WO2023234465A1

WO2023234465A1 - Diagnostic cartridge having improved flow control of solution

Info

Publication number: WO2023234465A1
Application number: PCT/KR2022/008939
Authority: WO
Inventors: 신경식; 전호승
Original assignee: 주식회사 바이오소닉스
Priority date: 2022-05-30
Filing date: 2022-06-23
Publication date: 2023-12-07
Also published as: KR20230166233A

Abstract

The present invention relates to a diagnostic cartridge having improved flow of a solution, and more particularly, to a diagnostic cartridge having a structure capable of improving the efficiency and accuracy of a diagnosis using the diagnostic cartridge by controlling whether or not a solution is discharged according to the volume of the solution injected through an inlet of the diagnostic cartridge. According to the present invention, whether or not the solution is discharged can be controlled according to the volume of the solution injected through the inlet when using the diagnostic cartridge according to the present invention, and thus the accuracy of an antigen-antibody reaction can be increased while lowering the rate of loss of the solution to improve the efficiency and accuracy of diagnosis through a kit.

Description

Diagnostic cartridge with improved solution flow control

The present invention relates to a diagnostic cartridge with improved solution flowability or improved solution flow control. More specifically, the present invention relates to a diagnostic cartridge by controlling whether or not the solution is discharged according to the volume of the solution injected into the injection portion of the diagnostic cartridge. When diagnosing using , the discharge of the solution can be easily controlled to increase the convenience, efficiency, and accuracy of the diagnosis.

ELISA {Enzyme-Linked ImmunoSorbent Assay} refers to an enzyme-linked immunosorbent assay, which is a general term for measuring antigen or antibody amounts using antigen-antibody reactions using enzymes as markers. Conventional ELISA plates use well-shaped reaction vessels. An immune reaction occurs by an antigen-antibody reaction on the surface of a well or reaction chamber equipped with this container-shaped substrate. The immune response due to the antigen-antibody reaction on the surface of the container is measured by changes in fluorescence or absorbance. For the immune response due to the antigen-antibody reaction, the analysis solution, washing solution, and reaction solution are sequentially added. Here, the reaction result can be analyzed by detecting the color change of the solution in the container using a colorimetric enzyme.

However, in such reaction vessel-type wells, there is a disadvantage that the analysis solution, washing solution, and reaction solution must be sequentially added and removed, and the washing process is not only cumbersome as the process of adding and removing the washing solution using a pipette must be repeated, and residues are formed. There is also a problem that the solution remains in the well, and the volume of the solution may vary because the solution is added and removed with a pipette.

Therefore, there is an urgent need to develop a diagnostic cartridge that can increase efficiency and accuracy while preserving solution capacity.

The present invention is intended to solve the problems of the prior art described above, and provides a diagnostic cartridge with improved flowability of the solution and a diagnostic method using the diagnostic cartridge that can easily adjust the flowability depending on whether the solution is discharged or not. The purpose is to do so.

In order to solve the above problems, the present invention provides a diagnostic cartridge with improved solution discharge control and flowability, and a diagnostic cartridge with improved solution flowability or solution flow control that can easily control the discharge of the solution using the same. Provides a diagnostic method using a diagnostic cartridge.

According to the present invention, when using a diagnostic cartridge with improved discharge control and flowability of the solution of the present invention, discharge of the solution can be easily controlled depending on the volume of the solution injected into the injection portion, so the accuracy of the antigen-antibody reaction It is possible to increase the efficiency and accuracy of diagnosis through the kit by lowering the loss rate of the solution while increasing the

Figure 1 is a partial cross-sectional view of a diagnostic cartridge with improved solution flow according to an embodiment of the present invention.

Figure 2 shows whether the solution is discharged according to the volume of the solution according to an embodiment of the present invention. Figure 2a shows that when 30 ul of a sample solution for detecting a target substance is injected through the injection part, the sample solution exists only in the reaction part and is not discharged through the discharge pipe. Figure 2b shows that when 70 ul of the cleaning solution is injected through the injection part after Figure 2a, the cleaning solution is discharged through the discharge pipe.

Figure 3a shows that in the case where the diagnostic cartridge of the present invention does not include an absorber, solution residues exist in the discharge pipe or discharge of the solution drained to the outside cannot be stably controlled due to surface tension at the end of the discharge pipe.

Figure 3b shows that in the case where the diagnostic cartridge of the present invention includes an absorber, there is no solution residue in the discharge pipe and the flow of solution discharge can be easily controlled by canceling out the effect of surface tension at the end of the discharge pipe.

The present invention relates to a diagnostic cartridge that includes a structure that can improve efficiency and accuracy when diagnosing using a diagnostic cartridge by controlling whether or not the solution is discharged depending on the volume of the solution injected into the injection portion of the diagnostic cartridge.

The language used in this specification and claims should not be construed as limited to the usual or dictionary meaning, and the inventor may appropriately define the concept of terms to explain his or her invention in the best way. It must be interpreted based on principles and with a meaning and concept consistent with the technical idea of the invention. Therefore, the configurations such as the examples described in this specification are only one of the most preferred embodiments of the present invention and do not represent the entire technical idea of the present invention, and various equivalents and It should be understood that there may be variations.

