本申请涉及生化物质分析技术领域，尤其涉及一种反应模块、样本制备系统、样本制备方法及生化物质分析系统。The present application relates to the technical field of biochemical substance analysis, and in particular to a reaction module, a sample preparation system, a sample preparation method and a biochemical substance analysis system.
随着高通量测序技术的发展和测序市场的逐步扩大，需要投入更多的人力和时间成本来完成样本制备工作。为了解决上述问题，目前出现了一些自动化样本制备设备，如：集成了定量移液、混匀、PCR反应、温度控制等功能的自动化移液工作站。但以上这种样本制备系统集成了过多的自动化设备，且操作复杂度和专业度要求较高，设备的购置成本、管理成本以及人员培训成本非常高；同时，系统体积较大，也为实验室的空间利用带来了挑战；另外，这种样本制备系统难以直接与现有基因测序仪整合。With the development of high-throughput sequencing technology and the gradual expansion of the sequencing market, more manpower and time are needed to complete sample preparation. In order to solve the above problems, some automated sample preparation equipment has emerged, such as automated pipetting workstations that integrate quantitative pipetting, mixing, PCR reaction, temperature control and other functions. However, the above sample preparation system integrates too many automated equipment, and the operation complexity and professional requirements are high. The equipment purchase cost, management cost and personnel training cost are very high; at the same time, the system is large in size, which also brings challenges to the space utilization of the laboratory; in addition, this sample preparation system is difficult to directly integrate with the existing gene sequencer.
发明内容Summary of the invention
为解决现有技术以上不足之处，有必要提供一种反应模块，以及应用该反应模块的自动化、一体化且小型化的样本制备系统及样本制备方法。In order to solve the above deficiencies of the prior art, it is necessary to provide a reaction module, and an automated, integrated and miniaturized sample preparation system and sample preparation method using the reaction module.
另，本申请实施例还提供了采用该样本制备系统的生化物质分析系统。In addition, the embodiment of the present application also provides a biochemical substance analysis system using the sample preparation system.
第一方面，本申请实施例提供了一种反应模块，所述反应模块包括流体反应结构，所述流体反应结构上设有反应流道。In a first aspect, an embodiment of the present application provides a reaction module, wherein the reaction module includes a fluid reaction structure, and a reaction channel is provided on the fluid reaction structure.
在一些可能的实施例中，所述反应流道弯曲设置于所述流体反应结构上。In some possible embodiments, the reaction channel is bent and arranged on the fluid reaction structure.
在一些可能的实施例中，所述流体反应结构包括基板和形成于所述基板上的凹槽，所述凹槽内设有中空的反应管路，所述反应管路的中空部分构成所述反应流道。In some possible embodiments, the fluid reaction structure includes a substrate and a groove formed on the substrate, a hollow reaction pipeline is provided in the groove, and the hollow portion of the reaction pipeline constitutes the reaction channel.
在一些可能的实施例中，沿所述基板的厚度方向，所述凹槽的深度大于或等于所述反应管路的外径。In some possible embodiments, along the thickness direction of the substrate, the depth of the groove is greater than or equal to the outer diameter of the reaction pipeline.
在一些可能的实施例中，所述反应管路可拆卸设于所述凹槽中。In some possible embodiments, the reaction pipeline is detachably disposed in the groove.
在一些可能的实施例中，所述流体反应结构包括叠设的基板和盖板，所述基板上形成有凹槽，所述盖板靠近所述基板的表面与所述基板密封连接以使所述凹槽形成所述反应流道；In some possible embodiments, the fluid reaction structure includes a stacked substrate and a cover plate, a groove is formed on the substrate, and a surface of the cover plate close to the substrate is sealed and connected to the substrate so that the groove forms the reaction channel;
或，所述流体反应结构包括叠设的基板和盖板、以及位于所述基板和所述盖板之间的两个支撑壁，每个所述支撑壁相对的两端面分别与所述基板和所述盖板连接，所述基板、两个所述支撑壁以及所述盖板共同围成所述反应流道。Alternatively, the fluid reaction structure includes a stacked substrate and a cover plate, and two support walls located between the substrate and the cover plate, and the opposite end surfaces of each support wall are respectively connected to the substrate and the cover plate, and the substrate, the two support walls and the cover plate together form the reaction channel.
在一些可能的实施例中，沿所述反应流道的延伸方向，所述反应流道包括多个反应区域，至少两个所述反应区域的温度不同。In some possible embodiments, along the extension direction of the reaction channel, the reaction channel includes a plurality of reaction areas, and temperatures of at least two of the reaction areas are different.
在一些可能的实施例中，所述反应模块还包括温控组件，所述温控组件用于控制所述流体反应结构的温度，以调控所述反应流道内的温度。In some possible embodiments, the reaction module further includes a temperature control component, and the temperature control component is used to control the temperature of the fluid reaction structure to regulate the temperature in the reaction channel.
第二方面，本申请实施例提供了一种样本制备系统，包括：流体存储模块、流体分配模块、流体驱动模块和反应模块，所述流体存储模块用于存储流体，所述反应模块具有反应流道，所述反应流道分别与所述流体分配模块和所述流体驱动模块连通；所述流体驱动模块用于制造压力梯度，使所述流体存储模块中的所述流体经由所述流体分配模块转运至所述反应流道；所述反应模块用于执行转运至所述反应流道内的所述流体的生化反应。In a second aspect, an embodiment of the present application provides a sample preparation system, comprising: a fluid storage module, a fluid distribution module, a fluid driving module and a reaction module, wherein the fluid storage module is used to store fluid, the reaction module has a reaction channel, and the reaction channel is respectively connected to the fluid distribution module and the fluid driving module; the fluid driving module is used to create a pressure gradient so that the fluid in the fluid storage module is transported to the reaction channel via the fluid distribution module; the reaction module is used to perform a biochemical reaction of the fluid transported into the reaction channel.
在一些可能的实施例中，所述流体驱动模块还用于制造压力梯度，使所述反应流道内反应后的所述流体经由所述流体分配模块排入所述流体存储模块存储另一种流体的容器中；所述流体存储模块还用于混合反应后的所述流体和所述另一种流体，得到混合流体。In some possible embodiments, the fluid driving module is also used to create a pressure gradient so that the fluid after the reaction in the reaction channel is discharged into the container of the fluid storage module that stores another fluid through the fluid distribution module; the fluid storage module is also used to mix the fluid after the reaction and the other fluid to obtain a mixed fluid.
在一些可能的实施例中，所述流体存储模块包括流体存储装置和流体切换装置，所述流体存储装置包括多个用于容置所述流体的容器，所述流体切换装置用于调整多个所述容器的位置，以使多个所述容器中的一个对准所述流体分配模块，所述流体切换装置还用于混合反应后的所述流体和所述另一种流体。In some possible embodiments, the fluid storage module includes a fluid storage device and a fluid switching device, the fluid storage device includes a plurality of containers for accommodating the fluid, the fluid switching device is used to adjust the positions of the plurality of containers so that one of the plurality of containers is aligned with the fluid distribution module, and the fluid switching device is also used to mix the reacted fluid and the other fluid.
在一些可能的实施例中，所述反应模块包括流体反应结构和温控组件，所述反应流道位于所述流体反应结构上，所述温控组件用于控制所述流体反应结构的温度，以调控所述反应流道内的温度。In some possible embodiments, the reaction module includes a fluid reaction structure and a temperature control component, the reaction channel is located on the fluid reaction structure, and the temperature control component is used to control the temperature of the fluid reaction structure to regulate the temperature in the reaction channel.
在一些可能的实施例中，所述反应流道弯曲设于所述流体反应结构上。In some possible embodiments, the reaction channel is bent and arranged on the fluid reaction structure.
在一些可能的实施例中，沿所述反应流道的延伸方向，所述反应流道包括多个反应区域，所述温控组件还用于控制至少两个所述反应区域的温度不同。In some possible embodiments, along the extension direction of the reaction channel, the reaction channel includes a plurality of reaction areas, and the temperature control component is further used to control the temperatures of at least two of the reaction areas to be different.
在一些可能的实施例中，所述反应流道通过第一连接端与所述流体分配模块连通，所述反应流道通过第二连接端与所述流体驱动模块连通，所述第一连接端与所述第二连接端位于所述流体反应结构的同一端，或，所述第一连接端与所述第二连接端位于所述流体反应结构相对的两端。In some possible embodiments, the reaction channel is connected to the fluid distribution module through a first connection end, and the reaction channel is connected to the fluid driving module through a second connection end, the first connection end and the second connection end are located at the same end of the fluid reaction structure, or the first connection end and the second connection end are located at opposite ends of the fluid reaction structure.
在一些可能的实施例中，所述反应流道与所述第一连接端和所述第二连接端为一体式结构。In some possible embodiments, the reaction channel, the first connecting end, and the second connecting end are an integrated structure.
在一些可能的实施例中，所述第一连接端和所述第二连接端均设有开关部件，所述开关部件用于打开或关闭所述反应流道。In some possible embodiments, both the first connection end and the second connection end are provided with a switch component, and the switch component is used to open or close the reaction channel.
在一些可能的实施例中，所述开关部件包括电磁阀或旋转阀。In some possible embodiments, the switch component includes a solenoid valve or a rotary valve.
在一些可能的实施例中，所述流体反应结构包括基板和形成于所述基板上的凹槽，所述凹槽内设有中空的反应管路，所述反应管路的中空部分构成所述反应流道，所述反应管路伸出所述凹槽的两端分别与所述流体分配模块和所述流体驱动模块连通。In some possible embodiments, the fluid reaction structure includes a substrate and a groove formed on the substrate, a hollow reaction pipeline is provided in the groove, and the hollow portion of the reaction pipeline constitutes the reaction channel. Two ends of the reaction pipeline extending out of the groove are respectively communicated with the fluid distribution module and the fluid driving module.
在一些可能的实施例中，沿所述基板的厚度方向，所述凹槽的深度大于或等于所述反应管路的外径。In some possible embodiments, along the thickness direction of the substrate, the depth of the groove is greater than or equal to the outer diameter of the reaction pipeline.
在一些可能的实施例中，所述反应管路可拆卸设于所述凹槽中；及/或，所述反应管路与所述流体分配模块和所述流体驱动模块可拆卸连接。In some possible embodiments, the reaction pipeline is detachably disposed in the groove; and/or the reaction pipeline is detachably connected to the fluid distribution module and the fluid driving module.
