Body fluid collection needle and body fluid collection device

Abstract

A body fluid collection needle according to the present invention comprises a base portion and a body portion having a needle-shape and protruding from the base portion, the body portion comprising a bottom end adjacent to the base portion, a tip positioned opposite to the base portion, and a side surface connecting the bottom end and the tip. The body portion has the shape tapered toward the tip from the bottom end. The body portion has a bottom end opening formed at the bottom end, a side surface opening formed on the side surface, and a through hole allowing communication between the bottom end opening and the side surface opening. The side surface opening comprises a first end positioned closest to the tip and a second end positioned closest to the bottom end. When the body portion is viewed from the side, the width W1 of the bottom end is 300-4000 μm, the distance X1 from the bottom end opening to the first end in the protruding direction of the body portion is 100-3900 μm, and the distance X2 from the second end to the first end in the protruding direction of the body portion is 10-3900 μm.

Description

Body fluid collection needle and body fluid collection device

[0001] The present invention relates to a body fluid collection needle and a body fluid collection device.

[0002] Conventionally, methods for collecting and analyzing blood or other samples have been known as methods for determining health conditions. Blood collection is performed using a syringe, which is very painful. From this perspective, minimally invasive methods are desired, and one such method is a device that uses fine microneedles to collect and analyze body fluids (see, for example, Patent Document 1).

[0003] Japanese Patent Application Laid-Open No. 2003-33336

[0004] From the viewpoint of minimal invasiveness, it is desirable for microneedles to be as small as possible, but if they are too small, the amount of bodily fluid collected may be insufficient. Conventional microneedles do not collect enough bodily fluid, and improvements are needed.

[0005] The present invention has been made to solve the above problems, and an object of the present invention is to provide a body fluid collection needle and device that can collect a sufficient amount of body fluid.

[0006] The present inventors have conducted extensive research to solve the above problems and have arrived at the present invention. That is, the present invention provides a body fluid collection needle comprising a base and a needle-shaped main body protruding from the base, wherein the main body has a bottom end on the base side, a tip end located on the opposite side of the base, and a side surface connecting the bottom end and the tip, the main body having a shape that gradually tapers from the bottom end to the tip, the main body having a bottom end opening formed at the bottom end, a side surface opening formed at the side surface, and a through hole communicating the bottom end opening and the side surface opening, The side opening has a first end located closest to the tip end and a second end located closest to the bottom end, and when the main body is viewed from the side, the width dimension W1 of the bottom end is 300 μm to 4000 μm, the distance X1 from the bottom end opening to the first end in the protruding direction of the main body is 100 μm to 3900 μm, and the distance X2 from the second end to the first end in the protruding direction of the main body is 10 μm to 3900 μm, making this a bodily fluid collection needle.

[0007] The present invention also provides a body fluid collection device comprising the body fluid collection needle of the present invention and a holding member that applies pressure to and holds the body fluid collection needle.

[0008] According to the present invention, it is possible to provide a body fluid collection needle and device that can collect a sufficient amount of body fluid.

