JP7083889B2 - Blood sampling device and blood test kit - Google Patents

Description

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

In general, blood collection is performed by a certain qualified person such as a doctor who collects blood from a vein using a syringe, and a self who collects blood by inserting a blood collection needle into the finger of his or her hand. There is blood sampling.

The blood collected by general blood collection is transported to a medical institution or a laboratory in a state of being sealed in a collection container, and the test is performed there. When the blood sample is transported without being separated into blood cells and plasma, the test is performed after the blood sample is separated into blood cells and plasma by a centrifuge at a medical institution or a testing institution. In the self-collection performed by the test subject, the blood sample after blood collection is separated into blood cells and plasma by a separation membrane, and the separated state is transported to the test site where the test is performed. In order to collect blood samples by themselves, a body fluid collection device is often used.

For example, Patent Document 1 discloses that when a body fluid collection device is provided with a step by a blocking portion to collect body fluid by a capillary phenomenon, a certain volume of body fluid is collected in the storage portion.

Further, in Patent Document 2, a communication relay path and a communication suction path are provided in the body fluid collection device, and the size of the inner diameters of both is specified. It is disclosed to collect in.

Japanese Unexamined Patent Publication No. 2016-118572 Japanese Unexamined Patent Publication No. 2017-173219

However, with the body fluid collecting devices shown in Patent Documents 1 and 2, if the blood sample is smaller than the volume required for the test, an additional blood sample cannot be collected. In addition, it is not possible to prevent the collected blood sample from being unintentionally released from the body fluid collection device.

The present invention has been made in view of such circumstances, and provides a blood sampling device and a blood test kit capable of collecting blood samples in stages and suppressing unintentional release of blood samples. The purpose is.

The blood collection device according to the first aspect is a blood collection device used in a blood test kit, and has an outer cylinder having a blood sample reservoir in which a tip opening and a proximal end opening are defined and communicate with the tip opening. A rod-shaped member that can move in the outer cylinder in the axial direction, and a rod-shaped member that sucks a blood sample from the tip opening to the blood sample reservoir as it moves from the tip opening to the proximal opening, and a rod-shaped member that sucks the blood sample from the distal opening to the proximal end. It has a movement adjusting mechanism that enables stepwise movement of the rod-shaped member to the opening and regulates the movement of the rod-shaped member from the proximal end opening to the tip opening.

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

In the blood collection 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 of a rod-shaped member engaged with the elastic member.

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

In the blood collection device according to the fifth aspect, in order to move the rod-shaped member from the tip opening to the proximal end opening, a protruding portion protruding from the outer cylinder on which the rod-shaped member is formed and an outer cylinder allowing the movement of the protruding portion are provided. It has an opening provided.

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

The blood sampling 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 capacity of the blood sample.

The blood test kit according to the ninth aspect is the above-mentioned blood sampling device for collecting a blood sample, a diluent for diluting the collected blood sample, and an accommodating device for accommodating a diluted product of the blood sample. And, the concentration of the target component in the blood sample is analyzed using the standard component that is constantly present in the blood or the standard component that is not present in the blood contained in the diluted solution.

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

An object of the present invention is to provide a blood sampling device and a blood test kit capable of collecting a blood sample stepwise and suppressing the unintentional release of the blood sample.

FIG. 1 is an exploded perspective view showing an example of a blood sampling device. FIG. 2 is an assembly drawing of a blood sampling device. FIG. 3 is a transmission view of an assembly drawing of the blood sampling device of FIG. FIG. 4 is an explanatory diagram illustrating the operation of the movement adjusting mechanism. FIG. 5 is an explanatory diagram illustrating the operation of the movement adjusting mechanism. FIG. 6 is an explanatory diagram illustrating the operation of the release member. FIG. 7 is an explanatory diagram illustrating the operation of the release member. FIG. 8 is a perspective view showing another example blood sampling device. FIG. 9 is a diagram showing an example of the configuration of an accommodating device for accommodating a diluted blood sample. FIG. 10 is a diagram showing an example of a holding device for holding the separating device. FIG. 11 is a diagram showing an example of a holding device for holding the separating device. FIG. 12 is a diagram showing an example of a holding device for holding the separating device.

