WO2007135826A1

WO2007135826A1 - Method of application of target substance and chemical microchip

Info

Publication number: WO2007135826A1
Application number: PCT/JP2007/058485
Authority: WO
Inventors: Yukio Yamada; Naoto Kakuta; Taisuke Hirono
Original assignee: The University Of Electro-Communications; Kowa Company, Ltd.
Priority date: 2006-05-23
Filing date: 2007-04-19
Publication date: 2007-11-29
Also published as: JP2007315754A

Abstract

A target substance is made applicable to a microfine area in the surface of the inner wall of a channel having a microfine section. A substance having an affinity is first applied to a first region (M1) in the inner wall of a channel (B3) (a region extending along directions (K1), (K2), and (K3) each intersecting the lengthwise direction (J) for the channel (B3)). A first solution (D1) containing a target substance and a second solution (D2) not containing the target substance are then caused to flow in a laminar-flow state through the channel (B3). Thus, the target substance adheres, with satisfactory precision, to that second region (M2) of the first region (M1) which is in contact with the first solution (D1).

Description

Specification

Application method of target substance and microchemical chip

Technical field

The present invention relates to a coating method and a microchemical chip for applying a target substance to a minute area of an inner wall of a flow channel having a minute cross section.

Background art

Conventionally, microchemical chips for realizing a chemical reaction in a minute space have been used in various fields (for example, see Patent Document 1).

[0003] A microchemical chip that has a strong cross section is formed with a channel having a small cross section. A specific substance required for a chemical reaction (referred to as "target substance" in this specification) is an inner wall of the channel. You may want to apply to

Patent Document 1: Japanese Patent Laid-Open No. 2003-215140

Disclosure of the invention

Problems to be solved by the invention

[0004] However, an effective application method for applying the target substance to an extremely small area has not been proposed yet.

[0005] An object of the present invention is to provide an application method for applying a target substance to a minute area of an inner wall of a flow path, and a micro-mouth chemical chip.

Means for solving the problem

[0006] The present invention comprises a step of applying an affinity substance to a first region on the inner wall of the flow path along a direction intersecting the longitudinal direction of the flow path;

A step of attaching the target substance to a second region in contact with the first solution in a region where the affinity substance is applied by flowing a first solution containing the target substance in a laminar flow through the channel. And a method for applying a target substance.

[0007] Further, the first solution and the second solution not containing the target substance are caused to flow through the flow path in a laminar flow state.

[0008] Further, the target substance is an aggregation inducer for aggregating platelets in blood, The affinity substance is a bioaffinity substance capable of adsorbing the aggregation-inducing agent.

[0009] The present invention also includes a first flow path through which a first solution containing a target substance flows,

A second flow path through which a second solution containing almost no target substance flows,

The present invention relates to a microchemical chip comprising: a third channel through which the first solution and the second solution are flowed in layers by being connected to the downstream side of the first and second channels.

[0010] Further, the present invention is configured to adjust a laminar flow width of the first solution in the third flow path based on controlling a supply amount of the first solution to the first flow path. First solution supply means,

A second solution supply means configured to adjust a laminar flow width of the second solution in the third channel based on controlling an amount of the second solution supplied to the second channel; It is characterized by having.

The invention's effect

[0011] According to the present invention, the target substance can be applied to a predetermined area of the inner wall of the flow channel with high accuracy.

Brief Description of Drawings

[0012] FIG. 1 (a) is a perspective view showing a process of applying an affinity substance to the inner wall surface of a flow path, and FIG. 1 (b) shows a layer of a first solution containing a target substance. FIG. 5 is a perspective view showing a step of attaching a target substance to a region coated with an affinity substance by flowing in a flowing state.

FIG. 2 is a plan view showing the structure of a microchemical chip to which a target substance is applied.

FIG. 3 is an enlarged view showing a detailed structure of the microchemical chip of FIG.

[FIG. 4] FIG. 4 is an enlarged view of a portion H in FIG. 2 for explaining an example of a method of using the microchemical chip.

FIG. 5 is a plan view showing an example of the configuration of an apparatus for applying a target substance to a microchemical chip.

FIG. 6 is a plan view showing an example of the configuration of an apparatus for applying a target substance to a microchemical chip.

Explanation of symbols Micro chemical chip

> B 1st channel

B Second flow path

B 3rd flow path

D First solution

D Second solution

J Longitudinal direction of flow path

M 1st area

M 2nd area

P First solution supply means

P Second solution supply means

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, the best mode for carrying out the present invention will be described with reference to FIGS. 1 to 4. Here, FIG. 1 (a) is a perspective view showing a process of applying an affinity substance to the inner wall of the flow path, and FIG. 1 (b) shows that the first solution containing the target substance flows in a laminar flow state. FIG. 2 is a perspective view showing a process of attaching a target substance to a region where an affinity substance is applied, FIG. 2 is a plan view showing the structure of a microchemical chip to which the target substance is applied, and FIG. FIG. 3 is an enlarged view showing a detailed structure of the microphone mouth chemical chip of FIG. FIG. 4 is a cross-sectional view for explaining an example of a method of using the microchemical chip.

