Multi-index quantitative detection kit for heart failure

Abstract

The utility model discloses a multi-index quantitative detection kit for heart failure. The multi-index quantitative detection kit comprises a detection card and a diluent box body, the detection card comprises a detection shell and a detection strip, the detection strip comprises a bottom plate as well as a sample pad, a combination pad, a detection pad and a sample absorption pad which are sequentially overlapped on the bottom plate, the multiple indexes comprise three indexes of adrenomedullin, peptin and angiotensin II, and the combination pad comprises a specific detection antibody which is marked by a fluorescent substance and aims at the indexes; a detection line and a quality control line are arranged on the detection pad, the detection line is coated with a specific capture antibody for capturing the index, and the quality control line is coated with a hapten or an antibody capable of being combined with the specific detection antibody; and a diluent is contained in the diluent box body. The combined detection of multiple indexes of heart failure is realized, the three indexes can be quantitatively detected within 15 minutes, the result is accurate, and the combined detection kit is suitable for hospital outpatient and emergency treatment and primary medical institutions.

Description

TECHNICAL FIELD

[0001] The utility model relates to the technical field of biotechnology diagnosis, especially to a multi-index quantitative detection kit for heart failure. BACKGROUND

[0002] Acute heart failure is an acute clinical syndrome caused by multiple causes. Heart failure symptoms and signs occur rapidly or acutely worsen, accompanied by elevated plasma natriuretic peptide levels, often life-threatening, requiring immediate medical intervention, usually requiring emergency admission. The common causes of new heart failure are acute myocardial necrosis and / or injury (such as ACS, severe myocarditis, etc.) and acute hemodynamic disorders (such as acute valve insufficiency, hypertensive crisis, pericardial tamponade). Acute decompensation of chronic heart failure often has one or more predisposing factors, such as significant blood pressure elevation, ACS, arrhythmia, infection, poor treatment adherence, acute pulmonary embolism, anemia, acute exacerbation of chronic obstructive pulmonary disease (COPD), perioperative period, renal function deterioration, thyroid function abnormalities, drugs (such as non-steroidal anti-inflammatory drugs, corticosteroids, negative inotropic drugs), etc.

[0003] According to the "China Heart Failure Diagnosis and Treatment Guidelines 2024", the diagnosis of heart failure patients mainly includes: according to the underlying disease, predisposing factors, clinical manifestations (medical history, symptoms and signs), and various examinations (electrocardiogram, transcutaneous arterial blood oxygen monitoring, chest imaging, echocardiogram, etc.), according to the "China Expert Consensus on Clinical Application of Heart Failure Biomarkers" for known or promising biomarkers in heart failure prediction, diagnosis, treatment guidance and prognosis evaluation, for reference by professionals in clinical decision-making. For neuroendocrine activation-related biomarkers, adrenomedulin (ADM), copeptin, and angiotensin II are recommended for detection. Therefore, the three markers are selected for joint detection to stage and monitor the diagnosis of patients. The three joint detection products have important value in clinical practice, but there is currently no joint detection reagent for these three indicators in China, which is not conducive to the rapid diagnosis of heart failure.

