JP4258311B2 - Chemical reaction cartridge - Google Patents

Description

  The present invention relates to a cartridge for chemical reaction, and more particularly to a cartridge for chemical reaction that can easily perform synthesis, dissolution, detection, separation, etc. of a solution according to a determined protocol without individual differences and at low cost. It relates to a structure that can easily provide heating, cooling, vibration, and light.

Conventionally, test tubes, beakers, pipettes, and the like have been used in processes such as solution synthesis, dissolution, detection, and separation. For example, as shown in FIG. 8, substance A and substance B are collected in a container 1 and a container 2 such as a test tube or a beaker, and injected into a container 3 such as a test tube or a beaker, and mixed and stirred. And make substance C. For the substance C synthesized in this way, for example, light emission, heat generation, coloration, colorimetry, and the like are observed.
Alternatively, the target substance may be separated and extracted by filtering or centrifuging the mixed substance.

  Further, the dissolution treatment, for example, the dissolution with an organic solvent is performed using a glass instrument such as a test tube or a beaker. Also in the case of the detection process, similarly to FIG. 8, the test substance A in the container 1 and the reagent in the container 2 are put in the container 3 and the reaction result is observed.

On the other hand, a bioanalyzer or the like uses a bag formed of a flexible material into a flat bag shape (see, for example, Patent Document 1).
FIG. 9 is a configuration diagram of a biochip described in Japanese Patent Application Laid-Open No. 2002-365299 of Patent Document 1. FIG. 4A is a sectional view, and FIG. 4B is a plan view. The flat blood collection bag 41 whose periphery is sealed has a fish-shaped bag at the center. The opening of the fish-shaped bag is sealed with a rubber stopper 42.

  In the blood collection bag 41, a collection part 43, a pretreatment part 44, a coupling part 45, and a waste liquid storage part 47 are formed in this order from the stopper 42 to the back. At the time of blood collection, the stopper 42 is inserted into a syringe (not shown). An injection needle protrudes inside the syringe and penetrates the stopper 42.

  At the time of blood collection, the subject is pierced with the needle tip that is outside the syringe, and the hooks 52 and 53 of the blood collection bag 41 are pulled outward to collect blood in the collection unit 43. After blood collection, remove the syringe from the blood collection bag. Thereafter, as shown in FIG. 10, the blood collection bag 41 is crushed from the collection unit 43 toward the pretreatment unit 44 with the rotation rollers 61 and 62 interposed therebetween. The collected blood is sent to the preprocessing unit 44.

  When the positions of the rollers 61 and 62 advance and crush the bag portion 48, the solution in the bag portion 48 breaks the valve 49 and flows into the pretreatment portion 44. Next, the solution of the bag part 50 flows into the pretreatment part 44 in the same manner. When the predetermined processing is completed in the preprocessing unit, the roller is rotated to send the processed blood to the coupling unit 45.

  A DNA chip 46 is disposed in the coupling part 45, and hybridization is performed. Excess blood and solution pushed out from the pretreatment unit 44 accumulate in the waste liquid storage unit 47. The state of the hybridized DNA chip is observed by a reading device arranged outside.

JP 2002-365299 A (page 3 to page 4, FIGS. 1 to 4)

However, the conventional method using a beaker or a pipette has a problem that the operation is complicated, individual differences are large, and labor is required. In the case of a blood collection bag, there is a problem that the solution cannot be easily moved due to lack of elasticity.
In order to solve this, there is an attempt to make a cartridge. However, when the cartridge is made, there are the following problems.
(1) For example, when gene amplification is performed, heating and cooling are required, and when handling samples in which DNA is bound to microparticles, the microparticles may be vibrated, but they are made of a thick material such as a tube. This cartridge has a drawback that it is difficult to transmit heat and vibration.
(2) When it is formed of thin glass, there is a disadvantage that a solution containing bacteria inside the cartridge is scattered when it is disposable, which is dangerous, and there is a disadvantage that a glass-structured cartridge is expensive.

