CN1558235B - 测定血样中分析物的存在和/或含量的方法以及检测元件 - Google Patents
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Abstract
一种测定全血样品中分析物的存在和/或含量的方法，包括用非裂解性高渗盐组合物处理样品，通过减小血红细胞的尺寸来降低血细胞比容。在光学检测系统中，较小的血红细胞产生较大的光散射，从而可在双波长检测系统中使用更加准确的校准。在电化学检测系统中，与在光学检测系统一样，较小的血红细胞为样品中分析物和试剂的扩散提供了较小的阻碍，从而有利于反应。
Description
技术领域
本发明是关于一种测定血样中分析物的存在和/或含量的方法，通过减少测定中血细胞比容的影响来提高其精确性和准确性。本发明还涉及用于实施该方法的检测元件，以及包括该检测元件的检测试剂盒。
背景技术
对医学科学来说，能对全血中的化学和生物化学成分进行定量变得日益重要。该能力在测定有害物质、麻醉剂、治疗药物的影响时以及在诊断中都是十分重要的。在一些应用中，一个非专业人士能够在实验室外实施检测并迅速准确得到结果是很重要的。例如，糖尿病患者必须每天数次测定他们自己的血样中葡萄糖水平并据此调节食物和药物。测试结果必须既快速又准确。血浆或全血中葡萄糖检测可通过采用比色或电化学检测系统的氧化或还原化学法进行。血液中其它可能的分析物包括胆固醇、甘油三酯、乙醇、乳酸、β-羟基丁酸、酮体及果糖胺。
测定血液中葡萄糖及其它分析物的检测试剂盒在本领域是公知的。这些检测试剂盒通常包含一种检测元件，例如，浸渍、包被、沉积或印制一种或多种化学物质的检测条或微流装置，该化学物质在葡萄糖存在时能与之反应，并引起可采用电化学或光学方法或者它们的任意组合测定的剂量依赖型响应。光学测定可包括透射、吸收和反射法。电化学测定可包括电流法或电量法。
众所周知，诊断测定中使用的全血样品血细胞比容的变化能够干扰对分析物的准确测定。全血血细胞比容(缩写为hct)是指血红细胞所占的全血体积的百分数。它也指压缩细胞体积，或血红细胞占血浆的比例。血细胞比容变化引起的干扰可至少由三种因素导致：1)干扰在分析物测定中使用的光反射、吸收或散射的光学信号的测定；2)通过阻碍全血样品中分析物的扩散来干扰化学反应的速率；3)通过减少样品中有效的体液量而对检测条或其它检测元件上干试剂的充分再水合构成干扰。因此以前的一些检测试剂盒要求使用者稀释样品，或者要求在将样品用于测定装置前将血红细胞滤出样品或使其裂解，或者设计为无需使用者介入，而由装置自身实现这些功能。
一系列转让给加利福尼亚Mountain View的生命扫描有限公司的关于在血液中葡萄糖的比色测定时减少血细胞比容的影响的专利，包括U.S.4935346，U.S.5049487，U.S.5049394，U.S.5179005，U.S.5304486，在此全部全文引用作为参考。这些专利中公开的方法涉及采用反射法分析惰性双面多孔基质的一个表面。该基质浸渍有一种当将被分析液体加到第一表面并通过基质迁移到第二表面时能够与分析物反应，产生光吸收反应产物的试剂。第二表面的反射测定用两种不同波长的光进行以减弱干扰，并且当液体通过惰性基质将第二表面湿润、在反射刚开始减弱时触发计时电路。该方法不需要将血红细胞从血清或血浆中分离。
也被转让给加利福尼亚州芒廷维市的的Lifescan有限公司的专利US5,789,255、题为“具有降低的红细胞比容敏感性的血液葡萄糖检测条”在此引用作为参考。该专利公开了一种试剂检测条，包括一个各向异性膜、其上具有相对较大的孔的样品面、和相对较小的孔的检测面，当样品被施加于样品面并通过膜向检测面迁移时，相对较大的血红细胞被滤出血液样品。该膜浸渍有一种试剂，试剂包括：一种使葡萄糖和氧反应生成过氧化氢的成分，一种能与过氧化氢反应的颜色指示剂，以及一种在测定葡萄糖浓度时可降低红细胞影响的丙烯酸聚合物。
也被转让给生命扫描有限公司的题为“用于分析测定的试剂检测条”的国际申请WO 01/57239A2描述了使用溶血剂溶解血红细胞以致不必将红细胞与血浆分离。如该申请所述，“本发明的试剂检测条以至少具有下述成分之一为特征：多孔基质，一种或多种分析物氧化信号生成系统；以及至少一种溶血剂。”
转让给Fuji Photo Film Co.有限公司的日本申请号为平1[1989]-262470，题为“干型全血分析元件”的专利申请，与日本专利文摘JP01262470、题为“干燥法全血分析元件-尤其是用于检测全血中高浓度血糖的分析元件”相关，描述了一种用于测定包含血红细胞的血液中给定成分的元件。该元件包括一个试剂层和一个多孔展开层，两层均是水可渗透性的。其中一层包括一种当分析物存在时能够形成可光学检测物质的试剂。多孔展开层将血红细胞附带的液体展开以湿润检测系统的其它层。多孔展开层包括至少5g/m2的NaCl或KCl。
Pegg，D.E.发表于Cryobiology(1984)，21(2)，第234-239页的期刊论文“在甘油/氯化钠/水混合物中的红细胞体积”公开了关于细胞冷藏时保持红细胞体积的方法。
发明概述
因此，本发明的一个目的在于提供一种测定全血样品中的一种分析物，而不需要将血红细胞从全血样品中分离的方法，以及用于该方法中的检测元件及检测试剂盒。
本发明的另一个目的在于提供一种分析全血样品中一种分析物的方法，该方法可以减少在不同的被分析血样中由于血细胞比容变化而引起的干扰，以及提供用于该方法中的检测元件及检测试剂盒。
本发明的另一个目的在于提供一种测定全血样品中的一种分析物，而不需要将血液细胞溶解来减少血细胞比容变化干扰的方法，以及提供用于该方法中的检测元件及检测试剂盒。
本发明的另一个目的在于提供一种测定全血样品中的一种分析物，而不需要将血液稀释来减少血细胞比容变化干扰的方法，以及提供用于该方法中的检测元件及检测试剂盒。
本发明的这些目的及其他目的是通过本发明的方法实现的，其中在对分析物分析之前，通过用非裂解性的高渗盐组合物对样品进行处理，以减少样品中血细胞的平均细胞体积来调节血样的血细胞比容。尤其是，该方法包括如下步骤：(a)提供用于定性或定量测定一种分析物的血样，(b)用高渗盐组合物处理样品来调节样品的血细胞比容，以及(c)测定样品中分析物的存在和/或含量。
附图描述
