CN1158998A - 对血球比率低敏感性的血糖试纸 - Google Patents
对血球比率低敏感性的血糖试纸 Download PDFInfo
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- CN1158998A CN1158998A CN96119240A CN96119240A CN1158998A CN 1158998 A CN1158998 A CN 1158998A CN 96119240 A CN96119240 A CN 96119240A CN 96119240 A CN96119240 A CN 96119240A CN 1158998 A CN1158998 A CN 1158998A
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Abstract
一种用于测定全血中葡萄糖浓度的试纸，测定时血球比率的干扰已被减弱。当生物液体接触到试纸时，它引起已浸渍到试纸上的试剂变色，从而测定液体中的葡萄糖浓度。但是，颜色的改变会受到红细胞浓度(血球比率)的影响，由此会降低葡萄糖测定的准确度。血球比率的影响可通过添加一种丙烯酸聚合物的方法来排除。
Description
本发明涉及一种测量全血样品中葡萄糖浓度的干相试纸；更确切地说，是一种对血样的血球比率相对不敏感的试纸。
目前在临床实验室、医生诊室、医院和家庭中广泛使用含有以酶为主的组合物的干相试纸测定生物液体样品的葡萄糖浓度。实际上，这种试纸已成为全球几百万糖尿病患者中多数人的每日必需品。因为糖尿病会引起血液化学中危险的异常变化，所以它会导致视力下降、肾衰竭以及其他严重的医学后果。为了把这些后果的危险性降到最低，多数糖尿病患者必须自已定期进行测试，然后再相应地通过例如控制饮食和/或注射胰岛素来调节自身的葡萄糖浓度。有些患者必须一天四次或多次经常性地测试其血糖浓度。
对那些为调整糖的摄取和/或胰岛素注射液的使用而必须控制饮食的糖尿病患者，以及在这方面必须通过频繁地检测血糖浓度来作为指导的那些糖尿病患者来说需要一种快速、廉价和精确的葡萄糖检测试纸。
含有指示剂的试纸是公知的，它能根据点到试纸上血样的葡萄糖浓度的不同而转变为不同深浅的颜色。这类试纸中的一些包括一种能够将葡萄糖氧化为葡糖酸内酯和过氧化氢的酶，如葡糖氧化酶。它们也含有一种可氧化的染料和一种具有过氧化活性的物质，其中的过氧化活性物质能在过氧化氢存在下有选择性地催化可氧化染料的氧化(参见，如1990年6月19日公布的Phillips等的美国专利4,935,346)。
无论是在家中、医生诊室中、临床或医院中进行葡萄糖测定，它的精确性和可重视性都十分重要，对颜色显示的试纸来说，理想地是颜色变化显著并且对血液中葡萄糖之外的其他化合物的变化不敏感。对可读试纸来说，视力可能已受到损害的糖尿病患者有一种能够根据葡萄糖浓度的不同显示出显著的颜色变化的检测试剂是更为重要的。在给定波长处具有吸收和/或反射的变化的颜色改变对读数试纸的精确性也是很重要的。
各种干扰因素的存在会影响试纸的性能，有些人已经认识到了降低或消除临床化学中的这些干扰因素影响的必要。例如1994年1月19公布的Arter等人的欧州专利申请93111290.8公开了一种测定含水液体中分析物的分析成分。该成分包括一种能与液体中存在的自由巯基键合的试剂。Arter等人的主要目的是测定被分析物如乙酰氨基笨、水扬酸酯、肌酸酐，胆固醇，HDL胆固醇，甘油酸酯，葡萄糖和尿酸。他们使用产生过氧化氢的酶，并通过过氧化物酶偶氧化还原化学对其测定。可能存在于液体中的干扰巯基(如存在于服用某些药的人的血清中的N-乙酰巯基丙氨酸)即使在被分析物不存在的情况下也可能诱发氧化/还原反应。Arter等人利用加入能与巯基反应并键合的试剂的方法来解决干扰自由巯基的问题。适宜的试剂包括马来酰亚胺，N-乙基马来酰亚胺、碘乙酰胺、硝酸银和氯化金。
