CN104023968A - 多层机织制品以及这种多层机织制品用作干基质点应用的载体的用途 - Google Patents

多层机织制品以及这种多层机织制品用作干基质点应用的载体的用途 Download PDF

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Publication number
CN104023968A
CN104023968A CN201280064010.0A CN201280064010A CN104023968A CN 104023968 A CN104023968 A CN 104023968A CN 201280064010 A CN201280064010 A CN 201280064010A CN 104023968 A CN104023968 A CN 104023968A
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goods
layer
laminar
layers
angle
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CN104023968B (zh
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恩泽·门格因克
约翰内斯·海伦娜·迈克尔·默梅尔斯
邱军
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DSM IP Assets BV
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DSM IP Assets BV
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    • B32B5/02—Layered products characterised by the non- homogeneity or physical structure, i.e. comprising a fibrous, filamentary, particulate or foam layer; Layered products characterised by having a layer differing constitutionally or physically in different parts characterised by structural features of a fibrous or filamentary layer
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Abstract

本发明涉及基本上薄片状的制品，其包含2个接触的基本上薄片状的层，其中这些层包含机织的亲水性材料。

Description

多层机织制品以及这种多层机织制品用作干基质点应用的载体的用途
本发明涉及基本上薄片状的制品，其包含2个接触的基本上薄片状的层，其中这些层包含机织的亲水性材料。
干血点(DBS)技术涉及一种采样方法，其中将血液(由例如手指或足底刺孔获得)点到载体上并干燥。这些干血点可以在例如萃取后通过诸如LC-MS/MS来分析。这种采样技术的主要优点是(1)仅需要少量(滴)的血液，(2)与静脉穿刺(venapunction)相比，通过侵入性更小的手指刺孔(prick)就能够获得血液，(3)干点更易于存储且不需要冷却，(4)通过邮寄方式就能够送出干血点，而且也不需要冷却，(5)分析物通常在干血中比在液体血中更稳定。考虑到通过进行手指刺孔获得血液、形成血点(blood spotting)并通过邮寄将干点送出都是非常快速的并且是很容易进行的步骤这个事实，该技术能够由非医学技术人员(例如患者)自己在非医学环境下(例如在家)进行。
主要的缺点是(1)该技术不能用于挥发性化合物，(2)在送出和储存前需要干燥，(3)对于大多数载体来说，每个载体区域中血的点量(以μL计)依赖于血液的血细胞比容值。当所定义的区域是从用于分析目的的血点(blood spot)打孔得到时，这种依赖性对定量结果具有影响。与具有较低血细胞比容值的血液相比，血细胞比容值越高，所测得的浓度就越高。
