WO2021037913A1 - Procédé et système de détermination d'une concentration de graisse dans un échantillon fluide par résonance magnétique nucléaire - Google Patents

Procédé et système de détermination d'une concentration de graisse dans un échantillon fluide par résonance magnétique nucléaire Download PDF

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WO2021037913A1
WO2021037913A1 PCT/EP2020/073854 EP2020073854W WO2021037913A1 WO 2021037913 A1 WO2021037913 A1 WO 2021037913A1 EP 2020073854 W EP2020073854 W EP 2020073854W WO 2021037913 A1 WO2021037913 A1 WO 2021037913A1
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data
sample
relaxation
nmr
flowable
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PCT/EP2020/073854
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English (en)
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Ole Nørgaard JENSEN
Morten Kjærulff SØRENSEN
Niels Christian NIELSEN
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Nanonord A/S
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N24/00—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
    • G01N24/08—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects by using nuclear magnetic resonance
    • G01N24/085—Analysis of materials for the purpose of controlling industrial production systems
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N24/00—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
    • G01N24/08—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects by using nuclear magnetic resonance
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/02—Food
    • G01N33/04—Dairy products
    • G01N33/06—Determining fat content, e.g. by butyrometer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
    • G01R33/281—Means for the use of in vitro contrast agents
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/448—Relaxometry, i.e. quantification of relaxation times or spin density

Definitions

  • the invention relates to a method of determining fat concentration in a flowable sample, such as a flowable sample preferably comprising food.
  • the invention also relates to a system for determining fat concentration in a flowable sample.
  • fat determinations have been determined using wet chemistry methods such as Soxhlet, Fosslet and tetrachloroethylene (TCE) extraction.
  • wet chemistry methods such as Soxhlet, Fosslet and tetrachloroethylene (TCE) extraction.
  • NMR measurement for fat determination is attended by the problem that the strong proton signal of the water, carbohydrates and/or proteins disturbs the measurement of the fat concentration. It has been proposed in DE 41 33 642 Cl to pre-dry the sample in an oven, for example a microwave oven, or to remove the water concentration at least partially by means of chemical drying.
  • U.S. Pat. No. 6,548,303 B2 describes a method and an apparatus of the type already mentioned, in the case of which method and apparatus the sample is relieved of its water constituent by pre-drying in a microwave oven.
  • the sample is firstly introduced into a separate microwave oven for this purpose. There, the sample is heated in a controlled fashion under the action of a microwave field with a frequency of 2.45 GHz and while being monitored by a sensor, and is thereby dried.
  • the sample is located in this case on a balance arranged in the microwave oven such that the weight loss of the sample is measured as drying proceeds, and it is therefore also possible in addition to determine the water concentration.
  • the sample is removed manually from the microwave oven and transferred into a separate NMR analyzer in which the nuclear magnetic resonance measurement then takes place.
  • This known mode of procedure has the disadvantage that the sample must be handled in a complicated fashion.
  • the substance of the sample must firstly be applied to a tissue fragment of quartz or glass fibers, which acts as a substrate.
  • This tissue fragment is transparent to microwaves and free from proton signals in the NMR measuring range of interest here. Since, because of the fat or oil fractions, the sample material liquefies as it dries out, at least for the NMR measurement the sample substance applied to the tissue fragment must further be wrapped in a film, which consists of polytetrafluoroethylene (PTFE). All these steps are clearly complicated and time-consuming. Automated measurements on a multiplicity of samples are therefore impractical or impossible with the aid of this known mode of procedure.
  • PTFE polytetrafluoroethylene
  • US2007010021 describes a method where the sample is dried under the action of a microwave field and is examined under the action of a radio frequency signal and of a constant magnetic field by means of nuclear magnetic resonance.
  • the sample may be exposed to the microwave field, the radio-frequency signal and the magnetic field at the same measuring place in a common measuring chamber.
  • the objective of the present invention is to provide a method of determining fat concentration in a flowable sample, which is fast, relatively simple and with a high accuracy even where the sample comprises non-fat, proton comprising components such as water, carbohydrates and/or proteins.
  • an objective of the present invention is to provide a system for use in determining fat concentration in a flowable, sample, such as a liquid sample, which is fast, relatively simple and with a high accuracy even where the sample comprises non-fat, proton comprising components such as water, carbohydrates and/or proteins.