Hereinafter, preferred embodiments of the present invention will be described with reference to the accompanying drawings. The present invention will be described by the following preferred embodiments. Changes can be made by many methods without departing from the scope of the present invention, and other embodiments other than the embodiment can be used. Therefore, all modifications within the scope of the present invention are included in the claims. In the present specification, when the numerical range is expressed by using “from”, the numerical range includes the upper and lower limits indicated by “from”. 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 sampling device>
The blood sampling device of the embodiment will be described with reference to FIGS. 1 to 3. Here, the "tip" means the side that sucks and discharges the 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 tip opening 112 and a proximal opening 114 are defined. The tip opening 112 and the base 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 is defined with a substantially cylindrical reservoir space 116A having a tip opening 112 as a bottom surface. The blood sample is stored in the reservoir space 116A. The blood sample is sucked into the blood sample reservoir 116 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 that communicates with the reservoir space 116A.

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

The outer cylinder main body 118 includes a bearing portion 120 between the blood sample reservoir 116 and the proximal end opening 114. A gear wheel 122 rotatably supported is attached to the bearing portion 120. The bearing portion 120 is composed of a first bearing portion 120A and a second bearing portion 120B. The gear wheel 122 is composed of a first gear 122A composed of 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 the region of the outer cylinder body 118 where the second gear 122B is located. The opening 121 penetrates the outer surface and the inner surface of the outer cylinder body 118. When the second gear 122B is supported by the second bearing portion 120B, the second gear 122B projects beyond the inner surface of the outer cylinder main body 118 through the opening 121.

A protective cover 124 for protecting the gear wheel 122 is attached to the outer cylinder body 118. The protective cover 124 is formed with a groove 124A 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 collector can rotate the first gear 122A with his 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 composed of 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 opening 114 toward the distal opening 112 is formed in the outer cylinder body 118. The groove portion 126 penetrates the outer surface and the inner surface of the outer cylinder body 118.

An elastic member fixing portion 130 is continuously provided on the tip end side of the groove portion 126. Two pins 130A are provided on the elastic member fixing portion 130. The pin 130A projects toward the outer surface of the outer cylinder body 118. An elastic member 132 made of a leaf spring is fixed to the elastic member fixing portion 130. The elastic member 132 is not limited to the leaf spring.

The elastic member 132 is composed of a fixing portion 132A attached to the elastic member fixing portion 130 and a bent portion 132B which is continuous with the fixing portion 132A and is bent so as to form 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 132B projects beyond the inner surface of the outer cylinder main body 118 via the groove portion 126. The base end side of the elastic member 132 is bent into a curved shape.

The release member 200 is attached to the side of the base end opening 114 of the outer cylinder 110. The release member 200 has a substantially cylindrical shape. An opening 200A is provided on the outer surface of the release member 200 on the tip side. The opening 200A penetrates the outer surface and the inner surface of the release member 200. Therefore, the opening 200A allows the passage of the bent portion 132B. A protrusion 200B is provided on the outer surface of the release member 200 on the side of the base end. The opening 200A and the protrusion 200B 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 body 118. The groove 126 of the outer cylinder body 118 allows the protrusion 200B to be received and moved. The release member 200 can be inserted into the outer cylinder body 118 from the base end opening 114. The release member 200 has a tubular 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 outer cylinder 110 in the axial direction. The rod-shaped member 300 is formed with a tip portion 310 that tapers toward the tip end. A rubber member 312 is attached to the tip portion 310. The rubber member 312 is inserted into the reservoir space 116A of the blood sample reservoir 116 and functions as a sealing 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 tip opening 112 along the axial direction.

A plurality of first claw portions 316 and a plurality of second claw portions 318 are provided between the tip portion 310 and the rear end surface 314 of the rod-shaped member 300 from the side of the rear end surface 314. 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-shaped 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 body 118. The protruding portion 200B of the release member 200 is inserted into the groove portion 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 portion 126 and the protrusion portion 200B restrict the release member 200 from rotating about the axis direction of the outer cylinder 110 as the rotation center. The groove portion 126 and the protrusion portion 200B allow the release member 200 to easily move along the axial direction of the outer cylinder 110. The rod-shaped member 300 is inserted from the base end opening 114 into the release member 200 and the outer cylinder 110 until the rear end surface 314 of the rod-shaped member 300 comes into contact with the base end opening 114 of the outer cylinder 110.

