JP2000185034A - Blood sampling needle, its manufacture, blood sample analysis device, and its manufacture - Google Patents

Abstract

PROBLEM TO BE SOLVED: To cause as little pain to a blood donor as possible and to reduce the amount of medical waste. SOLUTION: This blood sampling needle 3 is for piercing a living body and includes a needle body 3a made of silicon and formed in a microscopic needle shape and a hollow part provided inside the needle body 3a. The diameter of the blood sampling needle 3 thus formed is nearly equal to or smaller than that of the blood-sucking mouthparts of a mosquito. Sampling blood by use of such a blood sampling needle 3 almost eliminates pain to a blood sampled person. The blood sampling needle 3, a pump part, and an analytical part are arranged on the same substrate, whereby contact with blood from blood sampling to analysis can be limited to only one small part. Therefore, the amount of medical waste can be reduced.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a blood collection needle used for collecting blood from a human body, a method of manufacturing the same, a blood collection analyzer, and a method of manufacturing the same.

[0002]

2. Description of the Related Art When blood is collected from a living body such as a human body, the blood is collected from the human body using a syringe and a needle, and then the collected blood is put into a test tube. When analyzing, for example, the blood glucose level of the blood put in the test tube, the blood glucose level is analyzed using a blood glucose level analyzer. In addition, when performing, for example, DNA analysis of blood put in a test tube, DNA is extracted using a device such as PCR and then analyzed.

[0003]

In the case of the above conventional configuration,
When collecting blood, a considerably thick injection needle is pierced into the living body, which causes a problem that the blood recipient is considerably pained. In addition, since medical devices such as syringes, injection needles, test tubes, and pipettes cannot be reused, these medical devices must be discarded after being used only once for each blood sampler. There was also a drawback that it would increase considerably.

[0004] Further, when DNA is extracted using a device such as PCR, the time required for extraction becomes longer,
Since the reagent used for the analysis is expensive, there is also a disadvantage that the analysis cost is high. In this case, a configuration in which PCR is formed on a silicon substrate to extract DNA at high speed (a so-called DNA analysis chip) has been considered.
An operation of introducing blood into R is required. For this reason, there is a disadvantage that the amount of medical waste is increased.

[0005] Therefore, an object of the present invention is to minimize the pain of a blood-collected person, reduce the amount of medical waste, shorten the time required for analysis, and reduce the cost required for analysis. It is an object of the present invention to provide a blood collection needle and a method for manufacturing the same, and a blood collection analyzer and a method for manufacturing the same, which can reduce the cost.

[0006]

According to the first aspect of the present invention, a blood collection needle is made of silicon and has a fine needle shape, and a hollow provided inside the needle body. The thickness of the blood collection needle can be reduced to the same or smaller than the thickness of the mouthpiece for sucking blood of a mosquito. When blood is collected using such a blood collection needle, pain is hardly given to the blood collection subject.

According to the second aspect of the present invention, since the saw-shaped blade is protruded from the outer periphery of the needle body, the needle body can be stabbed more smoothly when piercing the living body. For this reason, it is possible to further prevent pain from being given to the blood collection subject.

According to the third aspect of the present invention, since the outer diameter of the needle main body is set to 100 μm or less, the thickness of the blood collection needle is reduced.
The same size as or smaller than the mouthpiece for sucking mosquitoes,
The same operation and effect as the first aspect can be obtained.

According to the invention of claim 4, the inner surface of the cavity of the needle body, is provided with the SiO ₂ film, when collected blood passes through a cavity of the needle body, eliminating adversely affected be able to.

According to the fifth aspect of the present invention, since the blood collecting needle according to the first aspect is provided with the blood collecting pump unit integrally, the configuration in which the blood collecting needle and the pump unit are combined can be downsized. In the case of this configuration, it is preferable that the pump section is configured by a diffuser type micro pump as in the invention of claim 6. It is preferable that the actuator of the pump unit be constituted by a unimorph actuator. It is also preferable that the actuator of the pump section be constituted by a piezoelectric unimorph actuator.

According to the ninth aspect of the present invention, since the actuator of the pump section is configured to vibrate the needle main body, it is possible to pierce the living body with the needle main body more smoothly.

According to the tenth aspect of the present invention, since the anticoagulant is fixed to the inner surface of the hollow portion of the needle main body, the blood passing through the hollow portion of the needle main body can be prevented from coagulating, and the blood collection needle can be used. Clogging can be prevented. In this case, it is preferable to use heparin sodium (Europe) as an anticoagulant as in the invention of claim 11.

According to the twelfth aspect of the present invention, the blood collecting part comprising the blood collecting needle and the blood collecting pump part according to the fifth aspect and the analyzing part for analyzing blood are provided on the same substrate, so that the blood collecting part and the blood collecting part can be analyzed. The configuration including the parts can be made very small. In the case of this configuration, devices such as an injection needle, a syringe, and a test tube are not required, and the amount of medical waste can be significantly reduced. Also, the amount of blood to be collected can be significantly reduced.

According to the thirteenth aspect of the present invention, the flow path of the blood collection section, the flow path of the analysis section for separating blood components,
The flow path for analyzing the separated blood component in the analysis section was provided on the same substrate. Thereby, the invention of claim 12 can be realized.