The terms used in the present invention are general terms that are currently widely used as much as possible while considering the function in the present invention, but this may vary depending on the intention or precedent of a person working in the art, the emergence of new technology, etc. In addition, in certain cases, there are terms arbitrarily selected by the applicant, and in this case, the meaning will be described in detail in the description of the relevant invention. Therefore, the terms used in the present invention should be defined based on the meaning of the term and the overall content of the present invention, rather than simply the name of the term.

Terms containing ordinal numbers, such as first, second, etc., may be used to describe various components, but the components are not limited by these terms. These terms are used only to distinguish one component from another.

When a component is said to be 'connected' or 'connected' to another component, it may be directly connected or connected to the other component, but other components may exist in between. It must be understood that there is. On the other hand, when it is mentioned that a component is 'directly connected' or 'directly connected' to another component, it should be understood that there are no other components in between.

The terms used in this application are only used to describe specific embodiments and are not intended to limit the invention. Singular expressions include plural expressions unless the context clearly dictates otherwise. In this application, terms such as 'comprise' or 'have' are intended to designate the presence of features, numbers, steps, operations, components, parts, or combinations thereof described in the specification, but are not intended to indicate the presence of one or more other features. It should be understood that this does not exclude in advance the possibility of the existence or addition of elements, numbers, steps, operations, components, parts, or combinations thereof.

Below, with reference to the attached drawings, embodiments of the present invention will be described in detail so that those skilled in the art can easily implement the present invention. However, the present invention may be implemented in many different forms and is not limited to the embodiments described herein. In order to clearly explain the present invention in the drawings, parts that are not related to the description are omitted, and similar parts are given similar reference numerals throughout the specification.

The diagnostic cartridge with improved discharge control and flowability of the solution of the present invention includes an injection part into which a sample solution for detecting a target substance is injected;

a reaction unit located below the injection unit and including a micro-well accommodating beads for an immune reaction;

A hinge part connecting the injection unit and the reaction unit so that the solution injected through the injection unit flows into the reaction unit;

A discharge pipe that has one side connected to the hinge portion and the other side connected to the absorbent portion to discharge the solution into the absorbent portion; and

An absorption unit that absorbs the discharged solution; It is characterized by including.

In one embodiment of the present invention, the injection unit is a place where a solution to be tested or a sample solution for detecting a target substance flows in, and specifically, a sample solution, an analysis solution, a cleaning solution, a reaction solution, etc. can flow into the injection part. The injection unit has a certain range of top diameter, bottom diameter, and height from the top to the bottom, so that it is possible to control whether or not the solution is discharged depending on the volume of the inflow solution.

In one embodiment of the present invention, the injection part preferably has a structure in which all or part of the upper and lower parts are open, and the lower part may have an area smaller than the open area of the upper surface.

In one embodiment of the present invention, the reaction unit accommodates or includes beads to which a substance for detecting a target substance contained in a reaction solution introduced or injected through the injection unit 10 is bound or connected, and is used to detect the target substance. The substance may include one selected from the group consisting of antibodies, antigens, enzymes, peptides, proteins, DNA, RNA, peptide nucleic acids (PNAs), protein-binding nucleotides, and aptamers. Additionally, the reaction unit may be located below the injection unit and include a micro-well accommodating beads for an immune reaction, and the beads may contain a substance for detecting a target substance. In addition, when the volume of the solution flowing through the injection unit is 10 to 60 ul, the solution flows into the reaction unit through the hinge unit, and the injected solution may not be discharged into the discharge pipe, and the solution flowing into the reaction unit may reach the target on the beads. An immune reaction may occur with the substance to detect it. However, when the volume of the solution flowing through the injection unit is 70 ul, substances that are not bound to the magnetic beads through an immune reaction can be discharged into the absorption unit 15 through the discharge pipe 14. The reaction unit may include a micro-well for fixing magnetic beads, and the micro-well may have a porous structure or porous pores, so that the beads are fixed to the porous structure or porous pores of the micro-well. there is.

In one embodiment of the present invention, the total length of the hinge portion may be 0.5 mm to 2 mm, and specifically, it may have a length of 1.2 mm, allowing the solution injected into the injection portion to flow into the reaction portion. As an example, the hinge part may have a branched structure in which one side is connected to the reaction part and the other side is connected to the absorption part through a discharge pipe. In this case, when a solution exceeding a certain volume flows into the injection part, the solution is discharged to the absorption part through the discharge pipe. In this case, the volume of the solution injected to discharge the solution may be 70 ul or more.

When the volume of the solution flowing through the injection unit is 10 to 60 ul, the solution flowing into the injection unit is not discharged to the absorption unit through the discharge pipe but exists in the reaction unit, and the volume of the solution flowing through the injection unit is If the volume is more than 70 ul, the solution flowing into the injection section through the pressure of the discharge pipe and absorption section may be discharged from the reaction section, and if the volume of the solution flowing through the injection section is less than 10 ul, the reaction section is not sufficiently wetted, causing immunity. Reactions, etc. may not occur. Additionally, if the total volume of the solutions flowing through the injection unit is 70 ul or more, the solutions flowing into the injection unit may be discharged from the reaction unit through the pressure of the discharge pipe and the absorption unit.

