Modular assembly-type diagnostic kit

Abstract

The present invention relates to a modular assembly-type diagnostic kit. The modular assembly-type diagnostic kit of the present invention enables diagnostic kits having various configurations to be easily manufactured by simply assembling modular kits that have passed QC, and is very useful since the problem, with respect to a conventional multi-diagnostic kit, of having to discard the entire kit even if a defect occurs in only one diagnostic unit from among several diagnostic units can be mitigated.

Description

Modular prefabricated diagnostic kit

[0001] This invention was made under the support of the Ministry of SMEs and Startups of the Republic of Korea under the task identification number 1425177624 and detailed task number S3363959. The task management specialized organization of the said task is the Small and Medium Business Technology Information Promotion Agency, the research project name is “Regional Specialized Industry Promotion”, the research project title is “Development of Malaria Diagnostic Kit and Treatment Pre-diagnosis Device Capable of Simultaneous Measurement of G6PD, Hb, and Bilirubin”, the task performing organization is Rebio Co., Ltd., and the research period is 2023.04.01-2024.12.31.

[0002] This patent application claims priority to Republic of Korea Patent Application No. 10-2023-0195816, filed with the Korean Intellectual Property Office on December 28, 2023, the disclosure of which is incorporated herein by reference.

[0003] The present invention relates to a modular assembly diagnostic kit.

[0004]

[0005] Plasmodium vivax malaria is a tropical disease that requires genetic screening before prescribing treatment. Specifically, malaria patients should be tested for Glucose-6-phosphate dehydrogenase (G6PD) deficiency before treatment.

[0006] Primaquine and tafenoquine, which are anti-malaria drugs, cause oxidative stress in the red blood cells of patients with G6PD deficiency, causing the oxidation of glutathione within the red blood cells. Red blood cells lacking G6PD have limited ability to regenerate glutathione, so glutathione is rapidly depleted. In the absence of glutathione, hemoglobin and proteins are oxidized, causing irreversible damage to the red blood cell membrane and destruction of the red blood cells. Therefore, if primaquine or tafenoquine is administered to patients with G6PD deficiency, acute hemolytic anemia can occur within 24 to 72 hours after administration, causing fatigue, back pain, jaundice, hyperbilirubinemia, and severe pernicious anemia requiring transfusion, which can actually put the patient at greater risk.

[0007] In particular, G6PD deficiency is asymptomatic, so in most cases even patients do not know that they have G6PD deficiency. Since symptoms are induced only by external factors such as malaria treatments such as primaquine and tafenoquine, antibiotics, and consumption of fava beans, it is essential to confirm the presence or absence of G6PD deficiency in advance. However, since many people suffer from G6PD deficiency in malaria-endemic areas, it is essential to perform a G6PD test quickly and accurately before administering primaquine and tafenoquine to patients with vivax malaria who require urgent treatment.

[0008] Numerous papers and patents are referenced and cited throughout this specification. The disclosures of these cited papers and patents are incorporated herein by reference in their entirety to provide a clearer understanding of the state of the art and the scope of the invention.

[0009]

[0010] In order to solve the above problems, the inventors of the present invention, while designing a pre-diagnosis kit for malaria treatment, came up with the idea of ​​combining kits with different purposes into a single kit to produce a kit capable of performing multiple diagnoses, including G6PD, in a single diagnostic kit, and completed the present invention.

[0011] Accordingly, an object of the present invention is to provide a modular assembly diagnostic kit.

[0012] Other objects and advantages of the present invention will become more apparent from the detailed description, claims and drawings below.

[0013]

[0014] The present invention provides a modular assembly diagnostic kit comprising the following configuration:

[0015] A cartridge upper case (10); two or more diagnostic kit module units (20); and a cartridge lower case (30).

[0016] In addition, the present invention provides a method for manufacturing the modular assembly diagnostic kit.

[0017] In addition, the present invention provides a method of using the modular assembly diagnostic kit.

[0018]

[0019] The present invention provides a modular assembly diagnostic kit.

[0020] When using the modular assembly diagnostic kit of the present invention, diagnostic kits of various configurations can be easily manufactured simply by assembling modular kits that have passed QC, and in the case of existing multi-diagnostic kits, the problem of having to discard the entire kit if a defect occurs in only one of several diagnostic units can be resolved, so it is very useful.