According to a fourteenth aspect of the present invention, in the method of manufacturing a blood collection needle according to the first aspect, a semiconductor process is used. Thereby, the blood collection needle of claim 1 can be actually manufactured. In this case, it is preferable to use an SOI substrate as the substrate. Further, as in the sixteenth aspect of the present invention, it is more preferable to include a step of providing a SiO ₂ film on the inner surface of the hollow portion of the needle main body.

According to a seventeenth aspect of the present invention, in the method of manufacturing a blood sampling analyzer for manufacturing the blood sampling analyzer according to the twelfth aspect, a semiconductor process is used. Thus, the blood collection analyzer according to claim 12 can be easily manufactured. In this case, as in the invention of claim 18, SOI is used as the substrate.
It is preferable to use a substrate. Further, as in the nineteenth aspect of the present invention, it is more preferable to include a step of providing a SiO ₂ film on the inner surface of the hollow portion of the needle main body.

Further, according to the invention of claims 20 to 23,
Almost the same functions and effects as those of the seventeenth aspect can be obtained.

According to the twenty-fourth aspect of the present invention, the method of dipping the anticoagulant in the solution of the anticoagulant is used as the method of holding the anticoagulant in the needle body. Can be easily held.

According to the twenty-fifth aspect of the present invention, as a method of holding the anticoagulant on the inner surface of the hollow portion of the needle body, a method of sucking the solution of the anticoagulant into the needle body by a pump is used. Therefore, the anticoagulant can be easily held with a simple configuration.

According to the twenty-sixth aspect of the present invention, as a method of holding the anticoagulant in the inner surface of the hollow portion of the needle body, a method of sucking the solution of the anticoagulant into the needle body by electrophoresis is used. Since it is used, the anticoagulant can be easily held with a simple configuration.

According to the twenty-seventh aspect of the present invention, since the pump electrode, the electrophoretic electrode and the analysis electrode are provided on the same substrate, the blood sampling analyzer according to the twelfth aspect can be made very small. Can be. In this case, as in the twenty-eighth aspect, since the part that comes into contact with blood from blood collection to analysis is configured as one part, the amount of medical waste can be significantly reduced. Further, since the memory for writing personal information and the like is integrated as in the invention of claim 29, it is possible to easily realize the use of the blood sampling analyzer in a one-to-one correspondence with an individual.

According to the thirty-first aspect of the present invention, a blood glucose level is measured by forming a gulcose oxydase (GOD) immobilized film on the inner surface of the analysis part and detecting a change in the electrical conductivity. A configuration for measuring a value can be specifically realized. In this case, as a method for forming a gulcose oxydase (GOD) immobilized film on the inner surface of the analysis section as in the invention of claim 31, gulcose oxydase (GOD) is used.
It is preferable to use a method of sucking the solution into the analysis section by electrophoresis. Also, as in the invention of claim 32,
As a method of forming a gulcose oxydase (GOD) immobilized film on the inner surface of the analysis unit, it is even more preferable to use a method of sucking a solution of gulcose oxydase (GOD) into the analysis unit by a pump.

[0023]

DESCRIPTION OF THE PREFERRED EMBODIMENTS One embodiment of the present invention will be described below with reference to the drawings. First, FIGS. 1 to 5 are views showing a blood sampling analyzer 1 of the present embodiment. The blood sampling analyzer 1 includes a rectangular plate-shaped device main body 2 and the device main body 2.
And a blood collection needle 3 protruding from the center of the left end face in FIG. The size of the apparatus main body 2 is, for example, 20 m.
m × 10 mm and the thickness dimension is 0.5
mm. The blood collection needle 3 is for piercing a living body, and its needle main body 3a is formed in a fine needle shape. Specifically, the outer diameter of the needle main body 3a is about 50 μm, and its length is at most about 2 mm.

The needle main body 3a is formed of silicon as described later. As shown in FIG. 4, a hollow portion 3b is provided inside the needle main body 3a.
Further, as shown in FIG. 1, a saw-shaped blade portion 3c protrudes from an outer peripheral portion of the needle main body 3a. This blade 3c
Is for making it easier to puncture the blood collection needle 3 into the living body.

As shown in FIG. 3, an analyzer 4 for analyzing the collected blood and a pump 5 for aspirating the blood are provided inside the apparatus main body 2. The device main body 2
As shown in FIG. 1, a pump unit 5
For example, a piezoelectric unimorph actuator 6 is provided as an actuator. A piezoelectric drive electrode 7 is provided at the right end of the upper surface of the device main body 2. Device body 2
A step portion 8 is formed at the right end of the lower surface portion of the device, and an analysis electrode 9 is provided on the lower surface of the step portion 8 as shown in FIG.

In addition, the blood sampling analyzer 1 includes two silicon substrates, for example, an SOI substrate 10 as described later.
a and 10b are bonded together. In the case of this configuration, as shown in FIGS. 4 and 5, two SOI substrates 1
A hollow portion 3b of the blood collection needle 3, a flow path 12 of the analysis unit 4, a diaphragm chamber 13 of the pump unit 5, and the like are provided at a joint portion where the Oa and 10b are bonded.

Next, a manufacturing process for manufacturing the blood sampling analyzer 1 will be described with reference to FIGS.
In the case of the present embodiment, the blood sampling analyzer 1 is manufactured using a semiconductor process. First, a process of forming the above-described two SOI substrates will be described with reference to FIG.

