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EP-3941623-B1 - METHOD FOR CHARACTERIZING AND IDENTIFYING SUBSTANCES

EP3941623B1EP 3941623 B1EP3941623 B1EP 3941623B1EP-3941623-B1

Inventors

  • GROVER, WILLIAM, H.
  • MCKENZIE, Brittney, A.

Dates

Publication Date
20260506
Application Date
20200317

Claims (14)

  1. A method of validating the identity of one or more components in a substance, comprising: obtaining the substance; placing the substance in a plenum with a sealed bottom; exposing the substance in the plenum to one or multiple types of perturbations selected from the group consisting of a thermal perturbation, a force perturbation and a physical perturbation, wherein the one or multiple types of perturbations cause time-dependent changes in the substance; digitally recording images of a change of the substance over a distance or space along the plenum over a period of time in response to exposing the substance to the one or multiple types of perturbations; producing a chronological fingerprint of the change of the substance over the distance or space by digitally stitching images of the change of the substance over the distance or space along the plenum as a function of time to create a plot of the change as a function of time, wherein the chronological fingerprint is a digital multi-dimensional image of the change of the substance over the distance or space along the plenum as a function of time; and comparing the chronological fingerprint to chronological fingerprints of known substances to validate the identity of the one or more components in the substance being measured.
  2. The method of claim 1, where the step of comparing comprises comparing the chronological fingerprint to chronological fingerprints for known substances via feature tracing, image differences, or image hashing.
  3. The method of claim 1, where the known substances comprise: (a) known substances measured in the same experiment; (b) known substances previously measured, from a database of chronological fingerprints; or (c) both known substances measured in the same experiment and known substances previously measured, from a database of chronological fingerprints.
  4. A system for validating the identity of one or more components in a substance comprising: a fluidic chip defining one or more plena with a sealed bottom where a substance is inserted into a first plenum; a mechanism for applying one or multiple types of perturbations selected from the group consisting of a thermal perturbation, a force perturbation and a physical perturbation to the one or more plena; an optical sensor for digitally recording images of a change of the substance over a distance or space along j the first plenum over a period of time when the fluidic chip is exposed to the one or multiple types of perturbations; and a processor configured to: produce a chronological fingerprint from the change of the substance over the distance or space in the first plenum by digitally stitching images of the change of the substance over the distance or space along the first plenum as a function of time to create a plot of the change as a function of time, wherein the chronological fingerprint is a digital image of the change of the substance over a distance or space along the first plenum as a function of time in response to exposing the substance to the one or multiple types of perturbations, and then compare the chronological fingerprint of the substance to one or more chronological fingerprints of known substances to validate the one or more components in the substance.
  5. The system of claim 4, where the fluidic chip comprises multiple plena with sealed bottoms, where a plurality of substances is optionally tested, one in each plenum.
  6. The system of any one of claims 4-5, where the mechanism for applying the one or multiple types of perturbations is a mechanism for applying a thermal perturbation comprising an apparatus containing a thermal perturbation substance, wherein the apparatus defines a chamber for storing the thermal perturbation substance, and wherein, when characterization is initiated, the thermal perturbation substance is placed in heat-transfer communication with part of the fluidic chip containing the one or more plena.
  7. The system of any one of claims 4-5, where the mechanism for applying the one or multiple types of perturbations comprises: (a) a mechanism for applying a force perturbation comprising an apparatus for exerting a force on the fluidic chip; or (b) a mechanism for applying a physical perturbation comprising one or more chambers for storing perturbation particles, and one or more particles that would be introduced into the substance in the plenum.
  8. The system of claim 7, where the one or more particles comprise spheres of poly-epoxide, polyvinyl alcohol, low density polyethylene, high density polyethylene, polycarbonate, polystyrene, polypropylene, polyurethane, polytetrafluoroethylene, polyvinyl chloride, polyamide, polyethylene glycol, polyethylene terephthalate, polybutylene terephthalate, polytrimethylene terephthalate, polyethylene naphthalate, polymethylmethacrylate, poly-epoxide, polyoxymethylene, acrylonitrile butadiene styrene, polyglycolic acid, polylactic acid, polycaprolactone, polyhydroxyalkanoate, polyhydroxybutyrate, polyethylene adipate, polybutylene succinate, or poly(3-hydroxybutyrate-co-3-hydroxyvalerate), plastic, wood, metals and their alloys and oxides, such as silicon, titanium, copper, silver, gold, platinum, aluminum, stainless steel, steel, brass, bronze, or a mixture thereof.
  9. The system of claim 8, where the one more particles comprise steel spheres.
  10. The system of any one of claims 1-5 and 7-9, where the processor compares: (a) the chronological fingerprint of the substance to a stored chronological fingerprint of a known substance; or (b) the chronological fingerprints of the plurality of substances to each other, the plurality of substances consisting of unknown substances, known substances, or both known and unknown substances.
  11. The system of claim 10, where the processor further compares the chronological fingerprints of the plurality of substances to a stored chronological fingerprint of a known substance.
  12. The system of any one of claims 4, 5 and 7-11, where relative position of the fluidic chip and the optical sensor are the same for each measurement.
  13. The system of any one of claims 9-12, where the optical sensor is used to track the location of one or more particles inside one or more plena on the chip.
  14. A computer program product comprising a non-transitory computer usable medium having computer readable code embodied therein which, when the program is executed by a computer, cause the computer to validate the identity of oneor more components in a substance, wherein the computer carries out the steps of: receiving digitally recorded images corresponding to a change of the substance over a distance or space along a plenum over a period of time in response to exposing the substance in the plenum to one or multiple types of perturbations selected from the group consisting of a thermal perturbation, a force perturbation and a physical perturbation, wherein the one or multiple types of perturbations cause time-dependent changes in the substance; producing a chronological fingerprint of the substance experiencing the one or multiple types of perturbations by digitally stitching images of the change of the sub stance over the distance or space along the plenum as a function of time to create a plot of the change as a function of time, wherein the chronological fingerprint is a multi-dimensional digital image of the change of the substance as a function of time; comparing the chronological fingerprint of the substance to chronological fingerprints of one or more known substances, wherein the known substances are either known substances measured in the same experiment or known substances previously measured, from a database of chronological fingerprints, to validate the one or more components in the substance being measured.

