TWI833614B - cell preparation system - Google Patents

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TWI833614B
TWI833614B TW112110962A TW112110962A TWI833614B TW I833614 B TWI833614 B TW I833614B TW 112110962 A TW112110962 A TW 112110962A TW 112110962 A TW112110962 A TW 112110962A TW I833614 B TWI833614 B TW I833614B
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楊宏智
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揚朋科技股份有限公司
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Abstract

一種細胞製備系統，包含至少一製備裝置，及一控制單元。該製備裝置包括一培養單元及一檢測單元。該培養單元具有一容裝一培養基的培養基存放區、一第一幫浦、一加熱區，及一容裝一細胞液的細胞培養區。該檢測單元具有一第二幫浦，及一觀測計數模組。該第二幫浦將該細胞培養區中的細胞液輸送至該觀測計數模組進行觀測及計數，並得到一檢測結果。該控制單元根據該檢測結果控制該第一幫浦調整自該培養基存放區輸送培養基至該加熱區進行加熱，再輸送至該細胞培養區的添加量。因此達成閉環式自動化的細胞培養，減少人為操作產生的細胞汙染風險。A cell preparation system includes at least one preparation device and a control unit. The preparation device includes a culture unit and a detection unit. The culture unit has a culture medium storage area containing a culture medium, a first pump, a heating area, and a cell culture area containing a cell liquid. The detection unit has a second pump and an observation and counting module. The second pump transports the cell fluid in the cell culture area to the observation and counting module for observation and counting, and obtains a detection result. The control unit controls the first pump to adjust the amount of medium transported from the medium storage area to the heating area for heating and then transported to the cell culture area according to the detection result. This achieves closed-loop automated cell culture and reduces the risk of cell contamination caused by manual operations.

Description

細胞製備系統cell preparation system

本發明是有關於一種微生物學裝置，特別是指一種細胞製備系統。The present invention relates to a microbiological device, and in particular to a cell preparation system.

在現有的細胞培養技術中，透過一細胞培養裝置進行細胞的培養。在培養細胞的過程中隨著細胞狀態的變化以及細胞數目的增長，需適量添加新的培養基。而為了觀察細胞的狀態以及計算細胞的數量，需以人工的方式將該細胞培養裝置中的細胞抽取出，以觀察細胞的狀態及計算細胞的數量，並據以注入適量的培養基。然而在培養細胞的過程中需不斷地重複上述的流程，不僅耗時且耗費人力成本，還增加細胞汙染的風險。In existing cell culture technology, cells are cultured through a cell culture device. During the process of culturing cells, as the cell state changes and the number of cells increases, an appropriate amount of new culture medium needs to be added. In order to observe the state of the cells and count the number of cells, the cells in the cell culture device need to be extracted manually to observe the state of the cells and count the number of cells, and then inject an appropriate amount of culture medium accordingly. However, in the process of culturing cells, the above process needs to be repeated continuously, which is not only time-consuming and labor-intensive, but also increases the risk of cell contamination.

因此，本發明的目的，即在提供一種閉環式自動化細胞培養的細胞製備系統。Therefore, an object of the present invention is to provide a closed-loop automated cell culture cell preparation system.

於是，本發明細胞製備系統，包含至少一製備裝置，及一控制單元。該至少一製備裝置包括一培養單元，及一檢測單元。該培養單元具有一用於容裝一培養基的培養基存放區、一第一幫浦、一加熱區，及一細胞培養區。該第一幫浦用於將該培養基自該培養基存放區輸送至該加熱區進行加熱後，再輸送至該細胞培養區。該細胞培養區存放有一含數個細胞的細胞液。該檢測單元具有一第二幫浦，及一觀測計數模組。該第二幫浦用於將該細胞培養區中的該細胞液輸送至該觀測計數模組，該觀測計數模組對該細胞液中的該等細胞進行觀測及計數而得到一檢測結果，並輸出含有該檢測結果的一檢測信號。該控制單元電連接該培養單元與該檢測單元。該控制單元接收該檢測信號後對該檢測信號的該檢測結果進行判讀，以產生一控制參數，並傳送一含有該控制參數的控制信號至該培養單元的該第一幫浦，以驅動該第一幫浦根據該控制參數調整自該培養基存放區輸送該培養基至該加熱區進行加熱，再輸送至該細胞培養區的添加量。Therefore, the cell preparation system of the present invention includes at least one preparation device and a control unit. The at least one preparation device includes a culture unit and a detection unit. The culture unit has a culture medium storage area for containing a culture medium, a first pump, a heating area, and a cell culture area. The first pump is used to transport the culture medium from the culture medium storage area to the heating area for heating, and then transport it to the cell culture area. The cell culture area stores a cell solution containing several cells. The detection unit has a second pump and an observation and counting module. The second pump is used to transport the cell fluid in the cell culture area to the observation and counting module. The observation and counting module observes and counts the cells in the cell fluid to obtain a detection result, and A detection signal containing the detection result is output. The control unit is electrically connected to the culture unit and the detection unit. After receiving the detection signal, the control unit interprets the detection result of the detection signal to generate a control parameter, and transmits a control signal containing the control parameter to the first pump of the culture unit to drive the third pump. A pump adjusts the addition amount of the medium that is transported from the medium storage area to the heating area for heating and then transported to the cell culture area according to the control parameter.

