WO2019188798A1 - Blood collection instrument and blood test kit - Google Patents

Abstract

A blood collection instrument which can extract a blood sample in stages and which can suppress the blood sample from being unintentionally discharged, and a blood test kit are provided. This blood collection instrument, which is used in a blood test kit, comprises: an outer tube in which a leading end opening and a base end opening are defined and which has a blood sample reservoir that communicates with the leading end opening; a rod member which can move inside the outer tube in the axial direction and which, with movement from the leading end opening to the base end opening, guides a blood sample from the leading end opening to the blood sample reservoir; and a movement adjustment mechanism which enables stepwise movement of the rod member from the leading end opening towards the base end opening and which restricts movement of the rod member from the base end opening towards the leading end opening.

Description

Blood collection instrument and blood test kit

The present invention relates to a blood collection device and a blood test kit.

In general, for blood collection, a general qualified blood sample is collected by a doctor or other qualified person using a syringe to collect blood from the vein, and the subject is self-collected by inserting a blood collection needle into his / her finger or the like. There is blood sampling.

Blood collected by general blood collection is transported to a medical institution or inspection in a state of being sealed in a collection container, where it is inspected. When a blood sample is transported without being separated into blood cells and plasma, a test is performed after the blood sample is separated into blood cells and plasma by a centrifuge at a medical institution or inspection institution. In the self-collection performed by the subject to be examined, the blood sample after blood collection is separated into blood cells and plasma by the separation membrane, and is transported to the examination site in this separated state, where the examination is performed. In order to collect a blood sample by itself, a body fluid collecting device is often used.

For example, Patent Document 1 discloses that when a bodily fluid is collected by a capillary phenomenon by collecting a step by a blocking unit in a bodily fluid collecting device, a certain volume of bodily fluid is collected in an accumulation unit.

In Patent Document 2, a body fluid collecting device is provided with a communication relay path and a communication suction path, and by defining the size of the inner diameter of both, when collecting body fluid by capillary action, a certain volume of body fluid is stored in the storage unit. Is disclosed.

JP 2016-118572 A JP 2017-173219 A

However, the body fluid collecting devices disclosed in Patent Documents 1 and 2 cannot additionally collect a blood sample when the blood sample is smaller than the volume necessary for the test. In addition, the collected blood sample cannot be prevented from being unintentionally released from the body fluid collecting device.

The present invention has been made in view of such circumstances, and provides a blood collection instrument and a blood test kit that can collect a blood sample in stages and suppress the blood sample from being unintentionally released. For the purpose.

The blood collection device according to the first aspect is a blood collection device used for a blood test kit, wherein a distal end opening and a proximal end opening are defined, and an outer cylinder having a blood sample reservoir that communicates with the distal end opening; A rod-shaped member that is movable in the axial direction in the outer cylinder, and a rod-shaped member that sucks a blood sample from the distal end opening to the blood sample reservoir in accordance with the movement from the distal end opening to the proximal end opening; And a movement adjusting mechanism that enables the stepwise movement of the bar-shaped member to the opening and restricts the movement of the bar-shaped member from the proximal end opening to the distal end opening.

The blood collection device according to the second aspect includes a release member that releases the restriction of the movement of the rod-shaped member in the movement adjustment mechanism.

In the blood sampling device according to the third aspect, the movement adjusting mechanism is composed of an elastic member fixed to the outer cylinder and a plurality of first claw portions formed with rod-shaped members engaged with the elastic member.

In the blood sampling device according to the fourth aspect, in order to move the rod-shaped member from the distal end opening to the proximal end opening, a rotatable gear wheel and a plurality of second claw portions formed with the rod-shaped member engaged with the gear wheel With.

In the blood sampling device according to the fifth aspect, in order to move the rod-shaped member from the distal end opening to the proximal end opening, a projecting portion projecting from the outer tube on which the rod-shaped member is formed, and an outer tube allowing movement of the projecting portion And an opening provided.

In the blood sampling device according to the sixth aspect, the blood sample reservoir is detachable.

The blood collection device according to the seventh aspect has an anticoagulant inside the blood sample reservoir.

In the blood sampling device according to the eighth aspect, the blood sample reservoir is provided with a scale indicating the volume of the blood sample.

A blood test kit according to a ninth aspect includes a blood collection instrument for collecting a blood sample, a diluent for diluting the collected blood sample, and a storage instrument for storing a dilution of the blood sample The concentration of the target component in the blood sample is analyzed using a standard component that is constantly present in the blood or a standard component that is not present in the blood contained in the diluent.

In the blood test kit according to the tenth aspect, the blood test kit includes a separation instrument for separating and collecting plasma from a diluted blood sample.

According to the present invention, it is an object to provide a blood collection device and a blood test kit that can collect a blood sample in a stepwise manner and can prevent the blood sample from being unintentionally released.

FIG. 1 is an exploded perspective view showing an example of a blood sampling device. FIG. 2 is an assembly drawing of the blood sampling device. FIG. 3 is a transparent view of the assembly drawing of the blood collection device of FIG. FIG. 4 is an explanatory diagram for explaining the operation of the movement adjustment mechanism. FIG. 5 is an explanatory diagram for explaining the operation of the movement adjustment mechanism. FIG. 6 is an explanatory diagram for explaining the action of the release member. FIG. 7 is an explanatory view for explaining the action of the release member. FIG. 8 is a perspective view showing another example of a blood sampling device. FIG. 9 is a diagram showing an example of the configuration of a storage device for storing a diluted blood sample. FIG. 10 is a diagram illustrating an example of a holding device that holds the separation device. FIG. 11 is a diagram illustrating an example of a holding device that holds the separation device. FIG. 12 is a diagram illustrating an example of a holding device that holds the separation device.