In one embodiment of the present invention, when a sample solution for detecting a target substance or a substance for detecting the same is injected through the injection unit, it flows from the injection unit to the reaction unit through the hinge unit, and the reaction unit is injected with the target substance present in the solution. The material for detecting this may be characterized in that it does not dry out for reaction or binding.

In one embodiment of the present invention, the structure may further include a sensor unit, and the sensor unit detects a change in impedance that occurs when a substance for detecting a target substance on a bead and a target substance present in a solution bind or react in an immune reaction. or when the substance for detecting the target substance on the beads and the target substance present in the solution bind or react in an immune reaction, the substance that specifically binds to the substance for detecting the target substance present on the bead. It may be characterized by calculating the amount of the target material present in the solution by measuring its presence.

In one embodiment of the present invention, the absorption portion may include an absorption pad for absorbing target molecules, cleaning solutions, and other impurities that are not bound to the reaction portion. The absorbent pad may include or be composed of a material with strong absorbent properties, and specifically includes paper (non-woven fabric), polymer chemicals (Super Absorbent Polymer), or natural super absorbent cellulose (Supre Absorbent Cellulose). can do.

In addition, the absorbent part includes an absorbent pad, and the absorbent pad absorbs the solution discharged through the discharge pipe to maintain constant surface tension and pressure conditions at the end of the discharge pipe, thereby allowing the solution to continuously move to the absorber along the discharge pipe, according to the present invention. It can play an important role in facilitating control of solution discharge from the cartridge and improving its flowability. Specifically, the amount of sample solution, reaction solution, cleaning solution, analysis solution, etc. injected into the injection unit through the absorption unit can be discharged to the absorption unit through the discharge pipe at a constant rate, and the discharge flow of the solution can be easily determined. It can be adjusted.

The flow of the solution injected into the injection unit from the hinge unit to the discharge pipe is controlled according to the volume, which is determined by the water level of the volume injected into the injection unit (the level of the solution injected based on the bottom of the reaction unit). The surface tension that occurs between the hinge part and the discharge pipe prevents the solution from flowing into the discharge pipe, and when the solution flows into the injection section at a certain volume and level or higher, the solution flows through the discharge pipe. Therefore, the diagnostic cartridge with improved discharge control and flowability of the solution of the present invention can control the flow of the solution discharged through the discharge pipe by adjusting the volume of the solution injected or introduced through the injection unit, and can control the flow of the solution discharged through the discharge pipe through the absorber. Moving solution may be discharged.

Hereinafter, the present invention will be described in detail with reference to the drawings.

As shown in the drawing, the diagnostic cartridge with improved solution flow of the present invention includes an injection unit 10, a reaction unit 11, a hinge unit 12, a sensor unit 13, a discharge pipe 14, and Includes an absorption portion (15).

The diagnostic cartridge with improved discharge control and flow of the solution of the present invention is used for diagnosis of neuropsychiatric diseases such as dementia diagnosis, diabetes diagnosis, myocardial infarction diagnosis, Parkinson's diagnosis, Alzheimer's disease diagnosis, cancer diagnosis, and protein detection based on immune response. can be used for Specifically, target substances for testing or detection for dementia diagnosis may include immune response-based diagnostic target substances such as Tau, amyloid beta, alpha-synuclein NFL, Troponin, and PSA protein.

In one embodiment of the present invention, when a sample solution for detecting a target substance, a reaction solution containing a substance for detecting the same, a washing solution, an analysis solution, etc. are injected through the injection unit, the solution flows from the injection unit to the reaction unit through the hinge unit. Sample solution, reaction solution, cleaning solution, analysis solution, etc. that are introduced and other than the amount required for the reaction can be removed through the absorption part through the discharge pipe connected to the hinge part. In this case, the target present in the sample solution is in the reaction part. The substance and the substance for detecting it may be present in an appropriate amount necessary for reaction or combination. also. Even if the solution introduced into the reaction unit through the pressure of the absorption unit is removed through the discharge pipe, the target substance present in the sample solution and the substance for detecting it may not be dried for reaction or combination.

Meanwhile, in the present invention, the sample solution is a solution containing the target substance for which the target substance is to be detected, and may refer to a solution obtained by processing blood, plasma, urine, tears, and sweat containing the target substance, and the analysis solution is the above. A solution containing substances (beads, antibodies, etc.) for detecting target substances present in the sample solution, and a solution such as beads with reacted antibodies, or a solution to activate the antibodies attached to the sensor unit when beads are not used. In the case of the labeling method, the antibody may refer to the primary antibody, and the washing solution is used to remove residual targets and impurities other than the amount required for the reaction in the solution introduced into the reaction section. It may refer to a solution for removing residues, and a reaction solution may refer to a solution containing a secondary antibody that reacts with a target material to cause an enzyme reaction, a fluorescence reaction, etc.