血细胞比容依赖性被认为是对在一些应用领域中(例如在药学领域中)采纳(acceptance)DBS技术的一个严重问题。该问题的解决方案是：例如形成已知的固定体积(例如通过使用(微)毛细管)的斑点，然后分析整个斑点。在该过程中，分析固定血液体积，与血液的血细胞比容值无关。该解决方案的主要缺点是，必须进行额外的步骤，这样的话，需要处理毛细管和精确成点。尤其对于自己进行手指刺孔和形成血点(例如用于治疗性药物监测)的非医学技术人员来说，此额外的步骤是一个重大缺点。
本发明通过提供基本上薄片状的制品来克服血细胞比容依赖性，该制品包含接触的至少两个基本上薄片状的层，其中这些层包含机织的亲水性材料。
优选地，本发明提供了所述制品，其中薄片状的层包含具有以下性质的材料：11至800μm的网状开口和38至520μm的层厚、1至65％的开口区域(open area)、270至9n/cm的网纱经线数(mesh count warp)、206至9n/cm的网纱纬线数(mesh count weft)、20至800μm(优选地24至480μm)的经线直径(wire diameter warp)和纬线直径(wirediameter weft)。本发明具体地提供了如下制品，其中各个层包含具有以下性质的材料：20至200μm的网状开口和38至200μm的层厚、30至50％的开口区域、100至200n/cm的网纱经线数、100至200n/cm的网纱纬线数、24至50μm的经线直径和纬线直径；并且本发明最具体地提供了如下制品，其中各个层包含具有以下性质的材料：约40μm的网状开口和约38μm的层厚、40％的开口区域、约158n/cm的网纱经线数、约158n/cm的网纱纬线数、均为约24μm的经线直径和纬线直径。典型地，接触的两个基本上薄片状的层由相同的材料构成，并且如果制品包含更多的基本上薄片状的层，那么优选的是所有层均由相同的材料构成。
本文中线直径是指形成织物的线的材料的最大直径。线可以是单丝或复丝材料。20μm至200μm的线直径是优选的，这是因为当后来通过对具有干基质点(dried matrix spot)的制品打孔对该干基质点进行采样时，较细的线更易于切割，因此更优选的是线直径20μm至150μm的薄片状的层。
发现对于非常宽的网状开口来说，在对具有干基质点的制品打孔时基质会损失。因此，在一个优选的实施方式中，网状开口为至多200μm，并且更优选地网状开口为至多125μm。非常小的网状开口会导致低的吸收容量，因此优选的是网状开口为至少20μm、以及更优选地至少25μm，以确保基本的开口区域和血细胞通过。
本文中开口区域是指当垂直于主表面观察时层中未被线占据的层的百分数。考虑经线方向与纬线方向之间的变化(如果存在的话)，开口区域可由线的直径和网状开口计算得到。因此，开口区域与薄片状层之间的间距无关，而与各个层有关。
本文中网状开口是指相邻经线的边缘之间和相邻纬线的边缘之间的最大开口距离。优选地，网状开口在经线方向和纬线方向上是相同的，并且如果网状开口在经线和纬线方向上不相同，则应指明网状开口是就哪个方向而言的。
在下文中参照附图来进一步说明本发明，在附图中：
图1示出了实验8中所描述的模拟结果的例子。
线通常为聚酯或聚酰胺。线应当优选地为非多孔的，因为发现在制品渗透时这会降低血细胞与血浆之间的分离。在根据本发明的一个实施方式中，线是多孔的，并且线的多孔表面至少部分地被涂层覆盖，该涂层优选地向线提供亲水性质。优选地，线的表面基本上被涂层覆盖或者被涂层完全覆盖，因此线成为非多孔的线。
为了改善根据本发明的制品的可操作性，例如用于DBS目的，优选地制品还包含与所述层中的一个层接触(例如在这些层之前或者之后)的刚性薄片状的框(passé partout)或框架。这种框通常包含一个或多个孔，基质材料诸如血液可以通过这些孔而被应用到制品的层上。通过这种方式，制品能够用作干基质点应用的载体。在一个实施方式中，所述框与两个或更多个不同的含亲水材料的基本上薄片状的制品接触，所有制品均位于分离的孔的后面。这使得可以在相同的制品上进行更多测试。更多测试可以是相同测试的重复或者是不同测试。孔的常见尺寸为1.5cm至4cm。对于DBS应用来说，优选的是孔的尺寸为约2cm至3cm。