图1A-E显示的是，不同浓度的高渗缓冲盐组合物对血红细胞形态的影响的光学显微图。
图2显示的是，当血细胞比容分别为全血样品的初始血细胞比容的20％，40％和60％时，在不同缓冲盐浓度时血细胞比容的变化。
图3显示的是，对于60％hct的全血样品和相应的血浆样品之间反射百分率的差异，每个点表示不同的NaHEPES缓冲液浓度水平。
发明详述
根据本发明，提供了测定血样中一种分析物的方法，在该方法中，血样的平均细胞体积被减小以降低血细胞比容对测定准确性的干扰作用。根据本发明的方法，在诊断过程的某些时刻，通过用非裂解性的高渗盐组合物处理样品来减少其平均细胞体积。本专利中使用的词语“高渗盐组合物”的意思是任何一种或多种有机或无机盐或其混合物的组合物，该组合物足以在血样中形成高于等渗液的渗透压。本专利中所使用的词语“非裂解的”指的是在采用本发明的方法进行分析时，组合物将不导致样品中血红细胞明显的细胞溶解。
尤其是，本发明的方法包括如下步骤：(a)提供用于定性或定量测定一种分析物的血样，(b)用高渗盐组合物处理样品来调节样品的血细胞比容，以及(c)测定样品中分析物的存在和/或含量。
例如，用非裂解性的高渗盐组合物处理样品的步骤可通过将预先定量的非裂解性的高渗盐组合物加入到样品中来实现。然而优选的是，该步骤可通过将样品(或其部分)置于已经提供了适当量的非裂解性高渗盐组合物的检测元件上来实现。
本发明还包括一种用于实施本发明方法的元件，该元件用非裂解性的高渗盐组合物处理。该元件可以是已用非裂解性的高渗盐组合物试剂处理过的检测条的形式，例如通过浸渍，包被，沉积或印制。当血样被置于检测条上时，盐组合物将调节样品的血细胞比容，从而获得对分析物的准确测定。作为替代，该元件可以是带有能够收集样品的孔或室的微流装置的形式。非裂解性的高渗盐组合物既可以是在制作该微流装置时预先沉积于孔或室中，也可以通过微通道，从该微流装置的另一个孔或室、或者从另外的来源例如外部的泵运送而来。用于阅读这样的检测条或微流装置的仪器在分析领域是公知的，且可通过商业途径得到。例如，在前面提到的U.S.5304486所描述的仪器。
本发明还进一步涉及包括这种检测条或微流装置的检测试剂盒。用于实施本发明方法的检测试剂盒包括一个或多个前面所描述的元件，此外还有从病人采集血样的穿刺针或其他装置，以及任选地还包括任何需要的试剂或溶液来处理待测定的特定分析物。本发明的试剂盒被设计为既适用于家用，又适用于实验室使用，例如在诊所或医院使用。
本发明通过减少血红细胞的尺寸，在对全血中分析物准确测定时降低了红细胞的干扰。本发明方法中红细胞尺寸的减小被认为至少通过两种机制降低了红细胞的干扰。首先，在光学检测系统中，较小的红细胞引起光散射增加。尽管被红细胞散射的光可以是一种干扰源，但是可通过以不同于测定分析物的波长测量此散射光来补偿这种干扰，并据此补偿测定干扰。较小的粒子比大的粒子散射更多的光。在本发明的方法中，使较小干扰的红细胞信号增加，超过了原有的红细胞信号。增加的散射信号使得对红细胞干扰的测定更加准确，因此使得对红细胞干扰的补偿也更加准确，从而使最终分析物的测定也更加准确。
对于在一种分析物的光学测定中使用的试剂盒，既可在选择用于分析物测定的第一波长处进行读取，也可在与分析物测定波长稍有重叠或没有重叠的第二波长处进行读取。在分析物测定波长，由于存在红细胞引起的光散射，该读数既是分析物含量的函数，也是血细胞比容的函数。在第二非分析物波长，由于红细胞引起的光散射，该读数是血细胞比容的函数，而基本上不是分析物的函数。在第二非分析物波长，该读数允许测定样品的血细胞比容。然后对在分析物波长进行的读取进行校准以计算样品的血细胞比容，从而确定样品中分析物的量。因此，分析物测定的准确性依赖于血细胞比容测定的准确性。虽然大多数诊断检测都尽量减少散射，从而降低血细胞比容对测定的影响，但是申请人惊奇的发现，散射和/或反射量的增加可根据本发明的方法用于在检测中获得更准确的血细胞比容测定。使得在分析物波长进行测定时得到更准确的校正，因而能够更准确地测定血样中分析物的含量。
其次，在光学和电化学系统中，较小的红细胞也为分析物微粒绕过红细胞运动，到达分析装置中的反应区提供了较小的扩散路径；这一点在电化学分析装置中尤为重要。减小具有不同初始血细胞比容的样品的平均细胞体积和压缩细胞体积范围，可通过缩短扩散路径来降低干扰。
使用非裂解性高渗盐溶液能通过减小血红细胞粒子的大小来减小样品的平均细胞体积。这一点可从图1a-e中看出，图1a-e显示在血细胞比容大约为40％的全血样品中，分别用浓度水平为0mM，50mM，100mM，200mM，400mM的NaHEPES溶液处理的红细胞的形态。将500ml预先配制的浓度为50，100，200及400mM的等分NaHEPES缓冲液加入1.5ml微离心管中，将此液体用SpeedVac浓缩仪(Savant Instruments，Inc.)30℃下蒸发浓缩。然后将每等分干缓冲盐用不同血细胞比容的全血样品重新稀释。将血细胞比容为20％、40％和60％的全血样品作为目标，并通过将压缩细胞与血浆混合配制而成。用每等分的少量样品于显微载玻片上制备血涂片，以在显微条件下观察血红细胞的形态。可以看出，在缓冲液浓度较高时，血红细胞占有明显较少的样品体积。这些较小的血红细胞增加了样品对光的散射。
下列表1说明了高渗缓冲盐溶液NaHEPES对血细胞比容(压缩的细胞体积)的影响。这些数据表示血细胞比容的读数，该读数是在将不同血细胞比容水平的全血与不同浓度NaHEPES缓冲液混合后测定的。每个样品的血细胞比容水平在加入盐之前和之后都用Compur M-1100微毛细管阅读仪装置检测以测量压缩的细胞。表1和图2的数据说明，随着缓冲盐浓度增加而引起细胞尺寸减小时，压缩细胞体积下降，因而血细胞比容也下降。图2中显示的理论趋势曲线表明所预期的血细胞比容将归因于被盐置换的体积。可以看出，对血细胞比容的影响明显大于理论预期，并且缓冲盐浓度的增加对较高hct水平的影响明显要比对较低hct水平的影响大。
图3显示的是高渗盐缓冲液浓度对在940nm处测定的反射率的影响，选择该波长是作为采用血红细胞散射对血细胞比容进行校准的示范波长。在图中，纵轴表示对血浆样品与初始hct为60％的全血样品之间测定的反射百分率差异，每种样品都标明缓冲液浓度。数据通过以下方式收集：在将血样加到等份的、用pH7.5的NaHEPES缓冲到特定浓度的葡萄糖试剂中之后得到混合物，用2002年4月19日提出的共同未决专利申请60/373583中描述的仪器测定其反射率。这些数据说明增加缓冲液浓度对高hct样品反射率的显著影响。
