JP2005300460A - Interaction detecting unit, bioassay substrate including the detecting unit, medium dropping method, and method for preventing evaporation of water in medium - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a technique capable of effectively preventing evaporation of moisture in a medium stored or held in a reaction region.
A reaction region 2 that provides a field of interaction between substances, and a capillary portion 3 that communicates with the reaction region 2 and feeds a hydrophilic medium M into the reaction region 2 by capillary action. A region 31b around the suction port 31a of the capillary section 3, an inner wall surface of the capillary 31 extending from the suction port 31a to the reaction region 2, and an interaction in which the inner wall surface of the reaction region 2 is made hydrophilic. A detection unit 1 and a biassay substrate B having the detection unit 1 are provided.
[Selection] Figure 1

Description

  The present invention relates to a technique for detecting an interaction between substances. More specifically, the present invention relates to a technique for facilitating introduction of a medium serving as an interaction field between substances into a reaction region and preventing evaporation of moisture in the medium.

  Recent progress in molecular biology, microfabrication technology represented by nanotechnology, bioinformatics, etc. has made use of various measurement principles to advance the interaction between substances on fine and narrow surfaces. A technology for detecting this (hereinafter referred to as “sensor technology”) has been developed and put into practical use.

  This sensor technology can be used for genome analysis, transcriptome analysis for all transcription from the genome, proteome analysis for functional analysis of all expressed proteins in vivo and in cells, or metabolome for all metabolism analysis. Widely used in the analysis of biological information such as analysis and signal analysis that analyzes signals of the whole body, and has already begun to solidify its technical position in fields such as drug discovery, clinical diagnosis, pharmacogenomics, and forensic medicine .

  Here are some typical sensor technologies that are currently known that can detect interactions between substances. First, a technique relating to an integrated substrate for bioassay called a so-called DNA chip or DNA microarray in which predetermined DNA is finely arranged by microarray technology (see, for example, Patent Document 1 and Patent Document 2). This technique is characterized in that a wide variety of DNA oligo chains, cDNA (complementary DNA), and the like are accumulated on a glass substrate or a silicon substrate, thereby enabling comprehensive analysis of hybridization. For this reason, it is used for gene mutation analysis, SNPs (single nucleotide polymorphism) analysis, gene expression frequency analysis, and the like.

  Next, it is a so-called “protein chip (or protein array chip)” in which purified proteins are arrayed on a microchip on the substrate surface. Although this protein chip has a problem that the activity of the protein to be immobilized may be impaired, a technique capable of analyzing the interaction between protein and protein and between protein and other chemical substances has been proposed. (For example, see Patent Documents 3 and 4).

  In addition, sensor technology using the surface plasmon resonance (SPR) principle, which is characterized by high-speed analysis of interactions between various substances in real time, has been developed (for example, Patent Document 5, Patent Document 5). 6). This SPR sensor technology has a three-layer structure consisting of an adsorption site, a substrate (substrate), and a prism, and measures the interaction of objects by changing the total reflection critical angle of incident light. It is the change of the dielectric constant due to the interaction that contributes to the change of the angle.

  Furthermore, a method for analyzing a structural change of a biopolymer by measuring a change in the frequency of a crystal resonator (quartz crystal oscillator) has been proposed (see Patent Document 7). Or the method of analyzing the interaction between a receptor and a ligand based on the same measurement is also proposed (refer patent document 8).

  In the sensor technology as described above, in many cases, it is a basic and important issue to rapidly and surely advance the interaction between substances in a predetermined region on the substrate and to detect the interaction with high accuracy. As a technique that contributes to the solution of this problem, a technique that suppresses moisture evaporation in a medium that provides a field of interaction between substances has been proposed.

  For example, Patent Document 9 discloses a technique for suppressing evaporation of moisture in the gel, gel contraction, and gel drop-off by containing a predetermined amount or more of polyhydric alcohol in the gel. Further, in Patent Document 9, it is possible to suppress moisture evaporation in the gel by immersing and storing the microarray in distilled water or the like. However, in this method, there is a concern about contamination of bacteria during storage. It is stated that it cannot be adopted.