FIG. 3 is a transmission diagram of FIG. As shown in FIG. 3, the rubber member 312 attached to the tip of the rod-shaped member 300 passes through the main body space 118A and reaches the base end of the reservoir space 116A. With the rubber member 312, the reservoir space 116A constitutes a space in which the base end is closed.

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

With the movement of the rod-shaped member 300, the rubber member 312 moves in the direction away from the tip opening 112 while sliding in the main body space 118A. When the blood sample is in contact so as to close the tip opening 112, the reservoir space 116A and the main body space 118A become negative pressure, and the blood sample is sucked into the reservoir space 116A 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 132B 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 adjusting mechanism for the rod-shaped member 300 in the embodiment.

The operation of the movement adjustment mechanism will be described with reference to FIGS. 4 and 5. 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 cross-sectional view. The trapezoidal shape is such that the base becomes shorter as the distance from the rod-shaped member 300 increases.

As shown in FIG. 5, by rotating the 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 tip opening 112 toward the proximal opening 114. The fixed portion 132A and the bent portion 132B are configured so that the narrower angle forms an obtuse angle. Elastic deformation of the bent portion 132B in a direction in which the angle with respect to the fixed portion 132A increases can be performed with a relatively small force. Therefore, as the rod-shaped member 300 moves, the bent portion 132B elastically deforms along the slope of the first claw portion 316. 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 the arrow B, when the bent portion 132B gets over the first claw portion 316, the bending portion 132B is placed between the bent portion 132B and the adjacent first claw portion 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 and 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 traveled by a certain distance.

Since the rod-shaped member 300 can move stepwise from the tip opening 112 toward the proximal opening 114, the blood sample can be sucked stepwise from the tip opening 112 into the blood sample reservoir 116.

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 by 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 capacity that can be sucked in one step is about 5 μL. Further, if the volume required for the blood test is 65 μL, the rod-shaped member 300 requires at least 13 steps of movement.

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 base end opening 114 toward the tip opening 112, the angle formed by 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 of the bent portion 132B in the direction in which the angle becomes smaller with respect to the fixing portion 132A requires a larger force than the elastic deformation in the direction of increasing the angle. The elastic member 132 restricts the movement of the rod-shaped member 300 from the proximal opening 114 to the distal opening 112.

Here, the term "regulation" means that the force for moving the rod-shaped member 300 is larger when it is moved from the proximal opening 114 to the distal opening 112 than when it is moved from the distal opening 112 to the proximal opening 114. Means to be.

Since the movement of the rod-shaped member 300 from the proximal opening 114 to the distal 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 tip opening 112 to the proximal opening 114, and a required amount of blood sample is sucked into the blood sample reservoir 116 (not shown) of the blood sampling device 100. It is necessary to transfer the aspirated blood sample from the blood collection device 100 to the storage device (not shown).

As shown in FIG. 6, when the release member 200 is moved toward the base end as shown by the arrow C, the edge on the tip end side of the opening 200A and the bent portion 132B come into contact with each other. When the release member 200 is further moved in the direction of the arrow C, the bent portion 132B is elastically deformed with respect to the fixed portion 132A in a direction in which the angle increases, as shown by the arrow D. Since the engagement between the bent portion 132B and the first claw portion 316 is released, the restriction on the movement of the rod-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 protrusion 200B and adding the finger 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, in the direction from the base end opening 114 to the tip opening 112. Since the elastic member 132 and the plurality of first claw portions 316 are disengaged, the rod-shaped member 300 can be smoothly moved toward the tip end side. The smooth movement of the rod-shaped member 300 allows the blood sample stored in the blood collection device 100 to be easily and quickly pushed out, and the blood sample can be transferred to the storage device (not shown).

Another example of the blood sampling device 100 will be described with reference to FIG. The same configurations as those of the blood sampling device 100 of FIGS. 1 to 7 described above may be designated by the same reference numerals and the description thereof may be 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 body 118. The opening 140 is formed along the axial direction of the outer cylinder 110. The rod-shaped member 300 is provided with a protrusion 330. The protrusion 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 toward the proximal end, the rod-shaped member 300 is moved from the distal end opening 112 toward the proximal end opening 114. 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 gradually sucked into the blood sample reservoir 116. Further, the elastic member 132 and the first claw portion 316 restrict the movement of the rod-shaped member 300 from the proximal end opening 114 to the distal end opening 112.

