KR20230032962A - Rotary rheometer with improved reliability and method for measuring viscosity of blood - Google Patents

Abstract

Since coupling of upper/lower plates and upper/lower kits is controlled by magnetic force or vacuum force in a rotational rheometer of the present invention, there is no deformation or gap due to coupling so that the reliability of a measurement result can be maintained excellently even if the gap between the upper and lower kits is fine. Thus, the present invention is suitable for measuring the viscosity of blood where only a small amount of sampling is possible. The rotational rheometer with improved reliability includes an upper plate and a lower plate; an upper kit; and a lower kit.

Description

Rotational rheometer with improved reliability and method for measuring blood viscosity

The present invention relates to a rotational rheometer and a method for measuring the viscosity of blood using the rotational rheometer. In addition, the present invention relates to a method for providing information necessary for diagnosis or prognosis of a disease using the rotational rheometer.

A rheometer measures the rheological properties of all liquid materials, gels, and sols that have viscoelastic properties. Among the types of rheometers, the capillary rheometer is a method in which a certain volume of liquid flows through a thin tube in the middle of a pipe and the viscosity is obtained from the flowing time (see Korean Patent Registration No. 10-0533598). On the other hand, the rotational rheometer is a rheometer that controls various flows using rotation, and can measure the rheological properties of various materials from very low viscosity to very high viscosity. Such rheometers are mainly used to measure viscosity to determine quality in industrial processes.

Variables that can be measured with a rotational rheometer include several rheological parameters, such as viscoelastic modulus, storage modulus, loss modulus, complex modulus, viscosity, shear stress, and shear rate. At this time, in a rotational rheometer, if the resistance increases linearly as the angular velocity increases, it is called a Newtonian fluid (eg water), and if it is non-linear, it is called a non-Newtonian fluid (eg lotion, toothpaste, blood). Unlike room temperature viscoelasticity measurement rheometers, high temperature viscoelasticity measurement rheometers can measure the viscosity by adjusting the temperature of the sample from -100°C to 400°C. In order to make the sample high temperature, it is heated with a heater, and in order to make the sample low temperature, a cryogenic fluid such as liquefied carbon dioxide or liquid nitrogen is injected into the heater instead of room temperature air to cool the sample to the desired temperature.

Recently, a technique for determining whether a patient has a disease using blood viscosity is being studied. For example, by measuring the viscosity of blood, it can be used to determine the severity of a disease in which blood components change, such as diabetes or anemia. In the case of a diabetic patient, a lot of glucose exists in the blood due to high blood sugar, and this large amount of glucose acts like a glue that binds the red blood cells together, making the surface area of the red blood cells small and preventing the hemoglobin of the red blood cells from holding oxygen well. As a result, oxygen cannot be supplied to the peripheral blood vessels, resulting in necrosis of the extremities of the body. At this time, focusing on the fact that the blood of patients with diabetes has a lot of glucose, the rheometer checks how much the viscosity of the blood is higher than that of normal people, so that the severity of diabetes can be grasped and an accurate prescription can be expected.

On the other hand, in order to analyze blood using a rotational rheometer, it is necessary to place blood between an upper plate and a lower plate and bring them into close contact with each other before operation. Accordingly, the upper plate and the lower plate come into contact with blood, and such contact surfaces are contaminated by blood, which may cause an error when measuring the viscosity of another sample later. In order to prevent this, the contact surfaces of the upper and lower plates must be washed before or after measuring the viscosity of blood. This washing process not only takes time and money, but also contaminates the contact surfaces by washing, affecting later viscosity analysis. can also give

Korean Patent Registration No. 10-0533598 (2005.11.29.)

Conventional rheometers have problems in that it is difficult to measure a large number in a medical field and is not hygienic because a part in contact with a blood sample must be washed and reused after measuring the rheological characteristics of blood.

Accordingly, a method of loading a blood sample after mounting a disposable kit on the upper and lower plates of the rheometer has been developed. , in particular, it was difficult to adjust the fine gap due to mechanical deformation or play occurring during the bonding process.

Accordingly, as a result of research by the present inventors, by using a coupling method by magnetic force or vacuum force rather than a mechanical coupling method between the rheometer plate and the kit, it is possible to attach and detach the kit more easily and to measure the viscosity of a small amount of blood Even when the interval between the upper and lower kits was finely adjusted, the reliability of the measurement could be improved.

Therefore, an object of the present invention is to provide a rotational rheometer capable of measuring blood in a convenient and hygienic manner while having excellent reliability, a method for measuring blood viscosity using the rotational rheometer, and a method for providing information necessary for diagnosis or prognosis of diseases using the rotational rheometer will be.

According to one aspect of the invention, the upper plate and the lower plate parallel to each other; an upper kit coupled to a lower surface of the upper plate; And a lower kit coupled to the upper surface of the lower plate, wherein the coupling is controlled by at least one of magnetic force and vacuum force, and a test sample is disposed between the upper kit and the lower kit. A rotational rheometer is provided do.

According to another aspect of the present invention, a method for measuring the viscosity of blood separated from a subject using the rotational rheometer is provided.

According to another aspect of the present invention, measuring the viscosity of blood separated from the object using the rotational rheometer; and using the viscosity of the blood for diagnosis or prognosis of a disease.

The rotational rheometer of the present invention introduces a disposable kit, and the sample can be easily and hygienically removed after measuring the viscosity.