在一些可能的实施例中，所述反应管路的内径为0.3mm～2mm。In some possible embodiments, the inner diameter of the reaction pipeline is 0.3 mm to 2 mm.
在一些可能的实施例中，所述流体反应结构包括叠设的基板和盖板，所述基板上形成有凹槽，所述盖板靠近所述基板的表面与所述基板密封连接以使所述凹槽形成所述反应流道。In some possible embodiments, the fluid reaction structure includes a stacked substrate and a cover plate, a groove is formed on the substrate, and a surface of the cover plate close to the substrate is sealed to the substrate so that the groove forms the reaction channel.
在一些可能的实施例中，所述流体反应结构包括叠设的基板和盖板、以及位于所述基板和所述盖板之间的两个支撑壁，每个所述支撑壁相对的两端面分别与所述基板和所述盖板连接，所述基板、两个所述支撑壁以及所述盖板共同围成所述反应流道。In some possible embodiments, the fluid reaction structure includes a stacked substrate and a cover plate, and two support walls located between the substrate and the cover plate, and opposite end surfaces of each support wall are respectively connected to the substrate and the cover plate, and the substrate, the two support walls and the cover plate together form the reaction channel.
在一些可能的实施例中，所述流体分配模块取液结构、连通所述取液结构和所述反应流道的分配管路以及取液驱动装置，所述取液驱动装置用于驱动所述取液结构与所述流体存储装置对准并伸入所述流体存储装置内。In some possible embodiments, the fluid distribution module includes a liquid collection structure, a distribution pipeline connecting the liquid collection structure and the reaction channel, and a liquid collection drive device, wherein the liquid collection drive device is used to drive the liquid collection structure to align with the fluid storage device and extend into the fluid storage device.
在一些可能的实施例中，所述取液结构为取液针。In some possible embodiments, the liquid collection structure is a liquid collection needle.
在一些可能的实施例中，所述流体驱动模块包括驱动泵，所述驱动泵为注射泵、柱塞泵、隔膜泵、齿轮泵或蠕动泵。In some possible embodiments, the fluid driving module includes a driving pump, and the driving pump is a syringe pump, a plunger pump, a diaphragm pump, a gear pump or a peristaltic pump.
在一些可能的实施例中，所述样本制备系统还包括废液收集装置和清洗液存储装置，所述废液收集装置和所述清洗液存储装置均与所述流体驱动模块连通。In some possible embodiments, the sample preparation system further includes a waste liquid collection device and a cleaning liquid storage device, and both the waste liquid collection device and the cleaning liquid storage device are connected to the fluid driving module.
在一些可能的实施例中，所述反应流道还与样本使用系统连通，所述流体驱动模块还用于驱动位于所述反应流道内反应后的所述流体转运至所述样本使用系统。In some possible embodiments, the reaction channel is also connected to a sample use system, and the fluid driving module is further used to drive the fluid after reaction in the reaction channel to be transported to the sample use system.
在一些可能的实施例中，所述流体分配模块与所述反应模块之间设有流体分配阀，所述流体分配阀还可与所述样本使用系统连通。In some possible embodiments, a fluid dispensing valve is provided between the fluid dispensing module and the reaction module, and the fluid dispensing valve can also be connected to the sample use system.
在一些可能的实施例中，所述样本制备系统还包括控制模块，所述控制模块用于控制所述流体存储模块、所述流体分配模块、所述流体驱动模块和所述反应模块协同作业。In some possible embodiments, the sample preparation system further includes a control module, and the control module is used to control the fluid storage module, the fluid distribution module, the fluid driving module, and the reaction module to work in coordination.
第三方面，本申请实施例提供了一种样本制备方法，包括：In a third aspect, an embodiment of the present application provides a sample preparation method, comprising:
通过流体驱动模块制造压力梯度，使位于流体存储模块中的流体经由流体分配模块转运至反应模块中的反应流道内；以及Creating a pressure gradient through the fluid driving module so that the fluid in the fluid storage module is transported to the reaction channel in the reaction module through the fluid distribution module; and
通过所述反应模块调控所述反应流道内的温度，使所述流体在所述反应流道内发生生化反应，从而获得所述样本。The temperature in the reaction channel is regulated by the reaction module to cause the fluid to undergo a biochemical reaction in the reaction channel, thereby obtaining the sample.
在一些可能的实施例中，所述流体在所述反应流道内发生生化反应之前，所述方法还包括：In some possible embodiments, before the fluid undergoes a biochemical reaction in the reaction channel, The method also includes:
关闭所述反应流道两端的开关部件，以密封所述反应流道；Closing the switch components at both ends of the reaction channel to seal the reaction channel;
所述流体在所述反应流道内发生生化反应之后，所述方法还包括：After the fluid undergoes a biochemical reaction in the reaction channel, the method further comprises:
打开所述反应流道两端的所述开关部件。Open the switch components at both ends of the reaction channel.
在一些可能的实施例中，所述流体存储模块包括流体存储装置和流体切换装置，所述流体存储装置包括多个用于容置所述流体的容器；In some possible embodiments, the fluid storage module includes a fluid storage device and a fluid switching device, and the fluid storage device includes a plurality of containers for accommodating the fluid;
所述通过流体驱动模块制造压力梯度，使位于流体存储模块中的流体经由流体分配模块转运至反应模块中的反应流道内的步骤之前，所述方法还包括：Before the step of creating a pressure gradient by the fluid driving module so that the fluid in the fluid storage module is transported to the reaction channel in the reaction module via the fluid distribution module, the method further includes:
通过所述流体分配模块和所述流体切换装置的协调动作，使所述流体分配模块与所述流体存储装置中存储一种流体的容器对准；以及The fluid dispensing module is aligned with a container storing a fluid in the fluid storage device through coordinated actions of the fluid dispensing module and the fluid switching device; and
将所述流体分配模块伸入所述容器中。The fluid dispensing module is extended into the container.
在一些可能的实施例中，所述通过所述反应模块调控所述反应流道内的温度，使所述流体在所述反应流道内发生生化反应的步骤之后，所述方法还包括：In some possible embodiments, after the step of regulating the temperature in the reaction channel by the reaction module so that the fluid undergoes a biochemical reaction in the reaction channel, the method further includes:
通过所述流体分配模块和所述流体切换装置的协调动作，使所述流体分配模块与所述流体存储装置存储另一种流体的容器对准；The fluid dispensing module is aligned with a container of the fluid storage device storing another fluid through coordinated actions of the fluid dispensing module and the fluid switching device;
将所述流体分配模块伸入存储所述另一种流体的容器中；extending the fluid dispensing module into a container storing the other fluid;
通过所述流体驱动模块制造压力梯度，使位于所述反应流道内反应后的所述流体经由所述流体分配模块转运至存储另一种流体的容器中，使所述另一种流体与反应后的所述流体混合得到混合流体；The fluid driving module creates a pressure gradient, so that the reacted fluid in the reaction channel is transferred to a container storing another fluid via the fluid distribution module, so that the another fluid is mixed with the reacted fluid to obtain a mixed fluid;
通过所述流体驱动模块制造压力梯度，使所述流体分配模块吸取所述混合流体，并将所述混合流体转运至反应模块中的反应流道内；以及Creating a pressure gradient by the fluid driving module so that the fluid distribution module absorbs the mixed fluid and transports the mixed fluid to a reaction channel in a reaction module; and
通过所述反应模块调控所述反应流道内的温度，使所述混合流体在所述反应流道内发生反应，直至反应完成，得到所述样本。The temperature in the reaction channel is regulated by the reaction module to make the mixed fluid react in the reaction channel until the reaction is completed to obtain the sample.
在一些可能的实施例中，获得所述样本的步骤之后，所述方法还包括：In some possible embodiments, after the step of obtaining the sample, the method further includes:
通过所述流体驱动模块将位于所述反应流道内的所述样本转运至样本使用系统。The sample in the reaction channel is transported to a sample using system through the fluid driving module.
在一些可能的实施例中，相邻两种所述流体进入所述反应流道的步骤之间，或得到所述样本的步骤之后，所述方法还包括：In some possible embodiments, between the steps of two adjacent fluids entering the reaction channel, or after the step of obtaining the sample, the method further includes:
通过所述流体驱动模块造压力梯度，使位于清洗液存储装置中的清洗液进入所述反应流道内对所述反应流道进行清洗，并使清洗后的废液转运至废液收集装置中。A pressure gradient is created by the fluid driving module, so that the cleaning liquid in the cleaning liquid storage device enters the reaction flow channel to clean the reaction flow channel, and the waste liquid after cleaning is transported to the waste liquid collection device.
第四方面，本申请实施例提供了一种生化物质分析系统，包括样本制备系统和与所述样本制备系统连通的样本使用系统，所述样本制备系统为如上所述的样本制备系统，所述流体驱动模块还用于将位于所述反应流道内的所述样本转运至所述样本使用系统。In a fourth aspect, an embodiment of the present application provides a biochemical substance analysis system, comprising a sample preparation system and a sample usage system connected to the sample preparation system, wherein the sample preparation system is the sample preparation system as described above, and the fluid driving module is also used to transport the sample located in the reaction channel to the sample usage system.
在一些可能的实施例中，所述样本使用系统包括测序芯片，所述反应流道与所述测序芯片连通，所述流体驱动模块用于将位于所述反应流道内的所述样本转运至所述测序芯片进行测序。In some possible embodiments, the sample use system includes a sequencing chip, the reaction flow channel and the The fluid driving module is connected to the sequencing chip, and the fluid driving module is used to transport the sample located in the reaction channel to the sequencing chip for sequencing.