As shown in FIG. 11A, as a substrate,
For example, a single crystal Si substrate 14 is prepared. This single crystal Si
The substrate 14 has a surface orientation set to (100), a thickness of at least about 300 μm, and a low impurity concentration. Then, as shown in FIG. 11B, a silicon oxide film 15 is deposited on the surface of the single crystal Si substrate 14, that is, on the entire mirror-finished surface by, for example, a plasma CVD method. in this case,
The silicon oxide film 15 is deposited so as to have a thickness of about 0.5 μm.

Subsequently, as shown in FIG. 11C, a mask 16 used for forming the blood collection needle 3 by etching is formed on the silicon oxide film 15. The mask 16 is formed by forming a platinum film by, for example, an electron beam evaporation method, and then patterning the platinum film using a photolithography technique and an etching technique.

Then, as shown in FIGS. 11 (d) and 11 (e), another single-crystal Si substrate 17 is bonded onto the single-crystal Si substrate 14 having the above-described structure, and heat-treated. Thus, an SOI substrate 18 in which the platinum mask 16 is embedded is formed. Thereafter, the single-crystal Si substrate 14 side of the SOI substrate 18 is polished so that the thickness of the single-crystal Si substrate 14, that is, the thickness of the single-crystal Si thin-film portion 14a is, for example, about 12 μm. . Thus, the base SOI substrate 10 is completed. In the present embodiment, a platinum film is used as the burying mask 16, but is not limited to this. For example, a silicon nitride film formed by CVD or the like may be used.

Next, as shown in FIG. 12A, one base SOI substrate 10a is prepared. And FIG.
As shown in (b), the single crystal S of the SOI substrate 10a
In the i-thin film part 14a, a cavity part 3a of the blood collection needle 3, a flow path 12 of the analysis part 4, and a groove part 19 for the diaphragm chamber 13 of the pump part 5 are formed. In this case, the single crystal Si thin film portion 14a of the SOI substrate 18a is patterned by using a photolithography technique and an etching technique to form a groove 19 having a depth dimension of, for example, about 10 μm. Here, the groove 19 shown in FIG. 12B is a groove for the cavity 3 a of the blood collection needle 3. FIG. 6 shows an upper surface of (the single-crystal Si thin-film portion 14a of) the SOI substrate 10a in a state where the groove 19 is formed.

In FIG. 6, the cavity 3a of the blood collection needle 3
The width of the groove is set to, for example, about 20 μm. The width of the groove for the flow channel 12 of the analysis unit 4 is set to, for example, about 100 μm. The groove for the flow path 12 is formed so as to have a meandering shape (a meandering shape), and its length dimension (that is, the flow path 12
Is longer. The groove for the diaphragm chamber 13 of the pump unit 5 is a substantially circular concave portion, and the diameter of the concave portion is set to, for example, about 9 mm.

Here, a diffuser section 20 is formed at a portion where the diaphragm chamber 13 and the flow path 12 of the analysis section 4 are connected, as shown in FIG. In the diffuser section 20, the inlet 13 of the diaphragm chamber 13 is provided.
a is formed smaller than the flap of the flow channel 12,
A taper portion 21 having an angle θ of, for example, about 20 degrees
Are formed. In the case of this configuration, when the piezoelectric unimorph actuator 6 is driven to deform the upper wall of the diaphragm chamber 13, that is, the diaphragm 22 (see FIG. 5, described later) so as to expand upward in FIG. The fluid in the flow channel 12 is sucked into the diaphragm chamber 13 by 20. In this case, the pump section 5 is constituted by a diffuser type micro pump.

In addition, a groove for a flow path 23 for supplying a methanol solution is formed on the upper side in FIG. 6 of the upper surface of the SOI substrate 10a. The right end of the flow path 23 is a methanol liquid supply port 24. The left end of the channel 23 is
The blood collection needle 3 is connected so as to communicate with a portion where the cavity 3a of the blood collection needle 3 and the flow path 12 of the analysis unit 4 are connected.

Next, as shown in FIG.
A silicon oxide film 25 is deposited on the entire upper surface of the substrate 10a by, for example, a plasma CVD method so as to have a thickness of, for example, about 2 μm. In this case, the SOI substrate 10a is set in a plasma CVD apparatus, and the degree of vacuum is 8.2 Torr.
The deposition was performed for 176 seconds under the conditions of r, RF power 725 W, oxygen 1000 sccm, helium 1200 sccm, TEOS 1000 mgm, and substrate temperature 389 ° C. After that, heat treatment is preferably performed for densification of the silicon oxide layer.

On the other hand, as shown in FIG.
A number of base SOI substrates 10b are prepared. And FIG.
As shown in FIG. 2E, a silicon oxide film 26 is deposited on the surface (mirror-finished surface) of the single crystal Si thin film portion 14a of the SOI substrate 10b by, for example, a plasma CVD method so as to have a thickness of about 2 μm. I do. The step of forming the silicon oxide film 26 is the same as that of the silicon oxide film 25 described above.
Are almost the same as the conditions of the step of forming.

Then, the analysis electrode 9 is formed on the upper surface of the silicon oxide film 26 of the SOI substrate 18b. Specifically, after a platinum film (not shown) is formed on the upper surface of the silicon oxide film 26 by, for example, vapor deposition, the analysis film 9 having a predetermined pattern shape is formed on the platinum film by using a photolithography technique and an etching technique. Form. Here, a top view of the SOI substrate 10b in a state where the analysis electrode 9 is formed is shown in FIG.
As shown in FIG.

