CN1301965A - 医学诊断装置的微滴分配 - Google Patents

医学诊断装置的微滴分配 Download PDF

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CN1301965A
CN1301965A CN00137319A CN00137319A CN1301965A CN 1301965 A CN1301965 A CN 1301965A CN 00137319 A CN00137319 A CN 00137319A CN 00137319 A CN00137319 A CN 00137319A CN 1301965 A CN1301965 A CN 1301965A
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I·A·哈丁
R·J·沙特勒
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Abstract

一种医学诊断装置,带有非吸收性基底,此基底有亲水性靶区域,可通过微滴非击打式打印,将试剂置于靶区域上。在试剂沉积过程中,该装置相对于微滴的液流移动,使之在基底上形成基本均匀的试剂层。此装置尤其适用于测定血液凝结时间。在一个优选实施方案中,当所测血样与试剂相互作用时,通过监测穿过靶区的透射光而测定凝结时间。

Description

医学诊断装置的微滴分配
本申请是1999年6月15日提交的申请NO.09/333,765的后续申请。
本发明涉及一种由非击打式打印法构建的医学诊断装置，更具体地说涉及由一种试剂以非击打式印于装置亲水性表面上而构建起来的医学诊断装置。
各种医学诊断方法，包括用生物液，如血液/尿液，或唾液进行的试验，是以此液体或其中的一种成分、如血清等的物理特性的变化为基础的。这些特性可以是电、磁、流体或光学性能。当检测一种光学性能时，可以用透明或半透明装置盛装生物液或试剂。液体在光吸收方面的变化与液体中被分析物的浓度或性能有关。典型的是，光源邻近装置的一个表面，而检测器与相对的表面邻近。检测器测定透过液体样品的光。另外，光源和检测器可以在装置的同一侧，在这种情况下，检测器测定样品的散射光和/或反射光。最后，可以将反射器置于或邻近于相对的表面。后一种类型的装置，其中光线透过样品区，然后第二次通过反射，它被称为“透射反射”(transflectance)装置。此说明书和权利要求书中所述的“光”包括红外和紫外光谱及可见光。“吸收”指光束通过介质后强度的减弱；因此它包括“真正的”吸收和散射。
1994年2月3日出版的Wells等的WO94/02850记载了一种透明的实验装置的例子。他们的装置包括一密封室，它是透明或半透明的、抗渗的、刚性或半刚性的。测定物和一种或多种测定试剂置于室中的预定位置处。在即将开始测定之前打开室加入样品。测定试剂和样品中的被测物结合，在测定结束时导致所选试剂的光学性质、如颜色等变化。可以用肉眼或光学仪器观察结果。
1971年11月16日授予的Davis的美国专利U.S.3,620,676公开了一种液体色度指示器。此指示器包括可压缩的“半球形腔室”。压缩再放开此球形以形成从液源抽吸液体的负压，使之通过半球形腔室，此半球形腔室的壁上压有指示器。只通过球被压缩的程度和当球被放开时指示剂入口浸在液源中的时间来控制液流进入指示器的流量。
1972年2月8日授予的Hurtig的美国专利U.S.3,640,267公开了一种收集体液样品的容器，其包括有弹性、可折叠壁的腔室。在容器入口放入被收集的液体前压缩其壁。放开后，此壁恢复到未折叠的状态，将液体从入口吸入。而用上述Davis的装置只能很有限地控制液流进入指示器。
1978年5月9日授予的Lilja等人的美国专利U.S.4,088,448公开了一种透明容器，可以对混有试剂的样品进行光学分析。该试剂覆于腔室的壁上，然后室中充以液体样品。样品与试剂混合产生能被光学检测的变化。