In particular, in the rotational rheometer of the present invention, since the coupling between the upper and lower plates and the upper and lower kits is controlled by magnetic force or vacuum force, there is no deformation or play due to the coupling, so even if the gap between the upper and lower kits is fine, measurement can be performed. The reliability of the results can be maintained excellently. Accordingly, the rotational rheometer of the present invention can be used to measure the rheology of various liquid substances, gels, and sols having viscoelasticity, and is particularly suitable for measuring the viscosity of blood, which can only be sampled in a small amount.

In addition, the rotational rheometer of the present invention can measure viscosity faster than other types of rheometers such as capillary type, so there is no need to use anticoagulants, and it can provide information necessary for diagnosis or prognosis of diseases simply and quickly. .

1 shows a configuration diagram of a rotational rheometer according to an embodiment.
2a and 2b respectively show a lower surface of an upper plate and an upper surface of a lower plate of a rotational rheometer according to an embodiment.
3a and 3b respectively show an upper kit and a lower kit of a rotational rheometer according to an embodiment.
4 is a front view of a rotational rheometer according to an embodiment.
5 illustrates a method of measuring blood viscosity using a rotational rheometer and providing information necessary for diagnosis or prognosis of a disease, according to an embodiment.
6a to 6c show the results of blood viscosity measurement using a rotational rheometer in Test Example 2 as a probability density function.

In the following description, the description that one component is formed above/under another component or is connected or coupled to each other does not mean that these components are formed, connected, or coupled directly or indirectly through another component. All inclusive. In addition, it should be understood that the criterion for the top/bottom of each component may vary according to the direction in which the object is observed.

If it is determined that a detailed description of a known configuration or function related to the present specification may obscure the gist of the present invention, the detailed description will be omitted. In addition, the size of each component in the drawings may be exaggerated or omitted for description, and may differ from the actually applied size.

"Including" a component in this specification means that other components may be further included, not excluding other components, unless otherwise stated.

In this specification, singular expressions should be interpreted as meaning including the singular or plural interpreted in context unless otherwise specified.

The present invention will be described in detail with reference to the drawings below.

rotational rheometer

According to one aspect of the present invention, a rotational rheometer in which coupling between a kit on which a test sample is placed and upper and lower plates is controlled by magnetic force and/or vacuum force is provided.

1 shows a rotational rheometer according to one embodiment.

Referring to FIG. 1 , a rotational rheometer 10 according to an embodiment includes an upper plate 110 and a lower plate 210 parallel to each other; an upper kit 120 coupled to the lower surface of the upper plate 110; and a lower kit 220 coupled to an upper surface of the lower plate 210 . A test sample 20 is disposed between the upper kit 120 and the lower kit 220 .

In the rotational rheometer 10, the coupling between the upper plate 110 and the upper kit 120 and the coupling between the lower plate 210 and the lower kit 220 are performed in a non-mechanical manner, specifically at least one of magnetic force and vacuum force made by

The magnetic force may be imparted using, for example, a magnet, and may be specifically implemented as a binding force between a magnet and a ferromagnetic material such as metal. The vacuum force may be applied, for example, through an adsorption hole, and may be specifically implemented as an adsorption force by a vacuum applied through an adsorption hole.

The magnetic force and the vacuum force correspond to forces required to separate the upper/lower plates and the upper/lower kits after they are coupled to each other. As a specific example, the upper plate coupled with the upper kit or the lower plate coupled with the lower kit is pulled along a direction perpendicular to the coupling surface at a rate of 500 mm/min to separate the applied force (kgf ) can be measured to determine the magnetic or vacuum force. In addition, the magnetic force or the vacuum force can be adjusted to a desired level through the above method.

The magnetic force and the vacuum force determined in this way may be 0.1 kgf to 10.0 kgf, respectively, and may be, for example, 0.5 kgf to 5.0 kgf. As a specific example, the magnetic force and the vacuum force determined in the above manner may be 1.0 kgf to 3.0 kgf, respectively. When it is within the above preferred range, it may be more advantageous in terms of dimensional stability after coupling as well as easy installation and detachment of the kit. As a more specific example, the magnetic force and the vacuum force determined in the above manner may be 1.5 kgf to 3.0 kgf, respectively.

The rotational rheometer of the present invention introduces a disposable kit, and the sample can be easily and hygienically removed after measuring the viscosity.

In particular, in the rotational rheometer of the present invention, since the coupling between the upper and lower plates and the upper and lower kits is controlled by magnetic force or vacuum force, there is no deformation or play due to the coupling, so even if the gap between the upper and lower kits is fine, measurement can be performed. The reliability of the results can be maintained excellently. Accordingly, the rotational rheometer of the present invention can be used to measure the rheology of various liquid substances, gels, and sols having viscoelasticity, and is particularly suitable for measuring the viscosity of blood, which can only be sampled in a small amount.

In addition, the rotational rheometer of the present invention can measure viscosity faster than other types of rheometers such as capillary type, so there is no need to use anticoagulants, and it can provide information necessary for diagnosis or prognosis of diseases simply and quickly. .

Hereinafter, components of the rotational rheometer of the present invention will be described in detail.

upper and lower plates

In the rotational rheometer, the upper plate and the lower plate are provided in parallel with each other at regular intervals.

The upper plate and the lower plate may have a flat and flat shape and have a thickness of, for example, 0.3 mm to 5 mm, specifically 0.5 mm to 2 mm, but are not limited thereto.