As shown in FIG. 9, an appropriate pair of electrodes 9 and 9 of the analysis electrodes 9 is connected to a meandering flow path 12.
(See a two-dot chain line in FIG. 9) so as to be separated by a predetermined distance d (see also FIG. 10). The pair of electrodes 9 is an electrode for measuring the conductivity between the electrodes 9. It is configured such that the blood glucose level of the collected blood can be detected by measuring the conductivity. A plurality of such pairs of electrodes 9, 9 are provided.
An analysis electrode 9 is constituted by the plurality of pairs of electrodes 9. The right end in FIG. 9 of the analysis electrode 9 extends to the right end of the SOI substrate 10b, and this portion becomes the step 8 shown in FIGS.

In the above embodiment, the liquid is sucked (pumped) by the diffuser type micropump 5. Alternatively, the liquid may be sucked (pumped) by electrophoresis. good. In the case of such a configuration, it is preferable that the electrode for electrophoresis is formed on the upper surface of the silicon oxide film 26 of the SOI substrate 10b.

Thereafter, as shown in FIGS. 12F and 12G, a step of bonding the two SOI substrates 10a and 10b is performed. In this step, the two SOI substrates 10
The silicon oxide films 25 and 26 of a and 10b were attached to each other so as to face each other, for example, by anodic bonding. By this bonding, the portion corresponding to the groove 19 becomes the hollow portion 3a of the blood collection needle 3, the flow path 12 of the analysis section 4, the diaphragm chamber 13 of the pump section 5, and the flow path 23 for supplying the methanol liquid.

Next, in order to form the blood collection needle 3 and the concave portion 27 (see FIGS. 5 and 8) for embedding the piezoelectric unimorph actuator 6, the bonded substrate 28 is formed.
Then, an etching mask is formed to protect a region not to be etched. Subsequently, etching is performed using, for example, KOH. In this case, the silicon oxide layers (that is, the silicon oxide films 25 and 26) serve as an etch stop, and FIG.
Etching is performed as shown in FIG. This FIG.
(H) shows a longitudinal section of only a portion corresponding to the blood collection needle 3.

Thereafter, in order to create the blood collection needle 3, the following processing is executed for the portion corresponding to the blood collection needle 3 described above. That is, as shown in FIG.
The silicon oxide layers (silicon oxide films 25 and 26) are removed by etching with a hydrofluoric acid solution. In this state, the silicon oxide layers (silicon oxide films 25 and 26) corresponding to the blood collection needle 3 are not etched because they are protected by the platinum mask 16.

Subsequently, by etching again with KOH, as shown in FIG. 12 (j), the silicon layer (single-crystal Si thin film portions 14a, 14a,
4a) is removed. Further, by dipping in a hydrofluoric acid solution, the thin silicon oxide layer (silicon oxide film 15) not protected by the mask 16 is removed by etching as shown in FIG. Thereby, the blood collection needle 3 is created.

On the other hand, when performing the etching step shown in FIG.
Recesses 27 (see FIGS. 5 and 8) for embedding are formed at the same time. In this case, the etching of the recess 27 is performed up to the silicon oxide layer (the silicon oxide film 26).
Depending on the structure of the piezoelectric unimorph actuator 6, the etching may be stopped halfway.
That is, the depth of the concave portion 27 may be set to a desired depth and the silicon layer may be left. In such a configuration, after the etching of the concave portion 27 is stopped halfway, only the portion corresponding to the blood collection needle 3 may be immersed in the etching solution to continue the etching.

As shown in FIGS. 5 and 8, the bottom wall of the recess 27, that is, the upper wall of the diaphragm chamber 13, becomes the diaphragm 22. Next, a process of forming an electrode (piezoelectric drive electrode 7) for supplying a voltage to the piezoelectric unimorph actuator 6 in the concave portion 27 will be described. In this embodiment, for example, the JPS (Jet Printing System)
m (manufactured by vacuum metallurgy)) to form the piezoelectric drive electrode 7 as shown in FIG. The JPS is a method of forming electrodes by spraying gold fine particles onto a substrate so as to draw them. According to this method, even if the depth of the concave portion 27, that is, the step is, for example, about 50 μm, a good electrode 7 (wiring pattern) without disconnection or the like could be formed.

Of the two piezoelectric driving electrodes 7, (the two conductor patterns) extending to the inner bottom of the concave portion 27 are for connecting to the electrodes on the lower surface of the piezoelectric unimorph actuator 6. Yes, the other electrode 7b
The (two conductor patterns) are for connecting to the electrodes on the upper surface of the piezoelectric unimorph actuator 6. On the upper and lower surfaces of the piezoelectric unimorph actuator 6, for example, silver electrodes are formed.

Next, in fitting the piezoelectric unimorph actuator 6 into the concave portion 27 and attaching it, the piezoelectric unimorph actuator 6 was bonded using, for example, a conductive adhesive (see FIG. 5). As a result, the electrode 7a extending to the inner bottom of the recess 27 and the electrode on the lower surface of the piezoelectric unimorph actuator 6 are connected. The connection between the other electrode 7b and the electrode on the upper surface of the piezoelectric unimorph actuator 6 was made by, for example, wire bonding (not shown). The thickness of the piezoelectric unimorph actuator 6 used in this embodiment is, for example, about 50 μm. As the piezoelectric unimorph actuator 6, an actuator having a thickness of about 100 μm or another thickness may be used as necessary.

