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CN115436617A - Dry analytical reagent for gamma-glutamyl transpeptidase detection - Google Patents

Dry analytical reagent for gamma-glutamyl transpeptidase detection Download PDF

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CN115436617A
CN115436617A CN202211010894.3A CN202211010894A CN115436617A CN 115436617 A CN115436617 A CN 115436617A CN 202211010894 A CN202211010894 A CN 202211010894A CN 115436617 A CN115436617 A CN 115436617A
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support layer
reagent
glutamyl transpeptidase
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孙伟娜
黄海水
任孟
文军
卢志凯
刘敏
易丹旸
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Lucky Healthcare Co ltd
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Abstract

A dry analytical reagent for detecting gamma-glutamyl transpeptidase comprises an upper support layer, a diffusion layer, a reagent layer, a support and a lower support layer from top to bottom in sequence, wherein the diffusion layer, the reagent layer and the support are arranged at the middle position between the upper support layer and the lower support layer from top to bottom in sequence, the pores at the two ends of the upper support layer and the lower support layer are bonded through the middle support layer, the middle positions of the upper support layer and the lower support layer are respectively provided with a sample adding hole and a test hole, and the porosity of the diffusion layer is 40-75%; the diffusion layer consists of high-crosslinked polymethyl methacrylate microspheres, an adhesive and a surfactant, and the particle size of the high-crosslinked polymethyl methacrylate microspheres is 5-50 mu m; the reagent layer comprises a surfactant, diglycine, L-gamma-glutamyl-3-carboxyl-p-nitroaniline, a buffer solution, a stabilizer and a water-soluble high polymer. The diffusion layer has the characteristic of isotropy, has good detection specificity, high accuracy and wide measurement range, meets the requirement of instant diagnosis and has great clinical application value.

Description

一种γ-谷氨酰转肽酶检测用干式分析试剂A dry analytical reagent for the detection of γ-glutamyl transpeptidase

技术领域technical field

本发明涉及一种γ-谷氨酰转肽酶检测用干式分析试剂,属于临床诊断领域。The invention relates to a dry analysis reagent for detecting gamma-glutamyl transpeptidase, which belongs to the field of clinical diagnosis.

背景技术Background technique

γ-谷氨酰转移酶(GGT)是一种肽酶,催化γ-谷氨酰基移换反应。血清 GGT是肝胆疾病的灵敏指标,各种原因引起的肝胆疾病可见血清GGT升高。 GGT临床检测分为湿化学法和干化学法,其中湿化学法是常用的分析方法,湿化学法试剂配制周期长,需专业人员操作,且检验结果易受操作人员水平影响,而干化学分析方法具有检测速度快、检测试剂易保存、不需配置任何液体试剂、检测门槛要求低、场合适应性强等优点,随着突发应急检验需求的提升,临床对生化分析的报告时间提出了更短的要求,推动了急诊生化检验技术逐渐从传统的湿化学向干式生化发展。干化学分析方法检验速度快,检测自动化水平高,可随时随地对零散样本进行个性化项目组合检测,尤其适合急诊、基层诊所、血站、体检机构、检验实验室等场景。γ-glutamyltransferase (GGT) is a peptidase that catalyzes γ-glutamyl transfer reactions. Serum GGT is a sensitive indicator of hepatobiliary diseases, and elevated serum GGT can be seen in hepatobiliary diseases caused by various causes. GGT clinical detection is divided into wet chemical method and dry chemical method, among which wet chemical method is a commonly used analysis method, wet chemical method reagent preparation cycle is long, requires professional operation, and the test results are easily affected by the level of operators, while dry chemical analysis The method has the advantages of fast detection speed, easy storage of detection reagents, no need to configure any liquid reagents, low detection threshold requirements, and strong adaptability to occasions. Short requirements have promoted the gradual development of emergency biochemical testing technology from traditional wet chemistry to dry biochemistry. The dry chemical analysis method has a fast test speed and a high level of test automation. It can perform individualized project combination tests on scattered samples anytime, anywhere, and is especially suitable for scenarios such as emergency departments, grassroots clinics, blood stations, physical examination institutions, and testing laboratories.

目前,常用干式分析试剂延续了感光胶片的涂层技术,将扩散层、光线阻挡层、试剂层等各功能层按顺序依次涂布支持体上,通过测定反射光密度的变化分析待测物的浓度。此类多层膜干片测试结果准确,但生产工艺复杂,扩散层的生产需要使用多种有机溶剂,产生大量有机废气,对环境有害的同时增加生产过程的危险性。另一类干化学分析试剂的组成为一个塑料支持层,一端为反应区包括样品层和试剂层,试剂层采用织物作为试剂载体,加样和测试均在其上部进行。At present, the commonly used dry analysis reagents continue the coating technology of photosensitive film, and the diffusion layer, light blocking layer, reagent layer and other functional layers are coated on the support in sequence, and the analyte is analyzed by measuring the change of reflected optical density. concentration. The test results of this kind of multilayer film dry film are accurate, but the production process is complicated. The production of the diffusion layer requires the use of various organic solvents, which generates a large amount of organic waste gas, which is harmful to the environment and increases the danger of the production process. Another type of dry chemical analysis reagent consists of a plastic support layer, one end of which is a reaction zone including a sample layer and a reagent layer, and the reagent layer uses fabric as a reagent carrier, and sample addition and testing are performed on the upper part.

专利CN201910219761.9公开了一种一种自动滤血干式光化学法微通道肝功三项检测卡,其中滤血膜采用市售产品,采用透射光度法测试,无法完全规避待检样本中的物质干扰。专利CN201910236059.3公开了测量γ-谷氨酰转移酶的试剂及诊断分析方法,其中诊断分析方法步骤较繁琐,仍需具备一定专业知识的人员操作,且微流控芯片的检测结果精密度无法保证。Patent CN201910219761.9 discloses an automatic hemofiltration dry-type photochemical microchannel liver function test card for three items, in which the hemofiltration membrane is a commercially available product and tested by transmission photometry, which cannot completely avoid substances in the sample to be tested interference. Patent CN201910236059.3 discloses reagents and diagnostic analysis methods for measuring γ-glutamyl transferase. The diagnostic analysis method steps are relatively cumbersome and still require personnel with certain professional knowledge to operate, and the precision of the detection results of the microfluidic chip is not high enough. ensure.

