WO2014044184A1 - Protéine pour la détection du diabète sucré de type 1, et peptide partiel associé - Google Patents

Protéine pour la détection du diabète sucré de type 1, et peptide partiel associé Download PDF

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Publication number
WO2014044184A1
WO2014044184A1 PCT/CN2013/083737 CN2013083737W WO2014044184A1 WO 2014044184 A1 WO2014044184 A1 WO 2014044184A1 CN 2013083737 W CN2013083737 W CN 2013083737W WO 2014044184 A1 WO2014044184 A1 WO 2014044184A1
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Prior art keywords
protein
diabetes
amino acid
acid sequence
seq
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PCT/CN2013/083737
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English (en)
Chinese (zh)
Inventor
马雄明
章为江
刘星
李钟�
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苏州偲聚生物材料有限公司
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Priority claimed from CN201210355395.8A external-priority patent/CN103665138B/zh
Priority claimed from CN201310115787.1A external-priority patent/CN104098672B/zh
Priority claimed from CN201310117129.6A external-priority patent/CN104098686B/zh
Priority claimed from CN201310116453.6A external-priority patent/CN104098675A/zh
Priority claimed from CN201310116801.XA external-priority patent/CN104098682B/zh
Application filed by 苏州偲聚生物材料有限公司 filed Critical 苏州偲聚生物材料有限公司
Publication of WO2014044184A1 publication Critical patent/WO2014044184A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/04—Endocrine or metabolic disorders
    • G01N2800/042—Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism

Definitions

  • the present invention relates generally to proteins, partial peptides of the proteins, detection devices comprising the same, and detection kits comprising the same, particularly proteins useful for diagnosis or typing of type 1 diabetes, partial peptides of the protein, including the same A detection device for a protein or a partial peptide of the protein and a detection kit comprising the protein, a partial peptide of the protein or the detection device. Background technique
  • Diabetes Mellitus, D is a group of clinical syndromes characterized by disorders of glucose metabolism caused by genetic and environmental factors. Insulin deficiency and insulin dysfunction cause metabolic disorders of carbohydrates, fats, proteins, water and dielectrics alone or simultaneously, and are characterized by chronic hyperglycemia. Typical cases can appear polyuria, polydipsia, polyphagia, weight loss, etc., that is, "three more one less" disease.
  • the International Diabetes Federation released the latest data: In 2001, the number of patients with diabetes in the world reached 366 million, an increase of nearly 30% compared with 285 million in 2010. Every year, 4.6 million people die of diabetes, and medical expenses for diabetes are as high as $465 billion.
  • Professor ID C. President Jean Claude Manbaya said: "In 201, one person died of diabetes every 7 seconds, and the alarm bell is ringing.” According to Voice of China, in November 2011, the number of confirmed diabetes patients in China reached 92.4 million, ranking first in the world. Among adults over 20 years old in China, the incidence of diabetes is as high as 9.7%.
  • Diabetes can be classified into type 1 diabetes, type 2 diabetes, gestational diabetes, and special types of diabetes according to its etiology.
  • the hospital is mainly based on clinical manifestations (such as type 1 diabetes, which occurs mostly in adolescence, and there are Types of "three more and one less" symptoms, depending on insulin, etc.) distinguish between type 1 and type 2 diabetes, and for patients with unclear type of diabetes such as latent autoimmune diabetes in adults (LAD A), And diagnosis of type 1 diabetes requires the detection of type 1 diabetes autoantibodies to aid diagnosis.
  • clinical manifestations such as type 1 diabetes, which occurs mostly in adolescence, and there are Types of "three more and one less" symptoms, depending on insulin, etc.
  • LAD A latent autoimmune diabetes in adults
  • diagnosis of type 1 diabetes requires the detection of type 1 diabetes autoantibodies to aid diagnosis.
  • An object of the present invention is to provide a protein, a partial peptide of the protein, a detection device comprising the protein or a partial peptide thereof, and a detection kit comprising the detection device, which are useful for diagnosis or typing of type 1 diabetes. It is an object of the present invention to provide a use of the protein or a partial peptide thereof for the preparation of a test kit useful for diagnosis or typing of type 1 diabetes.
  • the present invention includes the following technical solutions:
  • a protein consisting of the amino acid sequence shown in SEQ ID NO: 1, or a partial peptide of the protein:
  • a detection device comprising:
  • a detection kit comprising the detection device according to any one of items 2 to 4. 6.