Next, a description will be given of a process of fixing the blood glucose measuring bioelement and the anticoagulant to the blood collection analyzer 1 prepared as described above. First, a bio-element such as a commercially available gulcose oxydase (GOD)
A solution is prepared, and a blood collection needle 3 of the blood collection analyzer 1 is provided in the solution.
Soak the part. Then, by energizing the pump unit 5, the gulcose oxydase solution is supplied to the cavity 3 of the blood collection needle 3.
b and suction into the flow channel 12 of the analysis unit 4.

In this case, for example, a sine wave voltage of 15 V and 1 kHz was applied to the piezoelectric unimorph actuator 6 of the pump section 5. Also gulcose oxydas to suck
e The amount of the solution may be an amount enough to fill the Miranda-shaped portion (so-called Miranda line) of the flow channel 12 of the analysis unit 4. Specifically, the length of the miranda line is set to about 10
Assuming that the thickness is about 100 μm and the thickness is about 8 μm, the thickness may be about 80 nl.

Next, after the blood collection needle 3 was washed several times with distilled water, the pump unit 5 was driven to energize to draw distilled water into the hollow portion 3b of the blood collection needle 3. In this case, the amount of distilled water to be sucked may be about 0.2 nl, which is the internal volume of the cavity 3b. Subsequently, an anticoagulant, for example, heparin sodium (e.g.) solution was prepared, and this hepa was prepared.
The blood collection needle 3 is immersed in the rin sodium (pharmacopeia) solution, and the pump unit 5 is energized to drive the blood collection needle 3 into the cavity 3b.
The rin sodium (Europe) solution was sucked up to fill.
In this case, the amount of heparin sodium (Europe) solution to be aspirated is
What is necessary is just about 0.2 nl, which is the internal volume of the cavity 3b.

Thereafter, heparin sodium (Epo) and gulc
Perform the process of drying ose oxydase. Specifically, it is dried at 60 degrees for 30 minutes and at 80 degrees for 1 hour. Then, sterilization is performed by an autoclave at 135 degrees for 5 minutes. This allows heparin as an anticoagulant
Sodium (pharmacopeia) is fixed to the inner surface of the hollow portion 3b of the needle body 3a. At the same time, gulcose oxydase (GOD) as a glucose sensor is fixed on the inner surface of the flow channel 12 of the analyzer 4 and gulcoseoxyda
The se (GOD) immobilized film is formed.

When blood is collected and analyzed using the blood collection analyzer 1 prepared as described above, the injector 29 shown in FIGS. 13 and 14 is used. This injector 29 is, as shown in FIG.
And an inner cylinder 31 provided in the outer cylinder 30 so as to be vertically movable. A spring (not shown) is provided between the inner cylinder 31 and the outer cylinder 30, and the spring urges the outer cylinder 30 to move downward with respect to the inner cylinder 31 in FIG. .

As shown in FIG. 14, the blood sampling analyzer 1 is configured to be detachably mounted inside the inner cylinder 31. In this case, the blood collection analyzer 1 is mounted such that the blood collection needle 3 protrudes downward. At an upper portion of the inner cylinder 31, a connector connecting portion 34 for detachably connecting a connector 33 provided at one end of the cable 32 is provided. With the blood sampling analyzer 1 attached to the inner cylinder 31, the terminal (not shown) in the connector connection portion 34 and the electrodes 7, 9 of the blood sampling analyzer 1 are connected.

The other end of the cable 32 is connected to a control device (not shown) for controlling the operation of the blood sampling analyzer 1. This control device has a function of driving and controlling the pump unit 5 and the analysis unit 4 of the blood sampling analyzer 1, a function of inputting and analyzing an analysis signal from the analysis unit 4, and the like. The main body 2 of the blood sampling analyzer 1 is provided with, for example, an EEPROM (not shown) as a memory, and the control device stores data (for example, data such as personal information and analysis results) in the EEPROM. And a function of reading data. It should be noted that instead of attaching the above-mentioned EEPROM, a semiconductor process is used to
The EEPROM may be formed on the I substrate.

In the injector 29 having the above configuration, when the blood sampling analyzer 1 is mounted on the inner cylinder 31,
The blood collection needle 3 of the blood collection analyzer 1 is configured to be covered and protected by the outer cylinder 30. When blood is collected, when the inner cylinder 31 is pressed with the lower end of the outer cylinder 30 in FIG. 13 in contact with the blood collection site of the human body (subject), the blood collection needle 3 of the blood collection analyzer 1 By projecting downward from the lower end of the cylinder 30 in FIG. 13, the blood collection needle 3 is configured to pierce a blood collection site (for example, a capillary blood vessel) of a human body.

Subsequently, in this state, when the piezoelectric unimorph actuator 6 of the pump unit 5 of the blood sampling analyzer 1 is energized (for example, a voltage of 1 kHz is applied), blood in the human body is suctioned by the blood sampling needle 3 by the pump unit 5. As well as
The collected blood is configured to enter and fill the cavity 3b of the blood collection needle 3 and the flow path 12 of the analyzer 4. Here, since an anticoagulant (heparin sodium (Epo)) is fixed inside the hollow portion 3b of the blood collection needle 3,
Blood can be prevented from coagulating in the cavity 3b. Thus, the inside of the cavity 3b and the flow path 12 is not clogged with blood.

At this time, the methanol liquid supply port 24
And, through the channel 23, for example, a 30% aqueous methanol solution as a denaturant is mixed with the collected blood. The methanol aqueous solution is supplied from outside through a supply tube (not shown) provided in the cable 32 or a supply tube (not shown) provided separately from the cable 32.
4 is supplied at an appropriate pressure.