1993年2月9日公布的Ismail等人的美国专利5185247公开了一种以酶为主的试纸，它是通过添加了各种成分来稳定的。这些成分包括具有热稳定性试剂中的咪唑，但是它仅对浸渍了“抗坏血酸干扰成分”的试纸有效，其中的“抗坏血酸干扰成分”包括氧化汞和肌氨酸。因为重金属氧化物有毒，一般最好不加入试剂中。
1993年12月15日公布的Matzinger等人的欧州专利申请93303643、6公开了一种测定全血中葡萄糖浓度的试纸。该试纸有一个测试垫板，它含有通过改变颜色来指示葡萄糖浓度的试剂系统。测试垫板是由各向异性膜构成的，靠近主表面有相对较大的孔，靠近反面的孔较小。在垫板的大孔面粘附有一个多孔转运基质。将全血样品点到转运基质上，基质将样品中可检测部分转运到垫板的大孔面。然后样品中的葡萄糖向反面移动，并与试剂反应产生颜色变化，变色可从垫板的小孔面看到，并指示出样品中的葡萄糖浓度。
Kiser等人的美国专利5306623公开了一种测血糖试纸，它包括一个从全血中分离红细胞的分离基质。检测试剂与被分离后的成分反应引起变色，从而指示血液中的葡萄糖浓度。公开的分离层包涵物组分是聚丙烯聚合物(CarbopolR)，在这些“分离成分”(也称作“血球比率调节剂”，没有进一步解释)一般存在于单独的分离层中同时，Kiser等人还公开了一个单层基质，它包括既含有可产生信号的成分又含有分离血液成分的试剂。无论是任何情况下，确切地说分离成分的用量范围是7％到35％w/v。实际上在这些试剂中Cavbopol不会以这种浓度范围使用。
众所周知测血糖时干扰因素会影响试纸的颜色变化。例如，测定葡萄糖中颜色变化的强弱一般好象与血液中红细胞的浓度(血球比率)有关。
这就需要有一种试纸，该试纸在暴露于含葡萄糖的血液中时，它能随着葡萄糖浓度的持续产生显著的颜色变化。理想地是，即使该试纸暴露于血球比率水平在25％到60％的范围内变化的全血样品中时，它也能够精确地显示出大约40到500mg/dl范围内的葡萄糖浓度。
按照本发明，测定含有红细胞的全血样品葡萄糖浓度的试纸包括：
(a)一种各向异性膜，它的样品面上有较大的孔，检测面上的孔较小，该膜适合于在样品面上接受样品，然后使样品流向检测面；和
(b)浸渍到膜上的检测试剂，它包括：
(i)一种由葡萄糖和氧生成过氧化氢的成分；
(ii)一种与过氧化氢发生颜色变化的指示剂；
(iii)一种丙烯酸聚合物，浓度范围在约0.1％到约4％w/v，
这样，在测定葡萄糖浓度时红细胞产生的任何影响都可利用丙烯酸聚合物使其降低。
在本发明的方法中，测定含有红细胞的全血样品中的葡萄糖浓度的方法包括以下步骤：
(a)准备一个各向异性膜，该膜
(i)有一个样品面，上有较大的孔和一个上有较小孔的检测面；和
(ii)浸渍有能与葡萄糖反应而引起检测面变色的检测试剂，该试剂包括葡萄糖氧化酶，过氧化物酶，可氧化染料或染料对，和浓度约0.1％到4％w/v的丙烯酸聚合物；
(b)将血液点到膜的样品面上；
(c)测定检测面的颜色变化来检测血液中的葡萄糖浓度。
对于血样中的葡萄糖浓度超过了可检测范围的样品来说，本发明的试纸提供了一种相对简单并迅速测定葡萄糖浓度的方法。对于血球比率水平在25％到60％范围内的全血样品，试纸能得出基本不变的葡萄糖浓度值。
试纸的样品面用来接受含有红细胞和葡萄糖的全血样品，在合理的限度内，样品的体积既不需要测定，也不需要控制。膜的多孔性使得液体能够通过毛细管作用从样品面流到检测面。因此，检测试剂能与血液中的葡萄糖反应而引起检测面上或附近的颜色变化。颜色的改变取决于样品中的葡萄糖浓度。血液中的葡萄糖浓度可以用多种方式测定，例如，通过对此检测面的颜色与已校准过的参照物或色度表；通过反射光度学；或通过对应于葡萄糖浓度范围的一系列的段，观察在特定时间内最后一个变色的段来确定葡萄糖浓度。色泽深的红细胞会使颜色变化不易察觉，在各向异性膜的样品面附近会将其滤出，并逐渐由样品面上的大孔流向检测面上的小孔。能用于本发明试纸各种成分的物质有多种。其中一些已分别在1994年4月26日和1995年5月23日公布的Kiser等人的美国专利5306623和5418142中公开，本文将其引用为参考文献。
