JP2001153860A - Liquid processing conduit assembly - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a reactor device capable of arranging a larger number of reaction vessels at high density. SOLUTION: A liquid processing conduit assembly comprises a plurality of groups formed of a plurality of liquid processing conduits arranged in parallel on the same plane. Each liquid processing conduit comprises a reaction part 1 for performing a reaction in the inner part, a connection part 2 connected to both ends of the reaction part, and an opening part 3 formed at the terminal end of the connection part to introduce and discharge a fluid to and from the reaction part. Each group is bent at least in one position, and the groups are arranged so that the protruding parts formed by such a bending are mutually butted.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a reaction apparatus which is an assembly of liquid processing pipes for reacting a small amount of liquid therein. More specifically, the liquid processing pipes are a collection of liquid processing pipes in which a plurality of liquid processing pipes are densely integrated in a low area, and further, the inside of the liquid processing pipes can be optically observed. The present invention relates to a reactor that is a road aggregate.

[0002]

2. Description of the Related Art A nucleic acid probe is immobilized in a tubular reaction vessel, and a hybridization reaction is carried out through a single-stranded DNA sample fluorescently labeled in the reaction vessel. Whether a DNA having a specific base sequence is present in the sample is determined. A device has been invented for determining whether or not to make a decision. In such a device, a large number of reaction vessels are integrated, and all the reaction vessels are arranged on the same plane so as to be advantageous for optical observation.
The number that can be integrated as a device is limited.

On the other hand, when reacting a large number of samples as many as several hundreds, the amount of reagent to be used is reduced, and the use of containers as small as possible allows low-cost, multi-sample processing at a time. It is desirable to be able to do so. In recent years, it has been proposed to use a minute chamber or the like formed by a semiconductor processing technique on a silicon wafer or a glass wafer as a container having a minute capacity. Such a small volume reaction vessel is formed on a silicon wafer or glass about 4 inches in diameter. In general, the sample before the test has 96 holes, 38
A multi-well pipettor is used as a means for transferring such a sample solution from the plate to the reaction vessel, which is maintained in a plate having 4 or 1536 wells or the like. Therefore, it is desirable that the interval between the sample holes of the above-mentioned micro chamber or the like be an integral multiple of 9 mm, which is the interval between holes of a 96-well plate, for example. However, if the sample introduction holes are designed in a micro chamber at such intervals, the inlet / outlet occupies most of the surface area on a silicon wafer of about 4 inches, and a large number of reaction vessels are densely integrated. It is difficult to do.

[0004] When the reaction vessels are arranged on the same plane, there is a problem that the shape becomes complicated due to integration. When the shape is complicated, for example, even simple reading such as scanning with a linear optical sensor becomes difficult, and even if it is read, complicated image processing must be performed thereafter. It is.
In addition, as the shape becomes more complicated, there is a possibility that the flow of the liquid may be deteriorated, and the more bent portions, the more the tube may be clogged.

[0005]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a reactor in which more reaction vessels (or liquid processing lines or reaction tubes) are arranged at a high density. Another object of the present invention is to provide a reactor in which more reaction vessels are arranged in a simpler shape and at a higher density.

[0006]

Means for Solving the Problems As a result of earnest study, the inventor has found that the following means can solve the above problems and achieve the object. That is, the liquid processing pipeline assembly includes a plurality of groups each including a plurality of liquid processing pipelines arranged in parallel on the same plane, and each of the liquid processing pipelines is (1) A) a reaction section for performing a reaction therein;
(2) connecting portions connected to both end portions of the reaction portion;
(3) An opening formed at an end of the connection portion for flowing a fluid into and out of the reaction portion, and each group is bent at at least one position, and the protrusion formed by this bending is formed. A liquid processing pipeline assembly characterized in that the parts are arranged in abutment with each other.

[0007]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of the present invention will be described below. In a first preferred embodiment of the liquid processing pipeline assembly (hereinafter, also referred to as the present apparatus) of the present invention, a silicon wafer is used as a substrate, a groove is formed by etching the silicon wafer, and a sample flows into a desired position. It is manufactured by joining a light transmissive lid having a perforated opening to the substrate.

FIG. 1 is a plan view showing a silicon wafer 1 in which a groove is formed. The grooves can be formed by, for example, transferring a pattern onto a silicon wafer by photolithography and etching the resultant with a hydrofluoric-nitric-acetic acid solution. The conduit assembly for liquid processing of the present invention forms a groove by etching a silicon wafer in the pattern shown in FIG.
Thereafter, it can be manufactured by bonding a lid having an opening to the silicon wafer. Specifically, a silicon wafer having a thickness of 0.5 mm is etched at a depth of 0.1 mm in accordance with the pattern shown in FIG. 1 to form a groove, and further, a thin film having a desired opening formed therein, for example, 0.5 mm
By anodically bonding the lid of a thick light-transmissive plate, for example, a Pyrex glass plate, a reaction vessel having at least one surface that is optically transmissive can be manufactured. For example, the size of the silicon wafer may be about 25 mm to about 125 mm in diameter, the depth of the groove may be about 0.05 mm to about 0.4 mm, and the width of the groove may be about 0.05 m.
It may be about 5 mm from m.