在本发明的上下文中，薄片状指的是物体(在这种情况下制品或层)明显比其厚度更宽、更广阔，具体地是其厚度的25、50、100或更多倍数。宽度和广度(breadth)不一定是相同的。基本上薄片状是指厚度应当在整个表面区域上基本上相同，但不损害本发明所展现的性质的微观(小于0.5mm)厚度变化或类似变化是可接受的。在本发明的上下文中，对于“基本上薄片状”的各尺寸和各尺寸的比例来说，优选的实例包括***。
在本发明的上下文中，层指的是较大体系的一个基本上薄片状的部分，通过物理或化学性质的方式可以在微观或宏观上将该部分与体系的其他部分区分开。优选地，制品包含2至18个层，这些层布置于彼此的顶部上形成叠层。发现两层是实现适当捕捉血液的最小层数，并且发现超过约15个层也是可以的，但没有增加其他优点，而且倾向于使制造变得复杂、难于打孔且倾向于得到小的血点。更优选地，制品包含至少3个层，因为这使得各层之间可以更好地相互作用，并且还更优选地4至12个层、例如8至12个层。最优选地发现在所述材料的制品中使用约8或4个层。为了保持制品避免破裂，这些层优选地通过激光焊接、超声焊接、胶粘剂(punctual glue)(通过涂布和固化)相互接触，然而也可以通过局部熔化来机械固定例如使用刚性框架来保持各个层相互接触。这种刚性框架也可以形成本发明其他地方所描述的框的一部分。
制品通常具有适合在使用时接收流体的前表面和远离前表面朝向的后表面。优选的是，其中制品包含至少三个基本上薄片状的层，形成前表面和/或后表面的基本上薄片状的层具有较之在形成前表面和后表面的基本上薄片状的层之间所布置的至少一个基本上薄片状的层更小的网状开口。这降低了吸收到制品中的基质通过前表面或后表面损失的风险，并且还使得制品可以具有非常大的吸收容量，因为在布置于后表面和前表面之间的一个或多个薄片状层中具有大的网状开口。具体地，该实施方式可以降低或者甚至防止对制品打孔时干基质材料损失。
在本发明的一个实施方式中，各层的机织材料具有恒定的平均开口区域。
在另一个实施方式中，制品具有适合在使用时接收流体的前表面和远离前表面朝向的后表面，并且后表面不透水。后表面可以是布置于后表面上的额外的层，其中该额外的层与制品中的其他层不同；不透水的后表面可以通过用额外的涂层涂布后面来实现，或者不透水的后表面可以通过至少部分围绕制品布置的(刚性)框架来实现。不透水的后表面也不透血，并且在制品中起到阻挡层的作用，以防止使用时血液在制品中在与应用血液的地方相反的那侧上离开制品。
机织可以是平纹织法(例如1/1和2/2)、斜纹织法(例如2/2斜纹、2/1斜纹、1/2斜纹、3/3斜纹)或其他类型的机织。对于根据本发明的制品来说，平纹织法是优选的。在本发明的上下文中，亲水性材料指的是20μm的水滴在5s内被吸收到包含该材料的制品中。我们发现这是一个合适的定义，从而确保了根据本发明的制品的基本上薄片状的层中两个紧密地隔开的同轴表面会提高生物水性基质如血液的层流。亲水性能够通过以下来实现：材料本身是亲水性的或者材料被亲水性材料涂布而成为亲水性的。通常，使用聚酯(PET)或聚酰胺(PA)作为薄片状层的线，并且更优选地，用PEG基涂料涂布线。优选地，将涂布材料固化，以减少可萃取物或析出物。满足这些标准的涂料组合物可以从DSM，Netherlands的商品名下商业购得，美国专利申请20110263011描述了该涂料组合物。
可以通过湿涂料沉积领域中已知的任何方法在一步或多步中将亲水涂层涂覆于薄片状层上。合适的方法的实例为旋涂、浸涂、喷涂、流涂、弯面(meniscus)涂、毛细管(capillary)涂布和辊涂、抽吸(aspiration)涂布、吻(kiss)涂或其合适的组合。在一个实施方式中，涂料仅用于增加薄层的亲水性。在另一个实施方式中，涂料用于以下的组合：增加薄层的亲水性以及使各层相互连接。
