技术领域technical field
本发明涉及一种生物材料清洗装置及方法，特别是涉及细胞或组织等的生物材料。The invention relates to a biological material cleaning device and method, in particular to biological material such as cells or tissues.
背景技术Background technique
医学进步提供组织再生(Tissue Regeneration)领域新的希望。举例而言，近来生物工程所研发的软骨组织已能用外科手术方法植入病患受伤的膝盖，以修复其软骨。例如由供体组织(Donor Tissue)取得初代细胞(Primary Cell)后，在支架(Scafffold)中培养成新组织，在此过程中，取得及培养的细胞及/或组织经常需要清洗及过滤，以去除化学试剂和避免污染。传统清洗装置包括有离心机设备，可利用离心力将细胞/组织从混合液中分离出来，只是这样的离心机设备并不适合在手术室中使用。Medical advances provide new hope in the field of tissue regeneration. For example, recently bioengineered cartilage tissue has been surgically implanted into a patient's injured knee to repair the cartilage. For example, after the primary cell is obtained from the donor tissue (Donor Tissue), it is cultured into a new tissue in the scaffold (Scaffold). During this process, the obtained and cultured cells and/or tissues often need to be cleaned and filtered to Remove chemical reagents and avoid contamination. Traditional cleaning devices include centrifuge equipment, which can separate cells/tissues from the mixture by centrifugal force, but such centrifuge equipment is not suitable for use in the operating room.
进一步说明如下：目前在细胞的来源方面，主要来自细胞株(cell line)与取自活体组织的初代培养(primary culture)。在初代培养的培养过程中，需撷取特定部位活体的组织，将该活体组织在无菌操作的环境下切碎，再利用蛋白酵素将组织中的细胞间质溶解，游离出位于细胞间质中的细胞，经处理后再植回病人体内进行组织修复。Further explanations are as follows: At present, in terms of the sources of cells, they mainly come from cell lines and primary cultures from living tissues. In the culture process of the primary culture, it is necessary to extract the living tissue of a specific part, chop the living tissue under an aseptic operation environment, and then use protease to dissolve the intercellular substance in the tissue, and dissociate it from the intercellular substance. The cells are processed and then implanted back into the patient for tissue repair.
活体组织修复技术通常需要在手术房内进行。在手术过程中，取病人自体的组织，当场进行组织切碎后，再以酵素分解组织碎块；这时需要有一设备，进行酵素分解后的酵素移除清洗及组织、细胞收集，再将收集的组织、细胞，放置于适当的载体并植入病人组织受损部位，以进行组织修复。又，此一设备除了可应用在活体组织修复技术之外，也可应用于其他领域中须清洗、过滤及收集细胞、组织或是其他的生物材料等。Biopsy repair techniques usually need to be performed in the operating room. During the operation, the patient's own tissue is taken, chopped on the spot, and then the tissue fragments are decomposed by enzymes; at this time, a device is needed to remove and clean the enzymes after the enzyme decomposition, and collect the tissues and cells, and then collect them The tissue and cells are placed in an appropriate carrier and implanted into the damaged part of the patient's tissue for tissue repair. In addition, this device can be used in other fields besides living tissue repair technology, where cells, tissues or other biological materials need to be cleaned, filtered and collected.
目前已有数种细胞及组织的过滤收集装置被开发，其方法大致包含离心方式、滤网方式及滤膜结合离心方式，例如US65211990、US6123687、US5663051、US5976824等。然而因为酵素分解、酵素移除清洗，及组织、细胞的收集均须在手术房进行，而手术房内无法使用离心机设备，其他方式也无法进行酵素移除清洗，因此，开发一种可在手术房内同时清洗、过滤及收集细胞和组织或是其他的生物材料的装置实属必要。Currently, several cell and tissue filtration collection devices have been developed, and the methods generally include centrifugal methods, filter mesh methods, and filter-membrane combined centrifugal methods, such as US65211990, US6123687, US5663051, and US5976824. However, because enzyme decomposition, enzyme removal and cleaning, and tissue and cell collection must be carried out in the operating room, centrifuge equipment cannot be used in the operating room, and enzyme removal and cleaning cannot be performed by other methods. Devices for simultaneously washing, filtering and collecting cells and tissues or other biological materials in the operating room are necessary.
发明内容Contents of the invention
本发明的目的在于提供一种细胞、组织或生物材料清洗装置及方法，以解决上述问题。The object of the present invention is to provide a cell, tissue or biological material cleaning device and method to solve the above problems.
本发明的目的是这样实现的，即提供一种可同时清洗及过滤细胞及/或组织的装置，包括一外套管、一可活动内组件以及一过滤元件。该过滤元件可为一滤膜或一滤网。该外套管一端为封闭，一端为开放。该可活动内组件位于该外套管内部，且可在该外套管内部轴向移动。而该过滤元件固定于该可活动内组件，使该过滤元件、外套管及可活动内组件之间形成一密闭空间。The object of the present invention is achieved by providing a device capable of simultaneously cleaning and filtering cells and/or tissues, comprising an outer sleeve, a movable inner component and a filter element. The filter element can be a filter membrane or a filter net. One end of the outer sleeve is closed and the other end is open. The movable inner component is located inside the outer sleeve and can move axially inside the outer sleeve. And the filter element is fixed on the movable inner component, so that a closed space is formed between the filter element, the outer sleeve and the movable inner component.
在一实施例中，该外套管于封闭端包含一旋盖，以便收集清洗过滤完毕的细胞及/或组织。In one embodiment, the outer cannula includes a screw cap at the closed end for collecting washed and filtered cells and/or tissues.
在一实施例中，该可活动内组件为一内套管或一圈环。In one embodiment, the movable inner component is an inner sleeve or a ring.