  • the method of determining fat concentration in a flowable sample according to the invention has been found to be very fast and accurate and does not require drying of the sample.
  • the method and systems of the invention and preferred embodiments thereof will be described further below.
  • the method of determining fat concentration in a flowable sample comprises
  • ⁇ NMR signal • subjecting the sample to radio-frequency excitation to produce a free induction decay ⁇ NMR signal, • generating data of at least a part of the ⁇ NMR signal comprising TD (time-domain) data representing signal dependence on T1 (longitudinal) or T2 (transverse) relaxation,
  • the slow-relaxation TD data portion is selected to exclude data representing signal dependence on at least a part of short T1 or at least a part of short T2, wherein short T1 or T2 respectively is shorter than long T1 or long T2 of protons of a component in the sample.
  • the TD signal may also be described as the intensity versus time.
  • NMR signal intensity may be determined from the slow-relaxation TD data portion as the total intensity of the slow-relaxation TD data portion.
  • the slow-relaxation TD data portion is advantageously selected to suppress or exclude data representing a fast-relaxing portion of the Tl- and/or T2- dependent time-domain data.
  • the slow-relaxation TD data portion is obtained by suppressing or excluding signal from the protons having short (fast) relaxation time.
  • Data representing TD data may be in the form of the time-domain data or it may be data in any other form suitable for representing the TD data, such as mathematical transformed data, such as Fourier or inverse Laplace transformed data.
  • a main drawback of prior art fat determination concentration in for example food is that it is not possibly to distinguish between signals originating from water, protein, carbohydrates, and the fat.
  • the addition of relaxation agent dramatically reduce the 1 H relaxation times for water, sugar, protein surface protons (protein core protons have short relaxation time already), whereas 1 H relaxation time for the fat bound protons is conserved since the interaction with fat globules is very limited.
  • Nuclear magnetic resonance - abbreviated NMR- is a phenomenon, which occurs when the nuclei of an isotope with a nuclear spin in a magnetic field absorb and re-emit electromagnetic radiation.
  • the emitted electromagnetic radiation has a specific resonance frequency, which depends on the strength of the magnetic field and the magnetic properties of the isotope.
  • NMR allows the observation of specific quantum mechanical magnetic properties of the atomic nucleus.
  • Many scientific techniques exploit NMR phenomena to study molecular physics, crystals, and non-crystalline materials through NMR spectroscopy.
  • NMR is also routinely used in advanced medical imaging techniques, such as in magnetic resonance imaging (MRI).
  • An NMR measurement is performed by NMR spectrometer or NMR relaxometer, here also referred to as an analyzer.
  • spectroscopy and “spectrometry” are used interchangeable and in the same way the a spectroscope is the same as a spectrometer.
  • NMR spectroscopy is well known in the art and has for many years been applied for laboratory measurements in particular where other measurement methods could not be used. NMR spectroscopy is performed using an NMR spectrometer. Examples of spectrometers are e.g. described in US 6,310,480 and in US 5,023,551. The term NMR spectrometer also includes a NMR relaxometer. General background of NMR formation evaluation can be found, for example in U.S 5,023,551.
  • relaxation describes processes by which nuclear magnetization excited to a non-equilibrium state return to the equilibrium state.
  • relaxation describes how fast spins "forget” the direction in which they are oriented.
  • the relaxation time T2 is herein used to include "apparent T2" (sometimes also called T2*).
  • Apparent T2 includes a contribution caused by instrumental effects, such as magnetic field inhomogeneity. Instrumental effects (e.g. large magnet inhomogeneity) may cause that measured T2 relaxation times reflect apparent T2 relaxation times rather than pure natural T2 relaxation times. However, such instrumental effects may for example be minimized using a proper echo-train pulse sequence (e.g. CPMG) and may often be ignored (at least for the intensity determination), specifically where the same instrument is used for generating the standard curve and for performing the measurement.
  • the NMR spectrometer advantageously comprises an integrated or an external computer associated with a memory.
  • the method comprises NMR excitation of at least one *H NMR signal and generating data comprising Tl-dependent time-domain data.
  • the TD data is advantageously echo train time-domain data generated using a spin echo method as described below and as known in the art.
  • T1 relaxation is also called the longitudinal relaxation.
  • T1 relaxation involves redistributing the populations of nuclear spin states in order to reach the thermal equilibrium distribution.
