KR102007164B1 - Hybrid Rapid Diagnostic Kits Equipped with Multiple Micro-channels - Google Patents

Abstract

In embodiments of the present disclosure, multiple reliability can be improved by applying microfluidic technology to a membrane-type rapid diagnostic kit while simultaneously allowing liquid samples to be delivered to the test strip as much as possible without loss through the multiple microchannels provided in the kit. Provided are a hybrid rapid diagnostic kit having a microchannel and a diagnostic method using the same.

Description

Hybrid Rapid Diagnostic Kits Equipped with Multiple Micro-channels}

The present disclosure relates to a hybrid rapid diagnostic kit with multiple microchannels. More specifically, the present disclosure may improve detection reliability by applying microfluidic technology to a membrane-type rapid diagnostic kit while simultaneously allowing liquid samples to be delivered to the test strip as much as possible without loss through multiple microchannels provided in the diagnostic kit. The present invention relates to a hybrid rapid diagnostic kit having multiple microchannels and a diagnostic method using the same.

Diagnosis of disease markers (e.g. metabolites, proteins, cells, etc.) present in body fluids (e.g. blood, urine, etc.) of the human body is carried out using biological reactions such as enzyme reactions, antigen-antibody binding, etc. It is common to be. In this regard, conventionally known diagnostic (or detection) methods are performed with procedures involving cell culture, PCR, and enzymatic immunoassays, which point out that the problems are labor-intensive and take hours to days to obtain results. (Foudeh et al ., Microfluidic designs and techniques using lab-on-a-chip devices for pathogen detection for point-of-care diagnostics.Lab Chip, 2012, 12, 3249-3266). On the other hand, research on point of care (POC) related technologies that can be detected quickly and accurately using a small amount of samples has been actively conducted. Such POC testing is widely used in various hospitals and research institutes. Is being applied.

Commercialization is based on a wide variety of devices to perform POC testing, especially since microfluidic devices can achieve complex biochemical reactions using, for example, sample liquids having very small volumes. It is an area that is in the spotlight recently.

Currently, as technologies applied to biosensing and POC systems, (i) polymer-based microfluidic devices, (ii) membrane-based devices, and the like are used, which can perform analysis in a short time on a small scale. It is known to have low consumption of samples and reagents, and high reproducibility of analysis. At this time, the substance that can be analyzed or detected is glucose, cholesterol, protein, enzyme, bacteria, virus, nucleic acid sequence and the like.

In the diagnostic techniques described above, in the case of membrane-based devices, the capillary action of the microporous membrane is used, for example, samples contained in the mobile phase sample solution are separated from other compounds, which are immobilized on a fixed solid phase. By binding affinity with captured capture molecules. Membrane-based devices have been used in a number of research and industries because of the ease of fixing biomaterials and the simple detection of biomaterials at low cost. As a commonly used membrane type material, nitrocellulose is widely known. Nitrocellulose is basically required to have a hydrophilic porous structure, because it uses the absorption to the sample in a conventional POCT or rapid kit. In addition, nitrocellulose has advantages such as relatively low cost, capillary flow characteristics, high protein binding capacity, and relatively easy operation (direct cast method or supported membrane). In addition, attempts have been made to use other types of materials, including nylon and PVDF membranes.

Examples of the membrane-based biosensors described above include lateral flow assay (LFA) -based biosensors. This method is a test strip or an analysis strip of various regions to which a chemical component or molecule is attached that can interact with a sample of a fluid sample containing an analyte to be detected by an external force. Move through the assay strip. The sample reacts with a chemical component or molecule on the test strip to cause the strip to cause a change in properties. In this regard, the detection may use a visually identifiable indicator such as a home pregnancy tester, or a sensitive optical sensor (eg, US Pat. No. 7,297,529), a thermal contrast analysis reader (eg, domestic patent publication). No. 2014-127275) can be used to increase the accuracy of detection or reading.

 As such, the lateral flow analysis-based detection device has a relatively inexpensive, simple and portable advantage under the increasing need for rapid point-of-care diagnostic devices or systems. Increasingly, it has recently been used for the diagnosis of various infectious diseases such as AIDS-associated Cryptococcus meningitis, pneumococcal pneumonia, tuberculosis and the like.

However, the membrane type diagnostic kit has different wettability with respect to the liquid sample, and the speed at which the fluid is absorbed and moved is not constant. In addition, the membrane-type diagnostic kit is configured in the form of a plurality of pads on the main membrane, it takes a long time to move the fluid in the sample loading pad (sample loading pad) is collected by the first injection of the double liquid sample. This is because the sample fluid takes a relatively long time to sufficiently wet the sample loading pad.

In addition, in order to perform multiple diagnosis (detection) using one diagnostic kit, a branch channel through which fluid can move must be formed. However, in the membrane type diagnostic kit, it is difficult to manufacture such a branch channel, so that a plurality of single channels are arranged in a case. For example, in order to perform three types of diagnosis in one kit, three membrane strip sensors of the same type are arranged in one case, and the injection of the sample also causes the trouble of having to be performed three times.

To this end, the Applicant comprises a single kit consisting of a top plate and a bottom plate, and is equipped with a plurality of test strips capable of performing a plurality of diagnostics on the bottom plate, by connecting a sample loading unit and a plurality of microfluidic channels to a single sample input. We have developed a kit that can perform multiple diagnostics simultaneously.

However, in the above-described kit, the liquid sample moves directly through the channel, rather than via the sample loading pad used in the general side flow analysis-based diagnostic kit, and thus is not absorbed entirely by the test strip and flows around the test strip. The problem that causes the outgoing phenomenon is caused. For example, the loss of fluid to the joints of the upper and lower plates is caused. As a result, a sufficient amount of sample may not be provided in the strip, which acts as a factor to lower the reliability of the diagnosis. Therefore, there is a need for a method capable of quickly performing multiple analyzes with high reliability using a single diagnostic kit.

One embodiment of the present disclosure is to provide a hybrid rapid diagnostic kit that enables more efficient diagnosis by reducing the immune response diagnostic time and the amount of sample required.

In addition, according to one embodiment of the present disclosure, even when multiple diagnosis is performed in a single diagnostic kit, the reliability of diagnosis can be improved by efficiently delivering the injected liquid sample to each of the plurality of test strips efficiently. To provide a diagnostic kit.

In addition, one embodiment of the present disclosure is to provide a hybrid rapid diagnostic kit that can be manufactured in a convenient manner.

According to one aspect of the present disclosure,

An upper substrate including a first opening formed at one end side region to pass the injected liquid sample, and at least one second opening formed to observe or measure a signal generated from a detection reaction;

A pocket structure integrally formed to include a sample loading chamber for receiving the passed sample and a plurality of microfluidic channel portions for sample flow branch communicating with the sample loading chamber; And

A lower substrate having a support structure for guiding a plurality of test strips disposed to correspond to each of the plurality of microchannel channels in the pocket structure;

A hybrid rapid diagnostic kit is provided.