本申请实施例提供的样本制备系统通过流体存储模块、流体分配模块、流体驱动模块以及反应模块的协同作业，进行流体的移液/混合以及生化反应等工序，从而实现一站式的自动化样本制备，流程简单，样本制备效率高，且流体损耗量较小，节约成本。而且，由于减少人为干预，因此能够避免人工操作容易出错的情况，有利于提高后续生化物质分析的准确性。另外，通过前述多个模块可以构成一体化样本制备系统，且耗材少，设备成本较低，能融合在生化物质分析系统中，可与样本使用系统共享器部件，实现与样本使用系统的无缝衔接，能够减少甚至不需要增加额外的器部件，进一步降低整体生化物质分析系统的成本。本申请实施例提供的反应模块中反应流道通过盘旋环绕的方式设置在流体反应结构上，可以将长度较长的反应流道集中设置，缩小占用空间，有利于缩小流体反应结构的体积，以缩样本制备系统及整体生化物质分析系统的体积。The sample preparation system provided in the embodiment of the present application performs the processes such as fluid pipetting/mixing and biochemical reactions through the collaborative operation of the fluid storage module, the fluid distribution module, the fluid drive module and the reaction module, thereby realizing one-stop automated sample preparation, with simple process, high sample preparation efficiency, and small fluid loss, saving cost. Moreover, due to the reduction of human intervention, it is possible to avoid the situation where manual operation is prone to errors, which is conducive to improving the accuracy of subsequent biochemical substance analysis. In addition, an integrated sample preparation system can be formed by the aforementioned multiple modules, and consumables are few, the equipment cost is low, it can be integrated into the biochemical substance analysis system, and the sample use system can share the device components to achieve seamless connection with the sample use system, which can reduce or even do not need to add additional device components, and further reduce the cost of the overall biochemical substance analysis system. In the reaction module provided in the embodiment of the present application, the reaction flow channel is arranged on the fluid reaction structure in a circling manner, and the reaction flow channel with a longer length can be centrally arranged to reduce the occupied space, which is conducive to reducing the volume of the fluid reaction structure, so as to reduce the volume of the sample preparation system and the overall biochemical substance analysis system.
为了更清楚地说明本申请实施例的技术方案，下面将对本申请实施例中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本申请的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the embodiments of the present application will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.
图1为本申请一实施例提供的样本制备系统的系统架构示意图。FIG. 1 is a schematic diagram of the system architecture of a sample preparation system provided in an embodiment of the present application.
图2为本申请一实施例提供的样本制备系统的结构示意图。FIG. 2 is a schematic diagram of the structure of a sample preparation system provided in an embodiment of the present application.
图3为本申请另一实施例提供的样本制备系统中流体存储装置的结构示意图。FIG. 3 is a schematic structural diagram of a fluid storage device in a sample preparation system provided in another embodiment of the present application.
图4为图2所示的样本制备系统中流体反应结构的立体结构示意图。FIG. 4 is a schematic diagram of the three-dimensional structure of the fluid reaction structure in the sample preparation system shown in FIG. 2 .
图5为图4所示的样本制备系统中流体反应结构的平面结构示意图。FIG. 5 is a schematic diagram of a planar structure of a fluid reaction structure in the sample preparation system shown in FIG. 4 .
图6为本申请另一实施例提供的流体反应结构的结构示意图。FIG. 6 is a schematic structural diagram of a fluid reaction structure provided in another embodiment of the present application.
图7为图5中沿VII-VII的剖面图。FIG. 7 is a cross-sectional view along line VII-VII in FIG. 5 .
图8为图7所示的流体反应结构增加盖板后的结构示意图。FIG8 is a schematic structural diagram of the fluid reaction structure shown in FIG7 after a cover plate is added.
图9为本申请另一实施例中样本制备系统中流体反应结构的结构示意图。FIG. 9 is a schematic structural diagram of a fluid reaction structure in a sample preparation system in another embodiment of the present application.
图10为本申请又一实施例中样本制备系统中流体反应结构的结构示意图。FIG. 10 is a schematic structural diagram of a fluid reaction structure in a sample preparation system in another embodiment of the present application.
图11为本申请实施例提供的生化物质分析系统的系统架构图。FIG. 11 is a system architecture diagram of a biochemical substance analysis system provided in an embodiment of the present application.
图12为本申请一实施例提供的样本制备方法的流程图。FIG. 12 is a flow chart of a sample preparation method provided in an embodiment of the present application.
主要元件符号说明
样本制备系统 100 基板 321,321a,321b
流体存储模块 10 凹槽 322,322a,322b
流体存储装置 101 反应管路 323
流体切换装置 102 盖板 324
容器 103 支撑壁 325
容器托架 104 温控组件 303
移载机构 105 第一连接端 304
驱动机构 106 第二连接端 305
混合机构 107 开关部件 306
流体分配模块 20 流体驱动模块 40
取液结构 201 驱动泵 401
分配管路 202 泵驱动组件 402
取液驱动装置 203 控制模块 50
流体分配阀 204 废液收集装置 60
反应模块 30 清洗液存储装置 70
反应流道 301 生化物质分析系统 1000
流体反应结构 302,302a,302b 样本使用系统 200Description of the main components Sample preparation system 100 Base plate 321, 321a, 321b
Fluid storage module 10 grooves 322, 322a, 322b
Fluid storage device 101 Reaction pipeline 323
Fluid switching device 102 Cover plate 324
Container 103 Support wall 325
Container bracket 104 Temperature control assembly 303
Transfer mechanism 105 First connection end 304
Driving mechanism 106 Second connection end 305
Mixing mechanism 107 Switch component 306
Fluid distribution module 20 Fluid drive module 40
Liquid extraction structure 201 Drive pump 401
Distribution line 202 Pump drive assembly 402
Liquid taking drive device 203 Control module 50
Fluid dispensing valve 204 Waste collection device 60
Reaction module 30 Cleaning fluid storage device 70
Reaction channel 301 Biochemical material analysis system 1000
Fluid reaction structure 302,302a,302b Sample using system 200
如下具体实施方式将结合上述附图进一步说明本申请。The following specific implementation methods will further illustrate the present application in conjunction with the above-mentioned drawings.
下面将结合本申请实施例中的附图，对本申请实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本申请一部分实施例，而不是全部的实施例。基于本申请中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本申请保护的范围。The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.
需要说明的是，当一个组件被认为是“设置于”另一个组件，它可以是直接设置在另一个组件上或者可能同时存在居中组件；当一个组件被认为是“安装于”另一个组件，它可以是直接安装在另一个组件上或者可能同时存在居中组件。本文所使用的术语“及/或”包括一个或多个相关的所列项目的所有的和任意的组合。It should be noted that when a component is considered to be "set on" another component, it can be directly set on the other component or there may be a central component at the same time; when a component is considered to be "installed on" another component, it can be directly installed on the other component or there may be a central component at the same time. The term "and/or" used in this article includes all and any combinations of one or more related listed items.
请参阅图1所示，为本申请一实施方式中的样本制备系统100的系统架构示意图。样本制备系统100用于完成生物样本的前期制备，包括生物样本和试剂的转移、混合、生化反应等步骤。其中，生物样本可以是人体血液样本、组织样本或唾液样本以及其它半成品生化样本等，即，该样本制备系统100可以实现生物样本和试剂的转移、混匀、以及生化反应等步骤，完成生物样本与不同试剂之间的生化反应(例如，但不限于PCR反应)，制备得到的样本可以用于后续的诸如基因测序等生化物质分析。请一并参阅图2，样本制备系统100包括流体存储模块10、流体分配模块20、反应模块30和流体驱动模块40。Please refer to FIG. 1 , which is a schematic diagram of the system architecture of a sample preparation system 100 in one embodiment of the present application. The sample preparation system 100 is used to complete the preliminary preparation of biological samples, including the steps of transferring, mixing, and biochemical reactions of biological samples and reagents. Among them, the biological sample can be a human blood sample, a tissue sample, or a saliva sample, as well as other semi-finished biochemical samples, that is, the sample preparation system 100 can realize the steps of transferring, mixing, and biochemical reactions of biological samples and reagents, complete the biochemical reactions between biological samples and different reagents (for example, but not limited to PCR reactions), and the prepared samples can be used for subsequent biochemical substance analysis such as gene sequencing. Please also refer to FIG. 2 , the sample preparation system 100 includes a fluid storage module 10, a fluid distribution module 20, a reaction module 30, and a fluid drive module 40.
流体存储模块10用于存储流体，其中所述流体可以包括生物样本和用于生化反应的试剂。反应模块30具有反应流道301，反应流道301分别与流体分配模块20和流体驱动模块40连通。流体驱动模块40用于制造压力梯度(例如产生负压)，使流体存储模块10中的流体经由流体分配模块20转运至反应流道301，具体地，可以通过流体驱动模块40使流体分配模块20内形成负压，从而在流体存储模块10内吸取流体，同时反应流道301内也形成负压，使流体进一步进入反应流道301内。反应模块30用于执行转运至反应流道301内的流体的生化反应，具体地，发生生化反应的流体可以包括生物样本和所需要的试剂，例如反应流道301内可以实现PCR反应。在一些实施例中，流体驱动模块40还用于制造压力梯度(例如产生正压)，使反应流道301中反应后的流体经由流体分配模块20转运至流体存储模块10存储另一种流体的容器中，同时，流体存储模块10还用于产生一驱动力，使另一种流体与反应后的流体混合均匀，形成混合流体，混合流体进一步被转运至反应流道301内进行反应，以此类推，当需要几种试剂与生物样本进行反应，则需要混合几次，直至得到最终的产物样本。在一些实施例中，该样本制备系统100还包括控制模块50，控制模块50用于控制流体存储模块10、流体分配模块20、反应模块30和流体驱动模块40的协调作业。The fluid storage module 10 is used to store fluid, wherein the fluid may include biological samples and biochemical The reaction module 30 has a reaction channel 301, which is connected to the fluid distribution module 20 and the fluid driving module 40 respectively. The fluid driving module 40 is used to create a pressure gradient (for example, to generate negative pressure) so that the fluid in the fluid storage module 10 is transported to the reaction channel 301 via the fluid distribution module 20. Specifically, the fluid driving module 40 can form a negative pressure in the fluid distribution module 20, thereby sucking the fluid in the fluid storage module 10, and at the same time, a negative pressure is also formed in the reaction channel 301, so that the fluid further enters the reaction channel 301. The reaction module 30 is used to perform a biochemical reaction of the fluid transported to the reaction channel 301. Specifically, the fluid undergoing the biochemical reaction can include a biological sample and the required reagents. For example, a PCR reaction can be implemented in the reaction channel 301. In some embodiments, the fluid driving module 40 is also used to create a pressure gradient (e.g., generate positive pressure) so that the reacted fluid in the reaction channel 301 is transported to the container of the fluid storage module 10 storing another fluid via the fluid distribution module 20. At the same time, the fluid storage module 10 is also used to generate a driving force so that the other fluid is mixed evenly with the reacted fluid to form a mixed fluid, which is further transported to the reaction channel 301 for reaction. Similarly, when several reagents are required to react with the biological sample, they need to be mixed several times until the final product sample is obtained. In some embodiments, the sample preparation system 100 also includes a control module 50, which is used to control the coordinated operation of the fluid storage module 10, the fluid distribution module 20, the reaction module 30 and the fluid driving module 40.
