TWI567191B - Cell loading device and cell culture system - Google Patents
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Description
本發明是有關於一種細胞承載裝置，特別是指一種包含一聚氨酯彈性膜、一支撐結構及至少一孔道的細胞承載裝置，以及包含該細胞承載裝置的細胞培養系統。 The present invention relates to a cell carrying device, and more particularly to a cell carrying device comprising a polyurethane elastic film, a support structure and at least one channel, and a cell culture system comprising the cell carrying device.
由於生物體中許多細胞所生長的位置是處於動態環境，例如：心、肺或胃等器官壁會隨著壓力而膨脹及縮小，肌肉或皮膚表面會隨著壓力而拉伸，因此，當對於細胞進行體外觀察時，需要模擬出一個符合生物體的動態環境，以承載及培養細胞。 Since many cells in an organism grow in a dynamic environment, for example, the walls of the heart, lungs, or stomach expand and contract with pressure, and the muscle or skin surface stretches with pressure, so when When the cells are observed in vitro, it is necessary to simulate a dynamic environment in accordance with the organism to carry and culture the cells.
現有可提供動態環境以觀察細胞的裝置是使用一具有彈性的矽膠膜，並透過機械或流體施加外力，使承載在該矽膠膜上的細胞接受到動態刺激。然而，在長期使用下，該矽膠膜往往會因為彈性疲乏而降低裝置的耐用程度。 Existing devices that provide a dynamic environment for observing cells use a resilient silicone film and apply an external force through a mechanical or fluid fluid to impart dynamic stimulation to cells carried on the silicone film. However, under long-term use, the silicone film tends to reduce the durability of the device due to the fatigue fatigue.
此外，觀察附著型細胞(adherent cell)的裝置不僅需要提供良好的細胞生長環境，還需要具備良好的細胞附著效果，因此，通常需要額外進行化學修飾或蛋白質塗佈，以增進細胞附著效果。 In addition, the device for observing adherent cells not only needs to provide a good cell growth environment, but also needs to have a good cell adhesion effect. Therefore, it is usually necessary to additionally perform chemical modification or protein coating to enhance cell adhesion.
因此，本發明之目的，即在提供一種細胞承載裝置，適用於觀察附著型細胞。 Accordingly, it is an object of the present invention to provide a cell-carrying device suitable for observing adherent cells.
於是本發明細胞承載裝置，包含一彈性膜、一支撐結構及至少一孔道，其中，該彈性膜的材質為聚氨酯。該彈性膜是用以承載細胞。該支撐結構是固定在該彈性膜周緣。該至少一孔道是連通至該彈性膜底部，以施加應力於該彈性膜。 Therefore, the cell carrying device of the present invention comprises an elastic film, a supporting structure and at least one channel, wherein the elastic film is made of polyurethane. The elastic membrane is used to carry cells. The support structure is fixed to the periphery of the elastic film. The at least one channel is connected to the bottom of the elastic film to apply stress to the elastic film.
因此，本發明之另一目的，即在提供一種細胞培養系統，包含如上所述的細胞承載裝置，及一附著於該彈性膜上的附著型細胞。 Accordingly, another object of the present invention is to provide a cell culture system comprising the cell carrying device as described above, and an adherent cell attached to the elastic membrane.
本發明之功效在於，該細胞承載裝置的聚氨酯彈性膜，具備良好的彈性及耐用度，且無需額外進行化學修飾或蛋白質塗佈，即可增進細胞附著效果。 The effect of the present invention is that the polyurethane elastic film of the cell carrying device has good elasticity and durability, and can improve the cell adhesion effect without additional chemical modification or protein coating.
以下將就本發明內容進行詳細說明：較佳地，該支撐結構是固定在該彈性膜周緣的兩相反側。 DETAILED DESCRIPTION OF THE INVENTION The present invention will be described in detail below. Preferably, the support structure is fixed to opposite sides of the periphery of the elastic film.