Next, an analysis result when blood collection and analysis (for example, blood sugar level analysis) are executed using the blood collection analyzer 1 and the injector 29 will be described. In this case, the injector 29 is set near the forearm radial median mesothelial vein of the fasting test patient, the inner cylinder 31 is pushed, and the pump unit 5 of the blood sampling analyzer 1 is energized to drive, for example, about 0.5 mm. About 1 μl of blood was collected and its blood sugar level was analyzed. The result of this analysis was taken as Example 1.
It is shown in Table 1 below.

[0059]

[Table 1]

In Table 1, in Comparative Example 1, for example, about 50 ml of blood was collected from the testicular mesothelial vein of a fasting test patient using a syringe and a needle, and about 2 ml of the collected blood was collected by Cobas. It is the result of having measured the blood glucose level by the Cobas mirror S made from. Comparative Example 2 is a result of measuring the blood glucose level of about 30 μl of the blood collected in Comparative Example 1 using a tide manufactured by Miles Sankyo Co., Ltd.
From the above Table 1, it can be seen that the measurement results of Example 1 almost match the measurement results of Comparative Examples 1 and 2, and
It can be clearly seen that the blood sampling analyzer 1 of this embodiment has sufficient blood sampling analysis performance.

Further, the same subject was orally administered 1 unit of 75 g of tolerand, which is a hyperglycemic-inducing substance, for 30 minutes and 6 minutes.
After 0 minutes, 90 minutes, and 120 minutes have elapsed, about 5 μl were obtained using the blood collection analyzer 1 and the injector 29 of this example, respectively.
Was collected for analysis. The results of the measurement 90 minutes after the maximum blood sugar level among the analysis results are shown in Table 2 below as Example 2.

[0062]

[Table 2]

In Table 2, Comparative Example 3 shows that the same subject was orally administered 1 unit of 75 g of tolerand, which is a hyperglycemic substance, and then, after 30 minutes, 60 minutes, 90 minutes, and 120 minutes, a syringe and a needle were used. Approximately 50 ml of blood was collected by using the method described above, and the blood glucose level was measured by a Cobas mirror S made by Cobath for about 2 ml of the collected blood, and the measurement result 90 minutes after the maximum blood glucose level was shown It is.
In Comparative Example 4, about 30 μl of each blood sample collected in Comparative Example 3 was measured by a tide manufactured by Miles-Sankyo Co., Ltd., and the maximum blood sugar level was measured.
This is the measurement result after one minute. From Table 2 above, it can be seen that the measurement results of Example 2 almost coincide with the measurement results of Comparative Examples 3 and 4, and therefore, the blood collection analyzer 1 of this example has sufficient blood collection analysis performance. You can see that.

Here, the mechanism of the blood glucose level analysis of the blood sampling analyzer 1 of this embodiment will be described. The blood collected from the subject is supplied to the cavity 3 b of the blood collection needle 3 and the flow path 1 of the analysis unit 4.
2 is filled through. Here, the cavity 3 of the blood collection needle 3
Since an anticoagulant (heparin sodium (e.g.)) is fixed inside b, the blood is prevented from coagulating in the cavity 3b, and the blood in the cavity 3b and the channel 12 is prevented. No clogging. At this time, for example, 3
A 0% aqueous methanol solution is mixed with the collected blood to obtain a test solution.

This test solution was used as a bioelement.
The GOD consumption (speed) in the gulcose oxydase (GOD) immobilized membrane is measured based on a detection signal detected by the platinum electrode 9 (a signal indicating a change in conductivity), and a blood glucose level is measured from the measured value. I do. Here, in the enzyme electrode method (GOD-Pt electrode) used in the present example, it is necessary to prevent oxygen from being generated by blood catalase from hydrogen peroxide generated by the GOD reaction. Therefore, methanol is added to the test solution. In addition, you may comprise so that iodine and molybdic acid may be added to the said test solution.

According to the present embodiment having such a configuration, the blood collection needle 3 is provided with the needle main body 3a formed in a fine needle shape and the hollow portion 3b provided inside the needle main body 3a. With this configuration, the thickness of the blood collection needle 3 can be reduced to the same or smaller than the thickness of the mouthpiece for sucking blood of a mosquito. When blood is collected using such a minute blood collection needle 3, it is possible to almost completely prevent the subject from suffering pain, and to significantly reduce the amount of blood collected. That is,
Invasion to the human body can be extremely reduced.

In the above embodiment, the saw-shaped blade 3c is protruded from the outer periphery of the needle body 3a.
When a is stuck into a living body, it can be stuck more smoothly. Therefore, it is possible to further prevent the subject from giving pain. Further, it is preferable that the needle main body 3a is vibrated by the actuator 6 of the pump unit 5 when the needle main body 3a is pierced into the living body. With this configuration, it is possible to pierce the needle body 3a more smoothly when piercing the living body.

Furthermore, in the above embodiment, since the SiO ₂ film is provided on the inner surface of the hollow portion 3b of the needle main body 3a, when the collected blood passes through the hollow portion 3b of the needle main body 3a, the blood is removed. It is possible to prevent adverse effects.

On the other hand, in the above-described embodiment, an anticoagulant (heparin sodium (pharmacopoeia)) is applied to the inner surface of the hollow portion 3b of the needle body 3a.
Is fixed, the blood passing through the hollow portion 3b of the needle main body 3a can be prevented from coagulating, and the hollow portion 3b of the blood collection needle 3 and the flow path 12 of the analyzer 4 can be prevented from being clogged.