请参阅图2，一并参阅图1，流体存储模块10包括流体存储装置101和流体切换装置102。其中，流体存储装置101包括多个用于容置所述流体的容器103，通常包括一个样本容器和多个试剂容器。其中，容器103可以为试管或者其它可用于装载生物样本或试剂的任何形状的容器。如图2所示，本实施方式中的容器103为试管。容器103的开口处可以但不必须封有可刺破的密封膜(图未示)，当流体分配模块20需要吸取液体时，流体分配模块20可以伸入到容器103内部吸取流体。另外，盛放有生物样本的容器103上贴设有识别码(如二维码或条形码等，图未示)，识别码记载有对应的生物样本的识别信息，如测试对象的姓名、年龄、测试项目等，用于生物样本的跟踪和管理。容器103内的生物样本和试剂的量可以是定量的，根据生化反应需要提前将所需含量的生物样本和试剂分别放入容器103内，可实现定量移液的目的。可以理解的，也可以通过控制流体驱动模块40产生的压力梯度，来控制流体分配模块20吸取的流体的量，以实现定量移液的目的。在一些实施例中，流体存储装置101还可以包括容器托架104，容器103放置于容器托架104中，容器托架104放置于流体切换装置102上，可以实现多个容器103的稳定性，便于流体分配模块20的吸液操作。Please refer to FIG. 2, and refer to FIG. 1 together. The fluid storage module 10 includes a fluid storage device 101 and a fluid switching device 102. The fluid storage device 101 includes a plurality of containers 103 for accommodating the fluid, usually including a sample container and a plurality of reagent containers. The container 103 may be a test tube or other container of any shape that can be used to load biological samples or reagents. As shown in FIG. 2, the container 103 in this embodiment is a test tube. The opening of the container 103 may but need not be sealed with a puncturable sealing film (not shown). When the fluid distribution module 20 needs to absorb liquid, the fluid distribution module 20 can extend into the container 103 to absorb fluid. In addition, an identification code (such as a QR code or a bar code, etc., not shown) is affixed to the container 103 containing the biological sample. The identification code records the identification information of the corresponding biological sample, such as the name, age, test items, etc. of the test subject, which is used for tracking and management of the biological sample. The amount of biological samples and reagents in the container 103 can be quantitative. According to the needs of the biochemical reaction, the required amount of biological samples and reagents are placed in the container 103 in advance, respectively, to achieve the purpose of quantitative pipetting. It is understandable that the amount of fluid sucked by the fluid distribution module 20 can also be controlled by controlling the pressure gradient generated by the fluid driving module 40 to achieve the purpose of quantitative pipetting. In some embodiments, the fluid storage device 101 can also include a container holder 104, and the container 103 is placed in the container holder 104, and the container holder 104 is placed on the fluid switching device 102, which can achieve the stability of multiple containers 103 and facilitate the aspiration operation of the fluid distribution module 20.
其中，流体切换装置102用于调整前述多个容器103的位置，以使多个容器103中的一个对准流体分配模块20，以实现该容器103内流体转移的目的。如图2所示，流体切换装置102可以包括移载机构105和驱动机构106，将装载有生物样本和试剂的多个容器103按照特定顺序(例如加样顺序)依次排列在容器托架104上，并将容器托架104放置于移载机构105上，移载机构105在驱动机构106的驱动下将以上容器103依次移动至流体分配模块20的正下方，以供流体分配模块20依次吸取流体。可以理解的，在其他实施例中，如图3所示，多个容器103还可以呈阵列排布，移载机构105在驱动机构106的驱动下可以实现水平面上的多方向移动，以使多个容器103按预定顺序移动至流体分配模块20的正下方。The fluid switching device 102 is used to adjust the positions of the aforementioned multiple containers 103 so that one of the multiple containers 103 is aligned with the fluid distribution module 20 to achieve the purpose of transferring the fluid in the container 103. As shown in FIG. 2 , the fluid switching device 102 may include a transfer mechanism 105 and a drive mechanism 106. The multiple containers 103 loaded with biological samples and reagents are arranged in sequence on the container holder 104 in a specific order (e.g., a sample loading order), and the container holder 104 is placed on the transfer mechanism 105. The transfer mechanism 105 is driven by the drive mechanism 106. The above containers 103 are sequentially moved to the bottom of the fluid distribution module 20 under the action of the driving mechanism 106, so that the fluid distribution module 20 can absorb the fluid sequentially. It can be understood that in other embodiments, as shown in FIG. 3, the multiple containers 103 can also be arranged in an array, and the transfer mechanism 105 can achieve multi-directional movement on the horizontal plane under the drive of the driving mechanism 106, so that the multiple containers 103 are moved to the bottom of the fluid distribution module 20 in a predetermined order.
在一些实施例中，移载机构105可以是单轴滑轨，可以实现水平面内单一方向的往复移动，也可以是双轴滑轨，可以实现水平面内垂直的两个方向的往复移动，从而切换流体存储装置101内不同容器103的相对位置，以便于流体分配模块20的取液。In some embodiments, the transfer mechanism 105 can be a single-axis slide rail that can realize reciprocating movement in a single direction in the horizontal plane, or it can be a dual-axis slide rail that can realize reciprocating movement in two vertical directions in the horizontal plane, thereby switching the relative positions of different containers 103 in the fluid storage device 101 to facilitate liquid extraction by the fluid distribution module 20.
在一些实施例中，驱动机构106可以是驱动电机。In some embodiments, the drive mechanism 106 may be a drive motor.
在一些实施例中，流体切换装置102还包括混合机构107，可以位于移载机构105上，容器103位于混合机构107上。混合机构107可以将容器103内的流体混合均匀，例如可以采用超声、旋转、震荡、离心等方法实现容器103内流体的混匀，即该混合机构107可以采用能够产生超声、旋转、震荡以及离心等功能的机构即可。In some embodiments, the fluid switching device 102 further includes a mixing mechanism 107, which may be located on the transfer mechanism 105, and the container 103 is located on the mixing mechanism 107. The mixing mechanism 107 may mix the fluid in the container 103 uniformly, for example, by using ultrasound, rotation, oscillation, centrifugation, etc. to achieve the mixing of the fluid in the container 103, that is, the mixing mechanism 107 may be a mechanism that can generate ultrasound, rotation, oscillation, centrifugation, etc.
请再次参阅图1与图2，流体分配模块20包括取液结构201、分配管路202和取液驱动装置203，取液结构201和分配管路202相互连通，分配管路202还与反应流道301连通，进一步与流体驱动模块40连通。流体驱动模块40制造压力梯度，可以使反应流道301、分配管路202和取液结构201内形成压力梯度，例如负压或正压，从而实现流体的转移。其中，取液驱动装置203用于驱动取液结构201与流体存储装置101对准并伸入流体存储装置101内，具体地，取液驱动装置203可以带动取液结构201上下移动，使取液结构201伸入容器103内吸取流体。Please refer to Figures 1 and 2 again. The fluid distribution module 20 includes a liquid collection structure 201, a distribution pipeline 202 and a liquid collection drive device 203. The liquid collection structure 201 and the distribution pipeline 202 are interconnected. The distribution pipeline 202 is also connected to the reaction channel 301, and further connected to the fluid drive module 40. The fluid drive module 40 creates a pressure gradient, which can form a pressure gradient, such as negative pressure or positive pressure, in the reaction channel 301, the distribution pipeline 202 and the liquid collection structure 201, thereby realizing the transfer of fluid. Among them, the liquid collection drive device 203 is used to drive the liquid collection structure 201 to align with the fluid storage device 101 and extend into the fluid storage device 101. Specifically, the liquid collection drive device 203 can drive the liquid collection structure 201 to move up and down, so that the liquid collection structure 201 extends into the container 103 to absorb fluid.
在一些实施例中，取液结构201可以是试剂针，通过试剂针伸入容器103，并伸入到流体液面的下方吸取流体。In some embodiments, the liquid extraction structure 201 may be a reagent needle, which extends into the container 103 and extends below the fluid surface to absorb the fluid.
请再次参阅图1与图2，所述流体驱动模块40可以包括驱动泵401和泵驱动组件402，泵驱动组件402可以使驱动泵401制造压力梯度，例如可以产生负压或正压，实现流体驱动的目的。可以理解的，流体驱动模块40还可以采用其他能够产生压力梯度的结构或装置。Please refer to Figures 1 and 2 again, the fluid driving module 40 may include a driving pump 401 and a pump driving assembly 402. The pump driving assembly 402 may enable the driving pump 401 to create a pressure gradient, such as negative pressure or positive pressure, to achieve the purpose of fluid driving. It is understandable that the fluid driving module 40 may also use other structures or devices that can generate a pressure gradient.
在一些实施例中，驱动泵401可以是注射泵、柱塞泵、隔膜泵、齿轮泵或蠕动泵等。具体地，驱动泵401可以是注射泵，反应流道301与注射泵通过泵头的切换阀连通，其中，泵头切换阀可以实现反应流道301的开启和关闭，还可以实现与其他流体装置的连通，例如清洗存储装置以及废液装置等。In some embodiments, the driving pump 401 may be a syringe pump, a plunger pump, a diaphragm pump, a gear pump or a peristaltic pump, etc. Specifically, the driving pump 401 may be a syringe pump, and the reaction channel 301 is connected to the syringe pump through a switching valve of a pump head, wherein the pump head switching valve may realize the opening and closing of the reaction channel 301, and may also realize the connection with other fluid devices, such as a cleaning storage device and a waste liquid device, etc.
请再次参阅图1与图2，反应模块30包括流体反应结构302，反应流道301位于流体反应结构302上。在一些实施例中，反应模块30还包括温控组件303，温控组件303用于调控流体反应结构302的温度，进而控制反应流道301内的温度，以使生物样本和试剂发生生化反应。将反应流道301设计在流体反应结构302上，通过温控组件303可以直接控制反应流道301内的温度，以使反应流道301内可以实现诸如可变温度的PCR反应。Please refer to Figures 1 and 2 again. The reaction module 30 includes a fluid reaction structure 302, and the reaction channel 301 is located on the fluid reaction structure 302. In some embodiments, the reaction module 30 also includes a temperature control component 303, which is used to control the temperature of the fluid reaction structure 302, and then control the temperature in the reaction channel 301, so that the biological sample and the reagent undergo a biochemical reaction. The reaction channel 301 is designed on the fluid reaction structure 302, and the temperature in the reaction channel 301 can be directly controlled by the temperature control component 303, so that the reaction channel 301 can be realized. Such as variable temperature PCR reactions.