[0015] The present invention relates to a coating method for applying a target substance to a flow passage having a minute cross section (specifically, a minute region of an inner wall surface thereof), and a microchemical chip to which the target substance is applied. Is. The present invention also relates to a coating method for applying the target substance by utilizing the characteristics of a fluid flowing in a flow path having a minute cross section, and a microchemical chip to which the target substance is applied.

[0016] A method for applying a target substance according to the present invention is illustrated in FIG.

• Affinity substance is applied to the first region on the inner wall of channel B (the hatched region indicated by symbol M and the region along the direction κ, K, and K that intersects the longitudinal direction J of channel B) Process,

• By flowing the first solution D containing the target substance into the channel B in a laminar flow state, Of the first region M, the second region in contact with the first solution D (i.e., M in FIG.

1 1 2) to attach the target substance to

Consists of. Here, as a method of flowing the first solution D into the flow path B in a laminar flow state,

13

The second solution D that does not contain a target substance may be flown into the channel B together with the first solution D.

2 1 3

it can. The target substance may include an aggregation inducer for aggregating platelets in blood, and the affinity substance may include a biocompatible substance capable of adsorbing the aggregation inducer. Can do. The width of the first region M (longitudinal direction J

1

For example, the laminar flow width W of the first solution D is 50 zm.

1 1

Good. By the way, the flow path B in Fig. 1 is a force S with a rectangular cross section.

Three

Other shapes may be used. Figure 1 (a)

Then, the force of applying the affinity substance to the upper wall and both side walls is not limited to this.

[0017] On the other hand, as a microchemical chip to which the target substance is applied, the first channel B through which the first solution D containing the target substance flows, as illustrated by reference A in FIGS. 2 and 3, the target substance

1 1

2nd solution D that contains almost no (no or very little if any)

2 and the downstream of the first and second flow paths B and B.

2 1 2

The first solution D and the second solution D have a third flow path B through which the first solution D and the second solution D flow in layers.

one two Three

The ability to raise things S. Note that the symbol C in FIG. 2 indicates the sum of the first flow path B and the second flow path B.

1 2 Indicates the flow part. Further, symbol E in FIG. 3 denotes an interface between the first solution D and the second solution D.

1 Indicates 2. Further, the symbol I in FIG. 2 indicates the same direction as the symbol I in FIG.

In this case, the first solution supply means P is connected to the first channel B, and the first channel is connected.

1 1

It is possible to control the supply amount of the first solution D to B.

1 1

If the laminar flow width W of the first solution D in the third flow path B can be adjusted,

3 1 1

good. Similarly, a second solution supply means P is connected to the second flow path B so that the second flow

twenty two

The supply amount of the second solution D to the path B can be controlled, and by the control,

twenty two

The laminar flow width W of the second solution D in the third flow path B can be adjusted.

3 2 2

And good. The laminar flow width W, W of each solution D, D is adjusted by these solution supply means P, P

1 2 1 2 1 2 By doing this, the target substance can be applied to an area with an appropriate width. As shown in Fig. 5. As shown, the downstream side of the third channel B is connected to the fourth channel B arranged on the side where the first solution D flows.

3 1 4

The second solution D branches to the fifth channel B arranged on the flow side, and the first solution B

2 5 1 has an extrusion pump P as the first solution supply means, and a closed container L is installed in the fifth flow path B.

A first suction pump (second solution supply means) P may be arranged through 1 5 1. like this

Three

When the extrusion pump P is first operated in the apparatus, the first flow path B, the third flow path B, the fourth flow

1 1 3 Channel B and channel 5 B are filled with the first solution D. First suction in this state

4 5 1

When the pump P is operated, the suction force is changed from the air in the sealed container L to the 5th flow path B.

3 1 5

1 Solution D → extends from the first solution D in the third channel B to the second solution D in the second channel B

1 3 1 2 2 As a result, the first solution D in the fifth channel B and the first solution D in the third channel B

5 1 3 1 is discharged into the container L, and accordingly, the second solution D has the second flow path B force and the third flow path B.

1 2 2 3 and flows in a laminar flow state, and then discharged from the fifth flow path B into the container L

5 1

. Extrusion amount of first solution D by extrusion pump P and second solution D by first suction pump P

1 1 3 2 By adjusting the suction amount, the laminar flow width W of the first solution D and the laminar flow width W of the second solution D

1 1 2 2 can be changed. In addition, the second flow path B has an extrusion bonnet as a second solution supply means.