发明内容Contents of the invention

本发明为克服现有技术弊端,提供一种γ-谷氨酰转肽酶检测用干式分析试剂,扩散层选用遇水不溶胀且不渗透的高交联聚甲基丙烯酸甲酯微球,其与极少量的特定粘合剂组合形成高孔隙率结构的扩散层,对含有γ-谷氨酰转肽酶的待分析液体可实现高效快速渗透、扩散,其可在内部均匀分布、扩散和快速传递含有分析物的待检样品。In order to overcome the disadvantages of the prior art, the present invention provides a dry analytical reagent for the detection of γ-glutamyl transpeptidase. The diffusion layer is made of highly cross-linked polymethyl methacrylate microspheres that do not swell when exposed to water and are impermeable. It is combined with a very small amount of specific adhesive to form a high-porosity diffusion layer, which can achieve efficient and rapid penetration and diffusion of the liquid to be analyzed containing γ-glutamyl transpeptidase. It can be evenly distributed, diffused and Rapid delivery of test samples containing analytes.

本发明解决其技术问题所采用的技术方案是:The technical solution adopted by the present invention to solve its technical problems is:

一种γ-谷氨酰转肽酶检测用干式分析试剂,所述干式分析试剂由上至下依次包括上支持层、扩散层、试剂层、支持体和下支持层,所述扩散层、试剂层和支持体由上至下依次设置在所述上支持层和下支持层之间的中间位置,所述上支持层和下支持层的两端孔隙处通过中间支持层粘结,所述上支持层和下支持层中间位置分别设置有加样孔和测试孔,所述扩散层为各向均性的多孔扩散膜,其孔隙率为40-75%;所述扩散层由高交联聚甲基丙烯酸甲酯微球、粘合剂和表面活性剂组成,所述高交联聚甲基丙烯酸甲酯微球的粒径为5-50μm,所述粘合剂集中在高交联聚甲基丙烯酸甲酯微球表面与相邻微球相邻的区域,并将高交联聚甲基丙烯酸甲酯微球粘合成连贯的三维晶格;所述试剂层包括表面活性剂、双甘肽、L-γ-谷氨酰-3-羧基-对硝基苯胺、缓冲液、稳定剂和水溶性高分子聚合物。A dry analysis reagent for the detection of γ-glutamyl transpeptidase, the dry analysis reagent includes an upper support layer, a diffusion layer, a reagent layer, a support and a lower support layer from top to bottom, the diffusion layer , the reagent layer and the support body are sequentially arranged in the middle position between the upper support layer and the lower support layer from top to bottom, and the pores at both ends of the upper support layer and the lower support layer are bonded through the middle support layer, so The upper support layer and the middle position of the lower support layer are respectively provided with a sampling hole and a test hole, and the diffusion layer is an isotropic porous diffusion membrane with a porosity of 40-75%; Composed of linked polymethyl methacrylate microspheres, adhesives and surfactants, the particle size of the highly cross-linked polymethyl methacrylate microspheres is 5-50 μm, and the adhesive concentrates on the highly cross-linked The area adjacent to the adjacent microspheres on the surface of polymethyl methacrylate microspheres, and highly cross-linked polymethyl methacrylate microspheres are bonded into a coherent three-dimensional lattice; the reagent layer includes surfactants, Diglycyl peptide, L-γ-glutamyl-3-carboxy-p-nitroaniline, buffer, stabilizer and water-soluble polymer.

上述γ-谷氨酰转肽酶检测用干式分析试剂,所述高交联聚甲基丙烯酸甲酯微球采用悬浮聚合法制备而成,交联剂选自甲基丙烯酸酯、二甲基丙烯酸乙二醇酯、氨脂、二乙烯基苯以及N,N-亚甲基双丙烯酰胺中的一种或者任意两种以上的组合物,交联剂质量占甲基丙烯酸甲酯MMA单体质量的5wt%~ 30wt%。The above-mentioned dry analytical reagent for the detection of γ-glutamyl transpeptidase, the highly cross-linked polymethyl methacrylate microspheres are prepared by suspension polymerization, and the cross-linking agent is selected from methacrylate, dimethyl One of ethylene glycol acrylate, urethane, divinylbenzene and N,N-methylenebisacrylamide or any combination of two or more, the mass of the crosslinking agent accounted for 5wt% to 30wt% of the mass.

上述γ-谷氨酰转肽酶检测用干式分析试剂,所述粘合剂包括聚(丙烯酸丁酯-苯乙烯)、聚(丙烯酸正丁酯-丙烯酸)、聚丙烯酸乙酯、聚(N-异丙基丙烯酰胺)、聚(丙烯酸乙酯-苯乙烯)、聚(丙烯酸丁酯-甲基丙烯酸)、聚甲基丙烯酸正丁酯、聚(甲基丙烯酸甲酯-丙烯酸丁酯)或聚(乙烯基甲苯-叔丁基苯乙烯-甲基丙烯酸)中的一种。The dry analytical reagent for the detection of the above gamma-glutamyl transpeptidase, the binder includes poly(butyl acrylate-styrene), poly(n-butyl acrylate-acrylic acid), polyethyl acrylate, poly(N -isopropylacrylamide), poly(ethyl acrylate-styrene), poly(butyl acrylate-methacrylic acid), poly-n-butyl methacrylate, poly(methyl methacrylate-butyl acrylate) or One of poly(vinyltoluene-tert-butylstyrene-methacrylic acid).

上述γ-谷氨酰转肽酶检测用干式分析试剂,所述高交联聚甲基丙烯酸甲酯微球每单位平米加入量20-500g,所述粘合剂每单位平米加入量占所述高交联聚甲基丙烯酸甲酯微球每单位平米加入量的1.5-4.5%。The above-mentioned dry analysis reagent for γ-glutamyl transpeptidase detection, the addition amount of the highly cross-linked polymethylmethacrylate microspheres per unit square meter is 20-500g, and the addition amount of the adhesive per unit square meter accounts for 1.5-4.5% of the added amount per unit square meter of the high cross-linked polymethyl methacrylate microspheres.