2a and 2b respectively show a lower surface of an upper plate and an upper surface of a lower plate of a rotational rheometer according to an embodiment.

Referring to FIGS. 2A and 2B , in the present specification, the lower surface 111 of the upper plate and the upper surface 211 of the lower plate are illustrated as being circular, but are not limited thereto.

Areas of the lower surface of the upper plate and the upper surface of the lower plate may be the same as or different from each other. As an example, the lower surface of the lower plate may have a wider area than the upper surface of the upper plate. In this case, it is possible to reduce the concern that the test sample moves out of the lower plate by the rotational force during operation of the rotational rheometer.

Also, for example, the diameter of the lower surface 111 of the upper plate and the upper surface 211 of the lower plate may be 30 mm to 80 mm, respectively, and more specifically, 40 mm to 60 mm. As an example, the diameter of the lower surface 111 of the upper plate may be 30 mm to 60 mm, and the diameter of the upper surface 211 of the lower plate may be 40 mm to 80 mm.

The lower surface 111 of the upper plate and the upper surface 211 of the lower plate may have coupling means 115 and 215 by magnetic force and/or vacuum force. The coupling means (115, 215) may be arranged in a regular arrangement at the center of the lower surface 111 of the upper plate and the upper surface 211 of the lower plate, or at other locations, for example, at two or more locations on the surface. And, specifically, when the lower surface of the upper plate and the upper surface of the lower plate are circular, two or more may be disposed side by side with the circumference along the circumference.

According to one embodiment, a coupling means having a diameter of 5 mm to 30 mm may be provided at the center of the lower surface 111 of the upper plate, and the planar shape of the coupling means may be circular.

According to another embodiment, it may have coupling means having a diameter of 5 mm to 20 mm at two or more positions on the lower surface 111 of the upper plate, and more specifically, it may have 4 to 12 coupling means in a regular arrangement .

According to another embodiment, along the circumference of the lower surface 111 of the upper plate (inward of the circumference) may have two or more coupling means with a diameter of 5 mm to 20 mm arranged side by side with the circumference, more specifically, the circumference It may have 4 to 12 coupling means at regular intervals parallel to the circumference along the circumference.

According to another embodiment, a coupling means having a diameter of 5 mm to 30 mm may be provided at the center of the upper surface 211 of the lower plate, and the planar shape of the coupling means may be circular.

According to another embodiment, coupling means having a diameter of 5 mm to 20 mm may be provided at two or more locations on the upper surface 211 of the lower plate, and more specifically, 6 to 20 coupling means may be provided in a regular arrangement. there is.

According to another specific embodiment, two or more coupling means having a diameter of 5 mm to 20 mm disposed along the circumference of the upper surface 211 of the lower plate (inward of the circumference) and parallel to the circumference, more specifically, the circumference It may have 6 to 20 coupling means at regular intervals along the circumference along the circumference.

According to another embodiment, two or more coupling means each having a diameter of 5 mm to 20 mm may be provided along the first circumference and the second circumference of the upper surface 211 of the lower plate, wherein the first circumference is the first circumference. 2 having a smaller diameter than circumference 4 to 10 engaging means along the first circumference at regular intervals parallel to the first circumference, and having 10 to 20 coupling means along the second circumference at regular intervals alongside the second circumference It may have two coupling means.

As an example, the lower surface of the upper plate and the upper surface of the lower plate may have coupling means by magnetic force, for example, one or more magnets. As a specific example, the lower surface of the upper plate may have a magnet disposed in the center. In addition, the upper surface of the lower plate may also have a magnet disposed in the center. In addition, the lower surface of the upper plate may have a magnet disposed at an off-center position, and the lower plate is the same. For example, the lower surface of the upper plate and the upper surface of the lower plate may be circular, and may have two or more magnets arranged along the circumference along the circumference. The magnet may be attached to, for example, a lower surface of the upper plate and an upper surface of the lower plate. Alternatively, one or more grooves for mounting a magnet may be provided on the lower surface of the upper plate and the upper surface of the lower plate, and the magnet may be seated in each of the grooves.

As another example, the lower surface of the upper plate and the upper surface of the lower plate may have coupling means by vacuum force, specifically, one or more suction holes. As a specific example, the lower surface of the upper plate may have a suction hole disposed in the center. In addition, the upper surface of the lower plate may also have a suction hole disposed in the center. In addition, the lower surface of the upper plate may have a suction hole disposed at a location other than the center, and the upper surface of the lower plate is the same. For example, the lower surface of the upper plate and the upper surface of the lower plate may have two or more suction holes arranged along the circumference and parallel to the circumference. For example, the suction hole may be formed on the lower surface of the upper plate and the upper surface of the lower plate to operate in a pneumatic manner. The suction hole may be connected to a vacuum pump, and for this purpose, an internal passage, a nozzle, or a pipe may be further provided on the upper and lower plates.

In the upper plate 110 and the lower plate 210, bodies other than the coupling means 115 and 215 such as magnets or suction holes may be made of metal. The metal constituting the bodies of the upper plate and the lower plate may be, for example, one or more metals such as aluminum and iron.

upper and lower kits

3a and 3b respectively show an upper kit and a lower kit of a rotational rheometer according to an embodiment.

Referring to FIGS. 3A and 3B , the upper kit 120 and the lower kit 220 may further include one or more outer guide parts 123 and 223 at edges. The outer guide unit may align the upper kit and the lower kit with the upper plate and the lower plate, respectively.