  • the method comprises generating data of at least a part of the *H NMR signal comprising TD (time-domain) data representing signal dependence on Tl.
  • the method comprises generating data of at least a part of the *H NMR signal comprising TD data representing signal dependence on T2.
  • T2 relaxation is also called the transverse relaxation.
  • T2 relaxation is a complex phenomenon and involves decoherence of transverse nuclear spin magnetization.
  • T2 relaxation values are substantially not dependent on the magnetic field applied or the NMR frequency applied during excitation of the *H nuclei.
  • the generated data comprises T2- dependent time-domain data.
  • the magnetic field applied and/or the NMR frequency applied for generating the standard curve is the same or within +/- 20 % from the magnetic field applied and/or the NMR frequency applied when performing the fat concentration determination.
  • the magnetic field applied and/or the NMR frequency applied for generating the standard curve is the same or within +/- 10 %, such as within +/- 5 %, such as within +/- 1 %, from the magnetic field applied and/or the NMR frequency applied when performing the fat concentration determination.
  • a standard technique for measuring NMR signals and obtaining information about the spin-spin relaxation time T2 utilizing CPMG (Carr-Purcell-Meiboom - Gill) sequence is as follows. As is well known after a wait time that precedes each pulse sequence, a 90-degree exciting pulse is emitted by an RF antenna, which causes the spins to start processing in the transverse plane perpendicular to the external magnetic field. After a delay, a first 180-degree pulse is emitted by the RF antenna. The first 180-degree pulse causes the spins, which are dephasing in the transverse plane, to reverse direction and to refocus and subsequently cause an initial spin echo to appear.
  • CPMG Carr-Purcell-Meiboom - Gill
  • a second 180-degree refocusing pulse can be emitted by the RF antenna, which subsequently causes a second spin echo to appear. Thereafter, the RF antenna emits a series of 180-degree pulses separated by a short time delay. This series of 180-degree pulses repeatedly reverse the spins, causing a series of "spin echoes" to appear. The train of spin echoes is measured and processed to determine the spin-spin relaxation time T2.
  • the refocusing RF pulse(s) is/are applied after the exciting RF pulse with an echo-delay time-period between the exciting RF pulse and the subsequent refocusing RF pulse.
  • the refocusing RF pulses are typically separated by twice the delay from the exciting RF pulse to the first refocusing RF pulse.
  • the echo-delay time (also called echo time TE) is preferably of about 500 ps or less, more preferably about 150 ps or less, such as in the range from about 50 ps to about 100 ps depending on the homogeneity of the magnetic field applied (here assuming an inhomogeneity of the applied magnetic field of about 500 ppm, while longer an echo-delay time is suitable if a more homogenous magnetic field is applied).
  • This method is generally called the "spin echo” method and was first described by Erwin Hahn in 1950. Further information can be found in Hahn, E.L. (1950). "Spin echoes". Physical Review 80: 580-594, which is hereby incorporated by reference.
  • a typical echo-delay time is from about 10 ps to about 50 ms, preferably from about 50 ps to about 200 ps.
  • the repeat delay time (also called wait time TW) is the time between the last CPMG 180° pulse and the first CPMG pulse of the next experiment at the same frequency. This time is the time during which magnetic polarization or T1 recovery takes place. It is also known as polarization time.
  • the repeat delay time typically in the order of 2 s, should typically be sufficiently long to ensure full recovery of the polarization, but may also be shortened to obtain Tl-dependent data.
  • This basic spin echo method provides good results for obtaining Tl-modulated data by varying TW and T2-modulated data by varying the echo-delay time or by using plurality of refocusing pulses.
  • the delay between refocusing pulses is also called the Echo Spacing and indicates the time identical to the time between adjacent echoes.
  • the TE also reflects the time between 180° pulses.
  • the data representing signal dependence on T2 may advantageously be acquired using a spin echo train experiment (e.g. the CPMG pulse sequence) or a series of spin echo experiments.
  • the acquisition of T1 information may advantageously comprise one or more acquisitions with the saturation recovery or inversion recovery, or modified experiment versions based on these experiments.
  • This CPMG method is an improvement of the spin echo method by Hahn. This method was provided by Carr and Purcell and provides an improved determination of the T2 relaxation values, which again allows for better quantitative determination of the signal intensity via more precise consideration of T2 effects obtained from single or multi curve fitting for most precise envelope of spin echo amplitudes.
