JP2004279202A - Analysis chip, analyzer and analysis method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a chip for analysis, an analyzer, and an analysis method, for performing analysis by using a small amount of specimen and reagent without causing the upsizing of analyzers, and quickly and uniformly mixing the specimen with the reagent. <P>SOLUTION: A chip is used having a flow path 2 formed therein, the area of whose cross-section normal to a flow direction broadens toward the direction. The specimen and the reagent are made to flow through the flow path 2 in the chip, with the specimen and the reagent isolated from each other by an isolation liquid, thereby rapidly mixing the specimen with the reagent. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an analysis chip, an analysis device, and an analysis method.
[0002]
[Prior art]
2. Description of the Related Art Conventionally, in research and development in the fields of biology and chemistry, analysis that detects multiple types of samples using a single reagent (hereinafter referred to as multi-sample analysis as appropriate) and analysis of a single sample using multiple types of reagents (Hereinafter, appropriately referred to as multi-item analysis), or an analysis performed by combining these multi-sample test and multi-item test is widely performed.
[0003]
As a general method of these analyses, for example, as disclosed in Patent Literature 1, a method of separately putting a sample and a reagent in a container such as a cuvette or a titer plate, mixing and detecting the sample and the reagent is widely performed.
In addition, a method of performing the above analysis in a flow of a liquid has been performed. The general method is to mix and detect a sample and a reagent in a pressure flow while selectively supplying a sample or a reagent by switching a valve, as in Patent Literature 2, for example.
[0004]
[Patent Document 1]
JP 2001-318101 A
[Patent Document 2]
JP-A-61-217765
[0005]
[Problems to be solved by the invention]
However, in the method using the above cuvette, it is necessary to prepare cuvettes according to the number of combinations of the sample and the reagent, so that the apparatus becomes large, and the amount of the sample and the reagent to be used becomes large. There were challenges.
In addition, in the method using a titer plate, the titer plate itself is generally large, and the robot needs to be robotized. Therefore, the size of the entire apparatus is increased, and the amount of a sample or a reagent to be used is large. There was a problem of becoming.
[0006]
In addition, the method of performing analysis in the flow of a liquid has a problem that it takes a long time to uniformly mix the sample and the reagent, and that a large amount of the sample and the reagent are used.
[0007]
The present invention has been made in view of the above-described problems, and is portable and can perform analysis with a small amount of a sample and a reagent without increasing the size of the apparatus. An object of the present invention is to provide an analysis chip, an analysis device, and an analysis method that can be mixed.
[0008]
[Means for Solving the Problems]
The present inventors have conducted intensive studies in view of the above situation, and as a result, while using a chip having a flow path formed such that the area of a cross section perpendicular to the flow direction expands on the way, while isolating the sample and the reagent with an isolating solution. By flowing the sample through the flow path of the chip, the sample and the reagent can be quickly mixed, and the analysis can be performed with a small amount of the sample and the reagent without increasing the size of the apparatus. Heading, the present invention has been completed.
[0009]
That is, the present application relates to an analysis chip in which a flow path is formed in a substrate, wherein the flow path has a first flow path and a second flow path, and the first flow path and the second flow path And an analysis chip, wherein a cross-sectional area of the second flow path is larger than a cross-sectional area of the first flow path. 1). If the analysis chip is used, the sample, the reagent, and the separation solution are caused to flow through the first flow path such that the space between the sample and the reagent is isolated by the separation solution. The sample can be analyzed by mixing the sample and the reagent in a channel (claim 12). Therefore, the analysis can be performed with a small amount of the sample and the reagent without increasing the size of the apparatus, and the sample and the reagent can be quickly mixed.
[0010]
At this time, analysis may be performed on one type of sample using a plurality of types of reagents (claim 13), and analysis may be performed on a plurality of types of samples using one type of reagent. In some cases (claim 14), a plurality of types of samples may be analyzed using a plurality of types of reagents (claim 15). This makes it possible to easily analyze a combination of a plurality of samples and reagents using a flow without preparing for analysis for each combination of sample and reagent.
[0011]
Further, an electric field may be applied to the flow path so that the sample, the reagent, and the isolation solution flow (claim 16). Thereby, an electroosmotic flow can be generated in the flow path, and accurate analysis can be performed.