As an example, the outer guide part may have a continuous sidewall shape protruding along the front surface of the edge of the upper kit or the lower kit. As another example, the outer guide part may have a shape in which only a portion of an edge of the upper kit or the lower kit protrudes. However, the outer guide portion does not have a mechanical coupling means such as a hook. Accordingly, the outer guide portion only contributes to horizontal alignment between the upper/lower kits and the upper/lower plates, but does not participate in coupling between them.

The lower kit may further include a sample loading part 226 in the center and a sample receiving part 227 outside the sample loading part 226 . The sample loading part 226 is a part on which a test sample is placed and facing the upper kit, and may have substantially the same diameter as the upper kit. The sample receiving part 227 has a concave shape to have a lower basal surface than the sample loading part 226, and when measuring the viscosity, by accommodating the test sample out of the sample loading part due to the rotational force, contamination of the rheometer can prevent

The upper kit and the lower kit may be disposable kits that are replaced after one measurement.

According to one embodiment of the present invention, neither of the upper kit and the lower kit includes a means for mechanical coupling with the upper plate or the lower plate. According to one embodiment, neither of the upper kit and the lower kit includes a hook for engaging with the upper plate or the lower plate. Such a mechanical coupling means makes mounting and dismounting between the kit and the plate inconvenient, and in particular, mechanical deformation or clearance of the kit occurs during the coupling process, thereby reducing reliability of measurement results. However, according to the present invention, since the coupling between the plate kits is controlled by magnetic force and/or vacuum force, a mechanical coupling means is not required, so that a fine distance between the upper and lower kits can be maintained constant.

When the upper plate and the lower plate have one or more magnets, the upper kit and the lower kit may have ferromagnetic materials at portions 125 and 225 corresponding to the magnets. The ferromagnetic material is not particularly limited as long as it is a metal having a magnet and magnetic force, and may specifically include iron.

According to one embodiment, the upper kit and the lower kit may be composed of a ferromagnetic material. That is, the upper kit and the lower kit may be composed of a single component of ferromagnetic material. As a specific example, the upper kit and the lower kit may be made of iron.

According to another embodiment, the upper kit and the lower kit may partially include a ferromagnetic material. That is, the upper kit and the lower kit may be composed of a ferromagnetic material and a composite of other components. Specifically, the upper kit and the lower kit may include a ferromagnetic material in a portion corresponding to the magnet, and other portions may be made of other components, such as plastic.

As a specific example, the upper kit and the lower kit may have a plastic body, and the plastic body may include iron attached to a portion corresponding to the magnet. Alternatively, the plastic body may have one or more seating grooves at a portion corresponding to the magnet, and an iron may be inserted into the seating groove.

When the upper plate and the lower plate have one or more suction holes, vacuum may be applied to the surfaces of the upper kit and the lower kit through the suction holes. In this case, the upper kit and the lower kit may be made of, for example, plastic.

The plastic bodies constituting the upper kit and the lower kit may be manufactured by injection molding a polymer composition.

The polymer composition may include a thermoplastic resin, an antibacterial agent and a heat stabilizer. For example, the polymer composition may include 1 to 10 parts by weight of an antimicrobial agent and 1 to 5 parts by weight of a heat stabilizer based on 100 parts by weight of the thermoplastic resin.

Examples of the thermoplastic resin include acrylic resins such as polymethyl methacrylate, polyethyl methacrylate, polymethyl acrylate, polyethyl acrylate, and an acrylic copolymer; polystyrene; polycarbonate; polyesters such as polyethylene terephthalate and polybutylene terephthalate; polyamide; Acrylonitrile-butadiene-styrene (ABS) and the like can be used without limitation. For example, as the thermoplastic resin, an acrylic resin and polystyrene may be used at the same time. In this case, the weight ratio of the acrylic resin and polystyrene may be 70 to 90: 10 to 30, and the transparency, heat resistance, and surface flatness of the composition within the weight ratio range may be improved. can be further improved.

The antibacterial agent is used to impart antibacterial activity and bactericidal activity, and zinc oxide, silica, alumina, zeolite, bentonite, silver powder, silver ion antimicrobial agent powder, zinc powder, copper powder, and the like may be used. The amount of the antimicrobial agent may be 1 to 10 parts by weight based on 100 parts by weight of the thermoplastic resin, and excellent antibacterial properties within the above content range may prevent deterioration in transparency and heat resistance due to excessive addition.

The heat stabilizer is used to improve weatherability, heat resistance, and durability, and phenolic antioxidants, alkylated monophenols, alkylthiomethylphenols, hydroquinones, alkylated hydroquinones, hydroxybenzyls, triazines, and the like may be used without limitation. The content of the heat stabilizer may be 1 to 5 parts by weight based on 100 parts by weight of the thermoplastic resin, and weather resistance, heat resistance and durability are improved within the above content range, and transparency and processability deterioration due to excessive addition can be prevented.

