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WO2018199631A1 - Procédé pour quantifier un composant hydrophobe dans un liquide à l'aide d'un facteur de diffusion de zone de contact, et procédé utilisant ce procédé pour fournir des informations relatives au diagnostic d'une maladie - Google Patents

Procédé pour quantifier un composant hydrophobe dans un liquide à l'aide d'un facteur de diffusion de zone de contact, et procédé utilisant ce procédé pour fournir des informations relatives au diagnostic d'une maladie Download PDF

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Publication number
WO2018199631A1
WO2018199631A1 PCT/KR2018/004808 KR2018004808W WO2018199631A1 WO 2018199631 A1 WO2018199631 A1 WO 2018199631A1 KR 2018004808 W KR2018004808 W KR 2018004808W WO 2018199631 A1 WO2018199631 A1 WO 2018199631A1
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Prior art keywords
dementia
contact surface
droplet
liquid
fat
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English (en)
Korean (ko)
Inventor
이상현
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Femtobiomed Inc
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Femtobiomed Inc
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N13/00—Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N13/00—Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects
    • G01N13/02—Investigating surface tension of liquids
    • 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
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N13/00—Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects
    • G01N2013/003—Diffusion; diffusivity between liquids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N13/00—Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects
    • G01N13/02—Investigating surface tension of liquids
    • G01N2013/0283—Investigating surface tension of liquids methods of calculating surface tension
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/04—Endocrine or metabolic disorders
    • G01N2800/042—Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism

Definitions

  • the present invention relates to a method for quantifying hydrophobic components, specifically fat components, contained in a liquid using a contact area diffusion coefficient (CADF) on a solid surface of a liquid and metabolic diseases or dementia, specifically diabetes.
  • the present invention relates to a method for predicting the onset of fat embolism or dementia or for providing information for diagnosing the onset or course of the diseases.
  • Lipoembolism is one of the leading causes of death in the surgical procedure. Liposuction and orthopedic surgery, especially with a large number of surgeries per year, has a low mortality rate, but a high number of deaths each year. Is occurring.
  • Liposuction is the most frequently performed surgery in plastic surgery, but the risks that occur during liposuction are not well known to the public. Fat embolism is caused by the inflow of fat into the bloodstream through damaged blood vessels during liposuction, which can seriously impair lung function and penetrate other organs. Despite the relatively low incidence of fat embolism, hundreds of deaths are known worldwide due to very high mortality rates.
  • the amount of fat introduced into the bloodstream before, during and after surgery should be measured from time to time, but there is no device for quantifying the amount of fat.
  • the present inventors have mentioned the contact surface diffusion coefficient (CADF) of the liquid and the method of measuring the amount of fat penetrated through the liquid in the preceding patent application (Korean Patent Application No. 10-2012-0147029).
  • the CADF measuring method described in the above-mentioned prior application is to measure the degree of change in the contact diameter or the contact area of the droplet contacting surface in contact with the solid plane over time or by measuring the change in the amount of fatty components present in the liquid. Obtaining CADF.
  • the contact area diffusion coefficient has been improved by including both the contact area and contact diameter between the droplet and the solid surface as variables. Calculation method of was required.
  • the present inventors have completed a novel method for estimating a contact surface diffusion coefficient with improved accuracy while including a method for estimating a contact surface diffusion coefficient based on a contact area between a droplet and a solid surface and a method for calculating a contact surface diffusion coefficient based on a contact diameter. It came to the following.
  • the present invention relates to a method for quantifying hydrophobic components, specifically fat components, contained in a liquid by using a contact surface diffusion coefficient (CADF) on the solid surface of the liquid, and the possibility of developing a disease, in particular dementia, diabetes or fat embolism, using the same.
  • An object of the present invention is to provide a method for predicting or providing information for diagnosing the onset or course of the diseases.
  • a method for quantifying hydrophobic components contained in a liquid includes a) contacting a droplet of liquid to a solid surface, an initial area A 0 of the contact surface between the droplet and the solid surface, and an initial of the contact surface. Measuring the diameter d 0 ; b) after a predetermined time t , measuring the area A t of the contact surface between the droplet and the solid surface and the diameter d t of the contact surface; And c) obtaining a contact surface diffusion coefficient (CADF) according to the following formula (1):
  • the method of quantifying the hydrophobic component contained in the liquid further comprises the step of d) obtaining the content of the hydrophobic component contained in the droplet by using the contact surface diffusion coefficient and the following equation 2 can do:
  • the liquid may be a body fluid.
  • the body fluid may be selected from the group consisting of blood, serum, plasma, sweat and urine.
  • the hydrophobic component may be fat.
