QCM Sensor Arrays, Electroanalytical Techniques and NIR Spectroscopy Coupled to Multivariate Analysis for Quality Assessment of Food Products, Raw Materials, Ingredients and Foodborne Pathogen Detection: Challenges and Breakthroughs.

Quality checks, assessments, and the assurance of food products, raw materials, and food ingredients is critically important to ensure the safeguard of foods of high quality for safety and public health. Nevertheless, quality checks, assessments, and the assurance of food products along distribution and supply chains is impacted by various challenges. For instance, the development of portable, sensitive, low-cost, and robust instrumentation that is capable of real-time, accurate, and sensitive analysis, quality checks, assessments, and the assurance of food products in the field and/or in the production line in a food manufacturing industry is a major technological and analytical challenge. Other significant challenges include analytical method development, method validation strategies, and the non-availability of reference materials and/or standards for emerging food contaminants. The simplicity, portability, non-invasive, non-destructive properties, and low-cost of NIR spectrometers, make them appealing and desirable instruments of choice for rapid quality checks, assessments and assurances of food products, raw materials, and ingredients. This review article surveys literature and examines current challenges and breakthroughs in quality checks and the assessment of a variety of food products, raw materials, and ingredients. Specifically, recent technological innovations and notable advances in quartz crystal microbalances (QCM), electroanalytical techniques, and near infrared (NIR) spectroscopic instrument development in the quality assessment of selected food products, and the analysis of food raw materials and ingredients for foodborne pathogen detection between January 2019 and July 2020 are highlighted. In addition, chemometric approaches and multivariate analyses of spectral data for NIR instrumental calibration and sample analyses for quality assessments and assurances of selected food products and electrochemical methods for foodborne pathogen detection are discussed. Moreover, this review provides insight into the future trajectory of innovative technological developments in QCM, electroanalytical techniques, NIR spectroscopy, and multivariate analyses relating to general applications for the quality assessment of food products.

Application of Ionic Liquids in Pot-in-Pot Reactions.

Pot-in-pot reactions are designed such that two reaction media (solvents, catalysts and reagents) are isolated from each other by a polymeric membrane similar to matryoshka dolls (Russian nesting dolls). The first reaction is allowed to progress to completion before triggering the second reaction in which all necessary solvents, reactants, or catalysts are placed except for the starting reagent for the target reaction. With the appropriate trigger, in most cases unidirectional flux, the product of the first reaction is introduced to the second medium allowing a second transformation in the same glass reaction pot--albeit separated by a polymeric membrane. The basis of these reaction systems is the controlled selective flux of one reagent over the other components of the first reaction while maintaining steady-state catalyst concentration in the first "pot". The use of ionic liquids as tools to control chemical potential across the polymeric membranes making the first pot is discussed based on standard diffusion models--Fickian and Payne's models. Besides chemical potential, use of ionic liquids as delivery agent for a small amount of a solvent that slightly swells the polymeric membrane, hence increasing flux, is highlighted. This review highlights the critical role ionic liquids play in site-isolation of multiple catalyzed reactions in a standard pot-in-pot reaction.

Using magnetic levitation for non-destructive quality control of plastic parts.

Magnetic levitation (MagLev) enables rapid and non-destructive quality control of plastic parts. The feasibility of MagLev as a method to: i) rapidly assess injection-molded plastic parts for defects during process optimization, ii) monitor the degradation of plastics after exposure to harsh environmental conditions, and iii) detect counterfeit polymers by density is demonstrated.

Adaptive use of bubble wrap for storing liquid samples and performing analytical assays.

