JP2002369816A - Hollow needle, inspection chip using the same and blood analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a thin injection needle having sufficient strength. SOLUTION: A hollow needle 40 is formed in an almost hollow cylindrical shape with silicon. A tapered surface 46 is provided on one end, the outer diameter is equal to or less than 200 μm and the length is equal to or more than 500 μm.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a hollow needle, a test chip using the hollow needle, and a blood analyzer.

[0002]

2. Description of the Related Art In a conventional blood test, after collecting blood, blood is transferred to a test tube, centrifuged blood cells are separated, only the supernatant is collected, transferred to another test tube, and then transferred to a test device for testing. I am doing blood analysis. For this reason, it takes, for example, several days until an inspection result is obtained. In addition, blood is wasted on the way, and the amount of blood collected is as large as about 5 ml.

[0003] In general, a stainless steel injection needle is used for blood collection, but it is painful to pierce the injection needle. Therefore, especially for people who need frequent examinations, the elderly, and infants, it is extremely burdensome, and low-invasive blood sampling is strongly desired.

[0004] In order to minimize pain during blood collection, a thin injection needle may be used.

[0005] A commercially available stainless steel injection needle has an outer diameter of 0.3 mm or more. With current technology, outer diameter 0.2m
About m is a technical limit.

When a glass is stretched like a micropipettor, it is possible to make a needle having an outer diameter of 40 μm. However, since it is made by a skilled worker by hand, it is very expensive and cannot be made at once with high accuracy and low cost. Moreover, glass cannot secure sufficient strength as a hollow needle.

[0007] JP-A-2000-185034 discloses that
SOI (Silicon on Insulin)
g) 50 μm outer diameter integrated with pump using wafer
It has been proposed to create a degree needle. However, the specific shape and manufacturing method of the needle are not sufficiently disclosed.

[0008]

Accordingly, a technical problem to be solved by the present invention is to provide a thin injection needle having sufficient strength.

[0009]

The present invention provides a hollow needle having the following structure in order to solve the above technical problems.

[0010] The hollow needle is formed in a substantially hollow cylindrical shape from silicon. One end has a tapered surface. The outer diameter is 200 μm or less and the length is 500 μm or more.

In the above configuration, the tapered surface makes it easier to pierce the hollow needle. When a hollow needle is used for blood collection, a length of 500 μm or more is required so that the tip reaches a capillary. If silicon is used, a hollow needle having an outer diameter of 200 μm or less, which is a technical limit of a stainless steel tube, can be produced. Silicon is a material that has high breaking strength and is chemically stable, and thus is suitable as a material for the hollow needle. Further, if silicon is used, a large number of hollow needles can be manufactured with high processing accuracy, in large quantities and at low cost by a semiconductor process, and a tapered surface can be easily formed.

Therefore, a thin injection needle having sufficient strength can be provided.

Preferably, the tapered surface is a crystal orientation (111) plane of silicon.

The crystal orientation (111) plane of silicon is a mirror surface and has high strength, so that it is suitable for a tapered surface to which resistance is added during needle insertion. Further, if a silicon wafer having a surface of a predetermined orientation with respect to the crystal orientation (100) plane is used, a tapered surface at a desired angle can be formed.

Specifically, a silicon wafer whose surface has a predetermined off-angle with respect to the (100) crystal orientation plane is used. The tapered surface is formed by the crystal anisotropic etching. An outer peripheral surface and an inner peripheral surface are formed by wet etching.

Crystal anisotropic etching By combining dry etching and wet etching, hollow needles can be formed so that the thickness direction of the silicon wafer is the axial direction of the hollow needles.

Preferably, T is applied to a thick silicon wafer.
After forming an oxide film as a mask by EOS-CVD, an outer peripheral surface and an inner peripheral surface are formed by dry etching.

By using a silicon wafer thicker than a normal silicon wafer (eg, 525 μm in thickness), the thickness direction of the silicon wafer is set to be the axial direction of the hollow needles, and the silicon wafer having a length of 500 μm or more is used. Needles can be made. When dry etching is performed, not only silicon but also an oxide film of a mask is gradually removed. For example, the etching rate of the oxide film (SiO ₂ ) is 1/200 of the etching rate of silicon (Si). In order to perform deep processing (processing of the outer diameter and inner diameter of the hollow needle) on a thick silicon wafer by dry etching, it is necessary to increase the thickness of the oxide film. The oxide film can be formed only to a thickness of about 1.5 μm by the thermal oxidation method, but a thicker oxide film (for example, a thickness of 5 μm or more) can be formed by the TEOS-CVD. . Therefore, the hollow needle can be processed using a thick silicon wafer.