以上所述的和参考文献中的实验装置特别包括一干燥试验带，试剂被覆在其上一个或多个预定的位置。在大量的此装置的预定位置涂上试剂，大体上是通过标准的印刷方法完成的；然而非击打式印刷有某些显著的优势。如，非击打式印刷机可以更小、更轻和更价廉，因为他们不必持续进行印刷头在基片上的重复击打。他们也允许使用透明的基片，如涉及光透射变化的光学仪器所需要的。J.L.Johnson，的《非击打印刷原理》(第3版,Palatino出版社,Irvine,CA1998)一书中记载了各种非击打式印刷的资料(也可参见：《无溅射喷雾制备更好的胶片》,H.L.Berger,《机械设计》,1998年2月5日,52-55页)。在这些各种非击打印刷中，认为喷墨打印适用于液体试剂。
1978年9月27日出版的英国专利说明书1,526,708公开了一种试剂实验装置，其包括一载体，其上印有两种不同的物质，它们以“预定的间隔”分离开。喷墨打印是已公开的一种打印技术。
1989年10月31日授予的Hayes等的美国专利U.S.4,877,745公开了一种将试剂印到印刷介质上的系统，其从一喷射管推进微滴并重复此过程，直到理想的试剂轮廓印在介质上。该装置使用了一种压电印刷头。
1992年4月28日授予的Klebe的美国专利U.S.5,108,926公开了一种装置，该装置通过用喷墨打印机直接将细胞设置在基底上、或涂上细胞粘合材料上，以使细胞在基底上准确固定。所用的喷墨打印机是Hewlett-Packard ThinkjetTM打印机，其为热喷墨打印机(见Hewlett-Packard杂志,1985年5月)。
1995年1月3日授予的Deeg等的美国专利U.S.5,378,638公开了一种测定液体样品中的被分析物的分析元件。该元件装配有喷墨打印机、使用热喷墨打印头，将一系列分隔室中的试剂喷墨打印出。
上述各参考文献明确或含蓄地表明与印刷介质上的图像铺展有关，因为图像清晰度随液体“墨水”干燥前在表面的铺展程度而降低。对于诊断应用，尤其需要清晰的图像，因为在装置的表面上不同的试剂紧挨着放置在一起，但在装置被所测样品沾湿前试剂不能相互接触(例如反应)。
本发明提供一种构建医学诊断试剂装置的方法，包括以下步骤：
a)提供非吸收性基底，其表面至少有一亲水性靶区域，
b)以非击打式打印头对靶区以内的一点上提供诊断试剂液体的脉冲式液流，
c)相对于基底移动该液流，并
d)重复步骤b)和c)足够的遍数以在靶区域形成足够均匀的液层。
本发明的诊断试剂装置可测定生物液分析物的浓度和特性，包括：
a)接受分析用的生物液样品的样品复盖区域，和
b)一个预定的亲水试剂区，通过非击打式印刷将诊断试剂液体置于其上，使其与样品反应，产生与液体中的分析物的浓度或特性相关的样品的可检测的物理变化。样品复盖区和试剂区域可以相同，也可以隔有输送样品的中间通道。测定一般是、但不必须是当样品在试剂域上时进行，在以下的描述中，所研究的测定是样品在试剂区内时进行。
此方法尤其适用于构建一种测定凝血酶原时间(PT)的装置，靶区域被覆一试剂组合物，其催化血液的级联式凝结。类以地，本发明的诊断试剂带尤其适用于测定全血样品的PT时间。
用于本说明书和权利要求书的术语“微滴”指体积在1皮升(picoliter)至一微升的范围内的液滴。
我们惊奇地发现靶区域的亲水性产生了优越的效果，亲水表面能铺展沉积的试剂，而这曾被认为是不理想的。
图1：本发明装置的平面图
图2：图1装置的分解图
图3：图1装置的透视图
图4：用于本发明装置的计量器的简图
图5：用于测定PT时间的数据图
图6：本发明装置另一实施方案的平面图
图7：用本发明的方法制备的涂层的平面图
图8：本发明的非击打式印刷法的图解
图9：证明本发明优点的图表
本发明的医学诊断试剂装置是通过非击打印刷工艺将试剂沉积在非吸收基底的亲水“试剂区”上而构建的。此类装置涉及生物液或其中某成分的物理参数，涉及液体的分析物浓度或液体的性质。虽然各种物理参数，如电、磁、流体或光学的，可以成为测定的基础，但光学参数的变化是优选的，下述的记载涉及一种光学装置。本装置的一个优选实施方案包括平面基底，如一种热塑膜。基底表面有样品复盖区和试剂区，样品在此发生光学参数的变化，如光散射。基底，或“底层”，与“中间”层和“上”层形成囊，产生负压将样品吸入装置中，形成断流接点，在样品布满试剂区后精确地切断液流。