[0009] FIG. 1A is a perspective view schematically showing an example of a body fluid collection needle of the present invention. FIG. 1B is a cross-sectional view taken along line A-A in FIG. 1A. FIG. 1C is an enlarged view of the dashed line portion in FIG. 1B. FIG. 2A is a flow chart sequentially showing an example of a method for manufacturing a body fluid collection needle of the present invention. FIG. 2B is a flow chart sequentially showing an example of a method for manufacturing a body fluid collection needle of the present invention. FIG. 2C is a flow chart sequentially showing an example of a method for manufacturing a body fluid collection needle of the present invention. FIG. 2D is a flow chart sequentially showing an example of a method for manufacturing a body fluid collection needle of the present invention. FIG. 2E is a flow chart sequentially showing an example of a method for manufacturing a body fluid collection needle of the present invention. FIG. 2F is a flow chart sequentially showing an example of a method for manufacturing a body fluid collection needle of the present invention. FIG. 2G is a flow chart sequentially showing an example of a method for manufacturing a body fluid collection needle of the present invention. FIG. 2H is a flow chart sequentially showing an example of a method for manufacturing a body fluid collection needle of the present invention. FIG. 2I is a flow chart sequentially showing an example of a method for manufacturing a body fluid collection needle of the present invention. Fig. 3 is a cross-sectional view schematically showing an example of a body fluid collection device of the present invention. Fig. 4A is an explanatory diagram of an example of use of the body fluid collection device of the present invention. Fig. 4B is an explanatory diagram of an example of use of the body fluid collection device of the present invention. Fig. 5 is a schematic diagram of a method for collecting interstitial fluid in evaluating the amount of collected interstitial fluid. Fig. 6 is a chart showing changes in ethanol concentration in interstitial fluid and blood over time in a test to confirm the correlation between ethanol concentration in interstitial fluid and ethanol concentration in blood.

[0010] The body fluid collection needle of the present invention will be specifically described below. However, the present invention is not limited to the following embodiments, and can be appropriately modified and applied within the scope of the present invention.

[0011] Fig. 1A is a perspective view schematically showing an example of a body fluid collection needle of the present invention, Fig. 1B is a cross-sectional view taken along line AA in Fig. 1A, and Fig. 1C is an enlarged view of the dashed line portion in Fig. 1B.

[0012] 1A and 1B includes a base 20 and a plurality of needle-shaped main bodies 30 protruding from the base 20. The surface of the base 20 is flat, and the main bodies 30 protrude in a first direction perpendicular to the surface (the direction indicated by arrow Z in FIGS. 1A and 1B).

[0013] The body fluid collection needle of the present invention may be formed with only one main body portion. Furthermore, the body fluid collection needle of the present invention may have a curved surface as its base. Furthermore, the body fluid collection needle of the present invention may have a protruding direction of the main body portion that is not perpendicular to the surface of the main body portion, but may be oblique to the surface of the main body portion. For example, the main body portion may be formed so that the protruding direction is at an angle of 30° or more and less than 90° relative to the surface of the main body portion.

[0014] 1A to 1C, the body fluid collection needle 10 has a main body 30 which has a bottom end 31 on the base 20 side, a tip 32 located on the opposite side of the base 20, and a side surface 33 connecting the bottom end 31 and the tip 32. The body 30 also has a shape which gradually tapers from the bottom end 31 to the tip 32. In the body fluid collection needle 10, the tip 32 is flat and formed parallel to the surface of the base 20. In other words, the body 30 has a truncated cone shape.

[0015] In the body fluid collection needle of the present invention, the tip does not have to be formed parallel to the surface of the base. Furthermore, in the body fluid collection needle of the present invention, the tip does not have to be flat, but may have a sharp, pointed shape.

[0016] In the body fluid collection needle of the present invention, the main body may be a truncated polygonal pyramid rather than a truncated cone. The main body may also be conical or pyramidal. Furthermore, the main body may have a shape that flares out toward the base.

[0017] As shown in FIG. 1C, in the body fluid collection needle 10, the main body 30 has a bottom end opening 41 formed at the bottom end 31, a side opening 42 formed at the side surface 33, and a through hole 40 connecting the bottom end opening 41 and the side opening 42.

[0018] The body fluid collection needle 10 is used so that the tip 32 of the main body 30 is inserted into the skin. The side opening 42 of the main body 30 reaches the dermis, and interstitial fluid enters the through-hole 40 from the side opening 42. The interstitial fluid then passes through the through-hole 40 by capillary action and reaches the bottom opening 41. This allows the interstitial fluid to be collected.

[0019] 1C extends linearly from the bottom end 31 to the side surface 33. In the body fluid collection needle of the present invention, the through hole does not have to be formed linearly, but may be curved.

