M381634 五、新型說明： 【新型所屬之技術領域】 本創作是有關於一種生物反應裝置，特別是指朝 汐式生物反應裝置》 【先前技術】 如第三圖所示，為本案申請人所申請美國專利案第 5766949 號「Method and Apparatus f〇r Cu|tivating Anchorage Dependent Monolayer Cells」發明案，所揭示 生物反應裝置（1)適用於大規模之貼壁式細胞培養，並包含 一培養器（11 )、多數間隔設置於該培養器（1彳）中且能用以 供細胞附著固定生長的載板（12)、一位於該培養器（11)上 方的上儲存器（13)、一位於該培養器⑴）下方的下儲存器 ⑽、一能於該培養器⑴)與該上、下儲存器(13胸間循 環流動的液態培養基 脣丞（15)、一其兩端分別連接該上儲存器 (13)底部與該培養器（11) ° 梦择兼哭,“一 ）、一其兩端分別連接 …養器⑴）頂部與該下儲存器⑽m 一 端分別連接該培養器（^庙邱豳兮 八兩 ^ ( 1)底邛與該下儲存器（14)的虹吸管 器η編l这 儲存器（14)底部與該上儲存 ° 、送g (19)、一用以注入新鮮空氣至哕抖養 中的氣系⑽，以及四分、：養器⑴） 管（17)盘該虹级其進料管（16)、該溢流 該虹及管(18)上的流量控制闕(20)。 於操作時，培養基（15)會 器（13)持續地下流 重力作“自該上儲存 这培養器⑴）中，當該培養器⑴）中之 3 M381634 培養基（15)達一定液位高度後’便會自該溢流管（17)以因 重力作用而下流至該下健存器（14)，讓載板（12)完全浸浴 於培養基（15)中，附載於載板（12)上之細胞便能利用培養 基(」5)所提供養分進行成長；待一段時間後，再利用該虹 吸官（18)使該培養器⑴）中之培養基（15)於虹吸作用與重力 作用相配合下而導排入該下健存器（14)中，讓載板⑽完 全曝露於m(1Q)所輸人之^ «境下，㈣於載板（12) 上之細胞便能充分吸收氧氣以促進成長；另-方面，當該 下儲存器（14)所儲存之培養基（15)達一定量時便會利用 機械柚送作用以經該抽送管(19)抽送至該上儲存器(13) 中以再為循環流動。主要利用培養基（15)於重力梯度效 應下所形成之穩定、均勻的潮沙式循環供給機制能有效 :進系統的虱體父換率，而明顯提昇細胞生長效率及產 置 ° 如第四圖所不’另—種生物反應裝置⑶是適用於小量 ::式細胞培養’並包含一上培養器Ο”、—固定於該 二養器（川中且能供細胞附著生長的載 =上培養器(31)且可壓縮之下儲存器(33)，以及一； 上培養曰器（31)與該下儲存器（33)間上下流動的培養基 剪鹿λ主要疋利用該下儲存器（33)之屢縮作動，營造出低 剪應力的流體環境，能促 成潮沙式養分供m。養基(34)上下循環流動以形 器⑶)中，二效：同時㈣送空氣進入該上培養 產量。 a進乳體父換率，提昇細胞生長效率及 4 M381634 然而’本案申請人有鑑於前述二種生物反應裝置（彳）(3) 爲了達到主動控制培養基（15)(34)浸潰載板（12)或載床 (32) ’則必須於培養器（11)或上培養器（31)連接一控制裝置 [諸如經該抽送管（19)抽送培養基（15)的機械或者可壓縮的 下健存器（33)]，且其t培養基（15)(34)必須藉由該控制裝 置機械柚送方能再回流至培養器（11)或上培養器（31)之 中因此會具有設備成本以及操作複雜度較高的缺點。 【新型内容】 因此，本創作之目的，即在提供一種氣體交換率高、 細胞生長效率與產量高、設備成本低，與操作簡易的潮汐 式生物反應裝置。 爲了達到上述目的，本創作的一種潮汐式生物反應裝 置，包含： 第一單兀，具有—第一槽器，以及一容置於該第一 槽器中的第一載體；M381634 V. New description: [New technology field] This creation is about a bioreactor, especially a pilgrimage bioreactor. [Prior Art] As shown in the third figure, the applicant applied for this case. U.S. Patent No. 5,766,949, "Method and Apparatus f〇r Cu|tivating Anchorage Dependent Monolayer Cells", the disclosed bioreactor (1) is suitable for large-scale adherent cell culture and comprises an incubator (11) a plurality of spacers (12) disposed in the incubator and capable of being used for cell attachment and growth growth, an upper reservoir (13) located above the incubator (11), and a a lower reservoir (10) below the incubator (1), a liquid medium lip (15) capable of circulating between the upper and lower reservoirs (13), and a liquid medium lip (15) circulating therebetween At the bottom of the device (13) and the incubator (11) ° Dreaming and crying, "one", one end of which is connected to each other...the top of the device (1)) and the lower end of the lower reservoir (10)m are respectively connected to the incubator (^ Temple Qiu Eight ^ (1) The bottom 邛 and the siphon of the lower reservoir (14) η 编 l The bottom of the reservoir (14) with the upper storage °, send g (19), one for injecting fresh air into the 哕Gas system (10), and four points,: feeder (1)) tube (17) disk of the rainbow level of its feed pipe (16), the flow control of the rainbow and the pipe (18) flow control (20). In operation, the medium (15) means (13) continues to flow underground gravity "from the upper storage of the incubator (1)), when the 3 M381634 medium (15) in the incubator (1) reaches a certain liquid level height' From the overflow pipe (17), it flows down to the lower loader (14) due to gravity, and the carrier plate (12) is completely immersed in the medium (15) and attached