[0021]

[0022] Figure 1 is a perspective view showing a modular assembly diagnostic kit of the present invention.

[0023] Figure 2 is a diagram showing an exploded view of the modular assembly diagnostic kit of the present invention.

[0024] Fig. 3 is a perspective view showing the diagnostic kit array strip of the present invention.

[0025] Figure 4 is a diagram showing an exploded view of the diagnostic kit array strip of the present invention.

[0026]

[0027] Hereinafter, the present invention will be described in detail with reference to the attached drawings.

[0028] The present invention is susceptible to various modifications and may take various forms. Therefore, embodiments (or examples) are described in detail herein. However, this is not intended to limit the present invention to a specific disclosed form, and it should be understood that the present invention encompasses all modifications, equivalents, and alternatives falling within the spirit and technical scope of the present invention.

[0029] In each drawing, the same reference signs, especially the tens and units digits, or the tens, units digits, and alphabets, indicate parts having the same or similar functions, and unless otherwise specified, the parts referred to are understood to be parts that comply with these standards.

[0030] In addition, in each drawing, the components are expressed in an exaggerated (or thick) or simplified (or thin) size or thickness for convenience of understanding, but the scope of protection of the present invention should not be interpreted as being limited by this.

[0031] The terminology used herein is merely used to describe specific implementations (modes, aspects) (or examples) and is not intended to limit the present invention. The singular expression includes the plural expression unless the context clearly indicates otherwise.

[0032] In this application, terms such as “include” or “consist of” are intended to specify the presence of a feature, number, step, operation, component, part, or combination thereof described in the specification, but should be understood as not excluding in advance the possibility of the presence or addition of one or more other features, numbers, steps, operations, components, parts, or combinations thereof.

[0033] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs.

[0034] Terms defined in commonly used dictionaries should be interpreted to have a meaning consistent with their meaning in the context of the relevant technology, and will not be interpreted in an idealized or overly formal sense unless expressly defined in this application.

[0035]

[0036] FIGS. 1 and 2 are perspective and exploded views, respectively, of a modular assembly diagnostic kit according to one embodiment of the present disclosure.

[0037] According to one aspect of the present invention, the present invention provides a modular assembly diagnostic kit (1) comprising the following configuration:

[0038] A cartridge upper case (10); two or more diagnostic kit module units (20); and a cartridge lower case (30).

[0039] In the examples shown in FIGS. 1 and 2, the cartridge has a circular outer shape, but this should be understood as being exemplary and may be implemented in any shape, for example, a square, a rectangle, an oval, or other non-standard shapes.

[0040] In one embodiment of the present invention, the diagnostic kit module unit (20) is inserted between the cartridge upper case (10) and the cartridge lower case (30).

[0041] At this time, the cartridge upper case and the cartridge lower case can be connected by any method known in the art between multiple members.

[0042] For example, the cartridge upper case (10) and the cartridge lower case (30) are each provided with a joining projection (11) and a joining groove (31) so that they can be joined to each other, and can be fastened to each other in a fitting manner.

[0043] In another embodiment of the present invention, the coupling protrusion and the coupling groove may be provided in the cartridge upper case (10) and the cartridge lower case (30), respectively, or may be provided in the cartridge lower case (30) and the cartridge upper case (10), respectively.

[0044] According to another embodiment, a bolt (or screw) may be formed in the upper case (10) of the cartridge, and a screw (or bolt) may be formed in the lower case (30) of the cartridge, thereby utilizing a rotational fastening method.

[0045] According to another embodiment, holes may be formed at corresponding coupling positions in both the cartridge upper case (10) and the cartridge lower case (30), and the two may be fastened by a combination of bolts and nuts.

[0046] In addition, according to another alternative implementation example, the cartridge upper case (10) and the cartridge lower case (30) can be attached to each other using an adhesive. Examples of such adhesives include rubber-based adhesives, acrylic resin-based adhesives, silicone-based adhesives, optical adhesives, and heat-sensitive adhesives, but are not limited to those listed above. However, in order to facilitate assembly and disassembly of the modular diagnostic kit, bonding (fastening) using an adhesive may not be advantageous.