[0020] Furthermore, although the body fluid collection needle 10 has one through-hole 40 formed in the main body 30, the body fluid collection needle of the present invention may have a plurality of through-holes formed in the main body.

[0021] In the body fluid collection needle 10, the inner diameter of the through hole 40 is preferably 5 μm to 700 μm, and more preferably 30 μm to 600 μm. When the inner diameter of the through hole 40 is within the above range, interstitial fluid can be suitably collected.

[0022] As shown in Figure 1C, in the body fluid collection needle 10, the through hole 40 is formed along the first direction Z. That is, the axis 40a of the through hole 40 is parallel to the first direction Z. Note that in the body fluid collection needle of the present invention, the through hole 40 does not have to be formed along the first direction Z. For example, the through hole may be formed so that the axis 40a of the through hole is at an angle of 30° to 90° with respect to the first direction Z.

[0023] In the body fluid collection needle 10, the axis of the main body 30 is preferably misaligned with the axis 40a of the through hole. Alternatively, the axis of the main body 30 and the axis 40a of the through hole may intersect, for example, at the bottom end 31.

[0024] As shown in FIG. 1C, in the bodily fluid collection needle 10, the side opening 42 has a first end 42a located closest to the tip 32 and a second end 42b located closest to the bottom end 31.

[0025] In the body fluid collection needle 10, the width dimension W1 of the bottom end 31 when the main body 30 is viewed from the side is 300 μm to 4000 μm. The width dimension W1 is preferably 550 μm to 3000 μm, more preferably 750 μm to 3000 μm, and even more preferably 1000 μm to 2000 μm. If the width dimension W1 is less than 300 μm, the main body becomes thin and therefore prone to breaking. If the width dimension W1 exceeds 4000 μm, the main body is prone to coming off when piercing the skin.

[0026] In the bodily fluid collection needle 10, when the main body portion 30 is viewed from the side, the width dimension W2 of the main body portion is 50 μm to 500 μm at a position H1 that bisects the distance X3 from the bottom end 31 to the tip 32 of the main body portion 30 in the protrusion direction Z of the main body portion 30. The width dimension W2 is preferably 50 μm to 400 μm, and more preferably 150 μm to 250 μm. If the width dimension W2 is less than 50 μm, the main body portion becomes thin and therefore prone to breaking. If the width dimension W2 exceeds 500 μm, the main body portion is prone to coming out when piercing the skin. Note that if the width dimension W2 is 50 μm to 400 μm, pain when piercing the skin with the main body portion can be reduced.

[0027] In the body fluid collection needle 10, the ratio of the width dimension W1 to the width dimension W2 (W1 / W2) is preferably greater than 1.0 and equal to or less than 80, and more preferably 5.0 to 15.

[0028] In the body fluid collection needle 10, when the main body 30 is viewed from the side, the width W3 of the tip 32 is preferably 0 μm to 100 μm, and more preferably 20 μm to 50 μm. Note that a width W3 of 0 μm means that the tip does not have a flat surface and the tip 32 is sharply pointed. If the width W3 exceeds 100 μm, pain is likely to occur when the main body pierces the skin.

[0029] In the body fluid collection needle 10, the distance X1 from the bottom end opening 41 to the first end 42a in the protruding direction Z of the main body 30 is 100 μm to 3900 μm. The distance X1 is preferably 100 μm to 2900 μm, and more preferably 600 μm to 2000 μm. If the distance X1 is less than 100 μm, it will be difficult for the main body to reach the dermis when piercing the skin, making it difficult to collect interstitial fluid. If the distance X1 exceeds 3900 μm, the main body will be prone to breaking.