在本发明的上下文中，“接触”是指将两个物体的平坦表面靠在一起并在宏观水平上保持在一起。这可以通过例如本文中其他地方描述的框来实现。没必要使点有生物样品的区域例如粘接键的方式诸如胶在微观(即分子或原子水平)上靠在一起并保持在一起。与此相反，在本发明的上下文中，这种大量的粘接键可能会干扰制品内假定的毛血管力。丝或薄片状层的任选涂层可以在薄片状层之间产生接触。在这种情况下，高度优选的是，涂料以低的量存在，从而薄片状层的的开口区域的有限部分被涂料填充。
不受任何理论约束，我们相信在使用时，机织材料的网孔(开口空间)被血充分填充，以使每载体区域的血液体积是固定的。多个层确保了各层之间的斑点血液的横向流动，导致圆形血点，在圆形血点内所有层的所有网孔都被血充分填充。
尤其适合干血点应用的制品的实施方式具有适合在使用时接收流体的前表面。在空气中20℃下干燥2小时后，在该表面上的30μl80％血细胞比容血液样品的区域被称为第一干血点的区域A1；在空气中20℃下干燥2小时后，在该表面上的30μl20％血细胞比容血液样品的区域被称为第二干血点的区域A2。区域差异ΔA是A1-A2除以A1的数值，即：ΔA＝|A1-A2|/A1。我们发现，当区域差异ΔA＜20％、优选地ΔA＜15％、更优选地ΔA＜10％、最优选地ΔA＜8％时，本发明的制品尤其有用。ΔA是基于两种血细胞比容值的三个不同的点的平均尺寸来计算的。
在一个高度优选的实施方式中，至少两个基本上薄片状的层相对于彼此旋转一个角度。此处旋转一个角度是指，尽管叠层中各层保持基本平行，但旋转的层会具有与未旋转的层不同方向的经线，该角度被称为vnm，其中n和m表示相对层位置。因此，V12是相邻层之间的角度，v13是被一层隔开的各层之间的角度。我们发现，两个基本上薄片状的层中的第一层相对于两个基本上薄片状的层中的第二层旋转角度v12，并且角度v12是7°至83°；优选地，角度v12是10°至80°，并且更优选地v12是13°至77°时，是非常有利的。对于非常低的旋转角度，干基质点倾向于产生栅格区域(raster area)，即基质材料被浓缩的区域，从而导致基质材料诸如血的非常不均匀的分布。栅格的间距取决于网孔的间距以及相邻层之间旋转的角度，似乎遵循波纹状(moiré-like)图案(pattern)。特别地，我们发现，在较高的旋转角度下，栅格之间的距离变得非常小(例如小于0.5mm或小于0.3mm)，以致于在实际中未观察到影响，因为栅格过于接近。能够推理出，但不限于此，栅格的几何形状对应二维波纹状图案。有时对于v12＝0°的制品观察到的较大且有时不均匀的干血点可能是由于制品的某些网孔或区域因为这些区域的阻塞所造成的未被填充而引起的，并且因此观察到较大的不均点。总而言之，这意味着在制品的层之间经过缜密的且大量(substantial)的旋转会始终如一地导致更具有可重复性的干基质点形成，而小的变化诸如1-3°(其在倾向于以具有零旋转角度布置的制品的制备中很容易引起，除非使用时非常小心)会导致非常不均匀的点形成。
在一个尤其有利的实施方式中，制品包含与两个基本上薄片状的层中的第二层(即在第一个基本上薄片状的层的另外一侧)相连的第三个基本上薄片状的层，并且第三个基本上薄片状的层相对于两个基本上薄片状的层中的第二层旋转角度v23。我们发现，当角度v23较之角度v12基本上相同幅度且方向相反时，可以得到易于生产的制品，同时保持了采用旋转层的优点。在这种情况下，两个基本上薄片状的层中的第一层与第三个基本上薄片状的层之间的角度v13大约是零。换句话说，制品中的基本上薄的层是以A-B-A-B…排列的，其中第1、3、……层以经线在相同的方向(A)上排列，并且第2、4、……层以经线在不同于方向(A)的相同的方向(B)上排列。
在另一个实施方式中，制品包含与两个基本上薄片状的层中的第二层(即在第一个基本上薄片状的层的另外一侧)相连的第三个基本上薄片状的层，并且第三个基本上薄片状的层相对于两个基本上薄片状的层中的第二层旋转角度v23。在该实施方式中，两个基本上薄片状的层中的第一层与第三个基本上薄片状的层之间的角度v13以及角度v23为7°至83°；优选地角度v13和v23为10°至80°，并且更优选地角度v13和v23为13°至77°。我们发现这种实施方式减小了图案的任何波纹状作用，进一步导致更具有可重复性的干基质点。换句话说，制品的基本上薄的层是以A-B-C-D…排列的，其中至少第1、2和3层以经线在不同方向上排列。