在本發明的第一實施例中，該細胞承載裝置還包含一底座，間隔設置在該彈性膜底部，且該至少一孔道是貫穿該底座。 In a first embodiment of the present invention, the cell carrying device further includes a base spaced apart from the bottom of the elastic film, and the at least one hole is through the base.
在本發明的第二實施例中，該細胞承載裝置還包含一承載柱，設置在該彈性膜底部，並與該支撐結構間隔設置，且該彈性膜是部分貼附於該承載柱。 In a second embodiment of the present invention, the cell carrying device further includes a carrier column disposed at a bottom of the elastic film and spaced apart from the support structure, and the elastic film is partially attached to the carrier column.
較佳地，該聚氨酯是使聚醚多元醇與脂肪族多 異氰酸酯反應，接著與鏈延長劑反應而得。更佳地，該聚醚多元醇是選自於聚乙二醇(PEG)、聚丙二醇(PPG)或其組合。更佳地，PEG與PPG的莫耳比例為3：7以上。該脂肪族多異氰酸酯可避免芳香族化合物可能具有的毒性風險。更佳地，該脂肪族多異氰酸酯是選自於異佛酮二異氰酸酯(isophorone diisocyanate,IPDI)、1,6-己二異氰酸酯(hexamethylene diisocyanate,HDI)或其組合。該鏈延長劑是選自於1,4-丁二醇(1,4-BD)、乙二醇或其組合。 Preferably, the polyurethane is such that the polyether polyol and the aliphatic group are The isocyanate reaction is followed by reaction with a chain extender. More preferably, the polyether polyol is selected from the group consisting of polyethylene glycol (PEG), polypropylene glycol (PPG), or a combination thereof. More preferably, the molar ratio of PEG to PPG is 3:7 or more. The aliphatic polyisocyanate avoids the risk of toxicity that aromatic compounds may have. More preferably, the aliphatic polyisocyanate is selected from the group consisting of isophorone diisocyanate (IPDI), hexamethylene diisocyanate (HDI), or a combination thereof. The chain extender is selected from the group consisting of 1,4-butanediol (1,4-BD), ethylene glycol, or a combination thereof.
更佳地，該脂肪族多異氰酸酯、該聚醚多元醇與該鏈延長劑的莫耳比例範圍為2：1：1~3：2：1，以得到彈性佳(伸長率高)且耐用(強度高)的聚氨酯。 More preferably, the molar ratio of the aliphatic polyisocyanate, the polyether polyol and the chain extender ranges from 2:1:1 to 3:2:1 to obtain good elasticity (high elongation) and durability ( High strength polyurethane).
依據本發明的細胞培養系統，該附著型細胞包括那些為熟習此項技藝者可易於獲得的附著型細胞株(例如，可購自於國內或國外寄存機構者)，或者利用本技藝中所慣用的細胞分離方法而從天然來源中所分離純化出的附著型細胞株。較佳地，該附著型細胞是選自於由下列所構成的群組：間質幹細胞(mesenchymal stem cell)、纖維母細胞(fibroblast)、上皮細胞(epithelial cell)、內皮細胞(endothelial cell)、星狀細胞(astrocyte)、腎臟細胞(kidney cell)、肝細胞(hepatocyte)、表皮細胞(epidermal cell)、角膜細胞(corneal cell)，以及它們的組合。更佳地，該附著型細胞是選自於胎盤-衍生的間質幹細胞(placenta-derived mesenchymal stem cell，例如人類胎盤-衍生的間質幹細胞)、胚胎腎臟細胞(embryonic kidney cell，例如人類胚胎腎臟 細胞株HEK293)、胚胎纖維母細胞(embryonic fibroblast，例如老鼠胚胎纖維母細胞細胞株3T3)或其組合。 According to the cell culture system of the present invention, the adherent cells include those which are readily available to those skilled in the art (for example, those available from domestic or foreign hosting institutions), or utilize the art. An adherent cell strain isolated and purified from a natural source by a conventional cell separation method. Preferably, the adherent cells are selected from the group consisting of mesenchymal stem cells, fibroblasts, epithelial cells, endothelial cells, Astrocytic cells, kidney cells, hepatocytes, epidermal cells, corneal cells, and combinations thereof. More preferably, the adherent cells are selected from the group consisting of placenta-derived mesenchymal stem cells (eg, human placenta-derived mesenchymal stem cells), embryonic kidney cells (eg, human embryonic kidney cells). Cell line HEK293), embryonic fibroblast (eg, mouse embryonic fibroblast cell line 3T3), or a combination thereof.