Meanwhile, the non-labeling method directly measures the target material bound to the antibody, and the labeling method measures the target material bound to the primary antibody, and the diagnostic cartridge of the present invention can be applied to either the labeling method or the non-labeling method.

A solution to be tested through the injection unit 10 (sample solution for detecting the target material), a reaction solution containing a material for detecting the target material, a material for detecting the target material, and a solution for detecting the target material. A washing solution or a reaction solution to remove those that do not specifically bind or react with the solution may be introduced or injected.

The diagnostic cartridge of the present invention may be characterized in that it can improve whether the remaining solution is discharged through the discharge pipe and the flowability of the remaining solution discharged depending on the volume of the solution flowing in through the injection unit 10. According to one embodiment of the present invention, when the amount of the injected solution is 10 to 60 ul, the solution is not discharged through the discharge pipe 14 and can cause an immune reaction in the reaction unit 11. However, the amount of the injected solution If it is 70 ul or more, the solution may be discharged into the absorption unit 15 through the discharge pipe 14.

The shape or material of the injection unit 10 is not particularly limited and may include any material known to those skilled in the art. Preferably, it has the shape of a reaction well with U-shaped or V-shaped pores, and has a structure in which all or part of the upper and lower parts are open, and the lower part has an area narrower than the open area of the upper surface, and the discharge pipe and A shape in which the solution is discharged by being connected is preferred.

For example, the diameter of the open upper surface of the injection part 10 is preferably 3 mm to 5.5 mm, and the diameter of the lower part of the injection part 10 is 1 mm to 3 mm, which is the same as the diameter of the upper surface. It is narrower than this, and the height from the upper surface of the injection part to the lower part is preferably 5 mm to 25 mm in order to control the water level of the solution.

If the diameter of the lower part of the injection unit 10 exceeds 3 mm, the discharge speed of the solution is fast, so the immune reaction does not sufficiently occur through the reaction unit 11 and is discharged into the absorption unit 15 through the discharge pipe 14. In this case, if the diameter of the lower part of the injection unit 10 is less than 1 mm, the solution flows into the injection unit and is not discharged to the reaction unit, making it difficult for an immune reaction for testing to occur.

The reaction unit 11 is located below the injection unit and may include a microwell containing beads for an immune reaction, and the beads may contain a substance for detecting a target substance. The substance for detecting the target substance is preferably one that reacts selectively or specifically with the target substance or analyte contained in the sample solution for detecting the target substance. Examples include antibodies, antigens, enzymes, peptides, proteins, It may include one or more selected from the group consisting of DNA, RNA, PNA (peptide nucleic acids), protein-binding nucleotides, and aptamers.

The diagnostic cartridge of the present invention selectively or specifically reacts and reacts with a substance for detecting a target substance on a bead contained in a reaction unit or present in a reaction unit, and a target substance or analyte contained in a sample solution for detecting a target substance. It may be characterized by measuring the amount of target material or analyte present in the sample solution by combining it.

On the other hand, when the substance for detecting the target substance on the beads is an antibody, the target substance present in the sample solution injected through the injection unit and the antibody contained in the bead may bind or react in an immune reaction. In addition, when the substance for detecting the target substance is an antibody, the reaction unit uses a signal substance (gold nanoparticles, fluorescent substance, electrochemical luminescent substance) to measure the amount of antigen, which is a target substance or analyte present in the sample solution. etc.), and the secondary antibody sample can detect a substance (antibody) for detecting the target substance.

The beads may be magnetic, but are not limited thereto.

The reaction unit may include a micro well for fixing a magnetic bead containing a material for detecting the target material, and the micro well has a porous structure or porous pores, so that the magnetic beads have a porous structure or porous pores of the micro well. It may be characterized as being fixed to.

According to one embodiment of the present invention, when the volume of the solution flowing through the injection unit 10 is 10 to 60 ul, the solution flows into the reaction unit 11 through the hinge unit 12 to initiate an immune reaction. This can happen.

For example, the reaction unit 11 can accommodate a secondary antibody sample containing signal substances such as gold nanoparticles, fluorescent substances, and electrochemical luminescent substances. In one embodiment, when the signal material is gold nanoparticles, optical characteristics can be analyzed through an optical reader using 532nm light absorption characteristics using a generally green light source, and when the signal material is a fluorescent material, the excitation light source and the signal material are possible. Can it be analyzed using a fluorescence optical reader that detects light emitted from the luminescence? It is not limited to this and may include everything known to those with ordinary knowledge in this technical field (hereinafter referred to as 'person skilled in the art'). Additionally, if the signal material is an electrochemical sensor-based reactive material, analysis is possible using the electrochemical sensor electrode structure and a reader that measures the electrical signal generated between these electrodes and the reactive material.