According to an exemplary embodiment, the method further comprises a test strip supported on the lower substrate, the test strip comprising: a conjugation pad sequentially arranged while contacting or overlapping in a flow direction of a sample; Detection zone of membrane material; And absorbent pads.

According to an exemplary embodiment, the pocket-like structure comprises a third opening formed in the upper surface in communication with the first opening of the upper substrate;

A sample loading chamber for receiving a sample passing through the third opening; And

A plurality of microchannel channels having a partition structure that defines a boundary between the microchannels of the sample which is in communication with the sample loading chamber;

It may include.

According to an exemplary embodiment, the pocket structure may further include an insertion structure of a test strip to guide the samples discharged from each of the microchannel channels to a corresponding test strip, and to facilitate contact with the test strip. .

According to an exemplary embodiment, the sample loading chamber of the pocket-type structure may have an inclined surface for changing the flow direction of the sample introduced through the third opening in the direction of the partition structure.

According to an exemplary embodiment, the surface of the microchannel channel portion may be treated with an organic material and / or an inorganic material to impart hydrophilicity.

According to an exemplary embodiment, the test strip of the hybrid rapid diagnostic kit may not include a sample loading pad in front of the conjugation pad.

According to an exemplary embodiment, the pocket-shaped structure is injection molded, there may be no bonding surface between the sample loading chamber and the microchannel channel portion.

According to an exemplary embodiment, the upper substrate, the pocket structure and the lower substrate are respectively polyester, polyethylene (PE), polypropylene (PP), polyimide (PI), polystyrene (PS), polycarbonate (PC), poly Urethane, polyvinylidene fluoride, nylon, polymethylmethacrylate (PMMA), polyvinylchloride (PVC), cyclic olefin copolymer (COC), polyamide (PA), poly (phenylene ether) (PPE) , Polyoxymethylene (POM), polyether ether ketone (PEEK), polyether sulfone (PES), polytetrafluoroethylene (PTFE) or acrylic resins.

According to an exemplary embodiment, the lower substrate may further include a plurality of guide protrusion members to suppress the left and right movement of the individual test strip.

According to an exemplary embodiment, the lower substrate may further include a plurality of support protrusion members to adjust the height of the individual test strips.

According to an exemplary embodiment, the lower surface of the upper substrate and the upper surface of the lower substrate may further include a coupling element for fastening between the upper substrate and the lower substrate.

According to an exemplary embodiment, each of the plurality of test strips may be configured to diagnose the same or different target samples from each other.

According to another aspect of the present disclosure,

a) providing a sample for analysis of a liquid phase containing at least one target sample;

b) loading said sample into said sample loading chamber of said pocketed structure through said first and third openings of said hybrid rapid diagnostic kit; And

c) qualitatively and / or quantitatively analyzing the target sample contained in the analytical sample by observing or measuring a signal generated from each test strip in the hybrid rapid diagnostic kit;

Provided are a method for quickly diagnosing an analytical sample.

According to an exemplary embodiment, the sample may be loaded once.

According to an exemplary embodiment, the liquid analysis sample may be a whole blood state of blood, or a plasma component.

Hybrid rapid diagnostic kit with multiple microchannels according to an embodiment of the present disclosure, while the liquid sample is a plurality of test strips while omitting the sample loading pad typically provided in the conventional lateral flow analysis-based diagnostic kit for rapid diagnosis It is possible to carry out multiple diagnosis (detection) within a short diagnosis time compared to the conventional membrane type diagnostic kit by configuring to contact with each other, and also by introducing a pocket structure in which the microchannel channel portion for sample flow branch is integrally formed. In a diagnostic kit having a micro channel, the liquid sample flows to the surroundings. In addition, even when a plurality of microfluidic channels are formed, a plurality of diagnosis can be performed by one injection of a liquid sample, thereby reducing the amount of sample required for diagnosis as compared with a conventional membrane type diagnostic kit. In addition, since all components of the diagnostic kit can be manufactured by injection molding, the kit is easy to manufacture and is suitable for mass production. Therefore, broad commercialization is expected in the future.

1 is a perspective view of a hybrid rapid diagnostic kit having multiple microchannels assembled according to one embodiment;
2 is a plan view of an assembled state in a hybrid rapid diagnostic kit with multiple microchannels according to one embodiment;
3 is an exploded perspective view of a hybrid rapid diagnostic kit with multiple microchannels in accordance with one embodiment;
4 is a cross-sectional perspective view of the AA line in FIG. 1;
FIG. 5 shows the back side of an upper substrate in a hybrid rapid diagnostic kit with multiple microchannels in accordance with one embodiment; FIG.
6 is a plan view of a lower substrate in a hybrid rapid diagnostic kit with multiple microchannels in accordance with one embodiment;
FIG. 7 is a plan view illustrating a pocket-type structure inserted into a lower substrate in a hybrid quick diagnosis kit having multiple microchannels according to one embodiment; FIG.
8 is a front view of a pocketed structure in a hybrid rapid diagnostic kit with multiple microchannels in accordance with an exemplary embodiment; And
9 is a plan cross-sectional view of a pocketed structure in a hybrid rapid diagnostic kit with multiple microchannels in accordance with an exemplary embodiment.

The present invention can all be achieved by the following description. The following description is to be understood as describing preferred embodiments of the invention, but the invention is not necessarily limited thereto. In addition, the accompanying drawings are for ease of understanding, and the present invention is not limited thereto. Details of individual components may be appropriately understood by specific gist of the related description to be described later.

The terminology used herein may be understood as follows.

“Hybrid diagnostic kit” may mean a diagnostic kit configured in a combination of a membrane method and a microfluidic method as described below.

"Channel" may mean a cavity, opening or conduit that may contain a fluid.

“Microfluidic channel” may mean a channel having at least one cross-sectional dimension (eg, width, depth, height, diameter, etc.) of 10 mm or less.

The expression “specifically binds” refers to the specificity of a binding reagent, eg, an antibody, and may mean preferentially binding to a defined sample or target substance. Recognition by a specific reagent or binding agent or antibody of a particular sample in the presence of another potential target may be a feature of such binding. In some embodiments, binding reagents that specifically bind to a sample may avoid binding with other interfering moieties or moieties in the sample to be tested.

"Sample" is not particularly limited as long as it can contain a sample to be detected. By way of example, the sample may be a biological sample, for example a biological fluid or biological tissue. Examples of biological fluids include urine, blood, plasma, serum, saliva, semen, feces, sputum, cerebrospinal fluid, tears, mucus, amniotic fluid, and the like. Biological tissue is a collection of cells, usually a collection of certain kinds of intracellular substances that form one of the structural substances of human, animal, plant, bacterial, fungal or viral structures, as connective tissue, epithelial tissue, muscle tissue and nerves. This may be an organization. Examples of biological tissue may also include organs, tumors, lymph nodes, arteries and individual cell (s). Specifically, the sample may be provided in a liquid form while containing the aforementioned tissue. More specifically, a sample particularly suitable for the present disclosure may be plasma isolated from blood (or whole blood).

