Source: VERRAGLO, LLC submitted to NRP
COMMERCIAL ASSAY KIT USING NOVEL COMPOUND SEMICONDUCTOR MATERIALS FOR MEASURING PEROXIDE VALUE IN EDIBLE FATS & OILS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1022710
Grant No.
2020-33610-31693
Cumulative Award Amt.
$96,718.00
Proposal No.
2020-00828
Multistate No.
(N/A)
Project Start Date
Sep 1, 2020
Project End Date
Dec 31, 2021
Grant Year
2020
Program Code
[8.5]- Food Science & Nutrition
Recipient Organization
VERRAGLO, LLC
2029 HEATHER WAY
LEXINGTON,KY 405032639
Performing Department
(N/A)
Non Technical Summary
Collaborators at VerraGlo, LLC and the University of Kentucky have developed foundational technology for light-emitting crystals (LEC) that possess artificial peroxidase activity and emit luminescence in the visible region of the electromagnetic spectrum as a result of the peroxidase-like reaction. Luminescence emissions are proportional to the hydroperoxide content of samples (r-square > 0.98 using commercially available luminometers). Because of the combined peroxidase-like activity and luminescence emissions, LEC are very promising for use in a technique to measure peroxide value in edible fats and oils. Edible fats and oils exhibit inherent susceptibility to oxidation leading to rancidity. Throughout the food industry, from the edible oil refinery to foodservice and retail food processors, fats and oils must be continually tested to meet product and quality specifications. The industry standard for measuring levels of oxidation in edible fats and oils is the peroxide value (PV). The current American Oil Chemists' Society (AOCS) current official method for PV is an iodometric titration that requires laboratory glassware, the use of flammable and toxic solvents that are expensive to purchase and dispose after use, takes about 15 minutes to conduct, suffers from lack of sensitivity and poor endpoint determination and requires trained personnel. The goal of this project is to further develop a novel technique for measuring peroxide value in edible fats and oils using structured compound semiconductor materials that possess peroxidase-like activity and emit luminescence proportional to hydroperoxide contents. This method will be able to measure PV in about 5 minutes with an existing commercially available luminometer. The method will use no laboratory glassware, no solvents and require no cleanup (the sample vial is disposable).Implementation of this novel technology for measuring hydroperoxides in edible oil will also make a strong contribution to the sustainability of our natural resources by elimination of toxic solvents that are currently widely used in a variety of official methods that measure peroxide values (PV) in agricultural products, petrochemicals and pharmaceuticals. All these official methods are iodometric titration procedures that have several disadvantages and require the use of flammable and toxic solvents that are expensive to purchase and to dispose of after use. The waste product from conducting the "peroxide value" iodometric titration includes a mixture of isooctane, acetic acid, oils and iodine. These chemicals are ignitable, corrosive, and/or toxic. The best way to deal with hazardous waste is not to use/create it in the first place. The spillage or release of hazardous substances into the environment can have serious economic consequences. Sustainability of natural resources will also be enhanced by providing improved monitoring of oxidative conditions of an important agricultural commodity with a more convenient and less expensive technique, thus minimizing waste. This project will further develop the LEC material to provide a practical, reliable method to measure PV in the food industry that does not use any hazardous materials.