  • a method of predicting the possibility of developing a metabolic disease or dementia or providing information on the onset or course of a metabolic disease or dementia includes a) contacting a droplet of a body fluid of a subject to be contacted with a solid surface, Measuring an initial area A 0 of the contact surface between the solid surfaces and an initial diameter d 0 of the contact surface; b) after a predetermined time t , measuring the area A t of the contact surface between the droplet and the solid surface and the diameter d t of the contact surface; c) obtaining a contact surface diffusion coefficient (CADF) according to Equation 1 below; d) using the contact surface diffusion coefficient and the following formula 2 to obtain the content of the fat component contained in the droplets; And e) comparing the content of fat component obtained with the content of fat component obtained from the body fluids of a normal person:
  • CADF contact surface diffusion coefficient
  • the difference in the amount of fat component obtained from the body fluid of the normal person from the content of fat component obtained from the body fluid of the judgment object is positive, there is a high possibility of developing metabolic disease or dementia or metabolic disease Or diagnose the development of dementia.
  • the body fluid may be selected from the group consisting of blood, serum, plasma, sweat and urine.
  • the disease may be selected from the group consisting of dementia, diabetes and fat embolism.
  • the dementia may be selected from the group consisting of Alzheimer's disease, Parkinson's disease vascular dementia, mixed dementia and mild cognitive impairment.
  • the content of the fat component contained in the body fluid can be more accurately and simply by using a body fluid such as urine which can be obtained cheaply and conveniently from the test object. It can be measured.
  • the quantitative method according to the present invention increases the measurement accuracy of CADF by using both the contact area and the contact diameter of the droplet and the solid surface at the same time, and generates measurement errors caused by using only one of the contact area or the contact diameter. The likelihood can be greatly reduced.
  • FIG. 2 shows a graph comparing the CADF values of urine before (without fatty components) and after (without fatty components) liposuction.
  • Figure 3 shows the CADF value of the urine sample calculated every 0.5 days after liposuction.
  • Figure 4 shows a graph showing the relationship between the concentration of fat components and CADF obtained by varying the fat content concentration by diluting the urine sample containing fat components with ultrapure water after liposuction.
  • FIG. 5 shows a graph comparing fatty acid concentration conversion formulas by correcting the concentration of total fatty acids and CADF measurements measured by gas chromatography (GC).
  • Figure 6 shows a graph comparing the LDL value and CADF value of the fat component in the blood sample.
  • Figure 7 shows a graph comparing the fat component content in the urine of normal people and patients with six diseases measured by the GC method and the CADF method according to an embodiment of the present invention.
  • the six diseases are diabetes (DM), Alzheimer's disease (AD), Parkinson's disease (PDD), vascular dementia (VD), mixed dementia (VD + AD), mild cognitive impairment (MCI).
  • FIG 8 shows an apparatus for measuring the concentration of hydrophobic components contained in a liquid according to an embodiment of the present invention.
  • Method for quantifying the hydrophobic component contained in the liquid calculates the diffusion coefficient (CADF) of the contact surface when the droplet of the liquid contacts the solid surface, based on the hydrophobic component, For example, a method of quantifying fat component is provided.
  • CADF diffusion coefficient
  • the measuring principle is as follows.
  • ⁇ gl is the surface tension between the gas and the liquid
  • ⁇ ls is the surface tension between the liquid and the solid surface
  • ⁇ gs means the surface tension between the gas and the solid surface
  • ⁇ is the contact angle of the droplet to the solid surface
  • d is the contact diameter between the droplet and the solid surface.
  • the three surface tensions are in balance with each other. Over time, evaporation of volatile components such as moisture from the droplets can occur, so that the volume of the droplets decreases and the area of contact with the solid surface also decreases. Therefore, the contact area of the droplets in contact with the solid surface is constant or decreased with time, and the contact area is rarely increased.
  • an aqueous droplet containing a fatty component in a liquid may be mentioned.
  • Fatty components are generally not mixed with water, but in small amounts can be mixed uniformly in water.
  • Some fats can be dissolved in small amounts in water and stably mixed in water in the form of colloids.
  • contacting the fluid in the form of droplets with the solid surface can cause the oil component to stick to the surface of the solid, thus breaking the balance of the three surface tensions described above.
  • the surface tension of water is generally stronger than the surface tension of hydrophobic or lipophilic materials. For this reason, if the hydrophobic component dissolved in the aqueous fluid sticks to the solid surface, the balance of the three surface tensions may be broken, leading to an increase in the contact area of the droplet.
  • the amount of hydrophobic component, such as fat, that adheres to the solid surface is proportional to the fat concentration and surface adsorptivity in the aqueous fluid.