In addition, the polymer composition may further include a silane coupling agent. When the viscosity of blood is measured, since blood contains a large amount of water, a silane coupling agent may be used to improve wettability between the blood and the upper and lower sample holders. The silane coupling agent has an organic functional group capable of bonding with an organic compound and a hydrolysis group capable of reacting with an inorganic material, and improves interfacial adhesion of the composition to improve durability, weather resistance, heat resistance, and the like. Examples of the silane coupling agent include an alkyl group-containing silane coupling agent, an amino group-containing silane coupling agent, an epoxy group-containing silane coupling agent, an acrylate group-containing silane coupling agent, an isocyanate group-containing silane coupling agent, a mercapto group-containing silane coupling agent, and a fluorine group-containing agent. A silane coupling agent, a silane coupling agent containing a vinyl group, and the like are used. As a specific example, a silane coupling agent mixture composed of 60 to 80% by weight of an acrylate group-containing silane coupling agent and 20 to 40% by weight of an epoxy group-containing silane coupling agent may be used. The acrylate group-containing silane coupling agent includes 3-methacryloxypropylmethyldimethoxysilane, 3-methacryloxypropyltrimethoxysilane, 3-methacryloxypropylmethyldiethoxysilane, 3-methacryloxypropyltri ethoxysilane, 3-acryloxypropyltrimethoxysilane, methacryloxymethyltriethoxysilane, methacryloxymethyltrimethoxysilane and the like. The epoxy group-containing silane coupling agent includes 2-glycidoxyethylmethyldimethoxysilane, 2-glycidoxyethylmethyldiethoxysilane, 3-glycidoxypropylmethyldimethoxysilane, 3-glycidoxypropylmethyldiethoxy Silane, 2-glycidoxyethyltrimethoxysilane, 2-glycidoxyethyltriethoxysilane, 3-glycidoxypropyltrimethoxysilane, 3-glycidoxypropyltriethoxysilane, 2-(3 ,4-epoxycyclohexyl)ethylmethyldimethoxysilane, 2-(3,4-epoxycyclohexyl)ethylmethyldiethoxysilane, 3-(3,4-epoxycyclohexyl)propylmethyldimethoxysilane, 3-( 3,4-epoxycyclohexyl)propylmethyldiethoxysilane, 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane, 2-(3,4-epoxycyclohexyl)ethyltriethoxysilane, 3- (3,4-epoxycyclohexyl)propyltrimethoxysilane, 3-(3,4-epoxycyclohexyl)propyltriethoxysilane, and the like. The content of the silane coupling agent may be 1 to 10 parts by weight based on 100 parts by weight of the thermoplastic resin, and the effect of the silane coupling agent is exhibited within the above content range, and interfacial adhesion and heat resistance deterioration due to excessive addition can be prevented. .

In addition, the polymer composition may further include a copolymer of an acrylate group-containing silane coupling agent and an acrylic acid monomer. A plurality of carboxyl groups included in the copolymer can improve heat resistance and surface flatness of the composition. The acrylate group-containing silane coupling agent includes 3-methacryloxypropylmethyldimethoxysilane, 3-methacryloxypropyltrimethoxysilane, 3-methacryloxypropylmethyldiethoxysilane, 3-methacryloxypropyltri ethoxysilane, 3-acryloxypropyltrimethoxysilane, methacryloxymethyltriethoxysilane, methacryloxymethyltrimethoxysilane and the like. The acrylic acid monomer is acrylic acid, methacrylic acid, methyl acrylic acid, ethyl acrylic acid, butyl acrylic acid, 2-ethylhexyl acrylic acid, decyl acrylic acid, methyl methacrylic acid, ethyl methacrylic acid, butyl methacrylic acid, 2-ethylhexyl methacrylic acid , decyl methacrylic acid, and the like. The weight ratio of the acrylate group-containing silane coupling agent and the acrylic acid monomer may be 10 to 30:70 to 90, and within the weight ratio range, the composition may have better bonding strength and heat resistance. The content of the copolymer of the acrylate group-containing silane coupling agent and acrylic acid monomer may be 1 to 10 parts by weight based on 100 parts by weight of the thermoplastic resin, and within the above content range, bonding strength and heat resistance are further improved, and processability due to excessive addition degradation can be prevented.

In addition, the polymer composition may additionally include a copolymer of an acrylate group-containing silane coupling agent and 2-hydroxyethyl acrylate (HEA). The weight ratio of the acrylate group-containing silane coupling agent and 2-hydroxyethyl acrylate is preferably 20 to 40:60 to 80, and transparency and heat resistance can be further improved within the above range. The content of the copolymer may be 2 to 10 parts by weight based on 100 parts by weight of the thermoplastic resin, and transparency and heat resistance may be further improved within the above content range, and deterioration in processability due to excessive addition may be prevented.

In addition, the polymer composition may additionally include a copolymer of an acrylate group-containing silane coupling agent, an acrylic acid monomer, and 2-hydroxyethyl acrylate (HEA). The weight ratio of the acrylate group-containing silane coupling agent, acrylic acid monomer, and 2-hydroxyethyl acrylate is preferably 2 to 10:100:20 to 50, and transparency and heat resistance can be further improved within the above range. The content of the copolymer may be 2 to 10 parts by weight based on 100 parts by weight of the thermoplastic resin, and transparency and heat resistance may be further improved within the above content range, and deterioration in processability due to excessive addition may be prevented.

How rotational rheometers work

Referring to FIG. 1, a rotational rheometer 10 according to an embodiment includes an upper shaft 105 connected to an upper plate 110, a lower shaft 205 connected to a lower plate 210, and the lower shaft It includes a drive motor 300 connected to (205).

The upper shaft 105 moves the upper plate 110 up and down and adjusts the distance between the upper kit and the lower kit. The lower shaft 205 receives rotational force from the driving motor 300 to rotate the lower plate 210 in a predetermined direction. The upper shaft 105 and the lower shaft 205 may be made of a metal material and may have holes therein, if necessary.