[0004] Adrenomedullin (ADM) is a vasodilatory polypeptide found in resected human pheochromocytoma tumor bodies, consisting of 52 amino acids in a circular arrangement, with a disulfide bond between cysteine residues at positions 16 and 21, belonging to the calcitonin gene-related peptide (CGRP) superfamily and having homology with CGRP. ADM is mainly synthesized and secreted by vascular endothelial cells and smooth muscle cells, with endothelial cells being the main ones, and is highly expressed in important organs such as the heart and lungs. ADM has two types of receptors: ADM-specific receptors and CGRP receptors. After binding with the receptors, ADM activates protein kinases by increasing the content of cyclic adenosine monophosphate (cAMP) in cells, and also plays a role by regulating the production of nitric oxide (NO). ADM has multiple biological effects. In the body, it exerts vasodilatory, antihypertensive, diuretic, anti-inflammatory, oxidative stress, inhibition of smooth muscle cell proliferation, migration, and differentiation effects through autocrine or paracrine binding with the two types of receptors, and its secretion increases in hypoxic conditions, and has many studies in heart-lung related diseases. In heart failure, the serum ADM level of patients shows an increasing trend with the severity of heart failure, and shows a good positive correlation. On the one hand, the reduction of cardiac output in heart failure causes pulmonary congestion, stimulating pulmonary vascular endothelial cells to synthesize ADM; on the other hand, the increase of blood volume in the heart chamber in heart failure stimulates myocardial cells to also increase the secretion of ADM. Combined with echocardiography, it is found that the lower the left ventricular ejection fraction (LVEF), the higher the ADM level, while the serum ADM level and the early diastolic mitral valve flow velocity peak / late diastolic mitral valve flow velocity peak (E / A) do not show a significant correlation. Studies have found that there is no difference in ADM levels between the congenital heart disease with heart failure group and the pneumonia with heart failure group, indicating that the serum ADM level is not related to the cause, but is related to the severity of the disease.

[0005] Copeptin is the C-terminal part of the precursor of arginine vasopressin (AVP), which has antidiuretic and vasoconstrictor effects, leading to water retention and increased cardiac preload and afterload. Studies have shown that AVP levels are significantly elevated in heart failure and are associated with the severity and prognosis of heart failure. However, the short half-life and instability of AVP in vitro limit its clinical application. Copeptin can be used as a surrogate marker for AVP. Studies have shown that copeptin levels have high predictive value for the risk of heart failure in patients with diabetes at an early stage. Copeptin is also an independent risk factor for heart failure in patients with renal dysfunction. In addition to its elevation in heart failure, copeptin also has good predictive value for the severity of heart failure. In chronic heart failure, copeptin levels increase with increasing New York Heart Association (NYHA) classification. As cardiac function gradually declines, cardiac index gradually decreases, and copeptin levels also gradually increase. Copeptin also has good predictive value for end-point events in patients with advanced heart failure, and its value may be higher than that of BNP. For patients with advanced heart failure who develop dyspnea, copeptin is also a good predictor of poor prognosis. Given the above characteristics of copeptin, it can be used to guide the prevention of the stress system in patients with heart failure.

[0006] Angiotensin II (Ang II) is not only derived from the classic renin-angiotensin-aldosterone system (RAAS), but also synthesized and released by cardiac myocytes and fibroblasts in the heart, exerting biological effects in a paracrine or autocrine manner. RAAS regulates blood pressure stability, extracellular fluid homeostasis, and cardiovascular remodeling. Overactivation of RAAS can lead to various pathophysiological conditions, mainly hypertension. RAAS can cause end-organ damage by directly affecting cardiac, vascular, and renal tissues. In particular, intrarenal RAAS affects arterial blood pressure and the development and progression of chronic kidney failure. Angiotensin II receptor type 1 and type 2 (AT1 and AT2, respectively) regulate sodium excretion, but studies on kidney transplantation have shown that the AT1 receptor plays a major role in the blood pressure regulation of Ang II. The signaling pathway of Ang II-induced myocardial fibrosis is complex, mainly through binding to its specific receptor, Ang II type 1 receptor (AT1R), and activating a series of signal molecules to transmit extracellular signals to the cell interior to produce fibrosis effects.

[0007] In summary, a single biomarker can only reflect part of the disease information from one side and cannot accurately assess the type, pathology, and pathophysiological changes of the disease. Therefore, it is necessary to provide a multi-index detection kit to improve the accuracy and specificity of heart failure diagnosis and to address the shortcomings of existing detection. Utility model content

[0008] To solve the above technical problems, the utility model discloses a kind of multi-index quantitative detection kit for heart failure, and the index detected includes adrenal medulla, and peptide, angiotensin II, realizes the joint detection of multiple indexes of heart failure, can be quantitatively detected in 15 minutes to above-mentioned three indexes, result is accurate, suitable for use in hospital outpatient and primary health care institutions.