  • Carr and Purcell method which is a basic echo-train method and the fundament for the CPMG method
  • relaxation agents for enhanced T1 and/or T2 relaxation are known in the art. Such relaxation agents are routinely used in Magnetic Resonance Imaging (MRI) and are often referred to as "contrast agents”.
  • MRI Magnetic Resonance Imaging
  • the relaxation agent advantageously comprises a salt or an aqueous solution thereof.
  • the relaxation agent is added to the sample in dissolved form in order to ensure a fast distribution throughout the sample.
  • the salt in dissolved condition comprises a metal ion.
  • the metal ion is a divalent or trivalent metal ion.
  • preferred metal ions includes Cr 3+ , Mn 2+ , Mn 3+ , Fe 3+ , Gd 3+ , Eu 3+ , Cu 2+ ,
  • the relaxation agent comprises at least one of a paramagnetic element, a diamagnetic element or a ferromagnetic element.
  • the relaxation agent comprises a paramagnetic element.
  • the relaxation agent comprises a colloid of superparamagnetic iron oxide particles or a colloid of superparamagnetic iron- platinum particles.
  • the relaxation agent may advantageously comprise a complex, preferably the relaxation agent comprises a chelate, such as a manganese chelate or a gadolinium(III) chelate
  • a chelate such as a manganese chelate or a gadolinium(III) chelate
  • relaxation agent includes gadoterate meglumine, ferric-EDTA, GdC and [GdDTPA(H20)] 2 , preferably the relaxation agent comprises a gadolinium(lll) chelate.
  • the flowable sample may in principle be any type of flowable sample containing fat (or suspected of containing fat).
  • the flowable sample is sufficiently flowable for being mixed with the relaxation agent.
  • the flowable sample advantageously comprises liquid.
  • the flowable sample comprises at least about 10 % liquid by volume of the sample, such as at least about 25 %, such as from about 40 % to 100 % liquid by volume of the sample.
  • the flowable sample advantageously comprises at least about 10 % liquid by weight of the sample, such as at least about 25 %, such as from about 40 % to 100 % liquid by weight of the sample.
  • the liquid may be any liquid or a mixture of liquids, such as water, ethanol and/or oil, preferably comprising dissolved, dispersed and/or suspended component(s).
  • the sample may advantageously be an aqueous sample optionally comprising particles, such as dispersed particles, such as fat globules and/or protein particles (e.g., casein micelles).
  • particles such as dispersed particles, such as fat globules and/or protein particles (e.g., casein micelles).
  • the sample may comprise solid parts.
  • the solid parts comprise non-fat bound protons
  • solid parts including mobile protons in the bulk part has a volume of about 100000 nm 3 or less, such as of about 3000 nm 3 or less, of about 30 nm 3 or less.
  • the sample may be subjected to a blending/cutting process for reducing the size of solid particles.
  • Some, protons in non-fat solid parts e.g. some protein bound protons have naturally fast relaxation, i.e. a relative short signal decay time. Particles comprising such protons may in an embodiment be relatively large without corrupting the fat determination.
  • the flowable sample may for example comprise a food product, such as a dairy product, meat, fish, vegetables or any fragments or combinations thereof.
  • the NMR spectrometer may be a low field spectrometer, such as a NMR spectrometer having a relatively low magnetic field, and therefore may be compact and transportable.
  • the sample may be a multi component sample comprising at least one of water, small organic compounds, carbohydrates and/or proteins in addition to the fat.
  • the sample may for example comprise at least one of carbohydrates and proteins.
  • the flowable sample comprises small organic compounds, such as C1-C5 organic compounds, such as hydrocarbons and/or organic compounds comprising nitrogen, silicon, halogen or combinations thereof.
  • small organic compounds such as C1-C5 organic compounds, such as hydrocarbons and/or organic compounds comprising nitrogen, silicon, halogen or combinations thereof.
  • the flowable sample comprises a food product, such as a milk product, a protein drinkable product, a sauce or similar.
  • the flowable sample may for example be a dilution or a liquid concentration of the food product.
  • the flowable sample is a sample of raw milk.
  • the fat concentration determination may e.g. be performed on-the-spot at the dairy farm or in an industrial milk product production line.
  • the food product comprises a solid food product dissolved and/or suspended in liquid to form the flowable sample.
  • colloids or “suspended” include colloids, emulsions, sols and any other type of dispersions.