Animal Health Component
50%
Research Effort Categories
Basic
(N/A)
Applied
50%
Developmental
50%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
50172992000100%
Goals / Objectives
There are three major objectives of this project. The first is to determine the structure/function relationship affecting chemically-stimulated luminescence intensity as a result of the peroxidase mechanism from the novel VerraGlo light-emitting nanocrystals. This will involve correlating the luminescence intensity from a variety of compositional and processing variations, and parameters employed during the measurement of luminescence (including type of photomultiplier tube, effects of temperature, water content, types of reaction mediums and prior exposure to pressure). Additionally, the most effective materials (based on quantum yield, ease of use, and ease and cost of manufacturing) will be examined for structural determinations using a variety of techniques (e.g., x-ray photoelectron spectroscopy, EPR spectroscopy, x-ray diffraction, FTIR spectroscopy, and scanning electron microscopy). The bulk of the products from this first objective should be completed during the period of September 1, 2020-Feburary 28, 2021.This projects second objective is to determine if the current flowing from the peroxidase reaction can be measured using a potentiometric technique. This investigation will employ a potentiostat and a variety of different electrode compositions (both standard and screen-printed electrodes), reaction mediums and co-substrates used to bind the light-emitting materials to the electrodes. If successful, this technique will provide a high level of correlation between the hydroperoxide content of edible oils and the current measured by the potentiostat, and provide the bases for a simplified disposable test strip. The products from this second objective should be completed during the period of November 1, 2020-April 30, 2021.The third objective of this project incorporate the optimal compositions and techniques as determined during accomplishment the first two objectives into a commercially practical sensor for measuring the peroxide values in edible oils. A successful outcome will be an inexpensive assay kit (ca. $6 per assay) that eliminates the need for laboratory glassware and a fume hood, uses no flammable or toxic solvents that are expensive to purchase and dispose of after use, and can be conducted in less than 15 minutes by minimally trained personnel. Additional improvements will include overcoming the lack of sensitivity and poor endpoint determination inherent in the iodometric assay used in current official methods for determining peroxide value in edible oils. The products from this third objective will be completed during the period of November 1, 2020-April 30, 2021.
Project Methods
This Phase I SBIR project is designed to further improve the composition and manufacturing of VerraGlo, LLC light-emitting crystals (LEC) prototypes so as to provide a commercially practical alternative to the existing iodometric titration methods currently available. Examples of "Official methods" currently in use that rely upon iodometric titrations to measure peroxide values (PV) in agricultural products, petrochemicals and pharmaceuticals include the American Oil Chemists Society (AOCS) (official method Cd 8b-90)(AOCS, 1989), Association of Official Analytical Chemists (AOAC) 965.33, the International Union of Pure and Applied Chemistry (IUPAC) 2.501, the International Organization for Standardization (ISO) 3960:2017 and U.S. Pharmacopeia Convention methods (USP) 401. All these official methods are iodometric titration procedures that have several disadvantages and require the use of flammable and toxic solvents that are expensive to purchase and to dispose of after use. The following is the example of the procedure for using VerraGlo LEC to measure PV in edible oils.DEFINITION: This method determines hydroperoxides in edible oils, expressed as of milliequivilents of peroxide per 1000 grams of sample, using a structured semiconductor sensor with peroxidase-like activity. The light emitting crystals (LEC) of semiconductor material generate luminescence proportional to the hydroperoxide content of oils.SCOPE: The method is applicable to all edible oils (liquid at 20-25 degrees C)APPARATUS 1. Glass/Teflon syringe (e.g., 0.5 mL) capable of accurately measuring 0.40 mL of oil, equipped with an 18 gauge x 1.5 inch needle, or a pipette capable of accurately dispensing 0.4 mL of oil.2. Luminometer (e.g., Charm Scientific Novalum) (Lawrence, MA, USA)).3. Charm Sciences LUM-T holder (part No. MT-HLDR) and threaded polypropylene tubes, 2 mL.4. Vortex mixer.REAGENTSLight emitting crystals* (LEC) comprised of structured semiconductor material (e.g., VerraGlo P35e7, VerraGlo, LLC, Lexington, KY, USA), 20 mg per assay in sealed test vial with septa (See Notes, 3).SOLUTIONS: REAGENTS - No