  Therefore, the problem to be solved by the present invention is that even a cartridge can be heated and cooled at high speed, vibrations can be sufficiently transmitted, and the influence of heating and cooling and vibration on an adjacent part is small, and The object is to provide a chemical reaction cartridge having a safe and inexpensive structure.

In order to achieve such a problem, the invention according to claim 1 of the present invention is:
A cartridge used to perform a chemical reaction of a sample,
At least a part of the container is formed of an elastic body and is formed in a sealed shape.
In the container, two or more chambers arranged to be connected or connectable with a flow path are formed,
A thin elastic film is formed on a part of the elastic body so as to contact a working means outside the cartridge that applies heating or cooling or vibration to the sample in the room ,
The flow path or the chamber is crushed by a roller and is in contact with the action means in a state where the internal pressure of the chamber is equal to or higher than atmospheric pressure .

  In this way, if the elastic part of the part that contacts or introduces the action means is made into a thin film, the sample in the room can be heated and cooled at high speed, vibrations are transmitted well, and heating by light irradiation is also possible easily It has the effect of becoming.

In this case, it is appropriate that the thin elastic film has a thickness of 0.1 to 1 mm.
Further, when the action means is in contact, the flow path or the chamber is crushed by a roller so that the atmospheric pressure in the room covered with the thin elastic film becomes equal to or higher than the atmospheric pressure. As a result, the thin elastic film has no wrinkles in the stretched state and is in surface contact with the jig, so that heat and vibration from the jig are well transmitted to the room through the elastic film.

In addition, as in claim 3 , if the cutout portion is formed in the elastic body portion around the thin elastic film, or the heat insulating material or the vibration isolating material is buried, the influence of heat and vibration on the surroundings is reduced. .

As is apparent from the above description, the present invention has the following effects.
(1) Even with a cartridge, heating and cooling of an indoor sample can be easily performed at high speed.
(2) Vibration can be well transmitted to the sample.
(3) If the elastic body portion around the thin elastic film is notched or is filled with a heat insulating material or a vibration isolating material, the influence of heat and vibration on the surrounding can be easily reduced.
(4) Since it has a simple structure, it is inexpensive, and since it is a sealed type, there is no risk of dangerous samples leaking to the outside, and an inexpensive and safe cartridge can be easily realized.

Hereinafter, the present invention will be described in detail with reference to the drawings. FIG. 1 is a view showing an embodiment of a basic structure of a chemical reaction cartridge according to the present invention. 1A is a perspective view, FIG. 1B is an elastic body bottom view, and FIG. 1C is a ZZ ′ cross-sectional view. The chemical reaction cartridge 100 is formed of an elastic body 110 such as rubber that is airtight and elastic, and a flat substrate 120 made of a hard material.
Note that a viscoelastic body or a plastic body can be used as the elastic body 110 of the cartridge (however, in the embodiment, the case where an elastic body is used will be described as an example).

On the back surface of the elastic body 110, as shown in FIG. 1B, solution holes (hereinafter referred to as chambers) 111 and 112, which are recessed on the front surface side, and a reaction chamber (referred to as a reaction chamber) 113, respectively. A waste liquid storage chamber (referred to as a waste liquid storage chamber) 114 and a flow path 115 connected to each chamber are formed.
The planar adhesion region 116 other than the chamber of the elastic body 110 and the flow path is adhered to the surface of the substrate 120 as shown in FIG. As a result, each chamber and the flow path are sealed with the elastic body 110 and the substrate 120, so that external leakage of the solution can be prevented.

  The transfer of the solution in the cartridge having such a configuration will be described. Solution A and solution B are respectively injected into the chambers 111 and 112 formed in the cartridge 100 in advance. For example, as shown in FIG. 1 (c), the injection needle 117 is directly pierced into the elastic body 110 and injected by a syringe 118. Since the elastic body 110 is made of an elastic material, the needle hole is naturally closed when the injection needle 117 is pulled out. For complete sealing, the needle hole is filled with an adhesive or the like after the solution is sealed, but it may be sealed by heating and dissolving.