[0012]
Separately from the sample, the reagent and the separating solution, an osmotic flow liquid for generating an electroosmotic flow by applying an electric field to the flow path, and the osmotic flow liquid is separated from the sample and the reagent. It is preferable to isolate with an isolating solution (claim 17). Thus, when an electric field is applied to the flow path to flow the sample, the reagent, and the isolation solution, the sample, the reagent, and the isolation solution can efficiently flow through the flow path with a smaller electric field. It becomes.
[0013]
Further, the permeate liquid may be a cleaning liquid (claim 18) or a calibration liquid for optical analysis (claim 19). This enables more accurate analysis.
[0014]
Further, the flow path has a third flow path having a smaller cross-sectional area than the second flow path on the opposite side of the second flow path from the first flow path. (Claim 3). Thus, a large amount of information can be reliably obtained from the liquid flowing through the flow channel by using a small detection area when performing the analysis. For example, reducing the detection area when performing optical analysis means reducing noise factors such as surface scratches and deformation, so that analysis can be performed reliably.
[0015]
Further, the second flow path is formed such that a cross-sectional area of the second flow path becomes gradually larger than a cross-sectional area of the first flow path from a connection portion between the first flow path and the second flow path. (Claim 2), wherein the cross-sectional area of the second flow path is different from the cross-sectional area of the third flow path by the second flow path and the third flow path. The second flow path may be formed so as to become gradually smaller toward the connection portion with the connection (claim 4). This allows the liquid to flow in the flow path while preventing unintended mixing.
[0016]
Further, a pair of electrodes or more may be provided at both ends of the flow path (claim 5). Thus, an electric field can be applied to the flow channel with a simple configuration, and the liquid in the flow channel can easily flow by electroosmotic flow.
[0017]
The surface of the flow channel may be subjected to a hydrophilic treatment, or the surface of the flow channel may be formed in advance of a hydrophilic material (claim 6). Accordingly, when the isolation liquid is hydrophobic, the affinity of the isolation liquid with the surface of the flow channel is lower than that of the reagent or the sample, so that the sample and the reagent may The intervening liquid can be efficiently removed.
[0018]
Further, another gist of the present application is characterized by comprising the above-described analysis chip, a driving device that causes the liquid in the flow path to flow, and an analysis unit that analyzes an analysis target in the flow path. An analyzer exists (claim 7). According to this analyzer, the analysis can be performed with a small amount of the sample and the reagent without increasing the size of the device, and the sample and the reagent can be quickly mixed.
[0019]
At this time, it is preferable to install an electric field driving unit that can apply an electric field to the flow path as the driving device (claim 8). The electric field driving unit may be an electrode and a power source installed so as to be position-adjustable (claim 9) or may be an electrode and a power source installed on the surface of the flow path (claim 10). Thereby, an electroosmotic flow can be generated in the flow path, and accurate analysis can be performed.
[0020]
A supply device for selectively supplying one or more of the sample, the reagent, and the isolation solution may be provided (claim 11). Thus, the analysis can be performed more quickly and accurately.
[0021]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, embodiments of the present invention will be described with reference to the drawings.
[0022]
[First embodiment]
FIGS. 1 to 9 and 13 illustrate an analysis chip, an analysis apparatus, and an analysis method according to a first embodiment of the present invention. FIGS. 10 to 12 illustrate first and second embodiments of the present invention. 13 shows a modification of the embodiment. FIG. 1 is a schematic view showing an outline of the analyzer, FIG. 2 is an enlarged sectional view schematically showing a main part of the analyzer, and FIGS. 3 to 7 are enlarged views of a main part of an analysis chip. FIG. 8 is a schematic plan view illustrating a modification of the analysis chip, FIG. 9 is a cross-sectional view schematically illustrating an enlarged cross section of a modification of the main part of the analyzer, and FIG. FIGS. 11 and 12 are schematic diagrams of the chip, FIGS. 11 and 12 are schematic diagrams illustrating the analyzer, and FIG. 13 is a cross-sectional view schematically illustrating an enlarged main part for describing the analyzer.
[0023]
As shown in FIG. 1, a flow path 2 through which a liquid can flow is formed in a straight line on the surface of a base 1 constituting an analysis chip according to a first embodiment of the present invention, and a lid 1a covers the flow path. Have been. The base 1 is usually made of glass, quartz, synthetic resin, or the like. In addition, at a place where the connector 4 and the electrodes 6, 7 described later are disposed, an opening 1b is formed in the lid 1a, so that the connector 4 and the electrodes 6, 7 can reach the flow channel 2 from outside the analysis chip. It is configured as follows. Therefore, the flow path 2 has a closed cross section at a position other than the connector 4 and the electrodes 6 and 7, and is opened to the outside only through the opening 1b formed in the lid 1a only at the connectors 4 and the electrodes 6 and 7 (FIG. 13). reference).