上述γ-谷氨酰转肽酶检测用干式分析试剂,所述表面活性剂为非离子表面活性剂,包括对辛基苯氧基聚氧乙烯醚、对壬基苯氧基聚氧乙烯醚、聚氧乙烯山梨醇酐单月桂酸酯或辛基葡萄糖苷中的一种。The above-mentioned dry analytical reagent for the detection of γ-glutamyl transpeptidase, the surfactant is a nonionic surfactant, including p-octylphenoxypolyoxyethylene ether, p-nonylphenoxypolyoxyethylene ether , polyoxyethylene sorbitan monolaurate or octyl glucoside.

上述γ-谷氨酰转肽酶检测用干式分析试剂,所述表面活性剂优选为由相互连接的8到15个氧乙烯或氧丙烯基团组成的链结构的非离子表面活性剂。In the above-mentioned dry analytical reagent for detecting γ-glutamyl transpeptidase, the surfactant is preferably a nonionic surfactant with a chain structure consisting of 8 to 15 oxyethylene or oxypropylene groups connected to each other.

上述γ-谷氨酰转肽酶检测用干式分析试剂,所述缓冲液为pH值在7.0至 9.0范围内的pH缓冲液,所述缓冲液中含有三(羟甲基)氨基甲烷(tris)、磷酸盐、硼酸盐、赖氨酸;N、N-双(2-羟乙基)甘氨酸、N-2-羟乙基哌嗪-N'-2- 羟基丙烷-3-磺酸的钠盐或钾盐、N-2-羟乙基哌嗪-N'-3-磺酸的钠盐或钾盐、N-[三 (羟甲基)甲基]-3-氨基丙烷磺酸的钠盐或钾盐以及N-2-羟乙基哌嗪-N'-2-乙烷磺酸的钠盐或钾盐、1,4-哌嗪-二乙磺酸(PIPES)的钠盐或钾盐以及与上述任一化合物结合的酸、碱或盐中的一种。The dry analytical reagent for the detection of the above gamma-glutamyl transpeptidase, the buffer is a pH buffer with a pH value in the range of 7.0 to 9.0, and the buffer contains tris (hydroxymethyl) aminomethane (tris ), phosphate, borate, lysine; N, N-bis(2-hydroxyethyl)glycine, N-2-hydroxyethylpiperazine-N'-2-hydroxypropane-3-sulfonic acid Sodium or potassium salt, sodium or potassium salt of N-2-hydroxyethylpiperazine-N'-3-sulfonic acid, N-[tris(hydroxymethyl)methyl]-3-aminopropanesulfonic acid Sodium or potassium salt and sodium or potassium salt of N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, sodium salt of 1,4-piperazine-diethanesulfonic acid (PIPES) or Potassium salt and one of the acids, bases or salts combined with any of the above compounds.

上述γ-谷氨酰转肽酶检测用干式分析试剂,所述稳定剂为多糖或双糖中的一种或多种;所述水溶性高分子聚合物为明胶、明胶衍生物、琼脂糖、葡聚糖、聚乙烯醇、聚丙烯酰胺、亲水纤维素衍生物中的一种或多种的混合物。The dry analytical reagent for the detection of the above gamma-glutamyl transpeptidase, the stabilizer is one or more of polysaccharides or disaccharides; the water-soluble polymer is gelatin, gelatin derivatives, agarose , dextran, polyvinyl alcohol, polyacrylamide, a mixture of one or more of hydrophilic cellulose derivatives.

上述γ-谷氨酰转肽酶检测用干式分析试剂,所述上支持体、下支持体和中间支持体均为200nm-900nm波长光下的透光率在80%以上的透明塑料基材,包括聚对苯二甲酸乙二醇酯、聚碳酸酯、聚丙烯及聚乙烯中的一种,其厚度为 50-300μm。The dry analytical reagent for the detection of γ-glutamyl transpeptidase above, the upper support, the lower support and the middle support are all transparent plastic substrates with a light transmittance of more than 80% under 200nm-900nm wavelength light , including one of polyethylene terephthalate, polycarbonate, polypropylene and polyethylene, with a thickness of 50-300 μm.

本发明的有益效果是:The beneficial effects of the present invention are:

本发明γ-谷氨酰转肽酶检测用干式分析试剂制备过程中不使用有机溶剂,生产制备过程对环境友好;扩散层选用遇水不溶胀且不渗透的高交联聚甲基丙烯酸甲酯微球,其与极少量的特定粘合剂组合形成高孔隙率结构的扩散层,对含有γ-谷氨酰转肽酶的待分析液体可实现高效快速渗透、扩散,其可在内部均匀分布、扩散和快速传递含有分析物的待检样品;采用水溶性好的L-γ-谷氨酰 -3-羧基-对硝基苯胺做显色底物,测试结果准确度高、测量范围宽,满足即时诊断、现场诊断需求,临床应用价值大。No organic solvent is used in the preparation process of the dry analysis reagent for γ-glutamyl transpeptidase detection of the present invention, and the production and preparation process is environmentally friendly; the diffusion layer is made of highly cross-linked polymethylmethacrylate that does not swell when exposed to water and is impermeable Ester microspheres, which are combined with a very small amount of specific binder to form a high-porosity diffusion layer, can achieve efficient and rapid penetration and diffusion of the liquid to be analyzed containing γ-glutamyl transpeptidase, which can be uniform inside Distribution, diffusion and rapid transfer of the sample containing the analyte; L-γ-glutamyl-3-carboxy-p-nitroaniline with good water solubility is used as the chromogenic substrate, and the test results are highly accurate and the measurement range is wide , to meet the needs of instant diagnosis and on-site diagnosis, and has great clinical application value.

附图说明Description of drawings

图1为本发明多层膜干化学试剂片结构示意图;Fig. 1 is the structural representation of multilayer film dry chemical reagent sheet of the present invention;

图2为实施例1的本发明的方法和利用γ-谷氨酰羧基硝基苯胺对照法的多个检测样本相关性的分析图;Fig. 2 is the method of the present invention of embodiment 1 and utilizes the analytical diagram of the correlation of multiple detection samples of gamma-glutamyl carboxyl nitroaniline control method;

图3为实施例2的本发明的方法和利用γ-谷氨酰羧基硝基苯胺对照法的多个检测样本相关性的分析图;Fig. 3 is the method of the present invention of embodiment 2 and utilizes the analytical diagram of the multiple detection sample correlation of gamma-glutamyl carboxyl nitroaniline control method;

图4为实施例3的本发明的方法和利用γ-谷氨酰羧基硝基苯胺对照法的多个检测样本相关性的分析图。Fig. 4 is an analysis diagram of the correlation between the method of the present invention in Example 3 and the control method using γ-glutamylcarboxynitroaniline for multiple detection samples.