  • the flowable sample may e.g. comprise meat, which has been blended with a known amount of liquid, such as water, such that the fat concentration in the flowable sample can be directly correlated to the fat concentration in the meat or similar solid product.
  • a known amount of liquid such as water
  • the optimal amount of relaxation agent added to the flowable sample may depend on the selected relaxation agent. However, generally it is desirable that the amount of relaxation agent added to the liquid is such that the resulting flowable sample with relaxation agent has a concentration of relaxation agent of at least 0.1 mM, such as at least 1 mM, such as at least 5 mM, such as at least 10 mM, such as at least 20 mM, such as at least 30 mM. In an embodiment, the relaxation agent is added in an amount to provide that the flowable sample has a concentration of relaxation agent of between 0.1 and 50 mM.
  • a desired amount of a specific relaxation agent may be determined by a few tests using different amounts of the relaxation agent.
  • An optimal amount of relaxation agent may be determined by a few tests starting from adding a relative low amount of relaxation agent and gradually increasing the amount and for each amount determining the *H NMR signal intensity from the slow- relaxation TD data portion. When the determined *H NMR signal intensity does not change or does practically not change from one determination to another with higher amount of relaxation agent, a preferred amount of relaxation agent has been found.
  • the relaxation agent is advantageously mixed into the sample by stirring and/or shaking prior to performing the NMR excitation.
  • the NMR excitation and data generation (recording) also referred to as the NMR reading
  • the NMR reading is performed in a magnetic flux density of from 1 mT to 6 T. Higher magnetic flux may be used, but this adds to cost and is therefore not preferred.
  • the NMR reading is performed in a low field magnetic field, such as a magnetic field with a magnetic flux density up to 1.5 T. Using a low field magnetic field has shown to be sufficient and the fat content determinations obtained are very accurate. Simultaneous a low field NMR spectrometer may be very compact and may thereby be portable.
  • the step of subjecting the sample to excitation to produce a free induction decay *H NMR signal is a normal step in an NMR determination.
  • the free induction decay *H NMR signal starts practically immediately after the excitation as the exited protons returns to balance (i.e., relaxation)
  • the FID signal is approximately exponential and with a duration which is normally in the order of milliseconds for *H NMR .
  • the generating data of at least a part of the FID 1 H NMR signal comprising TD (time-domain) data representing signal dependence on T1 or T2, is advantageously performed by recording the at least a part of the FID 1 H NMR signal intensity as a function of time. Since the FID signal is approximately exponential, the time of recording will normally not include the entire signal but will stop when the signal is reduced to practically zero. In an embodiment, the recording is terminated when the signal is reduced 50 %, such as 75 %. In case inverse Laplace transformation is employed for data interpretation the recordings may be prolonged.
  • the FID 1 H NMR signal intensity comprises a slow-relaxation portion representing signal dependence on long T1 or long T2 and a fast-relaxation portion representing signal dependence on short T1 or short T2 respectively.
  • the inventors has found that by adding the relaxation agent to the flowable sample, the non-fat bound protons will return very fast to balance, meaning that the *H NMR signal from these protons will be relatively fast relative to the signal from the fat bound protons. Hence, by suppressing (e.g. fully eliminating) the fast relaxation portion of the FID, a direct determination suppressing or fully eliminating noise from the non-fat bound protons may be obtained.
  • the optimal threshold value defining the limit between the fast-relaxing portion and the slow-relaxing portion component may depend on the relaxation agent applied.
  • a desired threshold value defining the fast-relaxing portion of the time- domain data may for example be found by adding the selected relaxation agent to a fat-free sample comprising carbohydrates and/or protein, and performing a NMR excitation of at least one *H NMR signal and generating data comprising T1 and/or T2 information. From this the relaxation behavior of the desired fast-relaxing portion and/or desired length of the first time period from the time-domain data is determined, i.e. the period after the intensity of the T2-dependent signal is insignificant e.g. where the signal has reduced to less than 1 % of maximum signal or where relaxation is close to or fully complete - i.e. non detectable.
  • the generating data of at least a part of the FID 1 H NMR signal comprising TD (time-domain) data representing signal dependence on T1 or T2, is may include generating (recording) data of both the slow-relaxation portion and the fast-relaxation portion.