该过滤元件用以清洗及过滤细胞及/或组织，可依不同细胞组织类型及不同应用做更换。该过滤元件孔径可小于该细胞的径幅，以用来清洗过滤细胞，或是同时清洗过滤细胞及组织，此时过滤元件可为一滤膜，例如该滤膜孔径为介于1μm-30μm之间，例如为5μm-20μm。过滤元件孔径也可小于该组织的径幅，以用来清洗过滤组织，此时过滤元件可为以一固定孔径的金属滤网代替，例如该滤网孔径可介于100μm-3000μm之间。另，为避免清洗过滤过程中过滤元件破裂或形变，该过滤元件可包夹在一双层筛网套组中，并固定于可活动内组件内。The filter element is used for cleaning and filtering cells and/or tissues, and can be replaced according to different types of cells and tissues and different applications. The pore size of the filter element can be smaller than the diameter of the cells to clean the filter cells, or to clean the filter cells and tissues at the same time. At this time, the filter element can be a filter membrane, for example, the filter membrane pore size is between 1 μm-30 μm Between, for example, 5 μm-20 μm. The pore size of the filter element can also be smaller than the diameter of the tissue to clean and filter the tissue. At this time, the filter element can be replaced by a metal filter with a fixed pore size, for example, the filter size can be between 100 μm-3000 μm. In addition, in order to prevent the filter element from being broken or deformed during the cleaning and filtering process, the filter element can be clamped in a double-layer screen set and fixed in the movable inner component.
本发明另关于一种清洗细胞及/或组织的方法，包含：(a)提供上述清洗装置，其中该细胞及/或组织与一清洗液置于该密闭空间内；及(b)沿轴向往复移动该可活动内组件以清洗过滤该细胞及/或该组织。在一实施例中，该方法更包含(c)收集该清洗完毕的细胞及/或组织。其中，该细胞及/或组织为软骨组织、硬骨组织或其它组成器官的组织，也可以是经酵素处理后的细胞颗粒及/或组织碎块。The present invention also relates to a method for cleaning cells and/or tissues, comprising: (a) providing the above-mentioned cleaning device, wherein the cells and/or tissues and a cleaning solution are placed in the enclosed space; and (b) axially The movable inner component is moved back and forth to clean and filter the cell and/or the tissue. In one embodiment, the method further includes (c) collecting the washed cells and/or tissues. Wherein, the cells and/or tissues are cartilage tissues, hard bone tissues or other tissues constituting organs, and may also be cell granules and/or tissue fragments treated with enzymes.
本发明另关于一种生物材料的清洗装置，包括一外套管以及一内套管。外套管包括一开孔端以及一封闭端，生物材料从开孔端放入外套管中。内套管以可拆卸以及可滑动方式设置在外套管中，内套管包括一第一端口、一第二端口以及一过滤元件，第一端口用于接收与排出清洗液，第二端口为连通内套管的内部与外套管的内部的一液体流径，过滤元件设置于第二端口，能够允许清洗液通过，而生物材料无法通过。过滤元件以及外套管的封闭端之间会形成一密闭空间，清洗液可经由过滤元件流出密闭空间，而将生物材料局限滞留在密闭空间里。The present invention also relates to a biological material cleaning device, which includes an outer sleeve and an inner sleeve. The outer sleeve includes an open end and a closed end, and the biological material is put into the outer sleeve from the open end. The inner sleeve is disposed in the outer sleeve in a detachable and slidable manner. The inner sleeve includes a first port, a second port and a filter element. The first port is used to receive and discharge cleaning fluid, and the second port is for communication A liquid flow path between the inside of the inner casing and the inside of the outer casing, the filter element is arranged at the second port, which can allow cleaning liquid to pass through, but biological materials cannot pass through. A closed space is formed between the filter element and the closed end of the outer sleeve, and the cleaning liquid can flow out of the closed space through the filter element, and the biological material is restricted and retained in the closed space.
在一实施例中，外套管包括一第一套件、以及一第二套件以可拆卸方式连结于第一套件。In one embodiment, the outer casing includes a first set, and a second set detachably connected to the first set.
在一实施例中，内套管包括一弹性元件，紧密固定于外套管的内周表面。In one embodiment, the inner sleeve includes an elastic element tightly fixed on the inner peripheral surface of the outer sleeve.
在一实施例中，外套管包括一基底元件以及一延伸元件。基底元件包括一开孔端以及一封闭端。延伸元件包括一第一端以及一第二端，第一端以及第二端皆设置有开孔。其中延伸元件的第一端以可拆卸方式连结于基底元件的开孔端。In one embodiment, the outer sleeve includes a base member and an extension member. The base element includes an open end and a closed end. The extension element includes a first end and a second end, and the first end and the second end are both provided with openings. Wherein the first end of the extension element is detachably connected to the opening end of the base element.
在一实施例中，延伸元件的第二端以可拆卸方式连结于另一延伸元件。In one embodiment, the second end of the extension element is detachably connected to another extension element.
在一实施例中，弹性元件包括一环状橡胶元件。In one embodiment, the elastic element includes an annular rubber element.
在一实施例中，内套管的第一端口包括一停止件，用于限制内套管相对于外套管的最大轴向移动距离。In one embodiment, the first port of the inner sleeve includes a stop for limiting the maximum axial movement distance of the inner sleeve relative to the outer sleeve.
在一实施例中，过滤元件以可移除方式设置在第二端口内。In one embodiment, the filter element is removably disposed within the second port.
在一实施例中，过滤元件为一滤网，且滤网具有多个网孔。In one embodiment, the filter element is a filter screen, and the filter screen has a plurality of mesh holes.
在一实施例中，网孔的直径在100μm至3000μm之间。In one embodiment, the diameter of the mesh is between 100 μm and 3000 μm.
在一实施例中，过滤元件为一滤膜，且滤膜具有多个膜孔。In one embodiment, the filter element is a filter membrane, and the filter membrane has a plurality of membrane pores.
在一实施例中，膜孔的直径在5μm至20μm之间。In one embodiment, the diameter of the membrane pores is between 5 μm and 20 μm.