优选装置在试剂区上大体是透明的，所以可以用一侧的光源照亮此区，在另一侧测定透射光。非击打印刷试剂使样品发生变化，用透射光的变化测定所需的分析物或流体特性。或者，从流体样品散射出的光或通过样品的光、和从二次反射(通过对侧的反射器等)回的光，可以作为光源用同侧的检测器进行检测。
此类装置适用于各种生物流体的分析试验，如测定生物化学或血液学特性，或测定这些流体中的蛋白、激素、碳水化合物、脂类、药物、毒物、气体、电解质等的浓度。进行这些测定的方法在文献中已有描述。这些试验中，它们的记载见如下文献：
(1)产色因子Ⅻa测定(和其他凝结因子)：Rand,M.D.等，《血液》,88,3432(1996)。
(2)X因子测定：Bick,R.L.《血栓形成和止血失调：临床和实验室实践》，芝加哥，ASCP出版社，1992
(3)DRVVT(稀释的鲁塞尔氏蝰蛇毒试验)：Exner,T等，《凝血和纤维蛋白溶解作用》(Blood Coag.fibrinol.),1,259(1990)。
(4)蛋白质的免疫浊度和免疫比浊测定法：Whicher,J.T.,CRC Crit.Rev.临床实验室科学18:213(1983)。
(5)TPA测定：Mann,K.G.,等，《血液》,76,755,(1990)；和Hartshorn,J.N.等，《血液》,78,833(1991)
(6)APTT(活化的部分促凝血酶原激酶时间测定)：Proctor,R.R.和Rapaport,S.I.《美国临床病理学杂志》,36,212(1961)；Brandt,J.T.和Triplett,D.A.《美国临床病理学杂志》,76,530(1981)；和Kelsey,P.R.《血栓形成血细胞》(Thromb.Haemost.)52,172(1984)。
(7)HbAlc测定(糖基化的血红蛋白测定)：Nicol,D.J.等，《临床化学》29,1694(1983)。
(8)总血红蛋白：Schneck等，《临床化学》，32/33,526(1986)；和美国专利4,088,448。
(9)Ⅹa因子：Vinazzer,H.,Proc.Symp.Dtsch.Ges.Klin.Chem.,203(1977)，Witt,I编辑。
(10)氧化氮的比色法测定：Schmidt,H.H.等，《生物化学》2,22(1995)
本装置尤其适用于测定血液凝结时间-“凝血酶原时间”或“PT时间”-关于此装置的详述见下文。为使此装置适宜上述应用所需的改进仅需通过常规实验来实现。
图1是本发明装置10的平面图。图2是此装置的分解图，图3是其透视图。将气囊14压缩后样品置于样品口12处。显然，层26和/或层28区域，即与气囊14的开口毗连的区域必须是有回弹力的，以使气囊14被压缩。约0.1mm厚的聚酯有适宜的回弹力和弹性。优选，顶层26的厚度约为0.125mm，底层28的厚度约为0.100mm。当气囊被松开后，负压吸引样品通过通路16进入试剂区18，此区含有非击打印刷试剂20。为保证试剂区18充满样品，气囊14的体积优选至少约等于通道16和试剂区18的总体积。如果试剂区18从下面照亮，层28必须是透明的，在此它与试剂区18毗连。对于PT试验，试剂20含有促凝血酶原激酶，而不含通常在冷冻干燥试剂中发现的增量剂。
如图1、2、3所示，断流接点22连接气囊14和试剂区18；然而，通道16可以在断流接点22的一侧或两侧延伸，将断流接点与试剂区18和/或气囊14分隔开。当样品到达断流接点22时，样品流停止。对于PT测定，重要的是在样品到达会重复出现“红细胞钱串形成”，即红细胞堆叠的点时，便使样品流停止，这是用本发明监控血液凝结的重要步骤。U.S.专利5,230,866记载了断流接点的操作原理，将其结合于此作为参考。
如图2所示，所有上述元件是借助夹在顶层26和底层28之间的中间层24中的开口形成。优选层24是双面粘着带。借助层26和/或28中的附加开口形成断流接点22，与层24中的开口对准，用封闭层30和/或32进行密封。如所示优选断流接点包括层26和28中的开口、密封层30和32。断流接点的开口至少与通道16等宽。图2还显示一种覆盖样品入口12视需要配置的滤器12A。滤器可以从全血样品中分离红细胞，和/或可以含有与血液反应的试剂以提供额外的信息。适宜的滤器包括各向异性膜，优选聚砜膜，可以从加拿大Toronto的光谱诊断用品公司得到。视需要配置的反射器18A可以在层26表面上或与其相邻，并位于试剂区18上方。如果有反射器，此装置成为透射反射装置。
