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CN111356928A - 试剂递送系统 - Google Patents

试剂递送系统 Download PDF

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CN111356928A
CN111356928A CN201880073400.1A CN201880073400A CN111356928A CN 111356928 A CN111356928 A CN 111356928A CN 201880073400 A CN201880073400 A CN 201880073400A CN 111356928 A CN111356928 A CN 111356928A
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reagent
nozzle
delivery system
reservoirs
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D·A·阿莫雷塞
N·苏德
P·J·罗林斯
S·G·拉曼希伊
M·I·沃克尔
T·W·布劳顿
M·C·R·特维斯克
J·P·凯西
M·R·费尔斯
N·波拉克
N·瓦雷拉斯
G·H·W·桑德斯
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Abstract

具有相关联喷嘴的预包装试剂储集器允许在各种类型的反应中准确、可重复地分配试剂，从而降低人为误差的风险。一系列储集器可排列在薄片或平面上以用于自动化操控，从而提供用于组织、存储、运输和分配例如分子生物学领域中的那些反应等的复杂反应中所需的试剂的简单形式。

Description

试剂递送系统
相关申请的交叉引用
本申请要求2017年10月20日提交的美国申请第15/789,660号的优先权和权益，所述申请的内容以引用的方式并入本文中。
技术领域
本发明涉及试剂保存和递送。
背景技术
许多分析技术需要使用精确且有时少量的试剂。举例来说，在分子生物学中，反应通常在微流体环境中进行，且必须以精确量和比率组合若干试剂以确保可接受的结果。此外，许多反应对污染敏感，且因此必须在受控环境中存储和操控试剂。使试剂递送自动化的各种尝试可去除一些人为误差，但具有其自身缺点。
自动化试剂递送的现有方法包括自动式流体处理器和微流体装置。通常，将流体从中央储集器分配到反应孔中。在流体装置中使用的硬件具有许多移动零件，价格昂贵，维护具有挑战性，并且尺寸较大。控制微流体芯片的硬件更简单、更便宜且较小，但用于分配试剂和进行反应的芯片可能较为昂贵。与流体处理器一起使用的硬件提供可编程灵活性，但部分归因于相关编程成本而价格昂贵。
微流体芯片较不灵活，其可能难以定制，且成本可随着额外层、精度要求和额外通道或储集器而逐步增加。已将喷墨机耦接到自动式平台，但其通常专用于特定试剂(未洗涤和再填充)，具有死体积，必须进行预装填，且试剂必须在分配之前保持冷却。归因于设置时间和试剂过填充(死体积)，自动式平台在大量样品(例如待在相同条件下运作的大于96个样品)的情况下是最实用的。为了易于设计，微流体芯片频繁地通过多个步骤处理单一样品，或通过单一步骤处理多个样品。
发明内容
本发明提供用于精确递送限定试剂体积的试剂递送系统。根据本发明，递送系统包含具有可变形部分的储集器，所述可变形部分在经致动时使得通过集成到储集器的壁中的喷嘴递送其中所含有的试剂。