  • n, m, N and M are constants.
  • Equation 1 is a calculation formula of the dimensionless CADF.
  • a t is the contact area of the droplet after a predetermined time t has elapsed
  • a 0 is the initial contact area
  • d t is the contact diameter of the droplet after a predetermined time t has elapsed
  • d 0 means the initial contact diameter.
  • Equation 1 the constants n and m are respectively determined according to the sensitivity of the contact area and the contact surface diameter of the contact surface diffusion coefficient, and the constants N and M are the contact surface diffusion of the change ratio of the contact area and the change ratio of the contact diameter, respectively. Determined based on specific gravity for coefficients. Each constant can vary depending on the measurement environment of the contact surface diffusion coefficient.
  • the method for quantifying the hydrophobic component contained in the liquid using the obtained contact surface diffusion coefficient may further perform the following content calculation step:
  • k, C 0 , A, B, D, P and Q are correction constants.
  • the correction constants are determined to minimize errors through comparative corrections based on the measured data of CADF and fat content, respectively.
  • liquid refers to a material having a volume to be measured but having an unfixed shape.
  • the liquid may be a bodily fluid present in the body of an animal, including a human.
  • body fluid means, but is not limited to, blood, serum, plasma, sweat, urine, and the like of human or animal.
  • hydrophobic component or “lipophilic component” means a component having a small affinity for water and having no polarity.
  • the hydrophobic component may be a component that does not volatilize in the air and affects the properties of the liquid such as surface tension.
  • the hydrophobic component can be fat.
  • fat includes all solid fats, liquid fats, fatty acids and the like.
  • the solid or liquid fats include, but are not limited to, fatty acid triglycerides, rearranged or randomized fats, transesterified fats that occur naturally in vegetable or animal fats and oils.
  • the fatty acids include saturated or unsaturated (mono-, di- or poly-unsaturated) carboxylic acids containing 10 to 22, such as 12 to 24 carbon atoms.
  • the saturated fatty acid may include capric acid, lauric acid, myristic acid, palmitic acid, stearic acid or behenic acid
  • the unsaturated fatty acid may include oleic acid, linoleic acid or erucic acid, but is not limited thereto. no.
  • trans fat refers to unsaturated fats containing trans fatty acids. Trans fats increase LDL cholesterol in the body while also lowering HDL cholesterol in the blood.
  • trans fatty acid means a fatty acid that is typically produced by partial hydrogenation of unsaturated fatty acid vegetable oils. At this time, the term “trans” refers to a position where hydrogen atoms oppose when the unsaturated fat is partially hydrogenated.
  • solid means a solid having at least a certain parallel plane on which droplets can be loaded.
  • the solid may be a hydrophobic or water repellent solid, for example, teflon, but is not limited thereto.
  • Hydrophobic components such as fats, adhere well to hydrophobic surfaces, which can greatly increase the sensitivity of CADF measurements.
  • teflon plate when using a teflon plate as a solid, up to 1 ppm detection resolution can be obtained.
  • the "contact area of droplets (A 0 , A t ) means the area of the portion where the droplet directly contacts the surface of the solid.
  • the contact area of the droplet may be a sensor provided on the surface of the solid or the contact surface of the droplet and the surface of the solid. Orientation, for example, it can be measured by a method such as calculating the area of the contact surface after the shooting on the lower surface of the solid, but is not limited thereto.
  • the "contact diameter of the droplet (d 0 , d t ) means the length of the portion where the droplet is in direct contact with the surface of the solid observed in an arbitrary direction.
  • the contact diameter of the droplet is obtained by using a sensor provided on the surface of the solid or the droplet and the solid.
  • the contact surface of the surface may be measured by a method such as calculating the length of the contact diameter after photographing in one direction, for example, but not limited thereto.
  • contact angle ( ⁇ ) means the angle formed between the surface of the solid and the line in contact with the droplet radius from the point of contact with the solid.
  • predetermined time (t) refers to a time sufficient for a contact area diffusion (CAD) phenomenon to occur between a droplet and a solid surface, for example 5 minutes to 1 hour, such as 10 minutes. To 30 minutes, such as 20 minutes.
  • the predetermined time t may be adjusted according to measurement conditions such as fat concentration, temperature and humidity.
  • FIG. 2 shows the CADF values of urine before (without fatty component) and after (without fatty component) liposuction.
  • the horizontal axis represents elapsed time (minutes) and the vertical axis represents CADF values.
  • the CADF value is negative when the fat component is not contained in the urine, and the CADF value is positive when the fat component is contained in the urine. Using this, it can be confirmed that it is possible to detect the content of the fat component contained in the liquid.