to the carrier plate (12). The cells can be grown using the nutrients provided by the medium ("5); after a period of time, the siphon (18) is used to match the medium (15) in the incubator (1) with the action of gravity and gravity. The guide is discharged into the lower storage device (14), so that the carrier plate (10) is completely exposed to the environment of the input of the m(1Q), and (4) the cells on the carrier plate (12) can be fully sucked. Oxygen to promote growth; on the other hand, when the medium (15) stored in the lower reservoir (14) reaches a certain amount, the mechanical pomelo is used to be pumped to the upper reservoir via the pumping tube (19) ( 13) China and Israel are circulating again. The stable and uniform tidal circulation supply mechanism formed by the medium (15) under the gravity gradient effect can be effective: the scorpion parent turnover rate of the system is increased, and the cell growth efficiency and production are obviously improved. The other kind of biological reaction device (3) is suitable for small amount:: type cell culture 'and contains an upper culture device 、', - fixed in the two nutrient device (in Sichuan and can be used for cell attachment growth) The medium (31) and the compressible lower reservoir (33), and a medium culture medium shearer λ main between the upper culture buffer (31) and the lower storage (33), the main storage device (33) The repeated action to create a low shear stress fluid environment, which can promote the tidal sand nutrient for m. The nutrient (34) circulates up and down in the shape of the device (3)), the second effect: at the same time (four) send air into the upper culture Yield a. Entering the parental turnover rate, increasing cell growth efficiency and 4 M381634 However, the applicant in this case has considered the above two biological reaction devices (彳) (3) in order to achieve active control medium (15) (34) impregnation load Plate (12) or bed (32) 'must be in the incubator 11) or the upper incubator (31) is connected to a control device [such as a mechanical or compressible lower reservoir (33) for pumping the medium (15) via the pumping tube (19), and its t medium (15) ( 34) The mechanical teafruit can be returned to the incubator (11) or the upper incubator (31) by the control device, so that it has the disadvantages of high equipment cost and high operational complexity. [New content] Therefore, The purpose of this creation is to provide a tidal bioreactor with a high gas exchange rate, high cell growth efficiency and high yield, low equipment cost, and simple operation. In order to achieve the above object, a tidal bioreactor is created. The method includes: a first single cassette having a first trough, and a first carrier housed in the first trough;
第一單兀’具有—位在該第一槽器上方的第二槽 該第一槽益係與第—槽器相連通並且具有一氣孔； 控制單元’其係用以對該第一槽器内部進行增/洩 以及 培養基體’其能於該第二槽器與該第一槽器間流 動’且於該第一揭哭& y B is連行增壓時能自該第一槽器向上推送 至該第二槽器中，w „ 使該第一載體呈裸曝，並於該第一槽 裔進行洩壓時能因重力蚀腐 咕 置力政應而自該第二槽器向下迴流至該 第—槽器中，以譆兮筮 系这第一載體浸濡在該培養基體中。 5 M381634 本創作是將二反應槽作高度落差，使第—單元可以重 力自然輸出培養液，因此可節省至少一組控制翠元的使用 (成本），進而節約能源。因此’本創作之潮沙式生物反應 裝置不但提供潮沙式循環供給培養基之功效，且能於有效 增進氣體交換率並且提昇細胞生長效率與產量之際，仍兼 得進一步降低設備成本與簡化操作程序。 【實施方式】 φ 本創作將由下列的實施例做為進一步說明，這些實施 例並不限制本創作前面所揭示的内容。熟習本創作之技藝 者，可以做些許之改良與修飾’但不脫離本創作之範疇。 如第一圖所示，本創作之潮汐式生物反應裝置（2)可用 以進行動物細胞（如豬腎細胞株，Porcine Kjdney Ce丨丨Une) 之培養，當然也可以用作其他動物細胞或微生物細胞之培 養。