reagent solutions are required.STANDARDS - Because of potential variations among different types of luminometers, each instrument must be calibrated. Calibrate the luminometer against AOCS Official Method Cd 8b-90; iodometric titration method using a series of edible oil samples. PROCEDURETest sample preparation - Procedure for oils liquid at 20-25 degrees C -1. Equilibrate liquid oil test samples to 20-25 degrees C.2. Using a glass/Teflon syringe, inject 0.4 mL of oil (at 20-25 degrees C) through the septum into the vial containing LEC.3. Vortex for 3 seconds to thoroughly mix the LEC and oil.4. Wait 1 minute and take a single reading on the luminometer by placing the glass vial inside a 2 mL polypropylene tube, attach the tube to the Charm Sciences sample holder, and insert the sample into the luminometer. Record the value from the luminometer.PREPARATION OF THE CALIBRATION CURVECarry out iodometric titration and plot the results against triplicate luminescence readings from the VerraGlo PV assay. Figure 1 is an example of a standard curve for liquid oils (r-square = 0.995).CALCULATIONSFor a given oil take triplicate luminescence readings and calculate the peroxide value from the standard curve equation.The following are examples of analytical techniques that will be used to accomplish the project objectives and to further improve upon the use and manufacturing of LEC.Luminescence Measurements - Light emissions from all reaction mixtures will be recorded with either a bench-top luminometer (Promega Glomax, 20/20) with an internal heat block (which is adjustable from 22 to 70 degrees C), or a Novalum luminometer (Charm Sciences) with external dry block heater, where appropriate. Emission wavelengths will be determined using 25 mm optical filters (Omega Optical, Brattleboro, VT), of varying wavelength cutoffs, placed in the luminometer to measure luminescence at specific wavelength ranges. Results will typically be reported in 50 nm wavelength ranges (e.g., 500 to 550 nm, 550 to 600 nm, etc) with the ends of the photomultiplier tubes detection ranged measured with from the 450 short path (450sp) and 650 long path (650lp) filters, respectively. Accuracy of wavelength cutoffs for all optical filters were confirmed using an Ocean Optics HR4000 UV/Vis spectrometer (Dunedin, FL) equipped with a USB-DT light source (producing wavelengths from 200 to 900 nm), QP200-2-UV-Vis optical cables, CUV-FL-DA cuvette holder and SpectraView software.Iodometric Peroxide Value (PV) Determination will be carried out precisely according to the American Oil Chemists' Society (AOCS) official method Cd 8b-90 with results expressed as meq/kg oil.Cyclic Voltometry will be conducted on a PalmSens EmStat Blue using screen-printed carbon electrodes (CH Instruments, TE100) or standard electrodes. Light-emitting materials will be attached with a binder such as polyvinylidene fluoride (PVDF) matrix. In addition to CV other potentiometric assays will be examined such as linear sweep voltometery.Electron paramagnetic resonance (EPR) spectroscopy will be performed on a Bruker EMX EPR spectrometer (Billerica, MA). The EPR parameters for paramagnetic materials will be optimized for microwave power; microwave frequency (typically 9.86 GHz); receiver gain; modulation amplitude; modulation frequency; time constant; conversion time; resolution; center field at in Gauss; and field sweep width in Gauss. Detector response, where appropriate will be calibrated using the same EPR parameters with a standard curve prepared with Fremy's salt solutions in quartz capillary tubes. Analyses of EPR peaks and calibration of g-value relative to DPPH standard (2.0036) were performed using the Bruker WinEPR System softwareAtomic Absorption Spectrometry - Select metal contents will be analyzed with a PerkinElmer AAnalyst 200 atomic absorption spectrometer (PerkinElmer, Waltham, MA).. Powdered samples were ashed according to AOAC Official Method 985.35.Peroxidase Reaction Mechanisms and Kinetics will be monitored using gas chromatography/mass spectrometry, high performance liquid chromatography and UV-Vis spectrometry. In aqueous reaction mediums peroxidase activity will be monitored using ortho-Phenylenediamine dihydrochloride (OPD). Composition and structural analysis will be conducted at the University of Kentucky's Electron microscopy Center using a Zeiss EVO MA 10 scanning electron microscope (SEM), a FEI Talos F200X transmission electron microscope (TEM) and a Thermo K-Alpha XPS x-ray photoelectron spectroscopy (XPS).Statistical analysis will be conducted in triplicate unless specified otherwise. Statistical analysis was performed using Statistix software 9.0 (Analytical Software, Tallahassee, FL, USA). A linear model was used for the overall analysis of variance. When a significant treatment effect was found (P < 0.05), multiple comparisons were performed using Tukey HSD all-pairwise comparison test (P < 0.05).