本发明另关于一种清洗生物材料的方法，包括(a)提供一生物材料；(b)将生物材料置入一密闭空间中；(c)令密闭空间扩张以及压缩，使清洗液经由一过滤元件进出密闭空间，而生物材料被局限在密闭空间里。The present invention also relates to a method for cleaning biological materials, including (a) providing a biological material; (b) placing the biological material in a closed space; (c) expanding and compressing the closed space so that the cleaning liquid passes through a filter Components move in and out of confined spaces, and biomaterials are confined within confined spaces.
在一实施例中，上述清洗生物材料的方法更包括将清洗液加入密闭空间的步骤。In one embodiment, the above-mentioned method for cleaning biological materials further includes a step of adding a cleaning solution into the confined space.
在一实施例中，上述清洗生物材料的方法更包括将清洗液经由过滤元件而排出密闭空间的步骤。In one embodiment, the above-mentioned method for cleaning biological materials further includes a step of discharging the cleaning liquid out of the confined space through the filter element.
在一实施例中，上述清洗生物材料的方法更包括在排出清洗液之后将新鲜清洗液加入密闭空间的步骤。In one embodiment, the above method for cleaning biological materials further includes a step of adding fresh cleaning solution into the confined space after discharging the cleaning solution.
在一实施例中，上述清洗生物材料的方法更包括摇晃在密闭空间内的清洗液的步骤。In one embodiment, the above method for cleaning biological materials further includes a step of shaking the cleaning solution in the enclosed space.
在一实施例中，上述清洗生物材料的方法更包括在排放清洗液之后收集生物材料的步骤。In one embodiment, the above method for cleaning biological material further includes a step of collecting the biological material after discharging the cleaning solution.
在一实施例中，上述清洗生物材料的方法更包括(a)提供一外套管，此外套管包括一开孔端以及一封闭端，生物材料从开孔端放入外套管中；(b)提供一内套管，此内套管以可拆卸以及可滑动方式设置在外套管中，此内套管包括一第一端口以及一第二端口，其中第一端口用于接收与排出清洗液，第二端口为连通内套管的内部与外套管的内部的一液体流径，过滤元件设置于第二端口，在过滤元件以及外套管的封闭端之间形成一密闭空间。In one embodiment, the method for cleaning biological materials further includes (a) providing an outer sleeve, the outer sleeve includes an open end and a closed end, and the biological material is put into the outer sleeve through the open end; (b) An inner sleeve is provided, the inner sleeve is detachably and slidably disposed in the outer sleeve, the inner sleeve includes a first port and a second port, wherein the first port is used to receive and discharge cleaning fluid, The second port is a liquid flow path connecting the inside of the inner casing and the inside of the outer casing. The filter element is arranged at the second port to form a closed space between the filter element and the closed end of the outer casing.
在一实施例中，外套管包括一第一套件、以及一第二套件以可拆卸方式连结于第一套件。In one embodiment, the outer casing includes a first set, and a second set detachably connected to the first set.
在一实施例中，上述清洗生物材料的方法更包括将第一套件与第二套件分离以收集生物材料的步骤。In one embodiment, the above method for cleaning biological material further includes a step of separating the first set from the second set to collect the biological material.
本发明可应用于关节软硬骨的修复技术，也可应用于其他领域中须清洗、过滤及收集细胞、组织或其他生物材料者。The present invention can be applied to the articular soft and hard bone repair technology, and can also be applied to those who need to clean, filter and collect cells, tissues or other biological materials in other fields.
附图说明Description of drawings
图1A是本发明的第一实施例的外套管立体图；Figure 1A is a perspective view of an outer sleeve of the first embodiment of the present invention;
图1B是本发明的第一实施例的外套管剖视图；Figure 1B is a sectional view of an outer sleeve of the first embodiment of the present invention;
图2A是本发明的第一实施例的可活动内组件立体图；Fig. 2A is a perspective view of the movable inner component of the first embodiment of the present invention;
图2B是本发明的第一实施例的可活动内组件剖视图；Fig. 2B is a cross-sectional view of the movable inner component of the first embodiment of the present invention;
图3是本发明的第一实施例的细胞及/或组织清洗装置构造图；3 is a structural diagram of the cell and/or tissue cleaning device according to the first embodiment of the present invention;
图4是本发明的第一实施例的清洗细胞及/或组织的流程方块图；4 is a flow block diagram of cleaning cells and/or tissues according to the first embodiment of the present invention;
图5是本发明的第一实施例中，沿轴向移动该可活动内组件以清洗过滤该细胞及/或组织的方法流程图；Fig. 5 is a flowchart of a method for moving the movable inner component in the axial direction to clean and filter the cells and/or tissues in the first embodiment of the present invention;
图6是本发明的第一实施例中，清洗细胞及/或组织的方法示意图之一；Fig. 6 is one of the schematic diagrams of the method for cleaning cells and/or tissues in the first embodiment of the present invention;
图7是本发明的第一实施例中，清洗细胞及/或组织的方法示意图之二；Fig. 7 is the second schematic diagram of the method for cleaning cells and/or tissues in the first embodiment of the present invention;
图8是本发明的第二实施例的生物材料清洗装置构造图；Fig. 8 is a structural diagram of a biological material cleaning device according to the second embodiment of the present invention;
图9A是本发明的第二实施例的外套管立体图；Fig. 9A is a perspective view of the outer sleeve of the second embodiment of the present invention;
图9B是本发明的第二实施例的外套管剖视图；Fig. 9B is a sectional view of the outer sleeve of the second embodiment of the present invention;
图10A是本发明的第二实施例的内套管立体图；Figure 10A is a perspective view of the inner sleeve of the second embodiment of the present invention;
图10B是本发明的第二实施例的内套管剖视图；Fig. 10B is a sectional view of the inner sleeve of the second embodiment of the present invention;
图11是本发明的第二实施例的生物材料清洗方法的流程图；Fig. 11 is a flowchart of a biological material cleaning method according to the second embodiment of the present invention;
图12A是本发明的第二实施例中，清洗生物材料的方法示意图之一；Figure 12A is one of the schematic diagrams of the method for cleaning biological materials in the second embodiment of the present invention;
图12B是本发明的第二实施例中，清洗生物材料的方法示意图之二。Fig. 12B is the second schematic diagram of the method for cleaning biological materials in the second embodiment of the present invention.