在优选实施例中，递送系统为包含形成用于含有试剂的储集器的第一和第二阻挡层的泡壳包装。将喷嘴集成在阻挡层中的至少一个中，且形成储集器的阻挡层中的至少一个可变形，以便在可变形部分的致动后推动试剂通过喷嘴。储集器可具有任何适宜的形状和尺寸。优选系统包含第一可变形阻挡层和第二阻挡层，所述第二阻挡层包含集成喷嘴以形成储集器。喷嘴可制造在第二阻挡层中，或可简单地包含开口，试剂在可变形第一阻挡层缺乏致动的情况下不会流动通过所述开口。喷嘴允许试剂在致动后精确递送，且避免发生如在其它情形下在泡壳包装破裂中典型的“大量”试剂倾出或喷射。
预定体积的试剂被包装到待存储或运输的储集器中，备用于分配到反应环境中。因为以给定反应所需的精确量在制造或分配点处将一定体积的试剂添加到储集器，所以避免了台面处发生人为误差的可能性。另外，在临使用之前使试剂在储集器内的受控环境中保持密封，使污染的可能性降到最低。
在反应位点，试剂通过喷嘴分配以引导试剂排出、管理试剂流动速率或形成小液滴或以其它方式管理试剂的递送形式。喷嘴可预成型于储集器中或在未密封过程期间形成(例如用外部喷嘴穿过储集器)。
形成含有试剂的储集器的至少一个表面可变形，从而允许强制排出试剂。变形的速率和因此试剂递送的速率可通过改变施加到储集器的可变形部分的致动力来控制。本发明的储集器可经多路复用。举例来说，多个储集器可在薄片或平面上接合在一起，且可经定位以允许在各种时间将不同试剂依序添加到反应。
在已添加适当量的试剂之后，可以通过若干方法中的任一个密封储集器。可以施加密封膜或箔以覆盖喷嘴开口并且可以在从储集器排出试剂之前去除。膜或箔可以手动地或通过机器剥离掉，或可以形成易碎密封件并且响应于储集器内增加的压力(例如通过储集器的变形)而打开。喷嘴可包括阀门，其关闭或打开以允许所含有的试剂保留在储集器内或从储集器排出。
可针对所含有的试剂的机器操控和自动化递送优化薄片或平面。举例来说，储集器的平面阵列可包括通孔或开口以允许用移液管吸取或以另外方式将各种额外试剂添加到薄片下方的反应腔室以与从储集器排出的试剂反应。薄片或平面可包含待由机器读取的分度标记(indexing mark)或凹口以指示储集器中的一个或多个相对于反应腔室或操控工具(例如用于使储集器变形且排出其内含物的柱塞)的位置。因此，本发明的自动化试剂递送装备可以通过识别特定含有试剂的储集器并且以特定顺序且以特定间隔将其内含物添加到反应腔室来执行编程指令。
试剂可存储于平面或薄片中的中心储集器中，且通过歧管以指定部分分配于各种其它储集器，以经由喷嘴排出而进入反应。举例来说，干燥试剂可以存储在连接到含有液体的中心储集器的一系列储集器中。干燥试剂在所述状态下可更稳定，从而允许更长时间或更容易存储。液体试剂可在即将使用之前通过密封歧管(维持受控环境并使污染降到最低)分配到含有干燥试剂的各种储集器。
本发明的各方面可包括试剂递送系统，其包含由第一阻挡层和第二阻挡层界定的储集器，其中第一阻挡层和第二阻挡层中的至少一个包含可变形部分，且第一阻挡层和第二阻挡层中的至少一个包含喷嘴。储集器可经配置以在致动可变形部分后通过预成型喷嘴排出其中所含有的一种或多种试剂。
喷嘴可预成型，且储集器的内部体积可为约5μl到约100μl(包括端值)。喷嘴的直径可为约100μm到约600μm(包括端值)。喷嘴可从靠近储集器中的内部开口的约0.5mm的直径逐渐变窄到靠近储集器外部开口的约0.6mm的直径。或者，锥度可以为靠近内部约1mm到靠近外部约1.2mm或所述范围内的任何组合(例如1/0.6mm；1.8mm/1.2mm)。
储集器可以安置在包含多个储集器的平面或薄片中。
平面可包括用于定位多个储集器中的一个或多个的分度标记。平面可包括一个或多个开口。
预成型的喷嘴可经配置以将试剂保留在储集器中直到致动可变形部分。预成型的喷嘴可包括密封部件，其经配置以密封储集器中的试剂直到致动可变形部分。密封部件可为易碎的。密封部件可包括可去除膜。密封部件可包括阀门。密封部件还可包含插塞，且插塞可由惰性或活性材料构成。此外，插塞可在储集器被破坏时(即，当易碎部分经致动时)由试剂内含物弹出。或者，可在致动之前去除插塞。还预期插塞材料发生改变(以热方式或以其它方式)，使得其不再对试剂喷出提供障碍。喷嘴还可通过疏水性网状物与储集器中的空气分离。