Further, in the above embodiment, since the blood collecting needle 3 is provided with the blood collecting pump unit 5 integrally, the configuration in which the blood collecting needle 3 and the pump unit 5 are combined can be downsized. In this case, since the blood collecting unit including the blood collecting needle 3 and the blood collecting pump unit 5 and the analyzing unit 4 for analyzing the blood are provided on the same substrate, the configuration in which the blood collecting unit and the analyzing unit 4 are combined is very large. Can be miniaturized. In addition, in the case of this configuration, devices such as an injection needle, a syringe, and a test tube can be eliminated, and the amount of blood to be collected can be significantly reduced.

Further, in the above embodiment, since the pump electrode 7 and the analysis electrode 9 are provided on the same substrate, the blood sampling analyzer 1 can be made very small. In this case, since the portion that comes into contact with blood from blood collection to analysis is configured as one component (small component), the amount of medical waste can be significantly reduced. Further, in the above embodiment, the memory for writing personal information and the like is integrated into the blood sampling analyzer 1, so that a system that uses the blood sampling analyzer 1 in one-to-one correspondence with individuals can be easily realized. Can be.

On the other hand, in the above embodiment, a semiconductor process was used to manufacture the blood collection needle 3 and the apparatus main body 2 (that is, the blood collection analyzer 1). Thereby, the minute blood sampling needle 3 can be actually manufactured.

In the above embodiment, the analyzer 4 of the blood sampling analyzer 1 is configured to measure the blood glucose level of the collected blood. Instead, the analyzer is configured to perform DNA analysis of the collected blood. You may. Specifically, instead of the aqueous methanol solution, for example, chloroform phenol is mixed with the collected blood as a solvent. Examples of the solvent include DN
Any device having a function of separating A can be used.
The mixed liquid is supplied to a purification chamber, PCR (DN
A) is led to the analysis section and the analysis section to purify the necessary DNA,
What is necessary is just to comprise so that it may proliferate and analyze. As a configuration for performing such purification, propagation, and analysis, the same configuration as the configuration of a DNA analysis chip disclosed in literatures or the like in recent years may be used.

That is, the configuration of the analyzer 4 of the blood sampling analyzer 1 may be replaced with the configuration of the DNA analysis chip.
In addition, according to this configuration, the blood collection needle 3, the DNA analysis chip, and the pump unit 5 are one component (chip).
The amount of medical waste can be significantly reduced as compared with a configuration using only a DNA analysis chip.

In the above embodiment, the flow path 1
As a method for forming a gulcose oxydase (GOD) immobilized film on the inner surface of the sample 2, a method of sucking a solution of gulcose oxydase (GOD) into the analysis unit 4 by the pump unit 5 was used, but the method is not limited thereto. , Gulcose oxydase
A method of sucking the solution of (GOD) into the analysis unit 4 by electric conduction may be used.

Further, in the above embodiment, as a method of holding the anticoagulant on the inner surface of the hollow portion 3b of the needle body 3a, a method of sucking the solution of the anticoagulant into the needle body 3a by the pump unit 5 However, the method is not limited to this, and a method of sucking the solution of the anticoagulant into the needle main body 3a by electrophoresis may be used. Alternatively, a method of dipping the needle main body 3a into a solution of an anticoagulant may be used. In the case of this dipping, the anticoagulant is fixed mainly to the outer peripheral portion of the needle main body 3a. However, even with this configuration, it is possible to sufficiently prevent the blood passing through the hollow portion 3b of the needle main body 3a from coagulating.

[Brief description of the drawings]

FIG. 1 is a perspective view of a blood sampling analyzer showing one embodiment of the present invention.

FIG. 2 is a partial perspective view of the lower surface side of the blood collection analyzer.

FIG. 3 is a top view of the blood sampling analyzer.

FIG. 4 is an enlarged longitudinal sectional view of a part around a blood collection needle of the blood collection analyzer.

FIG. 5 is an enlarged vertical cross-sectional view of a portion around a pump section of the blood collection analyzer.

FIG. 6 is a top view of the SOI substrate in the step of FIG.

FIG. 7 is an enlarged top view of the diffuser unit.

FIG. 8 is a perspective view around a concave portion for accommodating a piezoelectric unimorph actuator.

FIG. 9 is a top view of the SOI substrate in the step of FIG.

FIG. 10 is a sectional view taken along line XX in FIG. 9;

FIG. 11 is a longitudinal sectional view showing a step of manufacturing a base SOI substrate.

FIG. 12 is a longitudinal sectional view showing a step of manufacturing a blood collection needle part of the blood collection analyzer.

FIG. 13 is a perspective view of an injector.

FIG. 14 is a perspective view showing a state in which the blood sampling analyzer is mounted on the inner cylinder.

[Explanation of symbols]

1 is a blood sampling analyzer, 2 is a device main body, 3 is a blood collecting needle, 3a is a needle main body, 3b is a hollow portion, 3c is a blade portion, 4 is an analyzing portion, 5 is a pump portion, 6 is a piezoelectric unimorph actuator, and 7 is a piezoelectric device. A drive electrode, 9 an analysis electrode, 10 and 11 an SOI substrate,
12 is a flow path, 13 is a diaphragm chamber, 14 is single crystal Si
Substrate, 15 is a silicon oxide film, 16 is a mask, 17 is S
OI substrate, 18 is a base SOI substrate, 19 is a groove, 20
Is a diffuser portion, 22 is a diaphragm, 23 is a flow path, 24 is a methanol liquid supply port, 25 and 26 are silicon oxide films, 27 is a concave portion, 28 is a substrate, 29 is an injector, 30 is an outer cylinder, and 31 is an inner cylinder. Show.