[0024]
The channel 2 is subjected to a hydrophilic treatment so that the surface has a hydrophilic property.
The method of the hydrophilic treatment is not particularly limited as long as the surface of the flow path 2 can have a hydrophilic property. Examples of the method include surface coating, wet chemical reforming, gas reforming, and surfactant treatment. , Corona discharge, surface roughening, metal deposition, metal sputtering, UV treatment, methods involving the addition of hydrophilic functional groups or hydrophilic molecules to the surface depending on the processing atmosphere (plasma method, ion implantation method, laser treatment Etc.).
[0025]
The flow path 2 includes a first flow path 2a, a second flow path 2b, and a third flow path 2c in this order from one end side, and the first flow path 2a, the second flow path 2b, The third channel 2c is formed at the same depth. Further, the first flow path 2a and the third flow path 2c are formed with the same width.
[0026]
Here, the second flow path 2b is formed so as to have a larger width than the first flow path 2a and the third flow path 2c, and extends from the first flow path 2a to the second flow path 2b. The width of the flow path 2 gradually increases from the connection between the first flow path 2a and the second flow path 2b, and the width of the flow path 2 increases from the second flow path 2b to the third flow path 2c. It is formed so as to become gradually smaller toward the connection between the second flow path and the third flow path. Therefore, the flow path 2 is formed so as to smoothly and continuously increase in width in the second flow path 2b, and thereafter smoothly and continuously return to the original width. It is shaped like a diamond with rounded corners.
[0027]
At the other end of the flow path 2, a waste liquid storage section 3 for storing the liquid flowing out of the flow path 2 is formed. Therefore, the liquid flowing through the flow path 2 from one end eventually flows into the waste liquid storage unit 3 and is accumulated in the waste liquid storage unit 3.
The dimensions of the flow path are determined in consideration of the characteristics of the liquid used. The depth of the flow path is 50 μm, and the width of the first flow path 2a and the third flow path 2c is 50 μm. A case where the maximum width of the second flow path 2b is set to 500 μm can be cited as an example of a practical range.
[0028]
The analysis chip according to the first embodiment of the present invention is configured as described above, and the analysis device according to the first embodiment of the present invention is configured using the analysis chip. Hereinafter, the analyzer will be described.
[0029]
At one end of the flow path 2, that is, at one end of the first flow path 2a, an opening is formed in the lid 1a. In this opening, the sample, the reagent, and the isolation liquid are supplied to the first flow path 2a. A connector 4 for supplying is mounted, and this connector 4 is connected to a supply device 5. The supply device 5 is for supplying a sample, a reagent, and an isolation solution to the first flow path 2a through the connector 4.
[0030]
The supply device 5 has a control valve (not shown) therein. The control valve controls which of the specimen, the reagent, and the isolation liquid is supplied from the connector 4 to the first flow path 2a. In addition, it controls the types and amounts of samples, reagents, and isolation solutions to be supplied.
[0031]
A linear electrode 6 is installed near one end of the flow path 2, ie, near one end of the first flow path 2a, so that the position of the linear electrode 6 can be adjusted from the flow path 2, and the other end of the flow path 2, ie, the third electrode A linear electrode 7 is also installed near the other end of the flow path 2c so as to be position-adjustable. These linear electrodes 6 and 7 are both connected to a power supply device 8 capable of adjusting the voltage, and are configured to generate an electric field in the flow path 2. The linear electrodes 6 and 7 and the power supply device 8 constitute an electric field drive device (drive device) 9. In addition, since the positions of the linear electrodes 6 and 7 can be adjusted, the positions of the linear electrodes 6 and 7 are adjusted so that the tips of the linear electrodes 6 and 7 come into contact with the liquid flowing through the flow path 2 during use (see FIG. 2).
[0032]
When an electric field is applied to the inside of the flow channel 2 by the electric field driving device 9, the direction of the electric field needs to be adjusted according to the electric charge on the wall surface of the flow channel 2. In order to uniformly form the wall charge (電荷 potential) of the flow channel 2, the material of the surface of the analysis chip on which the flow channel 2 is formed is equal throughout the flow channel 2, and the method of forming the surface of the flow channel 2 is the same. It is preferable that the hydrophilic treatment method is also uniform. Here, the method of forming the surface of the flow channel 2 refers to all operations performed when the flow channel 2 is formed, such as how to apply heat when the material of the analysis chip is a thermosetting resin. It should be understood that it includes.