  • the test kit of item 5 for use in the diagnosis or typing of type 1 diabetes.
  • test kit is for diagnosis or typing of type 1 diabetes.
  • Fig. 1 is a schematic view showing the process of producing SJ modified silica gel (iPDMS film).
  • Figure 2 illustrates a schematic of the peptide microarray spotting mode.
  • FIGS 3 to 4 show photographs of the results of testing for different sera.
  • Protein of the invention and partial peptide thereof
  • the present invention provides a protein (hereinafter also referred to as a protein of the present invention) useful for diagnosis or typing of type 1 diabetes.
  • This protein consists of the amino acid sequence shown in SEQ ID NO: 1, which is a type 1 diabetes autoantigen PDX-1 protein (Shi-Wu Li, Vijay Koya, YiLi, William Donelan, Peng Lin, Westley H Reeves and Li- Jim Yang, Pancreatic duodenal homeobox 1 protein is a novel b-cell-specific autoantigen for type I diabetes, Laboratory Investigation (2010) 90, 31 - 39 ) truncated protein, which can be associated with type 1 diabetes in patients with type 1 diabetes Autoantibodies specifically bind.
  • this protein is useful as a tool for diagnosis or typing of type 1 diabetes.
  • the proteins of the invention can be prepared by methods well known in the art. For example, a nucleotide sequence encoding the same can be inferred based on the above amino acid sequence, and the nucleotide sequence can be chemically synthesized, and the chemically synthesized nucleotide sequence can be inserted into a known expression vector, and the expression vector can be used to transform the host. Cells, cultured and expressed by the host cell, and then isolated and purified by conventional methods to obtain the protein of the present invention.
  • the present invention provides a polypeptide useful for diagnosis or typing of type 1 diabetes. Gold ⁇ ⁇ Rs ⁇ f ⁇ ⁇ ° tir ⁇ ⁇ ⁇ ⁇ ⁇ Non-YT harm ⁇ ⁇
  • L£L£80/£10Z 13/I3d In the case of a polypeptide, it is carried out by synthesizing or semi-synthesizing the polypeptide using a peptide synthesizer.
  • the chemical synthesis method include a peptide solid phase synthesis method and the like.
  • the peptide thus synthesized can be purified by a conventional means such as ion exchange chromatography, reversed phase high performance liquid chromatography, affinity chromatography or the like.
  • Such peptide solid phase synthesis methods and subsequent peptide purification are well known in the art.
  • the method described in International Publication No. WO2004/011653 can be employed. That is, it can be produced by: an amino acid or a dipeptide obtained by esterifying or amidating a carboxyl group of one amino acid or a dipeptide, and an amino acid having a free amino acid (for example, a carboxyl-protected amino acid) in a peptide synthetase.
  • the dipeptide or tripeptide formed in the presence of the reaction.
  • Examples of the peptide synthetase include a culture of a microorganism having the ability to produce a peptide, a microbial cell isolated from the culture, a bacterial cell treated product of the microorganism, or a peptide synthetase derived from the microorganism.
  • a genetic engineering method can be employed to produce the polypeptide of the present invention.
  • the amino acid sequence of the polypeptide of the present invention can be analyzed and confirmed by a conventional method, and can be analyzed and confirmed by, for example, mass spectrometry, chromatography or the like.
  • Detection device of the invention
  • the invention also provides a detection device (detection device of the invention) comprising a solid support, and a protein of the invention or a polypeptide of the invention linked to the solid support.
  • the detection device is useful for the diagnosis or typing of type 1 diabetes.
  • the carrier is not particularly limited as long as it is a carrier which is a solid or insoluble material (e.g., a material which can be separated from the reaction mixture by filtration, precipitation, magnetic separation, etc.).
  • the material constituting the body carriers include, but are not limited to: silicone (polydimethylsiloxane, the PDMS), cellulose, Teflon TM Yu nitro cellulose, agarose, dextran, chitosan, polystyrene , polyacrylamide, polyester, polyacrylate, polyamide, polypropylene, nylon, polyvinylidene fluoride, latex, silica, glass, fiberglass, gold, platinum, silver, copper, iron, stainless steel , ferrite, silicon wafer, polyethylene, polyethyleneimine, polylactic acid, resin, polysaccharide, protein (albumin, etc.), a combination thereof, and the like.