本发明制品还适用于除干血点应用之外的其他类型干点应用。这些应用也称为干基质应用，其中基质指的是吸收材料，其可以是血液以及有机和/或无机材料的其他水溶液或悬浮液，例如水样品(诸如饮用水、废水或工艺用水)；和食物样品(诸如果汁、酒、酱、苹果沙司、乳(产品))。即使干血点应用是本发明制品的非常优选且尤其有利的应用，但是还应当理解到干基质点应用也包含于本发明中。除非特定情况表明具体实施方式仅涉及干血点应用(例如涉及血细胞比容值无差异的优点)外，干基质点和干血点在本发明文件中可互换使用。
本文中所描述的本发明的实施方式的单个特征或特征的组合以及其显而易见的变体可以与本文中所描述的其他实施方式的特征相互组合或交换，除非本领域技术人员会立即意识到所得到的实施方式在实际上是不可行的。
实施例
实施例1
A)将新鲜全血离心，并且将分离的血浆和红细胞用于制备血细胞比容值水平为0、20、30、40、45、50、60、70和80％的血混合物。
B)提供机织的聚酯材料，其具有约40μm的网状开口和约38μm的层厚、约40％的开口区域、约158n/cm的网纱经线数、约158n/cm的网纱纬线数、均为约24μm的经线直径和纬线直径，其可以从Sefar(Switzerland)在商品名Medifab(聚酯)07-40/40(产品编号3053-1000-843-V1，charge3088149-00)下商业购得。网孔的聚酯线是非多孔的线，但是是亲水的。用夹子将网孔材料的所期望的层以各层之间的期望角度组装，并将其用2％涂料组合物浸涂，其中该涂料组合物包含被反应基团和亲水性聚合物链接枝的纳米颗粒(可以从DSM，Netherlands在商品名下商业购得)。干燥后，制品是亲水的。
实施例2
通过吸取不同体积量的红细胞和血浆来制备血细胞比容水平为30、50和70％的血液混合物。
对于该实施例来说，将20μl的血细胞比容值为30、50和70％的血液点到3层的制品上，制品如实施例1-B中所述。HT30％和50％的平均点直径为18mm，并且70％的为19mm。因此，从这些结果中可以得到出人意料的结论，当形成20μL固定体积的血的点时，30、50和70的不同血细胞比容值对点的直径无显著影响。
实施例3
如实施例1A中所述，制备血细胞比容水平为0、20、30、40、50、60、70和80％的血液混合物。对于该实施例来说，将20μl或50μl的血液点到4层的制品上，该制品如实施例1-B中所述，并且在相邻层之间或者四层纤维素基材料中未经涂布的组装件之间分别具有零旋转，其中在后框和前框之间将制品机械地保持在一起。干燥后，测量血点直径。
表1中给出了实施例1-B的4层制品和纤维素基材料所获得的点直径结果。表1中的结果清楚地表明，当将具有从0(血浆)到80％的不同血细胞比容值的血液点到如实施例1-B中所制备的根据本发明的4层制品上时，在点直径之间没有可测量的差异，而对纤维素基材料则观察到非常显著的点直径差异(＞50％)。该结果清楚地表明，对于实施例1-B的4层制品来说，每区域的体积是恒定的，但对于纤维素基材料来说不是恒定的。
表1
实施例4
该实施例示出了层数对血点直径的影响。
将恒定体积的血细胞比容水平为大约45％的血液点到4、6、8、10和12层如实施例1-B中所描述制备的制品上，这些制品在相邻层之间具有零角度。干燥后，测量血点直径。结果示于表2中。
表2
实施例1-B的制品的层数 点直径/mm
4 20
6 16
8 14
10 12
12 10
该结果清楚地表明层数与点直径或点面积之间的关系。一般来说，能够观察到点尺寸与各层的开口区域中体积和各层之间的体积的总和直接相关。结果是，可以通过改变层数来简单地调节每区域的血液体积(某些应用会对此有要求)。
实施例5
该实施例示出了血点体积对血点直径的影响。
将10、20、30和40μL体积的血点到如实施例1-B中所描述制备的4层制品上，这些制品在层之间具有零旋转。干燥后，测量血点直径。结果示于表3中。
表3
该结果清楚地表明，正如所预料的，形成点的血体积与点直径之间存在二次关系(quadratic relation)。
实施例6