主要元件符号说明Description of main component symbols
第一实施例first embodiment
10～外套管10～outer casing
11～外套管管身11～outer casing body
12～旋盖12～screw cap
13～第一开口13 ~ first opening
14～第二开口14～Second opening
20～可活动内组件20～movable inner components
21～内套管管身21～Inner casing body
22～内套管开口22～Inner casing opening
23～筛网套组23～Sieve set
24～O环24～O ring
25～把手25～handle
30～过滤元件30～filter element
40～细胞及/或组织40～cells and/or tissues
50～清洗液50～cleaning liquid
60～提供细胞及/或组织清洗装置，其中细胞组织与清洗液置于装置的密闭空间内60～Provide a cell and/or tissue cleaning device, in which the cell tissue and cleaning solution are placed in the closed space of the device
61～细胞及/或组织与清洗液置于外套管内61～Cells and/or tissues and cleaning solution are placed in the outer cannula
62～套上可活动内组件以形成密闭空间62～put on movable inner components to form a closed space
70～沿轴向移动可活动内组件以清洗过滤细胞及/或组织70 ~ move the movable inner component along the axial direction to clean the filter cells and/or tissues
71～沿第一轴向移动可活动内组件以压缩密闭空间71～moving the movable inner component along the first axis to compress the confined space
72～更换内套管内的清洗液72～Replace the cleaning fluid in the inner casing
73～沿第二轴向移动可活动内组件以扩张密闭空间73～Moving the movable inner component along the second axis to expand the confined space
74～摇晃装置以清洗细胞及/或组织74～Shake device to wash cells and/or tissue
75～移除内套管内的清洗液75～Remove the cleaning solution in the inner casing
80～收集清洗完毕的细胞及/或组织80～Collect the washed cells and/or tissues
D1～第一轴向D1～the first axis
D2～第二轴向D2～second axis
第二实施例second embodiment
100～生物材料清洗装置100～biological material cleaning device
110～外套管110～outer casing
111～第一套件111～First Kit
112～第二套件112～Second Kit
113～开孔113～Open hole
114～上端114～upper end
115～下端115～lower end
116～开孔116～hole
118～上端118～upper end
119～下端119～lower end
120～内套管120～inner casing
121～内套管管身121～inner casing body
122～第一端口122～first port
123～第二端口123～second port
124～弹性元件124～elastic element
125～停止件125～stop parts
126～螺纹126～Thread
127～螺纹127～Thread
128～螺纹128～Thread
129～支撑件129～support
130～过滤元件130～filter element
132～筛网套组132～Sieve set
134～筛网134～sieve
140～生物材料140～biological material
142～下端142～lower end
144～上端144～upper end
150～密闭空间150～Confined space
160～清洗液160～cleaning liquid
400～流程图400～flow chart
410～将生物材料从外套管开口放入外套管中410 - Inserting biological material into the outer cannula through the outer cannula opening
420～将内套管插入外套管以形成密闭空间420 ~ Insert the inner sleeve into the outer sleeve to form a closed space
430～从第一端口将清洗液加入密闭空间430 ~ Add cleaning solution into the confined space from the first port
440～清洗生物材料440～cleaning biological material
442～沿第一方向压缩密闭空间442～Compress the confined space along the first direction
444～沿第二方向扩张密闭空间444～Expand the confined space along the second direction
446～摇晃清洗液446～Shake cleaning solution
450～从第一端口移除清洗液450～Remove the cleaning fluid from the first port
460～结束460～End
470～收集生物材料470～Collect biological material
D1～第一轴向D1～the first axis
D2～第二轴向D2～second axis
具体实施方式Detailed ways
外套管10包含一封闭端及一开放端。在第一实施例中，为方便收集组胞及组织，外套管10包括一外套管管身11及一旋盖12(参照图1A及图1B)，外套管管身11具有一第一开口13以及一第二开口14，于第二开口14与旋盖12连接，细胞及组织可集中在旋盖12中以便收集。Outer sleeve 10 includes a closed end and an open end. In the first embodiment, in order to facilitate the collection of cells and tissues, the outer cannula 10 includes an outer cannula body 11 and a screw cap 12 (see FIGS. 1A and 1B ). The outer cannula body 11 has a first opening 13 And a second opening 14, where the second opening 14 is connected with the screw cap 12, cells and tissues can be concentrated in the screw cap 12 for collection.
可活动内组件20可为一内套管或一圈环。当可活动内组件20为一内套管时，其包括一内套管管身21、一筛网套组23、一橡胶O环24以及一把手25(参照图2A及图2B)。内套管管身21一端具有一内套管开口22以及一把手25，另一端包含一筛网套组23以及一橡胶O环24。筛网套组23是两片固定在内套管管身21一端内部的筛网，将过滤元件30包夹在两片筛网之中以免过滤元件30在清洗过程中破裂或产生形变。O环24套在内套管管身21的一端外，在本实施例中，O环24是套在内套管管身21的底端外，以提高可活动内组件20和外套管10之间的密合度。The movable inner component 20 can be an inner sleeve or a ring. When the movable inner component 20 is an inner sleeve, it includes an inner sleeve body 21 , a screen set 23 , a rubber O-ring 24 and a handle 25 (see FIGS. 2A and 2B ). The inner sleeve body 21 has an inner sleeve opening 22 and a handle 25 at one end, and a screen set 23 and a rubber O-ring 24 at the other end. The screen set 23 is two screens fixed inside one end of the inner casing body 21 , and the filter element 30 is sandwiched between the two screens to prevent the filter element 30 from being broken or deformed during cleaning. The O-ring 24 is sleeved outside one end of the inner sleeve body 21. In this embodiment, the O-ring 24 is sleeved outside the bottom end of the inner sleeve body 21 to improve the distance between the movable inner assembly 20 and the outer sleeve 10. The tightness between.