本發明的功效在於：藉由該至少一製備裝置將該培養單元與該檢測單元進行整合，使得在該細胞培養區進行培養的該等細胞，經由該第二幫浦輸送至該觀測計數模組進行觀測及計數，以確認細胞的狀態及數量，再藉由該控制單元判斷並控制該第一幫浦自該培養基存放區輸送培養基至該細胞培養區的添加量，以達成閉環式自動化的細胞培養，故能降低人力成本，及減少人為操作時產生的細胞污染風險，以提高細胞培養生產的穩定性與良率。The effect of the present invention is to integrate the culture unit and the detection unit through the at least one preparation device, so that the cells cultured in the cell culture area are transported to the observation and counting module through the second pump. Observe and count to confirm the status and number of cells, and then use the control unit to judge and control the amount of medium added by the first pump to transport the medium from the medium storage area to the cell culture area to achieve closed-loop automated cell processing. culture, it can reduce labor costs and reduce the risk of cell contamination during manual operations, thereby improving the stability and yield of cell culture production.

參閱圖1至圖3，本發明細胞製備系統1的一實施例，包含三個製備裝置2、一微量注射單元3、一控制單元4，及一觸控式螢幕5。每一製備裝置2用於培養單一種類的細胞，例如NK細胞、T細胞等。Referring to FIGS. 1 to 3 , an embodiment of the cell preparation system 1 of the present invention includes three preparation devices 2 , a microinjection unit 3 , a control unit 4 , and a touch screen 5 . Each preparation device 2 is used to culture a single type of cells, such as NK cells, T cells, etc.

每一製備裝置2包括一培養單元6，及一檢測單元7。該培養單元6電連接該控制單元4並具有一培養基存放區61、一第一幫浦62、一加熱區63、一細胞培養區64，及一環境控制模組65。該培養基存放區61具有一容裝一培養基（圖未示）的培養基容器611。該加熱區63具有一流體連接該培養基容器611並用於容裝待加熱之該培養基的加熱容器631，及二分別設置於該加熱容器631上方及下方的加熱模組(圖未示)。該細胞培養區64具有一流體連接該加熱容器631並容裝有一細胞液（圖未示）的細胞培養容器641，及一供該細胞培養容器641放置的搖晃機構642。該細胞液中含有待培養的多個細胞。Each preparation device 2 includes a culture unit 6 and a detection unit 7 . The culture unit 6 is electrically connected to the control unit 4 and has a culture medium storage area 61 , a first pump 62 , a heating area 63 , a cell culture area 64 , and an environment control module 65 . The culture medium storage area 61 has a culture medium container 611 containing a culture medium (not shown). The heating area 63 has a heating container 631 fluidly connected to the culture medium container 611 and used to contain the culture medium to be heated, and two heating modules (not shown) respectively disposed above and below the heating container 631 . The cell culture area 64 has a cell culture container 641 fluidly connected to the heating container 631 and containing a cell fluid (not shown), and a shaking mechanism 642 for placing the cell culture container 641. The cell fluid contains multiple cells to be cultured.

該環境控制模組65具有放置於該培養基存放區61以偵測該培養基存放區61的一環境溫度的一溫度感測器(圖未示)、一控制該培養基存放區61的該環境溫度的一溫度控制器(圖未示)、放置於該細胞培養區64以偵測該細胞培養區64的一環境溫度的另一溫度感測器(圖未示)、控制該細胞培養區64的該環境溫度的另一溫度控制器(圖未示)、一放置於該細胞培養區64以偵測該細胞培養區64的一環境CO 2濃度與其他氣體濃度的氣體偵測器(圖未示)，及一放置於該細胞培養容器641內以檢測該細胞液的一酸鹼值的酸鹼度計(圖未示)。藉由該環境控制模組65控制該細胞液的該等細胞的培養環境條件，該等細胞的生長曲線能呈指數型的成長。舉例來說，該培養基存放區61的該環境溫度較佳為4℃±2℃，該細胞培養區64的該環境溫度較佳為37℃±1℃，該細胞培養區64的該環境CO 2濃度較佳為5%±1%，該細胞液的該酸鹼值較佳為pH7.0~pH7.6。該環境控制模組65能即時地將該培養基存放區61的該環境溫度、該細胞培養區64的該環境溫度、該細胞培養區64的該環境CO 2濃度以及其他氣體濃度，及該細胞液的該酸鹼值等數值資訊傳送至該控制單元4，以即時監控該等細胞的培養環境狀態。 The environment control module 65 has a temperature sensor (not shown) placed in the culture medium storage area 61 to detect an environmental temperature of the culture medium storage area 61 , and a temperature sensor that controls the environmental temperature of the culture medium storage area 61 . A temperature controller (not shown), another temperature sensor (not shown) placed in the cell culture area 64 to detect an ambient temperature of the cell culture area 64, and controlling the temperature of the cell culture area 64. Another temperature controller (not shown) of the ambient temperature, and a gas detector (not shown) placed in the cell culture area 64 to detect an ambient CO 2 concentration and other gas concentrations in the cell culture area 64 , and a pH meter (not shown) placed in the cell culture container 641 to detect a pH value of the cell solution. By controlling the culture environment conditions of the cells in the cell fluid through the environment control module 65, the growth curve of the cells can grow exponentially. For example, the ambient temperature of the culture medium storage area 61 is preferably 4°C ± 2°C, the ambient temperature of the cell culture area 64 is preferably 37°C ± 1°C, and the ambient CO 2 of the cell culture area 64 is preferably The concentration is preferably 5%±1%, and the pH value of the cell solution is preferably pH7.0~pH7.6. The environment control module 65 can instantly control the ambient temperature of the culture medium storage area 61, the ambient temperature of the cell culture area 64, the ambient CO 2 concentration and other gas concentrations of the cell culture area 64, and the cell fluid. The pH value and other numerical information is sent to the control unit 4 to monitor the culture environment status of the cells in real time.

