CN108362889A - 一种poct荧光免疫层析定量试剂盒及其应用 - Google Patents
一种poct荧光免疫层析定量试剂盒及其应用 Download PDFInfo
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Abstract
本发明涉及一种POCT荧光免疫层析定量试纸条及试剂盒，所述试纸条包括底板、加样区、样本垫、结合垫和吸水垫，所述结合垫与吸水垫之间为硝酸纤维素膜，所述结合垫上喷涂有荧光微球标记抗体，其特征在于，所述硝酸纤维素膜上包被有待检测蛋白抗体、抗β‑Actin蛋白单克隆抗体和羊抗兔多克隆抗体。本发明以在细胞中恒定表达的β‑Actin蛋白的浓度作为内部参照，以消除取样样本中细胞个数对裂解液中相应蛋白浓度的影响，从而提高检测结果的准确性。
Description
技术领域
本发明属于癌症诊断技术领域，尤其涉及一种POCT荧光免疫层析定量试剂盒、特别是联合定量检测HPV16/18型E6蛋白的POCT荧光免疫层析定量试剂盒及其应用。
背景技术
荧光免疫层析技术结合了荧光免疫技术和免疫层析技术这两种先进技术，它是以免疫标记技术为基础的，免疫标记技术是指将已知的抗体或抗原标记上某种物质，通过检测标记物来反映抗原的情况，从而能够间接的检测出被测抗原或抗体的含量。荧光免疫层析技术支持全血、血清、血浆、尿液、细胞等样本的检测，在心内科、检验科、急诊科、ICU、肿瘤科、肾内科、儿科、内分泌科、妇科、老年科、呼吸科、胸外科、消化科、泌尿科等科室取得了广泛应用。研究表明，一些癌症的病发与体内存在的病毒密切相关，例如，人类乳头瘤病毒与咽喉癌、阴道癌、外阴癌、宫颈癌、肛门癌等相关；人类疱疹病毒4型与伯基特淋巴瘤、霍奇金淋巴瘤、鼻咽癌等相关；丙肝病毒与肝癌相关；艾滋病病毒与卡波西肉瘤相关；人类嗜T淋巴细胞病毒1型与白血病相关，因此，检测人体血液、组织或细胞中这些病毒本身、它们的基因和代谢物等浓度是筛查和诊断相关癌症的重要手段。
全球妇女恶性肿瘤中宫颈癌发病率仅次于乳腺癌，是居于第二位的恶性肿瘤，在中国女性恶性肿瘤中发病率居第一位。在全球范围内，每年新增宫颈癌病例约50万，我国每年新发病例为13.2万，占全球宫颈癌的28.8%，每年全球约有20万女性死于宫颈癌。HPV（人乳头瘤病毒，Human Papillomavirus）持续感染是宫颈癌及其癌前病变发生的必要条件，99.7%的宫颈癌发生与高危人乳头瘤病毒感染相关，HPV有超过100种不同的分离株，在引起宫颈癌及其癌前病变的高危型人乳头瘤病毒有13种，如HPV16、18、31、33、35、39、45、51、52、56、58等，其中高危型人乳头瘤病毒16型占55%以上，高危型人乳头瘤病毒18型占18%以上，所以研究HPV16和HPV18型对宫颈癌筛查和早期诊断具有代表性。
HPV是一种嗜上皮性病毒，共有3个基因区组成，包括早期转录区（Early Region E区）、晚期转录区（Late Region A区）与非转录区 (Uncoding Region,UCR）。早期转录区又称E区，由4500个碱基对组成，分别编码E1、E2、E3、E4、E5、E6、E7、E8共8个早期蛋白，具有参与病毒DNA复制、转录、翻译调控和细胞转化等功能。其中E6和E7是HPV的主要致癌基因，与病毒细胞转化功能及致癌性有关。高危型人乳头瘤病毒E6蛋白通过E6关联蛋白与P53结合从而影响细胞周期，HPV E6蛋白经过泛素蛋白连接酶系统降解p53，同时E6蛋白可提高端粒酶逆转录酶 mRNA 的水平，激活端粒酶，抑制细胞凋亡，使细胞无限增殖，最终导致宫颈上皮细胞发生恶性转化。因此，通过检测宫颈上皮脱落细胞中HPV16/18型E6蛋白含量可以对宫颈癌以及其癌前病变进行筛查和早期诊断。