用图1、2、3所示使用试验带的方法可以参考图4所示的计量器元件的图解进行理解，该计量器是一种自动计量器。或者，也可以进行手工操作(在此情况下，在样品加到样品入口12前以手工压缩气囊14，然后松开)。
使用者进行的第一步骤是接通计量器，由此给试验带检测器40、样品检测器42、测定系统44和视需要配置的加热器46供能。第二步是插入试验带。优选至少试验带上的一部分区域不透明，以便插入的试验带将阻挡检测器40b的LED40a的光照。(更优选的是，中间层由非透明材料组成，以使背照光不能进入测定系统44)。检测器40b因此感测到带已插入、并触发气囊驱动器48以压迫气囊14。计量器显示屏50然后引导使用者将样品置于样品入口12处作为第三步，使用者必须进行的最后一步是开始测定程序。
空的样品入口是反射性的。当将样品加入样品入口时，它从LED 42a吸收光，然后使反射到检测器42b的光减弱。此光的减弱又转过来向驱动器48发出信号以放开气囊14。由此在通道16中产生的负压吸引样品通过试剂区18到达断流接点22。从LED 44a发出的光通过试剂区18，当样品凝结时，检测器44b监测透过样品的光。当有多个试剂区时，测定系统44包括对每一个试剂区设置的LED/检测器对(如44a和44b)。将透射光作为时间的函数进行分析(如下所述)能够计算出PT时间，它显示于计量器显示屏50上。优选用加热器46将样品温度控制在37℃。
图5描述的是典型的“凝结特征”曲线，其中将从检测器44b通过的电流绘制成时间的函数。在试剂区内用44b于时间1首次检测血液。在1和2点间的间隔时间A内血液充满试剂区。由于红细胞使光散射，导致此时间间隔内电流降低，由此可近似地测定血细胞比容。在点2，样品充满试剂区并静止，断流接点使其停止运动。红细胞开始如硬币样堆叠(红细胞钱串形成)。红细胞钱串效应会增加点2和3时间间隔内通过样品的透射光(和减少散射)。在点3，凝块形成使红细胞钱串形成停止，而通过样品的透射光达到最大值。从1与3点或2与3点之间的间隔B可以计算出PT时间。然后，血液从液体变为半固体凝胶状，同时伴随相应的光透射降低。最大值3和终点4之间的电流C的降低与样品的血纤维蛋白原相关。
图6描述了本装置的一个优选实施方案。它是一个包括旁路52的多通道装置。旁路52为样品提供一个进入试剂区118、218和318后的流通通道。通过断流接点122处的气囊侧的负压将样品吸入旁路。当断流接点两侧的周围压力相等时样品流停止。试剂区118含有促凝血酶原激酶。优选试剂区218和318含有对照样，进一步优选下述对照样。试剂区218含有促凝血酶原激酶、牛洗脱物和重组因子Ⅶa，选择组合物，以便通过抗凝剂，如华法令的反作用使血样的凝结时间达正常。试剂区318仅含有促凝血酶原激酶和牛洗脱物，部分抑制抗凝剂的效应。因此，在此试验带上进行3种测定。在试剂区118测定样品的PT时间，这是主要的欲测项目。然而，仅当试剂区218和318的测定产生预定范围内的结果时，此测定才有效。如果一种或两种这种对照测定超出范围，就进行再次试验。延伸的断流接点122使3个试剂区内的所有液流停止。
上述图1和2画出的装置优选由热塑性片26和28层压到两侧表面均涂有粘合剂的热塑性中间层24上而形成。可以通过例如激光切割或冲切层24、26和28形成开口，该开口形成图1所示的元件。
底层28上的试剂区18由中间层24的开口限定。优选地，面向底层28的顶层26的底表面是疏水性的，至少在通道16和试剂区18的范围内如此。试剂区18的表面是亲水性的。优选样品入口12的表面也是亲水性的，以便于装置的灌注；即，使样品从入口12流向试剂区18。亲水性样品和试剂区所具有的常见方式是使底层28的全部表面都是亲水性的。市售的有适宜的亲水表面的热塑性膜包括3M9962防雾膜(“Antifog”)，可以从St.Paul,MN的3M健康护理公司、医疗专用品部购得；FMCGelBond膜可以从Rockland,ME的BioWhittaker分子应用公司购得；表面经火焰-电晕处理或等离子体处理的聚对苯二甲酸乙二醇酯(PET)膜；离聚物膜；和其他常用的有亲水性表面或涂层的热塑性膜。涂以一层3M专用涂层的PET防雾膜膜是优选的基底材料。