A "analyte" can be understood to mean a molecule or other substance in a sample to be detected. For example, the sample may include antigenic substances, ligands (mono- or polyepitopes), haptens, antibodies, and combinations thereof. Specifically, the sample may be, for example, toxins, organic compounds, proteins, peptides, microorganisms, amino acids, nucleic acids, hormones, steroids, vitamins, drugs, drug intermediates or by-products, bacteria, virus particles, yeasts, fungi, protozoa and said Metabolites of substances or antibodies thereto, but are not necessarily limited thereto. However, it may be conventionally an antigen or an antibody. In this regard, exemplary specimens include ferritin; Creatinine kinase MB (CK-MB); Digoxin; Phenytoin; Phenobarbitol; Carbamazepine; Vancomycin; Gentamycin; Theophylline; Valproic acid; Quinidine; Progesterone (LH); Vesicle stimulating hormone (FSH); Estradiol, progesterone; C-reactive protein (CRP); Lipocalin; IgE antibodies; Cytokines; Vitamin B2 micro-globulin; Glycated hemoglobin (Gly.Hb); Cortisol; Digitoxins; N-acetylprocaineamide (NAPA); Procaineamide; Antibodies against rubella, such as rubella-IgG and rubella IgM, for example, antibodies against toxoplasmosis, such as toxo (toxo-IgG) and toxoplasmosis IgM; Testosterone; Salicylates; Acetaminophen; Hepatitis B virus surface antigen (HBsAg); Antibodies to hepatitis B core antigens such as anti-hepatitis B core antigen IgG and IgM (anti-HBC); Human immunodeficiency virus 1 and 2 (HIV 1 and 2); Human T-cell leukemia virus 1 and 2 (HTLV); Hepatitis B e antigen (HBeAg); Antibodies to hepatitis B e antigen (anti-HBe); Influenza virus; Thyroid stimulating hormone (TSH); Thyroxine (T4); Total triiodothyronine (total T3); Free triiodotyronine (free T3); Carcinoma embryonic antigen (CEA); Lipid proteins, cholesterol, and triglycerides; And alpha fetoprotein (AFP). Drugs of misuse and control substances, specifically amphetamine; Metaamphetamine; Barbaturates such as amobarbital, secobarbital, pentobarbital, phenobarbital and barbital; Benzodiazepines such as librium and valerium; Cannabinoids such as hashish and marijuana; cocaine; Fentanyl; LSD; Metaqualon; Opiates such as heroin, morphine, codeine, hydromorphone, hydrocodone, methadone, oxycodone, oxymolphone and opium; Penciclidine; And propoxyhen, but are not limited thereto.

The expressions "on" and "on" may be understood to be used to refer to relative positional concepts. Thus, in addition to the presence of other components or layers directly in the mentioned layer, there may be at least one other layer (intermediate layer or intervening layer) in between, or additional components may be present or present. Similarly, the expressions "below", "below" and "below" and "between" may also be understood as relative concepts of position. In addition, the expression "sequentially" may also be understood as a relative positional concept.

If any component or member is described as being “connected” or “in communication with” another component or member, unless otherwise stated, as well as in direct connection or communication with said other component or member, as well as It is to be understood that this also includes cases where the components are connected or communicated with other components or members.

1 and 2 are a perspective view and a plan view, respectively, of a hybrid rapid diagnostic kit having multiple microchannels assembled according to one embodiment of the present disclosure. 3 is an exploded perspective view of a hybrid rapid diagnostic kit having multiple microchannels according to one embodiment, and FIG. 4 is a cross-sectional perspective view of a line A-A in FIG. 1.

In the illustrated embodiment, the hybrid diagnostic kit 100 largely comprises an upper substrate 110, a pocketed structure 120, and a lower substrate 130, and additionally or optionally a test strip 140 for diagnosis, Specifically, the test strip may further include a membrane material. However, in order to more easily understand the structure inside the diagnostic kit, the test strip 140 is not shown in FIG. 2.

For the example shown, the diagnostic kit 100 has a curved or streamlined appearance, but this should be understood as illustrative and may be implemented in any shape, for example rectangular, elliptical, or other unstructured shape. .

The pocket structure 120 is positioned between the upper substrate 110 and the lower substrate 130, and is mounted (or fixed) inside the case or housing formed as the upper and lower substrates 110 and 130 are coupled to each other. In this case, the coupling between the upper substrate 110 and the lower substrate 130 may be performed by a fastening method between any of a plurality of members known in the art. For example, a protrusion member (or a groove member) is formed on the lower substrate 130, and a groove member (or protrusion member) is formed on the upper substrate 110 to be fastened in an interference fit manner. According to an alternative embodiment, a bolt (or a screw) on the upper substrate 110, and a screw (or bolt) on the lower substrate 130 may be formed to use a fastening method by rotation. According to another embodiment, a hole may be formed at a coupling position corresponding to both the upper substrate 110 and the lower substrate 130 and fastened by coupling the bolt and the nut.

In addition, according to another alternative embodiment, the upper substrate 110 and the lower substrate 130 can be mutually attached using an adhesive, examples of such adhesives are rubber adhesives, acrylic resin adhesives, silicone adhesives, optical systems Adhesives, heat adhesives, and the like can be used, but are not limited to those listed above. However, in order to easily replace the test strip 140 with a new strip as a consumable, bonding (fastening) by an adhesive may not be advantageous.

According to one embodiment, each of the upper substrate 110, the pocket structure 120 and the lower substrate 130 may be formed through a conventional molding process, in particular injection molding process, in particular the micro flow path pocket structure 120 Since it can be formed together in the manufacturing process of the separate process can be omitted to form a fine flow path. In the case of an injection molding process, details of this are known in the art, such as by injecting the polymer melt into the mold and / or the mold, cooling and then separating from the mold. Therefore, the manufacturing process of the entire diagnostic kit 100 can be simplified.

In an exemplary embodiment, each of the upper substrate 110, the pocket structure 120, and the lower substrate 130 is polyester, polyethylene (PE), polypropylene (PP), polyimide (PI), polystyrene (PS). , Polycarbonate (PC), polyurethane, polyvinylidene fluoride, nylon, polymethyl methacrylate (PMMA), polyvinylchloride (PVC), cyclic olefin copolymer (COC), polyamide (PA), poly (Phenylene ether) (PPE), polyoxymethylene (POM), polyether ether ketone (PEEK), polyether sulfone (PES), polytetrafluoroethylene (PTFE) or acrylic resin, The above listed kinds are provided for illustrative purposes, and are not necessarily limited thereto. More specifically, the upper substrate 110, the pocket structure 120, and / or the lower substrate 130 may be made of polycarbonate (PC) material. In another embodiment, each of the upper substrate 110, the pocket structure 120 and the lower substrate 130 may be made of a different polymer material. Alternatively, two of the upper substrate 110, the pocket structure 120, and the lower substrate 130 may be made of the same material, and the rest may be made of different materials. According to certain embodiments, the upper substrate 110, the pocket structure 120, and the lower substrate 130 may be formed of the same polymer material, but may have different individual properties.