  • the fat-free urine's CADF value is measured negatively. That is, since the contact angle is maintained, as the water evaporates, the contact area and / or contact diameter of the urine droplet containing no fat decreases. In contrast, CADF values in urine containing fat are measured positive. That is, after a predetermined time elapses, the contact area and / or the contact diameter of the droplets are enlarged than the initial droplets.
  • the CADF of the urine sample collected 2.5 days after the liposuction was the largest and became negative after 3.5 days. This is consistent with the fact that patients who have undergone liposuction recover on average after 3 days. It is also shown that the sensitivity of fatty acid content in urine is high enough that the effects of medical treatments, such as compression bandages or infusions, are manifested in CADF values.
  • Figure 4 shows the relationship between the concentration of fat component and CADF obtained by varying the fat content concentration by diluting the urine sample containing fat component with ultrapure water after liposuction.
  • Urine samples containing fat from liposuction patients were diluted with ultrapure water to prepare relative concentrations from 100% (pure urine) to 0.4%. As the relative concentration decreased, the CADF also decreased, indicating a monotonic proportional relationship. This confirms that CADF can be used to quantify fat concentration.
  • FIG. 5 shows a graph comparing fatty acid concentration conversion formulas by correcting the concentration of total fatty acids and CADF measurements measured by gas chromatography (GC).
  • the concentration of CADF and fat component is monotonically proportional. Therefore, the concentration of fat content is formulated using a monotonic function such as an exponential function, a linear function, and a logarithmic function as shown in Equation 2 below.
  • the fat concentration value measured by the GC method is applied to Equation 2, and the correction coefficients may be determined and expressed as a simple monotonic increasing index function as in Equation 3 below.
  • the CADF value measured by the CADF measurement method and Equation 3 may quantify the fat content of the aqueous fluid as in the GC measurement method.
  • the correction constant value used in Equation 2 is not limited to the correction constant used in Equation 3.
  • the absolute concentration of fat in a urine sample containing fat taken from a liposuction patient by gas chromatography (GC) analysis is measured, CADF for the same sample is measured, and then the comparison is performed through the correction.
  • the correction coefficients of Equation 2 were determined and the results compared to those shown in FIG. 5.
  • the equation for C CADF can be determined as follows, with a correction constant A of 2.03, P of 3.65, Q of 5.53, D of 10, and k, C 0 and B determined to be 0:
  • FIG. 6 shows a correlation between low density lipoprotein (LDL) levels and CADF levels among fat components in blood samples.
  • Another embodiment of the present invention provides a method for predicting the occurrence of metabolic disease or dementia or providing information on the development or progress of metabolic disease or dementia, using the method for quantifying hydrophobic components contained in a liquid according to the embodiment. to provide.
  • the method of predicting the possibility of developing the metabolic disease or dementia or providing information on the onset or course of the metabolic disease or dementia may include the following steps:
  • metabolic disease includes obesity, nonalcoholic liver disease, glucose tolerance, hyperinsulinemia, hyperglycemia, diabetes, hypertension, arteriosclerosis, hyperlipidemia or fatty embolism, preferably diabetes or fatty embolism It may be, but is not limited thereto.
  • ementia includes, but is not limited to, Alzheimer's disease, Parkinson's disease vascular dementia, mixed dementia, mild cognitive impairment.
  • Urine free fatty acid preclinical test results measured by the GC method and the CADF method according to one embodiment are shown for 400 people and 100 normal people.
  • the urine of dementia patients such as Alzheimer's disease (AD) and Parkinson's disease (PDD)
  • AD Alzheimer's disease
  • PDD Parkinson's disease
  • CADF method of the present invention can be used as a diagnostic method for diabetes.
  • the method according to an embodiment of the present invention by using a urine sample to perform a convenient and steady diagnostic management at a low cost and can be a great help in managing individual diabetes, blood difficult patient Their blood sugar management can also be a great help.
  • the method of quantifying fat component using the CADF method enables diagnosing dementia by measuring the fatty acid content in readily available body fluids such as urine. Therefore, the effects of the implementation of various dementia treatment methods can be easily compared with each other, thereby finding an optimal treatment method for each individual.
  • diabetes can be diagnosed or managed by measuring the fat content of readily available body fluids such as urine. Therefore, the effects of various diabetes treatment methods can be easily compared with each other, and through this, an optimal diabetes treatment method for each individual can be found.
  • the method of measuring CADF according to an embodiment may be applied to a quantitative analysis technique, for example, to measuring the amount of fat contained in a sample.
  • a quantitative analysis technique for example, to measuring the amount of fat contained in a sample.