該潮汐式生物反應裝置（2)包含一高位的第一單元 (21)、一低位的第二單元（22)、一控制單元（23)、一能於該 籲-第一單元（21)與該第二單元（22)間上下循環流動的液態培 養基體（24)，以及一其兩端分別連接該第一單元（21)與該 第二單元（22)而用以導送該培養基體（24)的導送管（25)。本 實施例中，該培養基體（24)是含有5%小牛血清（Cosmic Calf Serum，CCS)的 MEM(Minimum Essential Medium) 者，體積約300毫升（mL)。 該第一單元（21)具有一第一槽器（211)、一固置於該第 一槽器（211)底部中且用以供動物細胞附著生長的第一載體 (212) ’以及一第一過濾件（213)。該第一槽器（211)具有一 6 M381634 能供外界空氣進出的氣孔（214)。其中，該第一過濾件（213) 是用以對將被吸入於該第一槽器（211)内部中的外界空氣進 订淨化。本實施例中，該第一載體（212)是為粒徑約6毫米 (mm)且量約10克的顆粒狀商用載體者，當然也可以是如 1平方公分的薄片狀原棉、0·5立方公分的塊狀菜瓜布、】 公分的長條狀椰子殼纖維…等已經前處理之天然载體者； —該第一過濾件（213)是濾材孔徑約0·2微米（#叫的空氣過 - 濾、器。 • 該第二單元（22)具有一位在該第一槽器（211)下方處且 能供該培養基體（24)容置的第二槽器（221)、一固置於該第 一槽器（221)底部中且用以供動物細胞附著生長的第二載體 (223)，以及一能輸入經淨化的氣體至該第二槽器（22彳）内 部的第二過濾件（222卜本實施例中，該第二載體223也 是為粒徑約6mm的顆粒狀商用載體者；以及該第二過濾 件（222)是濾材孔徑約〇·2微米（//m)的空氣過濾器者。 該導送管（25)之兩端是分別連接該第一槽器（21彳）底部 _與该第二槽器（221)底部，以使該培養基體（24)能於該第二 槽器（221)與該第一槽器（211)間上下循環流動。 該控制單元（23)是能對該第二槽器（221)内部進行增壓 /洩壓控制，並具有一能進氣以增加該第二槽器（22彳）内部 壓力的增壓件（231)、一用以控制該增壓件（231)之進氣量 的流量控制件（232)、一連接設置於該增壓件（23彳）與該第 二過濾件（222)之間而用以維持該第二槽器（22彳）内部壓力 狀態的逆止件（233)、一連接設置於該流量控制件（232)與 7 M381634 該第二過濾件（222)間而能排氣以降低該第二槽器221内 部壓力的洩壓件（234)，以及一用以控制該增壓件（231)、 該逆止件（233)與該錢件（234)等三者之作動狀態的計時 ，件(235)。本實施例中，該增愿件(231)是一氣泵；該流 董控制件（232)是一氣體流量計；該逆止件（233)是一止回 閥，該洩壓件（234)是一三通電子閥。 ' 其中’該計時組件（235)是由三個依序作動之計時器 • (236)(237)(238)所組成：第-個料it (236)能控制該增塵 •件（231)連續作動約30秒[此時該逆止件（233)與該洩壓件 (234)不作動]’以對該第二槽器（221)進行充氣增壓，導致 原本位於該第二槽器（221)中之培養基體（24)經該導送管 (25)而開始被向上推擠送至該第一槽器（211)中並使該第 一載體（212)與附著其上之動物細胞完全地浸濡其中（參見 第一圖）；接著，第二個計時器（237)能控制該逆止件（233) 作動[此時該增壓件（231)與該浪壓件（234)不作動】，抑制充 入該第二槽器（221)中之氣體回浪出’以維持該第二槽器 ⑩（221)内部之氣壓狀態，讓該培養基體（24)持續靜置於該第 -槽斋（211)中為30秒；續而，第三個計時器（238)能控制 該Λ壓件（234)連續作動約29分鐘[此時該增壓件（231)與 該逆止件（233)不作動]，使該第二槽器（221)中的氣體經該 洩壓件(234)洩出以進行減壓，讓位於該第一槽器(21”中 之培養基體（24)因重力作用而經該導送管（25)向下流回該 第二槽器（221)中，同時因培養基體（24)之流動而驅使外界 氣體自該氣孔(214)被吸弓丨入該第一槽器(21”内，該第一 8 M381634 载體（212)與附著其上之動物細胞便得以完全地裸曝於空氣 中約30秒。 於進行細胞培養階段前，必須先進行約3~4小時的細 胞固定化階段：首先讓該第一槽器（211)與該第二槽器（221) 進行高溫滅菌處理，並移送至無菌操作臺上再以含5% CCS的MEM培養基體24先潤濕該第一槽器（211)中的第 —載體（212广接著，將經繼代培養之動物細胞（本實施例 •是豬腎細胞株）以2·5χ105 (^丨匕/巾匕培養基體之密度量接種 ♦於該第-載體（212)上，並將300 mL的培養基體24加入 該第一槽器（211)中[即第一載體（212)與培養基體（24)的比 例為10g/300mL，接種細胞密度量為7 5x1〇5ce丨丨s/3〇〇mJ_ 培養基體（24)]，並將該潮汐式生物反應裝置（2)予以移置入 37 C、5% CQ2的培養箱中進行約3 、時的細胞固定化貼 附作用，過程中必須每30分鐘啟動該潮汐式生物反應裝 置（2)(其操作條件同於前述者）一次，使所接種之動物細胞 均勻地貼附、固定於該第一載體（212)表面上（經測可知所 達固定化效率> 90% )，以有助於其後續培養時能迅速進入 生長期，並迅速擴散成單層。 於完成細胞固定化階段後，便開始進行細胞培養階 段：配合透過該控制單元（23)之設定，以於培養基體（24) 流速為10 mL/sec、培養基體（24)停留於該第一槽器（211) 中之時間為30秒、第一載體（212)暴露於空氣中之時間為 1 〇分鐘等最佳化條件下進行培養。首先，第一個計時器 啟動該增壓件（231)，以對該第二槽器（221)進行約3〇秒的 9 M381634 進氣[已經該第二過濾件（222)淨]，使該第二槽器（221)之内 部壓力增高，而將該培養基體（24)向上推送入該第一槽器 (211)中；隨後’切換至第二個計時器（237)以啟動該逆止 件（233)，讓該培養基體（24)持續於該第一槽器（211)中靜 置約30秒’附著於第一載體（212)上的動物細胞便能充分 吸收該培養基體（24)中之養分，以進行代謝成長；續而a first unit 具有 having a second slot above the first slot, the first slot being in communication with the first slot and having a vent; the control unit 'which is used to the first slot Internally increasing/discharging and the medium body 'which can flow between the second tank and the first tanker' and can be lifted from the first tank when the first crying & y B is continuously pressurized Pushing into the second trough, w „ causing the first carrier to be barely exposed, and when the first trough is depressurized, it can be forced downward from the second trough due to gravity erosion Returning to the first tanker, the first carrier is dipped in the medium body. 5 M381634 The creation of the second reaction