在一些实施例中，如图4至图8所示，反应流道301弯曲设置于流体反应结构302上，反应流道301通过弯曲设置的方式设置在流体反应结构302上，可以将长度较长的反应流道301集中设置，缩小占用空间，有利于缩小流体反应结构302的体积。如图4所示，反应流道301采用盘旋环绕的方式设置在流体反应结构302上，如图6所示，反应流道301呈S形设置在流体反应结构302上。可以理解的，反应流道301还可以呈其他不规则的弯曲形状。还可以理解的，反应流道301还可以采用直线形设置在流体反应结构上。In some embodiments, as shown in FIGS. 4 to 8 , the reaction channel 301 is bent and arranged on the fluid reaction structure 302. The reaction channel 301 is arranged on the fluid reaction structure 302 in a bent manner, and the reaction channels 301 with longer lengths can be arranged in a centralized manner, thereby reducing the occupied space and facilitating the reduction of the volume of the fluid reaction structure 302. As shown in FIG. 4 , the reaction channel 301 is arranged on the fluid reaction structure 302 in a spiral manner, and as shown in FIG. 6 , the reaction channel 301 is arranged on the fluid reaction structure 302 in an S shape. It is understandable that the reaction channel 301 can also be in other irregular curved shapes. It is also understandable that the reaction channel 301 can also be arranged on the fluid reaction structure in a straight line.
在一些实施例中，沿反应流道301的延伸方向，反应流道301包括多个反应区域，温控组件303还用于控制至少两个反应区域的温度不同，例如，如图6所示，反应流道301包括反应区域A、反应区域B和反应区域C，具有不同的温度，可以实现生化反应的不同阶段，例如PCR反应的不同阶段需要不同的温度，可以通过控制流体液滴在反应区域A、反应区域B和反应区域C之间往复移动，以完成不同阶段的反应过程。In some embodiments, along the extension direction of the reaction channel 301, the reaction channel 301 includes multiple reaction areas, and the temperature control component 303 is also used to control the different temperatures of at least two reaction areas. For example, as shown in Figure 6, the reaction channel 301 includes reaction area A, reaction area B and reaction area C, which have different temperatures to achieve different stages of biochemical reactions. For example, different stages of PCR reactions require different temperatures, and the reaction process at different stages can be completed by controlling the fluid droplets to move back and forth between reaction area A, reaction area B and reaction area C.
在一些实施例中，反应流道301的内径可以为0.3mm～2mm，可以将反应流道301设计成细长的流道，并将细长的反应流道301弯曲设置在流体反应结构302上，可以在不改变反应流道301整体容量的前提下，从而降低反应物与大气的接触面积，避免试剂结晶的问题，避免手动维护反应流道301，提高了样本制备的效率和样本制备系统100的使用率。In some embodiments, the inner diameter of the reaction channel 301 can be 0.3 mm to 2 mm. The reaction channel 301 can be designed as a slender channel, and the slender reaction channel 301 can be bent and set on the fluid reaction structure 302. Without changing the overall capacity of the reaction channel 301, the contact area between the reactants and the atmosphere can be reduced, the problem of reagent crystallization can be avoided, and manual maintenance of the reaction channel 301 can be avoided, thereby improving the efficiency of sample preparation and the utilization rate of the sample preparation system 100.
在一些实施例中，反应模块30还包括反应流道301与流体分配模块20连接的第一连接端304、以及反应流道301与流体驱动模块40连接的第二连接端305，其中，如图5所示，所述第一连接端304与所述第二连接端305可以位于流体反应结构302的同一端，反应流道301盘旋环绕在流体反应结构302上，将第一连接端304和第二连接端305设置在流体反应结构302的同一端，便于样本制备系统100的整体线路布局和连接组装，使各个模块布局更集中，有利于充分利用空间，缩小整体样本制备系统100的占用空间，实现样本制备系统100的紧凑化和小型化。可以理解的，在其他实施例中，如图6所示，所述第一连接端304与所述第二连接端305还可以位于流体反应结构302相对的两端，可以根据实际布局需要，根据实际流体驱动模块40和流体分配模块20的布局位置，将第一连接端304和第二连接端305设置在流体反应结构302相对的两端，便于管路连接，提高空间的利用率。另外，可以理解的，还可以根据实际需要将所述第一连接端304和所述第二连接端305设置在流体反应结构302合适的位置。In some embodiments, the reaction module 30 also includes a first connection end 304 connecting the reaction channel 301 to the fluid distribution module 20, and a second connection end 305 connecting the reaction channel 301 to the fluid driving module 40, wherein, as shown in FIG. 5 , the first connection end 304 and the second connection end 305 can be located at the same end of the fluid reaction structure 302, and the reaction channel 301 is spirally wrapped around the fluid reaction structure 302. The first connection end 304 and the second connection end 305 are arranged at the same end of the fluid reaction structure 302, which facilitates the overall circuit layout and connection assembly of the sample preparation system 100, makes the layout of each module more centralized, is conducive to making full use of space, reduces the occupied space of the overall sample preparation system 100, and realizes the compactness and miniaturization of the sample preparation system 100. It is understandable that in other embodiments, as shown in FIG6 , the first connection end 304 and the second connection end 305 can also be located at opposite ends of the fluid reaction structure 302. According to actual layout requirements, according to the layout positions of the actual fluid driving module 40 and the fluid distribution module 20, the first connection end 304 and the second connection end 305 can be arranged at opposite ends of the fluid reaction structure 302 to facilitate pipeline connection and improve space utilization. In addition, it is understandable that the first connection end 304 and the second connection end 305 can also be arranged at appropriate positions of the fluid reaction structure 302 according to actual needs.
在一些实施例中，一并参阅图2所示，所述第一连接端304和所述第二连接端305均设有开关部件306，开关部件306可以用于打开或关闭反应流道301。具体地，一个开关部件306设置在反应流道301的第一连接端304，流体分配模块20中的分配管路202连接在该开关部件306上，通过控制该开关部件306可以实现反应流道301与分配管路202的连通和断开。另一个开关部件306设置在反应流道301的第二连接端305，流体驱动模块40中的驱动泵401连接在该开关部件306上，通过控制该开关部件306可以实现反应流道301反应流道301的连通和断开。具体地，如图2所示，驱动泵401的泵头切换阀可以作为开关部件306，实现对反应流道301的第二连接端305的打开和关闭的目的。通过在反应流道301的前后两端设置开关部件306，可以实现反应流道301的密封，与大气隔绝，从而实现在高温生化反应(例如高温PCR反应)过程中，尤其是在高海拔低气压地区，避免流体沸腾和蒸发损耗，影响生化反应质量，而且还可以免除传统PCR反应需要增加PCR热盖以及需要手动维护PCR热盖上试剂结晶等问题。In some embodiments, referring to FIG. 2 , the first connection end 304 and the second connection end 305 are both provided with a switch component 306, and the switch component 306 can be used to open or close the reaction channel 301. Specifically, a switch component 306 is provided at the first connection end 304 of the reaction channel 301, and the fluid distribution module 20 The distribution pipeline 202 of the reaction channel 301 is connected to the switch component 306, and the connection and disconnection between the reaction channel 301 and the distribution pipeline 202 can be achieved by controlling the switch component 306. Another switch component 306 is arranged on the second connection end 305 of the reaction channel 301, and the driving pump 401 in the fluid driving module 40 is connected to the switch component 306, and the connection and disconnection between the reaction channel 301 and the reaction channel 301 can be achieved by controlling the switch component 306. Specifically, as shown in FIG. 2, the pump head switching valve of the driving pump 401 can be used as the switch component 306 to achieve the purpose of opening and closing the second connection end 305 of the reaction channel 301. By arranging switch components 306 at the front and rear ends of the reaction channel 301, the reaction channel 301 can be sealed and isolated from the atmosphere, thereby avoiding fluid boiling and evaporation losses that affect the quality of the biochemical reaction during high-temperature biochemical reactions (such as high-temperature PCR reactions), especially in high-altitude and low-pressure areas. It can also avoid the need for traditional PCR reactions to add a PCR hot cover and the need to manually maintain reagent crystallization on the PCR hot cover.
在一些实施例中，开关部件306可以是能够实现反应流道301打开和关闭的器部件，例如，可以是电磁阀、旋转阀、定量泵、堵头等器部件，或者还可以是止流夹这类夹持部件等。具体地，反应流道301两端设置的开关部件306为截止阀或切换阀。In some embodiments, the switch component 306 may be a device component that can realize the opening and closing of the reaction channel 301, for example, it may be a device component such as a solenoid valve, a rotary valve, a metering pump, a plug, or a clamping component such as a stop clamp, etc. Specifically, the switch components 306 provided at both ends of the reaction channel 301 are stop valves or switching valves.
在一些实施例中，如图4至图8所示，流体反应结构302包括基板321和形成于基板321上的凹槽322，凹槽322内设有中空的反应管路323，反应管路323的中空部分构成所述反应流道301，反应管路323伸出凹槽322的两端分别构成所述第一连接端304和所述第二连接端305，从而实现与流体分配模块20和流体驱动模块40连通。具体地，反应管路323可以是细长的具有柔性的软管，可以采用诸如FEP、PFA、PTFE等特氟龙材质或其他不易被腐蚀同时具有一定柔韧性的材质。可以根据实际所需要的反应流道301的长度设计基板321上凹槽322的整体长度，根据基板321的面积合理设置凹槽322的弯曲方式，从而将细长的反应流道301设置在基板321上，便于反应流道301在基板321上的弯曲设置。具体地，凹槽322可以通过蚀刻开槽、激光开槽、机械开槽或注塑等方式形成，凹槽322的弯曲形状可以灵活设置，有利于充分利用基板321的空间，进而缩小反应模块30的体积。可以理解的，当流量较小时，所需反应管路323的长度较短，反应管路323也可以采用直线形设计方式，或者根据组装需求，为了合理利用空间，反应管路323也可以采用直线形方式设置在流体反应结构302上。In some embodiments, as shown in FIG. 4 to FIG. 8 , the fluid reaction structure 302 includes a substrate 321 and a groove 322 formed on the substrate 321, a hollow reaction pipeline 323 is arranged in the groove 322, the hollow part of the reaction pipeline 323 constitutes the reaction channel 301, and the two ends of the reaction pipeline 323 extending out of the groove 322 respectively constitute the first connection end 304 and the second connection end 305, thereby realizing communication with the fluid distribution module 20 and the fluid driving module 40. Specifically, the reaction pipeline 323 can be a slender and flexible hose, and can be made of Teflon materials such as FEP, PFA, PTFE or other materials that are not easily corroded and have a certain flexibility. The overall length of the groove 322 on the substrate 321 can be designed according to the actual required length of the reaction channel 301, and the bending mode of the groove 322 can be reasonably set according to the area of the substrate 321, so that the slender reaction channel 301 is set on the substrate 321, which is convenient for the bending setting of the reaction channel 301 on the substrate 321. Specifically, the groove 322 can be formed by etching, laser, mechanical or injection molding, and the curved shape of the groove 322 can be flexibly set, which is conducive to making full use of the space of the substrate 321, thereby reducing the volume of the reaction module 30. It can be understood that when the flow rate is small, the length of the required reaction pipeline 323 is short, and the reaction pipeline 323 can also be designed in a straight line, or according to assembly requirements, in order to reasonably use the space, the reaction pipeline 323 can also be set on the fluid reaction structure 302 in a straight line.