This paper demonstrates that the gas-filled compartments in the packing material commonly called "bubble wrap" can be repurposed in resource-limited regions as containers to store liquid samples, and to perform bioanalyses. The bubbles of bubble wrap are easily filled by injecting the samples into them using a syringe with a needle or a pipet tip, and then sealing the hole with nail hardener. The bubbles are transparent in the visible range of the spectrum, and can be used as "cuvettes" for absorbance and fluorescence measurements. The interiors of these bubbles are sterile and allow storage of samples without the need for expensive sterilization equipment. The bubbles are also permeable to gases, and can be used to culture and store micro-organisms. By incorporating carbon electrodes, these bubbles can be used as electrochemical cells. This paper demonstrates the capabilities of the bubbles by culturing E. coli, growing C. elegans, measuring glucose and hemoglobin spectrophotometrically, and measuring ferrocyanide electrochemically, all within the bubbles.

Separation and enrichment of enantiopure from racemic compounds using magnetic levitation.

Crystallization of a solution with high enantiomeric excess can generate a mixture of crystals of the desired enantiomer and the racemic compound. Using a mixture of S-/RS-ibuprofen crystals as a model, we demonstrated that magnetic levitation (MagLev) is a useful technique for analysis, separation and enantioenrichment of chiral/racemic products.

Paramagnetic ionic liquids for measurements of density using magnetic levitation.

Paramagnetic ionic liquids (PILs) provide new capabilities to measurements of density using magnetic levitation (MagLev). In a typical measurement, a diamagnetic object of unknown density is placed in a container containing a PIL. The container is placed between two magnets (typically NdFeB, oriented with like poles facing). The density of the diamagnetic object can be determined by measuring its position in the magnetic field along the vertical axis (levitation height, h), either as an absolute value or relative to internal standards of known density. For density measurements by MagLev, PILs have three advantages over solutions of paramagnetic salts in aqueous or organic solutions: (i) negligible vapor pressures; (ii) low melting points; (iii) high thermal stabilities. In addition, the densities, magnetic susceptibilities, glass transition temperatures, thermal decomposition temperatures, viscosities, and hydrophobicities of PILs can be tuned over broad ranges by choosing the cation-anion pair. The low melting points and high thermal stabilities of PILs provide large liquidus windows for density measurements. This paper demonstrates applications and advantages of PILs in density-based analyses using MagLev.

Paper-based electroanalytical devices with an integrated, stable reference electrode.

This paper describes the development of a referenced Electrochemical Paper-based Analytical Device (rEPAD) comprising a sample zone, a reference zone, and a connecting microfluidic channel that includes a central contact zone. We demonstrated that the rEPADs provide a simple system for direct and accurate voltammetric measurements that are referenced by an electrode with a constant, well-defined potential. The performance of the rEPADs is comparable to commercial electrochemical cells, and the layout can be easily integrated into systems that permit multiplexed analysis and pipette-free sampling. The cost of this portable device is sufficiently low that it could be for single-use, disposable applications, and its method of fabrication is compatible with that used for other paper-based systems.

Rhein inhibits angiogenesis and the viability of hormone-dependent and -independent cancer cells under normoxic or hypoxic conditions in vitro.

Hypoxia is a hallmark of solid tumors, including breast cancer, and the extent of tumor hypoxia is associated with treatment resistance and poor prognosis. Considering the limited treatment of hypoxic tumor cells and hence a poor prognosis of breast cancer, the investigation of natural products as potential chemopreventive anti-angiogenic agents is of paramount interest. Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid), the primary anthraquinone in the roots of Cassia alata L., is a naturally occurring quinone which exhibits a variety of biologic activities including anti-cancer activity. However, the effect of rhein on endothelial or cancer cells under hypoxic conditions has never been delineated. Therefore, the aim of this study was to investigate whether rhein inhibits angiogenesis and the viability of hormone-dependent (MCF-7) or -independent (MDA-MB-435s) breast cancer cells in vitro under normoxic or hypoxic conditions. Rhein inhibited vascular endothelial growth factor (VEGF(165))-stimulated human umbilical vein endothelial cell (HUVEC) tube formation, proliferation and migration under normoxic and hypoxic conditions. In addition, rhein inhibited in vitro angiogenesis by suppressing the activation of phosphatidylinositol 3-kinase (PI3K), phosphorylated-AKT (p-AKT) and phosphorylated extracellular signal-regulated kinase (p-ERK) but showed no inhibitory effects on total AKT or ERK. Rhein dose-dependently inhibited the viability of MCF-7 and MDA-MB-435s breast cancer cells under normoxic or hypoxic conditions, and inhibited cell cycle in both cell lines. Furthermore, Western blotting demonstrated that rhein inhibited heat shock protein 90alpha (Hsp90α) activity to induce degradation of Hsp90 client proteins including nuclear factor-kappa B (NF-κB), COX-2, and HER-2. Rhein also inhibited the expression of hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF(165)), epidermal growth factor (EGF), and the phosphorylation of inhibitor of NF-κB (I-κB) under normoxic or hypoxic conditions. Taken together, these data indicate that rhein is a promising anti-angiogenic compound for breast cancer cell viability and growth. Therefore, further studies including in vivo and pre-clinical need to be performed.