检测试剂含有一种成分如葡萄糖氧化酶，它能将葡萄糖转化为过氧化氢，和一种或多种用于测定由样品中的葡萄糖产生的过氧化氢的成分。测定过氧化氢的成分可以是过氧化物酶，优选马萝葡过氧化物酶，和一种在反应过程中能变色的“指示剂”。这种指示剂可以是一种可氧化染料或染料对，过氧化物酶能在过氧化氢存在的条件下催化指示剂的氧化反应。
检测试剂还包括一种丙烯酸聚合物，它能降低测定葡萄糖浓度时血球比率(全血样品中红细胞所占的百分比)的变化产生的影响。
本发明中的试纸和方法用于测定血样中的葡萄糖浓度时，所允许的葡萄糖浓度范围大约是40到500毫克/分升，血球比率水平范围大约是25％到60％。
图1是本发明中试纸膜的透视图。
图2是本发明中可直接读数的试纸样品面的平面图。
图3是图2所示试纸检测面的平面图。
图4是本发明中双层试纸的透视图。
本发明是一种测定全血中血糖浓度的干相试纸。这种试纸的关键部分是掺有检测试剂的多孔膜。试纸会随着点在其上的血样中的葡萄糖而变色。
该膜可以由一个均匀组分或一种包被基质组成，它有一个用于点样的样品面，和一个可观察到颜色变化的检测面。该膜优选是各向异性的；更优选有一个宽的孔径范围。例如，最大孔的孔径与最小孔的孔径的比率大约在100-400范围内。膜的孔径最小的一面，空体积也相对较小，一般膜物质非常紧密，其中的一层就可占膜厚度的20％。在这层中，孔径优选大约在0.1到0.8微米内，公称孔径优选在0.3-0.4微米内。大孔的一面，孔径优选在约40微米到125微米范围内。当血液被点到样品(大孔)面上后，样品逐渐穿透膜，流过的孔越来越小。最后，象红细胞这样的固体到达膜的某个位置就不再往下渗透。含有溶解的葡萄糖的剩余样品却会渗透到检测面上。膜本身的各向异性使得过滤固体的同时仍能保持相对迅速的流速。
由于样品穿透膜后与试剂反应引起检测面附近的空体积中的吸光材料出现颜色或被漂白，所以实际上它会影响膜的反射能力。
适宜的膜材料是聚砜和聚酰胺(尼龙)，也可使用其他具有类似性能的聚合物。可对聚合物进行改良，引进其他能提供带电结构的功能基团，使得膜表面可以是中性的，正电性的或负电性的。
制备构成膜的多孔材料的优选方法是铸造一个没有支持核芯的聚合物。这样的膜可以是各向异性的聚砜膜，可从Me mt ec、Inc，Ti mo nium，MD，得到。一般得到的膜的厚度大约小于200微米，优选115到155微米。当膜为尼龙或各向异性的聚砜时，最优选的厚度大约是130到140微米。
处理膜时，可将膜沉浸到检测试剂各组分的混合液中并使其饱和。最好至少把某些成分顺序掺入膜中。用机械方法如气刀，刮刀或玻璃棒除去过量的试剂，然后将膜干燥。试剂主要集中在膜的小孔(检测)面附近。
检测试剂包括(i)一种用来将葡萄糖转化为过氧化氢的成分，(ii)一种用于测定过氧化氢的成分，和(iii)一种在检测葡萄糖浓度时，用来降低血样的血球比率水平的影响成分。试剂也可以再包括一种分离成分，它能使把象红细胞这样的固体粘附或截留在膜中，从而有效地把固体从生物液体中除去。其他可添加的成分见下文的叙述及实施例。
将葡萄糖转化为过氧化氢的成分优选葡萄糖氧化酶，一般可由黑曲霉或青霉得到。葡萄糖氧化酶能与葡萄糖和氧反应生成葡糖酸内酯和过氧化氢。葡糖氧化酶的最佳浓度根据指示剂系统的组成而定。例如，如果指示剂系统是MBTHSB-ANS(见下文描述)，那么适宜的葡糖氧化酶浓度为500-10000u/ml，更优选约700-2000u/ml，最优选为1000u/ml。一般来说，葡糖氧化酶的浓度越大，反应开始进行得越迅速，反之亦然。
产生的过氧化氢与用来检测它的成分反应，其中包括一种过氧化物酶，它能选择性地催化过氧化氢与指示剂之间的反应。过氧化物酶利用过氧化氢作为氧化剂，它能从多种物质中转移氢原子。适宜的过氧化物酶可含有正铁血红素，这里从植物中得到的一种氯高铁血红素。从动物中得到的过氧化物酶也是合适的，例如从动物的甲状腺中得到的。作为检测过氧化氢的成分，更优选的是马萝葡过氧化物酶。