According to one embodiment, the hybrid diagnostic kit 100 has a first opening 111 formed in the upper substrate 110 to directly inject or introduce a sample into the pocket structure 120. In the illustrated embodiment, the first opening 111 is formed in a semi-elliptic shape, but this is exemplary and may be formed in any shape (for example, circular, rectangular, square, etc.).

In addition, the upper substrate 110 absorbs a fluid (specifically, a liquid sample) flowing through the plurality of microchannel channels 123a, 123b, and 123c, respectively, to qualitatively and / or quantitatively diagnose (detect) a specific sample. At least one second opening is formed in the length direction to observe or measure a signal generated from the plurality of test strips 140. For purposes of this disclosure, the second opening may be understood to include not only the case where the cavity is physically formed, but also the case where the cavity is additionally provided with a transparent cover for observation or measurement.

In the illustrated example, three types of second openings 112a, 112b and 112c are formed, for example, corresponding to respective regions constituting the test strip (conjugation pad, porous membrane and absorbent pad). However, the present invention is not limited thereto. In addition, the shape, shape, and size of the second openings 112a, 112b, and 112c are illustrated as slit in the accompanying drawings, but are not necessarily limited thereto, and may be changed in various ways.

One of the differences between the illustrated embodiment and the existing side flow analysis based diagnostic kit is that each of the second openings 112a, 112b, 112c is formed of a plurality of lines. This results in branching of the sample flow in a single sample injection to form multiple lines, observing signals generated from chemical and / or biological reactions in test strips disposed corresponding to each line (e.g., visual observation). Or for measurement. For example, a plurality of test strips or microfluidic channels may be formed in a number corresponding to the channel portion. To this end, each of the second openings 112a, 112b, 112c has a partition member, for example a straight section, to facilitate observation or measurement of the diagnostic results according to the plurality of test strips in each line in the diagnostic kit 100. Member, specifically, the string type partition members 113a and 113b may be formed. The width or diameter of the partition member is not particularly limited and may be determined according to the spacing between the plurality of microchannels (or test strips). The spacing may then be selected, for example, within the range of about 0.5 to 5 mm, specifically about 2 to 3 mm.

The first and second openings and the partition member described above may be integrally formed at the time of molding (specifically, injection molding) of the upper substrate 110. Although the number of observation or measurement lines is shown as three in the figure, this is exemplary and may be two or more than four.

Meanwhile, FIG. 5 illustrates a back side of an upper substrate in a hybrid rapid diagnostic kit having a plurality of microchannel channels (or multiple microchannels) according to one embodiment.

Referring to the drawings, in the upper substrate 110, a fastening element that forms a fastening or coupling structure with the lower substrate 130 along or near the periphery except for the first opening 11 is provided. These fastening elements can be formed corresponding to the positions of the fastening elements formed on the lower substrate 130 described later. In the illustrated example, the first groove member 114 is coupled to the first fastening protrusion member 133 formed on the lower substrate 130 in an interference fit manner. In addition, the second groove member 115 formed at an opposite side of the first opening 111 in the upper substrate 110 may be coupled to the second fastening protrusion member 134 formed in the lower substrate 130 by an interference fit method. Can be. Although the groove member is formed in the upper substrate 110 and the protrusion member is formed in the lower substrate 130 in the illustrated example, the reverse is also possible. In addition, one of the first groove member 114 and the second groove member 115 of the upper substrate 110 may be replaced with a protrusion member, in this case, the first fastening protrusion member 133 of the lower substrate 130. And one of the second fastening protrusion members 134 may be replaced with a groove member. In addition, the shape of each of the first groove member 114 and the second groove member 115 may accommodate each of the first fastening protrusion member 133 and the second fastening protrusion member 134 formed on the lower substrate 130. As to be combined in the fitting manner, it can be determined corresponding to the shape of the protruding member.

On the other hand, the pocket-shaped structure 120, the large opening through the third opening 121, the third opening 121 formed on the upper surface thereof so that the sample can be introduced through the first opening 111 of the upper substrate 110. The sample loading chamber 122 may provide a receiving space for a sample, and the microchannel channels 123a, 123b, and 123c may form a branched flow of the received sample. To this end, the microchannel channels 123a, 123b, and 123c have a plurality of partition structures defining boundaries of the microchannels of the sample which are branched while communicating with the sample loading chamber 122.

Such pocketed structure 120 can typically be integrally formed by molding, in particular by injection molding to form a suitable appearance and internal structure. In this case, there is no bonding surface between the sample loading chamber 122 and the microfluidic channel portion (specifically, the partition structure). Accordingly, the upper substrate 110 and the lower substrate 130 are prefabricated, but the diagnostic reaction in the plurality of test strips 140 without losing the liquid sample introduced from the single inlet through the pocket structure 120. Can be multi-distributed for That is, the liquid sample injected through the third opening 121 may be effectively delivered to each of the plurality of test strips 140 without loss of the sample introduced into the diagnostic kit 100.

Referring to FIGS. 3 and 4, in the case of the pocket structure 120, the test strips may be used to guide each of the plurality of test strips 140 to easily contact the corresponding microchannel channels 123a, 123b, and 123c. An insertion structure of 140 is additionally formed. Specifically, the barrier rib structures 124a and 124b are formed on the boundary between the microchannel channels 123a, 123b, and 123c (projection), and optionally, the transverse extension part corresponding to the extension (projection) dimension of the partition wall ( 125a, 125b, and 125c may be formed together to provide space for inserting each of the plurality of test strips 140. In the illustrated example, the upper surface of the partition wall and the upper surface of the microchannel channel portion are spaced apart from each other, but this is exemplary and may be in contact with or integrated with each other.

6 and 7 illustrate a form in which the lower substrate and the pocket-type structure are inserted into the lower substrate, respectively.

3 and 4, and FIGS. 6 and 7, the lower substrate 130 has a mounting region 135 formed at one side thereof to accommodate (store) the pocket structure 120. The mounting region 135 may be provided at a position corresponding to the first opening 111 of the upper substrate 110.

Further, the lower substrate 130 is disposed in contact with the opposite end (distal end) of the end (proximal end) of each of the plurality of test strips contacted (inserted) in the pocketed structure 120. It may be provided. In this case, the guide support structure 136 may have an integrated structure of a rake shape in which a plurality of rake-shaped members are formed to extend at a predetermined distance from the frame structure, and when forming the lower substrate 130. Or may be formed separately. At this time, it may be advantageous to define the spacing between the plurality of rake shaped members to have dimensions to allow insertion of the individual test strips 140. As such, the test strip 140 may be mounted in the diagnostic kit 100 in a manner supported by the guide structure 136 and supported on the lower substrate 130.