Preferably, unevenness is formed on the outer peripheral surface by light etching.

By making the outer peripheral surface of the hollow needle into a saw-tooth shape, the hollow needle can be easily pierced.

Further, the present invention provides an array needle in which a plurality of hollow needles having the above-mentioned constitutions are erected on the upper surface of a common base with the needle tips facing upward.

The use of a plurality of hollow needles increases the probability that any of the hollow needles will reach the blood capillaries at the blood collection site, so that blood can be collected reliably. Also, the amount of blood collected can be secured.

Further, the present invention provides a test chip provided with the hollow needle of each of the above structures or the array needle of the above structure.

The test chip can be tested in a short time by using a small amount of blood collected with a hollow needle or an array needle.

Further, the present invention provides a blood analyzer provided with the hollow needle of each of the above structures or the array needle of the above structure.

The blood analyzer can perform a test in a short time by using a small amount of blood collected by a hollow needle or an array needle.

[0027]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A hollow needle, a test chip and a blood analyzer using the hollow needle according to an embodiment of the present invention will be described below with reference to FIGS.

FIG. 4A shows a single needle 30. FIG.
(B) shows a case where a plurality of needles 31 are connected to a common base
Array needle part 32 arranged on the top 3 with the needle point up
Is shown.

FIG. 1 shows a test chip 10 having an array needle 32 on the upper surface 16 of the main body.

In the test chip 10, a blood cell separating unit 24 connected to the array needle 32 and the flow path 23 and a blood cell separating unit 2 are connected.
A mixing unit 26 connected to the mixing unit 4 by a flow path 25 and a detection unit 28 connected to the mixing unit 26 by a flow path 27 are arranged.

In the inspection chip 10, the main body and the needle 31 can be made by the same silicon process. Alternatively, the needle 31 prepared in advance may be incorporated into a resin body by insert molding or the like.

By pressing a blood collection site (for example, an earlobe or a finger) against the array needle portion 32 of the test chip 10,
Each needle 31 of the array needle part 32 pierces the blood collection site. Since the plurality of needles 31 are arranged at appropriate intervals in the array needle part 32, some of the needles 31 reach the blood capillaries at the blood collection site, and blood can be collected by capillary action. Thereby, the amount of blood collected can be ensured.

The collected blood is sent to the blood cell separation unit 24. A microstructure (not shown) is arranged in the blood cell separation unit 24, and large red blood cells and the like are caught and the plasma component excluding the blood cell component is sent to the mixing unit 26.

A reagent is arranged in the mixing section 26, and the plasma component mixes with the reagent. The mixed liquid is sent to the detection unit 28.

The test chip 10 is mounted on a blood analyzer (not shown). An analysis unit (not shown) is arranged in the blood analyzer so as to face the detection unit 28 of the test chip 10 mounted. The analysis unit is, for example, the detection unit 2
The light source 8 irradiates light and a light detector that detects reflected light or transmitted light from the detection unit 28, and detects a reaction result between the blood and the reagent.

FIG. 2 shows a test chip 12 according to a modification.
The inspection chip 12 has an array needle portion 32 disposed on the side surface 18 of the main body, and includes a pump 22. The array needle section 32 and the pump 22 are connected by a flow path 21, and the pump 22 and the blood cell separation section 24 are connected by a flow path 23a. Other parts are configured similarly to FIG. By providing the pump 22, it is possible to collect a certain amount of blood from the needle 31 which is thin and has a large flow path resistance.

FIG. 3 shows a test chip 14 according to another modification. The inspection chip 14 uses a single needle 30 instead of the array needle 32. The single needle 30 and the pump 22 are in the flow path 2
1a. The other parts are configured similarly to FIG. This test chip 14 is suitable when the vein to collect blood is fixed.

The single needle 30 and the needle 31 of the array needle part 32
Can be formed by, for example, a silicon process as described below.

As shown in FIG. 8, by using a silicon wafer, dry etching and wet etching are combined to form a needle having a tapered tip.

First, oxidation is performed on the upper and lower surfaces of the silicon substrate 50.
The films 52 and 54 are formed (see FIG. 8A). silicon
The substrate 50 is, for example, a silicon wafer having a thickness of 1.5 mm.
Use The oxide films 52 and 54 are, for example,
By TEOS-CVD so that the thickness becomes 10 μm
Form a film. Specifically, TEOS, that is, (C₂H ₅
O)₄The film is formed using Si gas as plasma. This
Thus, a thick film can be formed at a low temperature.