在对用于本装置和方法的基底的适用性所进行的测定中，可以用多种不同方法测定表面亲水性。
接触角是位于可湿润的表面上的液(通常是纯化水)滴的边缘，与此表面之间的标称角度。测定接触角的方法已经标准化，并可用手工或自动设备进行测定。(ASTM实验方法D5946-96，采用水接触角测定法的电晕处理聚合物膜的标准试验法。)当所测的角大于25°时，一般认为该数据是精确的和可再现的，如果接触角约为60°或更小，就认为膜是容易湿润的。测得的防雾膜的角约为25°。
通过已知表面张力的溶液在被测表面上铺展并观察该溶液是否“成珠”来测定湿润张力(ASTM实验方法D2578-94，测定聚乙烯和聚丙烯膜的湿润张力的标准试验法)。成珠表示液体内部吸引力超过了表面的吸附。将该液体以达因/cm单位校准，该溶液称为达因溶液。在30-60达因/cm的范围内它们可从市售获得。用最低值溶液开始测定表面，并逐渐增加，至最高值溶液。该表面的润湿张力达因/cm值，指定为在该表面上铺展需约2秒钟的溶液所具有的相应达因/cm值。因为防雾膜湿润了所有溶液，其特点即为表面湿润张力大于60达因/cm。
3M的医疗专业部已开发了一种表征膜的水湿润作用的湿润实验。(3M SMD#6122，湿润实验，12月4日，1998-能从3M中心得到，St,Paul,MN55144-1000)。该实验包括细心地将染料的水溶液置于表面上，使其干燥，测定干燥斑的直径。收集数据通常在35-40点范围内，其显示一个非常易湿润的表面。
基于上述测定，我们得出结论：防雾表面是十分亲水的。当一表面有足够的亲水性时，那么试剂滴在表面铺展，就有足够多的液滴沉积，在预定区域形成足够均匀的试剂层。如本说明书和权利要求书使用的，术语“基本均匀”不能解释为整个靶区域上被覆盖表面的厚度必需是相同的，甚至也不表示整个表面都被覆盖。
图7描述了一个典型的被覆盖靶区域的一部分的平面图。注意表面(A)的部分未被覆盖，虽然大部分表面(B)被覆盖了。优选至少80％靶区域是被覆盖的。优选被覆区(B)的厚度变化达最小化；如，最厚的区或小于被覆区平均厚度的3倍。根据试剂的性质和特定的应用，被覆区平均被覆厚度通常约为0.1mm-1mm。
图8描述了将试剂通过非击打方式印刷到本申请基底的试剂区的装置略图。印刷头60重复将试剂液滴的液流喷射到卷材(web)62上，卷材62按箭头所示的方向运动。视需要配置的罩64和66保证液滴流只到达试剂区18内的卷材62上。
为控制印刷，罩66，即最接近打印头60的罩，可视需要具有面向打印头的疏水表面68。从印刷头60的多重分配器喷嘴流出的试剂在罩表面68上形成多重试剂点。因为表面是疏水的，各点保持分隔，并可以用下游光学系统70分别观测。表面18的亲水性使液滴到达能使之铺展和/或融合的表面，所以使光学系统直接检测试剂区的各个液滴更困难。
如果需要，光学系统70可以检测并排除不合格产品。如若是缺少点，可以表示一个或多个分配器喷嘴不合格。适宜的光学检测法是暗视野显微镜检查、阴影、图形、激光照明等。可视需要将着色剂或荧光染料加到试剂中，使其更易被光学系统70所检出。如在试剂中加入亚甲蓝染料使其终浓度约为0.1％，可使试剂能被光学系统检出，而基本不改变用试剂进行的测定结果。
打印头60可以是任何本领域已知的非击打式打印头，包括超声波式、电记录式、离子喷射式等打印头。优选打印头60是喷墨打印头，更优选热喷墨打印头。
以下的实施例描述本发明的各种实施方案，但并不对本发明进行任何方式的限定。
实施例1(对比例)
制备上述用于PT测定类型的两个试验带(见图1-3)。试验带之间的不同在于：试验带A有未加以处理的聚对苯二甲酸乙二醇酯底层28，试验带B有FMC GelBond膜的底层28。把血样加到每个试验带上，按图4所述的装置测定PT时间。图9描述了得到的凝结曲线。试验带A的曲线有一比较平的峰(与图5中的峰3相应)。峰的平坦度限制了PT计算结果的精确度。相反，试验带B的曲线有非常尖的峰，拥有更大的精确度。(注意用两个试验带测定的样品的PT时间不同)。
实施例2