本发明的方法在非光学测定中也是十分有用的，例如用在电化学测定中。较小的血红细胞使得分析物和试剂在全血样品中扩散的阻碍减小，因而使得分析物测定中需要的化学反应变得更容易进行，从而得出更准确的结果。
相应地，本发明的方法包括如下步骤：(a)提供用于定性或定量测定一种分析物的血样，(b)用非裂解性高渗盐组合物处理样品来调节样品的血细胞比容，以及(c)测定样品中分析物的存在和/或含量。
Claims (17)
1.一种测定全血样品中分析物的存在和/或含量的方法，该方法包括如下步骤：(a)提供用于定性或定量测定一种分析物的全血样品，(b)用非裂解性高渗盐组合物处理全血样品来调节全血样品的血细胞比容，以及(c)通过测量所述经处理的全血样品来测定全血样品中分析物的存在和/或含量。
2.权利要求1的方法，其中所述分析物选自葡萄糖、胆固醇、甘油三酯、乙醇、乳酸、β-羟基丁酸、酮体及果糖胺。
3.权利要求1的方法，其中所述样品中分析物的存在和/或含量用一种光学检测方法测定。
4.权利要求3的方法，其中所述光学检测方法选自反射法、吸收法和透射法。
5.权利要求3的方法，其中在读数是分析物和血细胞比容的函数的波长处进行第一光学测量，在读数基本上不是分析物的函数的波长处进行第二光学测量，并且根据第二光学测量的读数校准第一光学测量的读数。
6.权利要求1的方法，其中所述样品中分析物的存在和/或含量用一种电化学方法测定。
7.权利要求6的方法，其中所述电化学方法选自电流法和电量法。
8.权利要求1的方法，其中所述高渗盐组合物包含一种或多种有机盐，或者一种或多种无机盐，或其任意组合。
9.一种用于权利要求1的方法中的检测元件，所述检测元件适合于接收所述血样，所述检测元件包括所述非裂解性高渗盐组合物。
10.权利要求9的检测元件，其中所述元件为一种检测条。
11.权利要求10的检测元件，其中所述检测条用所述非裂解性高渗盐组合物通过选自浸渍、包被、沉积和印制的方法进行处理。
12.权利要求9的检测元件，其中所述检测元件为一种微流装置。
13.权利要求12的检测元件，其中所述微流装置包括能够沉积所述高渗盐组合物的室或孔。
14.权利要求12的检测元件，其中所述非裂解性高渗盐组合物通过微通道运送至所述样品。
15.一种包含权利要求9所述检测元件的检测试剂盒。
16.一种包含权利要求10所述检测元件的检测试剂盒。
17.一种包含权利要求12所述检测元件的检测试剂盒。
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Families Citing this family (83)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6391005B1 (en) * | 1998-03-30 | 2002-05-21 | Agilent Technologies, Inc. | Apparatus and method for penetration with shaft having a sensor for sensing penetration depth |
| US20030235920A1 (en) * | 2000-02-28 | 2003-12-25 | James Wyatt | Diagnostic device and method |
| US8641644B2 (en) | 2000-11-21 | 2014-02-04 | Sanofi-Aventis Deutschland Gmbh | Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means |
| ES2352998T3 (es) | 2001-06-12 | 2011-02-24 | Pelikan Technologies Inc. | Accionador eléctrico de lanceta. |
| EP1404235A4 (en) | 2001-06-12 | 2008-08-20 | Pelikan Technologies Inc | METHOD AND DEVICE FOR A LANZETTING DEVICE INTEGRATED ON A BLOOD CARTRIDGE CARTRIDGE |
| US9427532B2 (en) | 2001-06-12 | 2016-08-30 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
| AU2002315177A1 (en) | 2001-06-12 | 2002-12-23 | Pelikan Technologies, Inc. | Self optimizing lancing device with adaptation means to temporal variations in cutaneous properties |
| US7981056B2 (en) | 2002-04-19 | 2011-07-19 | Pelikan Technologies, Inc. | Methods and apparatus for lancet actuation |
| US7025774B2 (en) | 2001-06-12 | 2006-04-11 | Pelikan Technologies, Inc. | Tissue penetration device |
| US9795747B2 (en) | 2010-06-02 | 2017-10-24 | Sanofi-Aventis Deutschland Gmbh | Methods and apparatus for lancet actuation |