[0030] In the body fluid collection needle 10, the distance X2 from the second end 42b to the first end 42a in the protrusion direction Z of the main body 30 is 10 μm to 3900 μm. The distance X2 is preferably 10 μm to 2900 μm, and more preferably 200 μm to 1000 μm. If the distance X2 is less than 10 μm, the diameter of the through hole becomes small, making it difficult to collect interstitial fluid. If the distance X2 exceeds 3900 μm, the diameter of the through hole becomes large, reducing the amount of material that constitutes the main body, making the main body more likely to break.

[0031] In the body fluid collection needle 10, the distance X3 is preferably 500 μm to 4000 μm, and more preferably 1000 μm to 3000 μm. If the distance X3 is less than 500 μm, it will be difficult for the main body portion to reach the dermis when piercing the skin, making it difficult to collect interstitial fluid. If the distance X3 exceeds 4000 μm, the main body portion will be prone to breaking.

[0032] In the body fluid collection needle 10, it is more preferable that the distance X1 is 100 μm to 2900 μm and the distance X2 is 10 μm to 2900 μm. In this case, it is even more preferable that the width dimension W2 is 50 μm to 400 μm. If the distances between the various parts of the main body 30 are within the above ranges, pain when the main body 30 is pierced into the skin can be further reduced.

[0033] In the body fluid collection needle 10, the ratio of the distance X1 to the distance X3 (X1 / X3) is preferably 0.03 to 0.98, and more preferably 0.03 to 0.96. When the ratio of the distance X1 to the distance X3 is within the above range, pain when the main body portion is pierced into the skin can be reduced. In this case, it is more preferable that the width dimension W2 is 50 μm to 400 μm.

[0034] There are no particular limitations on the arrangement of the main bodies 30 in the body fluid collection needle 10. For example, when the body fluid collection needle 10 is viewed in plan, the main bodies 30 may be arranged at the vertices of a square lattice, the main bodies 30 may be arranged at the vertices of a rectangular lattice, or the main bodies 30 may be arranged at each vertex of a triangle or other polygonal tessellation. Furthermore, when the body fluid collection needle 10 is viewed in plan, the main bodies 30 may be arranged in a circular or elliptical shape.

[0035] In the body fluid collection needle 10, the material of the main body 30 is not particularly limited, but it is preferable that it be made of various inorganic materials such as metals such as aluminum and stainless steel alloys, silicon, carbon, ceramics, and various mineral materials including calcium-based minerals, or organic polymer compounds.

[0036] The polymer compound may be any known compound (synthetic polymer or natural polymer), such as polyethylene terephthalate (PET), polyethylene, polypropylene, acrylic resin, epoxy resin, polystyrene, or other plastic materials, as well as bioabsorbable polymers.

[0037] Known compounds (synthetic polymers and natural polymers) can be used as bioabsorbable polymers. For example, ester compounds such as polylactic acid, polyglycolic acid, poly-ε-caprolactone, poly-ρ-dioxane, and polymalic acid, acid anhydrides such as polyacid anhydrides, orthoester compounds such as polyorthoesters, carbonate compounds such as polycarbonates, phosphazene compounds such as polydiaminophosphazene, peptide compounds such as synthetic polypeptides, phosphate ester compounds such as polyphosphoesterurethanes, carbon-carbon compounds such as polycyanoacrylates, ester compounds such as poly-β-hydroxybutyric acid and polymalic acid, polyamino acids, chitin, chitosan, hyaluronic acid, sodium hyaluronate, pectinic acid, galactan, and dendritic cells. Examples of suitable polysaccharides include glycoside compounds (polysaccharides) such as gluten, dextran, dextrin, alginic acid, sodium alginate, cellulose compounds (ethyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose), gelatin, agar, keltrol, rheosan, xanthan gum, pullulan, and gum arabic, peptide compounds (peptides, proteins) such as collagen, gelatin, fibrin, gluten, and serum albumin, phosphate ester compounds (nucleic acids) such as deoxyribonucleic acid and ribonucleic acid, and vinyl compounds such as polyvinyl alcohol.