According to an exemplary embodiment, the lower substrate 130 may further include a plurality of guide protrusion members 131 to suppress the left and right movement of the individual test strips, and to place in the correct position. For example, the guide protrusion members 131 may be arranged in a line at a predetermined interval in the longitudinal direction of the diagnostic kit 100, and the number in the width direction may vary depending on the number of test strips 140 or lines. Can be decided. In the illustrated example, the pair of guide protrusion members 131 are disposed at two positions spaced apart in the longitudinal direction in the width direction (that is, the pair of guide protrusion members). In this case, the arrangement of the guide protrusion member 131 may be applied to guide the three test strips 140. In the illustrated embodiment, the guide protrusion members 131 are arranged in a line in the width direction, but in some cases, an alternate arrangement is also possible.

In addition, when each of the plurality of test strips 140 is mounted on the lower substrate 130, the plurality of support protrusion members 132 may be regularly or irregularly distributed to support the bottom surface of the lower substrate at a predetermined interval. Can be. The number of the support protrusion members 132 is not particularly limited as long as the test strip 140 may be mounted as horizontally as possible in the diagnostic kit. In addition, the support protrusion member 132 may have a height within the diagnostic kit 100 so that the liquid sample can be readily absorbed into the test strip 140 in the flow direction thereof, according to an exemplary embodiment. The height of the protruding member 132 may be maintained at the same height as or slightly lower than the lateral extensions 125a, 125b, and 125c of the microchannel channel portions 123a, 123b, and 123c or the insertion structure of the test strip 140 described above. In some cases, it may have a height of the pattern is gradually reduced in the flow direction of the sample.

According to an exemplary embodiment, the height of the support protrusion member 132 is, for example, at least about 50%, specifically about 55 to 80%, more specifically about 60 to 70% relative to the height of the guide protrusion member 131. It can be a range.

Although the aforementioned guide protrusion member 131 and the support protrusion member 132 may be manufactured separately and attached to the lower substrate 130, the guide protrusion member 131 and the support protrusion member 132 may be advantageously formed together when forming the lower substrate in terms of ease of manufacture and integrity of the coupling surface. have.

 As described above, a fastening element for fastening with the upper substrate 110 is formed on the lower substrate 130. In the illustrated example, the fastening element corresponding to the first groove member 114 formed on the upper substrate 110 is formed. The first fastening protrusion member 133 is formed, and the second fastening protrusion member 134 corresponding to the second groove member 115 is formed. Shapes of the first and second fastening protrusion members may be the same or different from each other, for example, may have various shapes such as a rectangular parallelepiped, a cylindrical shape, and a wedge shape. The shape of the first and second fastening grooves is also determined. However, as described above, the protrusion member does not necessarily need to be formed on the lower substrate 130 and the groove member may be formed. In this case, the fastening protrusion member may be formed on the upper substrate. Furthermore, when it is desired to fasten in a manner other than an interference fit, the fastening protrusion member and the groove member may be deformed or replaced by a member of another shape.

Meanwhile, in one embodiment of the present disclosure, one of the most distinguished points compared to the prior art is to introduce a pocket structure in which the sample loading chamber and the micro flow channel portion for sample flow branch are integrally formed to minimize the loss of the injected sample. While it can be delivered uniformly to the plurality of test strips 140. In particular, since the sample injected once can be efficiently used for diagnosis, the amount of sample required for diagnosis can be minimized.

For example, in the conventional membrane-type diagnostic kit, a technique using multiple detection schemes has been developed, but since it is difficult to form branch channels using membrane materials, a single microchannel channel is separately manufactured and a plurality of microchannel channels are placed in a single case. Most of the production is made in the form of. For example, in order to perform three types of diagnosis in a single kit, substantially three membrane strip sensors are provided in a single case, and three sample injection portions for injecting a sample into each of them need to be configured. . In order to solve this problem, a method of forming a single sample injection unit and branching it into three microchannels may be considered, but in this case, the injected sample leaks to the surroundings in the process of being distributed to the branched microchannel. Can be.

On the other hand, the diagnostic kit provided according to one embodiment is integrally formed by molding a guide structure for delivering a sample loading chamber, a microfluidic channel portion, and optionally a sample passing through each of the microfluidic channel portions to a test strip. Implemented pocket structure 120 can effectively prevent the problems caused by the prior art described above and alternative configurations thereof.

According to an exemplary embodiment, for the diagnostic kit 100 with three test strips as shown, the required amount of sample may be, for example, at a level of about 50 to 200 μl, specifically about 100 to 150 μl. As it is, there is an obvious improvement compared to simply forming multiple microfluidic channels in a diagnostic kit, injecting a sample, and branching it to a plurality of test strips. Moreover, since the pocket-type structure can be manufactured by injection molding and can be simply inserted and mounted between the upper substrate 110 and the lower substrate 130 by the cartridge method, the time required for manufacturing the diagnostic kit can be significantly reduced. Hereinafter, a pocket structure will be described in more detail.

 8 and 9 are front and planar cross-sectional views, respectively, of a pocket-type structure in a hybrid rapid diagnostic kit having multiple microchannels according to an exemplary embodiment.

The shape of the third opening 121 and the sample loading chamber 122 formed on the upper surface of the pocket-shaped structure 120, branching the sample to the plurality of micro-channel channels (123a, 123b, 123c) test strip ( As long as it can be delivered to 140, it is possible to implement in various forms without particular limitation. In detail, one end of each of the micro channel channels 123a, 123b, and 123c is configured to be connected or communicated with the sample loading chamber 122. The liquid sample collected in the sample loading chamber 122 is transferred through the microchannel channels 123a, 123b, and 123c by capillary force, and is inserted into the test strip 140 (bulk structure and transverse side). And continuously contacted with the test strip 140 in the direction of the < RTI ID = 0.0 > Therefore, the liquid sample introduced through one sample injection may perform multiple diagnosis or detection by the number of the plurality of test strips 140 contacted through the pocket structure 120 (up to three types in the illustrated embodiment). Diagnosis or detection is possible). As such, the ability to perform multiple diagnostics or detection in a single kit is a differentiating factor from the prior art.

Referring to FIG. 4, in an exemplary embodiment, one side of the sample loading chamber 122 containing the sample introduced through the third opening 121 (that is, the side opposite to the formation surface of the microchannel channel portion) The inclined surface 126 may be formed to easily change the flow direction of the sample to be introduced or accommodated in the direction of the channel channel. The inclination of the inclined surface 126 may be in the range of about 1 to 60 degrees, specifically about 5 to 40 degrees, more specifically about 10 to 30 degrees on a vertical basis, and the inclined surface 126 may be curved. It may be shaped.

According to an exemplary embodiment, the width and depth of each channel of each of the microchannel channels 123a, 123b, and 123c may be formed at the nanometer level, the micrometer level, and / or the millimeter level. have. For example, the depth and / or width of the microfluidic channel may be appropriately selected within the range of about 20 μm to 1 mm, specifically about 20 to 300 μm, more specifically about 50 to 100 μm, which is specific for specific applications. The present invention is not limited to the above range because it may be changed accordingly. In another embodiment, the width and / or depth of the microfluidic channel may be appropriately selected within the range of tens of nanometers to several hundred nanometers. In addition, the plurality of microfluidic channel portions may be configured to have the same shape and dimensions, but in some cases, may be configured to have different shapes and dimensions (for example, depending on the detection response in each of the plurality of test strips). If the flow rate of the liquid sample in the microfluidic channel is required to be different).