[0047] In one embodiment of the present invention, the cartridge upper case (10) and the cartridge lower case (30) have a receiving groove (12, 32) therebetween that can receive the diagnostic kit module unit (20), and the cartridge upper case (10) and the cartridge lower case (30) each have a through hole (13, 33) formed by penetrating in the vertical direction, and the diagnostic kit module unit (20) is exposed to the outside through the through hole (13, 33).

[0048] In one embodiment of the present invention, the number of receiving grooves (12, 32) and through holes (13, 33) is the same as the number of the two or more diagnostic kit module units.

[0049] The diagnostic kit module unit (20) of the present invention may include layers of various configurations depending on the diagnostic purpose.

[0050] In one embodiment of the present invention, the diagnostic kit module unit (20) may include one or more layers selected from the group consisting of a layer having a mesh, a layer having glass fiber, a membrane containing a reagent or enzyme, etc., as needed.

[0051] The above mesh layer serves to ensure that when loading a liquid sample such as blood or urine, the sample is spread evenly rather than concentrated in one place.

[0052] The above glass fiber layer serves to separate red blood cells or delay the flow time of the sample in the case of a blood sample, and when two or more layers are laminated, the red blood cell separation ability is improved and the flow time of the sample is further delayed.

[0053] The layer containing the above reaction reagent or enzyme, etc., reacts with the target substance in the loaded sample by processing the reaction reagent. When the sample and reagent react, color development occurs, allowing the presence or absence of a reaction to be determined.

[0054] For example, in a specific embodiment of the present invention, when the diagnostic kit module unit (20) is for hemoglobin detection, it may include, from top to bottom, i) a first layer (21) having a mesh for loading a sample, and ii) a second layer (22) having a membrane including a reaction reagent for reacting with the loaded sample, but is not limited thereto.

[0055] In another specific embodiment of the present invention, when the diagnostic kit module unit (20) is for detecting G6PD, bilirubin, or PKU (phenylketone uria), it may include, but is not limited to, from top to bottom, i) a first layer having a mesh for loading a sample, ii) a first glass fiber layer, iii) a second glass fiber layer, and iv) a membrane containing a reaction reagent.

[0056] In specific embodiments of the present invention, the sample is not particularly limited to a substance containing the target to be detected. For example, the sample is a biological sample (biological fluid or tissue).

[0057] The biological fluid may be urine, blood, plasma, serum, saliva, semen, sputum, tears, amniotic fluid, cerebrospinal fluid, etc. The biological tissue may be epithelial tissue, muscle tissue, nervous tissue, etc. of a human, animal, etc. The sample may include cells, bacteria, viruses, etc.

[0058] The above detection targets may include, but are not limited to, proteins, genes, amino acids, nucleic acids, hormones, drugs, antibodies, etc.

[0059] In one embodiment of the present invention, the second layer (22) corresponds to a detection area.

[0060] In one embodiment of the present invention, the reaction reagent may be, but is not limited to, an antibody, an antigen, an enzyme, or an enzyme substrate. In addition, the membrane may contain a labeling substance (or signal-generating substance).

[0061] The above-mentioned labeling material (or signal generating material) may be a metal nanoparticle (e.g., gold, silver, copper nanoparticles, etc.), quantum dot nanoparticles, magnetic nanoparticles, enzymes, enzyme substrates, enzyme reaction products, light absorbing materials, fluorescent materials, or luminescent materials. More specifically, the labeling material may be a fluorescent material, such as fluorescein including umbelliferone, fluorescein, fluorescein isothiocyanate (FITC), rhodamine, TAMRA, dichlorotriazinylamine fluorescein, dansyl chloride, quantum dots, phycoerythrin, fluorecein amidite (FAM), alexa fluor, and cyanine including Cy3, Cy5, Cy7, and indocyanine green, and one or more of these may be used in combination.

[0062] In one embodiment of the present invention, the membrane may be formed in the form of a porous membrane. For example, the membrane may be selected from cellulose, glass fiber, nitrocellulose, polyvinylidene fluoride, charge-modified nylon, polyether sulfone, and the like. More typically, polyether sulfone (PES) may be used.

[0063] In a specific embodiment of the present invention, the detection region may include a test region and a control region.

[0064] Additionally, in one embodiment of the present invention, the diagnostic kit module unit (20) may additionally include a third layer (23) including a sample filter.