先将夹在两个可揭下式衬垫之间的双面涂有粘合剂的胶带(RX 675SLT，购自ScapaTapes,Windsor,CT)穿过层压和旋转冲切转化系统中而构建本发明装置。图2显示的方式，除断流接点外，是通过顶层的可揭下式衬垫和胶带(tape)进行切割，而不通过底层的可揭下式放衬垫切割，然后将该底衬垫与从胶带切下的一同作为废料除去。将3M防雾膜层压到胶带的暴露底面。然后通过热喷墨打印将试剂(促凝血酶原激酶，购自Ortho临床诊断剂公司，Raritan,NJ)打印到膜的试剂区(18)，使用的打印头为Hewlett Packard,Corvallis,OR的51612A。在未经处理的聚酯膜(AR1235，购自Glen Rock,PA,粘合剂研究所上切出样品入口，然后层压到双面胶带的顶层(除去可揭下层后)。然后以冲模通过三层夹层的切出断流接点。最后，将可以从3M,St.Paul,MN购得的单面粘合胶带-Catalog No.9843(MSX4841)铺到聚酯层的外面密封该断流接点。
实施例3
接着用类似于实施例1所述的方法，制备图6所述的试验带。通过热喷墨打印到区域118P、218P和318P的试剂分别是促凝血酶原激酶；促凝血酶原激酶，牛洗脱物和重组因子Ⅶa；以及仅有促凝血酶原激酶和牛洗脱物。可以从HaemotologicTechnologies,Burlington,VT得到牛洗脱物(血浆柠檬酸钡牛洗脱物)；从美国诊断用品公司，格林威治(Greenwich),Ct.得到重组因子Ⅶa。
可以用此实施例的试验带测定全血样品，得到图5所示的关于各个试剂区的曲线。用从曲线上得到的对照(试剂区218P和318P)数据评定从试剂区118P的曲线上得到的数据。结果是，比只用单个试剂区的试验带进行的测定，可以更可靠地确定PT时间。

Claims (10)

1．一种构建医学诊断试剂装置的方法，其特征在于包括以下步骤：
a)提供非吸附性基底，在其表面至少有一个亲水性靶区域，
b)以非击打式打印头对靶区域内的一点上提供诊断试剂液体的微滴脉冲液流，
c)相对于基底移动液流，并
d)至少重复步骤b)和c)足够的次数，以在靶区域形成基本均匀的液层。
2．根据权利要求1所述的方法，其特征在于至少一个靶区域各自有不大于约60°的水接触角度。
3．根据权利要求1所述的方法，其特征在于打印头是热喷墨打印头。
4．根据权利要求2所述的方法，其特征在于液流沿基本垂直于基底的方向运行，而通过沿基本垂直于液流运行方向的方向上移动基底，而使液流相对于基底移动。
5．根据权利要求1所述的方法，其特征在于试剂中含有着色剂。
6．一种用于测定生物液的分析物浓度或特性的诊断试剂装置，包括非吸收性基底，它含有
a)用于接受欲分析的生物液样品的样品复盖区，
b)预定的亲水试剂区，通过非击打式打印将与样品相互作用的诊断试剂液体置于其上，以便在样品中产生与液体的分析物浓度或特性相关的可检测的物理变化。
7．根据权利要求6所述的装置，其特征在于样品复盖区是亲水性的。
8．根据权利要求6所述的装置，其特征在于基底包括基本上透明的热塑性膜片。
9．根据权利要求6所述的装置，其特征在于试剂液体包括促凝血酶原激酶。
10．根据权利要求6所述的装置，其特征在于试剂液体含有着色剂。
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CN103143405A (zh) * 2007-09-20 2013-06-12 艾莱恩微观系统有限公司 确定流体凝结时间的微流体装置和方法
CN103143405B (zh) * 2007-09-20 2014-08-27 艾莱恩微观系统有限公司 确定流体凝结时间的微流体装置和方法
CN104995510A (zh) * 2012-12-20 2015-10-21 塞浦西斯有限公司 脓毒症的即时测定装置和方法
CN110554007A (zh) * 2014-04-30 2019-12-10 仪器实验室公司 用于通过光检测进行定点照护凝固测定的方法及系统
CN108369191A (zh) * 2015-10-19 2018-08-03 Dnt科研有限责任公司 快速挤压驱流体外诊断法

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