JP2004208949A - Puncturing needle and puncturing device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a puncturing needle for quickly and safely sampling body fluid without inflicting pains, and a puncturing device using it. <P>SOLUTION: In this puncturing needle, a cylindrical needle body 202 is formed on a base 201, and a linear recessed part 203 having a width and a depth equal to or less than the half of the diameter of the needle body 202 is formed in the outer peripheral part thereof. The body fluid such as blood is held or passed to the outside of the skin by the linear recessed part to efficiently perform sampling. The diameter of the puncturing needle is 10 to 60 μm and the ratio of diameter to length of the puncturing needle is 1:2 to 1:20. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
TECHNICAL FIELD The present invention relates to a puncture needle used for collecting blood or body fluid from a living body and a puncture device using the same.
[0002]
[Background Art]
With the increase in sensitivity and miniaturization of the analyzer, necessary and sufficient analysis information can be obtained with a very small amount of sample. In particular, in the microanalysis of biological components such as blood, valuable information for health management and disease diagnosis can be obtained. Individuals and medical institutions can be simplified with the advancement of μ-TAS (Total Analysis System) and Lab on a chip technology. Biological information can be obtained.
[0003]
As a sampling method for collecting blood or body fluid from a living body, a method using an injection needle is generally used, but a painful puncture causes a pain, and thus a more comfortable and less anxious sampling method is desired. For example, Patent Document 1 discloses an apparatus and a method for sampling blood using a hollow microneedle. Similarly, Patent Literature 2 discloses a device that includes a plurality of hollow needles having a small diameter and that collects blood by changing the pressure in the hollow needle.
[0004]
Non-Patent Document 1 discloses a painless needle in which a hollow stainless steel tube having an outer diameter of 70 μm is nitrided and hardened, the tip of which is polished by chemical mechanical polishing, and further sharpened by electrolytic polishing.
[0005]
Patent Literature 3 discloses a blood collection needle having a beveled surface and a slit formed in a longitudinal direction of the blood collection needle in a tubular blood collection needle having a beveled surface for the purpose of causing blood to exudate onto the skin painlessly.
[0006]
Patent Documents 4 to 8 disclose a hollow microneedle array and a method for manufacturing the same. Further, Patent Document 9 discloses a hollow or porous microneedle using a micromold.
[0007]
The above is an apparatus or method for puncturing skin with a needle to collect blood or the like. Patent Documents 10 to 11 disclose apparatuses for aspirating and collecting body fluid without puncturing.
[0008]
[Patent Document 1]
JP 2001-258868 A
[Patent Document 2]
Japanese Patent Application Laid-Open No. 07-132119 [Patent Document 3]
JP 08-187237 A [Patent Document 4]
US Pat. No. 6,256,533 [Patent Document 5]
US Pat. No. 6,326,612 [Patent Document 6]
US Pat. No. 6,379,324 [Patent Document 7]
US Pat. No. 6,451,240 [Patent Document 8]
US Pat. No. 6,471,903 [Patent Document 9]
US Pat. No. 6,334,856 [Patent Document 10]
Japanese Patent Application Laid-Open No. 04-060208 [Patent Document 11]
US Pat. No. 6,340,354 [Non-Patent Document 1]
A. OKI et. al, "Electrophoresis" 22, (2001), p. 341,
[0009]
[Problems to be solved by the invention]
The present invention has been made in view of such problems of the related art, and in a puncture needle used for collecting blood or body fluid from a living body, almost no puncture needle is used without using a conventional hollow puncture needle. An object of the present invention is to provide a puncture needle that can quickly and safely collect a bodily fluid without feeling pain, and a puncture device using the puncture needle.
[0010]
[Means for Solving the Problems]
That is, the present invention relates to a puncture needle for puncturing a living body with a needle to collect a bodily fluid, wherein the needle body is located on an outer surface of the needle body, and after puncturing the needle body into a living body, the needle body A puncture needle comprising: a body fluid adhering section for removing the body fluid in a state where the body fluid adheres to the puncture needle.
[0011]
It is preferable that the body fluid attachment portion of the puncture needle has a concave portion for containing the body fluid to be attached.