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

In the blood sampling device 100 described above, it is preferable that the blood sample reservoir 116 is removable. After the blood sample is sucked and released by the blood sampling device 100, only the blood sample reservoir 116 can be discarded. The portion other than the blood sample reservoir 116 can be reused. For reuse, a new blood sample reservoir 116 is attached to the outer cylinder body 118.

When the blood sampling device 100 of the embodiment directly collects blood obtained by puncturing with a lancet or the like, it is preferable that the blood sampling device 100 has an anticoagulant on the inner surface of the blood sample reservoir 116. 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 an external standard substance is used for the purpose of calculating the ratio of blood to a diluted solution during analysis, the external standard substance is substantially not contained. The one is selected.

It is preferable that the blood sample reservoir 116 is provided with a scale indicating the capacity of the blood sample. It is possible to determine 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 in about 65 μL, it is preferable to mark 55 μL and 75 μL, which are the allowable volume ranges (± 10 μL) of the blood sample. It is preferable to have a scale having a different appearance so as not to be mistaken for a scale indicating the lower limit or the upper limit. The volume range of the blood sample means a range allowed for accurate analysis of the target component contained in the blood sample.

The blood sampling method using the blood sampling device 100 described above 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 uses a device with a knife such as a lancet to injure a fingertip or the like to bring the blood sample out of the skin into contact with the tip opening 112 of the blood sampling device 100. By moving the rod-shaped member 300 stepwise to the side of 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 required for the blood test can be sucked by the scale attached to 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 above-mentioned blood sampling device 100, a diluting solution for diluting the collected blood sample and an accommodating device for accommodating the diluted product of the blood sample, and is constantly contained in the blood. It is a blood test kit for analyzing the concentration of a target component in a blood sample using an existing standard component or a standard component contained in the diluted solution and not present in blood.

Further, it is preferable to provide a separation device for separating and recovering plasma from the diluted product of the blood sample.

[Accommodation equipment]
FIG. 9 is a cross-sectional view showing an example of the configuration of an accommodating device for accommodating a diluted blood sample. As shown in FIG. 9, the containment device 400 has 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. Further, a conical bottom portion 416 protruding toward the lower end side is formed at the lower end portion of the blood collection container 410. Cylindrical legs 418 are formed around the bottom 416. "Upper" and "lower" mean "upper" and "lower" in a state where the legs 418 are installed on the mounting surface.

The leg portion 418 has the same outer diameter as the sample cup (not shown) used at the time of blood analysis and examination, and preferably, slit grooves 420 are formed in the vertical direction at opposite positions at the lower ends 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, prior to the use of the containment device 400, it is preferable that the upper end opening of the blood collection container 410 is sealed by the cap 424 via the packing 426.

[Standard component that is constantly present in blood]
High dilution ratio of plasma components In order to accurately analyze the concentration of the target component after dilution of diluted plasma in the plasma of blood before dilution, the rate of change in the concentration of substances pre-existing in the diluted solution The method obtained from can be adopted. It is also possible to adopt 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 adopt 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 the target component in a blood sample using a standard component that is constantly present in the blood. be.

Here, "using" the standard component means to analyze the concentration of the target component based on the standard value for the standard component (in the case of using a standard component that is constantly present in blood, the constant value). It is intended to determine the dilution ratio of. Therefore, when analyzing the concentration of the target component in a blood sample using a standard component that is constantly present in blood, it is diluted based on the constant value (standard value) of the standard component that is constantly present in blood. It is also to determine the magnification and analyze the concentration of the target component.