As shown in FIG. 1, each liquid processing pipeline has a reaction section 2 for performing a reaction therein, a connection section 3 connected to both ends of the reaction section, and a hole formed in a lid. And an opening formed at a position corresponding to a position directly above the end portion 4 of the connecting portion. A fluid such as a sample liquid flows in through an opening formed in the lid, and the terminal 4 of the connecting portion and the connecting portion 3
To the reaction section 2 via the connection section 3 'and the end section 4', and is discharged from the opening located just above the end section 4 '.

Each of the liquid processing pipelines is bent at a substantially right angle in the reaction section, and a plurality of liquid processing pipelines are arranged in parallel according to the shape thereof.
A group 5 consisting of twelve groups is formed. The four groups 5
The convex portions formed by the bending of the reaction portion are arranged so as to abut each other. With such an arrangement, the reaction section 2 can be integrated at a high density near the center of the silicon wafer 1. Thereby, it is possible to easily process a plurality of reaction units at the same time, and to facilitate observation by scanning of the detector.
That is, since the scanning range of the detector is narrowed, for example, a DNA probe is fixed to the reaction portion of the liquid processing pipeline assembly, and the DNA probe is labeled with a fluorescent substance in the sample.
This is advantageous when detecting by binding NA.

In the first aspect, openings are provided at both ends of the reaction section and the connection section, and the reaction section is bent and its projections are arranged to abut each other. An opening can be arranged. The opening is pierced and arranged in the lid at a position just above the ends 4 and 4 'of the connection. Therefore, the position of each opening can be arbitrarily determined by adjusting the length and bending of the connecting portions 3 and 3 '. As shown in FIG. 1, the reaction section is bent, the reaction section is located at the center of the apparatus, and the openings are arranged near the periphery of the apparatus, so that a number of openings maintaining a desired distance from each other can be arranged. It becomes possible. This makes it possible to arrange a large number of liquid processing pipelines in a small area at high density.

The advantages of the bent structure of the reaction section will be described below with reference to FIGS. Figures are each 5c
It is a figure which shows how many reaction parts can be arrange | positioned in a square of mx5cm. The distance between the reaction parts is 5 mm. FIG.
Fig. 3 shows a schematic diagram in which a plurality of liquid processing pipelines are arranged without bending and parallel to one side of a square. FIG. 3 is a schematic view showing a case where the reaction portion is not bent but is arranged so as to intersect one side of the square at an angle of 45 °. FIG. 4 is a schematic view showing a case where the reaction portion is bent at 90 ° and the obtained protrusions are arranged so as to abut each other. As shown in Table 1, by bending the reaction part, it is possible to increase the number of reaction parts without changing the total extension. Therefore, the arrangement used in the apparatus of the present invention allows more liquid processing conduits to be arranged in the same area than in the prior art.

[0013]

[Table 1] It is preferable that the angle of the bend of the reaction portion does not hinder the flow of the liquid and does not clog the liquid. Further, it is advantageous to make the depth and / or width of the groove constituting the liquid processing conduit constant, because the manufacture of the apparatus can be facilitated and the movement of the liquid due to the influence of gravity can be prevented. Yes, and
Also suitable for optical observation. However, it is not limited to this.

The width or thickness of each liquid processing line and the distance between the liquid processing lines are selected depending on the optical detection limit, processing accuracy, viscosity of the fluid used and the material of the apparatus. It is possible.

Various modifications and changes can be made to each configuration of the present apparatus. For example, the arrangement pattern of the pipe assembly for liquid treatment of the present apparatus may be a pattern as shown in FIGS. Further, it is possible to change the angle of bending of the reaction portion to another angle, or to change the number of times of bending.

In the first embodiment, a silicon wafer is used. However, the present invention is not limited to this.
It may be cast plastic or quartz glass. The thickness may be sufficient to form a groove of about 0.05 mm to about 1 mm. Further, in order to perform optical observation, it is preferable that at least one surface of the present apparatus has light transmittance.

As described above, the conduit assembly for liquid treatment of the present invention can be formed by forming a groove in a substrate and joining a light-transmissive lid by means of an adhesive or heat fusion. It is possible. Alternatively, the liquid processing conduit of the present invention can also be formed by irradiating an excimer laser to a light transmissive substrate to form a hollow tube.

Further, the liquid treatment pipeline of the present apparatus has the same width and / or depth over the entire length of the reaction section 2, the connection sections 3 and 3 ', and the end sections 4 and 4'. May also have different widths and / or depths from one another. Furthermore, the width and / or the depth may be equal or different between the plurality of liquid processing pipelines included in the present liquid processing pipeline assembly. Further, the cross section of the liquid processing pipeline of the present apparatus may be rectangular or circular.
The shape of the opening may be circular or rectangular. Furthermore,
The reaction section 2 may be a straight tube or a curved tube, or may be a tube surrounded by a polygon and / or a closed curve.