It is preferable that the tip of the needle main body of the puncture needle is closed.
It is preferable that the diameter of the puncture needle is 10 to 60 μm, and the ratio between the diameter and the length of the puncture needle is 1: 2 to 1:20.
[0012]
Further, the present invention is a puncture device comprising the puncture needle described above, and a puncture force applying means for applying a force for puncturing a living body to the puncture needle.
[0013]
The puncture needle of the device preferably further includes a sampling unit for sampling a body fluid attached to the body fluid attachment unit.
It is preferable that the collection unit of the device applies a negative pressure to the body fluid attachment portion of the puncture needle to collect the body fluid attached to the body fluid attachment portion.
It is preferable that the collecting means of the device collects the bodily fluid attached to the body fluid adhering portion by applying a physical force to the body fluid adhering portion of the puncture needle.
It is preferable that the physical force is a force when blowing a gas to the body fluid attaching portion.
It is preferable that the physical force is a force for wiping body fluid attached to the body fluid attaching portion.
[0014]
Next, a preferred embodiment of the puncture needle of the present invention will be described.
The puncture needle of the present invention is a liquid in the body of a human body, an animal, or the like, and is used to take out bodily fluids such as blood, lymph, tissue fluid, etc. out of the skin. The puncture needle has a diameter of 10 to 60 μm, The ratio between the diameter and the length of the needle is 1: 2 to 1:20.
[0015]
The body fluid attachment portion of the puncture needle has one or more linear grooves having a width and a depth equal to or less than half the diameter of the puncture needle in the length direction of the puncture needle in the outer peripheral portion of the puncture needle. Are preferred. Further, it is preferable that at least one spiral groove having a width and a depth equal to or less than half the diameter of the puncture needle is formed in an outer peripheral portion of the puncture needle in a length direction of the puncture needle.
[0016]
The piercing end of the puncture needle that pierces the skin is preferably cylindrical, conical or beveled.
It is preferable that the puncture needle is connected to means for storing, pretreating, concentrating, separating, and detecting a sample, and is formed integrally with the puncture device.
[0017]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, the present invention will be described in detail.
Pain when a needle is punctured into the skin is a sensation of pain points scattered on the skin, and it is said that there are 100 to 200 pain points per square cm of skin. The pain at the time of puncturing is a great stress for the subject, and there is a strong demand for less painful or painless sampling. Although there are several methods and devices for reducing pain as described in the background art, methods that are essentially painless can be broadly classified into sampling that does not stimulate pain or paralysis of pain.
[0018]
On the other hand, for quick and safe sampling, it is desirable not to perform any special pretreatment on the subject or the living body. Therefore, the sampling apparatus and method for preparing a needle smaller than the pain point interval of the skin and using the needle for collecting body fluid such as blood can collect a biological sample with substantially no pain and less stress.
[0019]
However, the painless or painless puncture needles disclosed so far are hollow fine needles and require a sufficient hollow diameter to sample a biological sample through the hollow part of the needle. Further, the mechanical strength of the needle is required to prevent the needle from breaking at the time of puncturing. For this purpose, it is desired to produce a hollow tube having a sufficient thickness with a hard material. In order to satisfy the required performance as such a puncture needle, it is difficult to use an extremely thin hollow tube of 50 μm or less, and it is also difficult to produce such a hollow tube in terms of process. .
[0020]
In order to solve such problems, the puncture needle of the present invention has a concave portion for holding and passing bodily fluids such as blood in the outer peripheral portion of the puncture needle without using a hollow tube, which makes it conventionally difficult. An object of the present invention is to provide a fine puncture needle.
[0021]
As a more specific shape of the puncture needle, the puncture needle has a diameter of 10 to 60 μm and a ratio of the diameter to the length of 1: 2 to 1:10.
[0022]
Further, the cross-sectional shape of the concave portion provided on the outer peripheral portion of the puncture needle is a puncture needle in which the width and the depth are not more than half of the diameter of the puncture needle and one or more linear concave portions are formed. Alternatively, a puncture needle having a recess having a similar cross-sectional shape formed in a spiral shape on the outer peripheral portion of the puncture needle may be used. Further, when the diameter of the puncture needle is 50 μm or less, the pierced end may be cylindrical, but if the pierced end is conical, it is possible to perform sampling with less pressure when puncturing.