Hereinafter, preferred embodiments of the present invention will be described with reference to the accompanying drawings. The invention is illustrated by the following preferred embodiments. Changes can be made by many techniques without departing from the scope of the present invention, and other embodiments than the embodiments can be utilized. Accordingly, all modifications within the scope of the present invention are included in the claims. In this specification, when the numerical range is expressed using “From”, the upper and lower numerical values indicated by “From” shall be included in the numerical range. A standard component that is constantly present in blood may be referred to as an external standard substance or an external standard. In addition, a standard component that does not exist in blood may be referred to as an internal standard substance or an internal standard.

<Blood collection device>
A blood sampling device according to an embodiment will be described with reference to FIGS. 1 to 3. Here, the “tip” means the side that sucks and discharges a blood sample, and the “base end” means the side opposite to the tip. FIG. 1 is an exploded view of a blood sampling device. As shown in FIG. 1, the blood collection device 100 includes an outer cylinder 110 in which a distal end opening 112 and a proximal end opening 114 are defined. The distal end opening 112 and the proximal end opening 114 communicate with each other. The outer cylinder 110 includes a blood sample reservoir 116 that communicates with the tip opening 112. The blood sample reservoir 116 defines a substantially cylindrical reservoir space 116A with the tip opening 112 as a bottom surface. A blood sample is stored in the reservoir space 116A. The blood sample is sucked into and discharged from the blood sample reservoir 116 through the tip opening 112. The outer cylinder 110 includes an outer cylinder main body 118 connected to the blood sample reservoir 116. The outer cylinder main body 118 is defined with a main body space 118A communicating with the reservoir space 116A.

The outer tube 110 has a tip opening 112 narrower than a base end opening 114 and has a cylindrical shape as a whole. A cross section in a direction orthogonal to the axial direction of the outer cylinder 110 is substantially circular. The overall cross-sectional size differs depending on the position, not the constant diameter as a whole.

The outer cylinder main body 118 includes a bearing 120 between the blood sample reservoir 116 and the base end opening 114. A gear wheel 122 that is rotatably supported by the bearing portion 120 is attached. The bearing unit 120 includes a first bearing unit 120A and a second bearing unit 120B. The gear wheel 122 includes a first gear 122A configured in two stages of a small diameter gear and a large diameter gear, and a second gear 122B larger than the small diameter gear that meshes with the small diameter gear of the first gear 122A. The first gear 122A is rotatably supported by the first bearing portion 120A, and the second gear 122B is rotatably supported by the second bearing portion 120B. An opening 121 is formed in a region of the outer cylinder main body 118 where the second gear 122B is located. The opening 121 penetrates the outer surface and the inner surface of the outer cylinder main body 118. When the second gear 122B is supported by the second bearing portion 120B, the second gear 122B protrudes beyond the inner surface of the outer cylinder main body 118 through the opening 121.

Protective cover 124 for protecting gear wheel 122 is attached to outer cylinder main body 118. The protective cover 124 is formed with a groove 124 </ b> A along the rotation direction of the gear wheel 122. The large-diameter gear of the first gear 122A protrudes from the groove 124A. The blood sampler can rotate the first gear 122A with a finger. The protective cover 124 includes a locking portion 124B extending opposite to the groove 124A. The protective cover 124 is fixed to the outer cylinder main body 118 by the locking portion 124B. In the embodiment, the case where the gear wheel 122 is configured by the first gear 122A and the second gear 122B is illustrated, but the number of gears is not particularly limited.

A groove 126 extending from the proximal end opening 114 toward the distal end opening 112 is formed in the outer cylinder main body 118. The groove part 126 penetrates the outer surface and the inner surface of the outer cylinder main body 118.

An elastic member fixing portion 130 is provided continuously to the tip end side of the groove portion 126. The elastic member fixing portion 130 is provided with two pins 130A. The pin 130A protrudes in the direction of the outer surface of the outer cylinder main body 118. An elastic member 132 composed of a leaf spring is fixed to the elastic member fixing portion 130. The elastic member 132 is not limited to a leaf spring.

The elastic member 132 includes a fixing portion 132A attached to the elastic member fixing portion 130, and a bent portion 132B that is continuous with the fixing portion 132A and is bent at a predetermined angle with the fixing portion 132A. Two through holes are formed in the fixing portion 132A. The fixing portion 132A is fixed to the pin 130A through the two through holes. When the elastic member 132 is fixed to the elastic member fixing portion 130, the bent portion 132 </ b> B protrudes beyond the inner surface of the outer cylinder main body 118 through the groove portion 126. The proximal end side of the elastic member 132 is bent into a curved shape.

The release member 200 is attached to the proximal end opening 114 side of the outer cylinder 110. The release member 200 has a substantially cylindrical shape. An opening 200 </ b> A is provided on the outer surface of the release member 200 on the tip side. The opening 200 </ b> A passes through the outer surface and the inner surface of the release member 200. Accordingly, the opening 200A can allow the bent portion 132B to pass. On the outer surface of the release member 200, a protruding portion 200 </ b> B is provided on the base end side. The opening 200 </ b> A and the protrusion 200 </ b> B are substantially parallel to the axial direction of the outer cylinder 110.

The outer diameter of the release member 200 is smaller than the inner diameter of the outer cylinder main body 118. The groove part 126 of the outer cylinder main body 118 accepts and moves the protruding part 200B. The release member 200 can be inserted into the outer cylinder main body 118 from the proximal end opening 114. The release member 200 has a cylindrical shape and has a hollow structure penetrating along the axial direction of the outer cylinder 110.

The blood collection device 100 includes a rod-shaped member 300 that can move in the axial direction in the outer cylinder 110. The rod-shaped member 300 has a tip portion 310 that is tapered toward the tip. A rubber member 312 is attached to the distal end portion 310. The rubber member 312 is inserted into the reservoir space 116A of the blood sample reservoir 116 and functions as a seal member. A rear end surface 314 is provided on the base end side of the rod-shaped member 300. By pressing the rear end surface 314, the rod-shaped member 300 can move to the front end opening 112 along the axial direction.