In addition, in the illustrated embodiment, the micro-channel channels 123a, 123b, and 123c have a straight pattern, but the present disclosure is not necessarily limited thereto, and various flow paths, for example, curved patterns (spiral, standing) Penpentine type, zigzag type, etc.) are also possible.

As described above, each of the upper substrate 110, the pocket structure 120, and the lower substrate 130, which is a constituent member of the diagnostic kit 100, may be made of a polymer material. The material typically exhibits hydrophobic (or nonpolar) or weak hydrophilicity. According to an exemplary embodiment, it may be desirable to properly adjust the flow rate of the fluid (sample) in the micro-channel channel portion in consideration of the detection efficiency, etc. In the side flow method using a capillary phenomenon, for example, about 0.1 to 10 ml / min, specifically about 0.1 to 5 ml / min.

Generally, a hydrophilic surface is a surface that attracts moisture, and an aqueous solution sample (eg, blood) is spread on this hydrophilic surface. Water drops on hydrophilic surfaces have the property of having low water contact angles at the interface, while hydrophobic surfaces exhibit high water contact angles. For this reason, in the case of hydrophobic or low hydrophilic surfaces, the flow characteristics of the liquid sample may not be good, which may reduce the flow rate of the sample and reduce the diagnostic or detection efficiency. Accordingly, in order to effectively transfer or transfer the liquid sample to the test strip 140 along the microchannel using capillary force, for example, about 60 kPa or less, specifically about 40 kPa or less, and more specifically about 20 kPa or less. It may be advantageous to indicate a number contact angle of.

According to an exemplary embodiment, in order to impart hydrophilicity to the surfaces of the microchannel channels 123a, 123b, and 123c in the pocket structure 120, surface treatment (or hydrophilicity treatment) may be performed using organic and / or inorganic materials. have. However, as long as the sample passes through the microchannel channel and undergoes chemical and / or biological reactions in the test strip, it is preferable to use a surface treatment material that is substantially non-reactive (ie, inactive) with respect to the sample containing the biomaterial. May be advantageous. Such surface treatment materials may be organic and / or inorganic.

In an exemplary embodiment, the organic surface treatment is, for example, a compound having an amine, hydroxy, carbonyl or epoxy functional group, a monomer having the functional group, a dimer and Polymers and the like, and these may be used alone or in combination of two or more. In addition, the inorganic surface treatment product may be, for example, a metal or a nonmetal, specifically, at least one metal selected from gold, silver, silicon, aluminum, nickel, iron, copper, manganese, silicon, titanium, chromium, or the like, or a metal thereof. It may be an oxide. In some cases, the organic surface treatment and the inorganic surface treatment may be combined, and the organic and inorganic surface treatment agents may be mixed, or any one of the organic surface treatment and the inorganic surface treatment may be performed first, followed by the remaining surface treatment.

In one embodiment, the hydrophilic surface treatment may be performed by coating silica (SiO ₂ ) on the surfaces of the microchannel channels 123a, 123b, and 123c.

The organic and / or inorganic materials described above may be thermally deposited, E-beam deposited, sputtered, chemical vapor deposition (CVD), sol-gel method, plasma treatment, liquid phase chemical treatment, vapor chemical treatment, or the like. And may be formed by a coating or attachment method known in the art. According to an exemplary embodiment, the thickness of the organic and / or inorganic coating layer formed on the surface of the microfluidic channel may be selected, for example, within the range of about 1 to 500 nm, specifically about 1 to 200 nm. It may be understood in an illustrative sense.

According to an exemplary embodiment, the plurality of microchannel channels 123a, 123b, and 123c formed in the pocket structure 120 may be formed in the same plane, but may also form an inclined surface between adjacent microchannel channels. In exemplary embodiments, the inclined surface may be formed to have an inclined surface that increases in both directions with respect to the horizontal flow path in the central region. As such, the reason for forming the inclination angles between the microchannel channels is that the liquid sample injected through the opening (specifically, the third opening) forms round droplets so that the surfaces of the droplets contact the microchannel channels at the same time. This is to adjust the amount of the sample flowing between the channel part of the micro channel equally.

Referring to FIG. 8, in the illustrated example, the microchannel channel portion 123b forms a horizontal plane, while each of the microchannel channel portion 123a and the microchannel channel portion 123c adjacent to each other is inclined with respect to the horizontal plane. Form. In this case, the inclination angle formed between the adjacent microchannel channels may be selected in a range of, for example, about 1 to 40 °, specifically about 5 to 35 °, and more specifically about 10 to 30 ° based on the horizontal plane.

On the other hand, according to another embodiment of the present disclosure, the above-described hybrid rapid diagnostic kit 100 is a test strip for allowing a liquid sample to observe or measure a signal generated from a variety of chemical and / or biological reactions ( 140 based on side flow analysis technology.

Referring to FIG. 3, the individual test strips 140 may include a conjugation pad or a bonding pad 141, a detection region 142 in the form of a porous membrane, and an absorbent pad 143 based on the moving direction of the sample from the pocket structure 120. May be sequentially included, and the three components constituting the test strip 140 are in fluid communication with each other in contact or overlapping manner. According to an exemplary embodiment, the detection area 142 may include a test area and a control area similar to a pregnancy diagnosis kit.

In addition, in the illustrated embodiment, the components 141, 142, and 143 of the test strip 140 may be disposed in contact or overlapping form with each other, whereby the liquid sample may be removed from the strip member during the analysis. This is to move along. Typically, the width of the overlap region may range from, for example, about 1 to 3 mm, specifically about 1.5 to 2 mm, but the present invention is not limited thereto.

For one embodiment of the present disclosure, one of the differences from conventional diagnostic kits is that the sample loading pad or sample pad, which is a component of a conventional side flow line or test strip in the kit, can be omitted.

In a conventional membrane-type side flow diagnostic kit, the sample is composed of a sample loading pad (sample pad), a conjugation pad or a bonding pad, a detection area of a membrane material, and four areas (membrane and / or pad) of an absorption pad. Of the four test strip components, the sample loading pad is responsible for uniformly distributing the sample when the liquid sample is injected and transferring the sample to the adjacent conjugation pad or the bonding pad. However, it takes a relatively long time for the sample to sufficiently wet the sample loading pad. In contrast, in the diagnostic kit 100 according to the present embodiment, instead of omitting a sample loading pad among components of a conventional membrane strip, the pocket structure 120 is inserted between the upper substrate 110 and the lower substrate 130. ) Into the sample loading chamber 122 and the microchannel channels 123a, 123b, and 123c. As a result, the introduced liquid sample may be delivered directly to the conjugation pad 141 of the test strip 140 along the microfluidic channel portion as soon as it is received or collected in the sample loading chamber 122. Therefore, it is possible to drastically reduce the time required to wet the sample loading pad, that is, the diagnostic time in the kit of the conventional side flow analysis method. In this regard, the inventors fabricated and tested a prototype of the hybrid rapid diagnostic kit 100 according to the present embodiment, and as a result, the conjugation pads of the test strip 140 from the sample loading chamber 122 through the microchannel channel portion ( It was confirmed that the time to reach the sample until 141), in the membrane-type diagnostic kit according to the prior art it was confirmed that about 50% reduction compared to the time to reach the sample from the sample loading pad to the conjugation pad.