| US9226699B2 (en) | 2002-04-19 | 2016-01-05 | Sanofi-Aventis Deutschland Gmbh | Body fluid sampling module with a continuous compression tissue interface surface |
| US8337419B2 (en) | 2002-04-19 | 2012-12-25 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
| US7976476B2 (en) | 2002-04-19 | 2011-07-12 | Pelikan Technologies, Inc. | Device and method for variable speed lancet |
| US7297122B2 (en) | 2002-04-19 | 2007-11-20 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US7175642B2 (en) | 2002-04-19 | 2007-02-13 | Pelikan Technologies, Inc. | Methods and apparatus for lancet actuation |
| US8360992B2 (en) | 2002-04-19 | 2013-01-29 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
| US8221334B2 (en) | 2002-04-19 | 2012-07-17 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
| US7892183B2 (en) | 2002-04-19 | 2011-02-22 | Pelikan Technologies, Inc. | Method and apparatus for body fluid sampling and analyte sensing |
| US7491178B2 (en) | 2002-04-19 | 2009-02-17 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US7547287B2 (en) | 2002-04-19 | 2009-06-16 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US8702624B2 (en) | 2006-09-29 | 2014-04-22 | Sanofi-Aventis Deutschland Gmbh | Analyte measurement device with a single shot actuator |
| US7198606B2 (en) | 2002-04-19 | 2007-04-03 | Pelikan Technologies, Inc. | Method and apparatus for a multi-use body fluid sampling device with analyte sensing |
| US7909778B2 (en) | 2002-04-19 | 2011-03-22 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US7648468B2 (en) * | 2002-04-19 | 2010-01-19 | Pelikon Technologies, Inc. | Method and apparatus for penetrating tissue |
| US9795334B2 (en) | 2002-04-19 | 2017-10-24 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
| US8579831B2 (en) * | 2002-04-19 | 2013-11-12 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
| US8784335B2 (en) | 2002-04-19 | 2014-07-22 | Sanofi-Aventis Deutschland Gmbh | Body fluid sampling device with a capacitive sensor |
| US7331931B2 (en) | 2002-04-19 | 2008-02-19 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US8267870B2 (en) | 2002-04-19 | 2012-09-18 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for body fluid sampling with hybrid actuation |
| US7901362B2 (en) * | 2002-04-19 | 2011-03-08 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US7674232B2 (en) | 2002-04-19 | 2010-03-09 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US9248267B2 (en) | 2002-04-19 | 2016-02-02 | Sanofi-Aventis Deustchland Gmbh | Tissue penetration device |
| US9314194B2 (en) * | 2002-04-19 | 2016-04-19 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
| US7892185B2 (en) | 2002-04-19 | 2011-02-22 | Pelikan Technologies, Inc. | Method and apparatus for body fluid sampling and analyte sensing |