A plurality of first claw portions 316 and a plurality of second claw portions 318 are provided from the rear end surface 314 side between the front end portion 310 and the rear end surface 314 of the rod-shaped member 300. The plurality of first claw portions 316 are arranged along the axial direction of the outer cylinder 110. Further, the plurality of second claw portions 318 are arranged along the axial direction of the outer cylinder 110. In the embodiment, the plurality of first claw portions 316 and the plurality of second claw portions 318 are arranged apart from each other by a certain distance.

The outer cylinder 110, the gear wheel 122, the protective cover 124, the release member 200, the rod-shaped member 300, and the like constituting the blood collection device 100 are made of synthetic resin.

FIG. 2 is a perspective view in which the outer cylinder 110, the gear wheel 122, the elastic member 132, the release member 200, and the rod-like member 300 (not shown) are assembled except for the protective cover 124. As shown in FIG. 2, the gear wheel 122 is rotatably supported by the bearing portion 120. The elastic member 132 is fixed to the elastic member fixing portion 130. The release member 200 is inserted through the outer cylinder main body 118. The protrusion 200B of the release member 200 is inserted into the groove 126 of the outer cylinder main body 118. The protruding portion 200B is exposed beyond the outer surface of the outer cylinder main body 118. The groove part 126 and the protrusion part 200 </ b> B restrict the release member 200 from rotating about the axial direction of the outer cylinder 110. The release member 200 can be easily moved along the axial direction of the outer cylinder 110 by the groove 126 and the protrusion 200B. The rod-shaped member 300 is inserted from the proximal end opening 114 into the release member 200 and the outer tube 110 until the rear end surface 314 of the rod-shaped member 300 is in contact with the proximal end opening 114 of the outer tube 110.

FIG. 3 is a transmission diagram of FIG. As shown in FIG. 3, the rubber member 312 attached to the distal end of the rod-shaped member 300 passes through the main body space 118A and reaches the base end of the reservoir space 116A. By the rubber member 312, the reservoir space 116 </ b> A constitutes a space where the proximal end is closed.

The second gear 122B engages with the plurality of second claw portions 318 of the rod-shaped member 300 through the opening 121. The plurality of second claw portions 318 and the second gear 122B of the gear wheel 122 constitute a rack and pinion. The plurality of second claw portions 318 corresponds to a rack, and the second gear 122B corresponds to a pinion. The rotational motion of the second gear 122B is converted into the linear motion of the rod-shaped member 300 by the plurality of second claw portions 318. For example, when the first gear 122A is rotated in the clockwise direction indicated by the arrow A, the second gear 122B is rotated in the counterclockwise direction, and the bar-shaped member 300 is indicated by the plurality of second claw portions 318 as indicated by the arrow B. It moves in a direction away from the outer cylinder 110.

As the rod-shaped member 300 moves, the rubber member 312 moves in a direction away from the tip opening 112 while sliding in the main body space 118A. When the blood sample is in contact with the tip opening 112, the reservoir space 116 </ b> A and the main body space 118 </ b> A become negative pressure, and the blood sample is sucked into the reservoir space 116 </ b> A through the tip opening 112.

As shown in FIG. 3, when the elastic member 132 is fixed to the elastic member fixing portion 130, the bent portion 132 </ b> B engages with the plurality of first claw portions 316 of the rod-shaped member 300 via the groove portion 126. The elastic member 132 and the plurality of first claw portions 316 form a movement adjustment mechanism for the rod-shaped member 300 in the embodiment.

The operation of the movement adjustment mechanism will be described with reference to FIGS. As shown in FIG. 4, the bent portion 132B of the elastic member 132 engages with the adjacent first claw portion 316 via the opening 200A. The first claw portion 316 has a trapezoidal shape in a sectional view. The trapezoidal shape is a shape in which the bottom side becomes shorter as the distance from the bar-shaped member 300 increases.

As shown in FIG. 5, by rotating a gear wheel 122 (not shown), the rod-shaped member 300 is moved in the direction of arrow B, that is, in the direction from the distal end opening 112 toward the proximal end opening 114. The fixed portion 132A and the bent portion 132B are configured such that the narrower angle forms an obtuse angle. The elastic deformation in the direction in which the angle of the bent portion 132B with respect to the fixed portion 132A is increased can be performed with a relatively small force. Accordingly, the bent portion 132B is elastically deformed along the slope of the first claw portion 316 as the rod-shaped member 300 moves. The elastic member 132 allows the rod-shaped member 300 to move in the direction of arrow B. When the rod-shaped member 300 is further moved in the direction of arrow B, when the bent portion 132B gets over the first claw portion 316, the bent portion 132B is located between the adjacent first claw portions 316 due to the restoring force of the bent portion 132B. Get in. By the operation of the bent portion 132B, the rod-shaped member 300 advances by a certain distance by the pitch of the plurality of first claw portions 316. Therefore, the rod-shaped member 300 can be moved stepwise by sliding the plurality of first claw portions 316 while the bent portion 132B repeats elastic deformation and restoration. The stepwise movement means that it can be recognized that the rod-shaped member 300 has advanced a certain distance.

Since the rod-shaped member 300 can move stepwise from the distal end opening 112 toward the proximal end opening 114, a blood sample can be aspirated from the distal end opening 112 to the blood sample reservoir 116 stepwise.

By changing the pitch of the plurality of first claw portions 316, it is possible to appropriately set the suction capacity for one time when the rod-shaped member 300 is moved in one step. For example, if the diameter of the tip opening 112 is 2 mm and the stroke length (pitch) for one step is 1.5 mm, the volume that can be sucked in one step is about 5 μL. In addition, if the volume necessary for the blood test is 65 μL, the rod-shaped member 300 needs to move at least in 13 stages.