  • the generating data of at least a part of the FID 1 H NMR signal comprising TD (time-domain) data representing signal dependence on T1 or T2 is may leave out the fast-relaxation portion, thereby a later filtering of the data may not be required.
  • the selection of the slow-relaxation TD data portion representing signal dependence on long T1 or long T2 in the generated TD data may be performed by simply selecting the entire generated data.
  • the fast-relaxation TD data comprises both fast-relaxation TD data and slow-relaxation TD data
  • the selection of the slow-relaxation TD data portion representing signal dependence on long T1 or long T2 in the generated TD data may be performed by filtering the data to omit the fast-relaxation TD data.
  • the generated data of at least a part of the ⁇ NMR signal excludes TD data representing signal dependence on at least a part of the short T1 or at least a part of the short T2 of protons of a component in the sample i.e. fast-relaxation TD data is excluded.
  • the selection of the slow-relaxation TD data portion comprises selecting substantially all the generated data.
  • the generated data of at least a part of the ⁇ NMR signal comprises TD data representing signal dependence on both long T1 and short T1 of both long T2 and short T2 of protons of a component in the sample.
  • the generated data is generated from substantially the entire ⁇ NMR signal.
  • the selection of the slow-relaxation TD data portion may comprise filtering the generated data to suppress the fast-relaxation TD data portion representing signal dependence on short T1 or short T2 of the generated TD data.
  • the method uses data representing signal dependence on T2. It has been found to be relatively simple to suppress e.g. remove and/or leave out fast-relaxation TD data representing signal dependence on at least a part of short T2.
  • the generation of data advantageously comprises generating data of at least a part of the ⁇ NMR signal comprising TD data representing signal dependence on T2 and the selection of the slow-relaxation TD data portion comprises selecting a slow-relaxation TD data portion representing signal dependence on long T2 of the generated TD data.
  • the short T2 may advantageously be or comprise T2 times up to about 200 ms, such as up to about 125 ms, such as up to about 100 ms, such as up to about 90 ms, such as up to about 80 ms, such as up to about 60 ms, such as up to 50 ms.
  • the long T2 comprises T2 times above 50 ms, such as above 60 ms, such as above 70 ms, such as above 80 ms, such as above 90 ms, such as above 100 ms, such as above 125 ms, such as above 200 ms.
  • the fast-relaxing portion is suppressed or left out simply by discarding (such as not recording) the first time-period of the FID ⁇ NMR signal.
  • the desired length of the first time-period of the time-domain data may advantageously be as the short T2 as given above and/or as the first time-period of the domain data given below.
  • the filtering of the generated data to suppress a fast- relaxation TD data portion representing signal dependence on short T2 of the generated TD data comprises filtering off data of at least one first time-period of the domain data.
  • the first time period of the domain data advantageously comprises a time period of at least 2 ms, such as from 10 ms to 200 ms, such as from 25 ms, to 125 ms, such as from 50 ms to 100 ms, such as from 60 ms to 80 ms.
  • the at least one first time period of the time-domain data starts from the start of the time-domain data or up to 25 ms from the start of the time-domain data, preferably the at least one first time period of the time- domain data starts from the start of the time-domain data.
  • the generation of data comprises generating data of at least a part of the ⁇ NMR signal comprising TD data representing signal dependence on T1 and the selection of the slow-relaxation TD data portion comprises selecting a slow-relaxation TD data portion representing signal dependence on long T1 of the generated TD data.
  • the slow- relaxation TD data portion is substantially free of data representing signal dependence on short T2 of the generated TD data
  • the method advantageously also comprises generating the standard curve.
  • Generating the standard curve based on measurement on only one single reference sample is usually not optimal, but it may be helpful in some situations and is accordingly an embodiment of the invention.
  • the generation of the standard curve comprises • providing a plurality of flowable reference samples with different and known fat concentration
  • the provision of the standard curve and the performing of the linear regression may comprise extrapolating from at least one point of a pair of the determined ⁇ NMR signal intensity and corresponding known fat concentration, such as from a pair representing a highest or a lowest fat concentration.
  • the linear regression uses several of the points (x,y) of respective pair of determined ⁇ NMR signal intensity and corresponding known fat concentration, ), such as 3, 4, 5 or more of the points (x,y).
  • the performing of the linear regression comprises interpolation and/or extrapolating from at least one point of a pair of the determined ⁇ NMR signal intensity and corresponding known fat concentration and/or involving pairs of the determined ⁇ NMR signal intensity and corresponding known fat concentration.