| US7229458B2 (en) | 2002-04-19 | 2007-06-12 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US7232451B2 (en) | 2002-04-19 | 2007-06-19 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US8574895B2 (en) | 2002-12-30 | 2013-11-05 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus using optical techniques to measure analyte levels |
| WO2004103147A2 (en) * | 2003-05-02 | 2004-12-02 | Pelikan Technologies, Inc. | Method and apparatus for a tissue penetrating device user interface |
| ES2347248T3 (es) | 2003-05-30 | 2010-10-27 | Pelikan Technologies Inc. | Procedimiento y aparato para la inyeccion de fluido. |
| DK1633235T3 (da) | 2003-06-06 | 2014-08-18 | Sanofi Aventis Deutschland | Apparat til udtagelse af legemsvæskeprøver og detektering af analyt |
| WO2006001797A1 (en) | 2004-06-14 | 2006-01-05 | Pelikan Technologies, Inc. | Low pain penetrating |
| US8282576B2 (en) | 2003-09-29 | 2012-10-09 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for an improved sample capture device |
| WO2005037095A1 (en) | 2003-10-14 | 2005-04-28 | Pelikan Technologies, Inc. | Method and apparatus for a variable user interface |
| US7822454B1 (en) | 2005-01-03 | 2010-10-26 | Pelikan Technologies, Inc. | Fluid sampling device with improved analyte detecting member configuration |
| WO2005065414A2 (en) | 2003-12-31 | 2005-07-21 | Pelikan Technologies, Inc. | Method and apparatus for improving fluidic flow and sample capture |
| BRPI0510779A (pt) * | 2004-05-14 | 2007-11-20 | Bayer Healthcare Llc | métodos para realizar ajuste de hematócrito em ensaios e dispositivos para os mesmos |
| US8828203B2 (en) | 2004-05-20 | 2014-09-09 | Sanofi-Aventis Deutschland Gmbh | Printable hydrogels for biosensors |
| US9775553B2 (en) | 2004-06-03 | 2017-10-03 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for a fluid sampling device |
| EP1765194A4 (en) | 2004-06-03 | 2010-09-29 | Pelikan Technologies Inc | METHOD AND APPARATUS FOR MANUFACTURING A DEVICE FOR SAMPLING LIQUIDS |
| WO2006072004A2 (en) * | 2004-12-30 | 2006-07-06 | Pelikan Technologies, Inc. | Method and apparatus for analyte measurement test time |
| US8652831B2 (en) | 2004-12-30 | 2014-02-18 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for analyte measurement test time |
| US20060167382A1 (en) * | 2004-12-30 | 2006-07-27 | Ajay Deshmukh | Method and apparatus for storing an analyte sampling and measurement device |
| US7722537B2 (en) * | 2005-02-14 | 2010-05-25 | Optiscan Biomedical Corp. | Method and apparatus for detection of multiple analytes |