Next, a resist is applied to the upper surface, a predetermined mask pattern is exposed, and developed. Then, after etching the oxide film, the resist on the upper surface is removed (FIG. 8).
(See (2)). As a result, as shown by reference numeral 52a, the oxide film 5 on the upper surface corresponds to the tapered portion of the needle.
2 is removed by etching. A spin coater is used for resist coating. For the resist, for example, OFPR8
00 is used. An aligner is used for exposure. NMD-3 is used for development. For example, RIE is used for etching the oxide film.

Next, similarly, a resist is applied to the lower surface, exposed and developed, the oxide film is etched, and then the resist is removed (see FIG. 8 (4)). Thereby, the oxide film 54
As shown by reference numeral 54a, the portion corresponding to the hollow hole of the needle and the periphery of the needle is completely removed, for example, in a double circle shape.

Next, the upper surface is subjected to wet etching (crystal anisotropic etching) to remove the portion denoted by reference numeral 50a, thereby forming a tapered portion of the needle (FIG. 8).
(4)). For wet etching, for example, 30
% Potassium hydroxide to a depth of 100 μm. The silicon substrate 50 has a (100) surface, and the (111) surface having a high mirror rigidity becomes a tapered surface by anisotropic etching.

Next, the lower surface is dry-etched to remove a portion 50b surrounding the outer periphery of the needle and a portion 50c to be a hollow hole of the needle (see FIG. 8 (5)). For example, ICP (Inductively Coupled Plasma, Inductively Coupled Pl) is used for dry etching.
asma). At this time, it is preferable that wax is applied and temporarily fixed, for example, from the upper surface side so that a portion serving as a needle is not completely separated from the silicon substrate 50.

Next, light etching is performed to roughen a portion 50d serving as the outer peripheral surface of the needle in a saw-tooth shape so that the needle is easily pierced. For example, etching is performed for several minutes by a wet method using 50% potassium hydroxide. This light etching step can be omitted.

Next, the oxide film 54 on the lower surface is peeled off and completely removed, and the needle portion 51 is separated from the substrate 50 (see FIG. 8 (7)). The removal of the oxide film 54 is performed by a wet method.

Lastly, a hydrophilic treatment is performed, and the hollow hole 51a is formed.
To make the liquid easier to flow. The hydrophilic treatment is performed by, for example, a dry method using O ₂ gas. Or 10%
This is performed by a wet method in which HCl flows into the hollow portion of the needle.

Through the above steps, needles with high processing accuracy can be mass-produced at low cost.

Usually, the surface of a silicon wafer on which an IC is formed has a crystal orientation (100) plane. When a needle is made using such a silicon wafer as described above, the tip angle of the needle tip is fixed at 35.3 °. However, for example, there is a research report that a tip angle of about 30 ° is suitable for a needle made by stretching glass.

In order to arbitrarily change the tip angle, an appropriate off-angle silicon wafer may be used.

According to an example of the simulation results, a silicon wafer having an off-angle of ± 9.6 ° with respect to the (100) crystal orientation was subjected to 40 ° C. at 40 ° C. If etching is performed, the tip angle can be set to 25.6 °.

Incidentally, the tensile strength (breaking strength) of glass is very weak. The breaking strength of nickel is 500 ~
900 MPa, 1 GPa for stainless steel, and 7 for silicon.
It is 0 GPa, and a needle made of silicon can secure sufficient strength.

Next, an example of stress calculation of a hollow needle using silicon will be described with reference to FIGS.

First, the calculation conditions will be described. As shown in FIG. 5, the axial length from the tip 40a to the root 40b of the hollow needle 40 is 1 mm, and the tip angle θ is 35.3 °. An axial direction indicated by an arrow 48 on the tapered surface 46 of the needle tip;
63.662N each in the bending direction indicated by the arrow 49
When a pressure of / mm ² (converted from the result that 2N is required for a diameter of 200 μm) was applied, the equivalent stress of Mises on the surface 40c that was 10 μm away from the constraint surface of the root 40b in the axial direction was calculated. Inner diameter of hollow hole 42 and outer peripheral surface 4
4 is fixed to 1: 2, and the outer diameters are 20, 60, 1
Calculation was performed for 00 and 150 μm. The material of the hollow needle 40 was silicon, the Young's modulus E = 127.4 GPa, and the Poisson's ratio was 0.3.

FIG. 6 shows the calculation results when pressure is applied in the axial direction. Since the calculation result is one order of magnitude smaller than the tensile strength of silicon of 7.0 GPa, it is understood that the hollow needle 40 has a sufficient strength.

FIG. 7 shows the calculation results when pressure is applied in the bending direction. When the outer diameter of the hollow needle 40 is smaller than 100 μm, the tensile strength of silicon exceeds 7.0 GPa, and it is understood that the hollow needle 40 may be damaged. If the length in the axial direction of the hollow needle 40 is reduced or the inner diameter is reduced, it is possible to secure the strength when pressure is applied in the bending direction.