高危型人乳头瘤病毒（HPV）16和18型持续感染己被确认为导致宫颈癌的首要因素，但90%以上的HPV感染是一过性的，在2年内会被免疫系统清除。当高危型HPV病毒发生持续性感染后，特别是HPV16/18型的DNA和人类宫颈上皮细胞的DNA发生整合后，E6基因会大量表达，从而大量产生E6癌蛋白，使宫颈上皮细胞逐渐发生癌变。
目前HPV感染的检测方法有3类：
1.传统的形态学方法检测HPV
包括巴氏涂片细胞病理学检测、阴道镜检查、宫颈活检组织病理学检查等。宫颈细胞形态学筛查特异性高，但是灵敏度较低，同时费用较高。且细胞出现明显病变前已经存在高危型HPV持续感染，所以必须结合其他方法。
2.HPV DNA的检测
以上已经提到高危型HPV的持续感染是宫颈癌的首要因素，在细胞学筛查正常时，HPVDNA的检测很重要。目前应用最多的是PCR，其次是杂交捕获技术。PCR检测HPV灵敏度高，可以同时检测多个亚型，但假阳性率高，特异性较低，且费用昂贵，对设备、人员及实验室有很高要求：杂交捕获技术灵敏度高，特异性好，但对专业设备、专业人才及实验室条件要求也较高，目前不能大范围推广，使之受到限制。
3.血清学方法和免疫学方法
主要是检测患者血清中的L1抗体或是用抗体检测抗原。但L1抗体在HPV清除后几个月到1年后都有较高的效价，所以血清中的L1抗体的检测并不能区分HPV持续性感染和既往感染。用ELISA法检测血清中的HPV E6特异性抗体，目前在HPV16阳性的口腔癌患者血清中可以检测E6特异性抗体，在其它HPV相关癌症中还没有研究过。用抗体检测抗原的方法主要指免疫组化，因为该方法需要的时间很长，操作繁琐，不能定量检测且对操作技术人员要求很高。所以血清学和免疫学方法检测的应用受到很大的限制。
为了应对以上检测方法在宫颈癌及癌前病变筛查诊断中存在的弊端，中国专利201611107990.4公开了一种HPV16型E7蛋白的POCT荧光定量检测试剂盒及其应用，所述试剂盒主要包含包被有HPV16型E7抗体的免疫层析试纸条，实现了对人体宫颈脱落细胞裂解液中HPV16型E7蛋白的定量检测。然而，人体宫颈脱落细胞样本的采集不同于血液、尿液等均相样本，由于采集操作手法的问题，采集的样本中细胞个数等参数难以定量控制，因而在样本人体宫颈脱落细胞裂解后获得的裂解液中HPV16型E7蛋白浓度并不能准确反映出单位组织或细胞中HPV16型E7蛋白的实际浓度，也就是说，当采集的样本中细胞数量过多或过少，会影响裂解液中HPV16型E7蛋白的浓度，进而造成宫颈癌及癌前病变筛查诊断结果不够准确。另一方面，上述文献所公开的POCT荧光定量检测试剂盒仅仅针对单一指标（HPV16型E7蛋白的浓度）进行检测，而高危型HPV16和18型持续感染是导致宫颈癌的首要因素，仅仅检测HPV16型E7蛋白会漏诊部分HPV18感染导致的宫颈癌患者。
发明内容
为了克服现有检测方法的不足，本发明提供了一种POCT荧光免疫层析定量试剂盒，创新性地在试纸条上添加了抗β-Actin蛋白抗体，以在细胞中恒定表达的β-Actin蛋白的浓度作为内部参照，以消除取样样本中细胞个数对裂解液中相应蛋白浓度的影响，从而提高检测结果的准确性。更具体地，本发明还提供了一种联合定量检测HPV16/18型E6蛋白的POCT荧光免疫层析定量试剂盒，所述试剂盒能够针对HPV的两种表达蛋白（HPV16型E6蛋白和HPV18型E6蛋白）同时进行检测，其准确性远高于单一指标的指示结果。
具体地，本发明提供了以下技术方案：