[0033]
Further, the third flow path 3c is provided with an analyzer 10 as an analysis unit capable of analyzing a liquid flowing through the third flow path.
[0034]
The analysis chip and the analysis device of the present invention are configured as described above. If this analyzer is used, it is possible to mix the sample with the reagent for analysis by flowing the sample, the reagent, and the isolation solution through the flow path 2.
[0035]
A sample is a compound to be analyzed by the analysis chip, the analysis device, and the analysis method of the present invention. In the present embodiment, the sample is a liquid that can flow through the flow channel 2 and is not particularly limited as long as the solvent in which the sample is dissolved or dispersed is hydrophilic. Usually, an aqueous solution prepared is used.
[0036]
The reagent is a liquid to be mixed with the sample in order to perform analysis by mixing with the sample. The type of the reagent is determined according to the sample to be analyzed and the item, but in the present embodiment, there is no particular limitation as long as the liquid is a hydrophilic liquid that can flow through the flow channel 2, and various types are used according to the sample. be able to.
[0037]
The separating liquid is not particularly limited as long as it is a liquid that is hardly soluble in the sample and the reagent and does not react with the sample and the reagent. Here, the term "slightly soluble in a sample and a reagent" means that it is insoluble in the sample and the reagent, or is dissolved only in a small amount so as not to affect the analysis even if dissolved. When the specimen and the reagent are hydrophilic liquids, examples of the isolation liquid include a hydrophobic liquid. Examples of the hydrophobic separating liquid include acetonitrile and an inert fluorine solvent, for example, Fluorinert (registered trademark of 3M), a mixture thereof and a salt thereof, and the like.
[0038]
The method for producing the flow channel 2 in the present embodiment may be any method as long as the above-described flow channel 2 can be produced. For example, transfer processing represented by machining, injection molding and compression molding, dry etching (RIE, IE, IBE, plasma etching, laser etching, laser ablation, blast processing, electric discharge machining, LIGA, electron beam etching, FAB), wet Surface micro-machining, which forms a microstructure by coating, vapor-depositing, sputtering, depositing and partially removing various materials in layers, such as etching (chemical erosion), stereolithography, ceramic molding, etc. A method of forming a groove by forming an opening portion with at least one sheet-like substance (film, tape, or the like), and dropping and injecting a material for forming the flow path 2 (hereinafter, appropriately referred to as a flow path forming material) by an inkjet or a dispenser. And forming it.
[0039]
In order to manufacture the analysis chip 1, a mask may be used in the above method. The mask may have any design or a plurality of masks as long as the analysis chip 1 can be finally manufactured. The mask is usually designed in a shape in which the flow path 2 is projected onto a plane. However, when processing is performed on both sides of the flow path constituent material to be laminated, or when the flow path 2 is formed using a plurality of members, the mask is used. Since a plurality of masks can be used or a part of them can be processed directly without using a mask, the mask is not always a projection of the final shape of the flow path 2. For example, as a mask for shielding electromagnetic waves used for a photocurable resin, a mask obtained by coating chromium on quartz or glass, or a mask obtained by baking a resin film with a laser, and the like can be given.
[0040]
The mask can be produced, for example, by drawing at least a part of the structure of the flow path 2 using appropriate software by using a computer and printing it on a transparent resin film. Electronic information of at least a part of the channel structure drawn by the software may be recorded on a computer-readable recording medium used for manufacturing the mask or the master chip. Examples of suitable recording media here include time media such as flexible disks, hard disks, and magnetic tapes, optical disks such as CD-ROMs, MOs, CD-Rs, CD-RWs, and DVDs, and semiconductor memories. .
[0041]
In manufacturing the analysis chip 1, the analysis chip 1 may be directly manufactured by the above method, or the analysis chip 1 may be molded using the manufactured analysis chip 1 as a mold. Naturally, it is also possible to mold the analysis chip 1 using the prepared analysis chip 1 as a mold. In the present invention, the mold at each stage from the mold initially produced to the front of the analysis chip actually used for the operation may be referred to as a “master chip”. As the master chip, a master chip having the same concavo-convex pattern as that of the actual analysis chip 1 (positive) is prepared and transferred twice, or a master chip having a concavo-convex pattern opposite to the actual analysis chip (negative). Is prepared and transferred once. The master chip of the present embodiment is not necessarily limited to this.