In Patent Document 10, a substrate surface that has been made hydrophobic in advance is formed, and a hydrophilic region and a hydrophobic region are patterned on the substrate surface by using a technique for forming a hydrophilic region by light irradiation or a photosensitive technology. The technique to do is disclosed.
Japanese National Patent Publication No. 4-505863. Japanese National Publication No. 10-503841. JP2003-130877A. JP2003-155300A. Japanese National Publication No. 4-501462. Japanese National Patent Publication No. 11-512518. JP2003-083864A. Unexamined-Japanese-Patent No. 2003-089373. Japanese Patent Application Laid-Open No. 2003-079377. Japanese Unexamined Patent Publication No. 2003-121442 (refer mainly to claim 1, claim 8, claim 10, etc.).

  In bioassay substrates such as various DNA chips currently proposed, a reaction region that provides a field of interaction between substances is set on the substrate in advance, and probe DNA or the like is detected in the reaction region. A step of immobilizing a substance (hereinafter referred to as “immobilization step”) and a step of advancing the interaction between the substance for detection and the target substance are performed.

  However, when the medium is dropped onto a minute reaction region by an inkjet nozzle or the like, the droplet of the medium is repelled, so that it is difficult to introduce a predetermined volume of medium into the reaction region. is there.

  In addition, since it takes time to diffuse and associate substances, there is a problem that moisture in a medium such as a solution or gel containing a substance for detection evaporates and immobilization or interaction becomes incomplete.

  Therefore, the main object of the present invention is to provide a technique that makes it easy to introduce the medium into the reaction region and can effectively prevent evaporation of moisture in the medium stored or held in the reaction region.

  In the present invention, first, a reaction region that provides a field of interaction between substances, and a capillary part that communicates with the reaction region and feeds a hydrophilic medium into the reaction region by capillary action are provided. A region around the suction port of the capillary unit, a capillary inner wall surface from the suction port to the reaction region, an interaction detection unit in which the inner wall surface of the reaction region is hydrophilic, and the interaction A bioassay substrate including a detection unit is provided. With these means, the medium can be smoothly fed into the reaction region based on the philicity relationship between the medium and the capillary part or the like.

  Furthermore, by keeping the reaction region and the capillary part airtight, the suction port and the outside air communication port of the capillary part are devised so as to be blocked with a hydrophobic substance capable of changing the solid-liquid phase, such as paraffin wax. , Preventing moisture evaporation of the medium present in the reaction zone.

  In the present invention, secondly, the medium is applied to an area around the opening of the inlet of the capillary part that feeds a hydrophilic medium to the reaction area that provides a field of interaction between substances by capillary action. A method of dropping by a nozzle or the like is provided.

  The dropped medium is guided to the reaction region by capillary action, and includes a region around the suction port of the capillary part, a capillary inner wall surface extending from the suction port to the reaction region, and an inner wall surface of the reaction region. By making it hydrophilic, it becomes possible to send a hydrophilic medium more smoothly into the reaction region.

  In the present invention, thirdly, the solid-liquid is directed against the suction port and the outside air communication port of the capillary part for feeding the hydrophilic medium by capillary action toward the reaction region that provides a field of interaction between substances. There is provided a method for preventing moisture evaporation of a medium in a reaction region by dropping a hydrophobic substance capable of phase change and closing the reaction region with the solidified material.

Here, definition of main technical terms used in the present invention is performed.

  The “reaction region” is a region that can provide a reaction field for hybridization and other interactions, and examples thereof include a reaction field having a well shape that can store a liquid phase, a gel, and the like. The interaction performed in this reaction region is not narrowly limited as long as the object and effect of the present invention are met. Further, the shape and size of the reaction region are not particularly limited, but the length, width, and depth are about several μm to several hundred μm, respectively. It can be determined based on the minimum possible dripping amount of the solution (detection substance-containing medium, target substance-containing medium).