2

(See symbol P in FIG. 2), the second channel as the first solution supply means is placed in the fourth channel B.

twenty four

A suction pump (not shown) may be arranged. Further, as shown in FIG. 6, an extrusion pump P as a first solution supply means is disposed in the first flow path B, and a valve V is disposed in the second flow path B.

1 1 2

And the second suction as the first solution supply means via the sealed container L in the fourth flow path B.

4 2

³ is arranged, and the 5th channel B is connected to the 5th channel B via the sealed container L as a second solution supply means.

4 5 1

Even if the first suction pump P is arranged, it is good. In such a device, valve V

Three

When the suction pumps P and P are stopped and only the extrusion pump P is operated

3 4 1

First channel B, third channel B, fourth channel B, and fifth channel B are filled with first solution D.

1 3 4 5 1

The Rukoto. When both suction pumps P and P are operated in this state, the suction power is

3 4

, Sealed container and air in L → first solution D → third channel 5 in channel B and channel B

1 2 5 4 1 It reaches the second solution D in the second channel B through the first solution D in the channel B. This

3 1 2 2

When the valve V is opened and at the same time the extrusion amount of the extrusion pump P is reduced to a certain level, the first solution D in each of the channels B and B and the first solution D in the third channel B Solution D is

4 5 1 3 1 Container and discharged into L, and accordingly, second solution D is second flow path B force third flow path Is supplied to B and flows in a laminar flow state, and then discharged from the fifth flow path B into the container L.

3 5 1

The The suction amount of the second solution D by the first suction pump P and the first solution by the second suction pump P

3 2 4

By adjusting the suction amount of liquid D, the laminar flow width W of the first solution D and the laminar flow of the second solution D

1 1 1 2 The width W can be changed. Or, with the suction pumps P and P,

2 3 4

P is also operated simultaneously, and both the suction pump P and the extrusion pump P

1 3 1 1 The channel width of the buffer D flowing through the third channel B and the fourth channel B may be adjusted.

3 4 1

[0019] The main body portion of the above-described microchemical chip A is preferably formed of glass or resin.

[0020] Next, a method of using the microchemical chip in which the aggregation-inducing agent is applied to the inner wall of the flow path as described above will be described.

[0021] In using this microchemical chip, a buffer solution is poured as the first solution D,

1

Blood flows as second solution D. Then, the buffer solution D is supplied by the first solution supply means P.

2 The supply amount of 1 is adjusted, and the supply amount of the blood D is adjusted by the second solution supply means P.

1 2 2

The laminar flow width of the buffer D and the blood D in the third channel B

3 1 2

W and W will be adjusted,

1 2

• As shown in Fig. 4 (a), aggregation inducer G is in contact with buffer D only, and blood D

1 2 No contact,

• As shown in Fig. 4 (b), blood D begins to contact the agglutinating agent G

2

• As shown in Fig. 4 (c), all areas where the aggregation-inducing agent G is applied are in contact with blood D

2

State

Can produce.

[0022] Thus, the unaggregated state of platelets and the state of aggregation can be observed, and detailed analysis (for example, analysis of how the size, area, and volume of aggregates change with time) )It can be performed. In addition, even when still images or moving images must be taken for comparison between the unaggregated state and the agglomerated state, it is only necessary to photograph “location G where the aggregating agent is applied”. Yes, it becomes easy.

Industrial applicability

The present invention is useful for applications in which a target substance is applied to a minute area on the inner wall of a flow passage having a minute cross section. Can be used.

Claims

The scope of the claims

[1] Applying an affinity substance to the first region of the inner wall of the flow path along the direction intersecting the longitudinal direction of the flow path;

A step of attaching the target substance to a second region in contact with the first solution in a region where the affinity substance is applied by flowing a first solution containing the target substance in a laminar flow through the channel. When,

A method for applying a target substance, comprising:

[2] In the flow path, the first solution and the second solution not containing the target substance are allowed to flow in a laminar flow state.

The method for applying a target substance according to claim 1, wherein:

[3] The target substance is an aggregation inducer for aggregating platelets in blood,

2. The method of applying a target substance according to claim 1, wherein the affinity substance is a biocompatible substance capable of adsorbing the aggregation-inducing agent.

[4] a first channel through which a first solution containing a target substance flows;

A third channel through which the first solution and the second solution are flowed in layers by being connected to the downstream side of the first and second channels;

Micro chemical chip equipped with.

[5] The first solution supply configured to adjust the laminar flow width of the first solution in the third channel based on controlling the supply amount of the first solution to the first channel. And a second solution supply configured to adjust a laminar flow width of the second solution in the third channel based on controlling a supply amount of the second solution to the second channel. The microchemical chip according to claim 4, further comprising: means.