1‧‧‧細胞承載裝置 1‧‧‧cell bearing device
2‧‧‧彈性膜 2‧‧‧elastic film
3‧‧‧支撐結構 3‧‧‧Support structure
4‧‧‧孔道 4‧‧‧ Holes
5‧‧‧底座 5‧‧‧Base
6‧‧‧承載柱 6‧‧‧Loading column
9‧‧‧附著型細胞 9‧‧‧ Attached cells
本發明之其他的特徵及功效，將於參照圖式的實施方式中清楚地呈現，其中：圖1是一剖視圖，說明本發明第一實施例之細胞承載裝置的結構；圖2是一剖視圖，說明該第一實施例之細胞承載裝置在施加鉛直方向的振動應力下的結構；圖3是一剖視圖，說明本發明第二實施例之細胞承載裝置的結構；及圖4是一剖視圖，說明該第二實施例之細胞承載裝置在施加水平方向的拉伸應力下的結構。 Other features and effects of the present invention will be apparent from the following description of the drawings, wherein: FIG. 1 is a cross-sectional view showing the structure of the cell carrying device of the first embodiment of the present invention; FIG. 2 is a cross-sectional view. The structure of the cell carrying device of the first embodiment under the application of the vibration stress in the vertical direction; FIG. 3 is a cross-sectional view showing the structure of the cell carrying device of the second embodiment of the present invention; and FIG. 4 is a cross-sectional view showing the The cell carrying device of the second embodiment is configured to apply a tensile stress in the horizontal direction.
在本發明被詳細描述之前，應當注意在以下的說明內容中，類似的元件是以相同的編號來表示。 Before the present invention is described in detail, it should be noted that in the following description, similar elements are denoted by the same reference numerals.
本發明將就以下實施例來作進一步說明，但應瞭解的是，該等實施例僅為例示說明之用，而不應被解釋為本發明實施之限制。 The invention is further described in the following examples, but it should be understood that these examples are for illustrative purposes only and are not to be construed as limiting.
<彈性膜的製備><Preparation of elastic film>
將IPDI、PEG1000(重量平均分子量為1,000)及PPG1000(重量平均分子量為1,000)以2：0.5：0.5的莫耳比例混合，在70℃下反應2小時得到預聚物後，再加入 1,4-BD(作為鏈延長劑，其與IPDI的莫耳比例為1：2)，在110℃下反應24小時，之後以固含量20%的比例溶於二甲基乙醯胺(DMAc)，並塗佈在一離型紙上，最後烘乾除去DMAc並撕除該離型紙，得到厚度約為0.025mm的聚氨酯彈性膜。 IPDI, PEG1000 (weight average molecular weight of 1,000) and PPG1000 (weight average molecular weight of 1,000) were mixed at a molar ratio of 2:0.5:0.5, and reacted at 70 ° C for 2 hours to obtain a prepolymer, and then added. 1,4-BD (as a chain extender with a molar ratio of 1:2 to IPDI), reacted at 110 ° C for 24 hours, then dissolved in dimethyl acetamide (DMAc at a solids content of 20%) And coated on a release paper, finally dried to remove DMAc and tear off the release paper to obtain a polyurethane elastic film having a thickness of about 0.025 mm.
<彈性膜的測試><Test of elastic film>
將上述製得的聚氨酯彈性膜以ASTM D5034進行伸長率(elongation)測試，結果為800%，顯示上述製得的聚氨酯彈性膜具有相當高的伸長率。 The polyurethane elastic film obtained above was subjected to an elongation test by ASTM D5034 and found to be 800%, showing that the polyurethane elastic film obtained above had a relatively high elongation.