It should be noted that the present invention is not limited to the above embodiment, but can be embodied in other various modes.

[0058]

Since the hollow needle is formed by chemical etching using a silicon process, it can be processed with high accuracy even if the inner diameter and outer shape are small. Also,
The tapered shape at the tip can also be created with high accuracy without defects.

The inner diameter and the outer diameter can be changed to arbitrary dimensions. The tip angle can be arbitrarily changed to some extent by changing the off angle of the surface of the silicon wafer to be used.

Further, since the outer diameter is as small as 200 μm or less, a large amount can be produced at once at low cost. For example,
Approximately 1,000 4 inch wafers and 4,000 8 inch wafers can be produced simultaneously. If the above method is used, processing can be performed up to an inner diameter of about 10 μm.

Since silicon is used as the material, the breaking strength is 7.0 GPa, which is greater in each stage than conventional glass or stainless steel. Extremely unlikely.

Further, since silicon is used as a material, it is chemically stable to living tissue.

Further, since one side can be tapered and the tapered surface is a (111) oriented surface of silicon, it is a mirror surface, has higher mechanical strength than other directions, and is more advantageous as a needle tip which requires relatively pressure.

By reducing the needle diameter, minimally invasive can be achieved.

When using a single needle or within several needles, a micropump made by the same silicon process can be arranged on the same substrate and used as an ultra-small blood collection set. Also, by the same silicon process,
It is also possible to form a test chip for performing blood analysis (diagnosis) on the same substrate.

If the needle is used as a sword-like needle in which a plurality of needles are set in an array, a necessary blood collection amount can be secured only by the capillary force. In addition, a test chip for performing blood analysis (diagnosis) can be formed on the same substrate by the same silicon process.

Further, by using a plurality of sets of arrayed needles, the probability of the needle tips reaching the capillaries when puncturing the earlobe, fingertips, etc. is increased, so that blood is more easily collected. .

Since the needle can be made by the silicon process,
A pumping mechanism, a blood cell separation mechanism, a mixing mechanism, and a detection mechanism are simultaneously arranged on the same chip by the same silicon process, and a total system chip (test chip) from micro blood collection to blood analysis can be configured. This leads to an increase in throughput, and can be performed in a very short time from blood collection to blood analysis, and waste of blood volume is eliminated.

[Brief description of the drawings]

FIG. 1 is a configuration diagram of a test chip according to an embodiment of the present invention.

FIG. 2 is a configuration diagram of a test chip according to a modified example.

FIG. 3 is a configuration diagram of a test chip according to another modification.

FIG. 4 is a configuration diagram of a single needle and an array needle according to the embodiment of the present invention.

FIG. 5 is an explanatory diagram of a calculation model.

FIG. 6 is a diagram showing the relationship between the outer diameter of a hollow needle and stress.

FIG. 7 is a diagram showing the relationship between the outer diameter of a hollow needle and stress.

FIG. 8 is an explanatory view of a manufacturing process of a hollow needle.

[Explanation of symbols]

 30, 31, 40 hollow needle 42 hollow hole 44 outer peripheral surface 46 tapered surface 50 silicon substrate (silicon wafer) 52, 54 oxide film θ tip angle

Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (Reference) A61M 5/14 369B F-term (Reference) 4C038 TA06 UJ01 4C066 BB01 CC01 FF05 KK03 KK04

Claims (8)

[Claims] 1. A substantially hollow cylindrical shape made of silicon, having a tapered surface at one end, an outer diameter of 200 μm or less, and a length of 5 μm.
Hollow needle of 00 μm or more. 2. The hollow needle according to claim 1, wherein the tapered surface is a (111) crystal orientation of silicon. 3. A tapered surface is formed by crystal anisotropic etching using a silicon wafer whose surface has a predetermined off angle with respect to the crystal orientation (100) plane, and the outer and inner peripheral surfaces are formed by wet etching. The hollow needle according to claim 1, wherein the hollow needle is formed. 4. A thick silicon wafer is provided with TEOS-C
2. The hollow needle according to claim 1, wherein an outer peripheral surface and an inner peripheral surface are formed by dry etching after forming the oxide film as a mask by VD. 5. The hollow needle according to claim 1, wherein irregularities are formed on the outer peripheral surface by light etching. 6. An array needle, wherein the plurality of hollow needles according to claim 1 are erected on the upper surface of a common base with the needle tips facing upward. 7. An inspection chip provided with the hollow needle according to claim 1 or the array needle according to claim 6. 8. A blood analyzer comprising the hollow needle according to claim 1 or the array needle according to claim 6.