tank is a height drop, so that the first unit can naturally output the culture liquid by gravity. Therefore, at least one group can be saved to control the use (cost) of the Tsui dollar, thereby saving energy. Therefore, the tidal sand bioreactor of the present invention not only provides the effect of the tidal sand circulation supply medium, but also effectively improves the gas exchange rate and When you improve cell growth efficiency and yield, you can still get along The method of reducing the equipment cost and simplifying the operation procedure. [Embodiment] φ This creation will be further explained by the following embodiments, and these embodiments do not limit the contents disclosed in the previous creation. Those skilled in the art can make some modifications. The improvement and modification 'but does not deviate from the scope of this creation. As shown in the first figure, the tidal bioreactor (2) of this creation can be used for animal cells (such as Porcine Kjdney Ce丨丨Une). The culture can of course be used for the cultivation of other animal cells or microbial cells. The tidal bioreactor (2) comprises a high-level first unit (21), a low-level second unit (22), and a control unit. (23) a liquid medium body (24) capable of circulating up and down between the first unit (21) and the second unit (22), and a first unit (21) connected to each other at both ends thereof a transfer tube (25) for guiding the medium body (24) with the second unit (22). In the present embodiment, the medium body (24) contains 5% calf serum (Cosmic Calf Serum, CCS) MM (Minimum Es The first unit (21) has a first trough (211), one of which is fixed in the bottom of the first trough (211) and is used for animal cells. Attaching the grown first carrier (212)' and a first filter member (213). The first tank (211) has a 6 M381634 air hole (214) for allowing outside air to enter and exit. wherein the first filter member (213) is for ordering and purifying the outside air to be sucked into the interior of the first tank (211). In the embodiment, the first carrier (212) is about 6 mm (mm) in particle diameter. And the amount of the granular commercial carrier of about 10 grams, of course, may be, for example, 1 square centimeter of flaky raw cotton, 0. 5 cubic centimeters of block-shaped melon cloth, and the long strip of coconut shell fiber... The natural filter carrier; - the first filter member (213) is a filter material having a pore size of about 0.2 micrometers (# called air-filter). • the second unit (22) has a second trough (221) below the first trough (211) and receivable for the medium body (24), one fixed in the first trough a second carrier (223) in the bottom of the device (221) for attaching and growing animal cells, and a second filter member (222) capable of inputting the purified gas into the interior of the second tank (22彳) In an embodiment, the second carrier 223 is also a particulate commercial carrier having a particle size of about 6 mm; and the second filter member (222) is an air filter having a filter pore size of about 2 micrometers (//m). The two ends of the guiding tube (25) are respectively connected to the bottom of the first trough (21) and the bottom of the second trough (221), so that the medium body (24) can be used in the second trough (221) circulating upward and downward with the first