  “Interaction” broadly means non-covalent bonds, covalent bonds, chemical bonds or dissociations including hydrogen bonds between substances, for example, hybridization that is a complementary bond between nucleic acids (nucleotide strands), polymer-high Widely includes molecules, macromolecule-small molecules, small molecule-small molecule specific bonds or associations.

  The “interaction detection unit” means a part that is provided with a field where the interaction between substances proceeds, and that can detect the presence and state of the interaction regardless of the means.

  “Hybridization” means a complementary strand (double strand) formation reaction between complementary base sequence structures.

  A “detection substance” is a substance that exists in a medium stored or held in a reaction region and functions as a probe for detecting a substance that specifically interacts with the substance. It exists fixed or free on the surface. A typical example is a nucleic acid for detection such as a DNA probe. The “target substance” is a substance that shows a specific interaction with the detection substance.

  The “hydrophobic substance capable of changing to a solid-liquid phase” means a hydrophobic substance that changes phase between a solid phase and a liquid phase depending on temperature conditions, and includes, for example, paraffin wax.

“Nucleic acid” means a polymer (nucleotide chain) of a nucleoside phosphate ester in which a purine or pyrimidine base and a sugar are glycosidically linked, and an oligonucleotide, a polynucleotide containing a probe DNA, a polynucleotide, a purine nucleotide and a pyrimidine nucleotide are polymerized. DNA (full length or a fragment thereof), cDNA obtained by reverse transcription (c probe DNA), RNA, polyamide nucleotide derivative (PNA) and the like are widely included.

  “Bioassay substrate” means a substrate for detecting the interaction by causing an interaction between substances to proceed in a predetermined reaction region on the substrate, and widely includes regardless of the type of the substance, The detection principle of the interaction is not limited.

  A “DNA chip” is one of the bioassay substrates, and means a hybridization detection substrate in which nucleic acids for detection such as DNA probes are immobilized and finely arranged. The concept of DNA microarray Including.

  The “inkjet nozzle” means a small jet nozzle whose position is controlled by an XYZ operation control system by a piezoelectric technique using an inkjet printing technique. This nozzle can accurately inject a solution-like medium containing a sample substance such as a DNA probe into a predetermined reaction region. The “inkjet printing method” is a method of applying nozzles used in an ink jet printer, and is a method of injecting and fixing a detection substance from a printer head onto a substrate using an electricity like an ink jet printer. This method includes a piezoelectric ink jet method, a bubble jet method, and an ultrasonic jet method. The piezoelectric ink jet method is a method in which a droplet is ejected by a displacement pressure generated by applying a pulse to a piezoelectric body. The normal bubble jet method is a thermal method in which droplets are ejected by the pressure of bubbles generated by heating a heater in a nozzle. A silicon substrate serving as a heater is embedded in the nozzle, controlled at about 300 ° C./s to create uniform bubbles, and eject droplets. However, since the liquid is exposed to a high temperature, it is considered unsuitable for a biological material sample. The ultrasonic jet method is a method in which an ultrasonic beam is applied to a free surface of a liquid and a droplet is ejected from the spot by locally applying a high pressure. No nozzle is required, and droplets having a diameter of about 1 μm can be formed at high speed. In the present invention, as the “ink jet printing method”, a method with less thermal influence on the medium, such as the “piezoelectric ink jetting method”, can be suitably employed. Since the size of the droplet (micro droplet) can be controlled by changing the shape of the pulse to be applied, it is suitable for improving the analysis accuracy. When the radius of curvature of the droplet surface is small, the droplet can be made small, and when the radius of curvature of the droplet is large, the droplet can be enlarged. It is also possible to reduce the radius of curvature by pulling the droplet surface inward by rapidly changing the pulse in the negative direction.