[0023]
These puncture needles can be produced directly by, for example, dry etching of a silicon substrate. Alternatively, a columnar structure can be formed on a substrate by electrolytic plating using a photoresist or the like as a mold. A puncture needle having a more complicated structure, for example, a puncture needle having a spiral concave portion, can be manufactured by using a stereolithography method. Furthermore, a puncture needle having a desired shape can be produced by forming a mold by stereolithography and finally by electrolytic plating.
[0024]
Next, the present invention will be described with reference to the drawings.
FIG. 1 is a schematic view showing an example of the puncture needle of the present invention. In the puncture needle of the present invention, a cylindrical needle body 102 is formed on a substrate 101, the diameter of the needle body 102 is 10 to 60 μm, and the ratio of the diameter to the length of the needle body 102 is 1: 2 to 1 : 20 is desirable. The needle body 102 pierced into the skin holds body fluid such as blood on its surface, and the body fluid can be taken out by extracting the needle body 102. Note that the base 101 is for holding the needle body 102, and its shape does not need to be particularly disk-shaped, and an optimum shape is selected for the manufacturing process and the purpose of use.
[0025]
FIG. 2 is a schematic view showing another example of the puncture needle of the present invention. FIG. 2 shows an example of a puncture needle in which a straight concave portion 203 is formed on the outer peripheral portion of the needle main body 202. In the puncture needle, a cylindrical needle body 202 is formed on a base 201 similarly to FIG. 1, and a linear concave portion 203 having a width and a depth equal to or less than half the diameter of the needle body 202 is formed on the outer periphery thereof. Have been. A biological sample such as blood can be held or passed out of the skin by the linear concave portion, and sampling can be performed efficiently. The width and depth of the linear concave portion 203 are designed so that the mechanical strength of the needle body 202 can be sufficiently secured practically and a required amount of sample can be collected.
[0026]
FIG. 3 is a schematic view showing another example of the puncture needle of the present invention. FIG. 3 shows an example of a puncture needle in which a spiral concave portion 303 is formed on the outer peripheral portion 304 of the needle main body 302. The puncture needle has a cylindrical needle main body 302 formed on a base body 301 as in FIG. 1, and a helical recess 303 having a width and a depth equal to or less than half the diameter of the needle main body 302 on an outer peripheral portion 304 thereof. Is formed.
[0027]
FIG. 4 is a schematic view showing another example of the puncture needle of the present invention. FIG. 4 shows an example of a puncture needle in which the tip 405 of the needle main body 402 is processed into a conical shape. In the puncture needle, a needle body 402 having an isotropic etching surface 404 whose tip 405 is conically pointed is formed on a base 401 similarly to FIG. A linear or spiral concave portion 403 having a width and a depth is formed.
[0028]
As the material of the puncture needle, an inorganic material such as silicon, nickel, or chromium, or an organic material such as polystyrene or polymethyl methacrylate can be used. In addition, it is non-toxic because it is directly punctured into a living body, it does not change its material due to autoclave heating, ultraviolet irradiation, or γ-ray irradiation so that it can be sterilized. It is desired to be a manufacturing process. In addition, it is desirable that the surface of the puncture needle is hydrophilically processed.
[0029]
If necessary, only the surface of the puncture needle can be coated using a dipping method or a sputtering method.
[0030]
Next, the puncture device of the present invention will be described.
A puncture device according to the present invention includes the puncture needle described above, and a puncture force applying unit for applying a force to puncture a living body to the puncture needle.
[0031]
Specifically, the puncture device of the present invention is not a hollow needle but a rod-shaped cross-section having a very small diameter in order to make the puncture needle as painless as possible, and is provided on the outer surface of the needle when pulled out after puncture. The method is characterized in that a body fluid such as blood is made to adhere to the recessed portion or the hydrophilic processed portion, and the body fluid is transferred to the biochip.