在一些实施例中，流体反应结构302可以具有导热功能，温控组件303可以通过直接控制流体反应结构302的温度，从而实现对内嵌在凹槽322内的反应管路323的温度控制，以对反应流道301内进行精确控温。例如温控组件303可以是热电冷却器(TEC)，能够实现对基板321的加热和制冷。In some embodiments, the fluid reaction structure 302 may have a heat conduction function, and the temperature control component 303 may directly control the temperature of the fluid reaction structure 302, thereby achieving temperature control of the reaction pipeline 323 embedded in the groove 322, so as to accurately control the temperature in the reaction channel 301. For example, the temperature control component 303 may be a thermoelectric cooler (TEC), which can achieve heating and cooling of the substrate 321.
在一些实施例中，沿基板321的厚度方向，凹槽322的深度(如图7中L2)大于或等于反应管路323的外径(如图7中L1)，通过将凹槽322的深度设计的大一些，可以使反应管路323全部内嵌在凹槽322内，使反应管路323内温度更均匀，以提高反应流道301内温控的精确性。In some embodiments, along the thickness direction of the substrate 321, the depth of the groove 322 (such as L2 in FIG. 7 ) is greater than or equal to the outer diameter of the reaction tube 323 (such as L1 in FIG. 7 ). By designing the depth of the groove 322 to be larger, the reaction tube 323 can be completely embedded in the groove 322, so that the temperature in the reaction tube 323 is more uniform. uniformity to improve the accuracy of temperature control in the reaction channel 301.
在一些实施例中，反应管路323可拆卸设于凹槽322中。当需要安装反应管路323时，直接将反应管路323的软管嵌入凹槽322内即可，方便快捷，便于维护和更换。In some embodiments, the reaction pipeline 323 is detachably disposed in the groove 322. When the reaction pipeline 323 needs to be installed, the hose of the reaction pipeline 323 can be directly embedded in the groove 322, which is convenient and fast, and easy to maintain and replace.
在一些实施例中，反应流道301、第一连接端304和第二连接端305为一体式结构，以上三部分的通路采用流体管线的方式，形成一体化设计，可以使反应模块30、流体分配模块20和流体驱动模块40中的反应区域、吸液针和泵阀等连接管路都在同一条流体通道上，例如实现PCR反应，则PCR区域与泵阀流体管线共用一根管路。以上设计相较于传统通过移液法样本制备(使用移液针，将反应物移液至专用的PCR模块进行PCR反应)的样本损耗量大大减小、耗材数量少、流程操作简单。可以理解的，反应管路323还可以与流体分配模块20和流体驱动模块40可拆卸连接，便于单独维护或更换各个部分。In some embodiments, the reaction channel 301, the first connection end 304 and the second connection end 305 are an integrated structure, and the passages of the above three parts are in the form of fluid pipelines to form an integrated design, so that the reaction area, the pipetting needle and the pump valve and other connecting pipelines in the reaction module 30, the fluid distribution module 20 and the fluid drive module 40 are all on the same fluid channel. For example, to achieve a PCR reaction, the PCR area and the pump valve fluid pipeline share a pipeline. Compared with the traditional sample preparation by pipetting (using a pipetting needle to pipette the reactant to a dedicated PCR module for PCR reaction), the above design greatly reduces the sample loss, the number of consumables is small, and the process operation is simple. It can be understood that the reaction pipeline 323 can also be detachably connected to the fluid distribution module 20 and the fluid drive module 40, which is convenient for separate maintenance or replacement of each part.
在一些实施例中，反应管路323可以是非耗材，通过清洗反应流道301可以实现反应管路323的反复利用，有效降低样本制备系统100的成本。可以理解的，反应管路323也可以是耗材，每次样本制备完成后更换反应管路323，无需清洗流程，且反应管路323更换容易。In some embodiments, the reaction line 323 may be a non-consumable material, and the reaction line 323 may be reused by cleaning the reaction channel 301, effectively reducing the cost of the sample preparation system 100. It is understandable that the reaction line 323 may also be a consumable material, and the reaction line 323 is replaced after each sample preparation, without the need for a cleaning process, and the reaction line 323 is easy to replace.
在一些实施例中，反应流道301的样本处理体积灵活，可以通过设计反应流道301的内径和长度，来调控样本处理体积。具体地，本实施例样本制备系统100的反应流道301可实现3μL～2500μL的样本处理体积，或更宽范围的样本处理体积。In some embodiments, the sample processing volume of the reaction channel 301 is flexible, and the sample processing volume can be controlled by designing the inner diameter and length of the reaction channel 301. Specifically, the reaction channel 301 of the sample preparation system 100 of this embodiment can achieve a sample processing volume of 3 μL to 2500 μL, or a wider range of sample processing volumes.
在一些实施例中，如图8所示，流体反应结构302还包括盖合在基板321上的盖板324，盖板324覆盖凹槽322，盖板324的增加可以使凹槽322内反应管路323受热更均匀，尤其能够使凹槽322开口处的反应管路323与凹槽322底部的反应管路323的受热情况保持一致。In some embodiments, as shown in FIG. 8 , the fluid reaction structure 302 further includes a cover plate 324 covering the substrate 321 , and the cover plate 324 covers the groove 322 . The addition of the cover plate 324 can make the reaction pipeline 323 in the groove 322 be heated more evenly, and in particular can make the heating conditions of the reaction pipeline 323 at the opening of the groove 322 and the reaction pipeline 323 at the bottom of the groove 322 consistent.
可以理解的，在其他实施例中，请参阅图9，反应流道301还可以是直接形成在流体反应结构上的。流体反应结构302a还可以包括叠设的基板321a和盖板324，基板321a上形成有凹槽322a，盖板324靠近基板321a的表面与基板321a密封连接以使该凹槽322a形成密封的反应流道301。即本实施例中直接在基板321a上形成凹槽322a从而形成反应流道301，使反应模块30结构更简单，凹槽322a形成的反应流道301的温度控制更容易，且温度更均匀。具体地，凹槽322a可以通过注塑成型或蚀刻等工艺成型得到。It is understandable that in other embodiments, please refer to FIG. 9 , the reaction channel 301 can also be directly formed on the fluid reaction structure. The fluid reaction structure 302a can also include a stacked substrate 321a and a cover plate 324, a groove 322a is formed on the substrate 321a, and the surface of the cover plate 324 close to the substrate 321a is sealed and connected to the substrate 321a so that the groove 322a forms a sealed reaction channel 301. That is, in this embodiment, the groove 322a is directly formed on the substrate 321a to form the reaction channel 301, so that the reaction module 30 structure is simpler, and the temperature control of the reaction channel 301 formed by the groove 322a is easier, and the temperature is more uniform. Specifically, the groove 322a can be obtained by injection molding or etching.
还可以理解的，在其他实施例中，请参阅图10，流体反应结构302b包括叠设的基板321b和盖板324、以及位于基板321b和盖板324之间的两个支撑壁325，每个支撑壁325相对的两端面分别与基板321b和盖板324连接，基板321b、两个支撑壁325以及盖板324共同围成所述反应流道301。且通过设计两个支撑壁325的厚度和间距可以试剂反应流道301的体积。两个支撑壁325可以是具有柔性的材质，可以根据所需反应流道301的弯曲的形状进行设计。It can also be understood that in other embodiments, refer to FIG. 10 , the fluid reaction structure 302b includes a stacked substrate 321b and a cover plate 324, and two support walls 325 located between the substrate 321b and the cover plate 324. The two opposite end surfaces of each support wall 325 are respectively connected to the substrate 321b and the cover plate 324. The substrate 321b, the two support walls 325 and the cover plate 324 together enclose the reaction channel 301. The volume of the reagent reaction channel 301 can be reduced by designing the thickness and spacing of the two support walls 325. The two support walls 325 can be made of a flexible material. The reaction channel 301 may be designed according to the desired curved shape.
如图9与图10所示的流体反应结构，在实现与流体分配模块20和流体驱动模块40连通时，可以采用管路插接在流体反应结构302a或302b对应的反应流道301的端口，实现连通。可以理解的，当反应流道301直接成型在流体反应结构302a或302b上的情况，整体流体反应结构302a或302b作为一个整体可以实现与流体分配模块20中的分配管路202和流体驱动模块40中的分配管路202可拆卸连接，便于维护和更换流体反应结构302a或302b。As shown in FIG9 and FIG10 , when the fluid reaction structure is connected with the fluid distribution module 20 and the fluid driving module 40, the pipeline can be inserted into the port of the reaction channel 301 corresponding to the fluid reaction structure 302a or 302b to achieve communication. It can be understood that when the reaction channel 301 is directly formed on the fluid reaction structure 302a or 302b, the overall fluid reaction structure 302a or 302b as a whole can be detachably connected with the distribution pipeline 202 in the fluid distribution module 20 and the distribution pipeline 202 in the fluid driving module 40, which is convenient for maintenance and replacement of the fluid reaction structure 302a or 302b.