[0065] The above sample filter is a filter for filtering out impurities that may affect the diagnostic efficacy of the diagnostic kit in a sample to be loaded into the diagnostic kit of the present invention. The sample filter may be a blood cell separation filter, for example, if the sample is blood. One or more of the sample filters may be included in the third layer (23).

[0066] Additionally, the third layer may be placed above the first layer (21) to achieve the purpose of filtering impurities.

[0067] In another embodiment of the present invention, the diagnostic kit module unit (20) may additionally include an absorbent pad for absorbing excess sample.

[0068] In one embodiment of the present invention, the detection targets of two or more diagnostic kit module units (20) included in the modular assembly diagnostic kit (1) of the present invention may be the same or different.

[0069] In a specific embodiment of the present invention, when the modular assembly diagnostic kit of the present invention is manufactured as a pre-diagnosis kit for malaria treatment, four diagnostic kit module units (20) may be combined, and the detection targets of each diagnostic kit module unit may be G6PD, bilirubin, Hb (hemoglobin), and a control group.

[0070] In one embodiment of the present invention, the first layer (21), the second layer (22), the third layer (23), etc., which constitute the diagnostic kit module unit, may each be provided with a joining projection (22-1, 22-2, 22-3, 22-4) and a joining groove (21-1, 21-2, 21-3, 21-4) so ​​that they can be joined to each other.

[0071] In one embodiment of the present invention, the modular assembly diagnostic kit has the following characteristics:

[0072] The cartridge upper case and the cartridge lower case have a receiving groove therebetween that can receive the diagnostic kit module unit,

[0073] The upper case of the cartridge and the lower case of the cartridge each have a through hole formed by penetrating in the vertical direction,

[0074] The above diagnostic kit module unit is inserted between the upper case of the cartridge and the lower case of the cartridge, and is exposed to the outside through the through hole.

[0075] In one embodiment of the present invention, the pre-diagnosis kit for malaria treatment is merely an example of a kit that can be manufactured as an assembly-type diagnostic kit of the present invention. Accordingly, the modular assembly-type diagnostic kit of the present invention can be manufactured as a multi-diagnosis kit for various purposes, such as pre-diagnosis for malaria treatment, malaria diagnosis, cholesterol level, liver function, sexually transmitted disease diagnosis, rare neonatal disease diagnosis, pregnancy diagnosis, and ovulation diagnosis.

[0076]

[0077] FIGS. 3 and 4 are perspective and exploded views, respectively, of a diagnostic kit array strip according to one embodiment of the present disclosure.

[0078] According to another aspect of the present invention, the present invention provides a method for manufacturing a modular assembly diagnostic kit of claim 1, comprising the following steps:

[0079] (a) A step of manufacturing a diagnostic kit array strip (100) in which two or more diagnostic kit module units (101) are connected in series with a cutting line (103) therebetween and include a jig fixing part (102) at both ends;

[0080] (b) a step of cutting and separating the diagnostic kit module unit (101) from the diagnostic kit array strip (100);

[0081] (c) a step of inserting the separated diagnostic kit module unit (101, 20) between the cartridge upper case (10) and the cartridge lower case (30), which are provided with two or more receiving grooves capable of accommodating the diagnostic kit module unit (101); and

[0082] (d) A step of combining the upper case (10) and the lower case (30) of the cartridge.

[0083] According to the specific examples illustrated in FIGS. 3 and 4, the diagnostic kit array strip (100) of the present invention is connected in series with diagnostic kit module units (101) interposed between the cutting lines. Accordingly, some of the multiple diagnostic kit module units can be easily cut and separated along the cutting lines.

[0084] In one embodiment of the present invention, the diagnostic kit array strip, the cartridge upper case, and the cartridge lower case can each be formed through a conventional molding process, particularly an injection molding process.

[0085] The injection molding process is a method of injecting a polymer melt into a mold and / or a mould, cooling it, and then separating it from the mould, and the detailed technology for this is known in the art.