| US20060281187A1 (en) | 2005-06-13 | 2006-12-14 | Rosedale Medical, Inc. | Analyte detection devices and methods with hematocrit/volume correction and feedback control |
| US8801631B2 (en) | 2005-09-30 | 2014-08-12 | Intuity Medical, Inc. | Devices and methods for facilitating fluid transport |
| EP1928302B1 (en) | 2005-09-30 | 2012-08-01 | Intuity Medical, Inc. | Fully integrated wearable or handheld monitor |
| US20090314066A1 (en) * | 2006-09-20 | 2009-12-24 | Koninklijke Philips Electronics N.V. | Sensor device for and a method of sensing particles |
| JP4814952B2 (ja) * | 2006-10-19 | 2011-11-16 | パナソニック株式会社 | 血液試料のヘマトクリット値の測定方法、血液試料中の分析物の濃度の測定方法、センサチップおよびセンサユニット |
| EP2058651B1 (en) | 2006-10-19 | 2015-09-02 | Panasonic Healthcare Holdings Co., Ltd. | Method for measuring hematocrit value of blood sample, method for measuring concentration of analyte in blood sample, sensor chip and sensor unit |
| US8597190B2 (en) | 2007-05-18 | 2013-12-03 | Optiscan Biomedical Corporation | Monitoring systems and methods with fast initialization |
| WO2009126900A1 (en) * | 2008-04-11 | 2009-10-15 | Pelikan Technologies, Inc. | Method and apparatus for analyte detecting device |
| EP2293719B1 (en) | 2008-05-30 | 2015-09-09 | Intuity Medical, Inc. | Body fluid sampling device -- sampling site interface |
| EP2299903B1 (en) | 2008-06-06 | 2021-01-27 | Intuity Medical, Inc. | Detection meter and mode of operation |
| DK3639744T3 (da) | 2008-06-06 | 2022-02-21 | Intuity Medical Inc | Blodglukosemåler og fremgangsmåde til anvendelse |
| JP2012504233A (ja) * | 2008-09-30 | 2012-02-16 | メナイ メディカル テクノロジーズ リミテッド | サンプル測定システム |
| US9375169B2 (en) | 2009-01-30 | 2016-06-28 | Sanofi-Aventis Deutschland Gmbh | Cam drive for managing disposable penetrating member actions with a single motor and motor and control system |
| WO2010105850A2 (de) * | 2009-03-20 | 2010-09-23 | Roche Diagnostics Gmbh | Testelement zum bestimmen einer körperflüssigkeit und verfahren zum messen |
| MX2011010826A (es) * | 2009-04-15 | 2012-01-20 | Relia Diagnostic Systems Inc | Dispositivos para diagnostico y métodos relacionados. |
| WO2011065981A1 (en) | 2009-11-30 | 2011-06-03 | Intuity Medical, Inc. | Calibration material delivery devices and methods |
| US8391940B2 (en) | 2010-02-04 | 2013-03-05 | Lifescan, Inc. | Methods and systems to correct for hematocrit effects |
| GB201005357D0 (en) | 2010-03-30 | 2010-05-12 | Menai Medical Technologies Ltd | Sampling plate |
| GB201005359D0 (en) | 2010-03-30 | 2010-05-12 | Menai Medical Technologies Ltd | Sampling plate |
| US8965476B2 (en) | 2010-04-16 | 2015-02-24 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