Ephedrinium-based protic chiral ionic liquids for enantiomeric recognition.

We report the synthesis of a series of novel structurally related protic chiral ionic liquids (PCILs) derived from ephedrines. Enantiopure norephedrine, ephedrine, and methylephedrine were neutralized by use of fluorinated acids, bis(trifluoromethanesulfonyl)imide, and bis(pentafluoroethanesulfonyl)imide to afford six PCILs with protonated primary, secondary, and tertiary amines. The goal of this study is to investigate the influence of structure on both chiral recognition abilities and physicochemical properties of these closely related PCILs. The newly synthesized PCILs were characterized by use of nuclear magnetic resonance (NMR), thermal gravimetric analysis, differential scanning calorimetry, circular dichroism (CD), mass spectrometry, and elemental analysis. The PCILs were thermally stable up to 220°C and had glass transition temperatures between -60 and -30°C. Both enantiomers of the PCILs retained chirality throughout the synthesis as demonstrated by use of CD measurements. More interestingly, these ephedrinium PCILs displayed strong chiral recognition capabilities as evidenced by peak splitting of the chemical shift of the trifluoro group of potassium Mosher's salt by use of (19)F-NMR. In addition, these PCILs demonstrated enantiomeric recognition capabilities toward a range of structurally diverse analytes using steady-state fluorescence spectroscopy.

Amino Acid-based fluorescent chiral ionic liquid for enantiomeric recognition.

We report on the synthesis and characterization of a new fluorescent chiral ionic liquid (FCIL), l-phenylalanine ethyl ester bis(trifluoromethane) sulfonimide (l-PheC(2)NTf(2)), capable of serving simultaneously as solvent, chiral selector, and fluorescent reporter in chiral analytical measurements. Enantiomers of different analytes, including fluorescent and nonfluorescent compounds, with a variety of structures were shown to induce wavelength- and analyte-dependent changes in the fluorescence intensity of this FCIL. This system may provide both chemo- and enantioselectivity toward multiple analytes simultaneously. The newly synthesized FCIL, derived from commercially available l-phenylalanine ethyl ester chloride and lithium bis(trifluoromethane) sulfonamide, was obtained as liquid at room temperature and is stable to thermal decomposition up to 270 degrees C. Absorption and fluorescence properties of neat l-PheC(2)NTf(2) were complex. While the absorption properties were similar to phenylalanine with a weakly absorbing tail extending beyond 400 nm, multiple excitation and emission bands were observed in its Excitation-Emission Matrix (EEM). A prominent excimer emission displayed the greatest intensity of all emission bands, and a long-wavelength emission shifted toward the red with increasing excitation wavelength. These different spectral regions were shown to respond differently toward several analytes, including sugars such as glucose and mannose, making this an ideal system to exploit the multidimensional properties of fluorescence. The unique properties of l-PheC(2)NTf(2) combined with EEMs resulted in reliable identification of different enantiomers and measurement of enantiomeric composition. Importantly, the choice of excitation and emission wavelength regions was an important variable shown to improve prediction of enantiomeric composition.