在某些方面，本发明可包括试剂递送系统，所述试剂递送系统包含：可变形储集器，其包含预成型喷嘴；上部密封层，其耦接到可变形储集器的顶部；以及可去除下部密封层，其以可去除方式耦接到预成型喷嘴，且与上部密封层组合，密封可变形储集器内的一种或多种试剂。所述系统可以经配置使得下部密封层的去除允许在可变形储集器的压缩之后通过预成型喷嘴分配一种或多种试剂。
上部和/或下部密封层可包括聚合物膜。上部和/或密封层可通过压敏粘合剂耦接到可变形储集器和/或喷嘴的顶部。本发明的储集器可包含塑料。
本发明的各方面可包括试剂递送系统，其包含多层薄片，所述多层薄片包含：泡壳层，其包含具有安置于其中的一种或多种试剂的多个密封可变形储集器；刺穿层，其包含多个中空刺穿部件，所述刺穿层安置成接近于泡壳层，使得多个中空刺穿部件与多个密封可变形储集器对准，其中多个中空刺穿部件中的每一个包含与泡壳层相对的喷嘴。多层薄片可经配置使得泡壳层通常不接触刺穿层，但在施加压缩多个密封可变形储集器中的一个朝向对应的中空刺穿部件的力之后，通过对应的中空刺穿部件的喷嘴分配一种或多种试剂。
附图说明
图1展示本发明的储集器。
图2展示具有可去除密封层的储集器。
图3展示作为平面的两个单独层的部分的储集器和刺穿喷嘴。
图4展示包含泡壳层和刺穿层的平面。
图5展示包含泡壳层和具有刺穿喷嘴和分度凹口的刺穿层的平面。
图6展示根据某些实施例的撕开储集器平面。
图7展示通过撕开储集器平面中的喷嘴排出的试剂。
图8展示经由歧管连接到中心试剂储集器和气压源的储集器的平面。
图9展示经由中央试剂储集器填充的储集器的平面的剖视图。
图10展示经由不同长度歧管路径连接到中央试剂储集器以均衡喷嘴压力的储集器的平面。
图11展示在经由储集器平面中的喷嘴喷出复原试剂之前用于从中心试剂储集器复原干燥试剂的过程。
图12展示经配置以用于依序试剂喷出的储集器平面。
图13展示经配置以用于依序试剂喷出的储集器平面的剖视图。
图14展示用于包含刺穿层和泡壳层的储集器平面的自动化处理的装备。
图15展示用于自动化试剂递送到一系列多孔板的装备。
具体实施方式
本发明的系统和方法提供适用于各领域(如分子生物学)中的反应的准确试剂体积的负担得起的自动化分配。单元填充储集器或泡壳用于存储、运输、组织和分配指定试剂体积以用于各种反应。所公开的系统和方法允许在最小设置时间且无死体积或预装填的情况下通过多个步骤处理少量样品。将某些反应所需的特定体积的各种试剂预包装到待存储或运输的储集器中，备用于分配到反应环境中。在使用时间之前试剂保持密封于储集器中，从而使污染的可能性降到最低。在反应位点，试剂通过喷嘴(预成型于储集器中或作为刺穿部件的一部分)分配，所述喷嘴引导试剂排出、管理试剂流动速率或形成小液滴或以其它方式管理试剂的递送形式。
一旦在例如试剂盒制造商现场填充，就可以用具有用于试剂递送的预成型喷嘴的膜密封本发明的储集器或泡壳。手动地或自动地操作的简单硬件装置压缩这些试剂填充的泡壳以将泡壳的内含物分配到位于喷嘴下方的反应容器中。一组预配置的泡壳和分度标记允许对多个试剂的机器控制分配和执行包括同时处理多个样品的复杂方法。
图1展示作为多个储集器101的薄片或平面103的一部分的储集器101，所述储集器101具有预成型喷嘴111、第一阻挡层105和第二阻挡层107，所述第二阻挡层107经配置以在其中含有试剂。储集器101还包含可变形部分109，其经配置以响应于施加力而收缩，由此减小储集器101的内部体积并且通过喷嘴111排出所含有的试剂。储集器可以由包括金属、玻璃、硅、塑料或复合材料的任何材料制成。在某些实施例中，可变形部分可由塑料或其它可容易变形的材料制成，而其余组件由更具硬性的材料(例如玻璃或金属)形成。所属领域的技术人员将认识到材料选择将取决于若干因素，包括避免与待与系统一起使用的试剂的反应性以及物理考虑因素，例如在实施例(诸如图6和7中所示的实施例)中的适当的变形性和易损性。