  • the plurality of flowable reference samples with different and known fat concentration comprises at least 3, such as at least 4, such as at least 5, such as at least 8 reference samples.
  • the plurality of flowable reference samples with different and known fat concentration may comprise a reference samples with zero fat. This reference sample may replace the point (x,y) of zero fat, zero signal.
  • the plurality of flowable reference sample with different and known fat concentration comprises a reference samples with a preselected highest fat concentration, wherein the preselected highest fat concentration is preselected to be larger than an estimated fat concentration of the flowable sample.
  • the reference samples and the flowable sample for which the fat concentration is to be determined are sample of same type, e.g. same type of food product.
  • the flowable sample is a milk product
  • the reference samples are preferably also milk products or dilutions thereof.
  • the plurality of liquid reference samples with different and known fat concentration comprises a group of liquid reference samples comprising concentrations of respective water, C 1 -C 5 organic compounds carbohydrates and/or proteins, which are within 10 % w/w from the highest concentration of respective water, carbohydrates and/or protein of the group of reference samples.
  • the reference samples are generated from one sample to which different and known amount of water has been added to generate the various reference samples.
  • the *H NMR signal intensity determination(s) is/are performed using the same method, which is used for determining fat concentration in the flowable sample.
  • the standard curve may be generated as a plotted curve and/or the standard curve may be generated as standard curve data representing the standard curve.
  • the standard curve may be in any other suitable form, which indicates the signal versus fat concentration or any derivatives thereof.
  • the invention also related to system for determining fat concentration in a flowable sample.
  • the systems may be used to perform the method of determining the fat concentration in a flowable sample as described above.
  • the system for determining fat concentration in a flowable sample comprises an NMR spectrometer, wherein the NMR spectrometer comprises a computer associated with a memory, wherein the spectrometer is configured (i.e. programmed) for generating a standard curve comprising
  • the spectrometer further is configured for • subjecting the flowable sample to excitation to produce a free induction decay ⁇ NMR signal and generating TD data representing signal dependence on T1 or T2 of the flowable sample,
  • the system for determining fat concentration in a flowable sample comprises an NMR spectrometer, wherein the NMR spectrometer comprises a computer associated with a memory, wherein the spectrometer is configured for generating a standard curve comprising
  • the spectrometer further is configured for • subjecting the flowable sample to excitation to produce a free induction decay ⁇ NMR signal and generating TD data representing signal dependence on T1 or T2 of the flowable sample,
  • the system for determining fat concentration in a flowable sample comprises an NMR spectrometer, wherein the NMR spectrometer comprises a computer associated with a memory, wherein the memory comprises data representing a standard curve of ⁇ NMR signal intensities relative to known fat concentrations, wherein the spectrometer is configured for
  • the system of the invention is advantageously programmed to performing the method of the invention as described above optionally excluding the preparation of the samples and arranging the sample in the NMR spectrometer, which may be performed manually or using an integrated, connected or external apparatus.
  • the system for determining fat concentration in a flowable sample comprises, NMR spectrometer with a computer associated with a memory e.g. as described above.
  • the memory comprises data representing a standard curve of ⁇ NMR signal intensities relative to known fat concentrations, wherein the standard curve of ⁇ NMR signal intensities relative to known fat concentrations represents signal intensities of Tl- and/or T2-dependent time-domain data with a suppressed fast-relaxing portion.
  • the fast-relaxing portion of the Tl/T2-dependent time-domain data may be as described above.
  • the fast-relaxing portion of the T1/T2- dependent time-domain data comprises time-domain data from at least one first time-period of the time-domain data.
  • the at least one first time period of time-domain data comprises a time period of at least 2 ms, such as from 10 ms to 150 ms, such as from 25 ms to 125 ms, such as from 50 ms to 100 ms, such as from 60 ms to 80 ms.
  • the NMR spectrometer is configured for performing the NMR reading is in a magnetic flux density of from 1 mT to 6 T, preferably the NMR reading is performed in a low field magnetic field, such as a magnetic field with a magnetic flux density up to 1.5 T, such as up to 1.3 T.
  • the NMR spectrometer is configured for generating the TD data to exclude TD data representing signal dependence on at least a part of the short Tl or at least a part of the short T2 of protons of a component in the sample.