tank (211). The control unit (23) is capable of performing pressure/pressure relief control on the inside of the second tank (221) and has an intake air a pressurizing member (231) for increasing the internal pressure of the second tank (22彳), a flow control member (232) for controlling the amount of intake of the pressurizing member (231), and a connection a checker (233) between the pressurizing member (23彳) and the second filter member (222) for maintaining the internal pressure state of the second tank (22彳), a connection is set at the flow rate a pressure releasing member (234) between the control member (232) and the 7 M381634 the second filter member (222) for exhausting to reduce the internal pressure of the second tank member 221, and a control member for controlling the pressurizing member (231) And timing of the actuating state of the backstop (233) and the money member (234), and the member (235). In the embodiment, the augmenting member (231) is an air pump; The piece (232) is a gas flow meter; the backstop (233) is a check valve, and the pressure relief member (234) is a three-way electronic valve. 'where the timing component (235) is composed of three The timer is operated in sequence: (236) (237) (238): the first material it (236) can control the dust-removing member (231) to continuously operate for about 30 seconds [this time the backstop ( 233) actuating with the pressure relief member (234) to inflate the second tank (221), thereby causing the medium body (24) originally located in the second tank (221) to pass through the guide. Feed pipe (25) and start to be up Squeezing into the first trough (211) and completely immersing the first carrier (212) with the animal cells attached thereto (see the first figure); then, the second timer (237) The backstop (233) can be controlled to operate [At this time, the pressurizing member (231) and the wave member (234) are not actuated], and the gas charged in the second tank (221) is suppressed from flowing back. In order to maintain the air pressure state inside the second tank 10 (221), the medium body (24) is continuously placed in the first tank (211) for 30 seconds; continued, the third timer (238) The pressure member (234) can be controlled to operate continuously for about 29 minutes [when the pressurizing member (231) and the backstop member (233) are not actuated], so that the gas in the second tank (221) passes through The pressure relief member (234) is vented for decompression, and the medium body (24) located in the first tank (21) flows downward through the conduit (25) to the second by gravity. In the tank (221), at the same time, the flow of the medium body (24) drives the outside air to be sucked into the first tank (21" from the air hole (214), the first 8 M381634 carrier (212) ) and the movement attached to it The cells are completely exposed to the air for about 30 seconds. Before the cell culture stage, the cell immobilization stage must be performed for about 3 to 4 hours: first, the first tanker (211) and the second tanker (221) are autoclaved and transferred to the aseptic operation. The first carrier in the first trough (211) is first wetted with a MEM medium 24 containing 5% CCS (212, then subcultured animal cells (this embodiment • is pig kidney) The cell strain is inoculated on the first carrier (212) at a density of 2. 