图2展示具有可去除密封层的储集器201的薄片或平面217。上部密封层203和下部密封层205在其通过一对滚轮207时从平面217剥离以暴露储集器201内的试剂体积。一旦至少下部密封层205剥离，暴露每一储集器201的喷嘴235，柱塞211便可经致动以使储集器201变形且迫使所含有的试剂209通过喷嘴235排出。上部和/或下部密封层(203、205)可例如由箔或聚合物膜制成，且可通过压敏粘合剂密封到平面217。储集器201的平面217可通过包含滚轮207和柱塞211的装备馈送，所述柱塞经配置以去除密封层(203、205)以解封储集器201且将其试剂209内含物喷出到反应腔室中。
图3展示不具有预成型喷嘴的储集器301，其中喷嘴307为邻近于含有各种储集器301的泡壳层303的刺穿层305的一部分。组合的刺穿层305和泡壳层303组成单个储集器薄片或平面，且当一起压缩时，刺穿层305的喷嘴307刺穿泡壳层303的对应储集器301且形成喷嘴307，储集器301中所含有的试剂可以通过所述喷嘴排出。
图4说明包含在泡壳层403中的多个储集器401和在刺穿层405中的对应喷嘴407的薄片或平面。刺穿层405和泡壳层403通过框架409相对于彼此定位。刺穿层405和/或泡壳层403可具有开口411，额外试剂可通过开口411用移液管吸取通过平面下方的反应腔室中。框架409或平面上的其它位置可包含分度标记415或凹口，从而允许机器识别和安置个别储集器401或相对于反应腔室或柱塞的多行储集器401。
图5展示包含泡壳层503和具有刺穿喷嘴507的刺穿层505的储集器平面。平面可通过操控框架509而馈送通过装备，且通过识别和操控索引凹口515而相对于等待反应腔室519(例如多孔板)定位。可以手动地或自动地操作移液管尖端531以通过泡壳层503和刺穿层505中的开口511将额外试剂添加到反应腔室519。储集器501可置于泡壳层503上，使得其在空间上对应于特定类型的板或其它反应腔室519的孔，使得在致动可变形部分后，在行或列中的每一储集器501可将试剂存放到下方板的单一对应孔中。类似地，开口511可以间隔开，使得其对应于下方板或其它类型的反应腔室519的个别孔。
图6展示撕开储集器平面603。平面603可包含配置成响应于如图6中所示的施加力而撕开的穿孔线或以其它方式易碎的区域。平面603内的多行储集器601可与每一行内的预成型喷嘴611相关联。喷嘴611可密封在平面603中，且平面的易碎区段可经配置以使得通过撕开每一先前行的储集器601，暴露下一行的喷嘴611。平面603接着可任选地弯曲以将喷嘴611引导到等待反应腔室，且所含有的试剂可喷出到腔室中。撕开平面603可经配置以使每一行通过手动或在自动化过程中经由装备而去除，所述装备经配置以在反应腔室上逐行馈送平面603且在使用之后撕开每一行，暴露下一行喷嘴611。
图7展示通过撕开储集器平面703中的喷嘴711排出的试剂。平面703弯曲，向下引导暴露的喷嘴711，且来自每一储集器701的试剂通过喷嘴711排出。喷嘴711已经通过平面703的一部分的剥离而暴露。