The hinge portion 12 connects the injection portion and the reaction portion so that the solution injected through the injection portion flows into the reaction portion. It has a branched structure in which one side is connected to the reaction portion and the other side is connected to the absorption portion through a discharge pipe. It can be characterized as:

The discharge pipe 14 may be characterized in that one side is connected to the hinge portion and the other side is connected to the absorption portion to discharge the solution into the absorption portion. Through the pressure of the absorption section, etc., the discharge pipe can remove sample solution, reaction solution, cleaning solution, analysis solution, etc. from the solution introduced into the reaction section other than the amount required for the reaction. In addition, the discharge pipe ensures that the target substance present in the sample solution in the reaction unit and the substance for detecting it are present in an appropriate amount necessary for reaction or combination, and that the solution in the reaction unit is dried so that the target substance present in the sample solution and the substance for detecting it are present in the appropriate amount. A certain amount of the solution introduced into the reaction section exists in the reaction section so that substances cannot react or combine, and a certain amount can be moved toward the absorption section to remove a certain amount.

The sensor unit 13 measures the amount of the target substance or analyte present in the sample solution. When the beads present in the reaction unit are magnetic, the substance for detecting the target substance on the beads is present in the sample solution. Measure the change in impedance that occurs when a target substance binds or reacts in an immune reaction, or when a substance for detecting a target substance on a bead and a target substance present in a sample solution bind or react in an immune reaction, the impedance on the bead is measured. The amount of the target substance present in the solution can be calculated by measuring the presence of a substance (such as a secondary antibody sample containing a signal substance) that specifically binds to the substance for detecting the target substance.

The sensor unit may include an impedance measurement reader unit, an optical reader unit, etc.

In one embodiment of the present invention, when the target material present in the sample solution binds to the antibody sample of the magnetic beads and is captured on the micro-well, the material that does not bind to the magnetic beads in the sample solution is washed with a washing solution of 70 degrees Celsius. If more than ul is injected, it can be discharged to the absorption unit (15) through the discharge pipe (14).

In one embodiment of the present invention, 30 ul of the analysis solution (about 5 mm water level based on the bottom of the reaction section) is injected through the injection section 10 to place the magnetic beads containing the antibody in the microwell of the sensor section, and then washed. More than 70 ul of solution (15 mm water level based on the bottom of the reaction section) was injected to remove magnetic beads that were not located in the micro-well. Afterwards, 30 ul of the sample solution is injected to cause an immune reaction between the magnetic beads containing the antibody and the target material, and the target material bound to the magnetic beads through the immune reaction is fixed on the microwell by the magnetic beads, and then By injecting more than 70 ul of the cleaning solution into the injection section 10, substances that are not bound to the magnetic beads through an immune reaction are discharged to the absorption part through the discharge pipe. Since residual target substances may remain, 70 ul of the cleaning solution are added twice more. By injection, residual target material was removed. Afterwards, 30 ul of the analysis solution capable of causing an enzyme reaction was injected to cause an enzyme reaction, and the impedance (or current) was measured to quantify the target substance. Through this method, by injecting a specific volume of reaction solution, sample solution, cleaning solution, and analysis solution, each solution is injected without the inconvenience of sequentially adding the analysis solution, sample solution, cleaning solution, and reaction solution and removing them from the injection port again. It was confirmed that only by doing so, it was possible to detect the target substance present in the sample solution and quantitatively analyze the amount of the target substance present in the sample solution.

In one embodiment, in order to detect the binding of the target material present in the sample solution and the antibody contained in the magnetic beads by an immune reaction, the sensor unit may include a detector module capable of measuring a change in impedance or a detector module capable of measuring an electrochemical reaction. It may further include a detector module into which an electrochemical sensor is inserted.

In one embodiment, the micro-well has a porous structure or porous pores, and the porous structure or porous pores have pores smaller than particles in which magnetic beads and target materials are bonded and larger than those in materials not bonded to the magnetic beads. However, it is not limited to this. The reaction unit containing the microwell has a porous structure or porous pore structure to fix the magnetic beads containing the antibody, and the target material to be tested based on the principle of an immune reaction or a specific reaction between biological materials is a magnetic bead containing the antibody. It is captured by binding, and if the target material is not captured by the magnetic beads containing the antibody, the sample solution residue can be discharged through the discharge pipe by injecting a certain amount of washing solution through the injection part 10. . For example, the washing solution may be PBS, and 70 ul or more of the washing solution may be injected, but is not limited thereto.

In one embodiment, when a solution of less than a certain volume (10 to 60 ul) is injected through the injection part so that the water level of the reaction part is less than a certain level (5 - 8 mm), the solution is injected into the discharge pipe 14 by the surface tension generated at the inlet of the discharge pipe. It cannot be continuously discharged to the absorption part through the solution, but if a certain volume (70 ul or more) of solution is injected through the injection part so that the water level in the reaction part exceeds a certain level (10 mm or more), the solution is discharged through the discharge pipe (14). In addition, the solution flows continuously due to pressure such as the suction force of the absorbent part, and the discharge and flow of the solution can be improved. At this time, the substances for which no immune response has occurred are discharged in one direction, and thus all unnecessary by-products and biological materials for which no immune response has occurred are washed in the direction of the flow of the solution and discharged through the discharge pipe 14.