In addition, when the rotational rheometer uses a vacuum coupling method, a vacuum pump may be additionally provided, and the vacuum pump may be connected to suction holes of the upper and lower plates through an internal flow path, a nozzle, or a pipe.

In use of the rotational rheometer of the present invention, first, the upper kit and the lower kit are coupled to the upper plate and the lower plate respectively by magnetic force and/or vacuum force. A test sample is placed on the surface of the lower kit, and a distance between the upper kit and the lower kit is adjusted by up and down movement of the upper shaft. Thereafter, the drive motor operates to rotate the lower plate connected to the lower shaft in a constant direction and speed, and the rheological characteristics are measured.

Meanwhile, a method in which the upper plate rotates instead of the lower plate is also possible, and the upper plate and the lower plate may rotate simultaneously.

In addition, the rotational rheometer of the present invention may further include a position sensor, a temperature sensor, and a control unit. The position sensor may be installed, for example, on the upper shaft to measure the degree of twist due to torque generated during operation of the rotational rheometer. The temperature sensor may be installed, for example, on the upper plate to measure the temperature of the test sample during operation of the rotational rheometer. The control unit may be installed in a separate location to control the speed of the driving motor and process the measured values of the temperature sensor and the position sensor. To this end, the control unit may include a motor controller, a converter, and a microcomputer. there is. In addition, the rotational rheometer may further include a digital display window connected to the control unit, and may also be connected to a PC having a monitor and a printer.

As a specific example, when a driving motor is operated by receiving a signal from the controller to rotate the lower plate connected to the lower shaft, a rotational load is applied to the test sample. At this time, the position sensor that measures the degree of twist by the generated torque transmits analog data to the control unit, and the transmitted analog data is converted into digital data through the converter of the control unit and then processed by the microcomputer. Similarly, the temperature sensor detects the temperature of the test sample and transmits analog data to the control unit, which is converted into a digital value through the converter of the control unit and then processed by the microcomputer. The microcomputer of the controller may be connected to a digital display window or a PC, and a printer or monitor may be connected to the PC as an interface to output measured data.

Uses of rotational rheometers

The rotational rheometer according to the present invention can be used to measure the rheological properties of all liquid or fluid materials, gels, sol, etc. in which viscoelasticity exists.

In particular, the rotational rheometer of the present invention can be used to measure the viscosity of blood separated from a subject.

Accordingly, according to another aspect of the present invention, there is provided a blood viscosity measuring method comprising measuring the viscosity of blood separated from a subject using the rotational rheometer.

5 shows a method for measuring blood viscosity according to an embodiment.

Referring to FIG. 5 , a method for measuring blood viscosity according to an embodiment includes preparing a rotational rheometer of the present invention (S100); combining the upper plate and the lower plate of the rotational rheometer with the upper kit and the lower kit by at least one of magnetic force and vacuum force (S200); Disposing a blood sample between the upper kit and the lower kit (S300); calculating the viscosity of the blood sample by measuring a torque while rotating at least one of the upper plate and the lower plate (S400); and removing the upper kit and the lower kit from the upper plate and the lower plate (S500).

4 is a front view of a rotational rheometer according to an embodiment.

Referring to FIG. 4 , the rotational rheometer according to the present invention can exhibit excellent reliability even when the distance d between the upper kit 110 and the lower kit 210 is finely adjusted. For example, the interval d between the upper kit 110 and the lower kit 210 may be 5 mm or less, 2 mm or less, 1 mm or less, or 0.5 mm or less. As a specific example, the rotation may be performed while maintaining a distance between the upper kit and the lower kit at 0.01 mm to 1.0 mm, more specifically at 0.1 mm to 1.0 mm.

Even if it rotates at such a minute interval, the measured value has very little variability, which can be confirmed by a coefficient of variation (CV). The coefficient of variation (CV) is a relative spread comparison method that can be applied to compare groups with different means and standard deviations or to groups with different units of measurement. For example, when the torque is measured 10 times using the rotational rheometer of the present invention, the coefficient of variation (CV) according to the equation below may be 10% or less, more specifically 5% or less.

CV (%) = (standard deviation/mean) x 100 (n=10).

According to the present invention, since the reliability of measured values is excellent even when rotating at minute intervals, it is useful for measuring rheological characteristics of a small amount of samples. From this point of view, since blood samples are difficult to obtain in large quantities from subjects, they are suitable for use with the rotational rheometer of the present invention.

The amount of the blood sample measured by the rotational rheometer of the present invention may be, for example, 5.0 cc or less, specifically 3.0 cc or less, or 2.0 cc or less. Also, the amount of the blood sample may be 0.5 cc or more, specifically 1.0 cc or more, or 1.5 cc or more. As a specific example, the amount of the blood sample disposed between the upper kit and the lower kit may be in the range of 1.5 cc to 3.0 cc. More specifically, the amount of the blood sample may range from 1.0 cc to 2.0 cc.

In addition, the rotational rheometer of the present invention is capable of rapid measurement, for example, it is possible to measure the viscosity within about 1 to 3 minutes. Due to such a fast measurement speed, the rotational rheometer of the present invention can measure the viscosity of a blood sample even without using a blood coagulant.

In order to measure the stable torque in the test using the rotational rheometer of the present invention, the LAOS (Large Amplitude Oscillatory Shear) method, which is the latest viscosity measurement method, can be used, and in this case, the oscillation amplitude of 100% to 700% Strain can be set.