请再次参阅图1与图2，样本制备系统100还包括废液收集装置60和清洗液存储装置70，废液收集装置60和清洗液存储装置70均与流体驱动模块40连通。具体地，废液收集装置60和清洗液存储装置70均与流体驱动模块40中的驱动泵401连通，当驱动泵401为注射泵时，废液收集装置60和清洗液存储装置70均通过管路连接在注射泵的泵头上。具体地，清洗液存储装置70内可以放置纯水，用于清洗整个流道。Please refer to Figures 1 and 2 again. The sample preparation system 100 also includes a waste liquid collection device 60 and a cleaning liquid storage device 70, and both the waste liquid collection device 60 and the cleaning liquid storage device 70 are connected to the fluid drive module 40. Specifically, the waste liquid collection device 60 and the cleaning liquid storage device 70 are both connected to the drive pump 401 in the fluid drive module 40. When the drive pump 401 is a syringe pump, the waste liquid collection device 60 and the cleaning liquid storage device 70 are connected to the pump head of the syringe pump through a pipeline. Specifically, pure water can be placed in the cleaning liquid storage device 70 to clean the entire flow channel.
本申请实施例提高的样本制备系统100具有以下有益效果：The sample preparation system 100 improved by the embodiment of the present application has the following beneficial effects:
1.通过流体存储模块10、流体分配模块20、流体驱动模块40以及反应模块30在控制模块50的的控制下协同作业，进行流体的移液、混合以及生化反应等工序，可以实现一站式的自动化样本制备(例如测序前的文库处理)，流程简单，样本制备效率高，且流体损耗量较小，节约成本，实现低成本的小型模块化设计；而且，通过前述多个模块可以构成一体化样本制备系统，使反应流道301与其他流体管路相连接形成一体化流体通道，样本损耗量减小，耗材少，设备成本较低，且操作流程简单。另外，样本制备系统100可以整合在样本使用系统(例如测序仪)中，可以共用样本使用系统中的部分部件，通量匹配性更好。1. Through the coordinated operation of the fluid storage module 10, the fluid distribution module 20, the fluid drive module 40 and the reaction module 30 under the control of the control module 50, the processes such as fluid pipetting, mixing and biochemical reaction can be performed, so that one-stop automated sample preparation (such as library processing before sequencing) can be realized, the process is simple, the sample preparation efficiency is high, and the fluid loss is small, which saves costs and realizes low-cost small modular design; moreover, the aforementioned multiple modules can constitute an integrated sample preparation system, so that the reaction flow channel 301 is connected with other fluid pipelines to form an integrated fluid channel, the sample loss is reduced, the consumables are small, the equipment cost is low, and the operation process is simple. In addition, the sample preparation system 100 can be integrated into a sample use system (such as a sequencer), and some components in the sample use system can be shared, and the flux matching is better.
2.该样本制备系统100，由于减少人为干预，因此能够避免人工操作容易出错的情况，有利于提高后续生化物质分析的准确性。2. The sample preparation system 100 can avoid the situation where manual operation is prone to errors due to reduced human intervention, which is beneficial to improving the accuracy of subsequent biochemical substance analysis.
3.通过在反应流道301的两端设置开关部件306，将流体本限制在反应流道301内，实现前后密闭，从而实现在高温生化反应过程中，尤其在高海拔低气压地区，避免液体沸腾和蒸发损耗；反应流道301密封后，反应物与大气隔绝，气液交界面大幅缩小、甚至无气液交界面，解决PCR高温蒸发导致的PCR质量下降，提升PCR质量；流体与大气隔绝，还可以避免增加传统自动化样本制备系统中常见的“PCR热盖”以及对“PCR热盖”进行手动维护的问题。3. By arranging switch components 306 at both ends of the reaction channel 301, the fluid is confined in the reaction channel 301 to achieve front-to-back sealing, thereby avoiding liquid boiling and evaporation loss during high-temperature biochemical reactions, especially in high-altitude and low-pressure areas; after the reaction channel 301 is sealed, the reactants are isolated from the atmosphere, and the gas-liquid interface is greatly reduced or even eliminated, thereby solving the problem of PCR quality degradation caused by PCR high-temperature evaporation and improving PCR quality; the fluid is isolated from the atmosphere, and the problem of adding a "PCR hot cover" commonly seen in traditional automated sample preparation systems and manual maintenance of the "PCR hot cover" can be avoided.
4.反应流道301内嵌在能够实现变温的流体反应结构302上，便于反应流道301的温度控制。4. The reaction channel 301 is embedded in the fluid reaction structure 302 that can achieve temperature change, which facilitates the temperature control of the reaction channel 301.
5.反应流道301可以设计成“非耗材”，降低了样本制备的成本。另外，反应流道301也可以设计为耗材，且更换简单，无需清洗，进一步简化操作和样本制备系统100的结构。5. The reaction channel 301 can be designed as “non-consumable”, reducing the cost of sample preparation. In addition, the reaction channel 301 can also be designed as a consumable, which is easy to replace and does not require cleaning, further simplifying the operation and structure of the sample preparation system 100.
6.该样本制备系统100的样本处理体积灵活，可实现3μL～2500μL，或更宽范围的样本处理。6. The sample preparation system 100 has a flexible sample processing volume, and can process samples in a range of 3 μL to 2500 μL, or a wider range.
请参阅图11，本申请实施例还提供了一种生化物质分析系统1000，请一并参阅图1与图2，生化物质分析系统1000包括如上所述的样本制备系统100和与样本制备系统100连通的样本使用系统200。样本制备系统100中的流体驱动模块40还用于将位于反应流道301内反应后得到的产物样本转运至样本使用系统200，即，流体驱动模块40可以制造压力梯度，以驱动位于反应流道301内反应后得到的产物样本转运至样本使用系统200。样本制备系统100可以直接与样本使用系统200融合，将反应流道301内制备的产物样本直接转运至样本使用系统200内，进行后续的生化物质分析过程。例如，样本制备系统100可以实现生物样本的PCR扩增，样本使用系统200可以是测序仪，包括用于实现基因测序的测序芯片，样本制备系统100的反应流道301与样本使用系统200的测序芯片连通，流体驱动模块40将位于反应流道301内经过PCR反应得到的产物样本转运至测序芯片进行测序。Please refer to FIG. 11 . The embodiment of the present application further provides a biochemical substance analysis system 1000. Please refer to FIG. 1 and FIG. 2 together. The biochemical substance analysis system 1000 includes the sample preparation system 100 as described above and a sample use system 200 connected to the sample preparation system 100. The fluid driving module 40 in the sample preparation system 100 is also used to transfer the product sample obtained after the reaction in the reaction channel 301 to the sample use system 200, that is, the fluid driving module 40 can create a pressure gradient to drive the product sample obtained after the reaction in the reaction channel 301 to be transferred to the sample use system 200. The sample preparation system 100 can be directly integrated with the sample use system 200 to directly transfer the product sample prepared in the reaction channel 301 to the sample use system 200 for subsequent biochemical substance analysis process. For example, the sample preparation system 100 can realize PCR amplification of biological samples, and the sample use system 200 can be a sequencer, including a sequencing chip for realizing gene sequencing. The reaction channel 301 of the sample preparation system 100 is connected to the sequencing chip of the sample use system 200, and the fluid driving module 40 transfers the product sample obtained by PCR reaction in the reaction channel 301 to the sequencing chip for sequencing.
在一些实施例中，流体分配模块20与反应模块30之间还设有流体分配阀204，流体分配阀204还可与样本使用系统200连通，通过控制流体分配阀204，可以实现流体方向的选择，即实现流体分配模块20与反应模块30连通，或反应模块30与样本使用系统200连通。具体地，流体分配阀204可以是一电磁阀，具有一常开端、一公共端和一常闭端，流体分配模块20连接在常开端上，反应模块30连接在公共端上，样本使用系统200连接在常闭端上，当需要向样本使用系统200转移产物样本时，打开常闭端，关闭常开端。具体地，分配管路202连接在常开端上，反应流道301的第一连接端304连接在公共端，样本使用系统200的测序芯片连接在常闭端上。In some embodiments, a fluid distribution valve 204 is further provided between the fluid distribution module 20 and the reaction module 30. The fluid distribution valve 204 can also be connected to the sample use system 200. By controlling the fluid distribution valve 204, the selection of the fluid direction can be realized, that is, the fluid distribution module 20 is connected to the reaction module 30, or the reaction module 30 is connected to the sample use system 200. Specifically, the fluid distribution valve 204 can be a solenoid valve, having a normally open end, a common end and a normally closed end. The fluid distribution module 20 is connected to the normally open end, the reaction module 30 is connected to the common end, and the sample use system 200 is connected to the normally closed end. When it is necessary to transfer the product sample to the sample use system 200, the normally closed end is opened and the normally open end is closed. Specifically, the distribution pipeline 202 is connected to the normally open end, the first connection end 304 of the reaction flow channel 301 is connected to the common end, and the sequencing chip of the sample use system 200 is connected to the normally closed end.
本申请实施例的样本制备系统100能与常规的样本使用系统200进行融合，可与样本使用系统200共享器部件(如泵、阀、管线、驱动器、控制软件、UI界面等)，可以整合在样本使用系统200中且不额外增加或较少增加其余组件。可以实现与样本使用系统200的无缝衔接，能够减少甚至不需要增加额外的器部件，进一步降低整体生化物质分析系统1000的成本，大幅缩短工作时间，减少人因失误。The sample preparation system 100 of the embodiment of the present application can be integrated with the conventional sample use system 200, can share components (such as pumps, valves, pipelines, drivers, control software, UI interface, etc.) with the sample use system 200, and can be integrated into the sample use system 200 without adding or adding less other components. It can achieve seamless connection with the sample use system 200, can reduce or even eliminate the need to add additional components, further reduce the cost of the overall biochemical substance analysis system 1000, significantly shorten working time, and reduce human errors.
请参阅图12，一并参阅图1与图2，本申请实施例还提供了一种采用前述样本制备系统100制备产物样本的方法，具体包括以下步骤：Please refer to FIG. 12 , and refer to FIG. 1 and FIG. 2 together. The embodiment of the present application further provides a method for preparing a product sample using the aforementioned sample preparation system 100 , which specifically includes the following steps:
步骤S01，通过流体驱动模块40制造压力梯度，使位于流体存储模块10中的流体经由流体分配模块20转运至反应模块30中的反应流道301内。In step S01 , a pressure gradient is created by the fluid driving module 40 , so that the fluid in the fluid storage module 10 is transported to the reaction channel 301 in the reaction module 30 via the fluid distribution module 20 .
步骤S02，通过反应模块30调控反应流道301内的温度，使所述流体在反应流道301内发生生化反应，从而获得所述样本，即产物样本。Step S02 , regulating the temperature in the reaction channel 301 through the reaction module 30 to cause the fluid to undergo a biochemical reaction in the reaction channel 301 , thereby obtaining the sample, ie, the product sample.