  • the shape of the solid carrier includes, but is not limited to, beads, magnetic beads, membranes, microtubes, membranes, Plates, microplates, carbon nanotubes, sensor chips, etc.
  • pits, grooves, filter bottoms, etc. can be placed on a flat solid support such as a film or sheet.
  • the magnetic beads may have a sphere diameter ranging from about 25 nm to about 1 mm. In a preferred embodiment, the magnetic beads have a diameter ranging from about 50 ⁇ to about ⁇ . The size of the beads can be selected according to the specific application.
  • beads made of highly crosslinked spherical agarose such as Sejpharose have a diameter ranging from about 24 ⁇ to about 165 ⁇ m.
  • the highly crosslinked spherical agarose beads have a diameter ranging from about 24 ⁇ to about 44 ⁇ .
  • the size of the highly crosslinked spherical blush beads can be selected according to the specific application.
  • solid carriers having a hydrophobic surface examples include those available from Polysciences, W arringtoii,
  • the silicon dioxide (S) 2 ) - treated or disilicon (Si0 2 ) based solid carrier inverted includes ultramagnetic dimethoxy beads available from Polysciences, Warrington, PA, etc., which can be used to capture nucleic acids. (eg DNA) copy or; M-280, etc., which can be purchased from Dynal Biotech.
  • Magnetic beads with a hydrophilic surface can be used to capture bacterial cells, nucleic acids, and other growth during the proliferative phase.
  • mag registered two standard L base
  • Bangs Laboratory inc.. Fishers, IN under the name MC02N/2928 bead.
  • the solid carrier is SJ modified silica gel, which is a silicone rubber microarray solid support material developed by Suzhou Yuju Biomaterial Co., Ltd. (iPDMS film, see Chinese patent publication) CN101265329A).
  • SIP surface initiated polymerization
  • polyethylene glycol sulfhydryl Acrylate poly(oligo(ethylene glycol) methacrylate), pOEGMA
  • SJ modified silica gel has excellent anti-protein non-specific adsorption (NPA) ability, which can control the adsorption of non-specific proteins in complex protein immunoassay to near the "absolute 0" level (close to or below the detection limit of the instrument) ), not only can avoid the trouble of blocking and multiple cleaning, but also can improve the sensitivity of protein microarray by using stronger signal amplification means.
  • NPA anti-protein non-specific adsorption
  • the nature of its silicone rubber gives the material strong mechanical properties and good operability.
  • Suzhou Jingju has successfully applied SJ modified silica gel to a multi-index combined microarray ELISA kit consisting of 11 tumor markers, which has achieved high-throughput and high-sensitivity detection, which proves that this material is an excellent one.
  • Protein microarray solid support material At the same time, this material also has the property of adjustable surface properties, which can be adjusted within a certain range by controlling the modification reaction time.
  • the attachment of the polypeptide of the present invention to a solid support can be carried out by a method of attaching a polypeptide to a solid support well known to those skilled in the art.
  • a polypeptide for the attachment of a protein/polypeptide to a surface of a modified silica gel, it can be passed through 1-ethyl-3-(3-diamidinopropyl)-carbodiimide [l-ethyl-3-(3- The reaction of dimethyl ami-nopropyl)carbodiimide, EDC] with N-hydroxysuccinimide (NHS) changes the carboxyl (-COOH) group on the polymer chain of the modified silica gel to an activating group.
  • EDC N-hydroxysuccinimide
  • the activating group can react with the amino group (-NH2) carried on the protein/polypeptide to immobilize the protein/polypeptide on the surface of the solid support (see, for example, Hongwei Ma, Yuanzi Wu, Xiaoli Yang, Xing Liu, Jian'an He, Long Fu, Jie Wang, Hongke Xu, Yi Shi and Renqian Zhong, Integrated poly(dimethysiloxane ) with an intrinsic nonfouling property approaching "Absolute " zero background in immunoassays, Anal. Chem., 82, 6338-6342, 2010 ).
  • the concentration of the polypeptide of the present invention in the spotting solution used for spotting is not particularly limited, and those skilled in the art can select it as usual, preferably lg ⁇ 100 ( ⁇ g/mL, more preferably l( ⁇ g ⁇ 50( ⁇ ) Further, the density of the polypeptide of the present invention distributed on a solid carrier is not particularly limited, and can be selected by a person skilled in the art, preferably from 1 to 100 points/10 mm 2 , more preferably from 5 to 50 points/10 mm 2 . .