該第一幫浦62為蠕動幫浦，用於將該培養基容器611中的培養基輸送至該加熱容器631，並由該等加熱模組對該加熱容器631內的培養基進行加熱，再經由該第一幫浦62將加熱後的培養基自該加熱容器631輸送至該細胞培養區64的該細胞培養容器641中。透過該搖晃機構642搖晃該細胞培養容器641，使新加入的培養基與原有的該細胞液均勻混合，並使該等細胞於混合後的細胞液中均勻分布。The first pump 62 is a peristaltic pump, used to transport the culture medium in the culture medium container 611 to the heating container 631, and heat the culture medium in the heating container 631 by the heating modules, and then through the third A pump 62 transports the heated culture medium from the heating container 631 to the cell culture container 641 of the cell culture area 64 . The cell culture container 641 is shaken by the shaking mechanism 642 to evenly mix the newly added culture medium and the original cell liquid, and to evenly distribute the cells in the mixed cell liquid.

參閱圖2至圖4，該檢測單元7電連接該控制單元4並具有一第二幫浦71、一觀測計數模組72、一緩衝液存放區73、一檢測管閥模組74，及一廢液槽75。Referring to Figures 2 to 4, the detection unit 7 is electrically connected to the control unit 4 and has a second pump 71, an observation and counting module 72, a buffer storage area 73, a detection tube valve module 74, and a Waste tank 75.

該第二幫浦71為蠕動幫浦，並用於將該細胞培養容器641中的細胞液輸送至該觀測計數模組72進行取樣檢測。該觀測計數模組72具有一微流體晶片76，及一光學組件77。該微流體晶片76具有一流體連接該第二幫浦71的第一入口761、流體連接該微量注射單元3的一第二入口762與一第三入口763、一流體連接該廢液槽75的排放口765，及一流體連接該第一入口761、該第二入口762、該第三入口763與該排放口765並供細胞液流通的微流道764。The second pump 71 is a peristaltic pump and is used to transport the cell fluid in the cell culture container 641 to the observation and counting module 72 for sampling and detection. The observation and counting module 72 has a microfluidic chip 76 and an optical component 77 . The microfluidic chip 76 has a first inlet 761 fluidly connected to the second pump 71 , a second inlet 762 and a third inlet 763 fluidly connected to the microinjection unit 3 , and a fluidly connected waste tank 75 . Discharge port 765, and a microfluidic channel 764 that fluidly connects the first inlet 761, the second inlet 762, the third inlet 763 and the discharge port 765 and allows cell fluid to circulate.

該光學組件77具有一顯微鏡771、一攝影機772，及一電連接該攝影機772的影像處理器773。The optical component 77 has a microscope 771, a camera 772, and an image processor 773 electrically connected to the camera 772.

該緩衝液存放區73具有一流體連接該第二幫浦71並容裝有一緩衝液（圖未示）的緩衝液容器731。The buffer storage area 73 has a buffer container 731 fluidly connected to the second pump 71 and containing a buffer (not shown).

該檢測管閥模組74用於控制流體連接該緩衝液容器731與該第二幫浦71，及該第二幫浦71與該微流體晶片76。The detection tube valve module 74 is used to control fluid connections between the buffer container 731 and the second pump 71 , and between the second pump 71 and the microfluidic chip 76 .

值得說明的是，在本實施例中，每一製備裝置2的該培養基容器611、該加熱容器631、該細胞培養容器641與該緩衝液容器731皆為袋裝容器，亦可為盒裝容器，故不以本實施例為限。It is worth noting that in this embodiment, the culture medium container 611, the heating container 631, the cell culture container 641 and the buffer container 731 of each preparation device 2 are all bagged containers or can also be boxed containers. , so it is not limited to this embodiment.