过滤元件30可以是滤膜或滤网。当待清洗的细胞组织为取自病人的软骨细胞组织时，所使用的过滤元件30可为一孔径10μm的TMTP滤膜(IsoporeTM membrane filters)。当仅须过滤、收集软骨组织而不需要收集其中的游离细胞时，可将过滤元件30更换成一片100μm的金属滤网。又，如果须收集脐带组织时，可使用孔径150μm-3000μm的滤网，其例如为孔径400μm-600μm的滤网。因此，使用者可依照欲清洗、过滤与收集的生物材料的不同，来选择适当孔径大小的过滤元件30。The filter element 30 may be a filter membrane or a filter screen. When the cell tissue to be cleaned is chondrocyte tissue from a patient, the filter element 30 used may be a TMTP filter membrane with a pore size of 10 μm ( Isopore™ membrane filters). When it is only necessary to filter and collect cartilage tissue without collecting free cells therein, the filter element 30 can be replaced with a piece of 100 μm metal filter screen. In addition, if the umbilical cord tissue needs to be collected, a filter screen with a pore size of 150 μm-3000 μm can be used, for example, a filter screen with a pore size of 400 μm-600 μm. Therefore, the user can select the filter element 30 with an appropriate pore size according to the different biological materials to be cleaned, filtered and collected.
参照图3，在组装时，可活动内组件20位于外套管10内部，过滤元件30固定于可活动内组件20，使该过滤元件30、外套管10及可活动内组件20之间形成一密闭空间，且可活动内组件20可在外套管10内部轴向移动。Referring to Fig. 3, when assembled, the movable inner component 20 is located inside the outer sleeve 10, and the filter element 30 is fixed to the movable inner component 20, so that a sealed airtight seal is formed between the filter element 30, the outer sleeve 10 and the movable inner component 20. space, and the movable inner component 20 can move axially inside the outer sleeve 10 .
参照图4，其是本发明第一实施例的清洗细胞及/或组织方法流程图。为达清洗细胞组织的目的，首先提供清洗装置，其中细胞及/或组织40与清洗液50置于装置的密闭空间内(步骤60)，亦即将细胞及/或组织40与清洗液50置于外套管10内(步骤61)，再套上可活动内组件20以形成一密闭空间(步骤62)，接着再沿轴向移动可活动内组件20以清洗及过滤细胞组织40(步骤70)，最后再收集清洗完毕的细胞组织40(步骤80)。Referring to FIG. 4 , it is a flow chart of the method for cleaning cells and/or tissues according to the first embodiment of the present invention. In order to achieve the purpose of cleaning the cells and tissues, a cleaning device is first provided, wherein the cells and/or tissues 40 and the cleaning solution 50 are placed in the closed space of the device (step 60), that is, the cells and/or tissues 40 and the cleaning solution 50 are placed In the outer casing 10 (step 61), the movable inner component 20 is put on to form a closed space (step 62), and then the movable inner component 20 is moved axially to clean and filter the cell tissue 40 (step 70), Finally, the washed cell tissue 40 is collected (step 80).
参照图5，其是本发明第一实施例中沿轴向移动该可活动内组件以清洗过滤该细胞及/或组织的流程图。Referring to FIG. 5 , it is a flowchart of moving the movable inner component axially to clean and filter the cells and/or tissues in the first embodiment of the present invention.
为重复进行过滤清洗步骤并使用新鲜清洁的清洗液，可如图6所示先将细胞组织40与清洗液50置于外套管10内，插入可活动内组件20以形成密闭空间(步骤60)，再沿第一轴向D1移动可活动内组件20以压缩密闭空间(步骤71)，此时清洗液50会滤至可活动内组件20内，经由内套管开口22倒除滤出的清洗液50并加入新鲜的清洗液50(步骤72)之后，再如图7所示沿第二轴向D2移动可活动内组件20以扩张密闭空间(步骤73)，然后再重复步骤71。如此重复进行数次可确保每次过滤清洗过程中所使用的清洗液都是新鲜清洁的。In order to repeat the filter cleaning step and use fresh and clean cleaning solution, as shown in FIG. 6, the cell tissue 40 and the cleaning solution 50 can be placed in the outer sleeve 10, and the movable inner component 20 is inserted to form a closed space (step 60) , and then move the movable inner component 20 along the first axis D1 to compress the confined space (step 71), at this time, the cleaning liquid 50 will filter into the movable inner component 20, and pour out the filtered cleaning solution through the inner sleeve opening 22 After cleaning liquid 50 and adding fresh cleaning solution 50 (step 72), move the movable inner component 20 along the second axis D2 as shown in FIG. 7 to expand the confined space (step 73), and then repeat step 71. Repeating this several times can ensure that the cleaning solution used in each filter cleaning process is fresh and clean.
为使清洗液能够充份与细胞及/或组织混合并充份清洗，在步骤73之后先不要拔出可活动内组件20，摇晃整个装置以清洗细胞组织40(步骤74)之后，再沿第一轴向D1移动可活动内组件20以压缩密闭空间(步骤71)，使清洗液滤至可活动内组件20内，然后再重复步骤73。In order to make the cleaning solution fully mix with the cells and/or tissues and fully clean, do not pull out the movable inner component 20 after step 73, shake the whole device to clean the cells and tissues 40 (step 74), and then follow the step 73. Move the movable inner component 20 along an axis D1 to compress the enclosed space (step 71 ), so that the cleaning fluid is filtered into the movable inner component 20 , and then repeat step 73 .