Progress 09/01/20 to 06/07/21

Outputs
Target Audience:Target audiences for the VerraGlo Peroxide Value products include producers, processors and end users of oilseeds and edible oils. Suppliers of analytical instrumentation and reagents are also targeted audiences. The "Peroxide Value" is the primary indication of edible oil quality across the food industry. Larger edible oils processors conduct thousands of these assays on the incoming raw material and the finished refined oils. Food processors use the "Peroxide Value" as the primary quality indicator for an ingredient that is often the most expensive and least stable to oxidative degradation in their finished product. Changes/Problems:VerraGlo, LLC requested a no-cost extension of this grant under the condition that a "written deviation from the primarily employment requirement" be allowed during the no cost extension (as indicated in the award Terms and Conditions). The no-cost extension was issued without the deviation from the "primarily employment requirement". Because of a previous entrepreneurial leave agreement made with the University of Kentucky covering the dates from September 1, 2020 to April 30, 2021, Dr. Boatright cannot continue to be primarily employed at VerraGlo beyond the original dates of the SBIR phase I project dates. After discussions with the USDA NPL it was agreed that VerraGlo should submit all final reporting materials (REEPort, Final report and Final SF425 form) with April 30, 2021 as the project termination date. What opportunities for training and professional development has the project provided?VerraGlo, LLC participated in the University of Kentucky's UAccel program for professional development and an experiential learning opportunity focused on learning the best commercialization path for new start-ups with novel technologies (https://www.research.uky.edu/office-technology-commercialization/ukaccel). This UAccel program began in January 2021 and continued for 15-weeks. This program has been described as an advanced and accelerated version of the LARTA training. During the program a VerraGlo, LLC employee presented the new "peroxide value" technology to participants in a diverse range of new scientific/innovation fields. Other training activities included SBIR/STTR Accounting Webinar sponsored by the Kentucky Cabinet for Economic Development (October 27, 2020) and USDA-LARTA TABA 2020-2021 Kickoff and company orientation webinar (December 2, 2020). How have the results been disseminated to communities of interest?In addition to commercialization activities, VerraGlo, LLC has been in direct contact with numerous potential customers and strategic partners. Target audiences for VerraGlo's products include the end users of the VerraGlo Peroxide Value Assay kit/reagents including producers, processors and end-user of oilseeds and edible oils. Suppliers of analytical instrumentation and reagents are also targeted audiences. During this project executives from VerraGlo, LLC have met and discussed the VerraGlo PV sensor material and assay kit with commodity trade organizations, two of the four larges edible oil processors in the world, smaller seed companies and processors of soybean oils, and two world-wide scientific instrument/reagent suppliers. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? During this project several advancements were made toward improving the commercial application of the VerraGlo structured metal luminophore sensor material for measuring peroxide values. These advancements can be best summarized by the need for additional intellectual property (IP) protection. Primarily based on accomplishments made prior to the start of this project, William Boatright and the University of Kentucky were awarded two U.S. Letters Patents during the time frame of the current project in September and October 2020 (US Patent Numbers 10,794,830 and 10,788,426). While William Boatright is the inventor of the IP included in these patents, the University of Kentucky is the owner. This IP is the foundation of the VerraGlo peroxide value sensor material. In March 2021 the University of Kentucky and VerraGlo, LLC signed a license option agreement that provides VerraGlo, LLC the exclusive rights to market products based on the subject IP. Continued advancements made during this project have resulted in new intellectual property, and an official IP disclosure was made to the University of Kentucky's IP office in December 2020. Subsequently, new U.S. patent application covering these new developments was filed on June 7, 2021 (patent application No. 63/197,593). During the USDA SBIR Phase I project VerraGlo, LLC has made significant advances toward improving the manufacturing and application of the novel peroxide value sensor