Next, returning to FIG. 4, when the rod-shaped member 300 is moved in the direction opposite to the arrow B, that is, in the direction from the proximal end opening 114 toward the distal end opening 112, the angle formed between the bent portion 132B and the fixing portion 132A is small. Therefore, it is necessary to elastically deform the bent portion 132B with respect to the fixed portion 132A. However, the elastic deformation in the direction in which the angle of the bent portion 132B becomes smaller with respect to the fixed portion 132A requires a larger force than the elastic deformation in the direction in which the angle increases. The elastic member 132 restricts the movement of the rod-shaped member 300 from the proximal end opening 114 to the distal end opening 112.

Here, “regulation” means that the force when moving the rod-shaped member 300 is larger when moving from the proximal end opening 114 to the distal end opening 112 than when moving from the distal end opening 112 to the proximal end opening 114. It means to become.

Since the movement of the rod-shaped member 300 from the proximal end opening 114 to the distal end opening 112 is restricted, it is possible to prevent the blood sample sucked into the blood sample reservoir 116 from being unintentionally released.

The operation of the release member 200 will be described with reference to FIGS. 6 and 7. FIG. 6 shows a state in which the rod-shaped member 300 is moved from the distal end opening 112 to the proximal end opening 114 and a necessary amount of blood sample is sucked into the blood sample reservoir 116 (not shown) of the blood collection device 100. It is necessary to transfer the aspirated blood sample from the blood collection device 100 to a storage device (not shown).

As shown in FIG. 6, when the release member 200 is moved to the proximal end side as indicated by an arrow C, the edge on the distal end side of the opening 200 </ b> A comes into contact with the bent portion 132 </ b> B. When the release member 200 is further moved in the direction of arrow C, as shown by arrow D, the bent portion 132B is elastically deformed in a direction in which the angle increases with respect to the fixed portion 132A. Since the engagement between the bent portion 132B and the first claw portion 316 is released, the restriction on the movement of the bar-shaped member 300 by the elastic member 132 is released. At this time, the release member 200 can be easily moved in the direction of the arrow C by pressing the finger against the protruding portion 200B and applying it in the direction of the arrow C.

Next, as shown in FIG. 7, the rod-shaped member 300 is moved in the direction of arrow E, from the proximal end opening 114 to the distal end opening 112. Since the engagement between the elastic member 132 and the plurality of first claw portions 316 is released, the rod-shaped member 300 can be smoothly moved to the tip side. By the smooth movement of the rod-shaped member 300, the blood sample stored in the blood sampling device 100 can be pushed out easily and quickly, and the blood sample can be transferred to a storage device (not shown).

Another example of the blood sampling device 100 will be described with reference to FIG. In addition, the same code | symbol may be attached | subjected to the structure similar to the blood sampling instrument 100 of FIGS. 1-7 mentioned above, and description may be abbreviate | omitted.

As shown in FIG. 8, an opening 140 is formed in the outer cylinder main body 118 of the outer cylinder 110. The opening 140 penetrates the outer surface and the inner surface of the outer cylinder main body 118. The opening 140 is formed along the axial direction of the outer cylinder 110. The bar-shaped member 300 is provided with a protrusion 330. The protruding portion 330 is inserted into the opening 140 of the outer cylinder main body 118 and is exposed beyond the outer surface of the outer cylinder main body 118. The protrusion 330 can move along the opening 140.

By moving the protrusion 330 to the proximal end side, the rod-shaped member 300 is moved from the distal end opening 112 to the proximal end opening 114 side. The rod-shaped member 300 can be moved stepwise by the elastic member 132 and the plurality of first claw portions 316, and the blood sample is sucked into the blood sample reservoir 116 stepwise. Further, the movement of the rod-shaped member 300 from the proximal end opening 114 to the distal end opening 112 is restricted by the elastic member 132 and the first claw portion 316.

Next, the engagement between the elastic member 132 and the plurality of first claw portions 316 is released by moving the release member 200 to the proximal end side. By moving the protrusion 330 to the distal end side, the rod-shaped member 300 is smoothly and quickly moved from the proximal end opening 114 to the distal end opening 112 side. By the smooth movement of the rod-shaped member 300, the blood sample stored in the blood sampling device 100 can be pushed out easily and quickly, and the blood sample can be transferred to a storage device (not shown).

In the blood sampling device 100 described above, the blood sample reservoir 116 is preferably detachable. After the blood sample is aspirated and released by the blood sampling device 100, only the blood sample reservoir 116 can be discarded. The portion excluding blood sample reservoir 116 can be reused. In the case of reuse, a new blood sample reservoir 116 is attached to the outer cylinder main body 118.

The blood collection device 100 of the embodiment preferably has an anticoagulant on the inner surface of the blood sample reservoir 116 when directly collecting blood obtained by puncturing with a lancet or the like. Anticoagulants suppress blood clotting. As the anticoagulant, for example, heparin or EDTA salt (Ethylenediaminetetraacetic acid) can be selected. Various anticoagulants can be used, but when using an external standard substance for the purpose of calculating the ratio of blood to the diluent during analysis, the external standard substance is substantially not included. The one is selected.

The blood sample reservoir 116 is preferably provided with a scale indicating the volume of the blood sample. It can be determined whether or not the volume of the blood sample sucked into the blood sample reservoir 116 is appropriate. For example, when it is preferable to collect a blood sample at about 65 μL, it is preferable to calibrate 55 μL and 75 μL, which are acceptable volume ranges (± 10 μL) of the blood sample. It is preferable to provide a scale with a different appearance so as not to misunderstand the scale indicating the lower limit or the upper limit. The volume range of the blood sample means an allowable range for accurately analyzing the target component contained in the blood sample.

A blood collection method using the blood collection device 100 will be described. The blood sample may be collected by the subject himself or by a qualified person such as a doctor. In a preferred embodiment, the subject himself / herself makes the tip opening 112 of the blood sampling device 100 contact a blood sample that has been injured with a fingertip or the like using a knife-equipped device such as a lancet. By moving the rod-shaped member 300 stepwise toward the proximal end, the blood sample is sucked into the blood sample reservoir 116 by negative pressure. For example, when it is confirmed that the blood sample necessary for the blood test can be aspirated on the scale with the blood sample reservoir 116, the collection of the blood sample is terminated.