[0038] In the bodily fluid collection needle 10, the preferred material for the base portion 20 is the same as the preferred material for the body portion 30.

[0039] In the bodily fluid collection needle 10, the base portion 20 and the body portion 30 are preferably made of the same material.

[0040] Furthermore, in the body fluid collection needle 10, the base portion 20 and the main body portion 30 may be integrally molded, or each member may be molded separately and then connected.

[0041] Next, a method for manufacturing the body fluid collection needle of the present invention will be described. The body fluid collection needle of the present invention may be molded, for example, by injection molding using a metal mold, by using a casting mold, or by using a 3D printer. Furthermore, after molding a main body portion without a through hole, the through hole may be formed by laser processing or the like, or the main body portion with the through hole may be molded all at once.

[0042] Hereinafter, a method for manufacturing a body fluid collection needle using a mold will be exemplified, and the method for manufacturing a body fluid collection needle of the present invention will be described.

[0043] 2A to 2I are process diagrams sequentially illustrating an example of a method for manufacturing a body fluid collection needle according to the present invention.

[0044] In the method for manufacturing a body fluid collection needle of the present invention, first, as shown in FIG. 2A, a substrate S is coated with a resin 50 for microneedles using a spin coater.

[0045] Next, as shown in Figure 2B, a pulling-up member 60 is prepared on which pillars 61 are formed in a predetermined arrangement. Then, the microneedle resin 50 is made fluid, and the pulling-up member 60 is positioned so that the pillars 61 contact the microneedle resin 50. Making the microneedle resin 50 fluid means, for example, raising the temperature to the melting point when the resin 50 is a thermoplastic resin. The pulling-up member 60 can also be produced using a 3D printer or the like.

[0046] Next, the resin for microneedles 50 is made viscous, the pillars 61 of the pulling-up member 60 are brought into contact with the resin for microneedles 50, and then the pulling-up member 60 is pulled upward as shown in Fig. 2C. As a result, the resin for microneedles 50 is pulled by the pulling-up member 60 and stretched. The resin for microneedles 50 is then cured, and the constricted portion of the resin for microneedles 50 is cut off.

[0047] As a result, the microneedle 51 shown in FIG. 2D is produced.

[0048] The dimensions and shape of the microneedle 51 can be adjusted by changing the viscosity, pulling speed, and pulling distance of the microneedle resin 50 when pulling up the microneedle resin 50. By adjusting the dimensions and shape of the microneedle 51, it is possible to adjust the dimensions and shape of the main body of the body fluid collection needle obtained through subsequent processes.

[0049] Next, as shown in FIG. 2E, the microneedle 51 is turned upside down and placed in a container 70, a mold resin 80 is poured into the container 70, and the mold resin 80 is cured.

[0050] Next, the microneedles 51 are removed to create a mold 81 as shown in FIG. 2F.

[0051] Next, as shown in FIG. 2G, a resin 10a for needles is poured into a mold 81.

[0052] The needle resin 10a is then hardened and removed from the mold 81, thereby producing a bodily fluid collection needle 10' having a base 20 and a main body 30' without a through hole, as shown in Figure 2H.

[0053] Next, as shown in FIG. 2I, a through-hole 40 is formed in the main body 30' of the body fluid collection needle 10' using a laser L, thereby manufacturing the body fluid collection needle 10.

[0054] Next, a description will be given of the body fluid collection device of the present invention, which is equipped with the body fluid collection needle of the present invention.

[0055] Fig. 3 is a cross-sectional view schematically showing an example of a body fluid collection device of the present invention. The body fluid collection device 1 shown in Fig. 3 comprises a cylindrical housing 5, a rod-shaped pressure ring 2 arranged inside the housing 5, a spring 3 for moving the pressure ring 2 up and down within the housing 5, a needle fixing jig 4 arranged at the tip of the pressure ring 2 so as to be exposed from one end of the housing 5, and a body fluid collection needle 10 fixed to the needle fixing jig 4.

