A Rapid Qualitative Screening Method for Isoniazid Tablets Using Handheld NIR Spectrometers in Two Countries.

BACKGROUND: Isoniazid is a leading tuberculosis treating medication. Global supply chains provide essential medicines such as isoniazid to resource-limited areas. Ensuring the safety and efficaciousness of these medicines is essential to public health programs. Handheld spectrometers are becoming increasingly approachable in cost and usability. As supply chains expand, quality compliance screening of essential medications is necessary in site-specific locations. Here, a brand-specific qualitative discrimination analysis of isoniazid is approached by collecting data from two handheld spectrometers in two countries with the intent to build a multi-location quality compliance screening method for a brand of isoniazid. METHODS: Two handheld spectrometers (900-1700 nm) were used to collect spectra from five manufacturing sources (N = 482) in Durham, North Carolina, USA, and Centurion, South Africa. A qualitative brand differentiation method was established from both locations by applying a Mahalanobis distance thresholding method as a measure of assessing similarity. RESULTS: Combining data from both locations resulted in a 100% classification accuracy, at both locations, for brand 'A' and resulted in the four other brands classifying as dissimilar. Bias was found between sensors in terms of resulting Mahalanobis distances, but the classification method proved to be robust enough to accommodate. Several spectral peaks found in isoniazid references appear within the 900-1700 nm range, as well as variation in the excipients per manufacturer. CONCLUSIONS: Results show promise for compliance screening isoniazid as well as other tablets in multiple geographic locations using handheld spectrometers.

Towards quantitative point of care detection using SERS lateral flow immunoassays.

The rapid detection of biomolecules in a point of care (POC) setting is very important for diagnostic purposes. A platform which can provide this, whilst still being low cost and simple to use, is paper-based lateral flow immunoassays (LFIA). LFIA combine immunology and chromatography to detect a target by forming an immunocomplex with a label which traps them in a test zone. Qualitative analysis can be performed using the naked eye whilst quantitative analysis takes place by measuring the optical signal provided by the label at the test zone. There are numerous detection methods available; however, many suffer from low sensitivity and lack of multiplexing capabilities or are poor at providing POC quantitative analysis. An attractive method to overcome this is to use nanoparticles coated in Raman reporters as the labelled species and to analyse test zones using surface-enhanced Raman scattering (SERS). Due to the wide variety of metal nanoparticles, Raman reporter and laser excitations that are available, SERS-based LFIA have been adapted to identify and quantify multiple targets at once. Large Raman microscopes combined with long mapping times have limited the platform to the lab; however, by transferring the analysis to portable Raman instruments, rapid and quantitative measurements can be taken at the POC without any loss in sensitivity. Portable or handheld SERS-LFIA platforms can therefore be used anywhere, from modern clinics to remote and resource-poor settings. This review will present an overview of SERS-based LFIA platforms and the major recent advancements in multiplexing and portable and handheld detection with an outlook on the future of the platform.

Predicting the performance of handheld near-infrared photonic sensors from a master benchtop device.

Many industries see a shifting focus towards performing on-site analysis using handheld spectroscopic devices. A determining factor for decision-making on the commissioning of these devices is available information on the potential performance of the device for specific applications. By now, myriad handheld solutions with very different specifications and pricing are available on the market. Although specifications are generally available for new devices, this does not directly quantify or predict how available devices will perform for targeted cases. We present a novel chemometric method to estimate the prediction performance of handheld NIR hardware and apply it to estimate the performance of two commercially available handheld NIR technologies in predicting protein content (ranging 120-180 g kg-1) in pig feed from existing data of a benchtop device. Adjusting benchtop data to the wavelength range and resolution of the handheld device lead to over-optimistic estimates of the handheld performances. Our method additionally utilizes information on the error structure of the handheld devices for the estimation. It yielded performance estimates differing less than 1 g kg-1 from the experimentally determined handheld performances and similar model parameters. Our method was effective for linear and nonlinear calibration algorithms, also when estimating performance after averaging multiple scans. Replicate spectra of twenty samples recorded using the handheld were required for replication error estimation to obtain an accurate performance estimation. The error structure could be reported by manufacturers in the future for this approach to be universally employed for predictive quantitative technology assessment. Overall, our method provides estimates of the performance of a handheld device for a specific task with minimal testing required and can thus be used as a device or application screening tool before committing to develop calibrations.

Establishment of instrument operation qualification and routine performance qualification procedures for handheld near-infrared spectrometers used at different locations within a laboratory network.

