



技术领域technical field
本发明属于生物仪器设备技术领域,具体涉及一种阵列式生物芯片点样装置。The invention belongs to the technical field of biological instruments and equipment, and in particular relates to an array type biological chip spotting device.
背景技术Background technique
目前在市场上点样仪采用的点样头是以接触式点样针为主,接触式点样在重复点样条件下具有较高的试剂交叉污染的风险,并且点样针的易损坏性、微阵列芯片的制备效率低。对于非接触式点样,点样过程独立可以较好的解决接触式点样交叉污染、点样针触碰基板损坏等问题。市面上已有的非接触式的点样喷头存在点样效率低,且在点不同的生物样品的时候需要反复清洗喷头、烘干等一系列过程,导致耗时较长、装置复杂、造价昂贵、非模块化装拆极其不方便等问题。At present, the spotting heads used in spotting instruments on the market are mainly contact pointing needles. Contact pointing has a high risk of cross-contamination of reagents under repeated spotting conditions, and the pointing needles are fragile. 1. The preparation efficiency of the microarray chip is low. For non-contact spotting, the independence of the spotting process can better solve the problems of cross-contamination of contact spotting and damage to the substrate when the spotting needle touches the substrate. The existing non-contact spotting nozzles on the market have low spotting efficiency, and a series of processes such as repeated cleaning of the nozzles and drying are required when spotting different biological samples, resulting in long time-consuming, complicated devices, and high cost. , Non-modular assembly and disassembly are extremely inconvenient and other issues.
发明内容Contents of the invention
针对现有技术中存在的技术问题,本发明的目的是提供一种微阵列式生物芯片点样装置,结构简单、造价较低、模块化装拆、点样效率高,可实现微阵列芯片的大面积,高密度的制作。In view of the technical problems existing in the prior art, the object of the present invention is to provide a microarray biochip spotting device, which has a simple structure, low cost, modular assembly and disassembly, and high spotting efficiency, and can realize large-scale microarray chips. area, high-density production.
为实现上述目的,本发明采用的技术方案为:To achieve the above object, the technical solution adopted in the present invention is:
一种阵列式生物芯片点样装置,包括喷头、安装在喷头内部的阵列喷孔组件以及安装在喷头上方的用于对阵列喷孔组件施加向下冲击力的动力组件;其中:An array biochip spotting device, comprising a spray head, an array nozzle assembly installed inside the nozzle, and a power assembly installed above the nozzle for exerting a downward impact on the array nozzle assembly; wherein:
喷头包括下盖板和用于盖合下盖板的上盖板,下盖板和上盖板的周侧对应开设有若干个第一螺纹孔,下盖板和上盖板通过穿设在第一螺纹孔内的螺栓固定连接;下盖板的中部具有用于容纳阵列喷孔组件的第一腔体,第一腔体的中部为贯通的喷头通孔;上盖板的中部具有贯通的导向孔;导向孔内放置有力传导定位柱,力传导定位柱位于动力组件底部的正下方,力传导定位柱可避免动力组件直接冲击阵列喷孔组件时出现的冲击位置偏移、冲击力不均匀现象;进一步的,上盖板的底面中部具有与阵列冲针形状相适配的第二腔体,用于限定阵列冲针的位置,保持阵列冲针位置的稳定性;导向孔位于第二腔体的上方中部且与第二腔体连通。The nozzle includes a lower cover plate and an upper cover plate used to cover the lower cover plate. There are several first threaded holes correspondingly opened on the peripheral side of the lower cover plate and the upper cover plate. The lower cover plate and the upper cover plate pass through the second The bolts in a threaded hole are fixedly connected; the middle part of the lower cover plate has a first cavity for accommodating the array nozzle assembly, and the middle part of the first cavity is a through hole for the nozzle; the middle part of the upper cover plate has a through guide Hole; A force-transmitting positioning column is placed in the guide hole, and the force-transmitting positioning column is located directly below the bottom of the power assembly. The force-transmitting positioning column can avoid the phenomenon of impact position deviation and uneven impact force when the power assembly directly impacts the array nozzle assembly. ; Further, the middle part of the bottom surface of the upper cover has a second cavity adapted to the shape of the array punch, which is used to limit the position of the array punch and maintain the stability of the position of the array punch; the guide hole is located in the second cavity The upper middle part and communicates with the second cavity.