优选用过氧化物酶催化；过氧化氢直接或间接反应生成或分解能在预定波长范围内吸光的指示剂染料。优选指示剂染料强吸收处的波长不同于样品或者检测试剂强吸收处的波长。指示剂被氧化后的最终产物可以是彩色的、暗淡色的、或者无色的，以此证明膜检测面的颜色变化。也就是说，通过彩色区域被漂白了。或者无色区域产生颜色，检测试剂可以指示样品中葡萄糖的存在。
本发明中有用的指示剂包括单一组分和两种组分的色原物质。单一组分系统包括芳香胺，芳香醇，吖嗪和联苯胺，如N-四甲联苯胺-HCL。适宜的两种组分系统包括：一种成分是MBTH，MBTH的衍生物(参见美国专利申请号08/302575，本文引用为参考文件)，或者4-氨基安替比林，另一种成分是芳香胺，芳香醇，结合胺，共轭醇或其香醛或脂族醛。典型的两种组分系统是3-二甲氨基苯甲酸、(DMAB)与3-甲基-2-苯并噻唑啉酮腙盐酸化物(MBTH)一起，3，5-二氯-2-羧基苯磺酸(DCHBS)，MBTH一起，以及8-苯胺基-1-萘磺酸铵(ANS)与【3-甲基-2-苯并噻唑啉酮腙】N-磺酰基苯磺酸钠(MBTHSB)一起。优选MBTHSB-ANS。
用于降低血样中血球比率对测定葡萄糖影响的成分是一种丙烯酸聚合物(-CH2-CH-COOH)n。这种聚合物的常用商品名为CARBOPOL。聚合物的分子量范围优选约是200000到4000000。最优选的分子量大约为750000。浓度的优选范围是0.1-4.0％ w/v，最优选大约为0.5％ w/v。
以50-400mg/dl的浓度含有葡萄糖的生物液体采用本发明方法最好。本发明的方法表明当所测样品的葡萄糖浓度在优选范围内时，特别是当血球比率水平在优选范围25-60％内时，样品中每单位葡萄糖浓度变色的一致性较常规试纸好。葡萄糖水平越高，这种有益效果越突出。
在本发明试纸的优选实施方案中，试剂包括用于抑制变色反应的抑制剂。在这种实施方案中，涂敷或浸渍在膜上的检测试剂在试纸表面上是不均匀的。实际上，优选用一系列平行带或“效果段”的形式把试剂掺入到膜中，相邻效果段的组分浓度逐渐增大，它的有效抑制浓度也逐渐增大。这样每个有效段就会需要样品的葡萄糖浓度越来越高才能引起变色。这样的试纸是可“直接读数”的，即，它能直接看见并读出定量结果。这一实施方案在1995年3月27日申请的美国专利号411238中有详细说明，本文把该申请作为参考文件。
在本发明的另一个实施方案中，试剂不合抑制剂，但是试纸除了被浸渍到膜上的试剂外，还包括一个粘附在膜样品面上的双层多孔转运层。在这个“双层”的实施方案中，转运层用来接受全血样品并将样品中的可检测部分转运到膜的样品面，样品可通过毛细管作用移动。转运层优选延伸到检测垫板的一个或多个底端，以便于形成一个容纳过量血样的蓄液池。相应地，转运层优选能容纳大约10-50微升血液，更优选大约35微升血液并将大约3-10微升血液转运到膜上。转运层可由天然纤维组成，如棉花或纸，也可以是聚酯，聚酰胺，聚乙烯和其他合成聚合物。聚乙烯是优选的转运层的材料，例如，可从the Porex Corp of Fairburn，Georgia，得到多孔聚乙烯。在这个实施方案中，任选的试纸也可包括一个粘附到膜检测面上的支持层，并且上有一个可观察颜色变化的孔。膜检测面的颜色变化优选用光敏元件测定，从而得出血糖浓度。
当通过光敏元件(即通过反射光度学)进行测定时，在检测面暴露于光源下之前或之后，一个或多个已校准的参照色泽表也暴露于光源下。例如，光可从色泽表和检测面顺序反射到光敏元件上。
光敏元件根据顺序暴露于光源下的参照物和检测面而产生信号变化。这些信号变化与样品中的葡萄糖浓度水平有定量的关系，样品中的葡萄糖浓度是根据由相似视图方法和已知葡萄糖浓度的样品而预先得到的数学公式计算出的。这一实施方案的细节参见1995年6月22日申请相关美国专利申请493435，本文将该专利引用为参考文件。
下面结合附图对本发明作进一步的描述。