图中:1、上支持层;1-1、加样孔;2、扩散层;3、试剂层;4、支持体;5、下支持层;5-1、测试孔;6、中间支持层。In the figure: 1, upper support layer; 1-1, sample injection hole; 2, diffusion layer; 3, reagent layer; 4, support body; 5, lower support layer; 5-1, test hole; 6, middle support layer .

具体实施方式detailed description

为使本发明实施例的目的、技术方案和优点更加清楚,下面将结合本发明实施例中的附图,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments It is a part of embodiments of the present invention, but not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without creative efforts fall within the protection scope of the present invention.

本发明干式分析试剂能够测定体液试样中的γ-谷氨酰转肽酶。所述体液,可以是血液或尿液等;体液试样可以直接使用血液或者尿,也可以使用进行适当前处理的试样。The dry analytical reagent of the present invention can measure γ-glutamyl transpeptidase in body fluid samples. The body fluid may be blood or urine, etc.; blood or urine may be used directly as a body fluid sample, or a sample that has undergone appropriate pretreatment may be used.

本发明干式分析试剂由上至下依次包括上支持层1、扩散层2、试剂层3、支持体4和下支持层5,所述扩散层、试剂层和支持体由上至下依次设置在所述上支持层和下支持层之间的中间位置,所述上支持层和下支持层的两端孔隙处通过中间支持层6粘结,所述上支持层1和下支持层5中间位置分别设置有加样孔1-1和测试孔5-1,由加样孔向扩散层上滴加待检液体,待检液体通过扩散层迅速四向均匀扩散的同时向试剂层纵向扩散,在试剂层产生生化反应,支持体是起支撑作用、透光载体的结构层,上支持层、下支持层和中间支持层是起到对分布有试剂层和扩散层的支持体固定和保护的作用的内包装结构。The dry analysis reagent of the present invention comprises an upper support layer 1, a diffusion layer 2, a reagent layer 3, a support 4 and a lower support layer 5 from top to bottom, and the diffusion layer, reagent layer and support are arranged in sequence from top to bottom In the middle position between the upper support layer and the lower support layer, the gaps at both ends of the upper support layer and the lower support layer are bonded by the middle support layer 6, and the upper support layer 1 and the lower support layer 5 are in the middle The position is respectively provided with a sampling hole 1-1 and a testing hole 5-1, and the liquid to be tested is dripped onto the diffusion layer from the sampling hole, and the liquid to be tested diffuses rapidly and uniformly in four directions through the diffusion layer and at the same time diffuses longitudinally to the reagent layer. Biochemical reactions occur in the reagent layer. The support is a structural layer that acts as a support and a light-transmitting carrier. The upper support layer, lower support layer and middle support layer are used to fix and protect the support distributed with the reagent layer and diffusion layer. Functional inner packaging structure.

本发明扩散层选用遇水不溶胀且不渗透的高交联聚甲基丙烯酸甲酯微球,与极少量的特定粘合剂组合形成高孔隙率结构的扩散层,粘合剂集中在高交联聚甲基丙烯酸甲酯微球表面与相邻微球相邻区域,将高交联聚甲基丙烯酸甲酯微球粘合成连贯的三维晶格,此三维晶格结构表现出高的空隙体积,控制高交联聚甲基丙烯酸甲酯微球的粒径分布和粘合剂的加入量,从而形成不同的孔隙率和孔径分布的各项均匀多孔扩散层,用于快速吸收、均匀分布、计量和快速传输多种分析物,从而分析生物液体中的不同分子量分布和组成的待检物质。The diffusion layer of the present invention selects highly cross-linked polymethyl methacrylate microspheres that do not swell when exposed to water and are impermeable, and are combined with a very small amount of specific adhesive to form a diffusion layer with a high-porosity structure. The surface of the linked polymethyl methacrylate microspheres and the adjacent area of the adjacent microspheres bond the highly cross-linked polymethyl methacrylate microspheres into a coherent three-dimensional lattice, and this three-dimensional lattice structure exhibits a high void Volume, control the particle size distribution of highly cross-linked polymethyl methacrylate microspheres and the amount of binder added, so as to form various uniform porous diffusion layers with different porosity and pore size distribution for rapid absorption and uniform distribution , metering and rapid delivery of multiple analytes to analyze substances of different molecular weight distributions and compositions in biological fluids.

本发明高交联聚甲基丙烯酸甲酯微球通过悬浮聚合技术制备,为了满足聚合物微球的不溶胀及不渗透要求,需在微球聚合时加入适当的交联剂从而获得高强度交联结构,本发明中的交联剂优选为二乙烯基苯,交联剂加入量优选为甲基丙烯酸甲酯MMA单体质量的5wt%~2wt%;并通过控制反应时间控制高交联聚甲基丙烯酸甲酯微球粒径为5-50μm,每单位平米加入量20-500g,优选每单位平米加入量50-300g,粘合剂每单位平米的加入量占高交联聚甲基丙烯酸甲酯微球加入量的1.5-4.5%,控制扩散层的孔隙率为40-75%,可形成数百纳米至数微米级的大量扩散通路,而γ-谷氨酰转肽酶相对分子质量在90kDa左右,分子尺寸在数十纳米上下,扩散层的扩散通路可允许水、小分子物质和γ- 谷氨酰转肽酶快速分布、计量和传输,并阻止红细胞等大分子物质通过,形成有效的过滤作用。The highly cross-linked polymethyl methacrylate microspheres of the present invention are prepared by suspension polymerization technology. In order to meet the non-swelling and impermeability requirements of the polymer microspheres, it is necessary to add an appropriate cross-linking agent during the polymerization of the microspheres to obtain high-strength cross-linking. linking structure, the crosslinking agent in the present invention is preferably divinylbenzene, and the crosslinking agent addition is preferably 5wt%~2wt% of the monomer quality of methyl methacrylate MMA; The particle size of methyl methacrylate microspheres is 5-50 μm, the amount added per unit square meter is 20-500 g, preferably 50-300 g per unit square meter, and the amount added per unit square meter of adhesive accounts for The amount of methyl ester microspheres added is 1.5-4.5%, and the porosity of the control diffusion layer is 40-75%, which can form a large number of diffusion channels from hundreds of nanometers to several microns, and the relative molecular mass of γ-glutamyl transpeptidase At about 90kDa, the molecular size is tens of nanometers, the diffusion channel of the diffusion layer can allow the rapid distribution, metering and transmission of water, small molecular substances and γ-glutamyl transpeptidase, and prevent the passage of red blood cells and other macromolecular substances to form Effective filtering action.