阵列喷孔组件包括阵列喷孔模块、硅胶膜片、膜片紧固板和阵列冲针;阵列喷孔模块包括喷孔基块,喷孔基块的中部向内凹陷形成喷孔腔体,喷孔腔体的中部具有若干个呈阵列排布的挤压腔,挤压腔的中部为贯穿喷孔基块的喷孔;进一步的,阵列喷孔模块中挤压腔的数量为1~48个,相邻两个喷孔之间的间距为0.1~5mm,多个喷孔的设计能够提高点样效率,满足高通量、模块化的点样需求。挤压腔的外侧且位于喷孔基块的周侧具有若干个用于存储生物样品的储液腔,储液腔的数量与挤压腔的数量相同,且每个储液腔分别通过开设在喷孔基块内的流道与挤压腔连通,储液腔和挤压腔之间可通过毛细力进样;为了防止点样过程中生物样品回流至储液腔中,流道在靠近挤压腔的一端设置有抑流结构,抑流结构为凸台状,抑流结构使流道靠近储液腔位置处的液体通量变小,在冲针头对硅胶膜片进行挤压过程中减少挤压腔内的液体沿着流道回流至储液腔。硅胶膜片位于挤压腔的正上方并用于密封挤压腔;阵列冲针位于硅胶膜片的正上方,阵列冲针的底部具有与挤压腔一一对应的冲针头,冲针头在动力组件产生的向下作用下能够对硅胶膜片进行挤压,进而使挤压腔内的生物样品从喷孔内以液滴形式喷出,完成点样。阵列冲针的顶面中部开设有定位槽,定位槽的形状与力传导定位柱底部的形状相适配,通过定位槽的设计可使力传导定位柱的作用力点位于阵列冲针的中部,提高定位精度的同时保证阵列冲针受力的均匀性。The array nozzle assembly includes an array nozzle module, a silica gel diaphragm, a diaphragm fastening plate and an array punch; There are several extrusion cavities arranged in an array in the middle of the orifice cavity, and the middle of the extrusion cavity is a nozzle hole that penetrates the nozzle base block; further, the number of extrusion cavities in the array nozzle module is 1 to 48 , the distance between two adjacent nozzle holes is 0.1-5mm, and the design of multiple nozzle holes can improve the efficiency of spotting and meet the requirements of high-throughput and modular spotting. There are several liquid storage chambers for storing biological samples on the outside of the extrusion chamber and on the peripheral side of the nozzle base block. The flow channel in the injection hole base block communicates with the extrusion chamber, and the capillary force can be used to inject samples between the liquid storage chamber and the extrusion chamber; One end of the pressure chamber is provided with a flow suppression structure, which is in the shape of a boss. The flow suppression structure reduces the liquid flux at the position of the flow channel close to the liquid storage chamber, and reduces the flow rate during the extrusion process of the silicone diaphragm by the punching needle head. The liquid in the extrusion chamber flows back to the liquid storage chamber along the flow channel. The silicone diaphragm is located directly above the extrusion chamber and is used to seal the extrusion chamber; the array punch is located directly above the silicone diaphragm, and the bottom of the array punch has a punch head corresponding to the extrusion chamber one by one, and the punch head is in the power assembly The resulting downward action can squeeze the silica gel diaphragm, and then the biological sample in the extrusion chamber is ejected from the nozzle hole in the form of droplets to complete sample application. There is a positioning groove in the middle of the top surface of the array punch, and the shape of the positioning groove matches the shape of the bottom of the force transmission positioning column. Through the design of the positioning groove, the force point of the force transmission positioning column can be located in the middle of the array punch, improving While ensuring the positioning accuracy, the force uniformity of the array punching pins is guaranteed.
膜片紧固板用于压紧硅胶膜片以于密封阵列喷孔模块内部的挤压腔,其位于阵列冲针和硅胶膜片之间;膜片紧固板的中部开设有与冲针头一一对应的限位孔,冲针头与限位孔间隙配合并能够穿过限位孔对硅胶膜片进行挤压;冲针头的长度比限位孔的深度长0.2~1mm。进一步的,膜片紧固板的纵切面为T型,包括位于上部的卡接部和位于下部的限位部;限位部的尺寸与喷孔腔体的尺寸相适配;喷孔腔体与喷孔基块之间形成有卡接台,卡接台的尺寸与卡接部超出限位部的区域的尺寸相适配。The diaphragm fastening plate is used to compress the silicone diaphragm to seal the extrusion chamber inside the array nozzle module, which is located between the array punching needle and the silicone diaphragm; the middle part of the diaphragm fastening plate is provided with a A corresponding limit hole, the punching needle head and the limit hole are in clearance fit and can pass through the limit hole to squeeze the silicone diaphragm; the length of the punching needle head is 0.2-1mm longer than the depth of the limit hole. Further, the longitudinal section of the diaphragm fastening plate is T-shaped, including a clamping part at the upper part and a limiting part at the lower part; the size of the limiting part matches the size of the spray hole cavity; the spray hole cavity A clamping platform is formed between the spray hole base block, and the size of the clamping platform is adapted to the size of the area where the clamping part exceeds the limit part.