將上述製得的聚氨酯彈性膜來培養人類胎盤-衍生的間質幹細胞(實驗組)，並以市售培養皿作為對照組，在37℃、5% CO2的環境中培養7天後，實驗組及對照組所測得的活細胞密度(viable cell density)分別為8.48×104/cm2及5.76×104/cm2，實驗組的活細胞密度相較於對照組大幅增加了47%，顯示上述製得的聚氨酯彈性膜能夠有效地促進附著型細胞的生長。 The above-prepared polyurethane elastic membrane was used to culture human placenta-derived mesenchymal stem cells (experimental group), and the cultured culture dish was used as a control group, and cultured in an environment of 37 ° C, 5% CO 2 for 7 days, and then the experiment was carried out. The viable cell densities measured in the group and the control group were 8.48×10 4 /cm 2 and 5.76×10 4 /cm 2 , respectively. The viable cell density of the experimental group was significantly increased by 47% compared with the control group. It is shown that the polyurethane elastic film obtained as described above can effectively promote the growth of adherent cells.
<細胞承載裝置及細胞培養系統><Cell bearing device and cell culture system>
參閱圖1與圖2，本發明細胞承載裝置1之第一實施例包含一彈性膜2、一支撐結構3、四孔道4及一底座5。該彈性膜2為上述製得的聚氨酯彈性膜，且該彈性膜2上附著有附著型細胞9(大小僅為示意)，可供模擬細胞在會頻繁膨脹及縮小的心、肺或胃等器官壁之動態生長環境。 Referring to Figures 1 and 2, a first embodiment of the cell carrying device 1 of the present invention comprises an elastic film 2, a support structure 3, four cells 4 and a base 5. The elastic film 2 is a polyurethane elastic film obtained as described above, and the elastic film 2 is adhered with an adherent type cell 9 (the size is only a schematic), and can be used for emulating cells in a heart, lung or stomach that frequently expands and contracts. The dynamic growth environment of the wall.
該支撐結構3是固定在該彈性膜2周緣的兩相 反側，以使該彈性膜2固定不移動。 The support structure 3 is two phases fixed to the periphery of the elastic film 2 The reverse side is such that the elastic film 2 is fixed and does not move.
該等孔道4是連通至該彈性膜2底部，並利用一外接的真空設備(圖未示)透過該等孔道4進行抽氣，以使該彈性膜2承載有該附著型細胞9的部分受到鉛直方向的應力而向下凹陷；當停止抽氣時，該彈性膜2會回復到抽氣前非凹陷的狀態。透過改變抽氣的壓力及頻率，該彈性膜2可在凹陷狀態與非凹陷狀態之間振動，藉以對該彈性膜2上的附著型細胞9提供鉛直方向的振動應力。 The channels 4 are connected to the bottom of the elastic film 2, and are evacuated through the holes 4 by an external vacuum device (not shown) so that the elastic film 2 carries the portion of the adherent cells 9 The stress in the vertical direction is recessed downward; when the pumping is stopped, the elastic film 2 is returned to the non-recessed state before the pumping. By changing the pressure and frequency of the pumping, the elastic film 2 can vibrate between a recessed state and a non-recessed state, thereby providing the vertical type of vibration stress to the adherent cells 9 on the elastic film 2.
該底座5間隔設置在該彈性膜2底部，且該等孔道4是貫穿該底座5，以控制該彈性膜2在抽氣時受到均勻的鉛直方向應力。 The base 5 is spaced apart from the bottom of the elastic film 2, and the holes 4 are penetrated through the base 5 to control the elastic film 2 to receive a uniform vertical direction stress during pumping.
參閱圖3與圖4，本發明細胞承載裝置1之第二實施例包含一彈性膜2、一支撐結構3、一孔道4及一承載柱6。該彈性膜2為上述製得的聚氨酯彈性膜，且該彈性膜2上附著有附著型細胞9(大小僅為示意)，可供模擬細胞在會頻繁拉伸的肌肉或皮膚表面之動態生長環境。 Referring to Figures 3 and 4, a second embodiment of the cell carrying device 1 of the present invention comprises an elastic film 2, a support structure 3, a channel 4 and a carrier column 6. The elastic film 2 is a polyurethane elastic film obtained as described above, and the elastic film 2 is adhered with an adherent type cell 9 (the size is only a schematic) for simulating the dynamic growth environment of the muscle on the muscle or skin surface which is frequently stretched. .