[0032]
The puncture device of the present invention includes a collection unit that collects blood from a living body, a filtration unit that obtains plasma by filtering at least the collected blood or a separation unit that separates serum from the blood, and analyzes substances in the blood. Analysis means, flow path means connecting those means, moving means for moving the components of blood present in each of these means, and output means for extracting information from the analysis means to the outside, The apparatus includes control means for controlling the operation of at least one of the means, holding means for holding the components of the blood in the substrate, and the like.
[0033]
FIG. 5 is a schematic view showing an example of the puncture device of the present invention. The device shown in FIG. 5 introduces blood into a microcapillary 503 on a quartz substrate 501 via a puncture needle 502 for collecting blood. At this time, the anticoagulant (sodium citrate, EDTA, heparin, etc.) stored in the liquid reservoir 504 is appropriately supplied to the capillary 503 by pressing the rubber stopper 505 so that blood does not coagulate in the capillary 503. Good. Next, the blood is introduced into the filtering means 506 to separate plasma and blood cells from the blood. The separated plasma is introduced into the analysis means 507. It is introduced into the analysis means 507 by an electroosmotic flow generated by applying an electric field between the electrodes 508 and 509, and detects the concentration of pH, sodium ion, potassium ion, glucose and the like in plasma. In the figure, a plurality of analysis means are provided, and it is possible to analyze the concentrations of the respective components at once.
[0034]
In the present invention, the bodily fluid attached to the body fluid attaching portion of the puncture needle is supplied to the puncture device by using a sampling unit. The collecting means can be performed by applying a negative pressure to the body fluid attaching portion of the puncture needle, applying a physical force, or utilizing a force when blowing gas. It is preferable that the physical force is a force at the time of wiping the body fluid attached to the body fluid attaching portion.
[0035]
The puncture needle of the present invention can be reused by washing after being used once. A denaturant is used as the washing liquid for the puncture needle when reused, and examples of the denaturant include sodium, potassium, lithium or ammonium salts of thiocyanic acid, guanidinium hydrochloride, guanidinium derivative hydrochloride, and urea. Used. Such a modifying agent is preferably used in combination with a surfactant. As the surfactant, a twin or triton-based nonionic surfactant or sodium deoxycholate is used. As the buffer, a phosphate buffer, a Tris buffer, an acetate buffer, or the like is used.
[0036]
【Example】
Hereinafter, the present invention will be described in more detail with reference to Examples.
Note that the dimensions, shapes, materials, and manufacturing process conditions in the following examples are merely examples, and can be arbitrarily changed as design items within a range that satisfies the requirements of the present invention.
[0037]
Example 1
In this example, the puncture needle shown in FIG. 1 was manufactured.
First, a silicon substrate was prepared as a base.
Next, a photoresist (AZ-P4620: manufactured by Clariant) was applied to the silicon substrate by a spin coating method so as to have a thickness of 8 μm. The photoresist was baked, exposed, and developed to form a circular resist pattern having a diameter of 10 μm on a silicon substrate.
[0038]
Next, the silicon substrate was dry-etched using the resist pattern as an etching mask. As the etching gas, C ₄ F ₈ gas and SF ₆ gas were used, and etching was performed perpendicularly to the substrate surface while protecting the etching side wall by alternately flowing the above two types of gases. The etching depth was 100 μm. As a result, the ratio between the diameter and the length of the puncture needle was 1:10.
[0039]
Next, after protecting the entire substrate surface with a photoresist, dicing was performed to take out one puncture needle made of silicon and the holding substrate.
Next, the resist film was removed by immersing the removed puncture needle and the holding substrate in acetone and isopropyl alcohol. The removed puncture needle was observed with a scanning electron microscope, and it was confirmed that the puncture needle was designed as designed.
[0040]
Next, the prepared puncture needle was washed with ethyl alcohol, sterilized and dried with ultraviolet rays, and directly punctured into a human body to confirm that there was no pain. Further, the extracted puncture needle was observed with an optical microscope, and it was confirmed that the blood component was retained in the outer peripheral portion and the concave portion of the puncture needle.