A second preferred embodiment of the present invention is as described below. That is, two of the above-mentioned liquid processing pipeline aggregates are prepared, and these are superimposed one on top of the other, but the two liquid processing pipelines provided in the upper and lower aggregates are not overlapped with each other. It is a device obtained by combining an assembly.

For example, it is possible to manufacture the three members shown in FIGS. The member 9 of FIG. 7 is an upper layer, the member 15 of FIG. 8 is an intermediate layer, and the member 17 of FIG.
7 can be obtained by bonding a light-transmissive lid (not shown) to the cover 7. The member 9 is formed with a reaction part 10, a joint part 11, and a terminal part 12 of the joint part.
An opening is perforated in the lid at a position corresponding to a position directly above the end portion 12. The fluid that has flowed in from the opening is
To form a structure capable of flowing into the reaction section 18 of the member 17 and flowing out of the further opening. The respective layers can be joined by printing an adhesive such as an epoxy resin based on screen printing. Since the two reaction sections are formed as separate layers in this manner, the interval between the reaction sections can be made zero, and the capacity can be increased without changing the size of the entire apparatus. It becomes possible.

Alternatively, there is also a form in which two pipe assemblies for liquid treatment shown in FIG. 1 are manufactured and used as an upper layer and a lower layer, and are overlapped and joined in a positional relationship such that the reaction portions overlap each other. It is included in a preferred embodiment of the present invention. By having such a structure, an advantage that the detection time can be shortened is obtained. For example, after immobilizing DNA probes in both the upper and lower reaction sections, the reaction section arranged in the lower layer has a specimen DNA labeled with a fluorescent substance Cy3.
When the hybridization reaction is carried out after injecting the specimen DNA labeled with the fluorescent substance Cy5 into the upper reaction section, the excitation light of two wavelengths suitable for each of Cy3 and Cy5 is simultaneously detected. Irradiation can be performed. This makes it possible to detect two wavelengths of fluorescence at the same time, greatly reducing the detection time.

Further, in the above-described examples, all the end portions are arranged at every third position along the flow path, but two end portions are arranged in accordance with the required number of conduits and the shape or size of the substrate. The degree of freedom of design may be improved by displacing the above arrangements.

The liquid processing pipeline assembly of the present invention can be used for various reactions using a small amount of sample. For example, electrophoresis of a sample, detection and separation of a target substance in the sample, polymerase chain reaction (PCR), and the like can be performed, but not limited thereto. Further, the liquid processing pipe assembly according to the present invention may be called a reaction vessel assembly, a liquid processing pipe assembly, a detection pipe assembly, a separation pipe assembly, or an electrophoresis pipe assembly, depending on its use. It is also possible to change the name according to the use such as the body. In such a case, the liquid processing pipeline provided in the present assembly may be referred to as a reaction vessel, a reaction tube, a detection tube, a separation tube, an electrophoresis tube, or the like, depending on the case. The application is not limited to this.

[0024]

According to the pipe assembly for liquid treatment of the present invention,
It is possible to obtain a reactor in which more liquid processing lines are arranged at a high density. Further, in the present apparatus, more liquid processing pipelines can be arranged at a higher density with a simpler shape, so that it is easy to simultaneously process a plurality of liquid processing pipelines, Optical observation can be performed easily and in a short time.

[Brief description of the drawings]

FIG. 1 is a diagram showing a preferred embodiment of a liquid processing pipeline assembly of the present invention.

FIG. 2 is a schematic diagram showing an arrangement of reaction units.

FIG. 3 is a schematic diagram showing an arrangement of reaction units.

FIG. 4 is a schematic diagram showing an arrangement of reaction units.

FIG. 5 is a view showing a preferred arrangement pattern of the liquid processing pipeline assembly of the present invention.

FIG. 6 is a view showing a preferred arrangement pattern of the liquid processing pipeline assembly of the present invention.

FIG. 7 is a view showing members constituting a liquid processing pipeline assembly according to a preferred embodiment of the present invention.

FIG. 8 is a diagram showing members constituting a liquid processing pipeline assembly according to a preferred embodiment of the present invention.

FIG. 9 is a diagram showing members constituting a liquid processing pipeline assembly according to a preferred embodiment of the present invention.

FIG. 10 is a diagram showing members constituting a liquid processing pipeline assembly according to a preferred embodiment of the present invention.

[Explanation of symbols]

1. Silicon wafer 2. Reaction part 3. Connection
4. End of connection 5A. Liquid treatment pipeline 5B. Liquid treatment pipeline
5. Group 6. Reaction section 9. Member 10. Reaction section 11. Joint 12. End of joint 16. Hole 18. Reaction section

Claims (1)

[Claims] 1. A liquid processing pipeline assembly comprising a plurality of groups of liquid processing pipelines arranged in parallel on a same plane, wherein each of the liquid processing pipelines is ,
(1) a reaction section in which a reaction is performed, (2) a connection section connected to both ends of the reaction section, and (3) a fluid to the reaction section formed at the end of the connection section. Openings for inflow and outflow, and each group has at least one
A liquid processing pipeline assembly characterized by being bent at a position and arranging convex portions formed by the bending so as to abut each other.