[0009] To realize the above technical purpose, reach the above technical effect, the utility model realizes by following technical scheme:

[0010] A kind of multi-index quantitative detection kit for heart failure, including detection card and diluent box body;The detection card includes detection shell and detection strip arranged in the detection shell, and the detection strip includes bottom plate and sample pad, combination pad, detection pad and sample pad that are successively lapped on bottom plate, wherein, sample pad and combination pad are arranged on one side of detection pad, and sample pad is arranged on the other side of detection pad, and the multi-index includes adrenal medulla, and peptide, angiotensin II three indexes, and the specific detection antibody for the index is contained on the combination pad with fluorescent substance label;Detection line and quality control line are provided on the detection pad, and the specific capture antibody for capturing the index is coated on the detection line, and the hapten or antibody capable of being combined with specific detection antibody is coated on the quality control line;

[0011] The detection shell includes upper shell and lower shell, and the lower end of the upper shell is provided with needle, and the end of the detection strip close to sample pad is stretched out from the upper shell, and the lower shell is covered below the upper shell;

[0012] Diluent is contained in the diluent box body, and recess is provided on the diluent box body, and film is provided on the bottom of the recess;The detection card is pierced through the film by needle, so that detection strip is contacted with diluent infiltrated into recess.

[0013] Preferably, the detection shell of the detection card is provided with viewing window.

[0014] Preferably, the number of the detection card is one, and the specific detection antibody for three indexes is contained on the combination pad of the detection strip in the detection card with fluorescent substance label, and three detection lines and a quality control line are distributed at intervals on the detection pad, and the three detection lines are coated with specific capture antibody of the three indexes respectively.

[0015] Preferably, the number of the detection cards is two; two detection lines and one quality control line are distributed on the detection pad of the detection strip in one of the detection cards, and the two detection lines are respectively coated with specific capture antibodies for capturing any two indexes of adrenomedullin, copeptin and angiotensin II; one detection line and one quality control line are distributed on the detection pad of the detection strip in the other detection card, and the detection line is coated with specific capture antibodies for capturing the third index.

[0016] Preferably, the number of the detection cards is three; one detection line and one quality control line are distributed on the detection pad of the detection strip in each of the detection cards, and the detection line of each of the detection strips is respectively coated with specific capture antibodies for capturing one index.

[0017] Preferably, the detection strip further comprises a blood filtration pad, and the blood filtration pad, the sample pad, the combination pad, the detection pad and the sample suction pad are sequentially connected to the bottom plate.

[0018] Preferably, the number of the grooves is multiple.

[0019] Preferably, the needle is a PP material needle, the sample pad and the combination pad are glass fiber pads or non-woven fabric pads, the material of the detection pad is a nitrocellulose membrane, the material of the sample suction pad is a water absorption filter paper, and the bottom plate is a PVC plate.

[0020] Preferably, the fluorescent substance is marked by time-resolved fluorescent microsphere marking or quantum dot immune microsphere marking.

[0021] The utility model discloses the beneficial effect:

[0022] The indexes detected by the utility model include adrenomedullin (ADM), copeptin and angiotensin II (Ang II), realize the combined detection of multiple indexes of heart failure, can quantitatively detect the above three indexes within 15 minutes, and the result is accurate.

[0023] The reagent box of the utility model comprises a diluent box body, the diluent box body is filled with diluent, the diluent box body is further provided with a groove, the bottom of the groove is provided with a film, the detection card after sample addition is pierced through the film by a needle, the detection strip is contacted with the diluent infiltrated into the groove, sample rapid detection can be realized, the sample dilution step is reduced, and the reaction speed can be controlled by the slow infiltration of the diluent into the groove.