图8展示经由分配歧管803连接到中心试剂储集器819和气压源821的储集器801的平面805。每一储集器801包含预成型喷嘴811，所述预成型喷嘴经密封或以其它方式经配置以保留其中所含有的试剂。试剂储集器819和气压源821可各自经由阀门817耦接到歧管。压力可施加到试剂储集器819以将试剂分配到各种密封储集器801。因此，平面805可经制备、装运并且与试剂一起存储在中心试剂储集器819中，并且仅在喷出到反应腔室中之前分配到最终喷嘴储集器801。试剂储集器819可为可变形的，使得向其施加压力迫使试剂流动通过歧管803进入各种其它储集器801中。或者，试剂储集器819可经加压，使得在打开将试剂储集器819耦接到歧管803的阀门817之后，试剂将流动到各种储集器801的低压环境以用于最终喷出。储集器801可在第一过程中填充，且接着通过单独过程通过喷嘴811喷出试剂。可以经由阀门817将气压源821(诸如填充有空气或其它气体或液体的可变形储集器)耦接到歧管803。在储集器801已填充有来自试剂储集器819的适当量的试剂之后，可关闭将试剂储集器819耦接到歧管803的阀门817。然后可以打开将气压源821耦接到歧管803的阀门817，并且通过歧管803和储集器801的加压，可以迫使试剂通过每个储集器801的喷嘴811进入到对应的反应腔室中。在某些实施例中，气压源821可以用于通过喷嘴811喷射试剂或通过改变施加力的量产生小液滴。或者，可以施加真空源将试剂抽取到储集器801中。
图9展示经由中心试剂储集器919填充的储集器901的平面905的剖视图。可以在经由分配歧管903通过预成型喷嘴911喷出之前从中心试剂储集器919填充储集器901，分配歧管903如图9中所示将储集器901串联连接。或者，歧管803可以如图8中所示并联连接储集器801。因此，每一储集器可从中央试剂储集器同时(例如如图8中并联)填充或可依次(例如如图9中串联)填充。如图9中所示，每一喷嘴911可以一定方式密封，以便允许在试剂通过喷嘴911喷出之前填充每一储集器901。举例来说，可去除密封层可保持在适当位置，仅在试剂从试剂储集器919分配到个别储集器901之后移除。或者，喷嘴911密封件可为易碎的且经配置以使得使密封件破裂所需的压力大于将试剂分配到储集器919所需的压力。在后一实例中，施加到试剂储集器919的力将首先通过歧管903填充每一储集器901，且随后，在施加进一步的力之后，内部压力将增加到使密封件破裂且试剂从喷嘴911中的每一个喷出所必需的量。
歧管1003流道长度可在如图10对照中所示的并联系统中变化，当在阀门1017打开且将力施加到可变形试剂储集器1019之后试剂到达来自试剂储集器1019的每个储集器1001之时。通过均衡试剂必须从试剂储集器1019流动以到达平面1005中的每个储集器1001的路径长度，可以在多个储集器1001上均衡喷嘴压力。
在某些实施例中，试剂可以干燥或非活性状态、组分形式或在预期反应中使用之前可能需要活化、添加或改变的任何状态保留于储集器中。举例来说，试剂在制备后可能具有有限的存放期，或可能具有专用存储要求(例如温度或光照要求)以避免发生降解或不利反应。通过以较稳定形式(例如组分形式、干燥形式或非活性形式)存储试剂且仅在使用之前复原，可增加存放期，且可从涉及试剂的后续反应获得较好结果。
图11展示用于在复原试剂经由储集器平面1105中的喷嘴1111喷出之前使用中心试剂储集器1119复原干燥试剂1135的过程。类似于图8到10中所展示的系统，可将最终试剂的一些所需部分维持在经由歧管1125和任选地阀门耦接到另一储集器1101的中心试剂储集器1119中。柱塞1131(例如由本发明的装备控制)可在使用试剂之前的某一位置压缩试剂储集器1119。保留在试剂储集器1119中的试剂部分(例如水)接着可流动通过歧管1125到各种储集器1101，剩余的试剂组分(例如干燥试剂粉末1135)在各种储集器1101中。在各种储集器1101内组合后，最终试剂备用于经由储集器1101的喷嘴1111喷出到等待反应容器中。额外柱塞1131可用于压缩储集器，且可关闭与歧管1125相关联的阀门以防止回流且迫使试剂通过喷嘴1111排出。