In an exemplary embodiment, the minimum amount of target sample in the sample (ie, the limit of detection; the minimum amount of target sample that must be present in the sample or sample solution upon detection) is, for example, at least about 0.01 ng / ml, specifically at least It may range from about 0.1 ng / ml, more specifically at least about 1 ng / ml, but this is exemplary and may vary depending on the type, characteristics, etc. of the target sample.

Conjugation pad or junction pad 141 may refer to a conjugate, i.e., a specific substance and a detectable label substance (or signal generating substance) conjugated thereto, specifically, a labeling substance and a binder (specifically, The first binder) may be bonded. In this case, the first binder may have a property of specifically binding to the target sample, and such specific binding may involve complementary binding. That is, the first binder may bind only to a specific target sample (ie, specifically bind), and may not bind to other molecules present in the sample. In exemplary embodiments, the first binder may be an antibody (or an antibody fragment), and the antibody may specifically (or selectively) bind to an antigen that is a target sample.

Labeling materials (or signal generating materials) include metal nanoparticles (eg gold, silver, copper nanoparticles, etc.), quantum dot nanoparticles, magnetic nanoparticles, enzymes, enzyme substrates, enzyme reaction products, absorbers, fluorescent materials Or a light emitting material. More specifically, the labeling substance is a fluorescent substance, umbelliferone, fluorescein, fluorescein isothiocyanate (FITC), rhodamine, tamra (TAMRA) , Fluorescein, including dichlorotriazinylamine fluorescein, dansyl chloride, quantum dots, phycoerythrin, fluorecein amidite, FAM, etc. Lexa fluor (alexa fluor) and Cy3, Cy5, Cy7, cyanine (cyanine) including indo cyanine green, and the like, one or more of these may be used in combination. Moreover, you may use combining 1 or 2 types or more of fluorescent microparticles or nanoparticles containing fluorescent substance. In particular, it may be desirable for the labeling material to be readily bound or coated onto the first binder (eg, an antibody).

In addition, in order to attach the conjugate to the conjugation pad 141 of the test strip 140, a method such as spraying or impregnation may be used, wherein the conjugation pad 141 is made of a porous material, specifically, a porous membrane material. Can be.

For example, when gold nanoparticles are used as the labeling substance to be conjugated with the first binder in the conjugate, the detectable property may be color, for example, orange, red, purple, or the like. The conjugate (conjugate of the first binder and the labeling substance) is combined with the target sample in the sample (when the target sample exists in the sample) and moves to the detection region 142.

In the illustrated embodiment, the detection region 142 may be in the form of a membrane, specifically a porous membrane. By way of example, the membrane can be selected from cellulose, glass fibers, nitrocellulose, polyvinylidene fluoride, charge modified nylon, polyether sulfone, and the like. More typically nitrocellulose can be used. In this case, the pore size of the membrane of the porous material may be, for example, about 0.05 to 12 ㎛, specifically about 0.1 to 7 ㎛ range.

According to an exemplary embodiment, the test region and the control region may be arranged in the detection region 142 sequentially in the flow direction of the sample, for example, each of the test region and the control region is a line pattern extending across the membrane It can be formed as.

When the target sample is present in the sample, the target sample specifically binds to the first binder bound to the conjugate to form a complex (eg, an antigen-antibody-labeled substance). The complex thus formed is divided into a detection region 142, for example, a test region and a control region, in a second binder (eg, an antibody that specifically binds to a target sample) fixed on the test region. As a result, the labeling substance accumulates in the detection region (eg, the test region) to express a specific signal (eg, color). In this case, the labeling material may be designed to move through the pore of the detection region 142 of the porous membrane.

Specifically, in the detection region 142, a second binder that specifically binds to the target sample bound to the first binder in the conjugate (conjugate of the first binder and the labeling substance) may be fixed. In this case, the second binder may also specifically (or selectively) bind to the target sample similarly to the first binder, specifically, a target sample specifically bound to the first binder of the conjugate (a target sample in the sample). Can be captured via (if present) (sandwich mode). In this regard, when the target sample is an antigen, the second binder may be an antibody.

As such, when a labeling substance (eg, gold nanoparticles) is captured in the detection region 142, a signal is generated, which is a change (specifically color, detectable by the naked eye or various detection devices (or analytical devices)). ). On the other hand, if the conjugate is not bound to the target sample, the conjugate will pass through the detection zone with the flow of the sample.

If the detection region 142 includes the control region, a third binder that binds to the first binder may be fixed, although not specifically bound to the target specimen. For example, the third binder can be specifically bound to the first binder. In this regard, the first binder may be a primary antibody bound to the target sample. Therefore, even if the conjugate passes through the test region without being bound to the target sample, the conjugate may be combined with the third binder and captured on the control region. For example, when a target sample does not exist in the sample, a signal is generated in the control region even if a signal (for example, color, etc.) is not generated in the test region of the detection region. As such, the response in the control region indicates that the liquid sample is properly passing through the kit (i.e., the signal from the control region indicates that the conjugate is present and that the third binder is bound to this conjugate). Diagnostic kit is operating properly).

Specifically, the third binder is bonded to the first binder bonded to the gold nanoparticles in the conjugate and accumulated on the control region, regardless of the presence of the target sample in the sample. According to an exemplary embodiment, the third binder may be a polyclonal antibody or monoclonal antibody that exhibits specificity for antibody fragments such as Fc region or Fab region or whole Ig molecule as secondary antibody. For example, when a conjugate of gold nanoparticles and a mouse anti-human IgG is used as the conjugate, the third binder in the control region 105 is an anti-mouse IgG as an antibody. ), For example goat anti-mouse IgG antibodies and the like.

In the above-described embodiment, the specific binding between the target sample and the biomaterial recognizer (binder) to the target sample mainly describes the antigen-antibody binding (ie, when the binder is an antibody), but this is for exemplary purposes. The present disclosure is not limited thereto. In this regard, in other exemplary embodiments, the binder may include proteins, hormones, and the like.

In another embodiment, it is to be understood that the binder may also comprise a gene (or genetic material), such as a nucleic acid (DNA or RNA). Specifically, ribonucleic acid (RNA), deoxyribonucleic acid (DNA), peptide nucleic acid (PNA), methylphosphonate nucleic acid, S-oligo, c-DNA, cRNA, miRNA, siRNA, aptamer and the like may also be included. In this case, the target sample may also be composed of hundreds, hundreds, thousands, or millions of nucleotides, and fragments such as DNA and RNA may also be applicable, and hybridization may be performed according to the base sequence of the target sample. Reactions may occur.