[0041]
In addition, it was also confirmed that the puncture needle shown in FIG. 2 could be manufactured by using a photoresist pattern serving as an etching mask having a cross-sectional shape of the needle body 202 in FIG. At this time, the diameter of the needle was 60 μm, the width and depth of the recess 203 were 10 μm, and the length of the needle was 300 μm.
[0042]
Since the photolithography method is used in the manufacturing method of this embodiment, it is possible to manufacture a puncture needle having an arbitrary cross-sectional shape. In addition, by using photolithography and dry etching, a large number of needles can be manufactured at the same time, and the manufacturing cost can be reduced. Further, by controlling the etching depth of the dry etching, a needle having an arbitrary length can be formed. Further, a tapered puncture needle can be formed by adjusting the pressure during dry etching, the gas ratio, and the like.
[0043]
Example 2
In this example, the puncture needle of FIG. 2 was manufactured by a process different from that of Example 1.
First, a glass substrate was prepared. A 50 nm thick titanium thin film serving as an adhesion layer was formed thereon by sputtering. Next, a gold thin film was formed in a thickness of 300 nm on the titanium thin film in the same manner as a seed layer in a later plating step.
[0044]
Next, a photoresist (PMER P-GH3000PM: manufactured by Tokyo Ohka Co., Ltd.) was formed to a thickness of 50 μm on the substrate on which the titanium and gold thin films were formed, by spin coating. At this time, the thickness of the photoresist is set to be thicker than the length of the puncture needle to be manufactured.
[0045]
Next, a negative pattern having a cross-sectional shape of the needle main body 202 (diameter of 20 μm, width and depth of the concave portion each being 5 μm), that is, a pattern to be a mold was formed by photolithography.
[0046]
Next, electrolytic nickel plating was performed on the substrate using a plating bath containing nickel sulfamate, nickel chloride, and boric acid as the main components at a bath temperature of 50 ° C., a cathode current density of 10 A / dm ² , and a pH of 4.2. Was done. As a result, nickel grew in a columnar shape on the portion of the surface of the gold thin film formed on the substrate where no resist pattern was formed. When the length of the columnar nickel structure reached the desired length of the puncture needle, the substrate was pulled out of the plating bath.
[0047]
Next, after washing with water, each was separated into a puncture needle made of nickel and a supporting substrate by dicing.
Next, the resist on the substrate was removed using a dedicated resist stripper.
Finally, the exposed needle portion was washed with ethyl alcohol, sterilized and dried with ultraviolet light, and the puncture needle shown in FIG. 2 was completed.
[0048]
Observation of the removed puncture needle with a scanning electron microscope confirmed that a puncture needle having a designed cross-sectional shape was successfully produced. The length of the puncture needle was 40 μm, and the ratio between the diameter and the length of the puncture needle was 1: 2.
[0049]
In the manufacturing method according to the present embodiment, since the mold for the puncture needle is manufactured using the photolithography method, it is possible to manufacture the puncture needle having an arbitrary cross-sectional shape. Further, a large number of needles can be manufactured at the same time, and the manufacturing cost can be reduced. Further, in the manufacturing method of the present embodiment, the material of the puncture needle can be selected from materials capable of electrolytic plating or electroless plating. is there.
[0050]
Example 3
In this example, the puncture needle shown in FIG. 3 was manufactured.
In the present embodiment, a “micro fabrication method” was used as a manufacturing method. The micro stereolithography is described, for example, in [A. Bertsch et al. : Proc. Of the IEEE International Works on Micro Electro Mechanical Systems (1998) p. 18], [K. Ikuta et al: Proc. Of the IEEE International Works on Micro Electro Mechanical Systems, (1998) p. 290]. In this manufacturing method, a liquid ultraviolet curing resin is irradiated with an ultraviolet beam, and a desired position is cured while operating the XY stage, thereby processing a single cross-sectional shape. After the processing of one layer is completed, the Z stage is lowered by one layer, and further processing is performed. By repeating the above steps, a structure having an arbitrary shape can be finally formed.
[0051]
In this example, SU-8 (manufactured by Micro Chemical Corp.) was used as an ultraviolet-curable resin, and a stereolithography method was performed using a UV lamp having a wavelength of 365 nm as a light source. By operating the XYZ stage while irradiating the SU-8 with the UV lamp, the shape of the puncture needle shown in FIG. 3 could be produced.