  • the CADF method of the present invention is inexpensive, fast and convenient.
  • CADF measurement of the present invention can be combined with conventional analytical techniques.
  • CADF measurement results according to the present invention can be applied to fat analysis that cannot be measured directly by UV or fluorescence spectroscopy.
  • the CADF method may be applied to body fat management in health care, diet, and obesity.
  • Another embodiment of the present invention provides an apparatus for quantifying hydrophobic components contained in a liquid, using the method for quantifying hydrophobic components contained in a liquid according to the above embodiment.
  • FIG 8 shows an apparatus for measuring the concentration of hydrophobic components contained in a liquid according to an embodiment of the present invention.
  • the apparatus 100 for measuring the concentration of hydrophobic components contained in a liquid includes a measuring unit 110, a calculating unit 120, and an output unit 130.
  • Each component of the concentration measuring device 100 may be implemented in a computing device or in another device operating in conjunction with such a computing device.
  • the measurement unit 110 is configured to obtain a value of the contact area or the contact diameter of the contact surface of the liquid droplet and the solid surface.
  • the measurement unit 110 may include a solid having a predetermined or more parallel plane on which the droplet can be raised.
  • the measuring unit 110 includes an imaging device capable of obtaining images of droplets and solids, for example, a charge-coupled device (CCD) camera, an optical sensor, or the like, for calculating the numerical value of the contact area or contact diameter. , But may include a touch sensor provided on the solid phase, but is not limited thereto.
  • the measuring unit 110 may simultaneously measure the contact area or the contact diameter of one or more droplets on the solid.
  • the measurement unit 110 may measure different contact areas or contact diameter values over time with respect to one droplet.
  • the measurement unit 110 may include a memory device for controlling the position, focus, and the like of the imaging device, and a memory stored in the memory for the obtained contact area or contact diameter.
  • the calculation unit 120 obtains a contact surface diffusion coefficient (CADF) according to Equation 1 using the obtained contact area or contact diameter, and uses the obtained contact surface diffusion coefficient (CADF) and Equation 2 below. Can be obtained by calculating the content of hydrophobic components contained in the droplets:
  • n, m, N and M are constants.
  • the calculation unit 120 compares the concentration of hydrophobic components in the liquid in the determination object based on the concentration data of the hydrophobic components in the liquid obtained from a normal person, such as a liquid obtained from a body fluid, and compares the metabolic properties of the determination object. Information on the likelihood of developing a disease or dementia, whether or not it has occurred, or the course of the disease can be obtained.
  • the output unit 130 may display the concentration of hydrophobic components, such as fat components, contained in the liquid obtained through the above configurations.
  • the output unit 130 displays a predicted result of the possibility of developing a metabolic disease or dementia in the object of determining the concentration of the obtained hydrophobic component, or provides information on whether or not the metabolic disease or dementia develops or progresses. It can also be displayed.

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Abstract

Le procédé de quantification d'un composant hydrophobe contenu dans un liquide, selon la présente invention, comprend les étapes consistant à : a) amener une gouttelette d'un liquide en contact avec une surface solide et mesurer la superficie initiale (A0) et le diamètre initial (d0) d'une surface de contact entre la gouttelette et la surface solide ; b) mesurer la superficie (At) et le diamètre (dt) d'une surface de contact entre la gouttelette et la surface solide après qu'un temps prédéterminé (t) s'est écoulé ; et c) obtenir un facteur de diffusion de surface de contact (CADF).
PCT/KR2018/004808 2017-04-26 2018-04-25 Procédé pour quantifier un composant hydrophobe dans un liquide à l'aide d'un facteur de diffusion de zone de contact, et procédé utilisant ce procédé pour fournir des informations relatives au diagnostic d'une maladie Ceased WO2018199631A1 (fr)

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JP4958272B2 (ja) * 2007-01-19 2012-06-20 学校法人北里研究所 アルブミン分子のブラウン運動の拡散係数変化に基づく血清または血漿粘度測定方法及び装置
JP2008249332A (ja) * 2007-03-29 2008-10-16 Univ Of Tokushima 唾液中の脂質・ラフトおよびａｑｐ５を用いた唾液腺機能検査と全身疾患検査法
US20130167621A1 (en) * 2011-12-29 2013-07-04 Yi-Hsin Lin Biological detection device and detecting method
KR101361072B1 (ko) * 2012-12-17 2014-02-10 이상현 접촉면 확산 계수 기반 액체 내 지방 침투도 측정 방법
KR20160148519A (ko) * 2014-02-07 2016-12-26 이상현 접촉면 확산계수를 이용한 액체 내 지방 함량 측정 방법

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