  ADVANTAGE OF THE INVENTION According to this invention, while being able to make it easy to introduce | transduce a medium into a reaction area | region, evaporation of the water | moisture content in the medium stored or hold | maintained at a reaction area | region can be prevented effectively. As a result, a desired assay related to the interaction between substances in the reaction region (for example, a detection substance immobilization assay, an interaction assay such as hybridization) can be reliably and smoothly performed.

  DESCRIPTION OF EXEMPLARY EMBODIMENTS Hereinafter, preferred embodiments for carrying out the invention will be described with reference to the accompanying drawings. Each embodiment shown in the attached drawings shows an example of a typical embodiment of the thing and method concerning the present invention, and, thereby, the scope of the present invention is not interpreted narrowly.

  FIG. 1 is a diagram for explaining a main configuration of an interaction detection unit according to the present invention and a bioassay substrate provided with the detection unit, and FIG. 2 communicates with a reaction region constituting the detection unit. It is the enlarged view which looked at the opening part of the capillary part from upper direction.

  Reference numeral 1 in FIG. 1 represents an embodiment of an interaction detection unit (hereinafter abbreviated as “detection unit”) provided on the bioassay substrate B. The illustrated detection unit 1 includes at least a reaction region 2 that provides a field of interaction between substances, and a capillary unit 3 (31, 32) that communicates with the reaction region 2.

  The bioassay substrate B can be formed from a substrate similar to an optical information recording medium such as a CD (Compact Disc), a DVD (Degital Versatile Disc), or an MD (Mini Disc). For example, it is molded into a desired shape by a synthetic resin such as quartz glass, silicon, polycarbonate, polystyrene, etc., preferably a synthetic resin that can be injection molded. By forming the substrate 1 using an inexpensive synthetic resin, a low running cost can be realized as compared with a conventionally used glass chip.

  The capillary part 3 communicating with the reaction region 2 includes fine capillaries 31 and 32 formed so as to exhibit a function of guiding the medium M to the reaction region 2 by capillary action, and an opening of one capillary is It functions as an inlet for the dropped medium M, and the other opening functions as an outside air communication port necessary for capillary action.

  For example, FIG. 1 shows a state in which the opening portion of the capillary 31 indicated by reference numeral 31a functions as an inlet for the medium M, and the other opening portion indicated by reference numeral 32a functions as an outside air communication opening. Has been. Note that the opening of the capillary 32 indicated by one reference numeral 32a may be selected as the suction port for the medium M.

  The medium M is a hydrophilic solvent containing a substance related to the interaction (detection substance or target substance) or a substance used for detection of the interaction (for example, an intercalator). Then, a predetermined volume is precisely dropped from above the selected opening 31a (of the capillary) on the side functioning as the suction port (or 32a), toward the opening 31a.

  FIG. 1 illustrates a mode in which the medium M is dropped into the opening (suction port) 31a and then sucked into the capillary 31 by capillary action to reach the reaction region 2 (see dotted arrows). ). The following will be described in accordance with this illustrated embodiment.

  The medium M includes a detection substance such as a DNA probe, a target substance such as a target nucleic acid that exhibits a specific interaction with the detection substance, a substance such as a detection intercalator, depending on the stage of the target assay. Is contained. Moreover, depending on the case, both a target substance and an intercalator may be contained. Further, the medium M may be mixed with an appropriate amount of gel (for example, a water-absorbing gel).

  Here, in the present embodiment, the substrate region 31b around the suction port 31a of the capillary 31 is hydrophilic (see particularly FIG. 2). The hydrophilic region 31b temporarily holds the hydrophilic medium M dripped from above through the nozzle N so as not to repel based on the principle of philicity, and then quickly in the capillary 31. The function of feeding the medium M to the center is exhibited.

  In the present embodiment, the inner wall surface 311 of the capillary 31 on the side of introducing the medium M and the inner wall surface 21 constituting the reaction region 2 are also made hydrophilic. With this configuration, the hydrophilic medium M entering from the suction port 31a can be smoothly introduced into the reaction region 2 in the end by causing the capillary phenomenon to be smoothly exhibited using the principle of lyophilicity. it can.