Claims (32)

[Claims] 1. A needle for piercing a living body, comprising a needle body formed of silicon and having a fine needle shape, and a hollow portion provided inside the needle body. Blood collection needle. 2. The blood collection needle according to claim 1, further comprising a saw-shaped blade protruding from an outer peripheral portion of the needle main body. 3. The blood collection needle according to claim 1, wherein an outer diameter of the needle body is set to 100 μm or less. 4. A inner surface of the hollow portion of the needle body, SiO ₂
The blood collection needle according to any one of claims 1 to 3, wherein the film is provided. 5. A blood collection device, wherein a blood collection pump is integrally provided with the blood collection needle according to claim 1. 6. The blood collection device according to claim 5, wherein the pump section is constituted by a diffuser-type micropump. 7. The blood collection device according to claim 5, wherein the actuator of the pump section is constituted by a unimorph actuator. 8. The blood collection device according to claim 5, wherein the actuator of the pump section is constituted by a piezoelectric unimorph actuator. 9. The blood collection device according to claim 5, wherein an actuator of the pump unit is configured to vibrate the needle main body. 10. The blood collection device according to claim 1, wherein an anticoagulant is fixed to an inner surface of the hollow portion of the needle body. 11. The anticoagulant, heparin sodium
The blood collection device according to claim 10, wherein (hospital) is used. 12. A blood collection analyzer, wherein the blood collection unit comprising the blood collection needle and the blood collection pump unit according to claim 5 and an analysis unit for analyzing blood are provided on the same substrate. 13. The flow path of the blood collection section, the flow path of the analysis section for separating blood components, and the flow path of the analysis section for analyzing separated blood components are the same. 13. The blood collection analyzer according to claim 12, wherein the blood collection analyzer is provided on a substrate. 14. The method of manufacturing a blood collection needle according to claim 1, wherein a semiconductor process is used. 15. The method according to claim 14, wherein an SOI substrate is used as the substrate. 16. The method for producing a blood collection needle according to claim 14, further comprising a step of providing a SiO ₂ film on the inner surface of the hollow portion of the needle main body. 17. A method for manufacturing a blood collection analyzer for manufacturing the blood collection analyzer according to claim 12, wherein a semiconductor process is used. 18. The method according to claim 17, wherein an SOI substrate is used as the substrate. 19. The method for manufacturing a blood collection analyzer according to claim 17, further comprising a step of providing a SiO ₂ film on the inner surface of the hollow portion of the needle main body. 20. The manufacturing of a blood sampling analyzer according to claim 17, wherein a channel of the needle body and a diaphragm for the diffuser type micropump are connected and provided on the same substrate by a semiconductor process. Method. 21. The method for manufacturing a blood collection analyzer according to claim 17, wherein a diffuser-type micropump for pumping blood from a blood collection unit is provided on the same substrate by a semiconductor process. 22. The method according to claim 20, wherein the blood collecting part and the analyzing part are connected by a semiconductor process. 23. A functional device for collecting blood, such as a blood collecting needle or a pump, and a functional device for analyzing, such as a flow path, an electrode, or a heater, are provided on the same substrate by a semiconductor process. A method for manufacturing the blood collection analyzer according to the above. 24. The method of manufacturing a blood collection needle according to claim 1, wherein the method of holding the anticoagulant in the needle body is a method of dipping in an anticoagulant solution. Method of manufacturing a blood collection needle. 25. The method of manufacturing a blood collection device according to claim 5, wherein the method of holding the anticoagulant on the inner surface of the hollow portion of the needle body is performed by pumping a solution of the anticoagulant. A method for manufacturing a blood collection device, comprising using a method of sucking into the needle body. 26. The method of manufacturing a blood collection apparatus according to claim 5, wherein the method of holding the anticoagulant on the inner surface of the hollow portion of the needle body includes electrolyzing a solution of the anticoagulant. A method for manufacturing a blood collection device, wherein a method of sucking the needle into the needle body by guiding is used. 27. The blood collection analyzer according to claim 12, wherein a pump electrode, an electrophoresis electrode, and an analysis electrode are provided on the same substrate. 28. The blood collection analyzer according to claim 27, wherein a portion that comes into contact with blood from blood collection to analysis is formed as one component. 29. The blood collection analyzer according to claim 27, wherein a memory for writing personal information and the like is integrated. 30. Gulcose oxydase (G) on the inner surface of the analyzer.
28. The blood collection analyzer according to claim 27, wherein an OD) immobilized film is formed, and a blood sugar level is measured by detecting a change in conductivity. 31. A method of manufacturing a blood sampling analyzer for manufacturing a blood sampling analyzer according to claim 30, wherein the method of forming a gulcose oxydase (GOD) immobilized film on the inner surface of the analysis section includes a solution of gulcose oxydase (GOD). Using a method of sucking blood into the analysis section by electric swimming. 32. A method of manufacturing a blood sampling analyzer for manufacturing the blood sampling analyzer according to claim 30, wherein a solution of gulcose oxydase (GOD) is used as a method for forming a gulcose oxydase (GOD) immobilized film on the inner surface of the analyzer. A method for sucking blood into the analysis section by a pump.