图12展示经配置以用于依序试剂喷出的储集器平面。一系列试剂储集器1217可通过例如阀门或易碎密封件1215与具有喷嘴1211的一系列喷出部分耦接。试剂可保留在试剂储集器1217中与喷出部分分离以用于存储和运输。压力源1209(例如可变形充气储集器)可通过阀门或易碎密封件1215耦接到试剂储集器1217中的第一个。阀门或易碎密封件1215可经配置以使得施加来自压力源1209的一定量的压力将使易碎密封件1215破裂，随后迫使试剂从第一试剂储集器1217进入邻接喷出部分且从喷嘴1211排出来，在这之前使连接下一试剂储集器1217的易碎密封件1215破裂且迫使其中的试剂进入其邻接喷出部分且从其喷嘴1211排出来。或者，各种试剂储集器1217与喷出部分1211之间的连接可由选择性地打开和关闭以提供对压力源1209的接入的阀门控制。
图13展示经配置以用于依序试剂喷出的储集器平面的剖视图。如在图12中，压力源1309可经压缩(例如通过柱塞1325)以将系统内的内部压力增加到使一系列易碎密封件1313破裂的点，随后迫使来自试剂储集器1301的试剂从先前密封的邻接喷嘴1311中排出来。
如所提到，本文中所论述的储集器和储集器平面可经配置以用于通过装备1401自动使用以进一步减少人为误差的可能并且确保反应方案的保真度。图14中展示此装备1401的实例。储集器平面(例如包含如上文所描述的泡壳层1419和刺穿层1413)可通过端口馈送到装备1401中。端口可设定大小或以其它方式经配置以仅允许将储集器平面以一个定向插入以防止出错。馈送滚轮1407与平面的边缘相互作用以将其抽取到装备中，且使其沿着装备1401内移动以用于处理，同时维持刺穿层1413与泡壳层1419之间的分离。装备1401的各种部分可取决于试剂存储和反应方案的要求而冷却和/或加热。刺穿/分度滚轮1405接着可将刺穿层1413压缩到泡壳层1419中，从而引起刺穿层1413中的喷嘴1411刺穿含有储集器1423的试剂。刺穿/分度滚轮1405可与平面中的分度标记或凹口相互作用以识别和定位相对于装备1401的其它固定组件的多行储集器1323。在刺穿/分度滚轮1405之后，平面移动到反应腔室1415(例如多孔板)上方的位置。反应腔室1415可在某一载台上，且可取决于反应方案的要求而经历装备1401内的受控加热、冷却、摇动、磁性操控或其它操作。当开口在穿过移液管1409与反应腔室1415之间时，一系列自动化移液管1409可经定位以通过刺穿1413层和泡壳1419层中的开口将试剂添加到反应腔室1415。诸如一个柱塞1425或一行柱塞1425的操控器定位在反应腔室1415上方且经配置以压缩平面的一行或多行中的一个或多个储集器1423的可变形部分，以将其相应试剂内含物喷出到下方的反应腔室1415中(例如多孔板的一个或多个孔)。所用平面或薄片接着可通过退出端口从装备1401中馈送出。装备1401可经配置以在柱塞1425下方的载台处交换多个反应腔室1415以自单个储集器平面进行多个反应。
平面可包含一系列行中的一连串试剂，使得整个反应可通过依序压缩每一行的储集器来进行。每一行可含有单一试剂且对应于多孔板中的孔或一行反应腔室。因此，可同时进行对应于每一行中的储集器数目的多个类似实验。需要添加的试剂的数目和需要添加的试剂的顺序将指示行的数目和位置。列的数目将对应于同时进行的实验的数目。
图15中展示另一示范性装备1501。如上文所描述，储集器平面1545可通过端口馈送到装备1501中。馈送滚轮1507与平面1555相互作用以将其抽取到装备1501中且将其沿着装备1501内移动以用于处理。装备1501的各种部分可取决于试剂存储和反应方案的要求而冷却和/或加热。分度滚轮1505与平面1545中的分度标记或凹口相互作用以识别和定位相对于装备1501的其它固定组件的多行储集器。在分度滚轮1505之后，平面1545移动到载台上方的位置，多个多孔板1515中的任一个可添加到所述载台且定位，使得所述孔在空间上对应于如由柱塞块1525和/或移液管1509以上所操作在平面1545中的储集器和开口的行。取决于反应方案的要求，所述载台可在装备1501内经历受控加热、冷却、摇动、磁性操控或其它操作。