material. The most important improvement accomplished during this SBIR Phase I project has been to replace the organic phytic acid scaffold material of the peroxide value sensor with a new inorganic phosphate material. The has resulted in an approximately ten-fold increase of the quantum yield (or light production) and a 6-fold decrease in the cost of manufacturing the sensor material. Also, this new phosphate material is readily available from sources in the United States. Light emissions from VerraGlo's peroxide value sensors, with corresponding peroxidase activity is a novel product, and this is supported by the two US patents issued in 2020 (Boatright 2020a, 2020b). Important developments were also made during this project regarding material packaging/application of the VerraGlo peroxide sensor material. Because of the hygroscopic nature of phytates and other phosphate salts, and the well documented ability of moisture to attenuate light emissions in luminescence materials, researchers at VerraGlo and the University of Kentucky have designed a sample tube/packaging process that protects the VerraGlo sensor material from variations in moisture and provides consistence performance regardless of local environmental conditions. One advantage of having a quick, easy and inexpensive method for measuring peroxide value is that researchers are more likely to conduct the test in situations where they might be apprehensive because of the complexity and effort involved with the AOCS Official iodometric titration method. Researchers at VerraGlo discovered that several different types of laboratory petrochemicals (mineral oils, hexanes and cyclohexane) were not stable to oxidation during extended storage. Indeed, several newly purchased mineral oils from different major U.S. suppliers had peroxide values above a 1.0. Development and characterization of the phytic acid and inorganic phosphate based peroxide sensor material have utilized a broad range of analytical/instrumental techniques. At every stage of development all samples were evaluated against the AOCS Official Peroxide Value method involving and iodometric titration (Official method Cd 8b-90). Characterization and identification of the VerraGlo sensor material compositions were accomplished using Electron Microscopy and Energy Dispersive X-Ray Spectroscopy (EDS) compositional analysis, X-ray photoelectron spectroscopy (XPS), X-ray diffraction analysis (XRD), spectral analysis of luminescence emissions, and gas chromatography/mass spectrometry of substrates and products of the peroxidase-like reactions. Potentiometric analyses of both the phytic acid and inorganic phosphate based peroxide value sensor material were conducted. These evaluations used screen-printed carbon electrodes with AgCl reference electrodes from two different manufactures, and SML sensor material was applied using three different types of adhesion (polyvinylidene fluoride, carbon conductive paint and nickel conductive paint). Both types of peroxide value seƱor materials were evaluated using linear sweep voltometry (LSV) and cyclic voltometry (CV). Regardless of the electrode manufacturer, the type of adhesion material or the type of scaffold used, there was a very poor correlation of potentiometric response to the AOCS Official Peroxide Value results (Method Cd 8b-90) with r-square values for the LSV analyses of 0.153 or lower. Measuring the peroxide value of edible oils with luminescence emissions from the VerraGlo sensor material has several major advantages over the existing methods for measuring the peroxide value in edible oils. The existing AOCS Official method for Peroxide Value in edible fats and oils (method Cd 8b-90) is an iodometric titration that utilizes toxic solvents, and thus the assay must be conducted in a laboratory setting under a fume hood. This method generates about 90 mLs of a hazardous solvent mixture per assay that must be disposed of as hazardous waste. Clean-up of oily glassware is also an expensive and time consuming problem. End-point determinations in the low PV range (0-0.5) are problematic with the AOCS Official Method. The VerraGlo PV assay: Does not use or generate toxic solvents. The method uses no laboratory glassware, no solvents and no cleanup; the sample vial is disposable. Assays can be conducted in the field with a commercially available handheld luminometer. Cost less & takes less time (about 2 minutes). Improved sensitivity, precision and readability in the low PV range.

Publications

  • Type: Other Status: Published Year Published: 2020 Citation: Boatright, WL, 2020. Detection of Hydroperoxides using Chemically-Stimulated Luminescence from Structured Compound Semiconductors, issued September 29, 2020, U.S. Letters Patent No.10,788,426.