一种POCT荧光免疫层析试纸条，包括底板、加样区、样本垫、结合垫和吸水垫，所述结合垫与吸水垫之间为硝酸纤维素膜，所述结合垫上喷涂有荧光微球标记抗体，其特征在于，所述硝酸纤维素膜上包被有待检测蛋白抗体、抗β-Actin蛋白单克隆抗体和羊抗兔多克隆抗体。
其中，所述待检测蛋白抗体为抗HPV16型E6蛋白单克隆抗体、和/或抗HPV18型E6蛋白单克隆抗体。
所述荧光微球标记抗体分别为荧光微球标记的抗HPV16型E6蛋白单克隆抗体、荧光微球标记的抗HPV18型E6蛋白单克隆抗体、荧光微球标记的抗β-Actin蛋白单克隆抗体和荧光微球标记的羊抗兔IgG。
优选地，所述抗β-Actin蛋白单克隆抗体为鼠源抗β-Actin蛋白单克隆抗体，所述β-Actin蛋白的氨基酸序列为SEQ ID No.1：
MDDDIAALVV DNGSGMCKAG FAGDDAPRAV FPSIVGRPRH QGVMVGMGQKDSYVGDEAQSKRGILTLKYP IEHGIVTNWD DMEKIWHHTF YNELRVAPEE HPVLLTEAPLNPKANREKMTQIMFETFNTP AMYVAIQAVL SLYASGRTTG IVMDSGDGVT HTVPIYEGYALPHAILRLDLAGRDLTDYLM KILTERGYSF TTTAEREIVR DIKEKLCYVA LDFEQEMATA ASSSSLEKSYELPDGQVITI GNERFRCPEA LFQPSFLGME SCGIHETTFN SIMKCDVDIR KDLYANTVLSGGTTMYPGIADRMQKEITAL APSTMKIKII APPERKYSVW IGGSILASLS TFQQMWISKQ EYDESGPSIV HRKCF。
所述HPV16型E6蛋白的氨基酸序列为SEQ ID NO.2：
MHQKRTAMFQDPQERPRKLPQLCTELQTTIHDIILECVYCKQQLLRREVYDFAFRDLCIVYRDGNPYAVCDKCLKFYSKISEYRHYCYSLYGTTLEQQYNKPLCDLLIRCINCQKPLCPEEKQRHLDKKQRFHNIRGRWTGRCMSCCRSSRTRRETQL。
其中，所述抗HPV16型E6蛋白单克隆抗体与HPV16型E6蛋白结合位点分别是：
1号抗体结合位点：HPV16型E6蛋白第34-48氨基酸；
2号抗体结合位点：HPV16型E6蛋白第62-76氨基酸；
3号抗体结合位点：HPV16型E6蛋白第116-129氨基酸；
4号抗体结合位点：HPV16型E6蛋白第129-143氨基酸。
所述HPV18型E6蛋白的氨基酸序列为SEQ ID NO.3：
MARFEDPTRRPYKLPDLCTELNTSLQDIEITCVYCKTVLELTEVFEFAFKDLFVVYRDSIPHAACHKCIDFYSRIRELRHYSDSVYGDTLEKLTNTGLYNLLIRCLRCQKPLNPAEKLRHLNEKRRFHNIAGHYRGQCHSCCNRARQERLQRRRETQV
其中，所述抗HPV18型E6蛋白单克隆抗体与HPV18型E6蛋白结合位点分别是：
1号抗体结合位点：HPV18型E6蛋白第3-14氨基酸；
2号抗体结合位点：HPV18型E6蛋白第67-81氨基酸；
3号抗体结合位点：HPV18型E6蛋白第113-122氨基酸；
4号抗体结合位点：HPV18型E6蛋白第126-138氨基酸。
优选地，所述硝酸纤维素膜上抗体的包被量为0.05～1.0µg，结合垫上荧光微球标记抗体的标记量为0.05～1.0µg。