Standard components that are constantly present in blood include, for example, sodium ion, chloride ion, potassium ion, magnesium ion, calcium ion, total protein, albumin and the like. The concentrations of these standard components contained in the serum and plasma of blood samples are as follows: sodium ion concentration is 134 mmol / L to 146 mmol / L (average value: 142 mmol / L), and chloride ion concentration is 97 mmol / L to 107 mmol. / L (average value: 102 mmol / L), potassium ion concentration from 3.2 mmol / L to 4.8 mmol / L (average value: 4.0 mmol / L), magnesium ion concentration from 0.75 mmol / L to 1 0.0 mmol / L (average value: 0.9 mmol / L), calcium ion concentration from 4.2 mmol / L to 5.1 mmol / L (average value: 4.65 mmol / L), 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 / 100 mL to 5.1 g / 100 mL (average value: 4.6 g / 100 mL). In the embodiment, it is intended to enable the measurement of the target component when the amount of blood to be collected is very small in order to relieve the pain of the subject, and when a small amount of blood is diluted with the diluted solution, the diluted solution is used. It is necessary to accurately measure the concentration of the "standard component that is constantly present in blood" that is present in the blood. When the dilution ratio becomes high, the concentration of the component originally present in the blood in the diluted solution decreases, and depending on the dilution ratio, a measurement error may be included when measuring the concentration. Therefore, in order to detect the standard component with sufficiently high accuracy when a trace amount of blood component is diluted at a high dilution ratio, it is preferable to measure the standard component present at a high concentration in the trace amount of blood. In the present invention, it is preferable to use sodium ion (Na ⁺ ) or chloride ion (Cl ⁻ ), which is present at a high concentration among the components constantly present in the blood sample. Furthermore, it is most preferable to measure the sodium ion having the highest amount present in the blood among the above-mentioned standard components constantly present in the blood. The average value of sodium ions 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 component not present in blood]
One of the preferred embodiments 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 for using a standard component that is not constantly present in the blood as well as a standard component that is constantly present in the blood, and the standard component that is constantly present in the blood is used. Instead, it may be for using a standard component that is not present in blood alone.

In either case, the standard component that is not present in blood can be added to the diluted solution described later to a predetermined concentration and used. As a standard component that is not present in blood, a substance that is not contained in the blood sample at all, or even if it is contained, can be used in a very small amount. Standard components that do not exist in blood include substances that do not interfere with the measurement of the target component in the blood sample, substances that do not decompose under the action of bioenzymes in the blood sample, substances that are stable during dilution, and blood cells. 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 the storage container of the buffer solution, and a substance that can be used by a detection system that can measure accurately.

As a standard component that does not exist in blood, a substance that is stable even when stored in a diluted solution for a long period of time is preferable. Examples of standard components that are not present in blood include glycerol triphosphate.

These standard components not present in blood can be colored by adding a second reagent at the time of concentration measurement after blood dilution, and the concentration in diluted blood can be determined from the color-developing concentration. For example, the measurement of glycerol triphosphate added to the diluted solution is described in, for example, "Home Medical Revolution" (Clinical Examination Vol. 59, p397, 2015), which is a publicly known material, for dye color development by oxidative condensation. A large amount of sample can be easily measured with a small amount of sample by an automatic biochemical analyzer using concentration measurement.

[Diluted solution]
The blood test kit contains a diluent for diluting the collected blood sample. The diluted solution is a standard component that is constantly present in the blood when the blood test kit is for analyzing the concentration of the target component in the blood sample using the standard component that is constantly present in the blood. Does not contain. "Not contained" means "substantially not contained". Here, "substantially free" means that the substance having homeostasis used when determining the dilution ratio is not contained at all, or even if it is contained, the dilution solution after diluting the blood sample is constant. It means that it is contained in a very small concentration that does not affect the measurement of a substance having sex. When sodium ion or chloride ion is used as a standard component constantly present in blood, a diluted solution containing substantially no sodium ion or chloride ion is used as the diluted solution.

Since the pH of blood is usually kept constant at about pH 7.30 to pH 7.40 in healthy subjects, the diluted solution is pH 6.5 to pH 8.0 in order to prevent decomposition and denaturation of the target component. The buffer solution has a buffering action in the range of pH 7.0 to pH 7.5, more preferably pH 7.3 to pH 7.4, and the diluted solution has a fluctuation in pH. It is preferable that the buffer solution contains a buffer component that suppresses the pH. These buffers can be selected from buffers that are substantially free of sodium 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 component to be analyzed stable. Examples of the chelating agent include ethylenediaminetetraacetic acid (EDTA) salt, citrate, oxalate and the like. Examples of the surfactant include a cationic surfactant, an anionic surfactant, an amphoteric surfactant or a nonionic surfactant. Examples of the preservative include sodium azide, antibiotics and the like. 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 an antibiotic, it is possible to suppress the growth of bacteria partially mixed from the surface of the finger when collecting blood from the finger, suppress the decomposition of the biological component by the bacterium, and stabilize the biological component.