最后，为了收集清洗完毕的细胞及/或组织，在步骤71之后经由内套管开口22倒除滤出的清洗液(步骤75)，拔出可活动内组件20，再旋转分离外套管管身11及旋盖12，自旋盖12中收集清洗完毕的细胞组织40即可。Finally, in order to collect the cleaned cells and/or tissues, after step 71, pour off the filtered cleaning solution through the inner sleeve opening 22 (step 75), pull out the movable inner component 20, and then rotate and separate the outer sleeve body 11 and the screw cap 12, it is enough to collect the cleaned cell tissue 40 in the spin cap 12.
请参阅图8，在本发明的第二实施例中，生物材料清洗装置100包括一内套管120以及一外套管110，内套管120以可拆卸以及可滑动方式设置在外套管110中，其中，内套管120以及外套管110皆为长管状，在本实施例中，内套管120以及外套管110的横断面皆为圆形。Please refer to FIG. 8, in the second embodiment of the present invention, the biological material cleaning device 100 includes an inner sleeve 120 and an outer sleeve 110, the inner sleeve 120 is detachably and slidably disposed in the outer sleeve 110, Wherein, both the inner sleeve 120 and the outer sleeve 110 are long tubular, and in this embodiment, the cross-sections of the inner sleeve 120 and the outer sleeve 110 are circular.
请参阅图9A以及图9B，外套管110包括一第一套件111以及一第二套件112。第二套件112为基底元件，其上端118有开孔，而下端119为封闭，其中「上」、「下」等用语仅是为方便说明而使用，并非用于限定本发明。第一套件111为延伸元件，其上端114以及下端115皆有开孔(图中将上端114的开孔标示为113，将下端115的开孔标示为116)。又，第一套件111的下端115以可拆卸方式连结于第二套件112的上端118。Referring to FIG. 9A and FIG. 9B , the outer sleeve 110 includes a first set 111 and a second set 112 . The second set 112 is a base element with an opening at its upper end 118 and a closed lower end 119 , where the words "upper" and "lower" are used for convenience of description and are not intended to limit the present invention. The first sleeve 111 is an extension element, and its upper end 114 and lower end 115 have openings (in the figure, the opening of the upper end 114 is marked as 113 , and the opening of the lower end 115 is marked as 116 ). Moreover, the lower end 115 of the first sleeve 111 is detachably connected to the upper end 118 of the second sleeve 112 .
在第二实施例中，第一套件111以及第二套件112通过螺纹加以连结，然而第一套件111以及第二套件112也可以用其他方式来连结，例如用紧配合方式(Press-fit Engagement)。详言之，在第二实施例中，第二套件112的上端118的外周设置有螺纹128，而第一套件111的下端115的内周设置有形状互补的螺纹127，用于和螺纹128螺合。另外在第一套件111的上端114的外周设置有螺纹126，可与另一延伸元件(未图示)的螺纹相螺合。In the second embodiment, the first sleeve 111 and the second sleeve 112 are connected by threads, but the first sleeve 111 and the second sleeve 112 can also be connected in other ways, such as press-fit engagement . Specifically, in the second embodiment, the outer circumference of the upper end 118 of the second sleeve 112 is provided with a screw thread 128, and the inner circumference of the lower end 115 of the first sleeve 111 is provided with a complementary screw thread 127 for screwing with the screw thread 128. combine. In addition, a thread 126 is provided on the outer periphery of the upper end 114 of the first sleeve 111 , which can be screwed with the thread of another extension element (not shown).
生物材料可从开孔113放入外套管110中，然后加以清洗。清洗结束后，可将第一套件111与第二套件112分离，而生物材料集中留在第二套件112内。Biological material can be placed into the outer sleeve 110 through the opening 113 and then washed. After cleaning, the first set 111 can be separated from the second set 112 , and the biological materials are concentrated in the second set 112 .
请参阅图10A以及图10B，内套管120在其上端144设置有一第一端口122，在其下端142则设置有一第二端口123，清洗液(例如食盐水)可从第一端口122加入内套管120，并且经由第二端口123在内套管120以及外套管110之间来回流动。过滤元件130设置于第二端口123，能够允许清洗液通过，并使生物材料无法通过。另外，内套管120在其上端144设置有一停止件125，此停止件125同时作为把手之用。10A and 10B, the inner sleeve 120 is provided with a first port 122 at its upper end 144, and a second port 123 is provided at its lower end 142, and a cleaning solution (such as saline) can be added into the inner sleeve through the first port 122. The sleeve 120 , and flows back and forth between the inner sleeve 120 and the outer sleeve 110 through the second port 123 . The filter element 130 is disposed at the second port 123 and is capable of allowing the cleaning fluid to pass through and preventing biological materials from passing through. In addition, the inner sleeve 120 is provided with a stopper 125 at its upper end 144, and the stopper 125 also serves as a handle.
停止件125为一向外延伸的突出部，其直径大于外套管110的上端开孔113的尺寸，因此内套管120在外套管110中移动的最大距离可由停止件125来决定。内套管120具有一由停止件125延伸而出的内套管管身121，此内套管管身121的长度(沿轴向)较外套管110为短，使得当内套管120完全插入外套管110时，内套管120的下端142与外套管110的下端119之间仍存在一距离，也就是说在内套管120的下端142与外套管110的下端119之间会形成一密闭空间150，可以用来收集生物材料。而停止件125可限制内套管120相对于外套管110的移动距离，以免因不当操作而损伤到生物材料。The stopper 125 is an outwardly extending protrusion with a diameter greater than the size of the upper opening 113 of the outer sleeve 110 , so the maximum distance that the inner sleeve 120 can move in the outer sleeve 110 can be determined by the stopper 125 . The inner sleeve 120 has an inner sleeve body 121 extending from the stopper 125. The length (in the axial direction) of the inner sleeve body 121 is shorter than that of the outer sleeve 110, so that when the inner sleeve 120 is fully inserted When the outer sleeve 110 is used, there is still a distance between the lower end 142 of the inner sleeve 120 and the lower end 119 of the outer sleeve 110, that is to say, a closed airtight space will be formed between the lower end 142 of the inner sleeve 120 and the lower end 119 of the outer sleeve 110. Space 150 may be used to collect biological material. The stopper 125 can limit the moving distance of the inner cannula 120 relative to the outer cannula 110, so as to avoid damage to the biological material due to improper operation.