图1所示为本发明用于测定全血样品中葡萄糖含量的膜10。尽管是以拱形位置显示的，但膜10是有柔韧性的，使用时一般为平面。膜包括一个用来点样的样品面12和一个控制面14，控制面14上或附近的颜色变化可指示葡萄糖的存在，变色是葡萄糖与浸渍在孔16中的试剂相互作用的结果。样品面12附近的孔径最好较大，接近检测面14的孔径逐渐减小。这样的孔径坡度是用来阻止样品面及附近的红细胞的，从而它们的颜色不会阻碍指示葡萄糖存在的变色观察。
在直接读数的试纸中，图1所示的膜是夹在两个覆盖层之间的，覆盖层可由本领域技术人员熟知的任何适当的热塑材料膜构成。图2和图3分别是试纸20样品面22和检测面24的平面图。使用时，把血样点到样品面22上的窗口26中。样品通过毛细管作用纵向扩展到试纸的顶层和底层并渗入膜内。通风孔28使样品更易流入试纸。样品在任意一个透明窗口30和32中的出现证明用于进行测定的样品已足够了。检测面24上的指示剂圈如34，允许显色反应所需的氧进入并标有血糖的浓度。在测定中，如果样品的血糖浓度刚好或超过了某指示剂圈对应的量，它就会随之变色。一个任选的化学计时器圈36指示读取试纸的足够时间已过去(有关计时器的细参参见1995年3月27日申请的相关美国专利411238)。图3显示的结果表明，样品的葡萄糖浓度至少为120mg/dl，但低于150mg/dl。注意图3所示的葡萄糖反应引起的变色是从白色变为彩色。然而，系统也可改变对指示剂染色的处理方式，使其通过诱导葡萄糖氧化作用而被破坏，与此相对应的变色是从彩色变为白色。
图4是一个双层试纸的透视图，其中图1所示的膜10的大孔面与转运层40粘合在一起。小孔面粘附到任选的支持物42上。支持物42有一个孔44，通过它，光敏元件(图中没有显示)能够测定由血样中的葡萄糖与膜10中的试剂相互反应而产生的检测面46上的颜色变化。
下面的实施例证明丙烯酸聚合物有效地降低了本发明的试纸对样品中血球比率水平的敏感性。实施例不起任何限制作用。
实施例
各级聚丙烯酸由Aldrich Chemical，Milwaukee，WI购得，使用时未精制。用作参照物的Carbopcl R910(聚丙烯酸)由BF Goodrich，Cleveland，OH购得。由Aldrich和BF Goodrich处购得的聚丙烯酸的物理和化学性质非常相似。
将聚丙烯酸悬浮于乙腈中并使其缓慢分散到搅拌的酶溶液中(表1)。用0.1M柠檬酸二钠调节该溶液后，所得到的混合物反应1小时。将所得到的黄褐色溶液涂覆到聚砜膜上，该聚砜膜由Memtec Corp，SanDiego，CA制造。把涂覆后的膜放在循环热气炉中56℃下干燥10分钟，它的颜色变为亮黄色。干燥后的膜再用染料溶液(表2)涂覆并在上述条件下再次干燥。然后将膜插入测定血糖的试纸中。
表1 酶溶液
| 成 分 | 用 量 |
| 水 | 575mL |
| 柠檬酸钠 | 6.96g |
| 柠檬酸 | 5.64g |
| EDTA的二钠盐 | 0.42g |
| 葡糖氧化酶 | 562，110U |
| 马萝葡过氧化物酶 | 403，676U |
| Crotein SPA(一种蛋白质稳定剂，包括水解胶原蛋白，由Croda，New York，NY得到) | 7.20g |
| Gantrez S95(一种着色剂，包括聚乙烯酸可由GAF，New York，NY得到) | 2.25g |
| 甘露糖醇 | 5.00g |
表2染料溶液
| 成 分 | 用 量 |
| 偏[3-甲基-2-苯并噻唑啉酮腙]N-磺酰基苯磺酸-钠 | 1.55g |
| 8-苯胺基-1-萘磺酸 | 2.52g |
| 变性酒精 | 280ml |
| 水 | 120ml |
| Maphos 60A(一种色泽增强剂，包括脂族磷酸酯，可由Mazer Chemicals，Gurnee，IL得到) | 3.68g |
把用三种不同分子量的聚丙烯酸以及Carbopol 910处理后的试纸用于三个血球比率值25％，43％和60％条件下测定全血的葡萄糖浓度。结果见表3，同时得到的结果包括不含聚丙烯酸的对照品。聚丙烯酸对血球比率调节的不同程度一般与聚合作用的水平相对应。当分子量增大时，血球比率的影响减弱，但是完成反应的时间延长，色彩强度降低了。进一步说，大分子量的聚合物是不可溶的，这是制造过程中所不希望的。因此，对于聚丙烯酸的最佳分子量的选择采用了一个折中值大约750000。