  Note that the lyophilicity of the substrate region 31c other than the region 31b is not particularly limited. For example, the hydrophilic medium M that has been dropped is made around the suction hole 31a (hydrophilic region 31b) by making it hydrophobic. ) And can be immediately introduced into the reaction region 2 via the capillary 31.

  The inner wall surface 321 of the capillary 32 on the side of the outside air communication port 32a may be hydrophilic, hydrophobic, or amphiphilic. For example, when the hydrophobic property is selected, the capillary 32 is lyophilic with respect to the medium M, and thus plays a role of holding the medium M that has passed through the capillary 31 in the reaction region 2.

  Here, an example of a method of lyophilic processing that can be employed in the present invention will be described. Next, a predetermined surface region of the substrate B on which the reaction region 2 that provides an interaction field such as hybridization is formed is treated with a hydrophobic substance to form a hydrophobic surface, followed by A method of performing a hydrophilization step in which part of the hydrophobic surface is converted to a hydrophilic surface is suitable.

  Further, by appropriately combining these steps, a predetermined region or partial region on the substrate B can be made a hydrophilic surface or a hydrophobic surface according to the object of the present invention.

  Since biological materials such as nucleic acids used in bioassays such as genetic analysis are mostly hydrophilic, the biological material is contained in a hydrophilic solvent such as an aqueous solution, and the reaction region of the substrate B Will be sent to 2.

  Therefore, by making the reaction region 2 on the substrate B hydrophilic, the medium M containing the biological material related to the interaction is accurately fed into the reaction region 2 or is securely held in the reaction region 2. be able to.

The hydrophobic step includes, for example, alkylsilane (R—Si—X ₁ , X ₂ , X ₃ , R: alkyl group (which may contain an unsaturated group), Xn: Cl, OR, which is a hydrophobic substance. ) On the surface of the substrate.

  The hydrophilization step for converting a part of the hydrophobic surface into a hydrophilic surface can be easily performed based on a reaction for forming a hydroxyl group on the hydrophobic surface. For example, when the hydrophobic surface is formed of the above-described alkylsilane, a hydroxyl group can be added to the alkyl group of the alkylsilane by irradiating the alkylsilane with ultraviolet light in the presence of oxygen. In the present invention, the amphiphilic processing itself is not limited to a narrow one, and can be appropriately employed. For example, plasma ashing treatment, hydrogen peroxide treatment, ozone water treatment, acid or alkali solution treatment, silane coupling or titanium coupling treatment can be used as appropriate.

  Next, a method for preventing moisture evaporation in the medium M will be described with reference to FIG. Note that FIG. 3 is an enlarged view of a portion X in FIG. This supplementary enlarged view (circled portion) shows that the detection substance D is contained in the medium M.

  In the present invention, the medium M is introduced into the reaction region 2 using the principle of capillary action, and then the openings 31a (suction ports) and 31b (outside air communication ports) of the capillaries 31 and 32 are closed, thereby It is characterized by preventing evaporation of moisture in M.

  In the process related to the plugging, a hydrophobic plugging substance 4 having physical properties capable of changing the solid-liquid phase is used. Specifically, the blocking substance 4 is dropped into the openings 31a and 31b in a solution state via another dedicated nozzle different from the nozzle N for dropping the medium M. That is, a suitable nozzle device configuration for carrying out the process related to the blockage is a nozzle N for dropping the medium M, and a dedicated nozzle N ′ for dropping the blocking substance 4 different from the nozzle N. (Refer to FIG. 3), and configured so that these nozzles can be used properly according to the timing and purpose of the assay.

  For example, since this blocking substance 4 has a property of solidifying under room temperature conditions, it functions as a sealing lid for the openings 31a and 31b. That is, the plugging substance 4 is a hydrophobic substance having a physical property that changes between a solid phase and a liquid phase depending on temperature conditions, and preferably, paraffin wax can be employed.