[0042]
The analysis chip 1 can also be manufactured by laminating two or more materials. Bonding methods include bonding with an adhesive, resin bonding with a primer, diffusion bonding, anodic bonding, eutectic bonding, heat fusion, ultrasonic bonding, laser melting, lamination with a solvent or dissolving solvent, adhesive tape, adhesive tape. , Pressure bonding, bonding with a self-adsorbent, physical holding, combination by unevenness, and the like.
In addition, a method is also possible in which the flow path 2, the liquid supply part of the connector 4, and the lid 1 a are integrally formed without the need for lamination. Specifically, it is possible to form a structure including a closed space by integral molding such as an optical molding method.
[0043]
Hereinafter, the analysis method will be described in detail.
First, an isolated liquid is supplied from the supply device 5 to the first flow path 2 via the connector 4. The supplied isolation liquid flows from the first flow path 2a to the third flow path 2c via the second flow path 2b by pressure supply or capillary action.
[0044]
Subsequently, the positions of the linear electrodes 6 and 7 are adjusted so that the ends of the linear electrodes 6 and 7 come into contact with the isolation liquid. FIG. 2 is a schematic cross-sectional view of a cross section obtained by cutting the vicinity of the linear electrodes 6 and 7 in this case in parallel to the flow direction of the flow channel 2 as viewed from the side. When the linear electrodes 6 and 7 are brought into contact with the separating liquid and a voltage is applied to the linear electrodes 6 and 7 from the power supply device 8, an electric field is generated in the flow path 2, and the separating liquid is connected to the connector by electroosmotic flow. It flows from the 4 side to the waste liquid storage section 3 side.
[0045]
Next, the sample, the isolation solution, the reagent, and the isolation solution are supplied from the supply device 5 to the first flow path 2a in this order. The amount of the isolation liquid supplied here must be an amount that allows the isolation liquid to isolate the sample and the reagent in order to prevent the sample and the reagent from being mixed in the first flow path 2a. . Further, in addition to the above conditions, the amount of the isolation solution supplied between the sample and the reagent is preferably as small as possible so that the sample and the reagent can be mixed quickly.
[0046]
Hereinafter, how the sample and the reagent are mixed will be described with reference to FIGS. 3 to 6.
The supplied sample and reagent flow through the first flow path 2a with an isolating solution interposed therebetween. As is well known, in the flow due to the electroosmotic flow in the minute space, the flow velocity is uniform at each position in the width direction of the flow path 2 or the difference in the flow velocity at each position is smaller than the pressure flow. . Therefore, as shown in FIG. 3, the sample and the reagent flow in the first flow path 2a in a belt shape extending in the width direction. Hereinafter, in FIG. 3 to FIG. 6, the portion of the sample extending in a belt shape is referred to as a sample 11, the portion of the reagent is referred to as a reagent 12, and the separated liquid separating the sample 11 and the reagent 12 is referred to as a separated liquid 13.
[0047]
When the sample 11 and the reagent 12 enter the entrance of the second flow path 2b, as shown in FIG. 4, the second flow path 2b is wider than the first flow path 2a and cuts perpendicularly to the flow direction. Since the area is large, the sample 11, the reagent 12, and the isolation solution 13 further extend in the width direction, and the thickness of the sample 11, the reagent 12, and the isolation solution 13 in the flow direction decreases. At this time, the sample 11 and the reagent 12 can flow in the second flow path 2b while maintaining a clean belt shape, since the second flow path 2b is formed so as to gradually increase in width. .
[0048]
When the sample 11 and the reagent 12 further advance, the difference between the width in the flow direction and the width in the direction perpendicular to the flow of the separation liquid 13 that separates the sample 11 and the reagent 12 is significantly different. Cannot maintain a thin belt-like shape necessary for isolating the fluid, and since the surface of the flow path 2 is hydrophilic, the hydrophobic separation liquid 13 is easily separated from the surface of the flow path 2. In addition, as shown in FIG. 5, the separation liquid 13 cannot separate the sample 11 and the reagent 12. Therefore, the isolation liquid 13 collects at a position distant from the surface of the flow channel 2, and as a result, the sample 11 and the reagent 12 come into direct contact with each other.
[0049]
As shown in FIG. 6, the sample 11 and the reagent 12 are mixed by being in direct contact with each other to form a mixed solution 14. At this time, since the thickness of the sample 11 and the reagent 12 in the flow direction is small, the two can be quickly and completely mixed.
[0050]
Further, as shown in FIG. 7, the isolation liquid 13 is discharged from the mixed liquid 14 in which the sample 11 and the reagent 12 are mixed due to poor affinity with the surface of the flow channel 2.