5 χ 105 (^ 丨匕 / 匕 匕 medium body, and 300 mL of the culture medium body 24 is added to the first tank (211) [ That is, the ratio of the first carrier (212) to the medium body (24) is 10 g / 300 mL, the inoculated cell density is 7 5 x 1 〇 5 ce 丨丨 s / 3 〇〇 mJ_ medium body (24)], and the tidal organism The reaction device (2) is transferred into a 37 C, 5% CQ2 incubator for cell immobilization at a time of about 3, and the tidal bioreactor (2) must be activated every 30 minutes. Operating conditions are the same as the above), so that the inoculated animal cells are evenly attached and fixed to the first carrier (212) On the surface (measured by the measured immobilization efficiency > 90%), it can quickly enter the growth phase during subsequent cultivation, and rapidly diffuse into a single layer. After completing the cell immobilization stage, the cells are started. Culture stage: with the setting of the control unit (23), the flow rate of the medium body (24) is 10 mL/sec, and the time period of the medium body (24) staying in the first tank (211) is 30 seconds. The first carrier (212) is exposed to air for a period of time such as 1 minute. The culture is first performed. First, the first timer activates the pressurizing member (231) to the second trough (221). 9 M381634 air intake [already the second filter element (222) net] is performed for about 3 sec seconds, so that the internal pressure of the second tank (221) is increased, and the medium body (24) is pushed up into the In the first tank (211); then 'switching to the second timer (237) to activate the backstop (233), allowing the medium body (24) to continue in the first tank (211) The animal cells attached to the first carrier (212) can be sufficiently absorbed in the medium body (24) for about 30 seconds. Points to metabolize growth; continued and
切換至第三個計時器（238)以啟動該洩壓件（234)，以對該 第一槽器（221)進行約40秒的洩壓，位在該第一槽器（211) 中的培養基體（24)則因重力作用而向下迴流入該第二槽器 (221)内，使附著於該第二載體212上的動物細胞完全地 浸濡其中，以充分吸取其中養分，同時吸引外界空氣[經該 第一過濾件（21 3)淨化】經該氣孔（21 4)而進入該第一槽器 (211)内部，使附著於該第一載體（212)上的動物細胞能完 全暴露於高氧的空氣環境中約1〇分鐘，而充分吸收氧氣 以促進代謝成長。故透過第一〜三個計時器（236)(237)(咖） 之反覆地依序作動，配合於適當時間點上進行培養基體（24) 更換，讓該培養基體（24)於該第—槽器（211)與該第二槽器 (221)中循環流動，以潮沙式循環供給方式而提供予動物細 胞充足的生長養分，並促使該第一槽器（211)以及第二槽器 叩）内之氣體不斷交換而持續維持在高氧環境下提供予 動物細胞充足的氧氣㈣行㈣，於驗8天培養後所得 細胞產量便已高達約2.2x1〇9ce丨丨咖机培養基體叫 明顯月b達到氣體交換率傷里、知& & ε 高等效果。乂換羊優異、細胞生長效率佳與細胞產量 M381634 因此，利用該計時組件（235)能控制該增壓件（231)、 洩壓件（234)與逆止件（233)之作動，控制該培養基體（24) 能於該第一槽器（211)與該第二槽器（221)間進行上下循環 机動’並構成潮沙式供給方式’而有良好的氣體交換率， 藉以讓所培養之動物細胞能充分吸收培養基體（24)所含養 分與氧氣，故有極佳的細胞生長效率與細胞產量；另一方 面，整體疋由該第一單元（21)、該第二單元（22)與該控制 單元（23)三者架構而成’於設備上相當簡化而成本低廉， 且於操作控制上更為簡易，能改善現有技術的二種生物反 應裝置（1)(3)(請參見第三圖與第四圖所示）之設備成本較高 且操作控制較困難的問題。現有技術必須於各個反應槽都 有設有控制單元（23)，而本創作是將二反應槽作高度落差， 使第一單元（21)可以重力自然輸出培養液，因此可節省至 少一組控制單元（23)的使用（成本），進而節約能源。 如第二圖所示，為本創作潮汐式生物反應裝置（2)之另 一較佳實施例，與前述較佳實施例之差異在於，潮沙式生 物反應裝置（2)之第一單元（21)是處於低位，該第二單元（22) 是處於南位；而該控制單元（23)是與該第一單元（21)之第 =過瀘、件（213)連接，並能對該第一單元（21)之第一槽器 (211)内部進行增壓/洩壓控制。另外，該第二槽器（221)具 有一能供空氣進出的氣孔（224)，該第二過濾件（222)是設 置於該第二槽器（221)之氣孔（224)處。 於該控制單元（23)之增壓件（231)啟動以對該第一槽器 (211)進行增壓時，原本位於該第一槽器（211)中之培養基 11 M381634 體（24)會經料送管（25)而％全地被向上推送至該第二槽 器（221)中，使附著於該第一載體（212)上的動物細胞裸曝 於空氣中，以能充分吸收氧氣；而於該控制單元（23)之洩 壓件（234)啟動以對該第一槽器（2n)進行洩壓時，位於該 第二槽器（221)中之培養基體（24)便因重力作用而經該導送 管（25)向下流回該第一槽器（21彳）中，使附著於該第一載體 (212)上的動物細胞完全地浸濡其中，以能充分吸取其中養 分。 因此’本較佳實施例同樣能利用簡單設備與簡易操 作’控制該培養基體（24)於該第一槽器（211)與該第二槽器 (221)間進行潮汐式循環供給’以達·到氣體交換率良好、細 胞生長效率佳’與細胞產量高等效能。