本发明试剂层中的显色底物选用水溶性良好的L-γ-谷氨酰-3-羧基-对硝基苯胺。现在常用的γ-谷氨酰转肽酶检测试剂盒基本都采用L-γ-谷氨酰-对硝基苯胺作为显色底物,但L-γ-谷氨酰-对硝基苯胺存在水溶性差及显色密度低等缺点,很难达到饱和底物浓度,不能显示L-γ-谷氨酰基转移酶的最大活性。经过筛选,本发明换用水溶性良好的底物L-γ-谷氨酰-3-羧基-对硝基苯胺作为显色底。L-γ-谷氨酰-3-羧基-对硝基苯胺每单位平米的加入量为0.01-1g,优选为每单位平米0.02-0.5g。The chromogenic substrate in the reagent layer of the present invention is selected from L-γ-glutamyl-3-carboxy-p-nitroaniline with good water solubility. The commonly used γ-glutamyl transpeptidase detection kits basically use L-γ-glutamyl-p-nitroaniline as the chromogenic substrate, but L-γ-glutamyl-p-nitroaniline exists in water-soluble Due to the disadvantages of poor performance and low color density, it is difficult to reach a saturated substrate concentration, and cannot show the maximum activity of L-γ-glutamyl transferase. After screening, the present invention replaces the substrate L-γ-glutamyl-3-carboxy-p-nitroaniline with good water solubility as the color development substrate. The amount of L-γ-glutamyl-3-carboxy-p-nitroaniline added per square meter is 0.01-1 g, preferably 0.02-0.5 g per square meter.

试剂层中的表面活性剂每单位平米加入量为1-25g,优选为每单位平米 2-15g;双甘肽每单位平米0.1-10g,优选为每单位平米0.2-5g;稳定剂每单位平米加入量为0.2-10g;水溶性高分子聚合物每单位平米1-50g,优选为每单位平米2-25g。The addition amount of the surfactant in the reagent layer is 1-25g per unit square meter, preferably 2-15g per unit square meter; 0.1-10g per unit square meter of glycylidene, preferably 0.2-5g per unit square meter; stabilizer per unit square meter The addition amount is 0.2-10g; the water-soluble polymer is 1-50g per square meter, preferably 2-25g per square meter.

本发明干式分析试剂的制备方法具体为:The preparation method of the dry analysis reagent of the present invention is specifically:

(1)试剂层试剂液在支持体上涂布,涂布方法可使用已知的方法,优选为丝棒涂布、刮涂、挤压涂布,试剂层湿膜厚度优选为50-500μm,在10℃-60℃范围内干燥,试剂层干膜厚度优选为5-50μm。(1) Reagent layer The reagent solution is coated on the support, and the coating method can use known methods, preferably wire bar coating, knife coating, extrusion coating, and the wet film thickness of the reagent layer is preferably 50-500 μm, Dry in the range of 10°C-60°C, and the dry film thickness of the reagent layer is preferably 5-50 μm.

(2)扩散层浆料在(1)试剂层上涂布,涂布方法可使用已知的方法,优选为丝棒涂布、刮涂、挤压涂布,扩散层湿膜厚度优选为60-600μm,在10℃ -60℃范围内干燥,扩散层干膜厚度优选为20-200μm。(2) The diffusion layer slurry is coated on the (1) reagent layer, and the coating method can use known methods, preferably wire bar coating, blade coating, extrusion coating, and the wet film thickness of the diffusion layer is preferably 60 -600μm, dry in the range of 10℃-60℃, the dry film thickness of the diffusion layer is preferably 20-200μm.

(3)将(2)步骤制备的材料裁剪成1.2cm2的小片,用定制的白色PET塑料片作为上支持层、下支持层和中间支持层,固定、组装成干式分析试剂。(3) Cut the materials prepared in step (2) into small pieces of 1.2 cm 2 , use custom-made white PET plastic sheets as the upper support layer, lower support layer and middle support layer, fix and assemble them into dry analysis reagents.

本发明的γ-谷氨酰转肽酶检测用干式分析试剂检测方法如下:γ-glutamyl transpeptidase detection of the present invention uses the dry analysis reagent detection method as follows:

在各项均性的多孔扩散层上滴加约10μL的待检液体,在约37℃条件下孵育5分钟,待检液体通过扩散层迅速四向均匀扩散的同时向试剂层纵向扩散,形成均一的浓度分布。GGT催化L-γ-谷氨酰-对硝基苯胺的谷氨酸盐部分转移为双甘氨肽,同时生成对硝基苯胺。通过速率法从支持体侧对干式分析试剂产生的变色反应开展反射密度检测,使用预先制成的校正曲线计算出待检液体中 GGT的浓度。目标物质GGT与干式分析试剂内的相应物质反应的方程式如下:Add about 10 μL of the liquid to be tested dropwise on the homogeneous porous diffusion layer, and incubate at about 37°C for 5 minutes. concentration distribution. GGT catalyzes the transfer of the glutamate moiety of L-γ-glutamyl-p-nitroaniline to glycylglycine, and simultaneously produces p-nitroaniline. The reflection density detection of the color change reaction produced by the dry analytical reagent is carried out from the support side by the rate method, and the concentration of GGT in the liquid to be tested is calculated using a pre-made calibration curve. The equation for the reaction of the target substance GGT with the corresponding substance in the dry analysis reagent is as follows:

Figure BDA0003810527420000061
Figure BDA0003810527420000061

本发明的γ-谷氨酰转肽酶检测用干式分析试剂制备过程无需有机溶剂,对环境友好,干式分析试剂稳定性好、易于存放和保管,检测准确度高、线性范围宽。The preparation process of the dry analysis reagent for gamma-glutamyl transpeptidase detection does not require organic solvents, is environmentally friendly, has good stability, is easy to store and keep, and has high detection accuracy and wide linear range.

下面结合实施例对本发明作进一步说明。The present invention will be further described below in conjunction with embodiment.