[0051]
Thereafter, the mixed solution 14 flows to the analyzer 10 in the third flow path 2c by the flow. At this time, since the width of the second flow path 2b is gradually reduced toward the third flow path 2c, the mixed liquid 14 can flow while maintaining a clean belt shape.
[0052]
When the mixed solution 14 flows to the analysis device 10, the analysis is performed by the analysis device 10. At this time, since the width of the third flow path 2c is reduced to the original width, and the thickness of the mixed liquid 14 in the flow direction is increased, the third flow path 2c flows through the flow path using a small detection area. Much information can be reliably obtained from liquids. For example, reducing the detection area when performing the optical analysis reduces noise factors such as surface scratches and deformation, and the analysis can be performed reliably. In addition, even when the separation liquid 13 remains in the mixed liquid 14 at the position of the analysis device 10, the analysis can be performed by appropriately changing the intensity of the fluorescence or the chemiluminescence, for example.
[0053]
In addition, electroosmotic flow is generally a phenomenon that is unlikely to occur in a hydrophobic liquid, and a large electric field is often required even if an electroosmotic flow occurs in a hydrophobic liquid. Therefore, it is preferable to use a small amount of the separating solution. Therefore, as shown in FIG. 8, it is preferable to flow the permeate liquid 15 which generates an electroosmotic flow by applying an electric field while being isolated by the separating liquid 13, separately from the sample 11 or the reagent 12. Thereby, the liquid in the flow path 2 can be made to flow more efficiently. However, the amount of the isolation liquid should be adjusted so that the sample 11 and the permeate liquid 15 are not mixed and the reagent 12 and the permeate liquid 15 are not mixed.
[0054]
The permeate liquid 15 is not particularly limited as long as it is a liquid that easily causes an electroosmotic flow. For example, an inexpensive liquid such as water may be used. By using a cleaning solution that can be used, impurities in the flow path 2 can be easily removed. In addition, if a calibration liquid is used as the permeate flow liquid 15 and the analysis is performed using the analyzer 10 for optical analysis, the analysis can be made more accurate.
[0055]
By the above operation, the sample can be analyzed by mixing the sample and the reagent. In addition, by repeating the above-described operation, a plurality of types of samples can be analyzed using one type of reagent using one flow path 2, and one type of sample can be analyzed using a plurality of types of reagents. In addition, it is possible to analyze a plurality of types of samples using a plurality of types of reagents, and it is possible to perform analysis using various types of samples and reagents without increasing the size of the apparatus.
[0056]
In addition, since the flow is created in the flow channel 2 using the electroosmotic flow, the flow velocity becomes uniform at each position in the width direction of the flow channel 2 or the flow velocity at each position is compared with the pressure flow in the minute space. Since the difference between the flow rates is small, the specimen 11 and the reagent 12 can be accurately and quickly mixed, and an accurate analysis can be performed.
[0057]
In addition, the analysis chip and the analysis device of the present invention have a simple configuration, so that the size can be reduced, and even if a small amount of a sample or a reagent is mixed in the second flow path 2b, it is surely mixed. Therefore, the amount of the sample and the reagent to be used can be reduced.
[0058]
Although the first embodiment of the present invention has been described above, the present invention is not limited to the above configuration, and can be variously modified and implemented without departing from the spirit of the present invention.
[0059]
For example, the electrodes constituting the electric field driving device are not limited to the linear electrodes 6 and 7, and any commonly used electrodes can be used. For example, as shown in FIG. 9, if the electrode 16 is previously provided on the surface of the flow path 2 instead of the linear electrode, the electric field driving device can be configured with a simple configuration.
[0060]
[Second embodiment]
In the present embodiment, an analysis chip in which a hydrophobic compound is applied to the surface of the flow channel 2 is used, and the solvent and the sample are dispersed or dissolved in the solvent, and the hydrophilic solution is used as the separating solution. It is characterized in that the analysis is carried out by using the above. Other configurations are the same as those of the first embodiment.
[0061]
In the second embodiment, since the isolation liquid is hydrophilic, the isolation liquid itself easily generates an electroosmotic flow. For this reason, the liquid in the flow path 2 can be made to flow efficiently by increasing the amount of the isolation liquid without using the permeate liquid 15. Of course, the analysis may be performed accurately by flowing the calibration liquid into the flow path 2 separately from the isolation liquid, or the flow path 2 may be washed by flowing the cleaning liquid through the flow path 2.