The buffer also contains a standard component that is not present in the blood in a blood test kit for analyzing the target component using a standard component that is not present in the blood. It is also important that it does not contain the internal standard substances described later and does not interfere with the measurement system of blood analysis.

From the viewpoint of diluting whole blood, the osmotic pressure of the buffer solution is equal to or higher than that of blood (285 mOsm / kg (mOsm / kg is the osmotic pressure of 1 kg of water in solution, which represents the number of millimoles of ions)) or higher. By doing so, hemolysis of blood cells can be prevented. The osmotic pressure can be adjusted isotonic with salts, saccharides, buffers, etc. 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 by an osmometer.

When testing a specific organ or a specific disease such as liver function, kidney function, or metabolic syndrome as a blood test, obtain information on multiple organs and components to be measured that are specific to the disease, and obtain information on the condition of the organ and life. In general, a plurality of components to be measured are analyzed at the same time in order to predict habits and the like. For example, in order to examine the condition of the liver, generally, ALT (alanine transaminase), AST (aspartate aminotransferase), γ-GTP (γ-glutamyltranspeptidase), ALP (alkaline phosphatase), total bilirubin, The concentration of several or more substances such as total protein and albumin in the blood is measured. As described above, in order to measure a plurality of target components from one blood sample, a certain amount of diluted blood is required in consideration of the possibility of remeasurement. Therefore, it is important to secure a certain amount of diluent for diluting the collected blood. However, considering that the invasiveness of the subject is suppressed to a low level as much as possible, the amount of blood collected is very small, so that the dilution ratio is, for example, a high ratio of about 7 times or more.

(Diluted blood sample)
Remove the cap 424 from the blood collection container 410 of the containment device 400. From the upper end opening of the blood collection container 410, the blood sample sucked into the blood sample reservoir 116 of the blood collection device 100 is transferred to the diluted solution 422. As a result, the diluted product of the blood sample is contained in the blood collection container 410. By moving the rod-shaped member 300 toward the tip side, the blood sample can be discharged from the blood sample reservoir 116.

[Separation device]
The blood sample collected by the blood collection device 100 may elapse in the containment device 400 for a long time in a diluted state until the analysis is performed. During that time, for example, when hemolysis of red blood cells occurs, substances and enzymes existing in blood cells elute into plasma or serum and affect the test results, or the absorption of the eluted hemoglobin causes the optics of the component to be analyzed. It may affect the measurement of the amount of components to be analyzed by optical information such as normal absorption. Therefore, it is preferable to prevent hemolysis. Therefore, it is preferable that the blood test kit includes a separation device for separating and recovering plasma from the diluted product of the blood sample. A preferred example of a separation device is a separation membrane. The separation membrane can be used, for example, by applying pressure to a diluted blood sample to capture the blood cell component in the separation membrane, allow the plasma component to pass through, separate the blood cell and recover the plasma component. In this case, it is preferable to use an anticoagulant. Further, in order to ensure the accuracy of measurement, it is preferable that the plasma that has passed through the separation membrane does not flow back to the blood cell side. Specifically, for that purpose, the backflow prevention means described in JP-A-2003-270239 is used. It can be a component of the kit.

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

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

The cap piston 512 is composed of a substantially cylindrical grip portion 532 and a mandrel portion 534 that is concentric with the grip portion 532 and extends downward. A cylindrical space 536 into which the enlarged diameter portion 516 of the tubular body 510 can be fitted is formed at the inner upper end portion of the knob portion 532, and the lower portion thereof is screwed so that it 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 silicone rubber. The lower end of the sealing lid 514 forms a substantially columnar shape formed in the shape of an outer collar, and a stepped 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 diameter-expanded 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 tubular 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. First, the knob 532 and the cylinder 510 rotate. When the locking portion 414 of the blood collection container 410 is locked to the stopper portion (not shown) formed on the outer peripheral surface of the tubular body 510, the rotation of the tubular body 510 is restricted and the thin-walled portion 518 is broken by twisting. As a result, the tubular body 510 is separated into a main body portion 520 and a diameter-expanded portion 516. Further, when the knob portion 532 is rotated, the upper end portion 542 of the main body portion 520 enters the space 536 inside the diameter expansion portion 516. Since the tubular body 510 is pressed downward by the inner surface of the top portion 544 of the knob portion 532, the tubular body 510 is further lowered.