实施例1Example 1

在无色透明175μm的PET膜支持体4上涂布下表1组成的试剂层涂布液并在40℃恒温干燥,使干燥后的厚度达到15μm。接着,在上述涂层上涂布下表2组成的扩散层涂布液并在35℃恒温干燥,使干燥后的厚度达到100μm。干燥后切成1.2cm2的小片,然后使用白色PET塑料片作为上支持层1、下支持层5和中间支持层6,组装后即可用于测定。On a colorless and transparent PET film support 4 with a thickness of 175 μm, the reagent layer coating liquid composed of the following Table 1 was coated and dried at a constant temperature of 40° C., so that the thickness after drying reached 15 μm. Next, the diffusion layer coating solution with the composition shown in Table 2 below was coated on the above coating layer and dried at a constant temperature of 35° C., so that the thickness after drying was 100 μm. Cut into small pieces of 1.2 cm after drying, and then use white PET plastic sheets as the upper support layer 1, the lower support layer 5 and the middle support layer 6, which can be used for measurement after assembly.

表1试剂层配方Table 1 Reagent Layer Recipe

试剂Reagent 涂布量/m<sup>2</sup>Coating amount/m<sup>2</sup> 明胶gelatin 10g10g 双甘肽Diglycine 1.8g1.8g L-γ-谷氨酰-3-羧基-对硝基苯胺L-γ-glutamyl-3-carboxy-p-nitroaniline 200mg200mg PIPES缓冲液PIPES buffer pH7.7pH7.7 Triton X-100Triton X-100 1.5g1.5g 蔗糖sucrose 1.2g 1.2g

表2扩散层配方Table 2 Diffusion layer formulation

材料Material 涂布量/m<sup>2</sup>Coating amount/m<sup>2</sup> 高交联聚甲基丙烯酸甲酯微球(10μm)Highly cross-linked polymethylmethacrylate microspheres (10μm) 150g150g 聚(丙烯酸正丁酯-丙烯酸)乳液Poly(n-butyl acrylate-acrylic acid) emulsion 3g3g 表面活性剂Surfactant 1.5g 1.5g

针对25个临床血清标本,针对本发明的方法与使用修改的γ谷氨酰羧基硝基苯胺对照法分析多个检测样本的相关性。结果如图2所示,本发明与基准参考方法比较,可以得到良好的相关性。For 25 clinical serum samples, the method of the present invention was used to analyze the correlation of multiple detection samples using the modified γ-glutamylcarboxynitroaniline control method. The results are shown in Fig. 2, and the present invention can obtain a good correlation compared with the benchmark reference method.

实施例2Example 2

在无色透明175μm的PET膜支持体4上涂布下表3组成的试剂层涂布液并在37℃恒温干燥,使干燥后的厚度达到10μm。接着,在上述涂层上涂布下表4组成的扩散层涂布液并在40℃恒温干燥,使干燥后的厚度达到150μm。干燥后切成1.2cm2的小片,然后使用白色PET塑料片作为上支持层1、下支持层5和中间支持层6,组装后即可用于测定。On a colorless and transparent PET film support 4 with a thickness of 175 μm, the reagent layer coating solution composed in Table 3 below was coated and dried at a constant temperature of 37° C., so that the thickness after drying reached 10 μm. Next, the diffusion layer coating liquid with the composition shown in Table 4 below was coated on the above coating layer and dried at a constant temperature of 40° C., so that the thickness after drying was 150 μm. Cut into small pieces of 1.2 cm after drying, and then use white PET plastic sheets as the upper support layer 1, the lower support layer 5 and the middle support layer 6, which can be used for measurement after assembly.

表3试剂层配方Table 3 Reagent Layer Recipe

试剂Reagent 涂布量/m<sup>2</sup>Coating amount/m<sup>2</sup> 明胶gelatin 10g10g 双甘肽Diglycine 3.5g3.5g L-γ-谷氨酰-3-羧基-对硝基苯胺L-γ-glutamyl-3-carboxy-p-nitroaniline 150mg150mg PIPES缓冲液PIPES buffer pH8.0pH8.0 Triton X-100Triton X-100 1.5g1.5g 蔗糖sucrose 2.0g 2.0g

表4扩散层配方Table 4 Diffusion Layer Recipe

材料Material 涂布量/m<sup>2</sup>Coating amount/m<sup>2</sup> 高交联聚甲基丙烯酸甲酯微球(30μm)Highly cross-linked polymethyl methacrylate microspheres (30μm) 100g100g 聚(丙烯酸丁酯-苯乙烯)乳液Poly(butyl acrylate-styrene) emulsion 1.5g1.5g 表面活性剂Surfactant 1g 1g

针对25个临床血清标本,针对本发明的方法与使用修改的γ谷氨酰羧基硝基苯胺对照法分析多个检测样本的相关性。结果如图3所示,本发明与基准参考方法比较,可以得到良好的相关性。For 25 clinical serum samples, the method of the present invention was used to analyze the correlation of multiple detection samples using the modified γ-glutamylcarboxynitroaniline control method. The results are shown in Fig. 3. Compared with the reference method, the present invention can obtain a good correlation.

实施例3Example 3

在无色透明175μm的PET膜支持体4上涂布下表5组成的试剂层涂布液并在40℃恒温干燥,使干燥后的厚度达到20μm。接着,在上述涂层上涂布下表6组成的扩散层涂布液并在45℃恒温干燥,使干燥后的厚度达到100μm。干燥后切成1.2cm2的小片,然后使用白色PET塑料片作为上支持层1、下支持层5和中间支持层6,组装后即可用于测定。On a colorless and transparent PET film support 4 with a thickness of 175 μm, the reagent layer coating liquid composed in Table 5 below was coated and dried at a constant temperature of 40° C., so that the thickness after drying reached 20 μm. Next, the diffusion layer coating solution with the composition shown in Table 6 below was coated on the above coating layer and dried at a constant temperature of 45° C., so that the thickness after drying was 100 μm. Cut into small pieces of 1.2 cm after drying, and then use white PET plastic sheets as the upper support layer 1, the lower support layer 5 and the middle support layer 6, which can be used for measurement after assembly.