密闭空间150的尺寸大小由内套管120以及外套管110的相对位置来决定，因此并非定值而可以改变。The size of the enclosed space 150 is determined by the relative positions of the inner sleeve 120 and the outer sleeve 110 , so it is not a fixed value but can be changed.
内套管120更具有一筛网套组132，筛网套组132设置在第二端口123中，并形成密闭空间150的上边界。生物材料放置于外套管110内，并在清洗过程中被局限在密闭空间150里(如图12A所示)。本发明所使用的生物材料可以包括细胞、细胞碎裂物(Cellular Lysates)、或者组织等，但不限于此。The inner casing 120 further has a screen set 132 , and the screen set 132 is disposed in the second port 123 and forms an upper boundary of the enclosed space 150 . The biological material is placed within the outer cannula 110 and is confined within the confined space 150 (as shown in FIG. 12A ) during the washing process. The biological material used in the present invention may include cells, cell lysates (Cellular Lysates), or tissues, etc., but is not limited thereto.
在内套管120的下端142设置有一弹性件124，用于密合于外套管110的内周表面。详言之，弹性件124固定在内套管120的外周表面上，其可以为一环状的橡胶件(如O环)，用于在外套管110的内周表面以及内套管120的外周表面之间产生密封效果，以免清洗液及生物材料从其中漏出。An elastic member 124 is disposed on the lower end 142 of the inner sleeve 120 for sealing the inner peripheral surface of the outer sleeve 110 . In detail, the elastic member 124 is fixed on the outer peripheral surface of the inner sleeve 120, which may be an annular rubber member (such as an O-ring), and is used on the inner peripheral surface of the outer sleeve 110 and the outer circumference of the inner sleeve 120. A seal is created between the surfaces to prevent cleaning fluids and biological material from escaping.
设置在第二端口123的筛网套组132为连通外套管110的内部与内套管120的内部的一液体流径，可让清洗液从中流过。筛网套组132包括有过滤元件130，该过滤元件130可包夹固定在一筛网134以及一支撑件129之间(图10B、图12A及图12B)，或者可包夹固定在二筛网(未图示)之间，此种配置方式可提供过滤元件130额外支撑，以避免在清洗过程中发生破裂或变形。又或者过滤元件130可安装在一支撑结构(例如筛网)上，此支撑结构可从第二端口123取下，以更换过滤元件，进行下次清洗操作。The screen set 132 disposed at the second port 123 is a liquid flow path connecting the inside of the outer casing 110 and the inside of the inner casing 120 , allowing cleaning liquid to flow therethrough. The screen set 132 includes a filter element 130, which can be clamped and fixed between a screen 134 and a support 129 (Figure 10B, Figure 12A and Figure 12B), or can be clamped and fixed between two screens. Between the mesh (not shown), this configuration provides additional support for the filter element 130 to avoid cracking or deformation during cleaning. Alternatively, the filter element 130 can be installed on a support structure (such as a screen), and the support structure can be removed from the second port 123 to replace the filter element for the next cleaning operation.
清洗装置100的筛网套组132可视情况而采用不同的过滤元件130。举例而言，当清洗的组织取自软骨时，则可采用孔径约100μm的滤网；当清洗的组织取自脐带时，则采用孔径范围大约在150μm至3000μm的滤网。另外，当欲清洗的生物材料为细胞而非组织时，则采用孔径更小的滤膜，举例而言，在清洗细胞时，采用孔径约10μm的滤膜；在其他实施例中，滤膜的孔径范围大约在5μm至20μm之间。The screen set 132 of the cleaning device 100 may use different filter elements 130 depending on the situation. For example, when the cleaned tissue is taken from cartilage, a filter with a pore size of about 100 μm can be used; when the cleaned tissue is taken from an umbilical cord, a filter with a pore size in the range of about 150 μm to 3000 μm can be used. In addition, when the biological material to be cleaned is cells rather than tissues, a filter membrane with a smaller pore size is used. For example, when cleaning cells, a filter membrane with a pore size of about 10 μm is used; in other embodiments, the filter membrane has a The pore size range is approximately between 5 μm and 20 μm.
请参阅图11所示的使用上述清洗装置100来清洗生物材料的流程图400。Please refer to the flow chart 400 shown in FIG. 11 for cleaning biological materials using the above-mentioned cleaning device 100 .
首先如步骤410所示，将生物材料(例如生物组织)140从外套管开口113放入外套管110中；在步骤420中，将内套管120插入外套管110以形成密闭空间150，而生物材料140在清洗过程中始终被局限在密闭空间150里；在步骤430中，从第一端口122将适合生物材料140的清洗液160加入密闭空间150里，例如清洗液160包括磷酸缓冲食盐水(Phosphate Buffer Saline，PBS)，但本发明并不限于此。First, as shown in step 410, biological material (such as biological tissue) 140 is put into the outer sleeve 110 from the outer sleeve opening 113; in step 420, the inner sleeve 120 is inserted into the outer sleeve 110 to form a closed space 150, and the biological The material 140 is always confined in the closed space 150 during the cleaning process; in step 430, a cleaning solution 160 suitable for the biological material 140 is added to the closed space 150 from the first port 122, for example, the cleaning solution 160 includes phosphate buffered saline ( Phosphate Buffer Saline, PBS), but the present invention is not limited thereto.