Near-infrared fluorescent nanoGUMBOS for biomedical imaging.

Herein, we report on near-infrared (NIR) fluorescent nanoparticles generated from an emergent class of materials we refer to as a Group of Uniform Materials Based on Organic Salts (GUMBOS). GUMBOS are largely frozen ionic liquids, although the concept is more general and is also easily applied to solid ionic materials with melting points in excess of 100 degrees C. Nanoparticles based on GUMBOS (nanoGUMBOS) derived from a NIR fluorophore are prepared using a reprecipitation method and evaluated for in vivo fluorescence imaging. Due to their uniformity, single-step preparation, and composite nature, nanoGUMBOS help to resolve issues with dye leakage problems innate to alternate cellular stains and unlock a myriad of applications for these materials, highlighting exciting possibilities for multifunctional nanoGUMBOS.

Magnetic chiral ionic liquids derived from amino acids.

Novel room temperature magnetic chiral ionic liquids derived from amino acids were synthesized and their magnetic properties as well as chiral discrimination abilities were investigated.

Combinatorial approach to enantiomeric discrimination: synthesis and (19)F NMR screening of a chiral ionic liquid-modified silane library.

A parallel library of chiral ionic liquid (CIL)-modified silanes as potential chiral selectors was synthesized, and their enantiomeric discrimination abilities were screened by use of (19)F NMR spectroscopy. The screening method allows for rapid identification of the most enantioselective members of the library and simultaneous investigation of their chiral recognition mechanisms. The library compounds were synthesized using quaternization and anion-exchange reactions. Three major parameters (type of chiral cations, anions, and linker chain lengths) were included and investigated during the synthesis and screening. As expected, the structure of the chiral cation was found to play an important role in determining chiral recognition abilities. In addition, several types of intermolecular interactions including ion-pair, hydrogen bonding, pi-pi stacking, dipole stacking, and steric interactions were found to impact chiral discrimination.

Controllable formation of ionic liquid micro- and nanoparticles via a melt-emulsion-quench approach.

We present a facile, scalable, and general method for the size-variable generation of monodispersed, near-spherical solid-state (frozen) ionic liquid nanoparticles based on a novel melt-emulsion-quench approach. Simple manipulation of the internal templating droplets within oil-in-water (o/w) microemulsions also permits the formation of well-defined microspheres. This simple and rapid preparation, requiring neither specialized equipment nor harsh conditions, suggests a wealth of potential for these designer nanomaterials within the biomedical, materials, and analytical communities.

Synthesis and characterization of novel chiral ionic liquids and investigation of their enantiomeric recognition properties.

We report the synthesis and characterization of amino acid ester based chiral ionic liquids, derived from L- and D-alanine tert butyl ester chloride. The synthesis was accomplished via an anion metathesis reaction between commercially available L- and D-alanine tert butyl ester chloride using a variety of counterions such as lithium bis (trifluoromethane) sulfonimide, silver nitrate, silver lactate, and silver tetrafluoroborate. Both enantiomeric forms were obtained as confirmed by bands of opposite sign in the circular dichroism spectra. The L- and D-alanine tert butyl ester bis (trifluoromethane) sulfonimide were obtained as liquids at room temperature and intriguingly exhibited the highest thermal stability (up to 263 degrees C). In addition, the ionic liquids demonstrated enantiomeric recognition ability as evidenced by splitting of racemic Mosher's sodium salt signal using a liquid state (19)F nuclear magnetic resonance (NMR) and fluorescence spectroscopy. The L- and D-alanine tert butyl ester chloride resulted in solid salts with nitrate, lactate, and tetrafluoroborate anions. This illustrates the previously observed tunability of ionic liquid synthesis, resulting in ionic liquids of varying properties as a function of varying the anion.