进一步的,动力组件为电磁动力组件,包括安装在喷头上方的电磁铁外壳和电磁铁铁芯,上盖板的顶部安装有用于固定电磁铁外壳的支撑座,支撑座的侧壁沿水平方向开设有第二螺纹孔,电磁铁外壳通过穿设在第二螺纹孔内的螺栓固定在支撑座的内部。电磁铁铁芯向下运动时其能够对力传导定位柱施加向下的作用力,在力传导定位柱向下运动过程中同步带动阵列冲针运动。此外,动力组件亦可更换为压电柱作为动力源,其均可以产生向下的冲击力,从而实现对阵列喷孔组件的挤压,完成点样过程。Further, the power assembly is an electromagnetic power assembly, including an electromagnet casing and an electromagnet core installed above the nozzle, a support seat for fixing the electromagnet casing is installed on the top of the upper cover, and the side wall of the support seat is opened along the horizontal direction. There is a second threaded hole, and the electromagnet housing is fixed inside the support base through bolts passing through the second threaded hole. When the electromagnet core moves downward, it can exert a downward force on the force transmission positioning column, and synchronously drives the array punching needles to move during the downward movement of the force transmission positioning column. In addition, the power component can also be replaced with a piezoelectric column as a power source, which can generate a downward impact force, so as to realize the extrusion of the array nozzle assembly and complete the sampling process.
进一步的,阵列喷孔模块、膜片紧固板、阵列冲针、力传导定位柱由光敏树脂材料光固化加工,喷头中的下盖板和上盖板由PMMA材料激光加工成型。Further, the array orifice module, the diaphragm fastening plate, the array punch, and the force transmission positioning column are processed by light curing of photosensitive resin material, and the lower cover plate and upper cover plate in the nozzle are formed by laser processing of PMMA material.
与现有技术相比,本发明的有益效果为:Compared with prior art, the beneficial effect of the present invention is:
本发明阵列喷孔组件中的阵列喷孔模块包括多个呈阵列排布的挤压腔,喷孔位于挤压腔的中部,即喷孔呈阵列排布,本发明提供的点样装置中每个喷孔独立进样,独立喷发,在满足无污染、高精度的同时,可对喷头中的不同储液腔添加不同的样品,从而实现多样品的同时喷射点样,减少了传统点样过程中换样品所需清洗、干燥以及再次加样的时间,提高生物芯片的制备效率;能够满足多喷孔同时点样,满足高通量、模块化的点样需求。另外,本发明提供的装置中储液腔和挤压腔之间通过毛细力进样,无需外部进样动力源,进样稳定且装置小巧,设计加工简单、造价低廉易于集成化和规模化。The array orifice module in the array orifice assembly of the present invention includes a plurality of extrusion chambers arranged in an array, and the orifices are located in the middle of the extrusion chamber, that is, the orifices are arranged in an array. Each nozzle hole injects samples independently and erupts independently. While meeting the requirements of no pollution and high precision, different samples can be added to different liquid storage chambers in the nozzle, so as to realize the simultaneous injection and spotting of multiple samples and reduce the traditional sample spotting process. The time required for cleaning, drying, and sample refilling in mid-change samples improves the preparation efficiency of biochips; it can meet the simultaneous sample placement of multiple nozzle holes, and meet the requirements of high-throughput and modular sample placement. In addition, in the device provided by the present invention, the sample is fed through the capillary force between the liquid storage chamber and the extrusion chamber, no external sample feeding power source is needed, the sample feeding is stable, the device is compact, the design and processing are simple, the cost is low, and it is easy to integrate and scale up.