<Blood test kit>
The blood test kit includes, in addition to the blood sampling device 100 described above, a diluent for diluting the collected blood sample and a storage device for storing the diluted blood sample, and is constantly in the blood. A blood test kit for analyzing the concentration of a target component in a blood sample using a standard component present or a standard component contained in the diluent and not present in blood.

Furthermore, it is preferable to provide a separation device for separating and collecting plasma from a diluted blood sample.

[Container]
FIG. 9 is a cross-sectional view showing an example of the configuration of a storage device for storing a diluted blood sample. As shown in FIG. 9, the storage device 400 includes a cylindrical blood collection container 410 made of a transparent material. On the upper end side of the blood collection container 410, a screw portion 412 is formed on the outer surface, and a locking portion 414 is projected on the inner surface. In addition, a conical bottom portion 416 that protrudes to the lower end side is formed at the lower end portion of the blood collection container 410. A cylindrical leg portion 418 is formed around the bottom portion 416. “Upper” and “lower” mean “upper” and “lower” in a state where the legs 418 are installed on the placement surface.

The leg portion 418 has the same outer diameter as a sample cup (not shown) used at the time of blood analysis test, and preferably, a slit groove 420 is formed in a vertical direction at a position opposite to the lower end thereof. . Further, as shown in FIG. 9, the blood collection container 410 preferably contains a required amount, for example, a diluted solution 422 of 500 mm ³ .

As shown in FIG. 9, it is preferable that the upper end opening of the blood collection container 410 is sealed with a cap 424 via a packing 426 before the storage device 400 is used.

[Standard components that are permanently present in the blood]
In order to accurately analyze the concentration of the target component after dilution of the diluted plasma with a high dilution ratio of the plasma component, in order to accurately analyze the concentration of the plasma in the blood before dilution, the rate of change in the concentration of the substance pre-existing in the diluted solution The method obtained from It is also possible to employ a method of analyzing the concentration of the target component in the blood sample using a standard component that is constantly present in the blood. When analyzing a blood component from a smaller amount of blood, it is preferable to employ a method using a standard component that is constantly present in the blood because measurement with a small measurement error is possible. Therefore, the blood test kit of the present invention is preferably a blood test kit for analyzing the concentration of a target component in a blood sample using a standard component that is constantly present in blood. is there.

Here, “using” the standard component is for analyzing the concentration of the target component based on the standard value for the standard component (or the constant value if a standard component that is constantly present in blood is used). Is intended to determine the dilution ratio. Therefore, when analyzing the concentration of a target component in a blood sample using a standard component that is constantly present in blood, dilution is performed based on the constant value (standard value) of the standard component that is constantly present in blood. It is also determining the magnification and analyzing the concentration of the target component.

Examples of standard components that are constantly present in blood include sodium ions, chloride ions, potassium ions, magnesium ions, calcium ions, total protein, and albumin. The concentration of these standard components contained in the serum and plasma of the blood sample is such that the sodium ion concentration is 134 mmol / L to 146 mmol / L (mean value: 142 mmol / L), and the chloride ion concentration is 97 mmol / L to 107 mmol. / L (average value: 102 mmol / L), potassium ion concentration is 3.2 mmol / L to 4.8 mmol / L (average value: 4.0 mmol / L), magnesium ion concentration is 0.75 mmol / L to 1 0.0 mmol / L (average value: 0.9 mmol / L), calcium ion concentration is 4.2 mmol / L to 5.1 mmol / L (average value: 4.65 mmol / L), and total protein concentration is 6.7 g. / 100 ml to 8.3 g / 100 ml (average value: 7.5 g / 100 mL), albumin concentration is 4.1 g / 10 mL from 5.1 g / 100 mL (mean: 4.6 g / 100 mL) is. In the embodiment, it is intended to enable measurement of a target component when the amount of blood collected to relieve pain of the subject is very small. When a very small amount of blood is diluted with a diluent, the diluent It is necessary to accurately measure the concentration of the “standard component that is constantly present in the blood” present in the blood. When the dilution rate is increased, the concentration of components originally present in the blood decreases in the diluted solution, and depending on the dilution rate, there is a possibility that a measurement error is included in the concentration measurement. Therefore, in order to detect the above-mentioned standard component with sufficient accuracy when a very small amount of blood component is diluted at a high dilution rate, it is preferable to measure a standard component present at a high concentration in a very small amount of blood. In the present invention, it is preferable to use sodium ions (Na ⁺ ) or chloride ions (Cl ⁻ ) that are present in a high concentration among the components that are constantly present in the blood sample. Furthermore, it is most preferable to measure sodium ion having the highest amount in the blood among the standard components that are constantly present in the blood. The average value of sodium ion represents a standard value (median value of the reference range), and the value is 142 mmol / L, which accounts for 90 mol% or more of the total cations in plasma.

[Standard components not present in blood]
One of the preferred aspects of the embodiment is a blood test kit for analyzing the concentration of a target component in a blood sample using a standard component that is not present in blood. Such a blood test kit may be used for using a standard component that does not exist in the blood together with a standard component that exists constantly in the blood, and uses a standard component that exists constantly in the blood. Alternatively, a standard component that does not exist in blood may be used alone.

In any case, standard components that are not present in the blood can be used by adding them to a diluting solution described later so as to have a predetermined concentration. As the standard component that does not exist in the blood, a substance that is not contained at all in the blood sample or is contained in a trace amount even if it is contained can be used. Standard components that are not present in blood include substances that do not interfere with the measurement of target components in blood samples, substances that do not degrade due to the action of biological enzymes in blood samples, substances that are stable in dilution, and blood cell membranes. It is preferable to use a substance that does not permeate and is not contained in blood cells, a substance that does not adsorb to a buffer storage container, and a substance that can use a detection system that can measure with high accuracy.

As a standard component that does not exist in blood, a substance that is stable even after being stored for a long time in a state of being added to a diluent is preferable. An example of a standard component that is not present in the blood is glycerol triphosphate.