該支撐結構3是固定在該彈性膜2周緣的兩相反側，以使該彈性膜2固定不移動。 The support structure 3 is fixed on opposite sides of the periphery of the elastic film 2 so that the elastic film 2 is fixed and does not move.
該孔道4是連通至該彈性膜2底部且環繞該承載柱6，並利用一外接的真空設備(圖未示)透過該等孔道4進行抽氣，以使該彈性膜2承載有該附著型細胞9的部分受到水平方向的應力而向外伸展；當停止抽氣時，該彈性膜2會回復到抽氣前非伸展的狀態。透過改變抽氣的壓力及頻率，該彈性膜2可在伸展狀態與非伸展狀態之間拉 伸，藉以對該彈性膜2上的附著型細胞9提供水平方向的拉伸應力。 The hole 4 is connected to the bottom of the elastic film 2 and surrounds the carrier column 6, and is evacuated through the holes 4 by an external vacuum device (not shown), so that the elastic film 2 carries the adhesion type. The portion of the cell 9 is stretched outward by the stress in the horizontal direction; when the pumping is stopped, the elastic film 2 is returned to the non-stretched state before the pumping. By changing the pressure and frequency of the pumping, the elastic film 2 can be pulled between the stretched state and the non-stretched state. Stretching, thereby providing the tensile stress in the horizontal direction to the adherent cells 9 on the elastic film 2.
該承載柱6設置在該彈性膜2底部，並透過該孔道4與該支撐結構3間隔設置，且該彈性膜2是部分貼附於該承載柱6，以控制該貼附的部分在抽氣時受到水平方向的應力。 The supporting column 6 is disposed at the bottom of the elastic film 2, and is spaced apart from the supporting structure 3 through the hole 4, and the elastic film 2 is partially attached to the supporting column 6 to control the attached portion to be pumped. It is subjected to stress in the horizontal direction.
綜上所述，本發明細胞承載裝置1藉由該彈性佳且耐用的彈性膜2，無需額外進行化學修飾或蛋白質塗佈，即可提供良好的細胞生長環境及細胞附著效果，適用於觀察附著型細胞9，故確實能達成本發明之目的。 In summary, the cell carrying device 1 of the present invention can provide a good cell growth environment and cell adhesion effect by using the elastic and durable elastic film 2 without additional chemical modification or protein coating, and is suitable for observing adhesion. The type cell 9 is indeed capable of achieving the object of the present invention.
惟以上所述者，僅為本發明之實施例而已，當不能以此限定本發明實施之範圍，凡是依本發明申請專利範圍及專利說明書內容所作之簡單的等效變化與修飾，皆仍屬本發明專利涵蓋之範圍內。 However, the above is only the embodiment of the present invention, and the scope of the invention is not limited thereto, and all the equivalent equivalent changes and modifications according to the scope of the patent application and the patent specification of the present invention are still The scope of the invention is covered.
1‧‧‧細胞承載裝置 1‧‧‧cell bearing device
2‧‧‧彈性膜 2‧‧‧elastic film
3‧‧‧支撐結構 3‧‧‧Support structure
4‧‧‧孔道 4‧‧‧ Holes
5‧‧‧底座 5‧‧‧Base
9‧‧‧附著型細胞 9‧‧‧ Attached cells
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| CN102676446B (en) * | 2012-05-04 | 2013-07-31 | 华中科技大学 | Method and device for loading cell fluid stress on deformable curved surface and experimental platform |
| TWM517199U (en) * | 2015-10-26 | 2016-02-11 | Taicend Technology Co Ltd | Cell carrying device and cell culture system |
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|---|---|---|---|---|
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| TW201715037A (en) | 2017-05-01 |
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