| EP3156796A1 (en) | 2010-06-09 | 2017-04-19 | Optiscan Biomedical Corporation | Measuring analytes in a fluid sample drawn from a patient |
| CN101963578A (zh) * | 2010-09-11 | 2011-02-02 | 大连工业大学 | 一种测定制浆黑液还原糖含量的方法 |
| JP5806884B2 (ja) * | 2010-09-24 | 2015-11-10 | 株式会社堀場製作所 | 全血免疫測定装置及び全血免疫測定方法 |
| CA2843945C (en) | 2011-08-03 | 2022-06-21 | Intuity Medical, Inc. | Devices and methods for body fluid sampling and analysis |
| US8623660B2 (en) * | 2011-09-30 | 2014-01-07 | Lifescan Scotland Limited | Hand-held test meter with phase-shift-based hematocrit measurement circuit |
| US9903830B2 (en) * | 2011-12-29 | 2018-02-27 | Lifescan Scotland Limited | Accurate analyte measurements for electrochemical test strip based on sensed physical characteristic(s) of the sample containing the analyte |
| US20150118689A1 (en) | 2013-10-24 | 2015-04-30 | Quidel Corporation | Systems and methods for whole blood assays |
| US11450430B2 (en) * | 2014-12-31 | 2022-09-20 | Invent.ly LLC | Remote analyte testing system |
| JP6487251B2 (ja) * | 2015-03-30 | 2019-03-20 | シーシーアイホールディングス株式会社 | バイオセンサ |
| US11541385B2 (en) * | 2018-07-06 | 2023-01-03 | Qorvo Us, Inc. | Methods of measuring hematocrit in fluidic channels including conductivity sensor |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0525398A2 (en) * | 1991-07-29 | 1993-02-03 | Toa Medical Electronics Co., Ltd. | Method of preparing specimen for classifying and counting leukocytes |
| WO2002014535A2 (en) * | 2000-08-11 | 2002-02-21 | Cambridge Sensors Limited | Electrochemical strip test for small volumes |
| CN1380976A (zh) * | 2000-05-26 | 2002-11-20 | 松下电器产业株式会社 | 生物传感器 |
| CN1380978A (zh) * | 2000-06-01 | 2002-11-20 | 松下电器产业株式会社 | 生物传感器及血液成分分析方法 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4935346A (en) | 1986-08-13 | 1990-06-19 | Lifescan, Inc. | Minimum procedure system for the determination of analytes |
| US5049487A (en) | 1986-08-13 | 1991-09-17 | Lifescan, Inc. | Automated initiation of timing of reflectance readings |
| US5049394A (en) | 1987-09-11 | 1991-09-17 | E. R. Squibb & Sons, Inc. | Pharmaceutical composition containing high drug load and method for preparing same |
| JPH01262470A (ja) * | 1988-04-12 | 1989-10-19 | Fuji Photo Film Co Ltd | 乾式全血分析要素 |
| EP0397424A3 (en) * | 1989-05-08 | 1991-08-21 | Biotrack, Inc. | Multiple analysis system |
| US5306623A (en) * | 1989-08-28 | 1994-04-26 | Lifescan, Inc. | Visual blood glucose concentration test strip |
| US5331958A (en) | 1992-03-31 | 1994-07-26 | University Of Manitoba | Spectrophotometric blood analysis |
| CA2127172C (en) * | 1993-08-05 | 1998-07-14 | Amy H. Chu | Analyte detection device and process |
| JP3586743B2 (ja) * | 1995-10-09 | 2004-11-10 | アークレイ株式会社 | ヘマトクリット値を補正した測定方法 |