表3 含有聚丙烯酸的葡萄糖试纸
的血球比率性能
*数值越大，意味着颜色越深**理想比值为1.00
| 实施例 | 聚丙烯酸 | 由25％血球比率形成的颜色* | 由43％血球比率形成的颜色* | 由60％血球比率形成的颜色* | 25％与43％的比** | 60％与43％的比** |
| 1 | 无 | 8.26 | 7.85 | 5.37 | 1.05 | 0.68 |
| 2 | MW＝450,000 | 8.68 | 9.51 | 6.71 | 0.91 | 0.71 |
| 3 | MW＝750,000 | 6.54 | 5.90 | 5.46 | 1.11 | 0.93 |
| 4 | MW＝1,250,000 | 5.56 | 5.52 | 5.21 | 1.01 | 0.94 |
| 5 | Carbopol 910 | 6.39 | 5.61 | 5.21 | 1.14 | 0.93 |
对本领域普通技术人员来说应当明白以上描述和实施例是对本发明的详细说明，并不用于限定本发明。可作出本文中所提到的详细说明的各种改变仍不超出本发明的范围和构思。
Claims (10)
1一种用于测定含有红细胞的全血样品中的葡萄糖浓度的试纸，它包括：
(a)一种各向异性膜，该膜具有一个上有相对较大孔的样品面和一个上有相对较小孔的检测面，该膜适用于样品面接受样品并通过它流向检测面，
(b)浸渍于膜上的检测试剂，包括
(i)一种用于把葡萄糖和氧转化为过氧化氢的成分；
(ii)一种能与过氧化氢反应而发生颜色变化的指示剂；
(iii)一种丙烯酸聚合物，其浓度在约0.1％到约4％ w/v的范围内，
由此，在测定葡萄糖浓度时，利用丙烯酸聚合物可降低红细胞产生的任何影响。
2按照权利要求1的试纸，还包括一个用来支持膜的热塑塑料板。
3按照权利要求1的试纸，其中用于把葡萄糖和氧转化为过氧化氢的成分包括葡糖氧化酶。
4按照权利要求1的试纸，其中指示剂包括过氧化物酶和一种选自下列基团中的成分：(a)3-甲基-2-苯并噻唑啉酮腙盐酸化物(MBTH)和3-二甲氨基苯甲酸(DMAB)；(b)MBTH和3，5-二氯-2-羟基苯磺酸(DCHBS)；(C)[3-甲基-2-苯并噻唑啉酮腙]N-磺氨基苯磺酸-钠(MBTHSB)和8-苯胺基-1-萘磺酸铵(ANS)。
5按照权利要求4的试纸，其中指示剂包括过氧化物酶和MBTHSB-ANS。
6按照权利要求1的试纸，其中丙烯酸聚合物的分子量在约200000到约4000000的范围内。
7按照权利要求6的试纸，其中丙烯酸聚合物的分子量约为750000。
8按照权利要求1的试纸，它还包括一个粘附到膜样品面上的多孔转运层，用它来接受样品并将样品的可检测部分转运到膜的样品面。
9按照权利要求1的试纸，其中检测试剂还包括一种抑制剂以抑制指示剂变色。
10一种测量含有红细胞的全血样品中的葡萄糖浓度的方法，包括以下步骤：
(a)准备一个各向异性膜，这种膜：
(i)有一个样品面，上有相对较大的孔；和一个检测面，上有相对较小的孔；
(ii)浸渍有能与葡萄糖反应而引起检测面变色的检测试剂，这些试剂包括葡糖氧化酶、过氧化物酶、可氧化染料或染料对，和浓度约0.1％到4％w/v的丙烯酸聚合物；
(b)将血液点到膜的样品面上；
(c)测定检测面的颜色变化来检测血液中的葡萄糖浓度。
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- 1996-10-15 CA CA002187861A patent/CA2187861C/en not_active Expired - Lifetime
- 1996-10-16 PT PT96307522T patent/PT769558E/pt unknown
- 1996-10-16 DK DK96307522T patent/DK0769558T3/da active