  For example, if this paraffin wax is dropped in a solution state under a temperature condition higher than its melting point, and after dropping, the paraffin wax is solidified at a temperature below the melting point and a temperature suitable for the target assay conditions. Good.

  Further, if a hydrophobic substance such as paraffin wax is employed as the occluding substance 4, the occluding substance 4 does not enter the capillary 31 made hydrophilic, which is opposite to the hydrophilic substance. Therefore, there is an advantage that the blocking material 4 does not interfere with the medium M.

  The steps suitable for carrying out by closing the openings 31a (suction ports) and 31b (outside air communication ports) of the capillaries 31 and 32 include the step of immobilizing the detection substance D, the detection substance and the target substance T. It is considered to be a step of causing the interaction between the two to proceed, or a step of inserting and binding an intercalator into the obtained double-stranded nucleic acid when the interaction is hybridization. This is because, since it takes time to complete these steps, the evaporation of moisture in the medium M is unavoidable, and this evaporation of moisture hinders each reaction.

  Here, FIG. 4 is a view showing an embodiment of the immobilization process of the detection substance D performed by closing the openings 31a (suction ports) and 31b (outside air communication ports) of the capillaries 31 and 32. FIG. .

In the embodiment shown in FIG. 4, a pair of upper and lower counter electrodes E ₁ -E ₂ are provided so as to sandwich the reaction region 2. The counter electrodes E ₁ and E ₂ can be formed of a metal such as aluminum or gold, or a transparent conductor such as ITO (indium-tin-oxide).

Further, as shown in FIG. 4, the area of one electrode E _1, by narrowly formed than the other electrode E _2, lines of electric force are concentrated on the edge portions of the electrodes E _1, not A uniform electric field is easily formed.

For example, when a high-frequency alternating electric field is applied to the counter electrodes E ₁ -E ₂ , a DNA probe, which is an example of the detection substance D, is stretched linearly by the action of so-called “dielectrophoresis”. drawn to the edge portion of E _1, end portions of the DNA probe D is avidin - via a chemical bond such as biotin binding or disulfide bonds can be surely immobilized on the electrode E ₁ surface.

Figure 5 is an enlarged view of an electrode E ₁ moiety in the reaction region 2, by hybridization, which is an example of the interaction, it illustrates the manner in which double-stranded nucleic acid is formed.

Reference numeral T in FIG. 5 shows the DNA probes immobilized D and hybridized target nucleic acid on the surface of the electrode E _1, reference numeral I is inserted into a double-stranded nucleic acids obtained by hybridization A bound intercalator (eg, fluorescently labeled) is shown.

  Nucleic acid molecules are known to extend or move in the liquid phase when subjected to the action of an electric field. The principle is thought to be that ion turbidity is formed by phosphate ions (negative charge) forming the skeleton and hydrogen atoms (positive charge) formed by ionization of water in the vicinity, and these negative charges and positive charges are generated. The polarization vector (dipole) is oriented in one direction as a whole by the application of a high frequency high voltage, and as a result, it expands. Move toward the site where the line is concentrated (Seiichi Suzuki, Takeshi Yamanashi, Shin-ichi Tazawa, Osamu Kurosawa and Masao Washizu: “Quantitative analysis on electrostatic orientation of DNA in stationary AC electric field using fluorescence anisotropy”, IEEE Transaction on Industrial Applications , Vol. 34, No. 1, P75-83 (1998)).

  Moreover, when a DNA solution is placed in a microelectrode having a gap of several tens to several hundreds of μm, and a high frequency electric field of about 1 MV / m or 1 MHz is applied thereto, dielectric polarization occurs in DNA present in a random coil shape. As a result, the DNA molecules are stretched linearly parallel to the electric field. Then, due to the electrodynamic effect called “dielectrophoresis”, the polarized DNA is spontaneously attracted to the end of the electrode, and is fixed in such a manner that the end is in contact with the electrode edge (Masao Awazu, DNA handling ", visualization information Vol.20 No.76 (January 2000)).