所述POCT荧光免疫层析试纸条的制备方法，包括以下步骤：采用Gold Bio三维点膜喷金仪，将待检测蛋白抗体、抗β-Actin蛋白单克隆抗体及羊抗兔多克隆抗体包被在硝酸纤维素膜上，分别作为检测线（T线）、内参线（A线）和质控线（C线），在37 ℃干燥箱中干燥2h；同时分别将偶联有荧光微球的待检测蛋白抗体、抗β-Actin蛋白单克隆抗体及羊抗兔IgG分别喷涂在结合垫上，在37℃下真空干燥2h；再将硝酸纤维素膜、结合垫、样品垫、吸水垫及PVC粘性底板组装好后，切割成试纸条，加干燥剂于2-8℃下密封保存。
其中，所述待检测蛋白抗体为抗HPV16型E6蛋白单克隆抗体、和/或抗HPV18型E6蛋白单克隆抗体。
包含上述POCT荧光免疫层析试纸条的试剂盒，进一步地，所述试剂盒还包含细胞裂解液。
具体地，所述细胞裂解液包含0.05%～2%（体积百分比）的表面活性剂、5mM ～1M缓冲液和0.5mM～10mM蛋白酶抑制剂。
优选地，所述表面活性剂为Tween 20、Tween 80、Triton 100或十二烷基苯磺酸钠中的一种或两种以上；所述缓冲液为phosphate buffered saline、Tris-HCL或硼酸盐溶液；所述蛋白酶抑制剂为PMSF、AEBSF、EDTA或Antipain中的一种或两种以上。
所述细胞裂解液的制备方法，包括以下步骤：以体积百分比计，将0.05%～2%的表面活性剂加入5mM～1M缓冲液中，使用之前加入终浓度为0.5mM～10mM的蛋白酶抑制剂。优选地，用100mM的Tris-HCL溶液配制1%的Triton-100，使用之前加入终浓度为1mM的蛋白酶抑制剂PMSF。
本发明的POCT荧光免疫层析试纸条的试剂盒还包含待检测蛋白校准品和质控品。
所述校准品和质控品均为冻干粉。
本发明的POCT荧光免疫层析定量试剂盒在使用前，首先用待检测蛋白校准品配制一系列线性浓度的校准品溶液，使用β-Actin蛋白校准品配制一系列线性浓度的校准品溶液，使用所述试剂盒中的试纸条进行层析，采用自动监测仪读取荧光强度。分别以校准品溶液浓度作为横坐标，分别以T线、A线与C线的荧光强度的比值作为纵坐标，采用拟合法得到标准曲线。
检测时，首先将1ml细胞裂解液加入样本采集管中，涡旋振荡，置于冰箱-20℃10min，之后置于37℃烘箱中烘烤2min，再次震荡，离心处理，收集上清液；将试剂盒中的荧光免疫层析试纸条在室温中恢复15min，于加样区加样，置于荧光检测仪孵育仓，10min后，仪器自动检测并读取T线、A线与C线的荧光强度。根据实际测得的A/C值与浓度-A/C标准曲线，得到样品中β-Actin蛋白浓度，再与标准取样时样本中β-Actin蛋白浓度对比，获得修正系数，再用实际测得的T/C荧光强度乘以修正系数，获得修正后的T/C值，再通过浓度-T/C标准曲线得到待检测蛋白的实际浓度，以校正细胞取样的误差，提高检测结果的准确性。
特别地，将本发明的POCT荧光免疫层析定量试剂盒用于宫颈癌及癌前病变筛查诊断中时，选择宫颈上皮脱落细胞作为样本，直接针对其中的高危型HPV16/18型E6蛋白的表达与否及表达量进行定性定量测定，当HPV16/18型E6蛋白含量<10ng/ml时，则为阴性，当HPV16/18型E6蛋白含量＞10ng/ml，则为阳性。
本发明的技术方案具有如下有益效果：
本发明在常规荧光免疫层析试纸条的基础上增加了一条内参A线，选择细胞内恒定表达的管家蛋白β-Actin蛋白作为内部参照，通过内参A线的荧光强度来衡量样本中细胞的取样量，用以校正样本细胞取样误差，使检测结果不受取样误差的影响，提高检测结果的准确性。