Description

Field Described are methods for identifying chemical substances and associated systems for implementing the methods. Background Techniques for identifying a substance, or the components in a mixture, have many applications across a wide range of different fields. Such applications include but are not limited to manufacturing quality control, counterfeit detection, purity quantification. Applicable fields include food, beverages, medicine, beauty products, petrochemicals, and energy. One area of concern is food and the $10 to $15 billion a year global problem of food fraud. See Grocery Manufacturing Association. Consumer product fraud: Deterrence and detection, 21 (2010). In some cases, food ingredients are substituted or diluted with potentially dangerous or toxic alternates, thereby producing a serious public health concern. For example, in 2008 twenty-two food companies in China used the toxic compound melamine, commonly used to produce plastic resins, in infant formula to artificially inflate the apparent protein content of their products resulting in six infant deaths and nearly 300,000 illnesses. Id.; Everstine, K. et al., Economically motivated adulteration (EMA) of food: Common characteristics of EMA incidents., 76 J. Food Prot. 723-35 (2013); Johnson, R., Food fraud and economically motivated adulteration of food and food ingredients, Congressional Research Service, Library of Congress, 40 (2014); Hong, E. et al., Modern analytical methods for the detection of food fraud and adulteration by food category: Adulterated food categories and their analytical methods., 97 J. Sci. Food Agric. 3877-96 (2017). Olive oil was found to be one of the most commonly adulterated food products worldwide between the years 1980 and 2010. See Moore, J. C. et al., Development and application of a database of food ingredient fraud and economically motivated adulteration from 1980 to 2010., 77 J. Food Sci. R118-26 (2012). The University of California, Davis' Olive Center reported in 2010 that 69% of imported olive oils and 10 % of California olive oils labeled "extra virgin" did not meet the legal standard. Frankel, E. et al., Tests indicate that imported "extra virgin" olive oil often fails international and USDA standards, Robert Mondavi Institute for Wine and Food Science, University of California, Davis Olive Center, 10 (2010). In some cases, "extra virgin" olive oil is diluted with other less expensive oils such as sunflower seed and peanut oils, which pose serious health risks to individuals who are allergic to these foodstuffs. Johnson, R. et al., supra at 40; Hong, E. et al., supra. at 3877-96. In response to the significant economic and health impact of food fraud, the Grocery Manufacturing Association and the United States Congressional Research Service recommend testing food products during and after their production and suggest that authenticating ingredients is the best way to detect adulteration. Another area of concern is medicine. It has been found that around 10% of all medications in low- and middle-income countries are counterfeit and may be worthless or even dangerous to patients. Blackstone, E. A. et al., The health and economic effects counterfeit drugs., 7(4) American Health Drug Benefits 216-24 (2014); World Health Organization. WHO global surveillance and monitoring system for substandard and falsified medical products, 73 (2017). Another example highlighting the need for substance identification techniques is the occasionally confused pharmaceutical ingredients glycerol, which is non-toxic, and diethylene glycol, which is toxic. The accidental or intentional substitution with diethylene glycol has led to hundreds of deaths. In 1937, a chemist at the SE. Massengill Company in Bristol, Tennessee, unwittingly substituted a toxic substance, diethylene glycol, for nontoxic glycerol in a liquid formulation of the early antibiotic sulfanilamide. The resulting medicine, called "Elixir Sulfanilamide," fatally poisoned over 100 persons. See Geiling, E. et al, Pathologic effects elixir sulfanilamide (diethylene glycol) poisoning: a clinical and experimental correlation., 111 J. Am. Med. Assoc. 919-26 (1938); Martin, B. J., Elixir: The American tragedy of a deadly drug (Barkerry Press: Lancaster, PA) (2014). The toxicity of diethylene glycol became common knowledge among pharmaceutical companies. However, remarkably, poisonings due to diethylene glycol in medicines remain tragically common today, with a mass poisoning occurring somewhere in the world on average every two years since 1985. Schep, L. J. et al, Diethylene glycol poisoning., 47 Clin. Toxicol. 525-35 (2009). Many of these poisonings occur in resource-limited settings where pharmaceutical companies may not have the resources needed to confirm the identity (and safety) of their manufacturing stocks. The problem of distinguishing diethylene glycol from glycerol is compounded by the fact that they both have very similar properties: they are both tran