[0024] The utility model discloses simple operation, high sensitivity, strong specificity, accurate result, and is more suitable for use in hospital outpatient service and primary medical institutions. BRIEF DESCRIPTION OF DRAWINGS

[0025] Figure 1It is the plane structure schematic view of the detection card in the utility model.

[0026] Figure 2 It is the three-dimensional structure schematic view of the detection card in the utility model.

[0027] Figure 3 It is the structure schematic view of the diluent box body in the utility model, wherein, (a) is a top view, and (b) is a front view.

[0028] Figure 4 It is the operation schematic view of the detection kit of the utility model.

[0029] Figure 5 It is the exploded structure schematic view of the detection strip of the embodiment 1 of the utility model.

[0030] Figure 6 It is the top view of the detection strip of the embodiment 1 of the utility model.

[0031] Figure 7 It is the exploded structure schematic view of the detection strip of the embodiment 2 of the utility model.

[0032] Figure 8 It is the top view of the detection strip of the embodiment 2 of the utility model.

[0033] Explanation of reference signs:

[0034] 1: detection shell, 11: upper shell, 12: lower shell, 111: inspection window, 112: needle; 2: detection strip, 21: bottom plate, 22: blood filter pad, 23: sample pad, 24: combination pad, 25: detection pad, 251: detection line, 2511: adrenomedullin detection line, 2512: and peptide detection line, 2513: angiotensin II detection line, 252: quality control line, 26: sample pad; 3: diluent box body, 31: groove, 32: film. Specific implementation

[0035] The preferred embodiments of the utility model are described in detail in combination with the drawings, so that the advantages and characteristics of the utility model can be more easily understood by the person skilled in the art, and the protection scope of the utility model is more clearly and explicitly defined.

[0036] In the description of the utility model, it should be understood that the orientation or position relationship indicated by the terms "front", "back", "left", "right", "up", "down" and the like is the orientation or position relationship based on the orientation or position relationship shown in the drawings, and is only for the convenience of describing the utility model and simplifying the description, and does not indicate or imply that the indicated device or element must have a particular orientation, be constructed and operated in a particular orientation, therefore, it cannot be understood as a limitation on the utility model.

[0037] AsFigures 1 to 6 As shown in the figure, the multi-index quantitative detection kit for heart failure of embodiment 1 comprises a detection card and a diluent box; the detection card comprises a detection shell 1 and a detection strip 2 arranged in the detection shell 1, the detection strip 2 comprises a bottom plate 21 and a sample pad 23, a combination pad 24, a detection pad 25 and a sample suction pad 26 which are sequentially overlapped on the bottom plate 21, wherein the sample pad 23 and the combination pad 24 are arranged on one side of the detection pad 25, and the sample suction pad 26 is arranged on the other side of the detection pad 25; the multi-index comprises three indexes of adrenomedullin, copeptin and angiotensin II; the combination pad 24 comprises time-resolved fluorescence microsphere-labeled specific detection antibodies for the three indexes; the detection pad 25 is provided with three detection lines 251 and a quality control line 252; the three detection lines and the quality control line are parallel to each other and arranged along the length direction of the detection pad 25; the quality control line is located on the right side of the sample suction pad 26, the quality control line is close to the sample suction pad 26, and the three detection lines are located on the same side of the quality control line. The interval between two adjacent detection lines is equal to the interval between the quality control line and the detection line close to the quality control line. The three detection lines are respectively coated with specific capture antibodies for capturing the three indexes, which are adrenomedullin detection line 2511, copeptin detection line 2512 and angiotensin II detection line 2513; the quality control line 252 is coated with a hapten or an antibody capable of binding with the specific detection antibody.

[0038] The detection shell 1 comprises an upper shell 11 and a lower shell 12, the lower end of the upper shell 11 is provided with a needle 112, one end of the detection strip 2 close to the sample pad 23 protrudes from the upper shell, and the lower shell 12 covers the lower part of the upper shell 11 to cover and protect the needle 112 and the protruding part of the detection strip 2.