本发明的POCT荧光免疫层析定量试剂盒可用于宫颈癌及癌前病变的筛查诊断，HPV16/18型E6蛋白浓度不仅直接明确反映患者高危型HPV感染状况，而且与宫颈癌前病变分期及癌变结合起来，市场定位于HPV基因筛查与宫颈涂片之间的空白市场，HPV基因筛查虽可确定HPV病毒携带，但其中约90 %为一过性的，不会导致宫颈癌，只有约10 %才会逐步导致宫颈癌，本发明的试剂盒在保证较低的假阴性的基础上，更高的阳性检出率是很有意义的。
宫颈癌筛查的最佳策略是实现益处最大化和危害最小化，我们既要追求它的“益”，尽早发现那些可能发展为癌症的宫颈癌前病变，做到“早发现，早诊断，早治疗”。同时也要减少它的“害”，避免对一过性HPV病毒感染导致的良性病变的检测和过度治疗，给病人和社会增加负担。相比传统的HPV DNA检测，HPV16/18型E6蛋白与宫颈癌的发生发展关系更为密切，可以避免一过性HPV病毒感染导致假阳性，从而减少受检妇女不必要的检查治疗和不必要的经济负担和心理压力。本发明提供的联合检测HPV16/18型E6蛋白的POCT荧光免疫层析定量检测试剂盒，使得对高危型HPV检测结果愈加直接准确，能早期发现宫颈上皮细胞癌前病变和癌变并与病变分期结合起来，使得治疗方案愈加明确，有助于减轻患者经济压力和社会负担，有助于患者早日康复。同时该方法操作简单快速，检测成本低，对实验室实验设备及操作人员要求较低，可作为宫颈癌筛查的首选方法。
附图说明
图1为本发明实施例中制备的POCT荧光免疫层析定量检测试纸条在测定样本宫颈上皮脱落细胞裂解液中HPV16/18型 E6蛋白含量时的荧光照片，
其中，
1：HPV16/18型E6蛋白均为阴性；
2：HPV16型E6蛋白为阳性；
3：HPV18型E6蛋白为阳性；
4：HPV16/18型E6蛋白均为阳性；
5：试纸条失效，需重新检测；
6：取样失败，需重新取样。
图2为本发明实施例中以β-Actin蛋白校准品浓度为横坐标，以A线/C线荧光强度比值为纵坐标，采用拟合法得到的标准曲线。
图3为本发明实施例中以HPV16型E6蛋白校准品浓度为横坐标，以T1线/C线荧光强度比值为纵坐标，采用拟合法得到的标准曲线。
图4为本发明实施例中以HPV18型E6蛋白校准品浓度为横坐标，以T2线/C线荧光强度比值为纵坐标，采用拟合法得到的标准曲线。
具体实施方式
下面结合具体实施例对本发明进行进一步说明。通过参考示范性实施例，本发明的目的和功能以及用于实现这些目的和功能的方法将得以阐明。然而，本发明并不受限于以下所公开的示范性实施例：可以通过不同形式来对其加以实现。说明书的实质仅仅是帮助相关领域技术人员综合理解本发明的具体细节。
实施例1：包被HPV16型E6抗体和HPV18型E6抗体的免疫层析试纸条的制备
采用如下方法进行制备：
采用Gold Bio三维点膜喷金仪，将HPV16型E6抗体、HPV18型E6抗体、鼠源抗β-Actin蛋白单克隆抗体及羊抗兔多克隆抗体包被在硝酸纤维素膜（NC膜）上，分别作为两条检测线(T1线、T2线）、内参线（A线）和质控线(C线），在37 ℃干燥箱中干燥2h；同时，分别将偶联有荧光微球的HPV16型E6抗体、HPV18型E6抗体、抗β-Actin蛋白单克隆抗体及羊抗兔IgG分别喷涂在结合垫上，在37℃下真空干燥2h；将NC膜、结合垫、样品垫、吸水垫及PVC粘性底板组装好后，切割成试纸条，加干燥剂于2-8℃密封保存。
实施例2：配制人体宫颈脱落细胞裂解液
用100mM Tris-HCL溶液配制1% Triton100，使用之前加入终浓度为 1mM的蛋白酶抑制剂PMSF。
实施例3：联合检测HPV16/18型E6蛋白的POCT荧光免疫层析定量检测试剂盒的制备
所述试剂盒包含：
①实施例1制备的包被有HPV16型E6抗体、HPV18型E6抗体、抗β-Actin蛋白单克隆抗体及羊抗兔多克隆抗体的免疫层析试纸条。