附图说明Description of drawings
图1为本发明提供的阵列式生物芯片点样装置的整体结构示意图;1 is a schematic diagram of the overall structure of an arrayed biochip spotting device provided by the present invention;
图2为图1的剖视图;Fig. 2 is the sectional view of Fig. 1;
图3为图1的爆炸结构示意图;Fig. 3 is a schematic diagram of the explosion structure of Fig. 1;
图4为阵列喷孔模块的结构示意图;Fig. 4 is a schematic structural diagram of an array nozzle module;
附图标记:1-喷头,11-下盖板,12-上盖板,13-第一螺纹孔,14-第一腔体,15-喷头通孔,16-导向孔,17-第二腔体,21-阵列喷孔模块,211-喷孔基块,212-喷孔腔体,213-挤压腔,214-喷孔,215-储液腔,216-流道,217-抑流结构,22-硅胶膜片,23-膜片紧固板,231-限位孔,232-卡接部,233-限位部,24-阵列冲针,241-冲针头,242-定位槽,25-卡接台,3-动力组件,31-电磁铁外壳,32-电磁铁铁芯,4-力传导定位柱,5-支撑座,6-第二螺纹孔,7-生物样品。Reference signs: 1-spray head, 11-lower cover plate, 12-upper cover plate, 13-first threaded hole, 14-first cavity, 15-spray head through hole, 16-guiding hole, 17-second cavity Body, 21-array nozzle module, 211-nozzle base block, 212-nozzle cavity, 213-extrusion chamber, 214-nozzle, 215-liquid storage chamber, 216-flow channel, 217-flow suppression structure , 22-Silicone diaphragm, 23-Diaphragm fastening plate, 231-Limiting hole, 232-Clamping part, 233-Limiting part, 24-Array punching needle, 241-Punching needle head, 242-Positioning groove, 25 - clamping platform, 3 - power assembly, 31 - electromagnet shell, 32 - electromagnet core, 4 - force transmission positioning column, 5 - support base, 6 - second threaded hole, 7 - biological sample.
具体实施方式detailed description
下面结合实施例对本发明作更进一步的说明,以使本领域的技术人员可以更好地理解本发明并能予以实施,但所举实施例不作为对本发明的限定。The present invention will be further described below in conjunction with the examples, so that those skilled in the art can better understand the present invention and implement it, but the given examples are not intended to limit the present invention.
在本发明的描述中,需要理解的是,术语“上”、“下”、“顶”、“底”、“内”、“外”等指示的方位或位置关系为基于附图所示的方位或位置关系,仅是为了便于描述本发明和简化描述,而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作,因此不能理解为本发明的限制。本发明中术语“第一”、“第二”不代表具体的数量及顺序,仅仅是用于名称的区分。In the description of the present invention, it should be understood that the orientations or positional relationships indicated by the terms "upper", "lower", "top", "bottom", "inner" and "outer" are based on those shown in the accompanying drawings. The orientation or positional relationship is only for the convenience of describing the present invention and simplifying the description, but does not indicate or imply that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and thus should not be construed as a limitation of the present invention. The terms "first" and "second" in the present invention do not represent specific numbers and sequences, but are only used to distinguish names.
在本发明中,除非另有明确的规定和限定,术语“安装”、“相连”、“连接”、“固定”等术语应做广义理解,例如,可以是固定连接,也可以是可拆卸连接,或一体连接;可以是直接相连,也可以通过中间媒介间接相连,可以是两个元件内部的连通。对于本领域的普通技术人员而言,可以根据具体情况理解上述术语在本发明中的具体含义。In the present invention, unless otherwise clearly specified and limited, terms such as "installation", "connection", "connection" and "fixation" should be understood in a broad sense, for example, it can be a fixed connection or a detachable connection , or an integrated connection; it can be directly connected, or indirectly connected through an intermediary, and can be the internal communication of two components. Those of ordinary skill in the art can understand the specific meanings of the above terms in the present invention according to specific situations.