[0052]
After removing the uncured SU-8, the exposed needle portion was washed with ethyl alcohol, sterilized and dried with ultraviolet rays, and the puncture needle shown in FIG. 2 was completed.
When the removed puncture needle was observed with a scanning electron microscope, it was confirmed that a puncture needle having a cross-sectional shape as designed was produced.In this example, the puncture needle was produced using micro stereolithography. . This makes it possible to form a puncture needle of an arbitrary shape, such as a puncture needle having a spiral concave portion formed on the outer peripheral portion.
[0053]
In this embodiment, the needle body is manufactured by the micro stereolithography method. However, a mold is formed by the micro stereolithography method, the mold is plated in the same manner as in the second embodiment, and after plating, the puncture is performed by removing the mold. Needles may be formed. In this case, it is possible to form a puncture needle made of a material other than the ultraviolet curable material, and it is possible to widen the selection range of the material.
[0054]
Example 4
In this example, the puncture needle shown in FIG. 4 was manufactured. First, a cylindrical puncture needle was produced in the same manner as in Example 1. Next, the tip 10 μm was immersed in an aqueous solution in which HF (hydrofluoric acid) and HNO ₃ (nitric acid) were mixed at a volume ratio of 1: 2, and the tip was processed into a conical shape by isotropic etching. This was observed with a scanning electron microscope, and it was confirmed that the puncture needle was designed as designed.
[0055]
【The invention's effect】
As described above, according to the present invention, it is possible to provide a puncture needle and a puncture device using the same, which can collect a biological sample quickly and safely with little pain when sampling blood or body fluid from a living body. did it.
[Brief description of the drawings]
FIG. 1 is a schematic view showing an example of a puncture needle of the present invention.
FIG. 2 is a schematic view showing another example of the puncture needle of the present invention.
FIG. 3 is a schematic view showing another example of the puncture needle of the present invention.
FIG. 4 is a schematic view showing another example of the puncture needle of the present invention.
FIG. 5 is a schematic view showing an example of the puncture device of the present invention.
[Explanation of symbols]
101, 201, 301, 401 Base 102, 202, 302, 402 Needle main body 203, 303, 403 Concave part 304 Peripheral part 404 Isotropic etching surface 405 Tip 501 Substrate 502 Puncture needle 503 Microcapillary 504 Liquid reservoir 505 Rubber stopper 506 Filtration Means 507 Analysis means 508, 509 Electrode

Claims (10)

A puncture needle for puncturing a living body with a needle to collect a bodily fluid, which is located on the outer surface of the needle main body and the needle main body, and in which a bodily fluid adheres to the needle main body after puncturing the needle main body into a living body. A puncture needle, comprising: a body fluid adhering portion for withdrawing the puncture needle with the puncture needle. The puncture needle according to claim 1, wherein the body fluid attaching portion has a concave portion for accommodating the body fluid to be attached. The puncture needle according to claim 1, wherein a distal end of the needle body is closed. 4. The puncture needle according to claim 1, wherein the puncture needle has a diameter of 10 to 60 μm, and a ratio between the diameter and the length of the puncture needle is 1: 2 to 1:20. A puncture device comprising: the puncture needle according to any one of claims 1 to 4; and a puncturing force imparting means for imparting a force for puncturing a living body to the puncture needle. The puncture device according to claim 5, further comprising a collection unit for collecting a body fluid attached to the body fluid attachment portion of the puncture needle. 7. The puncture device according to claim 6, wherein the collecting means collects the bodily fluid attached to the body fluid attaching portion by applying a negative pressure to the body fluid attaching portion of the puncture needle. The puncture device according to claim 6, wherein the collection unit collects the bodily fluid that has adhered to the body fluid attachment unit by applying a physical force to the body fluid attachment unit of the puncture needle. The puncture device according to claim 8, wherein the physical force is a force when blowing a gas to the body fluid attaching portion. The puncture device according to claim 8, wherein the physical force is a force for wiping a body fluid attached to the body fluid attachment portion.

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