In addition, since other configurations are the same as those of the first embodiment, the same effects as those of the first embodiment can be obtained.
[0062]
[Others]
Although the embodiments of the present invention have been described above, the present invention is not limited to such embodiments, and can be variously modified and implemented without departing from the spirit of the present invention.
[0063]
For example, a waste liquid discharge unit may be formed in the analysis chip 1 instead of the waste liquid storage unit 5 so that the liquid discharged from the flow path 2 is discharged outside the analysis chip 1.
The drive device is not particularly limited as long as it can flow the liquid in the flow path 2, and various devices such as a pump can be used. However, it should be understood that, when a pressure flow is used by using a pump or the like, the belt-like flow is generally difficult to form. That is, it is preferable to use a pressure flow when the entire flow path 2 is filled with one type of liquid or when a small amount of liquid is discontinuously injected.
[0064]
The analyzer 11 is not particularly limited, and may be an optical analyzer such as a fluorescence analyzer, an SPR sensor, an absorbance meter, an electrochemical measuring device using electrodes, or an ISFET (Ion Sensitive Field Effect Transistor). An electrical analyzer such as the above can be used.
[0065]
In addition, the specific method of the hydrophilic treatment or the hydrophobic treatment performed in the flow channel 2 is not particularly limited, and a commonly used method such as, for example, forming the analysis chip 1 itself with a substance having hydrophilicity or hydrophobicity. Can be used as appropriate.
[0066]
The shape of the flow path 2 is not limited to a straight line, but may be a curved line or a shape combining a straight line and a curved line.
[0067]
Further, the shape of the second flow path 2b is not limited to a rhombus as in the first embodiment or the second embodiment, and various shapes may be used.
[0068]
Further, the flow path 2 may be formed as a hole formed inside the base 1 without providing the flow path 2 on the surface of the base 1.
Alternatively, the analysis may be performed with the flow path 2 expanded without reducing the downstream width of the second flow path 2b.
[0069]
In addition, as shown in FIG. 10, by providing a plurality of independent flow paths 2 on one analysis chip 1, analysis efficiency can be improved.
[0070]
Further, when an electric field is applied to the flow path 2, the electric field density is reduced due to the enlarged cross-sectional area in the second flow path 2b, and the first and third flow paths 2a and 2c are transported by the electroosmotic flow. Efficiency may be reduced. In this case, the flow in the second flow path 2b is affected by the pressure (pressurized) by the first flow path 2a and the pressure (negative pressure) by the third flow path 2c, so that the second flow path 2c The internal flow is affected by the pressure transport in addition to the electroosmotic flow.
[0071]
In order to prevent this, an electric field driving device 9 may be provided in each of the first flow path 2a, the second flow path 2b, and the third flow path 2c as shown in FIG. Further, the electric field may be sequentially switched for each electric field driving device. That is, as shown in FIGS. 12A and 12B, for example, an electric field driving device 9a for applying an electric field to the entire flow path 2 and an electric field driving device 9b for applying an electric field only to the second flow path 2b are provided. If an electric field is applied to the flow path 2 while switching the driving devices 9a and 9b, the optimal electric field strength for the flow in the flow path 2 can be adjusted, and the flow in the flow path 2 is accurately and reliably controlled. be able to.
【The invention's effect】
As described above in detail, according to the analysis chip, the analysis device, and the analysis method of the present invention, analysis can be performed with a small amount of a sample and a reagent without increasing the size of the device. Can be quickly and uniformly mixed.
[Brief description of the drawings]
FIG. 1 is a schematic diagram showing an outline of an analysis chip and an analysis apparatus as a first embodiment of the present invention.
FIG. 2 is an enlarged cross-sectional view schematically showing a cross section around an electrode of an analysis chip and an analysis device according to a first embodiment of the present invention.
FIG. 3 is a schematic plan view illustrating an analysis chip, an analysis device, and an analysis method according to a first embodiment of the present invention.
FIG. 4 is a schematic plan view illustrating an analysis chip, an analysis device, and an analysis method according to a first embodiment of the present invention.
FIG. 5 is a schematic plan view illustrating an analysis chip, an analysis device, and an analysis method according to a first embodiment of the present invention.
FIG. 6 is a schematic plan view illustrating an analysis chip, an analysis device, and an analysis method according to a first embodiment of the present invention.
FIG. 7 is a schematic plan view illustrating an analysis chip, an analysis device, and an analysis method according to a first embodiment of the present invention.