②HPV16型E6蛋白校准品0、1、2、3、4、5、6、7、8：校准品为冻干粉，分别加入 1mlddH20 溶解，校准品溶液的线性浓度分别为 0、1、2、5、20、40、80、160、200ng/ml；
HPV18型E6蛋白校准品0、1、2、3、4、5、6、7、8：校准品为冻干粉，分别加入 1ml ddH20 溶解，校准品溶液的线性浓度分别为0、1、2、5、20、40、80、160、200ng/ml；
β-Actin蛋白校准品0、1、2、3、4、5、6、7：校准品为冻干粉，分别加入 1ml ddH20 溶解，校准品溶液的线性浓度分别为 0、0.1、0.2、0.5、1.5、2.5、5.0ug/ml。
③HPV16型E6蛋白质控品1、2：质控品为冻干粉，加入 1ml ddH20溶解、浓度分别为10和80ng/ml；
HPV18型E6蛋白质控品1、2：质控品为冻干粉，加入1mlddH20溶解、浓度分别为10和80ng/ml；
β-Actin蛋白质控品1、2：质控品为冻干粉，加入1ml ddH20溶解、浓度分别为0.2和1.5ug/ml。
④实施例2制备的人体宫颈脱落细胞裂解液。
分别采用HPV16型E6蛋白质控品、HPV18型E6蛋白质控品和β-Actin蛋白质控品对试剂盒中的试纸条定性检测的准确性进行评价，结果如下表1所示。
表1
由图1和表1可见，本发明的POCT荧光免疫层析定量试剂盒能够实现对HPV16/18型E6蛋白的定性、定量检测，检测误差在可接受的范围内。
实施例4：样本检测
样本处理：取出试剂盒中的人体宫颈脱落细胞裂解液，将1ml裂解液加入宫颈脱落细胞收集管中，涡旋震荡2min，置于20 ℃冰箱10min，之后置于 37 ℃烘箱2min，再次震荡，离心（20min , 13000rpm , 4℃），收集上清，作为裂解人体宫颈脱落细胞样本；
免疫层析试纸条准备：取出实施例3的试剂盒中的荧光免疫层析试纸条，室温放置15min恢复温度；
标准曲线绘制：首先用待检测蛋白校准品配制一系列线性浓度的校准品溶液，使用β-Actin蛋白校准品配制一系列线性浓度的校准品溶液，使用所述试剂盒中的试纸条进行层析，采用自动监测仪读取荧光强度，结果如表2-表4所示：
表2
表3
表4
| β-Actin蛋白浓度（ug/ml） | 0 | 0.1 | 0.2 | 0.5 | 1.5 | 2.5 | 5 |
| T1线荧光强度 | 28 | 101 | 909 | 2822 | 7752 | 12602 | 21032 |
| C线荧光强度 | 10021 | 10168 | 10098 | 10079 | 9938 | 10082 | 9874 |
分别以校准品溶液浓度作为横坐标，分别以T1线、T2线、A线与C线的荧光强度的比值作为纵坐标，采用最小二乘拟合法得到标准曲线，分别如图2-4所示；
样本检测：将准备好的裂解人体宫颈脱落细胞样本于加样区加样，置于荧光检测仪孵育仓，10min后，仪器自动检测并读取T1线、T2线、A线与C线的荧光强度；
计算：根据实际测得的A/C值与浓度-A/C标准曲线，得到样品中β-Actin蛋白浓度，再与标准取样时样本中β-Actin蛋白浓度（2ug/ml，以此浓度为标准）对比，获得修正系数，再用实际测得的T1/C、T2/C荧光强度比值乘以修正系数，获得修正后的T1/C、T2/C值，再通过浓度-T1/C、浓度-T2/C标准曲线得到HPV16型E6蛋白的实际浓度为56.2ng/mL、HPV18型E6蛋白的实际浓度为34.8ng/mL，结果均高于10ng/mL，诊断为宫颈癌高危型，需积极治疗。