These standard components that are not present in blood can be colored by adding a second reagent during concentration measurement after blood dilution, and the concentration in the diluted blood can be determined from the color density. For example, the measurement of glycerol triphosphate added to a diluted solution is performed by, for example, a known document, “home medical revolution” (clinical examination, Vol. 59, p397, 2015). It is possible to easily measure a large amount of sample with a small amount of sample using a biochemical automatic analyzer utilizing concentration measurement.

[Diluted solution]
The blood test kit includes a diluent for diluting the collected blood sample. The dilution liquid is a standard component that is constantly present in blood when the blood test kit is used to analyze the concentration of the target component in the blood sample by using the standard component that is constantly present in the blood. Does not contain. “Not contained” means “not substantially contained”. Here, “substantially does not contain” means that it does not contain a substance having homeostasis used at the time of determining the dilution factor, or even if it is contained, the homeostasis of the diluted solution after diluting the blood sample It means a case where it is contained at a very small concentration that does not affect the measurement of a toxic substance. When sodium ions or chloride ions are used as a standard component that is constantly present in blood, a diluent that does not substantially contain sodium ions or chloride ions is used as the diluent.

Since the pH of blood is normally kept constant at about pH 7.30 to about pH 7.40 in healthy individuals, the dilution solution is pH 6.5 to pH 8.0 in order to prevent decomposition and denaturation of the target component. It is preferable that the buffer solution has a buffering action in the pH range of pH 7.0, preferably pH 7.0 to pH 7.5, more preferably pH 7.3 to pH 7.4. It is preferable that it is a buffer solution containing the buffer component which suppresses. These buffers can be selected from buffers that are substantially free of sodium ions or chloride ions.

The buffer solution may contain a chelating agent, a surfactant, an antibacterial agent, a preservative, a coenzyme, a saccharide and the like for the purpose of keeping the analysis target component stable. Examples of the chelating agent include ethylenediaminetetraacetic acid (EDTA) salt, citrate, and oxalate. Examples of the surfactant include a cationic surfactant, an anionic surfactant, an amphoteric surfactant, and a nonionic surfactant. Examples of the preservative include sodium azide and antibiotics. Examples of the coenzyme include pyridoxal phosphate, magnesium, zinc and the like. Examples of the saccharide of the erythrocyte stabilizer include mannitol, dextrose, oligosaccharide and the like. In particular, by adding antibiotics, it is possible to suppress the growth of bacteria partially mixed from the finger surface at the time of hand blood collection, to suppress the degradation of the biological components by bacteria, and to stabilize the biological components.

The buffer also contains a standard component that is not present in blood in a blood test kit for analyzing a target component using a standard component that is not present in blood. It is also important not to include an internal standard substance to be described later and not to interfere with the blood analysis measurement system.

From the standpoint of diluting whole blood, the osmotic pressure of the buffer solution is equivalent to that of blood (285 mOsm / kg (mOsm / kg is the osmotic pressure of 1 kg of water in the solution and represents the number of millimolar ions)) or more By doing so, hemolysis of blood cells can be prevented. The osmotic pressure can be adjusted to be isotonic with salts, sugars, buffers or the like that do not affect the measurement of the target component and the measurement of the standard component that is constantly present in the blood. The osmotic pressure of the buffer solution can be measured with an osmometer.

When testing specific organs and specific diseases such as liver function, renal function, and metabolism as a blood test, obtain information on multiple components to be measured that are specific to the organ and the disease to determine the state of the organ, In order to predict habits or the like, generally, a plurality of components to be measured are analyzed simultaneously. For example, in order to examine the state of the liver, generally, ALT (alanine transaminase), AST (aspartate aminotransferase), γ-GTP (γ glutamyl transpeptidase), ALP (alkaline phosphatase), total bilirubin, The concentration in the blood of several or more substances such as total protein and albumin is measured. As described above, in order to measure a plurality of target components from one blood sample, the amount of diluted blood is required to some extent in consideration of the possibility of remeasurement. Therefore, it is important to secure a certain amount of the diluent for diluting the collected blood. However, considering that the invasiveness of the subject is kept as low as possible, the amount of blood collected is very small, so the dilution factor is, for example, a high factor of about 7 times or more.

(Diluted blood sample)
The cap 424 is removed from the blood collection container 410 of the storage device 400. The blood sample sucked into the blood sample reservoir 116 of the blood sampling device 100 is transferred to the diluent 422 from the upper end opening of the blood collection container 410. As a result, a diluted blood sample is stored in the blood collection container 410. By moving the rod-shaped member 300 to the tip side, the blood sample can be released from the blood sample reservoir 116.

[Separation device]
There is a possibility that the blood sample collected by the blood collection device 100 may elapse for a long time in the storage device 400 in a diluted state until analysis is performed. In the meantime, for example, when hemolysis of erythrocytes occurs, substances or enzymes present in the blood cells elute into the plasma or serum and affect the test results, or the absorption of the eluted hemoglobin causes the optical properties of the analyte to be analyzed. This may have an impact on the measurement of the amount of analysis target components using optical information such as typical absorption. Therefore, it is preferable to prevent hemolysis. Therefore, it is preferable that the blood test kit includes a separation device for separating and collecting plasma from a diluted blood sample. A preferred example of the separation device is a separation membrane. The separation membrane can be used, for example, by applying pressure to a diluted blood sample to capture blood cell components with the separation membrane, allowing plasma components to pass through, separating blood cells, and collecting plasma components. In this case, it is preferable to use an anticoagulant. In order to ensure measurement accuracy, it is preferable that the plasma that has passed through the separation membrane does not flow back to the blood cell side. Specifically, for this purpose, a backflow prevention means described in JP-A-2003-270239 is used. It can be a component of a kit.