- 1996-10-16 DE DE69627097T patent/DE69627097T2/de not_active Expired - Lifetime
- 1996-10-16 NO NO19964404A patent/NO323423B1/no not_active IP Right Cessation
- 1996-10-16 ES ES96307522T patent/ES2194961T3/es not_active Expired - Lifetime
- 1996-10-16 EP EP02078709A patent/EP1264898A3/en not_active Withdrawn
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- 1996-10-17 CN CN96119240A patent/CN1100267C/zh not_active Expired - Lifetime
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103966899A (zh) * | 2014-05-07 | 2014-08-06 | 重庆锐今生物制品有限公司 | 一种成膜材料及配制方法及用该成膜材料成膜的带膜试纸 |
| CN105572065A (zh) * | 2016-01-29 | 2016-05-11 | 福建医科大学 | 基于铂铋纳米模拟过氧化物酶的葡萄糖检测试剂盒 |
| CN105572065B (zh) * | 2016-01-29 | 2018-08-21 | 福建医科大学 | 基于铂铋纳米模拟过氧化物酶的葡萄糖检测试剂盒 |
| CN109916894A (zh) * | 2019-04-12 | 2019-06-21 | 吉林省汇酉生物技术股份有限公司 | 一种定量测定葡萄糖浓度的干化学试剂片及其制备方法 |
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| ATE236268T1 (de) | 2003-04-15 |
| DE69627097D1 (de) | 2003-05-08 |
| DK0769558T3 (da) | 2003-07-21 |
| JPH09121894A (ja) | 1997-05-13 |
| AU722471B2 (en) | 2000-08-03 |
| EP0769558A1 (en) | 1997-04-23 |
| MX9604885A (es) | 1997-10-31 |
| PT769558E (pt) | 2003-08-29 |
| DE69627097T2 (de) | 2003-12-24 |
| JP3850497B2 (ja) | 2006-11-29 |
| AU6799896A (en) | 1997-04-24 |
| EP1264898A2 (en) | 2002-12-11 |
| NO964404L (no) | 1997-04-18 |
| CN1100267C (zh) | 2003-01-29 |
| TW369599B (en) | 1999-09-11 |
| NO964404D0 (no) | 1996-10-16 |
| EP0769558B1 (en) | 2003-04-02 |
| CA2187861C (en) | 2007-04-10 |
| CA2187861A1 (en) | 1997-04-18 |
| NO323423B1 (no) | 2007-04-30 |
| EP1264898A3 (en) | 2005-04-20 |
| US5789255A (en) | 1998-08-04 |
| ES2194961T3 (es) | 2003-12-01 |
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