  • the detecting device of the present invention is useful for diagnosis or typing of type 1 diabetes, or it can be used for manufacturing a test kit which can be used for diagnosis or typing of type 1 diabetes.
  • Detection kit of the invention is useful for diagnosis or typing of type 1 diabetes, or it can be used for manufacturing a test kit which can be used for diagnosis or typing of type 1 diabetes.
  • the present invention also provides a detection kit (detection kit of the present invention) comprising the detection device of the present invention.
  • the test kit can be used for the diagnosis or typing of type 1 diabetes.
  • the detection kit of the present invention must contain the detection device of the present invention.
  • the detection kit of the present invention may further comprise:
  • Sample dilution such as sample dilution of Beijing Saichi Biotechnology Co., Ltd. (product number 070021-S2), Zhengzhou Boweijia Biotechnology Co., Ltd.
  • the company's sample color change sample dilution product number bwj010103
  • This type of sample dilution is a PBS solution containing BSA, sucrose and other ingredients, containing preservatives, clear liquid, and can be used directly.
  • the sample diluent is used to dilute the serum, and the serum detected by the kit is diluted by an appropriate multiple, for example, 2 to 200 times, preferably 10 to 100 times.
  • the detection kit of the present invention may further comprise:
  • Concentrated lotion and lotion After incubating the serum and the enzyme-labeled antibody on the surface of the solid carrier, the unbound antibody and the enzyme-labeled antibody on the surface of the solid carrier are washed away with a washing solution.
  • the concentrated washing solution is, for example, a 1% Tween 20 aqueous solution, which is diluted 2-40 times, preferably 5-20 times when used.
  • the lotion can be configured by diluting the concentrated washing solution (10x) with purified water or distilled water at 1:9. For example, add 450 mL of concentrated washing solution (10Ox) to 450 mL of purified water or distilled water and mix well.
  • the unused lotion is stored at 2 ⁇ 8 °C and can be stored for 3 months.
  • the detection kit of the present invention may further comprise:
  • Enzyme-labeled antibody solution The type 1 diabetes autoantibody in the serum of type 1 diabetic patients can be bound to the protein or polypeptide of the present invention on a solid carrier (for example, SJ modified silica gel), and the enzyme-labeled antibody can bind to the antibody, and the enzyme The label on the target antibody can react with the luminescent substrate to emit detectable light.
  • the enzyme-labeled antibody may be, for example, horseradish peroxidase-labeled goat anti-human IgG.
  • the enzyme-labeled antibody solution horseradish peroxidase-labeled goat anti-human IgG (H+L) produced by Beijing Zhongshan Jinqiao Biotechnology Co., Ltd., product number ZB-2304, can be cited.
  • concentration of the enzyme-labeled antibody in the enzyme-labeled antibody solution is not particularly limited and may be, for example, from 1 ng to 1000 ng/mL.
  • the detection kit of the present invention may further comprise:
  • Luminescent substrate mixed solution The luminescent substrate mixed solution can be reacted with the horseradish peroxidase labeled on the enzyme-labeled antibody, so that the reaction emitting device can detect the chemical photoluminescent substrate mixed solution including the luminescent substrate liquid A. - a hydrogen peroxide solution, and a luminescent substrate solution B - a luminescent ammonia (luminol) solution.
  • two kinds of luminescent substrate liquids are previously mixed in an equal volume to obtain a luminescent substrate mixed solution (used within 45 minutes).
  • Luminescent ammonia emits light only when it is treated with an oxidizing agent.
  • a mixed aqueous solution of hydrogen peroxide and a hydroxide base is usually used as an activator. Under the catalysis of horseradish peroxidase, the hydrogen peroxide is decomposed into oxygen and water:
  • luminol When luminol reacts with hydroxide, it forms a double negative ion, which is oxidized by oxygen decomposed by hydrogen peroxide, and the product is an organic peroxide.
  • the peroxide is unstable and immediately decomposes nitrogen to form an excited state of 3-aminophthalic acid. Energy released from the excited state to the ground state In the form of photons, the wavelength is in the blue portion of visible light.
  • the detection kit of the present invention may further comprise:
  • reaction chambers for example, Chinese Patent Authorization Announcement CN202054829U.
  • the detection kit of the present invention may further comprise:
  • test molecules eg, peptides, proteins, nucleic acids, etc.
  • Other test molecules used to detect diabetes (especially type 1 diabetes).