FIG. 10 is a view showing an example of a holding device for holding the separation device. As shown in FIG. 10, the holding device 500 is provided at a cylindrical body 510 that can be inserted into the blood collection container 410 of the storage device 400, a cap piston 512 attached to the cylindrical body 510, and a lower end of the cap piston 512. And a sealing lid 514 that functions as a sealing device.

The cylinder 510 is made of a transparent material and has a cylindrical shape. An enlarged diameter portion 516 is formed at the upper end portion 542 of the cylindrical body 510. The enlarged diameter portion 516 is connected to the main body portion 520 via the thin portion 518. A reduced diameter portion 522 is formed at the lower end of the cylindrical body 510. A locking projection 524 is formed on the inner surface of the reduced diameter portion 522. Further, an outer flange 526 is formed at the lower end of the reduced diameter portion 522. The lower end opening of the outer casing 526 is covered with a filtration membrane 528 that functions as a separation instrument. The filtration membrane 528 is configured to allow passage of plasma in the blood and prevent passage of blood cells. A cover 530 made of silicon rubber is attached to the outer periphery of the reduced diameter portion 522.

The cap piston 512 is configured by a substantially cylindrical knob 532 and a mandrel 534 that is concentric with the knob 532 and extends downward. A cylindrical space 536 into which the diameter-enlarged portion 516 of the cylindrical body 510 can be fitted is formed at the inner upper end of the knob portion 532, and the lower portion thereof is screwed and can be screwed into the screw. The lower end portion 538 of the mandrel portion 534 is formed in a pin shape, and a sealing lid 514 is detachably provided on the lower end portion 538. The sealing lid 514 is made of silicon rubber. A lower end portion of the sealing lid 514 has a substantially cylindrical shape formed in an outer casing shape, and a step portion 540 is formed over the outer periphery. The knob portion 532 has a top portion 544, and the inner surface of the top portion 544 and the enlarged diameter portion 516 are in contact with each other.

Next, as shown in FIG. 11, in the state of the blood collection container 410 containing the diluted blood sample, the cylindrical body 510 to which the cap piston 512 is attached is inserted into the blood collection container 410.

Next, as shown in FIG. 12, the knob portion 532 is screwed into the screw portion 412. Initially, the knob 532 and the cylinder 510 are rotated. When the locking portion 414 of the blood collection container 410 is locked to a stopper portion (not shown) formed on the outer peripheral surface of the cylindrical body 510, the rotation of the cylindrical body 510 is restrained, and the thin portion 518 is broken by torsion. As a result, the cylindrical body 510 is separated into the main body portion 520 and the enlarged diameter portion 516. When the knob portion 532 is further rotated, the upper end portion 542 of the main body portion 520 enters the space 536 inside the enlarged diameter portion 516. Since the cylinder 510 is pressed downward by the inner surface of the top portion 544 of the knob portion 532, the cylinder 510 is further lowered.

As the cylinder 510 descends, the filtration membrane 528 held by the cylinder 510 moves to the bottom 416 side of the blood collection container 410. At that time, plasma moves through the filtration membrane 528 to the cylindrical body 510 side, and blood cells cannot pass through the filtration membrane 528 and remain on the blood collection container 410 side.

Since the outer diameter of the cover 530 is larger than the outer diameter of the main body 520 of the cylinder 510, the cylinder 510 descends in a state of being in close contact with the inner surface of the blood collection container 410. Therefore, there is no possibility that the diluent 422 in the blood collection container 410 leaks outside through the gap between the blood collection container 410 and the cylinder 510 in the process of inserting the cylinder 510 into the blood collection container 410.

When the knob portion 532 is screwed to the screw portion 412 to the lowest position, the sealing lid 514 is fitted to the reduced diameter portion 522. The flow path between the blood collection container 410 and the cylinder 510 is sealed with a sealing lid 514. The sealing lid 514 prevents mixing of plasma and blood cells due to backflow.

The blood collection container 410 constitutes a storage device in which a diluent is stored, and also a storage device for storing a diluted blood sample. In addition, in a state where the blood plasma cell is inserted into the blood collection container 410 and plasma and blood cells are separated, the cylindrical body 510 constitutes a storage device for storing the collected plasma. The storage device for storing the blood sample corresponds to the combination of the blood collection container 410 and the cylindrical body 510. That is, the number of storage devices for storing the diluted blood sample may be one or a combination of two or more.

The blood test kit makes it possible to realize a method capable of analyzing a component to be analyzed with high measurement accuracy even with a blood collection volume of 100 μL or less. Blood including an instruction manual in which the subject can accurately measure even with a small blood collection volume of 100 μL or less, and information such as to what extent a blood sample should be collected by the blood collection device 100 A test kit is preferred.

<Blood analysis method>
A blood analysis method using the blood test kit of the embodiment will be described. The blood analysis method includes a mode that is a medical act on a human (an act performed by a doctor) and a mode that is not a medical act on a human (for example, a mode in which a blood sampler is a patient himself and an analyst is a person other than a doctor, Embodiments for human animals, etc.). The blood analysis method of the embodiment may be performed by self-collection in which the subject himself collects blood, or may be performed in general blood collection in which a qualified person such as a doctor collects blood using a syringe. Good. As a preferred embodiment, the patient himself / herself collects the blood that has come out of the skin by damaging a fingertip or the like using an instrument with a knife such as a lancet.

The biological sample to be analyzed is blood, and blood is a concept including serum or plasma. Preferably, plasma or serum obtained by collecting a small amount of blood from a subject, diluting with a buffer solution, and then separating blood cells by a filter or centrifugation can be used. The component of the blood sample is preferably a plasma component separated from the blood sample by the separation means. The origin of the blood sample is not limited to humans, and may be mammals, birds, fishes, etc., which are non-human animals (non-human animals). Examples of animals other than humans include horses, cows, pigs, sheep, goats, dogs, cats, mice, bears, pandas, and the like. Preferably, the source of the biological sample is human.

As a first aspect of the blood analysis method, the concentration of the target component is analyzed using standard components that are constantly present in the blood sample. For the standard components that are permanently present in the blood sample, the description in [1] applies here as it is.