表5试剂层配方Table 5 Reagent Layer Recipe

试剂Reagent 涂布量/m<sup>2</sup>Coating amount/m<sup>2</sup> 明胶gelatin 10g10g 双甘肽Diglycine 1.0g1.0g L-γ-谷氨酰-3-羧基-对硝基苯胺L-γ-glutamyl-3-carboxy-p-nitroaniline 100mg100mg Tris缓冲液Tris buffer pH7.8pH7.8 Triton X-100Triton X-100 1.5g1.5g 蔗糖sucrose 0.6g 0.6g

表6扩散层配方Table 6 Diffusion layer formulation

材料Material 涂布量/m<sup>2</sup>Coating amount/m<sup>2</sup> 高交联聚甲基丙烯酸甲酯微球(45μm)Highly cross-linked polymethyl methacrylate microspheres (45μm) 150g150g 聚(丙烯酸丁酯-甲基丙烯酸)乳液Poly(butyl acrylate-methacrylic acid) emulsion 4g4g 表面活性剂Surfactant 2g 2g

针对25个临床血清标本,针对本发明的方法与使用修改的γ谷氨酰羧基硝基苯胺对照法分析多个检测样本的相关性。结果如图4所示,本发明与基准参考方法比较,可以得到良好的相关性。For 25 clinical serum samples, the method of the present invention was used to analyze the correlation of multiple detection samples using the modified γ-glutamylcarboxynitroaniline control method. The results are shown in Fig. 4. Compared with the benchmark reference method, the present invention can obtain good correlation.

上述实施例只是为了说明本发明的技术构思及特点,其目的是在与让本领域内的普通技术人员能够了解本发明的内容并据以事实,并不能以此限制本发明的保护范围。凡是根据本发明内容的实质所作出的等效的替换或改进等,均应包含在本发明的权利要求范围以内。The above-mentioned embodiments are only to illustrate the technical concept and characteristics of the present invention, and its purpose is to enable those of ordinary skill in the art to understand the content of the present invention and based on the facts, and cannot limit the protection scope of the present invention. All equivalent replacements or improvements made according to the essence of the content of the present invention shall be included within the scope of the claims of the present invention.

Claims (9)