| AU722471B2 (en) | 1995-10-17 | 2000-08-03 | Lifescan, Inc. | Blood glucose strip having reduced sensitivity to hematocrit |
| JP3664278B2 (ja) | 1996-01-17 | 2005-06-22 | 富士写真フイルム株式会社 | 血漿または血清試料の調製方法 |
| JPH10108695A (ja) * | 1996-10-07 | 1998-04-28 | Kdk Corp | グルコース濃度の測定方法 |
| JP3704550B2 (ja) * | 1996-10-31 | 2005-10-12 | アークレイ株式会社 | 乾式測定試験素子 |
| US5948695A (en) * | 1997-06-17 | 1999-09-07 | Mercury Diagnostics, Inc. | Device for determination of an analyte in a body fluid |
| US6587705B1 (en) * | 1998-03-13 | 2003-07-01 | Lynn Kim | Biosensor, iontophoretic sampling system, and methods of use thereof |
| JP2000262298A (ja) | 1999-03-15 | 2000-09-26 | Fuji Photo Film Co Ltd | 全血中のグルコース濃度もしくはコレステロール濃度の定量方法 |
| EP1255978A1 (en) | 2000-01-18 | 2002-11-13 | Radiometer Medical A/S | Apparatus, sample cuvette and method for optical measurements |
| US6485923B1 (en) | 2000-02-02 | 2002-11-26 | Lifescan, Inc. | Reagent test strip for analyte determination having hemolyzing agent |
-
2004
- 2004-01-31 EP EP04002141.2A patent/EP1447665B1/en not_active Revoked
- 2004-02-02 US US10/770,235 patent/US7323315B2/en active Active
- 2004-02-10 AU AU2004200506A patent/AU2004200506B2/en not_active Ceased
- 2004-02-10 CA CA2457665A patent/CA2457665C/en not_active Expired - Fee Related
- 2004-02-10 JP JP2004033126A patent/JP4515786B2/ja not_active Expired - Lifetime
- 2004-02-10 CN CN2004100396202A patent/CN1558235B/zh not_active Expired - Lifetime
-
2005
- 2005-04-21 HK HK05103452.0A patent/HK1070942A1/xx not_active IP Right Cessation
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0525398A2 (en) * | 1991-07-29 | 1993-02-03 | Toa Medical Electronics Co., Ltd. | Method of preparing specimen for classifying and counting leukocytes |
| CN1380976A (zh) * | 2000-05-26 | 2002-11-20 | 松下电器产业株式会社 | 生物传感器 |
| CN1380978A (zh) * | 2000-06-01 | 2002-11-20 | 松下电器产业株式会社 | 生物传感器及血液成分分析方法 |
| WO2002014535A2 (en) * | 2000-08-11 | 2002-02-21 | Cambridge Sensors Limited | Electrochemical strip test for small volumes |
Non-Patent Citations (1)
| Title |
|---|
| JP特开平9-105750A 1997.04.22 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2457665C (en) | 2012-12-18 |
| AU2004200506B2 (en) | 2008-12-18 |
| EP1447665B1 (en) | 2016-06-29 |
| JP2004340923A (ja) | 2004-12-02 |
| CA2457665A1 (en) | 2004-08-11 |
| US7323315B2 (en) | 2008-01-29 |
| AU2004200506A1 (en) | 2004-08-26 |
| JP4515786B2 (ja) | 2010-08-04 |
| EP1447665A2 (en) | 2004-08-18 |
| EP1447665A3 (en) | 2005-12-28 |
| US20040157275A1 (en) | 2004-08-12 |
| HK1070942A1 (en) | 2005-06-30 |
| CN1558235A (zh) | 2004-12-29 |
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