[0039] The diluent box 3 is filled with diluent, and a plurality of grooves 31 are arranged on the diluent box 3, and a film 32 is arranged on the bottom of the groove 31; the detection card pierces the film 32 through the needle 112, so that the detection strip 2 is in contact with the diluent infiltrated into the groove 31.

[0040] The detection shell 11 of the detection card is provided with a viewing window 111. The viewing window 111 is arranged above the three detection lines 251 and the quality control line 252. The projection area of the viewing window 111 on the detection pad 25 is greater than or equal to the area defined by the three detection lines, the quality control line and the interval therebetween.

[0041] In this embodiment, the detection card further comprises a blood filtration pad 22, and the blood filtration pad 22, the sample pad 23, the combination pad 24, the detection pad 25 and the sample suction pad 26 are sequentially overlapped on the bottom plate 21.

[0042] The needle 112 is made of PP, the sample pad 23 and the binding pad 24 are made of glass fiber pad or non-woven fabric pad, the detection pad 25 is made of nitrocellulose membrane, the sample pad 26 is made of water absorption filter paper, and the bottom plate 21 is made of PVC plate.

[0043] The use process of the detection kit is as follows:

[0044] After the user takes out the detection card, the lower shell 12 is disassembled, the sample to be detected is added to the blood filter pad 22, and the detection card is vertically inserted into the groove 31 of the diluent box body 3. The needle 112 below the upper shell 11 pierces the membrane 32 in the groove 31, the diluent seeps into the groove 31, and the sample passes through the blood filter pad 22 and the sample pad 23. The antigen in the sample is combined with the time-resolved fluorescence microsphere labeled adrenomedullin, and the peptide, and the angiotensin II monoclonal antibody (specific detection antibody) to form a reaction complex. The reaction complex moves along the detection pad 25 made of nitrocellulose membrane under the chromatography effect, moves to the detection line 251 (T line), and the reaction complex is captured by the hapten or antibody (specific capture antibody) coated on the detection line 251 which can be combined with the specific detection antibody to form a final reaction complex. The corresponding monoclonal antibody at the quality control line 252 (C line) captures the complex.

[0045] During detection, the quality control line 252 and the detection line 251 are detected by using a special fluorescence detector. If no fluorescence signal appears at the quality control line 252, it means that the detection is invalid. If a fluorescence signal appears at the quality control line 252, but no fluorescence signal appears at the detection line 251, it means that the sample to be detected does not contain the antigen. If a fluorescence signal appears at one or more detection lines 251, it means that the sample to be detected contains the corresponding antigen, and the content of the corresponding antigen is read from the fluorescence detector.

[0046] Example 2

[0047] As shown in Figure 7 and Figure 8 The difference between this embodiment 2 and the embodiment 1 is that the number of detection cards is three, and the number of detection strips is three. One detection line 251 and one quality control line 252 are distributed on the detection pad of each detection strip, and the detection line 251 of each detection strip is coated with a specific capture antibody for capturing one index. That is, each detection strip detects one index (adrenomedullin, peptide, and angiotensin II).

[0048] The application method of the detection kit of this embodiment 2 is referred to the embodiment 1.

[0049] Example 3

[0050] The difference between the present embodiment 3 and the embodiment 1 is that the number of detection cards is two, and the number of detection strips is two accordingly; two detection lines and one quality control line are distributed on the detection pad of one detection strip, and the two detection lines are coated with specific capture antibodies for capturing any two indexes of adrenomedullin, copeptin and angiotensin II; one detection line and one quality control line are distributed on the detection pad of the other detection strip, and the detection line is coated with specific capture antibodies for capturing the third index.

[0051] The application method of the detection kit of the present embodiment 3 is referred to the embodiment 1.

[0052] Embodiment 4

[0053] The difference between the embodiment 4 and the embodiment 1 is that the fluorescent substance label in the embodiment 4 is quantum dot immune microsphere label.

[0054] The application method of the detection kit of the present embodiment 4 is referred to the embodiment 1.