該微量注射單元3電連接該控制單元4，並包括一流體連接每一製備裝置2的該微流體晶片76的該第二入口762的第一微量注射器31、一流體連接該第一微量注射器31並容裝有一緩衝液（圖未示）的緩衝液槽32、一流體連接每一製備裝置2的該微流體晶片76的該第三入口763的第二微量注射器33、一流體連接該第二微量注射器33並容裝有一染劑（圖未示）的染劑槽34，及一電連接該控制單元4的驅動馬達35。該驅動馬達35透過螺桿機構來驅動該第一微量注射器31與該第二微量注射器33同時作動，以使該第一微量注射器31與該第二微量注射器33分別將該緩衝液槽32的緩衝液與該染劑槽34的染劑同時輸送至該微流道764內。The microinjection unit 3 is electrically connected to the control unit 4 and includes a first microsyringe 31 fluidly connected to the second inlet 762 of the microfluidic chip 76 of each preparation device 2 and a first microsyringe 31 fluidly connected to the second inlet 762 of the microfluidic chip 76 of each preparation device 2 . A buffer tank 32 containing a buffer solution (not shown), a second microsyringe 33 fluidly connected to the third inlet 763 of the microfluidic chip 76 of each preparation device 2, a second microsyringe 33 fluidly connected to the second The microsyringe 33 also contains a dye tank 34 containing a dye (not shown), and a drive motor 35 electrically connected to the control unit 4 . The driving motor 35 drives the first micro-syringe 31 and the second micro-syringe 33 to operate simultaneously through a screw mechanism, so that the first micro-syringe 31 and the second micro-syringe 33 respectively transfer the buffer solution in the buffer tank 32 The dye in the dye tank 34 is simultaneously transported into the microfluidic channel 764 .

在每一製備裝置2中，該控制單元4控制該第二幫浦71自該細胞培養容器641中將部分的細胞液經由該微流體晶片76的該第一入口761輸送至該微流道764內後，該控制單元4控制該驅動馬達35驅動該第一微量注射器31將該緩衝液槽32的緩衝液經由該第二入口762輸送至該微流道764，並於該微流道764內推送細胞液流動，該驅動馬達35同時驅動該第二微量注射器33將該染劑槽34的染劑經由該第三入口763輸送至該微流道764內，使染劑將細胞液中的該等細胞進行染色，以便於觀察該等細胞的狀態。In each preparation device 2 , the control unit 4 controls the second pump 71 to transport part of the cell fluid from the cell culture container 641 to the microfluidic channel 764 through the first inlet 761 of the microfluidic chip 76 Afterwards, the control unit 4 controls the driving motor 35 to drive the first microsyringe 31 to transport the buffer in the buffer tank 32 to the microfluidic channel 764 through the second inlet 762, and in the microfluidic channel 764. Pushing the flow of cell fluid, the driving motor 35 simultaneously drives the second microsyringe 33 to transport the dye in the dye tank 34 into the microfluidic channel 764 through the third inlet 763, so that the dye can transfer the dye in the cell fluid. Stain the cells to facilitate observation of the status of the cells.

該攝影機772經由該顯微鏡771對該微流道764內的細胞液進行拍攝並產生數個細胞影像資訊至該影像處理單元。該影像處理單元對該等細胞影像資訊進行影像辨識而得到一檢測結果，並將含有該檢測結果的一檢測信號傳送至該控制單元4。其中該影像處理單元對該等細胞影像資訊所做的影像辨識為觀察該微流道764中細胞液的該等細胞的狀態及數量，據以計算出含有該等細胞的存活率、細胞密度、活細胞數等資訊的該檢測結果。The camera 772 takes pictures of the cell fluid in the microfluidic channel 764 through the microscope 771 and generates a plurality of cell image information to the image processing unit. The image processing unit performs image recognition on the cell image information to obtain a detection result, and sends a detection signal containing the detection result to the control unit 4 . The image recognition performed by the image processing unit on the cell image information is to observe the status and number of the cells in the cell fluid in the microfluidic channel 764, and thereby calculate the survival rate, cell density, and The test results include viable cell count and other information.

接著，該控制單元4繼續控制該驅動馬達35驅動該第一微量注射器31與該第二微量注射器33分別將緩衝液與染劑同時輸送至該微流道764內，以繼續推送細胞液於該微流道764內流動，直至細胞液由該排放口765流至該廢液槽75。Then, the control unit 4 continues to control the driving motor 35 to drive the first microsyringe 31 and the second microsyringe 33 to deliver the buffer and dye to the microfluidic channel 764 simultaneously, so as to continue to push the cell fluid in the microfluidic channel 764 . The microfluidic channel 764 flows until the cell fluid flows from the discharge port 765 to the waste liquid tank 75 .

其中，藉由調整該驅動馬達35驅動該第一微量注射器31與該第二微量注射器33分別輸送緩衝液與染劑至該微流道764內的速度，而得以控制細胞液於該微流道764內的流動速度，使該攝影機772便於對該微流道764內的細胞液進行拍攝。Among them, by adjusting the speed at which the driving motor 35 drives the first microsyringe 31 and the second microsyringe 33 to respectively deliver buffer solution and dye into the microfluidic channel 764, the cell fluid in the microfluidic channel can be controlled. The flow speed in the microfluidic channel 764 makes it easy for the camera 772 to photograph the cell fluid in the microfluidic channel 764 .