[0086] In one embodiment of the present invention, each of the diagnostic kit module unit, the diagnostic kit array strip, the cartridge upper case, and the cartridge lower case may be formed of a resin of polyester, polyethylene (PE), polypropylene (PP), polyimide (PI), polystyrene (PS), polycarbonate (PC), polyurethane, polyvinylidene fluoride, nylon, polymethyl methacrylate (PMMA), polyvinyl chloride (PVC), cyclic olefin copolymer (COC), polyamide (PA), poly(phenylene ether) (PPE), polyoxymethylene (POM), polyether ether ketone (PEEK), polyether sulfone (PES), polytetrafluoroethylene (PTFE), or an acrylic series, but the types listed above are exemplary and not limited thereto.

[0087] The above diagnostic kit array strip (101) can also be manufactured by combining the first layer, the second layer, and the third layer, etc., which constitute the diagnostic kit module unit.

[0088] In a specific embodiment of the present invention, the diagnostic kit array strip (100) may include 10 diagnostic kit module units (101) connected in series and a jig fixing portion (102) at both ends.

[0089] The above diagnostic kit array strip can be manufactured by combining a first layer having a mesh for loading a sample, and ii) a second layer including a membrane containing a reagent for reacting with the loaded sample, as described in the modular assembly diagnostic kit according to one aspect of the present invention described above. As a result, a plurality (e.g., 10) diagnostic kit module units can be manufactured at once.

[0090] According to an exemplary embodiment of the present invention, when manufacturing a diagnostic kit in this manner, a diagnostic kit array strip for G6PD diagnosis is manufactured in the process of step (a), a diagnostic kit array strip for Hb diagnosis is manufactured in another process, and a diagnostic kit array strip for bilirubin diagnosis is manufactured in yet another process, so that diagnostic kit module units suitable for each diagnostic purpose can be mass-produced [diagnostic kit array strip manufacturing step of step (a)].

[0091] In addition, by going through the process of cutting each mass-produced diagnostic kit array strip [the cutting and separation step of step (b)], a G6PD diagnostic kit module unit, an Hb diagnostic kit module unit, and a bilirubin diagnostic kit module unit can each be obtained in large quantities.

[0092] Next, a quality inspection is performed on the mass-produced purpose-specific diagnostic kit module units, and only the good products that have passed the quality inspection are combined into a prototype type cartridge. As a result, the manufactured diagnostic kit can be a multi-diagnostic kit capable of multiple diagnosis of G6PD, Hb, and bilirubin, and only good products can be produced.

[0093]

[0094] According to another aspect of the present invention, the present invention provides a method of using a modular assembly diagnostic kit comprising the following steps:

[0095] (a) loading a sample into two or more diagnostic kit module units;

[0096] (b) a step of allowing the sample to sufficiently react with each diagnostic kit module unit; and

[0097] (c) A step of sensing a signal from each diagnostic kit module unit for which a reaction has been completed using a signal reader.

[0098]

[0099] The method for manufacturing and the method for using the modular assembly diagnostic kit according to one aspect of the present invention are respectively related to the method for manufacturing the modular assembly diagnostic kit according to one aspect of the present invention described above and the method for using the same, so overlapping configurations between the two inventions can be commonly applied.

[0100] According to one aspect of the present invention, the modular assembly diagnostic kit first loads samples into two or more diagnostic kit module units, and if there is a test target in each sample, incubation is performed for a certain period of time so that the test target can sufficiently react with the diagnostic kit module unit, and then a signal is generated depending on whether a detection reaction occurs.

[0101] The above signal can be sensed by a signal reader, which can be, but is not limited to, an optical sensor such as a spectrophotometer capable of detecting UV or fluorescent signals.

[0102] In a specific embodiment of the present invention, if the modular assembly diagnostic kit of the present invention is a multi-diagnostic kit for G6PD, Hb, and Bilirubin for pre-diagnosis of malaria treatment, a blood sample is used as the sample. In another embodiment, if the diagnostic kit is for another purpose, various types of samples such as saliva, nasal mucus, urine, stool dilution, and plasma can be loaded as samples depending on the diagnostic purpose.

[0103] In a specific embodiment of the present invention, when a blood sample is loaded into the diagnostic kit module unit of the present invention, the sample flows in according to the vertical flow, and the loaded sample dissolves the reaction reagent immersed / dried in the membrane constituting the diagnostic kit module unit, and when it reacts with the reaction reagent, a specific luminescence signal is generated. When this luminescence signal is irradiated with, for example, an LED light source, and a PD (photodiode) receives the light and converts it into a digital signal, the color of the luminescence signal and the reflectance value according to the color concentration can be obtained. The obtained signal value is calculated according to a predetermined formula provided for each diagnostic factor and converted into a measurement value of the diagnostic factor, so that a quick and precise diagnosis is possible.