Therefore, the diagnostic cartridge with improved discharge control and flowability of the solution of the present invention allows the sample solution, reaction solution, cleaning solution, analysis solution, etc. present in the reaction part to flow through the discharge pipe through the volume of the solution flowing in or injected through the injection part. It is possible to easily control the discharge and the flow of the solution so that it is discharged through the discharge.

In addition, the flow rate and flow rate of the solution passing through it can be controlled by varying the location, size, and type of the discharge pipe 14, or by varying the negative pressure or the amount of solution injected into the injection section. For example, during an immune reaction, the solution is slowly injected. The reaction sensitivity can be improved by moving and moving quickly during washing.

The absorbent portion 15 makes the discharge flow of the solution continuous and stable, and may include an absorbent pad. The absorbent pad may include or be composed of a material with strong solution absorption properties, Specifically, it may be paper (non-woven fabric), polymer chemical (Super Absorbent Polymer), or natural super absorbent (Supre Absorbent Cellulose). For example, the polymer chemical may be a thermoplastic resin, nitrocellulose, or a synthetic hydrogel-forming polymer, but is not limited thereto.

The absorption unit includes an absorption pad, and the absorption pad absorbs the solution discharged through the discharge pipe to maintain constant surface tension and pressure conditions at the end of the discharge pipe, allowing the solution to continuously move to the absorption unit along the discharge pipe. The amount of sample solution, reaction solution, cleaning solution, analysis solution, etc. injected into the injection part through the absorption part can be kept constant while the discharge of the solution can be easily controlled.

Due to the absorption part, the unbound substances are discharged in one direction through the discharge pipe 14, and all unnecessary by-products and biological substances that do not cause an immune response are washed in the direction of the flow of the solution and included in the absorption section through the discharge pipe 14. It is absorbed with an absorbent pad. In addition, the flow rate and flow rate of the solution passing through the well can be controlled by varying the position, size, and type of the absorption pad or by applying negative pressure, and the flow of the solution can be continuously controlled under certain conditions due to the discharge flow of the solution as described above. It becomes possible.

According to one embodiment of the present invention, when the absorbent part does not exist, as shown in FIG. 3a, after a solution less than a certain volume is injected through the injection part ((1) in FIG. 3a), it is not discharged due to surface tension (FIG. 3a) (2)), when additional solution is injected to exceed a certain volume ((3) in Figure 3a), the solution moves through the discharge pipe and is discharged outside the kit, but because there is no absorber, the solution moving to the discharge pipe forms drops at the end of the discharge pipe. Since it falls off and is discharged, not all of the solution moved to the discharge pipe is discharged, and some residue remains in the discharge pipe ((4) in FIG. 3a). Afterwards, when additional solution is injected ((5) in Figure 3a), some residue is present in the discharge pipe and surface tension and pressure conditions are different from those in (1) to (4) shown in Figure 3a, so the solution is discharged. In order to do this, a problem occurs in that a larger volume is needed than the specific volume required to discharge the solution in (1) to (4) shown in FIG. 3A.

On the other hand, in the case where an absorption part is present, when the solution is injected through the injection part as shown in Figure 3b ((1) in Figure 3b), the absorption pad present in the absorption part absorbs the solution moving to the discharge pipe and the solution is continuously discharged from the discharge pipe. It is discharged to the absorption part so that there is no residual solution in the discharge pipe ((2) to (4) in FIG. 3B). Even when the solution moves to the absorption pad of the absorption section through the discharge pipe, the target material present in the sample solution and the material for detecting it are required for reaction or combination in the reaction section due to the step difference between the reaction section and the discharge pipe above a certain height. Reaction is possible because an appropriate amount is present and a certain amount of solution is present so that the reaction zone does not dry out and prevent the target material present in the sample solution from reacting or combining with the material for detecting it ((4) in FIG. 3b). When additional solution is injected again ((5) in Figure 3b), unlike in Figure 3a, there is no solution residue in the discharge pipe, so the surface tension and pressure conditions are the same as before injecting the solution, and (shown in Figure 3b) Discharge of the solution can be controlled by using a volume equal to the specific volume required to discharge the solution in 1) to (4).

Therefore, the amount of sample solution, reaction solution, cleaning solution, analysis solution, etc. injected into the injection part through the absorption part can be kept constant while the discharge of the solution can be easily controlled.

Figure 2 confirms whether the injected solution is discharged according to an embodiment of the present invention.

As shown in the figure, in one embodiment of the present invention, the target material present in the solution injected through the injection unit 10 combines with the antibody sample of the magnetic beads included in the reaction unit 11 to form the reaction unit 11. When captured by the micro-well of (11), substances in the solution composition that do not bind to the magnetic beads are discharged through the discharge pipe (14).