該控制單元4於接收到其中一該製備裝置2的該檢測信號後，對該檢測信號的該檢測結果進行判讀，並能根據一應對機制產生一控制參數，並傳送一含有該控制參數的控制信號至對應的該製備裝置2的該第一幫浦62，以驅動該第一幫浦62根據該控制參數調整自該培養基容器611輸送培養基至該加熱容器631進行加熱，再輸送至該細胞培養容器641的添加量。該應對機制有多種模式可供選擇，其中可採用預設的一數據表來計算要添加至該細胞培養容器641之培養基的添加量，或由使用者依照需求進行設定。該數據表可參考下表1，為了方便理解，舉例說明如下，若當前該細胞培養容器641中的細胞液的體積為10ml，而該等細胞的數量未知，該第二幫浦71將該細胞培養容器641中部分的細胞液輸送至該觀測計數模組72進行取樣檢測，計算出該細胞培養容器641中的細胞液具有2000000個細胞的檢測結果時，則該控制單元4判讀該檢測結果以計算出需將該細胞培養容器641中的細胞液補充至20ml，因此該細胞培養容器641需另外添加的培養基為10ml，並控制該第一幫浦62自該培養基容器611輸送10ml的培養基至該細胞培養容器641中與當前該細胞培養容器641中的細胞液混合。 表1 活細胞數 細胞液體積(ml) 1000000 10 2000000 20 4000000 40 8000000 80 10000000 100 20000000 200 40000000 400 80000000 800 100000000 1000 After receiving the detection signal from one of the preparation devices 2, the control unit 4 interprets the detection result of the detection signal, generates a control parameter according to a response mechanism, and transmits a control containing the control parameter. The signal is sent to the corresponding first pump 62 of the preparation device 2 to drive the first pump 62 to transport the medium from the medium container 611 to the heating container 631 for heating according to the control parameter adjustment, and then to the cell culture. The amount added to container 641. The response mechanism has multiple modes to choose from, in which a preset data table can be used to calculate the amount of culture medium to be added to the cell culture container 641, or the user can set it according to needs. The data table can be referred to Table 1 below. For ease of understanding, an example is as follows. If the volume of cell fluid in the cell culture container 641 is currently 10 ml, and the number of cells is unknown, the second pump 71 will Part of the cell fluid in the culture container 641 is transported to the observation and counting module 72 for sampling and detection. When it is calculated that the cell fluid in the cell culture container 641 has a detection result of 2,000,000 cells, the control unit 4 interprets the detection result to determine It is calculated that the cell liquid in the cell culture container 641 needs to be replenished to 20 ml, so the additional culture medium that needs to be added to the cell culture container 641 is 10 ml, and the first pump 62 is controlled to transport 10 ml of culture medium from the culture medium container 611 to the cell culture container 641 . The cell liquid in the cell culture container 641 is mixed with the cell liquid currently in the cell culture container 641 . Table 1 number of viable cells Cell fluid volume (ml) 1000000 10 2000000 20 4000000 40 8000000 80 10000000 100 20000000 200 40000000 400 80000000 800 100000000 1000

該控制單元4在接收到其中一該製備裝置2的該檢測信號後，即控制對應的該製備裝置2的該第二幫浦71自該緩衝液容器731將緩衝液經由該檢測管閥模組74注入該微流體晶片76的該第一入口761，使該緩衝液於該微流道764內流動，直至經由該排放口765排放至該廢液槽75。因此，每一製備裝置2透過該緩衝液容器731中的緩衝液來清洗該檢測管閥模組74與該微流道764中殘餘的細胞液，以避免影響下次取樣檢測時的檢測結果。After receiving the detection signal from one of the preparation devices 2, the control unit 4 controls the second pump 71 of the corresponding preparation device 2 to pass the buffer from the buffer container 731 through the detection pipe valve module. 74 is injected into the first inlet 761 of the microfluidic chip 76, causing the buffer to flow in the microfluidic channel 764 until it is discharged to the waste tank 75 through the discharge port 765. Therefore, each preparation device 2 uses the buffer in the buffer container 731 to clean the remaining cell fluid in the detection tube valve module 74 and the microfluidic channel 764 to avoid affecting the detection results of the next sampling test.

該控制單元4在接收其中一該製備裝置2的該檢測信號後，可對該製備裝置2同時進行培養基的自動添加以及該檢測管閥模組74與該微流道764的清洗作業。After receiving the detection signal from one of the preparation devices 2 , the control unit 4 can simultaneously automatically add culture medium to the preparation device 2 and clean the detection tube valve module 74 and the microfluidic channel 764 .

於本實施例中，該細胞製備系統1的三個製備裝置2整合在同一機台中，而該等製備裝置2共用同一培養基存放區61，及同一細胞培養區64，因此該等製備裝置2各自的該培養基容器611皆放置於該培養基存放區61，該等製備裝置2各自的該細胞培養容器641皆放置於該細胞培養區64。In this embodiment, the three preparation devices 2 of the cell preparation system 1 are integrated into the same machine, and the preparation devices 2 share the same culture medium storage area 61 and the same cell culture area 64. Therefore, each of the preparation devices 2 The culture medium containers 611 are placed in the culture medium storage area 61 , and the cell culture containers 641 of each of the preparation devices 2 are placed in the cell culture area 64 .