具体地，产物样本的制备方法包括以下步骤：Specifically, the method for preparing the product sample includes the following steps:
步骤S1，通过流体分配模块20和流体切换装置102的协调动作，使流体分配模块20与流体存储装置101中存储第一种流体的容器103对准。Step S1, through the coordinated action of the fluid distribution module 20 and the fluid switching device 102, the fluid distribution The module 20 is aligned with a container 103 storing a first fluid in the fluid storage device 101 .
步骤S2，将流体分配模块20伸入存储第一种流体的容器103中。Step S2, extending the fluid distribution module 20 into the container 103 storing the first fluid.
步骤S3，通过流体驱动模块40制造压力梯度，使位于存储第一种流体的容器103中的第一种流体经由流体分配模块20转运至反应模块30中的反应流道301内。Step S3 , creating a pressure gradient through the fluid driving module 40 , so that the first fluid in the container 103 storing the first fluid is transported to the reaction channel 301 in the reaction module 30 through the fluid distribution module 20 .
步骤S4，关闭反应流道301两端的开关部件306，以密封反应流道301。Step S4 , closing the switch components 306 at both ends of the reaction channel 301 to seal the reaction channel 301 .
步骤S5，通过反应模块30调控反应流道301内的温度，使第一种流体在反应流道301内发生生化反应。Step S5 , regulating the temperature in the reaction channel 301 through the reaction module 30 , so that the first fluid undergoes a biochemical reaction in the reaction channel 301 .
步骤S6，打开反应流道301两端的开关部件306。Step S6, opening the switch components 306 at both ends of the reaction channel 301.
步骤S7，通过流体分配模块20和流体切换装置102的协调动作，使流体分配模块20与流体存储装置101存储第二种流体的容器103对准。Step S7 , through the coordinated action of the fluid dispensing module 20 and the fluid switching device 102 , the fluid dispensing module 20 is aligned with the container 103 storing the second fluid of the fluid storage device 101 .
步骤S8，将流体分配模块20伸入存储所述另一种流体的容器103中。Step S8, extending the fluid distribution module 20 into the container 103 storing the other fluid.
步骤S9，通过流体驱动模块40制造压力梯度，使位于反应流道301内反应后的第一种流体经由流体分配模块20转运至存储第二种流体的容器103中，使第二种流体与反应后的第一种流体混合得到混合流体。Step S9, creating a pressure gradient through the fluid driving module 40, so that the first fluid after reaction in the reaction channel 301 is transferred to the container 103 storing the second fluid through the fluid distribution module 20, so that the second fluid is mixed with the first fluid after reaction to obtain a mixed fluid.
步骤S10，通过流体驱动模块40制造压力梯度，使流体分配模块20吸取所述混合流体，并将所述混合流体转运至反应模块30中的反应流道301内。In step S10 , a pressure gradient is created by the fluid driving module 40 so that the fluid distributing module 20 absorbs the mixed fluid and transfers the mixed fluid to the reaction channel 301 in the reaction module 30 .
步骤S11，通过反应模块30调控反应流道301内的温度，使所述混合流体在反应流道301内发生反应，直至反应完成，得到产物样本。In step S11 , the temperature in the reaction channel 301 is regulated by the reaction module 30 to allow the mixed fluid to react in the reaction channel 301 until the reaction is completed to obtain a product sample.
在一些实施例中，获得产物样本的步骤之后，所述方法还包括：In some embodiments, after the step of obtaining a product sample, the method further comprises:
通过流体驱动模块40将位于反应流道301内的所述样本转运至样本使用系统。The sample in the reaction channel 301 is transported to the sample using system through the fluid driving module 40 .
在一些实施例中，相邻两种所述流体进入反应流道301的步骤之间，或得到所述样本的步骤之后，所述方法还包括：In some embodiments, between the steps of two adjacent fluids entering the reaction channel 301, or after the step of obtaining the sample, the method further includes:
通过流体驱动模块40造压力梯度，使位于清洗液存储装置70中的清洗液进入反应流道301内对反应流道301进行清洗，并使清洗后的废液转运至废液收集装置60中。The pressure gradient is created by the fluid driving module 40 , so that the cleaning liquid in the cleaning liquid storage device 70 enters the reaction channel 301 to clean the reaction channel 301 , and the waste liquid after cleaning is transferred to the waste liquid collection device 60 .
具体地，以制备基因测序所需样本为例，请一并结合参阅图1和图2，控制模块50包括用于控制流体存储模块10、流体分配模块20、流体驱动模块40和流体反应模块30协同作业的控制程序，所述控制程序运行时用于执行以下方法：Specifically, taking the preparation of samples required for gene sequencing as an example, please refer to FIG. 1 and FIG. 2 together. The control module 50 includes a control program for controlling the coordinated operation of the fluid storage module 10, the fluid distribution module 20, the fluid driving module 40 and the fluid reaction module 30. When the control program is running, it is used to execute the following method:
第1步：流体切换装置102中的移载机构105与取液驱动装置203协调动作，使取液结构201(如试剂针)的针尖在垂直方向上对准存放第1流体的容器(样本容器)，准备吸取第1流体，这里第1流体可以是生物样本，如DNA样本。Step 1: The transfer mechanism 105 in the fluid switching device 102 coordinates with the liquid extraction drive device 203 to align the needle tip of the liquid extraction structure 201 (such as a reagent needle) in the vertical direction with the container (sample container) storing the first fluid, ready to absorb the first fluid, where the first fluid can be a biological sample, such as a DNA sample.
第2步：试剂针下降插入样本管的液面以下，驱动泵401(如注射泵)动作，将第1流体引导至反应流道301内。Step 2: The reagent needle is lowered and inserted below the liquid level of the sample tube, driving the pump 401 (such as a syringe pump) to operate and guide the first fluid into the reaction channel 301 .
第3步：温控组件303控制流体反应结构302的温度，使第1流体在反应流道301中实现不同温度的反应(如PCR反应)。在温控反应过程中，将开关部件306关闭，使得反应流道301内的流体处于与大气隔绝状态。温控结束后，将开关部件306打开。Step 3: The temperature control component 303 controls the temperature of the fluid reaction structure 302, so that the first fluid can achieve different temperature reactions (such as PCR reactions) in the reaction channel 301. Close the switch component 306 so that the fluid in the reaction channel 301 is isolated from the atmosphere. After the temperature control is completed, open the switch component 306.
第4步：移载机构105与取液驱动装置203协调动作，使试剂针的针尖在垂直方向上对准放置第2流体的容器103。Step 4: The transfer mechanism 105 and the liquid extraction drive device 203 work in coordination to align the needle tip of the reagent needle with the container 103 containing the second fluid in the vertical direction.
第5步：控制注射泵，控制试剂针在垂直方向上的运动，将反应流道301内反应后的第1流体引导至试剂针，排入放置有第2流体的容器103中。Step 5: Control the syringe pump to control the vertical movement of the reagent needle, guide the first fluid after the reaction in the reaction channel 301 to the reagent needle, and discharge it into the container 103 containing the second fluid.
第6步：混合机构107使反应后的第1流体和第2流体在容器103中混合均匀得到混合流体，例如可以采用超声、旋转、震荡、离心等方法。Step 6: The mixing mechanism 107 mixes the first fluid and the second fluid after the reaction in the container 103 to obtain a mixed fluid, for example, by using methods such as ultrasound, rotation, vibration, centrifugation, etc.
第7步：注射泵动作，控制试剂针在垂直方向上的运动，将混合流体引导至反应流道301内进行第二步反应。Step 7: The syringe pump is activated to control the movement of the reagent needle in the vertical direction and guide the mixed fluid into the reaction channel 301 for the second step reaction.
第8步：再重复第3步～第7步。实现对多种流体的混匀、定量移液、密闭微腔体的生化反应等步骤，最终得到产物样本，以供后续生化物质分析(例如基因测序)使用。Step 8: Repeat steps 3 to 7 to achieve the steps of mixing multiple fluids, quantitative pipetting, biochemical reaction in a closed micro-chamber, etc., and finally obtain a product sample for subsequent biochemical substance analysis (such as gene sequencing).
最后应说明的是，以上实施例仅用以说明本申请的技术方案而非限制，尽管参照较佳实施例对本申请进行了详细说明，本领域的普通技术人员应当理解，可以对本申请的技术方案进行修改或等同替换，而不脱离本申请技术方案的精神和范围。Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present application and are not intended to limit it. Although the present application has been described in detail with reference to the preferred embodiments, a person of ordinary skill in the art should understand that the technical solution of the present application may be modified or replaced by equivalents without departing from the spirit and scope of the technical solution of the present application.
| Application Number | Priority Date | Filing Date | Title |
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| PCT/CN2023/117644WO2025050373A1 (en) | 2023-09-08 | 2023-09-08 | Reaction module, sample preparation system, sample preparation method, and biochemical substance analysis system |
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| PCT/CN2023/117644WO2025050373A1 (en) | 2023-09-08 | 2023-09-08 | Reaction module, sample preparation system, sample preparation method, and biochemical substance analysis system |
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| WO2025050373A1true WO2025050373A1 (en) | 2025-03-13 |
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| PCT/CN2023/117644PendingWO2025050373A1 (en) | 2023-09-08 | 2023-09-08 | Reaction module, sample preparation system, sample preparation method, and biochemical substance analysis system |
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| CN107988044A (en)* | 2017-12-29 | 2018-05-04 | 东南大学 | A kind of big reaction volume flow channel type PCR amplification device |
| CN110560184A (en)* | 2018-06-06 | 2019-12-13 | 厦门大学 | Microfluidic chip, microfluidic reaction system and driving method |
| KR20210015292A (en)* | 2019-08-01 | 2021-02-10 | 한국과학기술원 | Modular microfluidic device and method for manufacturing thereof |
| CN110951610A (en)* | 2019-12-31 | 2020-04-03 | 苏州缔因安生物科技有限公司 | Fully-integrated miniaturized chip type digital PCR detection system and detection method |
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| CN113145185A (en)* | 2021-02-08 | 2021-07-23 | 北京理工大学 | Modular microfluidic nucleic acid detection chip and system |
| CN113122613A (en)* | 2021-04-09 | 2021-07-16 | 四川微康朴澜医疗科技有限责任公司 | Totally enclosed fluorescence quantitative PCR micro-fluidic detection chip |
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