  • the detection kit of the present invention may further comprise:
  • test kit can be used for diagnosis or typing of type 1 diabetes.
  • the reaction device and the reaction kit can be subjected to chemiluminescence imaging, for example, using a gel imager.
  • a gel imager for example, a GE LAS4000mini type or a Tianneng 5500 array imager can be used.
  • polypeptides used in the examples were synthesized by Jill Biochemical (Shanghai) Co., Ltd., and the polypeptide was confirmed by mass spectrometry.
  • the detection chip is prepared by using SJ modified silica gel (iPDMS film) as a solid support material, and the polypeptide solution is fixed by spotting.
  • the modified silica gel is an initiator for surface-initiated polymerization with an olefin end added to a conventional polydisiloxane siloxane material, and is fixed to polydidecyl siloxane by thermal crosslinking (silicon hydrogen bonding).
  • SJ modified silica gel is obtained, and the production process thereof is shown in FIG. 1 .
  • a and B are two components of polydidecylsiloxane, and poly(dimethylsiloxane) (Sylgard 184) is purchased from Dow Corning, USA, and contains liquid component A (The composition is a mixture of a metal platinum catalyst and a vinyl disiloxane polymer precursor) and a crosslinking agent B (the composition is a dimercaptosiloxane precursor having an ethyl group and a Si-H group) Two ingredients.
  • C is an initiator with a vinyl group at the end and was purchased from Hangzhou Dongwei Company.
  • a transparent elastic silicone rubber is prepared by a curing reaction, and then surface-modified by a SIP technique to obtain an SJ-modified silica gel.
  • SIP surface initiated polymerization
  • Poly(OEGMA) polyethylene glycol methacrylate
  • PEG polyethylene glycol
  • the prepared SJ modified silica film should be stored in a 4 ° C refrigerator.
  • the peptide microarray was prepared on modified silica gel using a Crystal Core® PersonalArrayerTM 16 Personal Spotter. The process was:
  • the SJ modified silica gel sheet (15 x 15 mm 2 ) was immersed in the activation solution, and after 30 minutes, it was taken out and rinsed with deionized water three times, and dried with nitrogen, and immediately used for spotting.
  • the prepared peptide microarray should be fixed in a constant temperature and humidity chamber (26 ° C, 60% humidity) for at least 6 h.
  • the chemical fixation process is as follows:
  • the buffer containing the capture polypeptide molecule is spotted on the modified silica gel membrane by the spotter, and then the buffer begins to evaporate, and the capture polypeptide molecules are in intimate contact with the surface of the SJ modified silica gel and interact with each other.
  • the terminal-COOH of the purified (OEGMA) polymer on the surface of the modified silica gel forms a stable covalent bond with the -NH 2 of the polypeptide molecule, thereby immobilizing the chemically active polypeptide molecule on the surface of the SJ modified silica gel.
  • the peptide microarray fixed for 6 h must be assembled within two days.
  • the SJ modified silicone rubber sheet is pasted on a special reaction column by a backing, and the reaction chamber is covered.
  • One reactor consists of two reaction columns and one reaction chamber.
  • the assembled peptide microarray needs to be vacuum sealed and stored in a refrigerator at 4 ° C for use.
  • the concentrated washing solution Before starting the test, add the concentrated washing solution to the purified water or distilled water for dilution in the ratio of 1:10. After the dilution is completed, the washing liquid is used. Directly use, add 2 mL of the washing solution to the surface of the chip with a pipetting gun, soak the chip 3 Minutes to ensure that the surface of the chip is completely wetted.
  • the luminescent substrate liquid A and the luminescent substrate liquid B may be mixed in an equal volume in advance to obtain a luminescent substrate mixed solution (used within 45 minutes). After the cleaning is completed, the reaction chamber is removed, and 15 L of the luminescent substrate mixed solution is added to each chip surface to uniformly spread the luminescent substrate mixed solution. On the surface of the chip.
  • the chip with the luminescent liquid is placed in a gel imager for chemiluminescence imaging, and the results are interpreted.
  • Negative controls were PBS buffer (ie, incubated with the serum to be tested in step 3, but incubated with PBS, the rest of the steps were the same), serum dilution control, and negative serum (referring to healthy people and non-type 1 diabetes) Control of the patient's serum).