FIG. 8 is a schematic plan view illustrating a modification of the analysis chip, the analysis device, and the analysis method according to the first embodiment of the present invention.
FIG. 9 is a cross-sectional view schematically showing an enlarged cross section around an electrode of a modification of the analysis chip and the analysis device according to the first embodiment of the present invention.
FIG. 10 is a schematic diagram showing a modification of the analysis chip of the first embodiment or the second embodiment of the present invention.
FIG. 11 is a schematic diagram illustrating a modification of the analyzer according to the first embodiment or the second embodiment of the present invention.
FIG. 12 is a schematic diagram illustrating a modification of the analyzer according to the first embodiment or the second embodiment of the present invention.
FIG. 13 is a cross-sectional view schematically showing an enlarged main part for describing an analysis chip and an analysis apparatus as a first embodiment of the present invention.
[Explanation of symbols]
1 Substrate
1a Lid
1b Open mouth formed in main part
2 Channel
2a First flow path
2b Second flow path
2c Third channel
3 Waste liquid storage
4 Connector
5 Supply device
6,7 electrode
8 Power supply
9, 9a, 9b Electric field drive (drive)
10 Analysis unit
11 samples
12 reagents
13 Isolate
14 Mixed solution (mixture of sample and reagent)
15 Seepage liquid
16 electrodes

Claims (19)

An analysis chip having a flow path formed in a substrate,
The flow path has a first flow path and a second flow path, and the first flow path and the second flow path are connected in series, and the disconnection of the second flow path is performed. An analysis chip having an area larger than a cross-sectional area of the first flow path. The second flow path is formed such that a cross-sectional area of the second flow path becomes gradually larger than a cross-sectional area of the first flow path from a connection portion between the first flow path and the second flow path. The analysis chip according to claim 1, wherein a flow path is formed. The flow path has a third flow path having a smaller cross-sectional area than the second flow path, on a side opposite to the first flow path with respect to the second flow path. The analysis chip according to claim 1 or 2, wherein the analysis chip is used. The second flow path is formed such that a cross-sectional area of the second flow path is gradually reduced toward a connecting portion between the second flow path and the third flow path with respect to a cross-sectional area of the third flow path. The analysis chip according to claim 3, wherein two flow paths are formed. The analysis chip according to any one of claims 1 to 4, wherein a pair of electrodes or more are provided at both ends of the flow path. The surface of the flow path is subjected to a hydrophilic treatment, or the surface of the flow path is formed of a hydrophilic material in advance, according to any one of claims 1 to 5, Analysis chip. An analysis chip according to any one of claims 1 to 6,
A driving device for flowing the liquid in the flow path,
An analyzer for analyzing an analysis target in the flow path. The analyzer according to claim 7, wherein the driving device is an electric field type driving device capable of applying an electric field to the flow path. 9. The analyzer according to claim 8, wherein the electric field type driving device includes an electrode and a power source which are installed so as to be position adjustable. 9. The analyzer according to claim 8, wherein the electric field type driving device includes an electrode provided on the surface of the flow path and a power supply. 12. A supply device capable of selectively supplying one or more of a specimen, a reagent, and an isolated liquid to the first flow path, respectively. The analyzer according to any one of the above. 7. The first flow path of the analysis chip according to any one of claims 1 to 6, wherein a sample, a reagent, and the sample and the reagent are sparingly soluble in the sample and the reagent. Flowing an unreacted isolating solution so that the sample and the reagent are isolated by the isolating solution;
An analysis method, characterized in that the sample and the reagent are mixed in the second flow path to analyze the sample. 13. The analysis method according to claim 12, wherein one type of sample is analyzed using a plurality of types of reagents. 13. The analysis method according to claim 12, wherein an analysis is performed on a plurality of types of samples using one type of reagent. 13. The analysis method according to claim 12, wherein analysis is performed on a plurality of types of samples using a plurality of types of reagents. The analysis method according to any one of claims 12 to 15, wherein an electric field is applied to the flow path so that the sample, the reagent, and the isolation liquid flow through the flow path. Separately from the sample, the reagent, and the separating solution, an osmotic flow liquid for generating an electroosmotic flow by applying an electric field to the flow path, and the osmotic flowing liquid is separated from the sample and the reagent by the separating solution. The analysis method according to claim 16, wherein the analysis is carried out at a time. The method according to claim 17, wherein the permeate liquid is a washing liquid. The analysis method according to claim 17, wherein the permeate liquid is a calibration liquid for optical analysis.

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