For example, as shown in Figure 2a, when the amount of solution injected through the injection unit 10 is 10 to 60 ul, it is not discharged to the absorption unit 15 through the discharge pipe 14 and an immune response occurs in the reaction unit 11. Therefore, first, 10 to 60 ul of the sample solution for detecting the target material containing the target material is injected into the injection section 10, and then the magnetic sample containing the antibody previously placed in the micro-well of the reaction section 11 An immune reaction is caused with the beads, and the target substance present in the sample solution combined with the magnetic beads through the immune reaction is fixed to the micro-well included in the reaction unit by the magnetic beads, and is then mixed with the sample solution as shown in FIG. 2b. By injecting the cleaning solution into the injection unit (10) so that the total volume of the cleaning solution is 70 ul or more, substances that are not bound to the magnetic beads through an immune reaction are discharged into the absorption unit (15) through the discharge pipe (14). Thus, target substances present in the sample solution can be specifically detected.

In addition, the present invention includes the steps of injecting a first volume of an analysis solution containing beads for an immune response through the injection portion of a diagnostic cartridge with improved discharge control and flowability of the solution of the present invention;

Injecting a second volume of a sample solution for detecting a target material through the injection unit to bind or react with the sample solution for detecting a target material and a substance for specifically detecting a target material on a bead; and

Injecting a third volume of the cleaning solution through the injection unit to remove residual substances that have not specifically bound or reacted with the sample solution for detecting the target substance; A diagnostic method using a diagnostic cartridge with improved discharge control and flowability of a solution containing is provided.

The diagnostic method may further include measuring the amount of the target material or analyte present in the sample solution through the sensor unit. The measuring step measures the change in impedance that occurs when the substance for detecting the target substance on the bead and the target substance present in the sample solution bind or react in an immune reaction when the beads present in the reaction section are magnetic. , when the substance for detecting the target substance on the bead and the target substance present in the sample solution bind or react in an immune reaction, the presence of a substance that specifically binds to the substance for detecting the target substance on the bead (signal substance) It can be characterized by calculating the amount of target material present in the solution by measuring the secondary antibody sample (including secondary antibody sample, etc.).

When using the above diagnostic method, the flowability of the solution injected through the injection unit can be adjusted by injecting a specific volume of solution.

Specifically, the solution injected so that the first volume of the solution containing beads for the immune reaction and the second volume of the sample solution for detecting the target material each or the combined volume of the first volume and the second volume are 10 to 60 ul. The material for detecting the target material on the beads and the target material present in the sample solution can bind or react through an immune reaction without being discharged into the discharge pipe and the solution does not dry out in the reaction section, and among the first and second volumes The combined volume of the remaining solution volume and the third volume can be adjusted to be 70 ul or more so that substances not bound to the magnetic beads through an immune reaction can be discharged into the absorption unit 15 through the discharge pipe 14. If multiple cleaning operations are required, additional cleaning operations can be performed by injecting 70 ul or more of the cleaning solution.

In one embodiment, in the step of injecting the first volume of the solution containing beads for an immune reaction through the injection unit, if the volume of the solution flowing through the injection unit is 10 to 60 ul, the solution is injected into the reaction unit through the hinge unit. Since the solution flowing in through the injection unit is not discharged to the absorption unit through the discharge pipe, an immune reaction may occur if a sample solution containing the target material is subsequently injected through the injection unit.

For example, the beads may be injected through an injection unit and positioned in the reaction unit through a hinge unit.

The second volume injected in the step of injecting the second volume of the sample solution for detecting the target material through the injection unit to bind or react with the sample solution for detecting the target material and the material for specifically detecting the target material on the bead; In the step of injecting the first volume of the solution containing beads for an immune reaction through the injection part of the diagnostic cartridge, if the sum of the first volume introduced is 10 to 60 ul, the injected solution is not discharged into the discharge pipe and is discharged from the reaction part. The material for detecting the target material on the beads and the target material present in the sample solution can combine or react in an immune reaction without the solution drying out.

The step of injecting the third volume of the cleaning solution through the injection unit to remove residual substances that have not specifically bound or reacted with the sample solution for detecting the target substance is to remove substances that have not been bound to the magnetic beads by an immune reaction through the discharge pipe (14). It is discharged to the absorption unit 15 through, and the third volume is magnetic by making the sum of the remaining solution volume and the third volume among the first volume and the second volume (total residual solution) more than 70 ul. Substances that are not bound to the beads through an immune reaction can be discharged into the absorption unit 15 through the discharge pipe 14.

For example, the washing solution may be PBS, but is not limited thereto.

The step of injecting the cleaning solution through the injection unit to remove residual substances that have not specifically bound or reacted with the solution for detecting the target substance involves injecting a certain volume of the cleaning solution to raise the water level above a certain level in the reaction zone through the injection unit. As the cleaning solution is injected, residual substances that have not specifically bound or reacted with the cleaning solution and the solution for detecting target substances can be removed without separate pipetting.

The diagnostic method using the diagnostic cartridge with improved solution flowability of the present invention may be characterized by controlling whether or not the solution is discharged depending on the volume of the solution flowing in through the injection unit. According to one embodiment of the present invention, When the amount of solution injected into the injection port of the diagnostic cartridge with improved flowability of the solution of the present invention is 10 to 60 ul, the solution may not be discharged through the discharge pipe and may cause an immune reaction in the reaction portion, but the injected solution If the amount is more than 70 ul, the solution can be discharged into the absorption unit through the discharge pipe.