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

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

When the knob portion 532 is screwed to the screw portion 412 to the lowermost portion, the sealing lid 514 fits into the diameter reduction portion 522. The flow path between the blood collection container 410 and the tubular body 510 is sealed by the sealing lid 514. The sealing lid 514 prevents the mixing of plasma and blood cells due to reflux.

The blood collection container 410 constitutes an accommodating device for accommodating the diluted solution, and also constitutes an accommodating instrument for accommodating the diluted product of the blood sample. Further, in a state of being inserted into the blood collection container 410 and separating plasma and blood cells, the tubular body 510 constitutes an accommodating device for accommodating the collected plasma. The accommodating device for accommodating the blood sample corresponds to the combination of the blood collection container 410 and the tubular body 510. That is, the containment device for accommodating 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 an analysis target component with high measurement accuracy even if the blood collection amount is 100 μL or less. Blood containing an instruction manual that describes information such as the ability to accurately measure even a small blood sampling volume of 100 μL or less and the extent to which a blood sample should be collected with the blood sampling device 100. It is preferably a test kit.

<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 in which it is a medical practice for humans (an act performed by a doctor) and a mode in which it is not a medical practice for humans (for example, the blood collector is the patient himself and the analyst is a person other than the doctor). Aspects for human animals, etc.) are included. The blood analysis method of the embodiment may be carried out by self-collecting blood in which the subject himself / herself collects blood, or in general blood sampling in which a qualified person such as a doctor collects blood using a syringe. good. In a preferred embodiment, the patient himself / herself uses a device with a knife such as a lancet to injure a fingertip or the like to collect blood that has come out of the skin.

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 it 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 a separation means. The origin of the blood sample is not limited to humans, and may be mammals, birds, fish, etc., which are animals other than humans (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 origin of the biological sample is human.

As a first aspect of the blood analysis method, the concentration of the target component is analyzed using a standard component that is constantly present in the blood sample. As for the standard component that is constantly present in the blood sample, the explanation in [1] still applies here.

The occupancy rate of plasma components in the blood of the subject is about 55% by volume, but it varies depending on the change in the salt intake of the subject and the like. Therefore, in the embodiment, the dilution ratio of plasma is calculated using the standard value of the standard component 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 ratio, a measured value (concentration X) of an external standard substance (for example, sodium ion) in a diluted solution of plasma and the above external standard substance (for example, sodium) contained in the plasma of a blood sample are used. The dilution ratio can be obtained by calculating the dilution ratio (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 (ion, etc.). .. Using this dilution ratio, the measured value (concentration Z) of the target component in the diluted solution of plasma is measured, and by multiplying this measured value by the dilution ratio, the analysis target actually contained in the plasma of the blood sample. It becomes possible to measure the concentration [Z × (Y / X)] of the component.

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 selection electrode method, an enzyme activity method, or a method using β-galactosidase.

Also, in order to confirm that a blood test kit that specifies the amount of standard components derived from the member is actually used, and that the method of diluting blood and collecting plasma is performed normally, plasma is used. It is preferable to additionally determine the dilution factor independently of the other standard component of and confirm that the value is consistent with the dilution factor determined above. To match means that, in the two measured values (a, b), the ratio of the difference to the average value, that is, | ab | / {(a + b) / 2} × 100 is 20% or less. It is preferably 10% or less, and more preferably 5% or less. This makes it possible to verify that the concentration of the target component in the blood sample has been analyzed normally. Here, as an example of the standard component constitutively present in plasma other than sodium ion or chloride ion, it is preferable to select from total protein or albumin, and more preferably total protein. There are known methods for measuring total protein, such as the Buret method, ultraviolet absorption method, Breadford method, Lowry method, Bicinchoninic Acid (BCA) method, and fluorescence method. The method to be used can be appropriately 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 a standard component that does not exist in the blood. In this case, a blood test kit containing a diluted solution containing a standard component that is not present in blood is used.