現有技術必須於各 個反應槽都有設有控制單元（23)，而本創作是將二反應槽 作尚度落差，使第一單元（21)可以重力自然輸出培養液， 因此可節省至少一組控制單元（23)的使用（成本），進而節 約能源。 【圖式簡單說明】 第一圖是本創作之潮汐式生物反應裝置的一較佳實施 例的結構示意圖》 第一圖是本創作之潮汐式生物反應裝置的另一較佳實 施例的結構示意圖。 第二圖是現有技術的生物反應裝置的結構示意圖，說 明一現有生物反應裝置。 第四圖是現有技術的生物反應裝置的結構圖。 12 M381634 【主要元件符號說明】 (1) 生物反應裝置 (12)載板 (14)下儲存器 (16)進料管 (18)虹吸管 ' (20)流量控制閥 (31)上培養器 # (33)下儲存器 (2) 潮汐式生物反應 (211)第一槽器 (213)第一過濾件 (22)第二單元 (222)第二過濾件 (224)氣孔 (231)增壓件 籲 （233)逆止件 (235)計時組件 (24)培養基體 (11)培養器 (13)上儲存器 (15)液態培養基 (17)溢流管 (19)柚送管 (3)生物反應裝置 (32)載床 (34)培養基 置 （21)第一單元 (212)第一載體 (214)氣孔 (221)第二槽器 (223)第二載體 (23)控制單元 (232)流量控制件 (234)浪壓件 (236)(237)(238)計時器 (25)導送管 13Switching to the third timer (238) to activate the pressure relief member (234) to relieve the first tank (221) for about 40 seconds, in the first tank (211) The medium body (24) is returned downward into the second tank (221) by gravity, so that the animal cells attached to the second carrier 212 are completely immersed therein to fully absorb the nutrients therein while attracting The outside air [purified by the first filter (21 3)] enters the inside of the first tank (211) through the air hole (21 4), so that the animal cells attached to the first carrier (212) can be completely Exposure to high oxygen in an air environment for about 1 minute, while fully absorbing oxygen to promote metabolic growth. Therefore, the first to third timers (236) (237) (cafe) are repeatedly operated in sequence, and the medium body (24) is replaced at an appropriate time point, so that the medium body (24) is in the first The tanker (211) and the second tanker (221) circulate and flow to provide sufficient growth nutrients to the animal cells in a tidal circulation supply manner, and urge the first tanker (211) and the second tanker气体) The gas in the 不断) is continuously exchanged to maintain sufficient oxygen supply to the animal cells in a high-oxygen environment (4). (4) After the 8-day culture, the yield of the cells is as high as about 2.2x1〇9ce. Obviously, the monthly b reaches the gas exchange rate, and the && ε high effect. Excellent sheep replacement, good cell growth efficiency and cell yield M381634 Therefore, the timing component (235) can control the operation of the pressurizing member (231), the pressure releasing member (234) and the backstop (233), and control the The medium body (24) can perform a vertical gas exchange between the first tank (211) and the second tank (221) and constitute a tidal sand supply mode, and has a good gas exchange rate, thereby allowing the culture to be cultivated. The animal cells can fully absorb the nutrients and oxygen contained in the medium (24), so that there is excellent cell growth efficiency and cell yield; on the other hand, the whole unit is composed of the first unit (21) and the second unit (22). And the control unit (23) is structured as 'simplified and low cost on the equipment, and is easier to operate and control, and can improve the two kinds of biological reaction devices (1) (3) of the prior art (please See the third and fourth figures for the high cost of equipment and difficult operation control. The prior art must have a control unit (23) in each reaction tank, and the present invention is to make the two reaction tanks have a height drop, so that the first unit (21) can naturally output the culture liquid by gravity, thereby saving at least one set of control. The