該細胞製備系統1中的三個製備裝置2除了可同時培養同 一種類的細胞，亦可分別獨立培養不同種類的細胞，並且能分別進行不同的動作。舉例來說，當其中一該製備裝置2在進行細胞培養時，另一該製備裝置2在進行細胞的取樣檢測，而再另一該製備裝置2在進行培養基的添加以及檢測管閥模組74與微流道764的清洗。The three preparation devices 2 in the cell preparation system 1 can not only culture cells of the same type at the same time, but also independently culture cells of different types, and can perform different actions respectively. For example, when one of the preparation devices 2 is performing cell culture, the other preparation device 2 is performing cell sampling and detection, and the other preparation device 2 is adding culture medium and detecting the valve module 74 Cleaning with Microfluidic Channel 764.

該觸控式螢幕5電連接該控制單元4，並能用於顯示每一製備裝置2中該培養基存放區61的該環境溫度、該細胞培養區64的該環境溫度、該環境CO 2濃度及其他氣體濃度，以及該細胞培養容器641中該細胞液的該酸鹼值等數值資訊，並能顯示該攝影機772拍攝該微流道764中該細胞液的影像資訊，讓使用者能即時確認該等細胞的生長狀況。使用者亦能透過該觸控式螢幕5操控該控制單元4來設定每一製備裝置2的該應對機制，以及設定該培養基存放區61的該環境溫度與該細胞培養區64的該環境溫度等。此外，該控制單元4還可經由通訊網路遠端連接使用者的個人裝置，如電腦、手機等，讓使用者能透過個人裝置即時監控該細胞製備系統1、即時接收該細胞製備系統1運作異常的通知，或是可預測該細胞製備系統1的狀態、細胞的生長曲線，以及可能發生的異常事件，並提前通知。 The touch screen 5 is electrically connected to the control unit 4 and can be used to display the ambient temperature of the culture medium storage area 61 in each preparation device 2, the ambient temperature of the cell culture area 64, the ambient CO 2 concentration and Other gas concentrations, as well as numerical information such as the pH value of the cell fluid in the cell culture container 641, and can display the image information of the cell fluid in the microfluidic channel 764 captured by the camera 772, allowing the user to instantly confirm the and other cell growth conditions. The user can also control the control unit 4 through the touch screen 5 to set the response mechanism of each preparation device 2, as well as set the environmental temperature of the culture medium storage area 61 and the environmental temperature of the cell culture area 64, etc. . In addition, the control unit 4 can also be remotely connected to the user's personal device, such as a computer, a mobile phone, etc. via a communication network, so that the user can real-time monitor the cell preparation system 1 through the personal device and receive real-time notification of abnormal operation of the cell preparation system 1 notifications, or can predict the status of the cell preparation system 1, the growth curve of the cells, and possible abnormal events, and notify them in advance.

綜上所述，本發明細胞製備系統1，藉由每一該製備裝置2將該培養單元6與該檢測單元7進行整合，使得細胞能在該培養單元6的該細胞培養容器641中進行培養，並由該檢測單元7的該第二幫浦71將該細胞培養容器641中部分的細胞液輸送至該微流體晶片76，透過該第一微量注射器31與該第二微量注射器33控制細胞液於該微流道764內的移動，再由該攝影機772對細胞液進行拍攝，並由該影像處理單元計算出含有該等細胞之資訊的檢測結果，再藉由該控制單元4判讀該檢測結果並根據該應對機制產生該控制參數，以控制該第一幫浦62根據該控制參數調整自該培養基容器611輸送培養基至該細胞培養容器641的添加量，達成閉環式自動化的細胞培養，故能降低人力成本，並減少人為操作時產生的細胞污染風險，以提高細胞培養生產的穩定性與良率，故確實能達成本發明的目的。In summary, the cell preparation system 1 of the present invention integrates the culture unit 6 and the detection unit 7 through each preparation device 2 so that cells can be cultured in the cell culture container 641 of the culture unit 6 , and the second pump 71 of the detection unit 7 transports part of the cell liquid in the cell culture container 641 to the microfluidic chip 76 , and controls the cell liquid through the first micro-syringe 31 and the second micro-syringe 33 As the cell fluid moves within the microfluidic channel 764, the camera 772 captures the cell fluid, and the image processing unit calculates a detection result containing information about the cells, and then the control unit 4 interprets the detection result. And generate the control parameter according to the response mechanism to control the first pump 62 to adjust the addition amount of the medium transported from the medium container 611 to the cell culture container 641 according to the control parameter to achieve closed-loop automated cell culture, so it can Reduce labor costs and reduce the risk of cell contamination generated during manual operations to improve the stability and yield of cell culture production, so the purpose of the present invention can indeed be achieved.