According to another aspect of the present invention, a method of using the previously measured blood viscosity for diagnosis or prognosis of a disease is provided.

Referring to FIG. 5 , the present invention includes the steps of measuring the viscosity of blood separated from a subject using the rotational rheometer (S100 to S500); and using the viscosity of the blood for diagnosis or prognosis of a disease (S600).

Specifically, by measuring the viscosity of blood separated from a subject using the rotational rheometer and analyzing a correlation with a disease of the subject, a blood viscosity standard required for diagnosis or prognosis of a disease may be determined. According to this criterion, more specialized examination, hospitalization or discharge can be suggested by using the blood viscosity information measured by the rotational rheometer for diagnosis or prognosis of disease.

The present invention will be described in more detail through the following examples. However, the following examples are only for exemplifying the present invention, and the scope of the present invention is not limited thereto.

Example 1: Rotational Rheometer with Magnetic Force Coupling Method

As shown in FIG. 1, a rotational rheometer having an upper plate 110 connected to the upper shaft 105, a lower plate 210 connected to the lower shaft 205, and a drive motor 300 connected to the lower shaft 205 ( 10) was produced. The upper plate 110 is made of a circular plate with a diameter of 60.0 mm using aluminum, and the lower plate 210 is made of a circular plate with a diameter of 90.0 mm using aluminum.

On the lower surface 111 of the upper plate, coupling means 115 are formed at regular intervals along the center and circumferential directions as shown in FIG. On the upper surface 211 of the lower plate, coupling means 215 are formed at regular intervals along the first circumferential direction and the second circumferential direction having a larger diameter, as shown in FIG. settled down The force required for coupling between the upper plate and the upper kit by magnetic force and for separation after coupling between the lower plate and the lower kit was configured to be about 1.5 kgf, respectively.

The upper kit 120 was manufactured by injection molding of plastic in the form of a disk having a guide part 123 formed at the edge as shown in FIG. The sample loading part 226 and the sample receiving part 227 along the circumferential direction were molded by injection molding in the form of a disc. In the upper kit and the lower kit, iron was attached to a position corresponding to the connecting means of the upper plate and the lower plate.

In addition, the rotational rheometer controls the speed of the position sensor, the temperature sensor for measuring the temperature of the test sample, and the drive motor for measuring the degree of torsion due to torque, and processing the measured value of the temperature sensor and the measured value of the position sensor It was manufactured to have a control unit including a motor controller, a converter and a microcomputer, and a digital display window connected to the control unit, and output the result to a monitor and printer by connecting to a PC.

Example 2: Rotational rheometer with vacuum force coupling method

Similar to Example 1, a rotational rheometer is manufactured, but suction holes are formed at the lower surface of the upper plate and the upper surface of the lower plate at the positions of the coupling means (115, 215), and the coupling means in the upper and lower kits No iron was attached to the corresponding location. In addition, a vacuum pump was installed and connected to the suction hole so that they were combined by a pneumatic method, and the force required for coupling between the upper plate and the upper kit by vacuum force and separation after coupling between the lower plate and the lower kit was about 1.3 kgf, respectively. It was configured to be.

Comparative Example 1: Hook-coupled rotational rheometer

A rotational rheometer was fabricated similarly to Example 1, but coupling means by magnetic force or vacuum force was not formed on the upper and lower plates, and iron was not attached to the upper and lower kits. Instead, hooks capable of mechanical coupling with the upper and lower plates were formed on the outer guide parts 123 and 223 of the upper and lower kits.

Test Example 1: Bonding test by magnetic force or vacuum force

An upper plate was mounted on the upper clamp of a universal testing machine (UTM, Instron), and an upper kit was mounted on the lower clamp. The upper plate and the upper kit were joined by magnetic force or vacuum force, and the upper clamp was raised at a rate of 500 mm/min while the lower clamp was fixed. Through this, the force (kgf) required when the upper plate and the upper kit are separated was measured, and the above measurement procedure was repeated 10 times to take an average value. In the same way, the force required for separation after the lower plate and the lower kit were coupled by magnetic force or vacuum force was measured.

Test Example 2: Viscosity measurement of blood using rotational rheometer

Viscosity of blood was measured using the rotational rheometer of Comparative Example 1 and Examples 1 and 2. In order to measure the stable torque in the test, the LAOS (Large Amplitude Oscillatory Shear) method, which is the latest viscosity measurement method, was used (Strain 140% adopted). The amount of the blood sample was 1.5 cc, and the distance between the upper kit and the lower kit was maintained at 0.5 mm to ensure the accuracy of measurement of such a small sample. In order to analyze the viscosity of blood, the rotational torque generated by operating the rotational rheometer was measured.

The test was performed 10 times for each rheometer, and after calculating the average and standard deviation of the measured torque values, the coefficient of variation (CV) was calculated according to the formula below.