1.一种γ-谷氨酰转肽酶检测用干式分析试剂,所述干式分析试剂由上至下依次包括上支持层(1)、扩散层(2)、试剂层(3)、支持体(4)和下支持层(5),所述扩散层、试剂层和支持体由上至下依次设置在所述上支持层和下支持层之间的中间位置,所述上支持层和下支持层的两端孔隙处通过中间支持层(6)粘结,所述上支持层(1)和下支持层(5)中间位置分别设置有加样孔(1-1)和测试孔(5-1),其特征在于:所述扩散层为各向均性的多孔扩散膜,其孔隙率为40-75%;所述扩散层由高交联聚甲基丙烯酸甲酯微球、粘合剂和表面活性剂组成,所述高交联聚甲基丙烯酸甲酯微球的粒径为5-50μm,所述粘合剂集中在高交联聚甲基丙烯酸甲酯微球表面与相邻微球相邻的区域,并将高交联聚甲基丙烯酸甲酯微球粘合成连贯的三维晶格;所述试剂层(3)包括表面活性剂、双甘肽、L-γ-谷氨酰-3-羧基-对硝基苯胺、缓冲液、稳定剂和水溶性高分子聚合物。1. A dry analysis reagent for gamma-glutamyl transpeptidase detection, the dry analysis reagent comprises an upper support layer (1), a diffusion layer (2), a reagent layer (3), A support (4) and a lower support layer (5), the diffusion layer, the reagent layer and the support are sequentially arranged in the middle between the upper support layer and the lower support layer from top to bottom, and the upper support layer and the two ends of the lower support layer are bonded through the middle support layer (6), and the middle positions of the upper support layer (1) and the lower support layer (5) are respectively provided with a sample hole (1-1) and a test hole (5-1), characterized in that: the diffusion layer is an isotropic porous diffusion membrane with a porosity of 40-75%; the diffusion layer is made of highly cross-linked polymethyl methacrylate microspheres, Composed of an adhesive and a surfactant, the particle diameter of the highly cross-linked polymethyl methacrylate microspheres is 5-50 μm, and the adhesive is concentrated on the surface of the highly cross-linked polymethyl methacrylate microspheres and Adjacent areas of adjacent microspheres, and highly cross-linked polymethyl methacrylate microspheres bonded into a coherent three-dimensional lattice; - Glutamyl-3-carboxy-p-nitroaniline, buffer, stabilizer and water-soluble polymer. 2.根据权利要求1所述的γ-谷氨酰转肽酶检测用干式分析试剂,其特征在于:所述高交联聚甲基丙烯酸甲酯微球采用悬浮聚合法制备而成,交联剂选自甲基丙烯酸酯、二甲基丙烯酸乙二醇酯、氨脂、二乙烯基苯以及N,N-亚甲基双丙烯酰胺中的一种或者任意两种以上的组合物,交联剂质量占甲基丙烯酸甲酯MMA单体质量的5wt%~30wt%。2. The dry analytical reagent for γ-glutamyl transpeptidase detection according to claim 1, characterized in that: the highly cross-linked polymethyl methacrylate microspheres are prepared by suspension polymerization, cross-linked The coupling agent is selected from one of methacrylate, ethylene glycol dimethacrylate, urethane, divinylbenzene and N,N-methylenebisacrylamide, or any combination of two or more. The mass of the coupling agent accounts for 5wt%-30wt% of the mass of the methyl methacrylate MMA monomer. 3.根据权利要求2所述的γ-谷氨酰转肽酶检测用干式分析试剂,其特征在于:所述粘合剂包括聚(丙烯酸丁酯-苯乙烯)、聚(丙烯酸正丁酯-丙烯酸)、聚丙烯酸乙酯、聚(N-异丙基丙烯酰胺)、聚(丙烯酸乙酯-苯乙烯)、聚(丙烯酸丁酯-甲基丙烯酸)、聚甲基丙烯酸正丁酯、聚(甲基丙烯酸甲酯-丙烯酸丁酯)或聚(乙烯基甲苯-叔丁基苯乙烯-甲基丙烯酸)中的一种。3. The dry analytical reagent for gamma-glutamyl transpeptidase detection according to claim 2, characterized in that: the adhesive comprises poly(butyl acrylate-styrene), poly(n-butyl acrylate -acrylic acid), polyethyl acrylate, poly(N-isopropylacrylamide), poly(ethyl acrylate-styrene), poly(butyl acrylate-methacrylic acid), poly-n-butyl methacrylate, poly (methyl methacrylate-butyl acrylate) or poly(vinyltoluene-tert-butylstyrene-methacrylic acid). 4.根据权利要求3所述的γ-谷氨酰转肽酶检测用干式分析试剂,其特征在于:所述高交联聚甲基丙烯酸甲酯微球每单位平米加入量20-500g,所述粘合剂每单位平米加入量占所述高交联聚甲基丙烯酸甲酯微球每单位平米加入量的1.5-4.5%。4. The dry analytical reagent for γ-glutamyl transpeptidase detection according to claim 3, characterized in that: the amount of highly cross-linked polymethylmethacrylate microspheres per unit square meter is 20-500g, The added amount per unit square meter of the adhesive accounts for 1.5-4.5% of the added amount per unit square meter of the highly cross-linked polymethyl methacrylate microspheres. 5.根据权利要求4所述的γ-谷氨酰转肽酶检测用干式分析试剂,其特征在于:所述表面活性剂为非离子表面活性剂,包括对辛基苯氧基聚氧乙烯醚、对壬基苯氧基聚氧乙烯醚、聚氧乙烯山梨醇酐单月桂酸酯或辛基葡萄糖苷中的一种。5. The dry analytical reagent for gamma-glutamyl transpeptidase detection according to claim 4, characterized in that: the surfactant is a nonionic surfactant, including p-octylphenoxypolyoxyethylene Ether, p-nonylphenoxy polyoxyethylene ether, polyoxyethylene sorbitan monolaurate or octyl glucoside. 6.根据权利要求5所述的γ-谷氨酰转肽酶检测用干式分析试剂,其特征在于:所述表面活性剂优选为由相互连接的8到15个氧乙烯或氧丙烯基团组成的链结构的非离子表面活性剂。6. The dry analytical reagent for gamma-glutamyl transpeptidase detection according to claim 5, characterized in that: the surfactant is preferably composed of 8 to 15 oxyethylene or oxypropylene groups connected to each other Composed of nonionic surfactants with a chain structure. 7.根据权利要求6所述的γ-谷氨酰转肽酶检测用干式分析试剂,其特征在于:所述缓冲液为pH值在7.0至9.0范围内的pH缓冲液,所述缓冲液中含有三(羟甲基)氨基甲烷(tris)、磷酸盐、硼酸盐、赖氨酸;N、N-双(2-羟乙基)甘氨酸、N-2-羟乙基哌嗪-N'-2-羟基丙烷-3-磺酸的钠盐或钾盐、N-2-羟乙基哌嗪-N'-3-磺酸的钠盐或钾盐、N-[三(羟甲基)甲基]-3-氨基丙烷磺酸的钠盐或钾盐以及N-2-羟乙基哌嗪-N'-2-乙烷磺酸的钠盐或钾盐、1,4-哌嗪-二乙磺酸(PIPES)的钠盐或钾盐以及与上述任一化合物结合的酸、碱或盐中的一种。7. The dry analytical reagent for detecting γ-glutamyl transpeptidase according to claim 6, characterized in that: the buffer is a pH buffer with a pH value in the range of 7.0 to 9.0, and the buffer is Contains tris (hydroxymethyl) aminomethane (tris), phosphate, borate, lysine; N, N-bis (2-hydroxyethyl) glycine, N-2-hydroxyethylpiperazine-N Sodium or potassium salt of '-2-hydroxypropane-3-sulfonic acid, sodium or potassium salt of N-2-hydroxyethylpiperazine-N'-3-sulfonic acid, N-[tri(hydroxymethyl )Methyl]-3-aminopropanesulfonic acid sodium or potassium salt and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid sodium or potassium salt, 1,4-piperazine - Sodium or potassium salt of diethanesulfonic acid (PIPES) and one of the acids, bases or salts in combination with any of the above compounds. 8.根据权利要求7所述的γ-谷氨酰转肽酶检测用干式分析试剂,其特征在于:所述稳定剂为多糖或双糖中的一种或多种;所述水溶性高分子聚合物为明胶、明胶衍生物、琼脂糖、葡聚糖、聚乙烯醇、聚丙烯酰胺、亲水纤维素衍生物中的一种或多种的混合物。8. The dry analytical reagent for γ-glutamyl transpeptidase detection according to claim 7, characterized in that: the stabilizer is one or more of polysaccharides or disaccharides; the water-soluble high The molecular polymer is one or more mixtures of gelatin, gelatin derivatives, agarose, dextran, polyvinyl alcohol, polyacrylamide and hydrophilic cellulose derivatives. 9.根据权利要求8所述的γ-谷氨酰转肽酶检测用干式分析试剂,其特征在于:所述上支持体(1)、下支持体(5)和中间支持体(6)均为200nm-900nm波长光下的透光率在80%以上的透明塑料基材,包括聚对苯二甲酸乙二醇酯、聚碳酸酯、聚丙烯及聚乙烯中的一种,其厚度为50-300μm。9. The dry analytical reagent for γ-glutamyl transpeptidase detection according to claim 8, characterized in that: the upper support (1), the lower support (5) and the middle support (6) Both are transparent plastic substrates with a light transmittance of more than 80% under 200nm-900nm wavelength light, including one of polyethylene terephthalate, polycarbonate, polypropylene and polyethylene, and its thickness is 50-300μm.
CN202211010894.3A 2022-08-23 2022-08-23 Dry analytical reagent for gamma-glutamyl transpeptidase detection Pending CN115436617A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102253229A (en) * 2011-06-15 2011-11-23 钱辉 High-flux dry biochemical chip
CN109916896A (en) * 2019-04-12 2019-06-21 吉林省汇酉生物技术股份有限公司 A kind of dry chemistry reagent piece of quantitative detection content of hemoglobin and preparation method thereof
CN114002422A (en) * 2021-10-15 2022-02-01 乐凯医疗科技有限公司 Multilayer film dry chemical reagent sheet for biochemical analysis

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102253229A (en) * 2011-06-15 2011-11-23 钱辉 High-flux dry biochemical chip
CN109916896A (en) * 2019-04-12 2019-06-21 吉林省汇酉生物技术股份有限公司 A kind of dry chemistry reagent piece of quantitative detection content of hemoglobin and preparation method thereof
CN114002422A (en) * 2021-10-15 2022-02-01 乐凯医疗科技有限公司 Multilayer film dry chemical reagent sheet for biochemical analysis

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