  After the injection, as shown in FIG. 2, the roller 130 is pressed from above at the left end of the cartridge 110 to such an extent that the chamber 111 is crushed. The roller 130 presses the cartridge 110 over its entire width. In this state, when the roller 130 is rotated from the position 1 and moved rightward as shown in FIG. 3A, the solution A stored in the chamber 111 is pushed rightward. Solution A is fed into the reaction chamber 113 through the flow path 115. The air that has entered the chamber 113 is sent out to the waste liquid storage chamber 114.

Subsequently, when the roller 130 is rotated and moved to the position 2 as shown in FIG. 3B, the delivery of the solution B in the chamber 112 starts. The solution B is pushed out to the reaction chamber 113 through the flow path 115. At this time, the flow path 115 is also crushed by the pressing of the roller 130, and this becomes a check valve, preventing the backflow of the solution B into the chamber 111.
In this way, fluid substances in the room can be moved or blocked.

Solutions A and B enter reaction chamber 113 and mix to react. The reaction referred to here is, for example, mixing, synthesis, dissolution, separation, and the like.
In addition, by using such a cartridge, for example, dioxin and DNA can be detected.

Further, as shown in FIG. 3C, after the roller 130 is rotated and moved to positions 3 to 6 and then reversely moved to position 7 as shown in FIG. 3D, the solution is easily mixed. be able to.
Normally, the roller 130 is ended by a rotational movement in one direction (one pass).

  Such a cartridge can be manufactured in a small size, light weight, and low cost, and processing protocols such as mixing, synthesis, dissolution, separation, and detection of substances can be easily performed without individual differences in a sealed cartridge.

The present invention is obtained by adding a configuration that can heat and cool a sample in a room at a high speed and can sufficiently transmit vibration to the sample.
FIG. 4 is a block diagram showing the main part of one embodiment of the present invention, which is suitable for amplifying a gene by a PCR (Polymerase Chain Reaction) method in a cartridge or handling a sample in which DNA is bound to magnetic particles. It has a structure. Hereinafter, the characteristic part will be described in detail. Since other parts are the same as the above-described basic configuration, the description thereof is omitted.

In FIG. 4, reference numeral 200 designates the tip of the cartridge in contact with the thin elastic film 110a of the cartridge to heat or cool the sample in the chamber A (for example, the reaction chamber 113 in FIG. 1) or to apply vibration. It is an action means. In the following embodiments, this action means is called an external jig. The sample refers to a solution such as DNA or magnetic particles.
The formation part of the elastic film 110a is local and is limited to the upper part of the chamber A where the jig 200 abuts. The elastic film 110a in that portion is thinner than the other elastic body portions and has a thickness of 1 mm or less. The optimum film thickness t is, for example, 0.1 to 1 mm.

Next, the operation in such a configuration will be described. A sample is introduced into the chamber A of the cartridge, and the internal pressure of the chamber A is increased by closing the flow path in the cartridge. The elastic film 110a is in a tensioned state.
The internal pressure is not limited to the local chamber A portion, but may be increased over the entire chamber and the flow path in the cartridge.

The tip of the external jig 200 is pressed and brought into close contact with the surface of the elastic film 110a having a high internal pressure. Depending on the treatment, the sample can be heated, cooled or vibrated.
In the process of amplifying genes by PCR, heating and cooling are repeated. Since the elastic film 110a is thin and the sample is directly heated and cooled through the elastic film 110a that is in close contact, the response is much faster than the conventional indirect heating and cooling.

  In addition, when diffusing the DNA-bonded magnetic particles placed in the chamber A, the tip of the external jig 200 is vibrated, and the vibration is transmitted to the sample through the closely contacted elastic film 110a. This vibration causes the magnetic particles in the sample to diffuse.