[0056] In the body fluid collection device 1, the pressure ring 2, spring 3, needle fixing jig 4 and housing 5 are holding members for pressurizing and holding the body fluid collection needle, and the body fluid collection needle 10 is detachable.

[0057] In the body fluid collection device 1, the pressure ring 2 to which the body fluid collection needle 10 is fixed can be pulled upward by contracting the spring 3, and the pressure ring 2 can be moved downward by releasing the contracted spring 3.

[0058] Next, a method for collecting body fluids using such a body fluid collection device will be described. Figure 4A is an explanatory diagram of an example of using the body fluid collection device of the present invention. Figure 4B is an explanatory diagram of an example of using the body fluid collection device of the present invention.

[0059] When using the body fluid collection device 1, first, as shown in Figure 4A, the spring 3 is contracted and the pressure ring 2 is pulled upward. Then, the end of the housing 5 on which the body fluid collection needle 10 is located is pressed against the skin.

[0060] 4B, the spring 3 is then released, causing the body fluid collection needle 10 to move downward and puncture the skin. The pressure ring 2 is then pushed in, applying pressure to the area around the body fluid collection needle 10, allowing the body fluid to be collected.

[0061] This specification describes the following inventions:

[0062] The present invention (1) is a bodily fluid collection needle comprising a base and a needle-shaped main body protruding from the base, wherein the main body has a bottom end on the base side, a tip located on the opposite side of the base, and a side surface connecting the bottom end and the tip, the main body having a shape that gradually narrows from the bottom end to the tip, the main body having a bottom end opening formed at the bottom end, a side surface opening formed at the side surface, and a through hole that communicates the bottom end opening and the side surface opening, The bodily fluid collection needle is characterized in that the face opening has a first end located closest to the tip end and a second end located closest to the bottom end, the width dimension W1 of the bottom end is 300 μm to 4000 μm when the main body is viewed from the side, the distance X1 from the bottom end opening to the first end in the protruding direction of the main body is 100 μm to 3900 μm, and the distance X2 from the second end to the first end in the protruding direction of the main body is 10 μm to 3900 μm.

[0063] The present invention (2) is the body fluid collection needle according to the present invention (1), wherein the distance X1 is 100 μm to 2900 μm, and the distance X2 is 10 μm to 2900 μm.

[0064] The present invention (3) is a bodily fluid collection needle according to the present invention (1) or (2), in which, when the main body is viewed from the side, the width dimension W2 of the main body is 50 μm to 500 μm at a position that bisects the distance X3 from the bottom end of the main body to the tip in the protruding direction of the main body.

[0065] The present invention (4) is the body fluid collection needle according to the present invention (3), wherein the width dimension W2 is 50 μm to 400 μm.

[0066] The present invention (5) is the body fluid collection needle according to the present invention (3) or (4), wherein the ratio (X1 / X3) of the distance X1 to the distance X3 is 0.03 to 0.98.

[0067] The present invention (6) is the body fluid collection needle according to any one of the present inventions (3) to (5), wherein the width dimension W1 is 550 μm to 4000 μm.

[0068] The present invention (7) is a bodily fluid collection device comprising the bodily fluid collection needle according to any one of the present inventions (1) to (6) and a holding member that applies pressure to and holds the bodily fluid collection needle.

[0069] The present invention will now be described in detail with reference to examples, but the present invention is not limited to these examples as long as they do not depart from the gist of the present invention.

[0070] Example 1 Using a spin coater (Opticoat MS-A100, manufactured by MIKASA Corporation), an epoxy resin SU-8 3050 (manufactured by Nippon Kayaku Co., Ltd.) was coated onto a glass substrate (26×76 mm, thickness 1.5 mm) at 1000 rpm for 30 seconds.