[0104]

[0105] While specific aspects of the present invention have been described in detail above, it is clear to those skilled in the art that these specific descriptions are merely preferred implementation examples and that the scope of the present invention is not limited thereto.

[0106]

[0107] [Explanation of symbols]

[0108] 1: Modular assembly diagnostic kit

[0109] 10: Cartridge top case

[0110] 11: Binding projection

[0111] 12: Reception Home

[0112] 13: Through hole

[0113]

[0114] 20: Diagnostic Kit Module Unit

[0115] 21: First layer

[0116] 21-1, 21-2, 21-3, 21-4: Combined home

[0117] 22: Second layer

[0118] 22-1, 22-2, 22-3, 22-4: Connective tissue

[0119] 23: Third Layer

[0120]

[0121] 30: Cartridge lower case

[0122] 31: Combination Home

[0123] 32: Reception Home

[0124] 33: Through hole

[0125]

[0126] 100: Diagnostic Kit Array Strip

[0127] 100-1: Array strip first layer

[0128] 100-2: Array strip second layer

[0129] 101: Diagnostic Kit Module Unit

[0130] 102a, 102b: Jig fixing part

Claims

1. A modular assembly diagnostic kit comprising a cartridge upper case; two or more diagnostic kit module units; and a cartridge lower case, A modular assembly diagnostic kit, wherein the above diagnostic kit module is inserted between the upper cartridge case and the lower cartridge case.

2. In the first paragraph, the upper cartridge case and the lower cartridge case have a receiving groove therebetween capable of receiving the diagnostic kit module unit, The upper case of the cartridge and the lower case of the cartridge each have a through hole formed by penetrating in the upper and lower directions. A modular assembly diagnostic kit, wherein the above diagnostic kit module unit is exposed to the outside through the above through hole.

3. A modular assembly diagnostic kit according to claim 1, wherein the number of receiving grooves and penetration holes is the same as the number of the two or more diagnostic kit module units.

4. A modular assembly diagnostic kit in the first paragraph, wherein the upper cartridge case and the lower cartridge case are each provided with a joining projection and a joining groove so that they can be joined to each other.

5. In the first paragraph, the diagnostic kit module unit is a modular assembly diagnostic kit that may include one or more layers selected from the group consisting of a layer having a mesh, a layer having glass fibers, a membrane containing a reagent or enzyme, etc.

6. A modular assembly diagnostic kit in the first paragraph, wherein the detection targets of the two or more diagnostic kit module units are the same or different.

7. A modular assembly diagnostic kit in claim 5, wherein the first layer and the second layer each have a joining projection and a joining groove so as to be joined to each other.

8. In paragraph 1, The upper case of the cartridge and the lower case of the cartridge have a receiving groove therebetween capable of receiving the diagnostic kit module unit, The upper case of the cartridge and the lower case of the cartridge each have a through hole formed by penetrating in the upper and lower directions. The above diagnostic kit module is a modular assembly diagnostic kit, wherein the diagnostic kit module unit is inserted between the upper case of the cartridge and the lower case of the cartridge, and is exposed to the outside through the through hole.

9. A method for manufacturing a modular assembly diagnostic kit of claim 1, comprising the following steps: (a) a step of manufacturing a diagnostic kit array strip in which two or more diagnostic kit module units are connected in series with a cutting line therebetween and a jig fixing portion is included at both ends; (b) a step of cutting and separating a diagnostic kit module unit from the diagnostic kit array strip; (c) a step of inserting the separated diagnostic kit module unit between the upper cartridge case and the lower cartridge case, which are provided with two or more receiving grooves capable of accommodating the diagnostic kit module unit; and (d) A step of combining the upper case and the lower case of the cartridge.

10. A method of using a modular assembly diagnostic kit of paragraph 1 comprising the following steps: (a) loading a sample into two or more diagnostic kit module units; (b) a step of allowing the sample to sufficiently react with each diagnostic kit module unit; and (c) A step of sensing a signal from each diagnostic kit module unit for which a reaction has been completed using a signal reader.

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