惟以上所述者，僅為本發明的實施例而已，當不能以此限定本發明實施的範圍，凡是依本發明申請專利範圍及專利說明書內容所作的簡單的等效變化與修飾，皆仍屬本發明專利涵蓋的範圍內。However, the above are only examples of the present invention. They cannot be used to limit the scope of the present invention. All simple equivalent changes and modifications made based on the patent scope of the present invention and the contents of the patent specification are still within the scope of the present invention. within the scope covered by the patent of this invention.

1:細胞製備系統 2:製備裝置 3:微量注射單元 31:第一微量注射器 32:緩衝液槽 33:第二微量注射器 34:染劑槽 35:驅動馬達 4:控制單元 5:觸控式螢幕 6:培養單元 61:培養基存放區 611:培養基容器 62:第一幫浦 63:加熱區 631:加熱容器 64:細胞培養區 641:細胞培養容器 642:搖晃機構 65:環境控制模組 7:檢測單元 71:第二幫浦 72:觀測計數模組 73:緩衝液存放區 731:緩衝液容器 74:檢測管閥模組 75:廢液槽 76:微流體晶片 761:第一入口 762:第二入口 763:第三入口 764:微流道 765:排放口 77:光學組件 771:顯微鏡 772:攝影機 773:影像處理器1: Cell preparation system 2: Preparation device 3:Microinjection unit 31: The first microsyringe 32:Buffer tank 33: Second microsyringe 34:Dye tank 35: Drive motor 4:Control unit 5:Touch screen 6:Cultivation unit 61: Culture medium storage area 611: Medium container 62:First Pump 63:Heating area 631: Heating container 64: Cell culture area 641: Cell culture container 642: Shaking mechanism 65:Environment control module 7:Detection unit 71:Second pump 72: Observation counting module 73: Buffer storage area 731: Buffer container 74: Detection pipe valve module 75: Waste liquid tank 76:Microfluidic chip 761:First entrance 762:Second entrance 763:The third entrance 764: Microfluidic channel 765: Discharge port 77:Optical components 771:Microscope 772:Camera 773:Image processor

本發明的其他的特徵及功效，將於參照圖式的實施方式中清楚地呈現，其中： 圖1是本發明細胞製備系統的一實施例的一立體圖； 圖2是該實施例的一不完整的前視圖； 圖3是該實施例的一功能方塊圖； 及 圖4是該實施例的一製備裝置的一微流體晶片的管路連接示意圖。 Other features and effects of the present invention will be clearly presented in the embodiments with reference to the drawings, in which: Figure 1 is a perspective view of an embodiment of the cell preparation system of the present invention; Figure 2 is an incomplete front view of this embodiment; Figure 3 is a functional block diagram of this embodiment; and Figure 4 is a schematic diagram of the pipeline connection of a microfluidic chip in a preparation device of this embodiment.

1:細胞製備系統 1: Cell preparation system

2:製備裝置 2: Preparation device

5:觸控式螢幕 5:Touch screen

61:培養基存放區 61: Culture medium storage area

611:培養基容器 611: Medium container

62:第一幫浦 62:First Pump

63:加熱區 63:Heating area

631:加熱容器 631: Heating container

64:細胞培養區 64: Cell culture area

641:細胞培養容器 641:Cell culture container

642:搖晃機構 642: Shaking mechanism

71:第二幫浦 71:Second pump

72:觀測計數模組 72: Observation counting module

73:緩衝液存放區 73: Buffer storage area

731:緩衝液容器 731: Buffer container

74:檢測管閥模組 74: Detection pipe valve module

75:廢液槽 75: Waste liquid tank

Claims (8)