[0071] A 3D printer (Anycubic Photon M3 Plus, manufactured by Anycubic) was used to fabricate a lifting member with pillars. The lifting member had a shape of a 10 × 10 mm, 1 mm thick flat plate with cylindrical pillars having a diameter of 0.45 mm arranged at the vertices of a square lattice spaced 2 mm apart.

[0072] The SU-8 on the glass substrate was held at 120°C for 15 minutes. After that, the outermost surface of the pillar of the pulling member was brought into contact with the SU-8, and then cooled at a rate of 20°C / min. When the temperature reached 60°C, it was pulled up 2000µm at a rate of 25µm / sec. After that, it was left to stand at 25°C for 20 minutes, and then the constricted portion of the SU-8 was cut to prepare a microneedle.

[0073] Next, the obtained microneedles were placed in a glass petri dish, and SYLGARD 184 (manufactured by DAW SLICONES) was poured into the dish at a ratio of base agent: curing agent = 10: 1, and the dish was cured at 100 ° C. for 30 minutes. After that, the microneedles were peeled off, and a mold made of PDMS (polydimethylsiloxane) to which the shape of the microneedles was transferred was prepared.

[0074] 1 g of polylactic acid (Musashino Chemical Co., Ltd.) was placed in a mold, and after adjusting the temperature to 240°C using a nanoimprinting device (SCIVAX Corporation), it was pressed for 5 minutes with a load of 10 N. It was then cooled to 25°C, and the cured product was removed from the mold to produce a body fluid collection needle with a main body portion without a through-hole.

[0075] Next, using a femtosecond laser (Pharos, manufactured by PhotoTechnica Corporation), laser light was irradiated from the back side of the body fluid collection needle, which had a main body portion without a through hole, to form a through hole with an inner diameter of 40 μm at a position 50 μm away from the central axis of the main body portion.

[0076] The above steps were used to manufacture the body fluid collection needle according to Example 1. The sizes of the main body and through-hole of the body fluid collection needle according to Example 1 are shown in Table 1.

[0077] The dimensions of the body and through-hole of the obtained body fluid collection needle according to Example 1 are shown in Table 1.

[0078] (Examples 2) to (Example 16) and (Comparative Examples 1) to (Comparative Examples 13) Body fluid collection needles according to Examples 2 to 16 and Comparative Examples 1 to 13 were manufactured in the same manner as in Example 1, except that the dimensions of the main body and the through-hole were adjusted as shown in Tables 1 and 2.

[0079]

[0080]

[0081] (Evaluation of Interstitial Fluid Collection Amount) Figure 4 is a schematic diagram of the interstitial fluid collection method for evaluating the interstitial fluid collection amount. The body fluid collection needles according to each Example and Comparative Example were punctured into the skin of a subject at a puncture pressure of 9 N and a puncture speed of 240 mm / sec. Next, as shown in Figure 4, a resin pressure ring 2 with an outer diameter of 9 mm, an inner diameter of 7 mm, and a height of 10 mm was placed around the body fluid collection needle 10, and pressure was applied at 10 N for 30 seconds.

[0082] The entire amount of interstitial fluid that had leaked out of the skin through the through-holes 40 was then collected using a moisture test strip. The amount of interstitial fluid that had leaked out of the skin was measured based on the area of ​​the color-changed portion of the moisture test strip. That is, a known, predetermined amount of water was absorbed into the moisture test strip, and a calibration curve was created based on the area of ​​the color-changed portion of the moisture test strip. The calibration curve was then compared with the color-changed portion of the moisture test strip that had absorbed the interstitial fluid, and the amount of interstitial fluid that had leaked out of the skin was calculated. The area of ​​the color-changed portion of the moisture test strip was measured using image analysis software ImageJ. The results are shown in Tables 1 and 2.

[0083] (Evaluation of pain) The subjects were also asked about the pain they felt when the body fluid collection needle was inserted into their skin. The evaluation criteria were as follows: 1: No pain, 2: Slight pain, 3: Painful (unwilling to use). The results are shown in Tables 1 and 2.