use (cost) of the unit (23), which in turn saves energy. As shown in the second figure, another preferred embodiment of the present tidal bioreactor (2) differs from the foregoing preferred embodiment in that the first unit of the tidal sand bioreactor (2) 21) is in the low position, the second unit (22) is in the south position; and the control unit (23) is connected to the first unit (21) of the first unit (21), and can The first tank (211) of the first unit (21) performs pressure/pressure relief control inside. Further, the second tank (221) has a gas hole (224) for allowing air to enter and exit, and the second filter member (222) is disposed at the air hole (224) of the second tank (221). When the pressurizing member (231) of the control unit (23) is activated to pressurize the first tank (211), the medium 11 M381634 body (24) originally located in the first tank (211) will The feed pipe (25) is pushed all the way up to the second tank (221), so that the animal cells attached to the first carrier (212) are barely exposed to the air to fully absorb oxygen. And when the pressure releasing member (234) of the control unit (23) is activated to relieve the first tank (2n), the medium body (24) located in the second tank (221) is caused by Gravity flows back through the guiding tube (25) back into the first trough (21彳), so that the animal cells attached to the first carrier (212) are completely immersed therein so as to be fully absorbed therein. nutrient. Therefore, the present preferred embodiment can also control the medium body (24) to perform tidal circulation supply between the first tank (211) and the second tank (221) by simple equipment and simple operation. · The gas exchange rate is good, the cell growth efficiency is good, and the cell yield is high. In the prior art, it is necessary to provide a control unit (23) in each reaction tank, and the present invention is to make the second reaction tank as a grace drop so that the first unit (21) can naturally output the culture liquid by gravity, thereby saving at least one group. The use (cost) of the control unit (23), which in turn saves energy. BRIEF DESCRIPTION OF THE DRAWINGS The first figure is a schematic structural view of a preferred embodiment of the tidal bioreactor of the present invention. The first figure is a schematic structural view of another preferred embodiment of the tidal bioreactor of the present invention. . The second figure is a schematic view of the structure of a prior art bioreactor, illustrating a prior art bioreactor. The fourth figure is a structural view of a prior art bioreactor. 12 M381634 [Description of main components] (1) Bioreactor (12) Carrier (14) Lower reservoir (16) Feed tube (18) Siphon tube ' (20) Flow control valve (31) Upper incubator # ( 33) lower storage (2) tidal biological reaction (211) first trough (213) first filter (22) second unit (222) second filter (224) vent (231) pressurized part (233) Backstop (235) Timing component (24) Medium body (11) Incubator (13) Upper reservoir (15) Liquid medium (17) Overflow tube (19) Pomelo delivery tube (3) Bioreactor (32) Carrying bed (34) Medium setting (21) First unit (212) First carrier (214) Air hole (221) Second tank (223) Second carrier (23) Control unit (232) Flow control member (234) wave pressure member (236) (237) (238) timer (25) guide tube 13