对于血细胞比容依赖性，测试具有五种不同材料(网状开口、开口区域和线直径(相同的经线与纬线的网状开口和线直径))的制品。所有卡片如实施例1B中所描述来制备，均具有8层聚酯，并且相邻层以ABAB..堆叠并且朝向彼此45°取向。将这些卡片用2％除料组合物浸涂，并在纸框中固化。分别将血细胞比容值为20％、45％和80％的30μl血液混合物应用于每血细胞比容2至8个制品，此后可以使这些点干燥。测量干点尺寸，并计算干点尺寸面积的标准偏差。结果示出表4中。对于所有的研究材料来说，标准偏差为≤8％。
表4
观察到，对于形成点的血样品的血细胞比容值来说，每个特定材料内所观察到的干血点尺寸没有显著的差异。
实施例7
通过实施例1B中所描述的方法，制备具有定向层的三种不同的制品，采用具有40μm网状开口、40％开口区域和24μm线直径的聚酯机织材料。对于这些制品，使用8个层，并且将这些层组装并浸涂，以形成制品。第3、5和7层取向如第1层(因此相对于第1层的角度为0°，即v13＝0°)。第2、4、6和8层均相对于第1层以相同的角度v12取向。分别制备v12＝0°、v12＝15°和v12＝45°的三种制品。所有制品均涂有(spiked with)30μl具有相同血细胞比容值的血液。结果示出表5中。v12＝0°的制品(即所有层取向平行)示出了较大的点尺寸和不均匀干血分布。v12＝15°和v12＝45°的制品示出了非常均匀的干血分布并形成圆的干血点。此外，与定向层(v12＝15°和v12＝45°)相比，v12＝0°的制品示出了较大的点尺寸。
表5
实施例8
网孔参数与实施例7中所使用的网孔的参数接近(此处在经线和纬线方向上均使用网状开口40μm和线直径25μm)，将网孔模拟为具有0°、3°、15°和45°的角度v12。模型化的制品的点示于图1中。每个点对应约1.5x3mm的面积。在图1A中，观察到网孔的完美对准(对应于v12＝0°)导致完美的网格。然而，即使很小的偏差如v12＝3°(参见图1B)，对于相距离较大(此处约1-2mm)的基质(本文中也称为栅格)来说，也会导致非常清楚地形成具有非常不同的透明度的区域。对于v12＜约10°的旋转角也看到类似的观察结果，其中观察到具有重叠的网状开口的非常清楚的点的图案，这些网状开口被重叠或平行的线所封闭的区域包围。能够推理出，但不限于此，这些点对应于血点干燥后不时地出现在制品上的栅格。对于较大的v12值来说，重叠的网状开口的点之间的距离变得非常短，如诸如15°的v12时所示，并且出人意料的是该距离不影响点形成，而对于较低的v12值来说，点之间的距离变得非常大，并且会出现非常不均匀的点形成，除非在将层对准时特别小心。对于非常大的旋转角度(此处如v12＝45°所示)来说，没有观察到栅格形成。看来，栅格的几何形状对应于二维波纹状图案(参见下面的图)。在v12＝0°的制品中有时观察到较大且有时不均匀的干血点，这可能是由于制品的某些网孔或区域因为这些区域的阻塞所造成的未被填充而引起的，并且因此，观察到较大的不均点。取向似乎并不影响材料的血细胞比容依赖行为。
实施例9
使用液相色谱串联质谱法LCMSMS，来确定层之间的相对取向(旋转角v12)对干基质点的均匀性的影响。将等体积的加入可待因的血(Ht＝45)点到根据本发明的制品上。每个制品具有8个基本上薄片状的层，这些层以相邻层之间不同角度排列，而无层定向。三种制品分别为v12＝0°、v12＝15°和v12＝45°。对于所有制品来说，使用v13＝0°(换句话说，这些层取向为ABAB…)。对于每个制品来说，形成6个点，并且用LCMSMS分析每个点的三个不同的打出孔，以确立可待因含量。观察到，45°取向层得到最好(最低)的标准偏差，即RSD5％(参见表6)。
表5

Claims (18)

1.基本上薄片状的制品用作干基质点应用的载体的用途、优选地用作干血点应用的载体的用途，所述制品包含接触的两个基本上薄片状的层，其中所述层包含机织的亲水材料。
2.基本上薄片状的制品，其包含接触的两个基本上薄片状的层，其中所述层包含机织的亲水材料。
3.如权利要求2所述的制品，其中所述层包含具有以下性质的材料：11μm至800μm的网状开口和38至520μm的层厚、1％至65％的开口区域、270至9n/cm的网纱经线数、206至9n/cm的网纱纬线数、24n/cm至480μm的经线直径和纬线直径。