  In this way, only the elastic body at the upper part of the target chamber is formed as a thin film of 1 mm or less, and the external jig 200 can be brought into close contact with each other so that the sample can be directly heated / cooled or vibrated easily. Heating / cooling is limited to the sample and acts directly, and is hardly transmitted to other parts and has no effect, so that the speed can be increased. Similarly, the vibration acts directly on the sample only, hardly transmits to other parts and has no effect.

The present invention is not limited to the above-described embodiments, and includes many changes and modifications without departing from the essence thereof.
For example, as shown in FIG. 5, the internal pressure of the chamber A may be generated by pressing (or introducing) an external jig. In this case, the inlet / outlet channels 113a and 113b formed in the same direction from the chamber A are simultaneously crushed by the rollers 130 (to be valve-stopped), the chamber A is sealed, and the jig 200 is pressed against the elastic membrane. Thereby, the internal pressure of the chamber A becomes high.

  Further, in order to reduce the transmission of heat and vibration to other parts, as shown in FIG. 6A, a notch 110b may be formed in the elastic body part around the area where the external jig 200 contacts. Good. Or as shown in FIG.6 (b), you may embed the filling member 110c of a heat insulating material or a vibration isolator in the notch.

  Further, as shown in FIG. 7, the elastic film 110a may be formed of a transparent film. When formed with a transparent film, fluorescence during DNA hybridization can be easily observed by the reader 300 through the window (elastic film 110a) of the transparent film. When the sample is heated, laser irradiation through a window may be used instead of heating with an external jig.

Further, if the elastic film 110a is not wrinkled or contains bubbles, the internal pressure of the chamber can be almost atmospheric pressure.
Further, the substrate may be formed of an elastic body.

Further, the vertical relationship between the cartridge and the external jig may be reversed from that in the embodiment. That is, the cartridge may be turned upside down and the external jig pressed against the elastic film 110a from below.
Further, the elastic body is not limited to pressing over the entire width of the cartridge by the roller as in the embodiment, but an external force is applied from the outside of the container to partially block the flow path or the chamber or both, and the fluid in the flow path or the chamber. The substance may be moved or blocked.
Further, the pump or valve that plays such a role is not based on an external force, but an external pump from the outside of the cartridge or an internal valve made of a shape memory alloy or the like may be used.

It is a figure which shows the basic composition of the cartridge for chemical reactions which concerns on this invention. It is a figure which shows an operation state. It is a figure which shows the other example of an operation state. It is a principal part block diagram which shows one Example of the cartridge for chemical reaction which concerns on this invention. It is a principal part block diagram which shows the other Example of this invention. It is a principal part block diagram which shows the further another Example of this invention. It is a principal part block diagram which shows the further another Example of this invention. It is a figure explaining the conventional processing system. It is a block diagram of the conventional blood collection bag. It is a figure for demonstrating the operating method of a blood collection bag.

Explanation of symbols

DESCRIPTION OF SYMBOLS 100 Cartridge 110 Elastic body 110a Elastic film 110b Notch 110c Filling member 111,112, A chamber 113 Reaction part chamber 114 Waste liquid storage chamber 115 Flow path 116 Adhesion area | region 117 Injection needle 118 Syringe device 120 Substrate 130 Roller 200 External jig 300 Reader

Claims (3)

A cartridge used to perform a chemical reaction of a sample,
At least a part of the container is formed of an elastic body and is formed in a sealed shape.
In the container, two or more chambers arranged to be connected or connectable with a flow path are formed,
A thin elastic film is formed on a part of the elastic body so as to contact a working means outside the cartridge that applies heating or cooling or vibration to the sample in the room ,
A chemical reaction cartridge , wherein the cartridge or the chamber is crushed by a roller so that the internal pressure of the chamber is equal to or higher than atmospheric pressure, and the cartridge is in contact with the action means .   The chemical reaction cartridge according to claim 1, wherein the thin elastic film has a thickness of 0.1 to 1 mm. 3. The chemical reaction cartridge according to claim 1, wherein a cutout portion is formed in the elastic body portion around the thin elastic film, or a heat insulating material or a vibration isolating material is embedded .

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