The occupation ratio of plasma components in the blood of the subject is about 55% in terms of volume, but varies depending on changes in the amount of salt intake of the subject. Therefore, in the embodiment, the dilution ratio of plasma is calculated using the standard value of the standard component that is constantly present in plasma, and the concentration of the target component in plasma in the blood sample is calculated using the calculated dilution ratio. analyse. As a method for calculating the dilution rate, a measured value (concentration X) of an external standard substance (for example, sodium ion) in a diluted plasma solution and the external standard substance (for example, sodium) contained in the blood sample plasma. The dilution factor can be obtained by calculating the dilution factor (Y / X) of the plasma component in the blood sample from the known concentration value (concentration Y; 142 mmol / L in the case of sodium ion) of ions, etc. . Using this dilution factor, the measurement value (concentration Z) of the target component in the plasma dilution is measured, and this measurement value is multiplied by the dilution factor, so that the analyte actually contained in the plasma of the blood sample The component concentration [Z × (Y / X)] can be measured.

The concentration of sodium ions and the like can be measured by a known method such as a flame photometric method, a glass electrode method, a titration method, an ion selective electrode method, an enzyme activity method, or a method utilizing β-galactosidase.

In addition, in order to confirm that blood test kits that specify the amount of standard components derived from components are actually used, and that blood dilution and plasma recovery methods are performed normally, It is preferable to additionally obtain a dilution factor independently from the other standard components and confirm that the value matches the dilution factor obtained above. The coincidence means that in two measured values (a, b), the ratio of their difference to their average value, that is, | a−b | / {(a + b) / 2} × 100 is 20% or less. Preferably, it is 10% or less, more preferably 5% or less. Thereby, it is possible to verify that the analysis of the concentration of the target component in the blood sample is performed normally. Here, as an example of a standard component that is constantly present in plasma other than sodium ions or chloride ions, it is preferably selected from total protein or albumin, and more preferably total protein. There are known methods for measuring total protein, such as the Burette method, the ultraviolet absorption method, the Breadford method, the Raleigh method, the bicinchoninic acid (BCA) method, and the fluorescence method. A method to be used as appropriate can be selected according to the amount and the like.

As a second aspect of the blood analysis method, the concentration of the target component is analyzed using standard components that are not present in the blood. In this case, a blood test kit containing a diluent containing standard components not present in blood is used.

100 Blood collection instrument 110 Outer cylinder 112 Front end opening 114 Base end opening 116 Blood sample reservoir 116A Reservoir space 118 Outer cylinder main body 118A Main body section space 120 Bearing section 120A First bearing section 120B Second bearing section 121 Opening 122 Gear wheel 122A First gear 122B Second gear 124 Protective cover 124A Groove 124B Locking portion 126 Groove portion 130 Elastic member fixing portion 130A Pin 132 Elastic member 132A Fixing portion 132B Bending portion 140 Opening 200 Release member 200A Opening 200B Protruding portion 300 Bar-shaped member 310 Tip 312 Rubber member 314 Rear end surface 316 First claw part 318 Second claw part 330 Projection part 400 Storage instrument 410 Blood collection container 412 Screw part 414 Locking part 416 Bottom part 418 Leg part 420 Slit groove 422 Diluent 424 Cap 426 Packing 500 Holding device 510 Cylindrical body 512 Cap piston 514 Sealing lid 516 Expanded portion 518 Thin portion 520 Main body portion 522 Reduced diameter portion 524 Locking projection portion 526 Outer flange portion 528 Filtration membrane 530 Cover 532 Knob portion 534 Mandrel portion 536 Space 538 Lower end portion 540 Stepped portion 542 Upper end 544 Top

Claims (10)

1. A blood collection device used in a blood test kit,
   An outer cylinder having a blood sample reservoir that is defined by a distal end opening and a proximal end opening and communicates with the distal end opening;
   A rod-shaped member that is movable in the axial direction in the outer cylinder, and a rod-shaped member that sucks a blood sample from the distal end opening to the blood sample reservoir in accordance with the movement from the distal end opening to the proximal end opening;
   A movement adjustment mechanism that enables stepwise movement of the rod-shaped member from the distal end opening to the proximal end opening, and restricts movement of the rod-shaped member from the proximal end opening to the distal end opening;
   A blood collection device having:
2. The blood collection device according to claim 1, further comprising a release member that releases the restriction of movement of the rod-shaped member in the movement adjustment mechanism.
3. The said movement adjustment mechanism is comprised of the 1st nail | claw part in which the elastic member fixed to the said outer cylinder and the said rod-shaped member engaged with the said elastic member were formed. Blood collection device.
4. A movable gear wheel and a plurality of second claw portions formed with the rod-shaped member engaged with the gear wheel are provided to move the rod-shaped member from the distal end opening to the proximal end opening. The blood sampling device according to any one of 1 to 3.
5. In order to move the rod-shaped member from the distal end opening to the base end opening, a projecting portion projecting from the outer tube on which the rod-shaped member is formed, and an opening provided in the outer tube allowing movement of the projecting portion The blood sampling device according to any one of claims 1 to 3, comprising:
6. The blood sampling device according to any one of claims 1 to 5, wherein the blood sample reservoir is detachable.
7. The blood sampling device according to any one of claims 1 to 6, which has an anticoagulant inside the blood sample reservoir.
8. The blood sampling device according to any one of claims 1 to 7, wherein a scale indicating a volume of the blood sample is attached to the blood sample reservoir.
9. A blood collection device according to any one of claims 1 to 8 for collecting a blood sample;
   A diluent for diluting the collected blood sample;
   A storage device for storing a dilution of a blood sample;
   A blood test kit for analyzing the concentration of a target component in a blood sample using a standard component that is constantly present in blood or a standard component that is not present in blood contained in the diluent.
10. The blood test kit according to claim 9, wherein the blood test kit includes a separation instrument for separating and collecting plasma from the diluted blood sample.

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