  • the spotting pattern of the polypeptide microarray is shown in Figure 2: wherein the sample of the 20 points of the triangle is human IgG as the anchor point; the sample of the 4 points of the square is the PB spotting solution, as a blank control;
  • the sample is another type 1 diabetes autoantigen protein polypeptide, which is used as a detection index (these peptides have responses indicating that the detected serum has type 1 diabetes autoantibodies);
  • the star point sample polypeptide is the polypeptide sp- ⁇ of the present invention, It is a type 1 diabetes autoantigen protein peptide that responds to serum in patients with type 1 diabetes.
  • the polypeptide microarray was used to detect the serum and negative control of type 1 diabetic patients according to the above detection steps.
  • the response patterns are shown in Figures 3 to 4: wherein, Figure 3 shows the results of the negative control, only the points indicated by the triangles. The sample is responsive.
  • Figure 4 shows the results of serum testing for patients with type 1 diabetes, with samples from triangles, circles, and star points responding. It should be noted that the signal value measured by the instrument is from low to high, and the corresponding signal point color is changed from black to red and white.
  • any of the other polypeptides of the invention (sp-6, sp-8, sp-14, sp-15, sp-1, l-1-2, sp-1-3, sp-1) 4, sp-1-5 and sp-1-6) instead of the above-mentioned polypeptide sp-1, were spotted according to the above pattern, and different polypeptide microarrays were obtained, and the polypeptide microarrays were used according to the above detection steps for type 1 respectively.
  • the serum of the diabetic patient and the negative control were tested, and as a result, the same response pattern as that obtained using the above-described sp-1-containing polypeptide microarray was obtained.

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Abstract

La présente invention concerne une protéine utile pour le diagnostic du diabète sucré de type 1, un polypeptide, un dispositif de détection contenant la protéine ou le polypeptide, et une trousse de diagnostic contenant le dispositif de détection.
PCT/CN2013/083737 2012-09-21 2013-09-18 Protéine pour la détection du diabète sucré de type 1, et peptide partiel associé WO2014044184A1 (fr)

Applications Claiming Priority (10)

Application Number Priority Date Filing Date Title
CN201210355395.8A CN103665138B (zh) 2012-09-21 2012-09-21 多肽、包含该多肽的检测器件和检测试剂盒
CN201210355395.8 2012-09-21
CN201310115787.1A CN104098672B (zh) 2013-04-03 2013-04-03 多肽、包含该多肽的检测器件和检测试剂盒
CN201310117129.6A CN104098686B (zh) 2013-04-03 2013-04-03 多肽、包含该多肽的检测器件和检测试剂盒
CN201310116453.6A CN104098675A (zh) 2013-04-03 2013-04-03 多肽、包含该多肽的检测器件和检测试剂盒
CN201310117129.6 2013-04-03
CN201310116453.6 2013-04-03
CN201310116801.X 2013-04-03
CN201310116801.XA CN104098682B (zh) 2013-04-03 2013-04-03 多肽、包含该多肽的检测器件和检测试剂盒
CN201310115787.1 2013-04-03

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105572379A (zh) * 2014-11-05 2016-05-11 苏州偲聚生物材料有限公司 可用于诊断间日疟和/或恶性疟的试剂盒
CN105628928A (zh) * 2014-11-11 2016-06-01 深圳国际旅行卫生保健中心 可用于辅助诊断疟疾的试剂盒
CN105628925A (zh) * 2014-11-05 2016-06-01 苏州偲聚生物材料有限公司 可用于诊断间日疟和/或恶性疟的试剂盒
CN107764991A (zh) * 2016-08-22 2018-03-06 苏州偲聚生物材料有限公司 能够提高检测灵敏度的固相载体及检测器件
CN110501505A (zh) * 2018-05-18 2019-11-26 中国兽医药品监察所 小反刍兽疫诊断试剂盒
CN110498843A (zh) * 2018-05-18 2019-11-26 中国兽医药品监察所 小反刍兽疫诊断试剂盒
CN110498845A (zh) * 2018-05-18 2019-11-26 中国兽医药品监察所 小反刍兽疫诊断试剂盒
CN110498842A (zh) * 2018-05-18 2019-11-26 中国兽医药品监察所 小反刍兽疫诊断试剂盒
EP3502257A4 (fr) * 2016-08-22 2020-05-13 Suzhou SJ Biomaterials, Ltd. Co. Support en phase solide capable d'améliorer la sensibilité de détection, et composant de détection

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