In addition, the diagnostic method using the diagnostic cartridge with improved discharge control and flow of the solution of the present invention includes diagnosis of neuropsychiatric diseases such as dementia diagnosis, diabetes diagnosis, myocardial infarction diagnosis, Parkinson's diagnosis, Alzheimer's disease diagnosis, cancer diagnosis, and immune response. It can be used for basic protein detection, etc.

The description of the present invention described above is for illustrative purposes, and those skilled in the art can understand that the present invention can be easily modified into other specific forms without changing the technical idea or essential features of the present invention. There will be. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive. For example, each component described as single may be implemented in a distributed manner, and similarly, components described as distributed may also be implemented in a combined form.

The scope of the present invention is indicated by the claims described below rather than the detailed description above, and all changes or modified forms derived from the meaning and scope of the claims and their equivalent concepts should be construed as being included in the scope of the present invention. do.

[Explanation of symbols]

10: injection part

11: reaction unit

12: Hinge part

13: sensor unit

14: discharge pipe

The diagnostic cartridge with improved solution flow according to the technical idea of the present invention can increase the efficiency and accuracy of diagnosis using the diagnostic cartridge by controlling whether the solution is discharged depending on the volume of the solution injected into the injection portion of the diagnostic cartridge. Therefore, it has industrial utility in that it can increase the efficiency and accuracy of diagnosis through the kit by increasing the accuracy of the antigen-antibody reaction and lowering the loss rate of the solution.

Claims

An injection unit where a sample solution for detecting target substances is injected;

a reaction unit located below the injection unit and including a micro-well accommodating beads for an immune reaction;

A hinge part connecting the injection unit and the reaction unit so that the solution injected through the injection unit flows into the reaction unit;

A discharge pipe that has one side connected to the hinge portion and the other side connected to the absorbent portion to discharge the solution into the absorbent portion; and

An absorption unit that absorbs the discharged solution; A diagnostic cartridge with improved discharge control and flowability of a solution containing a.
According to paragraph 1,

A diagnostic cartridge with improved discharge control and flowability of the solution, characterized in that the hinge portion has a branched structure in which one side is connected to the reaction portion and the other side is connected to the absorption portion through a discharge pipe.
According to paragraph 1,

A diagnostic cartridge with improved discharge control and flowability of the solution, wherein the reaction unit includes a bead and the bead includes a material for detecting a target material.
According to paragraph 3,

The substance for detecting the target substance contains one or more selected from the group consisting of antibodies, antigens, enzymes, peptides, proteins, DNA, RNA, PNA (peptide nucleic acids), protein-binding nucleotides, and aptamers. A diagnostic cartridge with improved discharge control and flowability of the solution.
According to paragraph 4,

When the substance for detecting the target substance is an antibody, the target substance present in the solution injected through the injection unit and the antibody contained in the bead bind or react with an immune reaction, controlling the discharge and flow of the solution. Diagnostic cartridge with improved performance.
According to clause 5,

A diagnostic cartridge with improved discharge control and flowability of the solution, characterized in that the reaction portion does not dry out in order for the immune response to occur.
According to paragraph 1,

A diagnostic cartridge with improved discharge control and flowability of the solution, wherein the beads of the reaction unit are magnetic.
According to paragraph 1,

The absorbent portion includes an absorbent pad, and the absorbent pad absorbs the solution discharged through the discharge pipe and allows the solution to continuously move to the absorbent portion along the discharge pipe. A diagnostic cartridge with improved discharge control and flowability of the solution. .
According to paragraph 1,

A diagnostic cartridge with improved discharge control and flowability of the solution, characterized in that it additionally includes a sensor unit.
According to clause 9,

The sensor unit measures the change in impedance that occurs when the target material present in the sample solution and the material for detecting the target material on the beads bind or react in an immune response, or detects the target material on the bead and the sample solution. When the target substance present in the bead is bound or reacted with an immune response, the amount of the target substance present in the solution is calculated by measuring the presence of a substance that specifically binds to the substance for detecting the target substance on the bead. A diagnostic cartridge characterized by improved discharge control and flowability of the solution.
According to paragraph 1,

A diagnostic cartridge with improved discharge control and flowability of the solution, characterized in that it is possible to control whether or not to discharge the solution flowing into the discharge pipe through the volume of the solution flowing into the injection unit.
Injecting a first volume of a solution containing beads for an immune response through an injection portion of the diagnostic cartridge with improved discharge control and flowability of the solution of claim 1;

Injecting a second volume of a sample solution for detecting a target material through the injection unit to bind or react with the sample solution for detecting a target material and a substance for specifically detecting a target material on a bead; and

Injecting a third volume of the cleaning solution through the injection unit to remove residual substances that have not specifically bound or reacted with the sample solution for detecting the target substance; A diagnostic method using a diagnostic cartridge with improved discharge control and flowability of a solution containing.