采用经临床病理确诊的宫颈癌样本46份、癌前病变CIN III样本38份及健康样本52份，对本发明建立的联合检测HPV16/18型E6蛋白荧光免疫层析试剂盒的检测结果进行验证，结果显示，本发明的联合检测HPV16/18型E6蛋白荧光免疫层析定量试剂盒检测宫颈癌和癌前病变CIN III的敏感性分别为91.3%、84.2%，特异性达到100%。
以上仅描述了本发明的较佳实施方式，但本发明并不限于上述实施例。本领域技术人员可以理解的是，能够实现本发明技术效果的任何相同或相似手段，均应落入本发明的保护范围内。
序列表
<110> 河南省生物工程技术研究中心有限公司
河南省生物工程技术研究中心
<120> 一种POCT荧光免疫层析定量试剂盒及其应用
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Claims (10)
1.一种POCT荧光免疫层析试纸条，包括底板、加样区、样本垫、结合垫和吸水垫，所述结合垫与吸水垫之间为硝酸纤维素膜，所述结合垫上喷涂有荧光微球标记抗体，其特征在于，所述硝酸纤维素膜上包被有待检测蛋白抗体、抗β-Actin蛋白单克隆抗体和羊抗兔多克隆抗体。
2.根据权利要求1所述的POCT荧光免疫层析试纸条，其中，所述待检测蛋白抗体为抗HPV16型E6蛋白单克隆抗体、和/或抗HPV18型E6蛋白单克隆抗体。
3.根据权利要求1所述的POCT荧光免疫层析试纸条，其中，所述荧光微球标记抗体分别为荧光微球标记的抗HPV16型E6蛋白单克隆抗体、荧光微球标记的抗HPV18型E6蛋白单克隆抗体、荧光微球标记的抗β-Actin蛋白单克隆抗体和荧光微球标记的羊抗兔IgG。
4.根据权利要求1所述的POCT荧光免疫层析试纸条，其中，所述硝酸纤维素膜上抗体的包被量为0.05～1.0µg，结合垫上荧光微球标记抗体的标记量为0.05～1.0µg。
5.权利要求1-4中任一项所述的POCT荧光免疫层析试纸条的制备方法，包括以下步骤：采用Gold Bio三维点膜喷金仪，将待检测蛋白抗体、抗β-Actin蛋白单克隆抗体及羊抗兔多克隆抗体包被在硝酸纤维素膜上，分别作为检测线（T线）、内参线（A线）和质控线（C线），在37 ℃干燥箱中干燥2h；同时分别将偶联有荧光微球的待检测蛋白抗体、抗β-Actin蛋白单克隆抗体及羊抗兔IgG分别喷涂在结合垫上，在37℃下真空干燥2h；再将硝酸纤维素膜、结合垫、样品垫、吸水垫及PVC粘性底板组装好后，切割成试纸条，加干燥剂于2-8℃下密封保存。
6.包含权利要求1-4中任一项所述的POCT荧光免疫层析试纸条的试剂盒，所述试剂盒还包含细胞裂解液。
7.根据权利要求6所述的试剂盒，其中，所述细胞裂解液包含体积百分比为0.05%～2%的表面活性剂、5mM ～1M缓冲液和0.5mM～10mM蛋白酶抑制剂。
8.根据权利要求7所述的试剂盒，其中，所述表面活性剂为Tween 20、Tween 80、Triton100或十二烷基苯磺酸钠中的一种或两种以上；所述缓冲液为phosphate bufferedsaline、Tris-HCL或硼酸盐溶液；所述蛋白酶抑制剂为PMSF、AEBSF、EDTA或Antipain中的一种或两种以上。
9.根据权利要求7所述的试剂盒，其中，所述细胞裂解液的制备方法包括以下步骤：以体积百分比计，将0.05%～2%的表面活性剂加入5mM～1M缓冲液中，使用之前加入终浓度为0.5mM～10mM的蛋白酶抑制剂。
10.根据权利要求6所述的试剂盒，所述试剂盒还包含待检测蛋白校准品和质控品。
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