  • the NMR spectrometer is configured for generating the TD data to comprise TD data representing signal dependence on both long Tl and short Tl and/or on both long T2 and short T2 of protons of protons in the sample and to suppress the TD data representing signal dependence on short T1 and/or on short T2 of protons of protons in the sample.
  • the method of the invention may be combined with additional NMR measurements involving NMR enhancement such as enhancement involving polarization transfer, e.g. DEPT (Distortionless Enhancement by Polarization Transfer) or INEPT (Insensitive nuclei enhanced by polarization transfer).
  • DEPT Deviceless Enhancement by Polarization Transfer
  • INEPT Insensitive nuclei enhanced by polarization transfer
  • concentrations of the presence of primary, secondary and tertiary carbon atoms CH, CH2 and CH3 groups
  • This determination may be combined with the determination of the method of the present invention and thereby further refine the determination of fat concentration.
  • Fig. 1 shows a standard curve.
  • Fig. la shows the content of the actual flowable samples of example 1.
  • Fig. 2 is a zoom of the standard curve of Fig. 1.
  • Fig. 3 shows an example of T2-dependent time-domain data (an example of CPMG echo-train data).
  • Example 1 A standard curve was generated by the method of the invention.
  • a number of reference samples with known fat concentration were provided.
  • the reference samples included a variety of milk types including the following test samples (mainly supermarket milk) and mixtures of these:
  • the fat content varied from 0 to 15%, the sugar (lactose) content from 0 to 4.9%, and the protein content from 0 to 3.6%.
  • the content of the actual flowable samples can be seen in Fig. 1a
  • a relaxation agent was added to a concentration of 30 mM.
  • the relaxation agent used was DOTAREM® (gadoterate meglumine).
  • T2- dependent time-domain data was generated for each reference sample.
  • the T2-dependent time-domain data was filtered, suppressing (discarding) the first 70 ms of the T2-dependent time-domain data. Thereby the fast- relaxation portion of the TD data has been filtered of.
  • a ⁇ NMR signal intensity was determined from the filtered time- domain data, thereby generating points of respective pair of determined ⁇ NMR signal intensity and corresponding known fat concentration of the respective reference samples.
  • Fig. 2 show a zoom of the standard curve of Fig. 1, and it can be seen that even in this explored view correlation between the ⁇ NMR signal intensity and the fat content is linear and with very low noise.
  • T2 time-domain data showing a signal of a slow-relaxing fat component versus a signal of all components in the sample.
  • the figure illustrates that, after less than 100 ms, e.g. about 80 ms, the total signal reflects to a high precision solely the content of fat since the signal from protons of other components has been suppressed.
  • the fast-relaxation TD data portion may thus be the first about 80 ms.
  • the fast-relaxation TD data portion may be set to the first 100 ms and the slow-relaxation data portion used may be a data portion after the first 100 ms.
  • the slow-relaxation data portion used may advantageously include intensity data from a time range of at least 10 ms, preferably at least 50 ms or more.

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Abstract

L'invention concerne un procédé et un système permettant de déterminer la concentration de graisse dans un échantillon fluide. Le procédé comprend un certain nombre d'étapes comprenant l'ajout d'un agent de relaxation à l'échantillon fluide, la soumission de l'échantillon à une excitation dans un spectromètre de RMN pour produire un signal de RMN1 de décroissance d'induction libre, la génération de données d'au moins une partie du signal de RMN1H comprenant de données de TD (de domaine temporel) représentant une dépendance de signal de T1 ou T2, la sélection d'une partie de données de TD de relaxation lente représentant une dépendance de signal d'un T1 long ou d'un long T2 dans les données de TD générées, la détermination d'une intensité de signal de RMN 1H à partir de la partie de données de TD à relaxation lente, et la corrélation de l'intensité de signal de RMN 1H déterminée à une courbe d'étalonnage de signaux de RMN 1H par rapport à des concentrations de graisse connues.
PCT/EP2020/073854 2019-08-27 2020-08-26 Procédé et système de détermination d'une concentration de graisse dans un échantillon fluide par résonance magnétique nucléaire WO2021037913A1 (fr)

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CN113125488A (zh) * 2021-04-21 2021-07-16 南京农业大学 一种注脂人造雪花牛肉的快速鉴别方法
CN113125488B (zh) * 2021-04-21 2023-04-18 南京农业大学 一种注脂人造雪花牛肉的快速鉴别方法

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