[0084] As shown in Tables 1 and 2, it was found that the body fluid collection needles according to each example were capable of collecting interstitial fluid and caused little pain.

[0085] <Test to confirm the correlation between ethanol concentration in interstitial fluid and blood> A phosphate buffer solution containing 15% v / v ethanol was administered into the blood of a pig (female, 2 months old, weighing 28.9 kg, obtained from Tokyo Experimental Animals Co., Ltd.) at a rate of 50 ml / h for 3 hours. Interstitial fluid was collected using the body fluid collection needle of Example 4 at the start of administration and every hour thereafter. Blood was also collected at the same time using a blood collection syringe. The ethanol concentrations in the collected interstitial fluid and blood were quantified using an enzyme-containing sensor. The results are shown in Figure 6. Figure 6 is a chart showing the changes in ethanol concentration in the interstitial fluid and blood over time in the test to confirm the correlation between ethanol concentration in interstitial fluid and blood.

[0086] As shown in Figure 6, it was found that there is a correlation between the ethanol concentration in interstitial fluid and the ethanol concentration in blood. In other words, it was suggested that by collecting interstitial fluid using the body fluid collection needle according to Example 1, it is possible to measure the concentrations of components such as biomarkers and drugs in a living body.

[0087] The body fluid collection needle of the present invention can be used for collecting body fluids. Furthermore, the body fluid collection needle of the present invention can be used as a biosensor by arranging a member having a sensor function in the through-hole.

[0088] REFERENCE SIGNS LIST 1 Body fluid collection device 2 Pressure ring 3 Spring 4 Needle fixing jig 5 Housing 10, 10' Body fluid collection needle 10a Needle resin 20 Base 30, 30' Main body 31 Bottom end 32 Tip 33 Side 40 Through hole 40a Axis of through hole 41 Bottom end opening 42 Side opening 42a First end 42b Second end 50 Microneedle resin 51 Microneedle 60 Pulling member 61 Pillar 70 Container 80 Mold resin 81 Mold

Claims

1. A bodily fluid collection needle comprising a base and a needle-shaped main body protruding from the base, wherein the main body has a bottom end on the base side, a tip located on the opposite side of the base, and a side surface connecting the bottom end and the tip, the main body having a shape that gradually tapers from the bottom end to the tip, the main body having a bottom end opening formed at the bottom end, a side opening formed at the side surface, and a through hole connecting the bottom end opening and the side opening, the side opening having a first end located closest to the tip and a second end located closest to the bottom end, when the main body is viewed from the side, the width dimension W1 of the bottom end is 300 μm to 4000 μm, and the distance X1 from the bottom end opening to the first end in the protruding direction of the main body is 100 μm to 3900 μm, A body fluid collection needle, characterized in that a distance X2 from the second end to the first end in a protruding direction of the main body portion is 10 μm to 3900 μm.

2. The body fluid collection needle according to claim 1, wherein the distance X1 is 100 μm to 2900 μm, and the distance X2 is 10 μm to 2900 μm.

3. A body fluid collection needle as described in claim 1 or 2, wherein, when the main body is viewed from the side, the width dimension W2 of the main body is 50 μm to 500 μm at a position that bisects the distance X3 from the bottom end of the main body to the tip in the protruding direction of the main body.

4. The body fluid collection needle according to claim 3, wherein the width dimension W2 is 50 μm to 400 μm.

5. The body fluid collection needle according to claim 3, wherein the ratio (X1 / X3) of the distance X1 to the distance X3 is 0.03 to 0.

98.

6. The body fluid collection needle according to claim 3, wherein the width dimension W1 is 550 μm to 4000 μm.

7. A bodily fluid collection device comprising the bodily fluid collection needle according to claim 1 or 2 and a holding member that applies pressure to and holds the bodily fluid collection needle.

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