CV (%) = (standard deviation/mean) x 100 (n=10)

The test results are shown in Table 1 and FIGS. 6a to 6c below.

test Torque (μN m) Comparative Example 1 Example 1 Example 2 One 0.1267 0.1662 0.1762 2 0.1633 0.1619 0.1729 3 0.154 0.1768 0.1888 4 0.1771 0.1643 0.1773 5 0.1646 0.1627 0.1717 6 0.1519 0.1609 0.1519 7 0.1437 0.1590 0.1460 8 0.1910 0.1665 0.1545 9 0.1987 0.1567 0.1457 10 0.1841 0.1605 0.1511 average 0.16551 0.16355 0.16355 Standard Deviation 0.02245 0.00557 0.01463 Coefficient of Variation (CV) 13.6% 3.4% 8.94%

As shown in Table 1 and FIGS. 6a to 6c, the rotational rheometer of Comparative Example 1 of the hook coupling method had a low coefficient of variation (CV) of more than 10%, while the coupling method by magnetic force or vacuum force Rotational rheometers 1 and 2 were excellent in coefficient of variation (CV) of 10% or less, and in particular, Example 1 was very excellent at 5% or less.

This is because the hook coupling method creates mechanical deformation to tightly adhere the plastic kit to the metal plate, and the gap between the upper and lower kits is only 500 ㎛ (0.5 mm), so the deformation by the hook is 100 ㎛. This is because even if it occurs, it corresponds to a change in interval of 20%. On the other hand, the coupling method by magnetic force or vacuum force can prevent such distortion in advance, greatly improving the reliability of measurement and enabling more precise measurement.

10: rotational rheometer,
20: test sample,
105: upper shaft,
110: upper plate,
111: the lower surface of the upper plate,
115: upper plate coupling means,
120: upper kit,
123: outer guide part of the upper kit,
125: counterpart of coupling means in the upper kit;
205: lower shaft,
210: lower plate,
211: upper surface of the lower plate,
215: coupling means of the lower plate,
220: lower kit,
223: outer guide part of the lower kit,
225: corresponding part of the coupling means in the lower kit;
226: sample loading unit,
227: sample receiving unit,
300: motor,
d: Gap between upper and lower kits.

Claims (20)

an upper plate and a lower plate parallel to each other;
an upper kit coupled to a lower surface of the upper plate; and
Including a lower kit coupled to the upper surface of the lower plate,
The coupling is controlled by at least one of magnetic force and vacuum force,
A rotational rheometer, wherein a test sample is disposed between the upper kit and the lower kit.
According to claim 1,
The magnetic force and the vacuum force pull the upper plate combined with the upper kit or the lower plate coupled with the lower kit at a speed of 500 mm/min along a direction perpendicular to the coupling surface, and when they are separated A rotational rheometer determined by measuring the applied force, each ranging from 1.0 kgf to 3.0 kgf.
According to claim 1,
The lower surface of the upper plate and the upper surface of the lower plate have one or more magnets,
The upper kit and the lower kit have a ferromagnetic material in a portion corresponding to the magnet, the rotational rheometer.
According to claim 3,
The rotational rheometer, wherein the ferromagnetic material includes iron.
According to claim 3,
The rotational rheometer, wherein the upper kit and the lower kit are made of iron.
According to claim 3,
The upper kit and the lower kit have plastic bodies,
The rotational rheometer, wherein the plastic body includes iron attached to a portion corresponding to the magnet.
According to claim 3,
The lower surface of the upper plate has a magnet disposed in the center, the rotational rheometer.
According to claim 3,
The rotational rheometer, wherein the lower surface of the upper plate and the upper surface of the lower plate are circular and have two or more magnets arranged along the circumference and parallel to the circumference.
According to claim 1,
The lower surface of the upper plate and the upper surface of the lower plate have one or more suction holes, and vacuum is applied to the surfaces of the upper kit and the lower kit through the suction holes.
According to claim 9,
The rotational rheometer, wherein the upper kit and the lower kit are made of plastic.
According to claim 1,
The upper kit and the lower kit further include one or more outer guides at edges,
The outer guide unit aligns the upper kit and the lower kit with the upper plate and the lower plate, respectively.
According to claim 1,
wherein neither the upper kit nor the lower kit includes a means for mechanical coupling with either the upper plate or the lower plate.
According to claim 1,
The rotational rheometer, wherein the upper kit and the lower kit are disposable kits that are replaced after one measurement.
According to claim 1,
The rotational rheometer, wherein the lower surface of the lower plate has a larger area extended than the upper surface of the upper plate.
According to claim 1,
The rotational rheometer is used for measuring the viscosity of blood separated from a subject.
Preparing the rotational rheometer of claim 1;
coupling the upper plate and the lower plate of the rotational rheometer to the upper kit and the lower kit by at least one of magnetic force and vacuum force;
placing a blood sample between the upper kit and the lower kit;
calculating a viscosity of the blood sample by measuring a torque while rotating at least one of the upper plate and the lower plate; and
Method for measuring blood viscosity, which is performed including the step of removing the upper kit and the lower kit from the upper plate and the lower plate.
17. The method of claim 16,
Wherein the rotation is performed while maintaining a distance between the upper kit and the lower kit at 0.1 mm to 1.0 mm.
17. The method of claim 16,
Method for measuring blood viscosity, wherein the torque has a coefficient of variation (CV) of 10% or less according to the equation below when measured 10 times:
CV (%) = (standard deviation/mean) x 100 (n=10).
17. The method of claim 16,
The method of measuring blood viscosity, wherein the amount of blood sample disposed between the upper kit and the lower kit is 1.5 cc to 3.0 cc.
Measuring the viscosity of blood separated from a subject using the rotational rheometer of claim 1; and
A method of providing information necessary for diagnosis or prognosis of a disease, comprising using the viscosity of the blood for diagnosis or prognosis of a disease.

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