100 Blood sampling device 110 Outer cylinder 112 Tip opening 114 Base end opening 116 Blood sample reservoir 116A Reservoir space 118 Outer cylinder body 118A Main body space 120 Bearing section 120A First bearing section 120B Second bearing section 121 Opening 122 Gear wheel 122A 1st gear 122B 2nd gear 124 Protective cover 124A Groove 124B Locking part 126 Groove part 130 Elastic member fixing part 130A Pin 132 Elastic member 132A Fixing part 132B Bending part 140 Opening 200 Release member 200A Opening 200B Protruding part 300 Rod-shaped member 310 Tip 312 Rubber member 314 Rear end surface 316 1st claw part 318 2nd claw part 330 Protruding part 400 Containment device 410 Blood collection container 412 Screw part 414 Locking part 416 Bottom part 418 Leg part 420 Slit groove 422 Diluting liquid 424 Cap 426 Packing 500 Holding device 510 Cylinder 512 Cap Piston 514 Sealing lid 516 Enlarged part 518 Thin-walled part 520 Main body part 522 Reduced diameter part 524 Locking protrusion 526 Outer flange part 528 Filtering membrane 530 Cover 532 Grip part 534 Mandrel part 536 Space 538 Lower end part 540 Step Part 542 Top part 544 Top part

Claims (7)

A blood sampling device used in blood test kits.
An outer cylinder having a blood sample reservoir in which the tip opening and the proximal opening are defined and communicate with the tip opening,
A rod-shaped member that can move in the outer cylinder in the axial direction, and a rod-shaped member that sucks a blood sample from the tip opening into the blood sample reservoir as it moves from the tip opening to the proximal opening.
A movement adjusting mechanism that enables the stepwise movement of the rod-shaped member from the tip opening to the proximal opening and regulates the movement of the rod-shaped member from the proximal opening to the distal opening.
It is a blood sampling device with
In order to restrict the movement of the rod-shaped member, the movement adjusting mechanism includes an elastic member fixed to the outer cylinder, a plurality of first claw portions formed of the rod-shaped member engaged with the elastic member, and the like.
A release member that lifts the restriction on the movement of the rod-shaped member, and
Blood sampling comprising a rotatable gear wheel and a plurality of second claws on which the rod-shaped member is formed that engages the gear wheel in order to move the rod-shaped member from the tip opening to the proximal end opening. Instrument . A blood sampling device used in blood test kits.
An outer cylinder having a blood sample reservoir in which the tip opening and the proximal opening are defined and communicate with the tip opening,
A rod-shaped member that can move in the outer cylinder in the axial direction, and a rod-shaped member that sucks a blood sample from the tip opening into the blood sample reservoir as it moves from the tip opening to the proximal opening.
A movement adjusting mechanism that enables the stepwise movement of the rod-shaped member from the tip opening to the proximal opening and regulates the movement of the rod-shaped member from the proximal opening to the distal opening.
It is a blood sampling device with
In order to restrict the movement of the rod-shaped member, the movement adjusting mechanism includes an elastic member fixed to the outer cylinder, a plurality of first claw portions formed of the rod-shaped member engaged with the elastic member, and the like.
A release member that lifts the restriction on the movement of the rod-shaped member, and
In order to move the rod-shaped member from the tip opening to the base end opening, a protrusion protruding from the outer cylinder on which the rod-shaped member is formed and an opening provided in the outer cylinder that allows the protrusion to move. A blood sampling device with and. The blood sampling device according to claim 1 or 2 , wherein the blood sample reservoir is removable. The blood sampling device according to any one of claims 1 to 3 , which has an anticoagulant inside the blood sample reservoir. The blood sampling device according to any one of claims 1 to 4 , wherein the blood sample reservoir is provided with a scale indicating the capacity of the blood sample. The blood collection device according to any one of claims 1 to 5 for collecting a blood sample, and the blood collection device.
Diluting solution for diluting the collected blood sample,
A containment device for accommodating diluted blood samples,
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 diluted solution. The blood test kit according to claim 6 , wherein the blood test kit includes a separation device for separating and recovering plasma from a diluted product of the blood sample.

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