Quality assurance of finished pharmaceuticals is a necessity in ensuring the safety of consumers. There is a need for low-cost and portable rapid screening methods of pharmaceuticals in resource limited areas. Recent advances in technology have made handheld and low-cost diffuse reflectance spectrometers available to the public. While these handheld spectrometers offer advantages over benchtop spectrometers, the accuracy and repeatability must be assessed before these instruments can be used for quality assurance screening. Here, five handheld spectrometers of the same model were purchased, where an in-house installation qualification and operational qualification (IQOQ) was subsequently established for the instruments. Wavelength and photometric accuracy (and repeatability), spectroscopic noise, stray light, and bandpass were assessed between instruments. Results were found to be consistent between the spectrometers, passing IQOQ procedures, and were determined to be ready for field use. Once the handheld spectrometer's performance was verified, a practical and low-cost daily performance verification was established using common high density polyethylene vial caps on location in South Africa, Thailand, and the United States. A Mahalanobis distance-based classifier found the five spectrometers to be in agreement.

Raman spectral analysis for rapid determination of zearalenone and alpha-zearalanol.

Mycotoxins, including zearalenone, are important natural products produced by fungi that occasionally contaminate agricultural commodities and pose serious health risks to consumers of food and feed. Zearalenone and its metabolite, α-zearalanol, are of significant concern due to their estrogenic and anabolic steroid activity. Several governments have regulatory standards and advisory guidelines for zearalenone and α-zearalanol. Raman and ultraviolet spectroscopy were employed with density functional theory methods to evaluate spectroscopic properties to distinguish between zearalenone and α-zearalanol systematically. Raman bands were assigned based on vibrational frequency calculations. A portable Raman spectroscopy instrument (785 nm laser) distinguished between zearalenone and α-zearalanol in a label-free manner. Many vibrational bands of zearalenone and α-zearalanol are similar, including high-intensity peaks at 1315 cm-1 and 1650 cm-1. However, the intensities in the Raman spectra at 1465 cm-1, 1495 cm-1, and 1620 cm-1 enabled the identification of zearalenone. The Raman peak at 1450 cm-1 is associated with α-zearalanol. These vibrational bands serve as spectral indicators to differentiate between the structurally similar zearalenone and α-zearalanol.

A low-cost and portable near-infrared spectrometer using open-source multivariate data analysis software for rapid discriminatory quality assessment of medroxyprogesterone acetate injectables.

Medroxyprogesterone acetate (MPA) injectable suspensions are used by millions of women for family planning and hormonal therapy. Falsified or substandard medications may result in a health risk for consumers. Near-infrared spectroscopy (NIR) has previously been applied as a means of non-destructive and rapid screening of product quality compliance. These methods offer advantages but can be logistically and cost prohibitive for field use in resource limited areas. Here, a handheld spectrometer (900-1700 nm) with open-sourced software is used to evaluate vials of MPA from three suppliers (N = 227 vials) and verified by a benchtop UV-VIS-NIR (350-2500 nm) with licensed software. Multivariate data analysis assesses the spectral signatures of samples and builds a discriminant classification method based on Mahalanobis distances calculated from a principal component analysis scores. The handheld device paired with open-source software resulted in a product discrimination accuracy of 100% (verified by benchtop UV-VIS-NIR and chemical testing data) as well indicating that the low-cost field portable device is suitable for rapidly assessing samples in resource limited areas for consistency of manufacturing and sourcing.

Feasibility study on the use of a portable micro near infrared spectroscopy device for the "in vineyard" screening of extractable polyphenols in red grape skins.

There is substantial variation in levels of extractable phenolic compounds of red grapes (Vitis vinifera L.). Therefore, it could be desirable to known the aforesaid parameter at least for each vine. Nowadays, interest has shifted toward the development of portable vis/NIR systems, innovation in optical system design and miniaturization for its friendly use directly in the field. Spectra of intact grapes and grapes skins were recorded at harvest time in two different vintages (2016 and 2017 respectively) using a portable micro NIR spectrophotometer (908-1676 nm). A number of chemometric approaches have been used for spectral interrogation and evaluation of the aforesaid device. Spectral data have been correlated with red grape skin extractable polyphenols (total phenolic, anthocyanins and flavanols) by modified partial least squares regression (MPLS) using a number of spectral pretreatments. Moreover, different statistics strategies have been performed to develop a qualitative analysis of the data (linear discriminant analysis, discriminant partial least square analyses and Pearson's similarity index). After an exhaustive analysis of the obtained results in two different seasons, it can be concluded that the use of the portable micro NIR device for the "in vineyard" screening of extractable polyphenols in red grape skins is hampered by a number of factors. Environmental and physiological conditions should be considered to evaluate and remove factors that hamper a good sorting the berries according to their extractable polyphenol contents.