 immobilised onto a nanostructured SERS substrate

In this work, we propose a new sensitive, selective and portable surface enhanced Raman spectroscopy (SERS) methodology for the rapid on site detection of Pb(II) pollution in water. The new method utilises aminobenzo-18-crown-6 (AB18C6) as a selective recognition molecule to form a spontaneous complex with Pb(II) ions. The formed AB18C6-Pb(II) complex was rapidly immobilised onto a nanostructured gold substrate via Au-N bond formation and reproducibly screened by SERS using a handheld Raman device. For the SERS measurements, a substrate was fabricated by electrochemical deposition of gold nanostructures onto a flat gold disc, creating multiple hotspots for ultrasensitive SERS measurements. The limit of quantification (LOQ) for Pb(II) ions by the SERS method was 2.20pM. The limit of detection (LOD) was 0.69pM which is five orders of magnitude lower than the maximum Pb(II) level of 72nM allowed by the US Environmental Protection Agency. The high sensitivity of the SERS substrate is attributed to the coupling between the Surface Plasmon Polariton (SPP) of its gold surface, the localised Surface Plasmon Resonance (SPR) of the gold nanostructures and the Raman radiation from the immobilised AB18C6-Pb(II) complex. The new SERS detection method was successfully applied for the selective and rapid screening of Pb(II) ion contamination in water proving its practical application for environmental analysis.

Rapid screening for ricin toxin on letter papers using surface enhanced Raman spectroscopy

Ricin has been involved in historic and recent biothreat events. Here we developed a rapid screening method for ricin laced papers using surface enhanced Raman spectroscopy (SRES). Three sample preparation methods and two SERS substrates were evaluated and optimized for their performance on three types of letter papers. The best approach was the use of non-destructive extraction coupled with silver dendrites, which can detect ricin B chain surrogate as low as 0.044μg in less than 10min from paper. The extraction efficiency for the hydrophobic letters was the highest (90%) compared to the other two types of letters. We also demonstrated the great capacity of this method to discriminate ricin B from common beverage residues on letter papers, and the feasibility of using a handheld Raman device for rapid and on-site screening.

Prediction of pork quality at the slaughter line using a portable Raman device

Raman spectroscopy is providing a fingerprint of the early postmortem metabolism in meat. In this study, for the first time, Raman spectroscopy is shown to measure and predict quality traits of intact muscles at the slaughtering process. Porcine semimembranosus muscles (N=151) were measured 30–60min post mortem at the veterinarian line of a commercial abattoir using a prototype handheld Raman device. The Raman spectra were regressed against technologically important quality traits as measured with classic reference methods. Predicting pH35, pH24 and drip loss with PLSR yielded coefficients of determination of 0.75, 0.58 and 0.83 and root mean square errors of cross validation of 0.09, 0.05 and 0.6%, respectively. This is demonstrating the on-line potential of early postmortem Raman spectra to measure pH35 and to predict pH24 and drip loss.

Assessment of the performance of a handheld Raman device for potential use as a screening tool in evaluating medicines quality

The TruScan® handheld Raman device is used for testing finished pharmaceutical products in the field to detect counterfeit and substandard medicines. Present work reports on the device's ability to discriminate between a specific product and similar products from different manufacturers, unrelated medicines, and medicines with different strengths. This investigation evaluated its ability to differentiate between similar drug products of similar or different strengths, focusing on the specificity and precision of the testing. First, several units of the same medicine's dosage form were compared; then comparisons were made between unrelated products, similar products, and products with different strengths. The six pharmaceutical products used in testing were from commonly used analgesic, antimalarial, and antidiarrheal medicines. The results showed that the performance of the TruScan® device depends on the nature and the strength of the dosage form tested; while the device could be suitable for authentication of some finished pharmaceutical products and, hence, could be used to detect some counterfeit medicines, it could not be used to detect substandard medicines. Careful consideration should be given when using the device as a screening tool for counterfeit medicines.