As described above, the sample (or liquid sample) passing through the detection region 142 is absorbed by the absorption pad 143 which is located downstream and is in contact with or overlapping with the detection region 142 of the membrane material. The absorbent pad 143 is located close to the opposite end of the pocketed structure 120 in the strip-shaped side flow analysis-based diagnostic kit 100 and absorbs excess reaction reagent to prevent backflow of the liquid. Prevent and collect the treated liquid. In particular, the absorbent pad 143 may increase the sensitivity of the test by allowing the use of larger volumes of liquid samples. In an exemplary embodiment, the absorbent pad 143 may be a material such as a cellulose filter.

Meanwhile, according to an exemplary embodiment of the present disclosure, the plurality of test strips 140 mounted in the diagnostic kit may be configured to diagnose the same or different target samples from each other. For example, different detection antibodies can be immobilized on each test strip 140, thereby quantitatively and / or qualitatively diagnosing two or more samples present in the sample. Therefore, multiple detections are possible by a hybrid diagnostic kit having a single structure.

Simple modifications and variations of the present invention can be readily used by those skilled in the art, and all such variations or modifications can be considered to be included within the scope of the present invention.

100: Hybrid Rapid Diagnostic Kit
110: upper substrate
111: first opening
112a, 112b, 112c: second opening
113a, 113b: partition member
114: first groove member
115: second groove member
120: pocket structure
121: third opening
122: sample loading chamber
123a, 123b, and 123c: micro channel channel section
124a, 124b: bulkhead structure
125a, 125b, 125c: transverse extension
126: slope
130: lower substrate
131: guide protrusion member
132: support protrusion member
133: first fastening protrusion member
134: second fastening protrusion member
135: mounting area
136: support structure for the guide
140: test strip
141: Conjugation pad or bond pad
142: detection area
143: absorbent pad

Claims (23)

An upper substrate including a first opening formed at one end side region to pass the injected liquid sample, and at least one second opening formed to observe or measure a signal generated from a detection reaction;
A pocket structure integrally formed to include a sample loading chamber for receiving the passed sample and a plurality of microfluidic channel portions for sample flow branch communicating with the sample loading chamber; And
A lower substrate having a support structure for guiding a plurality of test strips disposed to correspond to each of the plurality of microchannel channels in the pocket structure;
Including,
The pocket-shaped structure may include a third opening formed on an upper surface of the pocket-shaped structure to communicate with the first opening of the upper substrate; A sample loading chamber for receiving a sample passing through the third opening; And a plurality of microchannel channels having a partition structure that defines a boundary between the microchannels of the sample branched while communicating with the sample loading chamber.
The sample loading chamber of the pocket-type structure has an inclined surface for converting the flow direction of the sample introduced through the third opening into the partition structure direction, and
The plurality of micro-channel channel portion is a hybrid rapid diagnostic kit for forming a slope between the adjacent micro-channel channel portion to uniformly control the amount of the sample flowing between the micro-channel channel portion. The method of claim 1, further comprising a test strip supported on the lower substrate,
The test strips may include: conjugation pads sequentially arranged while being in contact or overlapping in a flow direction of a sample; Detection zone of membrane material; And an absorption pad, wherein the hybrid rapid diagnostic kit does not include a sample loading pad in front of the conjugation pad. The hybrid rapid diagnostic kit of claim 1, wherein the plurality of microchannel channels have an inclined surface that increases in an angle ranging from 1 ° to 40 ° in both directions relative to a horizontal plane with respect to a central microchannel. The method of claim 1, wherein the pocket-type structure is characterized in that it further comprises a test strip guide structure for guiding the samples from each of the micro-channel channel portion to a corresponding test strip, and facilitates contact with the test strip. Quick Diagnostic Kit. delete The rapid diagnostic kit of claim 1, wherein the surface of the microchannel channel portion is treated with an organic material and / or an inorganic material to impart hydrophilicity. 7. The quick diagnosis kit of claim 6, wherein the surface of the microchannel channel portion has a water contact angle of 60 ° or less. The rapid diagnostic kit of claim 6, wherein the organic material is selected from the group consisting of a compound having an amine, hydroxy, carbonyl or epoxy functional group, and a monomer, dimer and polymer having the functional group. The method of claim 6, wherein the inorganic material is gold, silver, silicon, aluminum, nickel, iron, copper, manganese, silicon, titanium and chromium is one or more metals selected from the group consisting of oxides thereof quick Diagnostic kit. The rapid diagnostic kit of claim 9, wherein the surface of the microchannel channel part is coated with silica (SiO ₂ ). The method of claim 1, wherein the upper substrate, the pocket structure and the lower substrate is polyester, polyethylene (PE), polypropylene (PP), polyimide (PI), polystyrene (PS), polycarbonate (PC), polyurethane , Polyvinylidene fluoride, nylon, polymethylmethacrylate (PMMA), polyvinylchloride (PVC), cyclic olefin copolymer (COC), polyamide (PA), poly (phenylene ether) (PPE), Rapid diagnostic kit, characterized in that formed of polyoxymethylene (POM), polyether ether ketone (PEEK), polyether sulfone (PES), polytetrafluoroethylene (PTFE) or acrylic resin. delete The quick diagnosis kit of claim 1, wherein the lower substrate further comprises a plurality of guide protrusion members to suppress left and right movement of individual test strips. The quick diagnosis kit of claim 13, wherein the lower substrate further comprises a plurality of support protrusion members to adjust the height of the individual test strips. The quick diagnosis kit of claim 1, wherein the lower surface of the upper substrate and the upper surface of the lower substrate further include coupling elements for fastening between the upper substrate and the lower substrate. 16. The quick diagnosis according to claim 15, wherein the coupling element is included in an interference fit method by a groove member (or protrusion member) formed in the upper substrate and a protrusion member (or groove member) formed in the lower substrate. Kit. The quick diagnosis kit of claim 1, wherein the pocket structure is injection molded, and there is no bonding surface between the sample loading chamber and the microchannel channel portion. The conjugate pad of claim 2, wherein the conjugation pad of each of the plurality of test strips comprises conjugates to which a first binder and specifically a labeling substance are bonded, the first binder specifically binding to a target sample; And the detection region comprises a second binder specifically binding to a target sample bound to the first binder of the conjugate. 19. The quick diagnosis kit of claim 18, wherein each of the plurality of test strips comprises a first binder and a second binder for the diagnosis of the same or different target specimens. The rapid diagnostic kit of claim 18, wherein the target sample is an antigen and each of the first binder and the second binder is an antibody. delete a) providing a sample for analysis of a liquid phase containing at least one target sample;
b) loading said sample into a sample loading chamber of said pocketed structure through the first and third openings of the hybrid rapid diagnostic kit according to claim 2; And
c) qualitatively and / or quantitatively analyzing the target sample contained in the analytical sample by observing or measuring a signal generated from each test strip in the hybrid rapid diagnostic kit;
Rapid diagnostic method of the sample for analysis comprising a. 23. The method of claim 22, wherein the liquid sample for analysis is a plasma component of blood.

Images