一種細胞製備系統，包含： 至少一製備裝置，包括一培養單元，及一檢測單元， 該培養單元具有一用於容裝一培養基的培養基存放區、一第一幫浦、一加熱區，及一細胞培養區，該第一幫浦用於將該培養基自該培養基存放區輸送至該加熱區進行加熱後，再輸送至該細胞培養區，該細胞培養區存放一含數個細胞的細胞液， 該檢測單元具有一第二幫浦，及一觀測計數模組，該第二幫浦用於將該細胞培養區中的該細胞液輸送至該觀測計數模組，該觀測計數模組對該細胞液中的該等細胞進行觀測及計數而得到一檢測結果，並輸出含有該檢測結果的一檢測信號；及 一控制單元，電連接該培養單元與該檢測單元，該控制單元接收該檢測信號後對該檢測信號的該檢測結果進行判讀，以產生一控制參數，並傳送一含有該控制參數的控制信號至該培養單元的該第一幫浦，以驅動該第一幫浦根據該控制參數調整自該培養基存放區輸送該細胞液至該加熱區進行加熱，再輸送至該細胞培養區的添加量。 A cell preparation system comprising: At least one preparation device includes a culture unit and a detection unit, The culture unit has a culture medium storage area for containing a culture medium, a first pump, a heating area, and a cell culture area. The first pump is used to transport the culture medium from the culture medium storage area to the cell culture area. After heating in the heating area, it is then transported to the cell culture area, which stores a cell fluid containing several cells. The detection unit has a second pump and an observation and counting module. The second pump is used to transport the cell fluid in the cell culture area to the observation and counting module. The observation and counting module monitors the cells. Observe and count the cells in the liquid to obtain a detection result, and output a detection signal containing the detection result; and A control unit is electrically connected to the culture unit and the detection unit. After receiving the detection signal, the control unit interprets the detection result of the detection signal to generate a control parameter and transmits a control signal containing the control parameter to The first pump of the culture unit is used to drive the first pump to adjust the addition amount of the cell fluid transported from the medium storage area to the heating area for heating and then transported to the cell culture area according to the control parameter. 如請求項1所述的細胞製備系統，還包含一電連接該控制單元微量注射單元，其中，該至少一製備裝置的該觀測計數模組具有一供該細胞液流通的微流體晶片，及一光學組件，該微流體晶片具有一供該細胞液流通的微流道，該微量注射單元包括一流體連接該微流道的第一微量注射器，該第二幫浦用於將該細胞培養區中部分的該細胞液輸送至該微流體晶片，並由該第一微量注射器將該細胞液於該微流道內推送，該光學組件用於對該微流道內的該細胞液進行觀測並計算該細胞液中該等細胞的數量。The cell preparation system according to claim 1, further comprising a microinjection unit electrically connected to the control unit, wherein the observation and counting module of the at least one preparation device has a microfluidic chip for the circulation of the cell fluid, and a Optical component, the microfluidic chip has a microfluidic channel for the circulation of the cell fluid, the microinjection unit includes a first microsyringe fluidly connected to the microfluidic channel, and the second pump is used to inject the cell culture area into the A portion of the cell fluid is transported to the microfluidic chip, and the first microsyringe pushes the cell fluid in the microfluidic channel. The optical component is used to observe and calculate the cell fluid in the microfluidic channel. The number of these cells in the cell fluid. 如請求項2所述的細胞製備系統，其中，該微量注射單元還包括一流體連接該微流道的第二微量注射器，及一流體連接該第二微量注射器並容裝有一染劑的染劑槽，該第二微量注射器將該染劑輸送至該微流道內，使該染劑對該微流道內的該細胞液進行染色。The cell preparation system of claim 2, wherein the microinjection unit further includes a second microsyringe fluidly connected to the microfluidic channel, and a dye fluidly connected to the second microsyringe and containing a dye. The second microsyringe transports the dye into the microfluidic channel, so that the dye stains the cell fluid in the microfluidic channel. 如請求項2所述的細胞製備系統，其中，該至少一製備裝置的該檢測單元還具有一容裝有一緩衝液的緩衝液存放區，及一檢測管閥模組，該檢測管閥模組用於控制流體連接該緩衝液存放區與該第二幫浦，及該第二幫浦與該微流體晶片，該控制單元控制該第二幫浦自該緩衝液存放區經由該檢測管閥模組將該緩衝液輸送至該微流體晶片中，並於該微流道內推送，以同時清洗該檢測管閥模組與該微流體晶片的該微流道。The cell preparation system according to claim 2, wherein the detection unit of the at least one preparation device also has a buffer storage area containing a buffer solution, and a detection tube valve module, the detection tube valve module For controlling the fluid connection between the buffer storage area and the second pump, and the second pump and the microfluidic chip, the control unit controls the second pump from the buffer storage area through the detection tube valve module The group transports the buffer solution into the microfluidic chip and pushes it in the microfluidic channel to simultaneously clean the detection tube valve module and the microfluidic channel of the microfluidic chip. 如請求項1所述的細胞製備系統，其中，該至少一製備裝置的該培養單元還具有一電連接該控制單元的環境控制模組，該環境控制模組用於偵測並控制該培養基存放區的一環境溫度、該細胞培養區的一環境溫度、一環境CO 2濃度，及該細胞液的一酸鹼值。 The cell preparation system according to claim 1, wherein the culture unit of the at least one preparation device also has an environment control module electrically connected to the control unit, the environment control module is used to detect and control the storage of the culture medium an ambient temperature of the zone, an ambient temperature of the cell culture zone, an ambient CO 2 concentration, and a pH value of the cell fluid. 如請求項1所述的細胞製備系統，其中，該至少一製備裝置的該細胞培養區具有一容裝該細胞液的細胞培養容器，及一供該細胞培養容器放置的搖晃機構，該搖晃機構用於搖晃該細胞培養容器，使該細胞培養容器中的該細胞液的該等細胞均勻分布。The cell preparation system of claim 1, wherein the cell culture area of the at least one preparation device has a cell culture container containing the cell fluid, and a shaking mechanism for placing the cell culture container, the shaking mechanism It is used to shake the cell culture container to evenly distribute the cells in the cell liquid in the cell culture container. 如請求項1所述的細胞製備系統，其中，該至少一製備裝置的該培養基存放區具有一容裝該培養基的培養基容器，該加熱區具有一用於容裝待加熱之該培養基的加熱容器。The cell preparation system of claim 1, wherein the medium storage area of the at least one preparation device has a medium container for holding the medium, and the heating area has a heating container for holding the medium to be heated. . 如請求項1所述的細胞製備系統，其中，該第一幫浦與該第二幫浦皆為蠕動幫浦。The cell preparation system as claimed in claim 1, wherein both the first pump and the second pump are peristaltic pumps.
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