[0055] It is obvious for those skilled in the art that the present application is not limited to the details of the above exemplary embodiments, and the present application can be realized in other specific forms without departing from the spirit or essential characteristics of the present application. Therefore, the embodiments should be regarded as exemplary and non-limiting, and the scope of the present application is defined by the appended claims rather than the above description, and all changes falling within the meaning and scope of the equivalent elements of the claims are intended to be included in the present application. Any reference signs in the claims should not be regarded as limiting the claims involved.

[0056] In addition, it should be understood that although the present specification is described in terms of embodiments, not every embodiment contains only one independent technical solution, and the description manner of the specification is only for the sake of clarity, and those skilled in the art should regard the specification as a whole, and the technical solutions in each embodiment can also be properly combined to form other embodiments that those skilled in the art can understand.

Claims

1. A multi-marker quantitative test kit for heart failure, characterized by, The application relates to a multi-index detection card and a diluent box body, wherein the detection card comprises a detection shell and a detection strip arranged in the detection shell; the detection strip comprises a bottom plate and a sample pad, a combination pad, a detection pad and a sample suction pad which are sequentially connected to the bottom plate; the sample pad and the combination pad are arranged on one side of the detection pad, and the sample suction pad is arranged on the other side of the detection pad; the multi-indexes comprise three indexes of adrenomedullin, peptide and angiotensin II; the combination pad comprises fluorescent substance marked specific detection antibodies for the indexes; the detection pad is provided with a detection line and a quality control line; the detection line is coated with specific capture antibodies for capturing the indexes; and the quality control line is coated with a hapten or an antibody which can be combined with the specific detection antibodies. The detection shell comprises an upper shell and a lower shell; the lower end of the upper shell is provided with a needle; one end of the detection strip close to the sample pad is arranged outside the upper shell; and the lower shell is arranged below the upper shell. The diluent box body is filled with diluents; the diluent box body is provided with a groove; the bottom of the groove is provided with a film; the detection card is pierced through the film by the needle so that the detection strip is contacted with the diluents in the groove.

2. The multi-marker quantitative test kit for heart failure according to claim 1, characterized by, The detection shell of the detection card is provided with a viewing window.

3. The multi-marker quantitative test kit for heart failure according to claim 1, characterized by, The number of the detection cards is one; the combination pad of the detection strip in the detection card comprises fluorescent substance marked specific detection antibodies for the three indexes; the detection pad is provided with three detection lines and one quality control line which are spaced apart; and the three detection lines are respectively coated with specific capture antibodies for capturing the three indexes.

4. The multi-marker quantitative test kit for heart failure according to claim 1, wherein The number of the detection cards is two; the detection pad of the detection strip in one of the detection cards is provided with two detection lines and one quality control line; the two detection lines are respectively coated with specific capture antibodies for capturing any two indexes of adrenomedullin, peptide and angiotensin II; and the detection pad of the detection strip in the other detection card is provided with one detection line and one quality control line; the detection line is coated with specific capture antibodies for capturing the third index.

5. The multi-marker quantitative test kit for heart failure according to claim 1, characterized by, The number of the detection cards is three; the detection pad of the detection strip in each of the detection cards is provided with one detection line and one quality control line; and the detection line of each of the detection strips is respectively coated with specific capture antibodies for capturing one index.

6. The multi-marker quantitative test kit for heart failure according to claim 1, wherein The detection strip further comprises a blood filtration pad; the blood filtration pad, the sample pad, the combination pad, the detection pad and the sample suction pad are sequentially connected to the bottom plate.

7. The multi-marker quantitative test kit for heart failure according to claim 1, wherein The number of the grooves is multiple.

8. The multi-marker quantitative test kit for heart failure according to claim 1, wherein The needle is a PP needle; the sample pad and the combination pad are glass fiber pads or non-woven fabric pads; the material of the detection pad is nitrocellulose membrane; the material of the sample suction pad is water absorption filter paper; and the bottom plate is a PVC plate.

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