接着在步骤440中，迫使清洗液160经由过滤元件130流进及流出于密闭空间150来清洗生物材料140，其中包括步骤442的借着移动内套管120沿第一方向(轴向)D1压缩密闭空间150(图12A)；步骤444的移动内套管120沿第二方向(轴向)D2扩张密闭空间150(图12B)。步骤442以及步骤444可轮流实施多次以去除(例如)含在生物材料中的化学试剂。某些情况下如步骤446所示，轻轻摇晃清洗液160可有助于改善清洗效率，而摇晃动作可以在步骤442及/或步骤444之后进行。Then in step 440, the cleaning fluid 160 is forced to flow into and out of the closed space 150 through the filter element 130 to clean the biological material 140, including step 442 by moving the inner sleeve 120 to compress along the first direction (axial direction) D1 Confined space 150 ( FIG. 12A ); step 444 of moving the inner sleeve 120 to expand the confined space 150 along the second direction (axial direction) D2 ( FIG. 12B ). Step 442 and step 444 may be performed multiple times in turn to remove, for example, chemical reagents contained in the biological material. In some cases, as shown in step 446 , gently shaking the cleaning solution 160 can help improve cleaning efficiency, and the shaking action can be performed after step 442 and/or step 444 .
在清洗过程中，当清洗液160经由过滤元件130进出密闭空间150时，生物材料140大致上局限在密闭空间150里，而固定在内套管120外部的橡胶弹性元件124可防止清洗液160通过，使得清洗液160仅能从过滤元件130来进出密闭空间150。During the cleaning process, when the cleaning liquid 160 enters and exits the closed space 150 through the filter element 130, the biological material 140 is generally confined in the closed space 150, and the rubber elastic element 124 fixed on the outside of the inner sleeve 120 can prevent the cleaning liquid 160 from passing through. , so that the cleaning liquid 160 can only enter and exit the confined space 150 from the filter element 130 .
在清洗步骤440结束后，令密闭空间150中的清洗液160经由过滤元件130以及第一端口122而排放至废弃槽(步骤450)，可将(例如)清洗装置100倒转来排放除清洗液160。After the cleaning step 440 is completed, the cleaning solution 160 in the closed space 150 is discharged to the waste tank through the filter element 130 and the first port 122 (step 450), and the cleaning device 100 can be turned upside down to discharge the cleaning solution 160 .
在某些情况下，可能需要清洗生物材料140许多次，才能够完全将化学试剂及其他不要的物质去除，此时在排放清洗液160(步骤450)之后，可将新鲜清洗液160’经由第一端口122而补充至密闭空间150(步骤430)，然后重复实施清洗步骤440以及排放步骤450。In some cases, it may be necessary to wash the biological material 140 many times before the chemical reagents and other unnecessary substances can be completely removed. At this time, after the cleaning solution 160 is discharged (step 450), the fresh cleaning solution 160' can be passed through the first step. A port 122 is added to the confined space 150 (step 430), and then the cleaning step 440 and the draining step 450 are repeated.
如果已经完全将生物材料清洗干净(步骤460)，则将内套管120与外套管110分离，其中生物材料140被收集在外套管110内(步骤470)，有些情况下还可进一步拆解第一套件111以及第二套件112，以方便取出生物材料140。If the biological material has been completely cleaned (step 460), the inner sleeve 120 is separated from the outer sleeve 110, wherein the biological material 140 is collected in the outer sleeve 110 (step 470), and in some cases the second sleeve can be further disassembled. A set 111 and a second set 112 are used to remove the biological material 140 conveniently.
虽然结合以上实施例揭露了本发明，然而其并非用以限定本发明，任何熟悉此技术者，在不脱离本发明的精神和范围内，可做些许的更动与润饰，因此本发明的保护范围应以附上的权利要求所界定的为准。Although the present invention has been disclosed in conjunction with the above embodiments, it is not intended to limit the present invention. Anyone familiar with the art can make some changes and modifications without departing from the spirit and scope of the present invention. Therefore, the protection of the present invention The scope should be defined by the appended claims.
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910126668.XACN101544946B (en) | 2008-03-27 | 2009-03-10 | Cell, tissue or biological material cleaning device and method |
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810090530.4 | 2008-03-27 | ||
| CN200810090530 | 2008-03-27 | ||
| CN200910126668.XACN101544946B (en) | 2008-03-27 | 2009-03-10 | Cell, tissue or biological material cleaning device and method |
| Publication Number | Publication Date |
|---|---|
| CN101544946A CN101544946A (en) | 2009-09-30 |
| CN101544946Btrue CN101544946B (en) | 2015-02-18 |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910126668.XAActiveCN101544946B (en) | 2008-03-27 | 2009-03-10 | Cell, tissue or biological material cleaning device and method |
| Country | Link |
|---|---|
| CN (1) | CN101544946B (en) |
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|---|---|---|---|---|
| CN105985903A (en)* | 2015-02-12 | 2016-10-05 | 谭巍 | Cell collecting device and application thereof |
| CN111979093B (en)* | 2020-08-28 | 2023-11-17 | 北京盛拓达生物技术有限公司 | Enzyme preparation apparatus for producing |
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| US1386340A (en)* | 1920-08-02 | 1921-08-02 | Wuster Robert | Filtering apparatus |
| US5330916A (en)* | 1990-06-26 | 1994-07-19 | E. I. Du Pont De Nemours And Company | Cellular component extraction apparatus and disposable vessel useful therein |
| Publication number | Priority date | Publication date | Assignee | Title |
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| US1386340A (en)* | 1920-08-02 | 1921-08-02 | Wuster Robert | Filtering apparatus |
| US5330916A (en)* | 1990-06-26 | 1994-07-19 | E. I. Du Pont De Nemours And Company | Cellular component extraction apparatus and disposable vessel useful therein |
| Publication number | Publication date |
|---|---|
| CN101544946A (en) | 2009-09-30 |
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| EE01 | Entry into force of recordation of patent licensing contract | Application publication date:20090930 Assignee:Bo Sheng medical Limited by Share Ltd Assignor:Industrial Technology Research Institute Contract record no.:2018990000304 Denomination of invention:Apparatus and method for cleaning cell, tissue or biological material Granted publication date:20150218 License type:Exclusive License Record date:20181121 | |
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