实例1
初始研究预期泡壳/喷嘴组合的特性类似于喷墨机，其中喷嘴直径将较小并且泡壳压缩对于高效小液滴递送来说至关重要。出人意料地，直径显著较大的喷嘴表现最佳，且其效率很大程度上不依赖于泡壳压缩特征(力或速度)。优选的喷嘴直径为约100μm到约600μm，包括端值。另外，需要关注的是，如喷墨机所经历的一般，因为空气随着液体而被迫排出，泡壳中空气的存在将引起卫星形成(satellite formation)(喷雾)。观察结果是使用较大喷嘴使这种现象降到最少。这产生泡壳不需要与试剂体积紧密配对的额外益处。另外，标准尺寸的泡壳可填充有不同体积。使用较大喷嘴的第三未预期益处为分配效率在很大程度上不依赖于所研究的试剂(具有和不具有盐、表面活性剂和甘油的水溶液)范围内的溶液粘度。
通过使用简单机械加工方法产生泡壳包装的技术原型获得结果。将圆形空腔机械加工成薄塑料载体。在喷出一侧，使用压敏粘合剂(PSA)连接含有小孔或喷嘴(通过激光钻孔产生)的聚合物膜。接着，将待喷出的试剂用移液管吸取到载体上。最后，通过使用PSA连接真空形成的泡壳层来封闭泡壳。接着借助于线性电动机械式电动机致动所存储的试剂的喷出，所述电动机可设定为目标速度。
通过引用的方式并入
贯穿本发明已经参考且引用了其它文档，如专利、专利申请、专利公开、期刊、书籍、论文、网络内容。所有此类文档在此用于所有目的以全文引用的方式并入本文中。
等效方案
根据包括对本文中引用的科学和专利文献的参考的本文档的完整内容，所属领域的技术人员将显而易见除本文示出和描述的之外的本发明的各种修改以及其许多其它实施例。本文中的主题含有重要信息、范例和指南，其可以适于以各种实施例及其等效方案实践本发明。

Claims (12)

1.一种试剂递送系统，其包含：
由第一阻挡层和第二阻挡层界定的储集器，其中所述第一阻挡层和第二阻挡层中的至少一个包含可变形部分，并且所述第一阻挡层和第二阻挡层中的至少一个包含集成喷嘴；
其中所述储集器经配置以在由柱塞致动所述可变形部分后通过所述喷嘴排出其中所含有的试剂，
其中所述储集器安置于包含多个储集器的阵列中，且
其中所述阵列包含用于识别所述多个储集器中的一个或多个相对于所述柱塞以及反应腔室的位置的分度标记，所述反应腔室用于接收经排出的试剂。
2.根据权利要求1所述的系统，其中所述喷嘴包含易碎阀门。
3.根据权利要求1所述的系统，其中所述喷嘴包含开口，所述开口在致动所述可变形部分后保留试剂直到迫使所述试剂通过所述开口。
4.根据权利要求1所述的试剂递送系统，其中所述储集器的内部体积为约5μl到约100μl。
5.根据权利要求1所述的试剂递送系统，其中所述喷嘴的直径为约100μm到约600μm。
6.根据权利要求1所述的试剂递送系统，其中所述喷嘴从所述储集器中的内部开口处约0.5mm逐渐变窄到靠近所述储集器外部开口的约0.6mm。
7.根据权利要求1所述的试剂递送系统，其中所述喷嘴包含密封部件，所述密封部件经配置以密封所述储集器中的所述试剂直到致动所述可变形部分。
8.根据权利要求7所述的试剂递送系统，其中所述密封部件为易碎的。
9.根据权利要求7所述的试剂递送系统，其中所述密封部件包含可去除膜。
10.根据权利要求1所述的试剂递送系统，其中所述阵列包含一个或多个通孔，所述通孔经配置以允许通过所述阵列将额外试剂添加到所述反应腔室。
11.根据权利要求1所述的试剂递送系统，其中所述分度标记包含凹口，所述凹口经配置以与分度滚轮相互作用以相对于所述柱塞和所述反应腔室操控所述阵列。
12.根据权利要求1所述的试剂递送系统，其中所述多个储集器按多行安置于所述阵列中，且每一分度标记对应于所述多行中的一个。
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