4.如权利要求3所述的制品，其中所述层包含具有以下性质的材料：20μm至200μm的网状开口和38μm至200μm的层厚、30至50％的开口区域、100n/cm至200n/cm的网纱经线数、100n/cm至200n/cm的网纱纬线数、24μm至50μm的经线直径和纬线直径。
5.如权利要求4所述的制品，其中所述层包含具有以下性质的材料：约40μm的网状开口和约38μm的层厚、约40％的开口区域、约158n/cm的网纱经线数、约158n/cm的网纱纬线数、约24μm的经线直径和纬线直径
6.如权利要求2-5中任意一项所述的制品，其中两个层由相同的材料构成，优选地所有层均由相同的材料构成。
7.如权利要求2-6中任意一项所述的制品，其中所述制品包包含2至18层的所述材料、优选地3至15层的所述材料、更优选地4至12层的所述材料、更优选地约8层或约4层的所述材料。
8.如权利要求2-7中任意一项所述的制品，其中所述层通过激光焊接、超声焊接、胶粘剂、薄层胶或者通过使用刚性框架来保持接触。
9.如权利要求2-8中任意一项所述的制品，其还包含与所述层中的一层接触的刚性的薄片状片材或框架。
10.如权利要求9所述的制品，其中所述片材包含一个或多个孔。
11.如权利要求9或10所述的制品，其中所述片材与如权利要求2-8中任意一项所述的2个或更多个不同的制品接触，所有制品均位于孔的后面。
12.如权利要求2-11中任意一项所述的制品，其具有适合在使用时接收流体的前表面，并且第一干血点与第二干血点之间的区域差异ΔA小于20％，其中所述第一干血点的区域为在空气中20℃下干燥2小时后在所述表面上的30μl80％血细胞比容血液样品的区域，并且所述第二干血点的区域为在空气中20℃下干燥2小时后在所述表面上的30μl20％血细胞比容血液样品的区域；优选地，第一干血点与第二干血点之间的区域差异ΔA小于15％，更优选地第一干血点与第二干血点之间的区域差异ΔA小于10％，并且最优选地第一干血点与第二干血点之间的区域差异ΔA小于8％。
13.如权利要求2-12中任意一项所述的制品，其中所述两个基本上薄片状的层中的第一层相对于所述两个基本上薄片状的层中的第二层旋转角度v12，并且所述角度v12是7°至83°时；优选地，所述角度v12是10°至80°，并且更优选地所述角度v12是13°至77°。
14.如权利要求13所述的制品，其包含与所述两个基本上薄片状的层中的第二层相连的第三个基本上薄片状的层，并且所述第三个基本上薄片状的层相对于所述两个基本上薄片状的层中的第二层旋转角度v23，并且所述角度v23较之角度v12基本上相同幅度且方向相反，以使所述两个基本上薄片状的层中的第一层与第三个基本上薄片状的层之间的角度v13大约是零。
15.如权利要求13所述的制品，其包含与所述两个基本上薄片状的层中的第二层相连的第三个基本上薄片状的层，并且所述第三个基本上薄片状的层相对于所述两个基本上薄片状的层中的第二层旋转角度v23，从而所述两个基本上薄片状的层中的第一层与第三个基本上薄片状的层之间的角度v13以及所述角度v23是7°至83°；优选地，所述角度v13和v23是10°至80°，并且更优选地所述角度角度v13和v23是13°至77°。
16.如权利要求2-15中任意一项所述的制品，其中所述制品具有适合在使用时接收流体的前表面和远离所述前表面朝向的后表面，并且所述后表面不透水。
17.如权利要求2-16中任意一项所述的制品，其中所述制品具有适合在使用时接收流体的前表面和远离所述前表面朝向的后表面，并且所述制品包含至少三个基本上薄片状的层，其中形成所述前表面和/或所述后表面的基本上薄片状的层具有较之在形成所述前表面和所述后表面的所述基本上薄片状的层之间所布置的至少一个基本上薄片状的层更小的网状开口。
18.如权利要求1-17中任意一项所述的制品用作干基质点应用的载体的用途、优选地用作干血点应用的载体的用途。
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US9630374B2 (en) 2017-04-25
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