  Next, an example of a method for detecting the interaction that has proceeded in the reaction region 2 will be described. For example, when the detection substance D is a DNA probe and the target substance T is a single-stranded DNA having a base sequence complementary to this DNA probe, for example, the target substance T is passed through a nozzle N (see FIG. 1). At the same time as or after hybridization of the single-stranded nucleic acid, a fluorescently labeled intercalator I is dropped into the reaction region 2, and this intercalator I is inserted and bonded to the double-stranded nucleic acid obtained by the hybridization. (See FIG. 5).

  Then, the fluorescence intensity obtained by irradiating the reaction region 2 with excitation light having a predetermined wavelength is detected using an optical pickup means. That is, the intensity of the fluorescence emitted from the intercalator I can be detected, and the status of hybridization between the nucleic acid D for detection and the target nucleic acid T can be determined.

  INDUSTRIAL APPLICABILITY The present invention can be used as a technique for constructing a bioassay substrate for the purpose of detecting an interaction between substances based on various sensor techniques or detection principles. In particular, it can be effectively used as a technique for preventing water evaporation in the medium in the reaction region, or as a technique for transporting or dropping the medium into the reaction region.

It is a figure for demonstrating the principal part structure of the board | substrate for bioassay (B) in which the interaction detection part (1) based on this invention and this detection part (1) were provided. It is the enlarged view which looked at the opening part of the capillary part (3) connected to the reaction region (2) which comprises the said detection part (1) from upper direction. It is a figure for demonstrating the embodiment example of the method of preventing the water | moisture content evaporation in a medium (M). It is a figure which shows one Embodiment of the immobilization process of the substance for a detection (D) implemented by obstruct | occluding the opening part (31a, 32a) of a capillary (31, 32). It is an enlarged view of the electrode (E ₁ ) portion in the reaction region (2), and shows a state in which double-stranded nucleic acid is formed by hybridization, which is an example of interaction.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Interaction detection part 2 Reaction area | region 3 Capillary part 4 Occlusion substance 31 Capillary 31a on the suction side Capillary 32a on the suction side 32 Capillary 32a on the communication side of the outside air Dent substance for detection (eg, DNA probe)
M Medium N Nozzle N ′ (for dropping medium) Nozzle T (for dropping substance for closing) Target substance

Claims (9)

A reaction region that provides a field of interaction between substances, and a capillary portion that communicates with the reaction region and feeds a hydrophilic medium into the reaction region by capillary action,
An area around the suction port of the capillary unit, an inner wall surface of the capillary extending from the suction port to the reaction region, and an interaction detection unit in which the inner wall surface of the reaction region is made hydrophilic.   2. The interaction detection unit according to claim 1, wherein the suction port and the outside air communication port of the capillary unit are closed with a hydrophobic substance capable of changing a solid-liquid phase.   3. The interaction detection unit according to claim 2, wherein the suction port and the outside air communication port of the capillary unit are sealed with the hydrophobic substance so as to keep the reaction region and the capillary unit airtight.   The method according to claim 2, wherein the hydrophobic substance is paraffin wax.   A bioassay substrate comprising the interaction detection unit according to claim 1.   A medium dropping method in which a medium is dropped onto a peripheral area of an opening of a capillary part that feeds a hydrophilic medium to a reaction area that provides an interaction field between substances by capillary action.   The region around the suction port of the capillary section, the inner wall surface of the capillary from the suction port to the reaction region, and the inner wall surface of the reaction region are made hydrophilic. Medium dripping method.   The medium dropping method according to claim 6, wherein the ink is dropped by an ink jet type nozzle.   A hydrophobic substance capable of changing a solid-liquid phase to an inlet and an outside air communication port of a capillary part for feeding a hydrophilic medium by capillary action toward a reaction region that provides a field of interaction between substances. A method of preventing evaporation of water in a medium in the reaction region by dripping and closing the reaction region with the solidified substance.