参考图1至图4,一种阵列式生物芯片点样装置,包括喷头1、安装在喷头1内部的阵列喷孔组件以及安装在喷头1上方的用于对阵列喷孔组件施加向下冲击力的动力组件3;其中:With reference to Fig. 1 to Fig. 4, a kind of arrayed biochip spotting device comprises spray head 1, array nozzle assembly installed inside nozzle 1 and is installed on nozzle head 1 and is used for applying downward impact force to array nozzle assembly The
喷头1包括下盖板11和用于盖合下盖板的上盖板12,下盖板11和上盖板12的周侧对应开设有若干个第一螺纹孔13,下盖板11和上盖板12通过穿设在第一螺纹孔13内的螺栓固定连接;下盖板11的中部具有用于容纳阵列喷孔组件的第一腔体14,第一腔体14的中部为贯通的喷头通孔15;上盖板12的中部具有贯通的导向孔16;导向孔16内放置有力传导定位柱4,力传导定位柱4位于动力组件3底部的正下方,力传导定位柱4可避免动力组件3直接阵列喷孔组件时出现的冲击位置偏移、冲击力不均匀现象;进一步的,上盖板12的底面中部具有与阵列冲针24形状相适配的第二腔体17,第二腔体17用于限定阵列冲针24的位置;导向孔16位于第二腔体17的上方中部且与第二腔体17连通。The nozzle 1 includes a
阵列喷孔组件包括阵列喷孔模块21、硅胶膜片22、膜片紧固板23和阵列冲针24;阵列喷孔模块21包括喷孔基块211,喷孔基块211的中部向内凹陷形成喷孔腔体212,喷孔腔体212的中部具有若干个呈阵列排布的挤压腔213,挤压腔213的中部为贯穿喷孔基块的喷孔214;进一步的,阵列喷孔模块中挤压腔213的数量为1~48个,相邻两个喷孔214之间的间距为0.1~5mm。挤压腔213的外侧且位于喷孔基块211的周侧具有若干个用于存储生物样品7的储液腔215,储液腔215的数量与挤压腔213的数量相同,且每个储液腔215分别通过开设在喷孔基块内的流道216与挤压腔213连通;为了防止点样过程中生物样品回流至储液腔215中,流道216在靠近挤压腔213的一端设置有抑流结构217,抑流结构217为凸台状,抑流结构使流道靠近储液腔位置处的液体通量变小。硅胶膜片22位于挤压腔213的正上方,用于密封挤压腔213;阵列冲针24位于硅胶膜片22的正上方,阵列冲针24的底部具有与挤压腔213一一对应的冲针头241,冲针头241在动力组件产生的向下作用下能够对硅胶膜片进行挤压;阵列冲针24的顶面中部开设有定位槽242,定位槽242的形状与力传导定位柱4底部的形状相适配,通过定位槽242可使力传导定位柱4的作用力点位于阵列冲针24的中部,增加阵列冲针受力的均匀性。The array nozzle assembly includes an
膜片紧固板23用于压紧硅胶膜片22以于密封阵列喷孔模块内部的挤压腔213,其位于阵列冲针24和硅胶膜片22之间;膜片紧固板23的中部开设有与冲针头241一一对应的限位孔231,冲针头241与限位孔231间隙配合并能够穿过限位孔对硅胶膜片进行挤压;冲针头241的长度比限位孔231的深度长0.2~1mm,以确保挤压过程中冲针头能够穿设限位孔并对硅胶膜片进行挤压。进一步的,膜片紧固板23的纵切面为T型,包括位于上部的卡接部232和位于下部的限位部233;限位部233的尺寸与喷孔腔体212的尺寸相适配;喷孔腔体212与喷孔基块211之间形成有卡接台25,卡接台25的尺寸与卡接部超出限位部的区域的尺寸相适配,膜片紧固板23通过其卡接部232卡接在卡接台25上,从而将膜片紧固板23限位在阵列喷孔模块中的喷孔腔体212内。The
在一个实施方式中,动力组件3为电磁动力组件,包括安装在喷头上方的电磁铁外壳31和电磁铁铁芯32,上盖板12的顶部安装有用于固定电磁铁外壳的支撑座5,支撑座5的侧壁沿水平方向开设有第二螺纹孔6,电磁铁外壳31通过穿设在第二螺纹孔6内的螺栓固定在支撑座5的内部,以方便调节电磁铁的冲击高度。电磁铁铁芯31向下运动时其能够对力传导定位柱4施加向下的作用力,在力传导定位柱4向下运动过程中同步带动阵列冲针24运动。需要说明的是,动力组件亦可更换为压电柱作为动力源,其均可以产生向下的冲击力,从而实现对阵列喷孔组件的挤压,完成点样过程。本领域技术人员,可根据实现需要选择合适的动力源作为本申请中的电磁动力组件,只要其能产生向下的冲击力,均可以应用在本方案中。In one embodiment, the
本发明提供的点样装置的工作过程为:The working process of the sample pointing device provided by the invention is:
在电磁铁通高电平时,电磁铁铁芯32向下冲击力传导定位柱4,力传导定位柱4冲击硅胶膜片22,硅胶膜片22向下变形,挤压腔213压力骤增,使挤压腔内的待点样试剂(生物样品)从喷孔214中呈液滴状喷射出;当电磁铁通低电平时,电磁铁铁芯32向上抬起,硅胶膜片22变形复原,挤压腔213压力骤减,基于毛细进样原理位于储液腔内的待点样试剂填充进入挤压腔213内,即为一个完整喷射过程;重复上述步骤即可进行后续点样。When the electromagnet is connected to a high level, the
显然,所描述的实施例是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。Apparently, the described embodiments are some, but not all, embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.
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| CN202211066755.2ACN115452507B (en) | 2022-09-01 | 2022-09-01 | An array type biochip spotting device |
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