TWM642644U

TWM642644U - Cell production system

Info

Publication number: TWM642644U
Application number: TW112202633U
Authority: TW
Inventors: 楊宏智
Original assignee: 揚朋科技股份有限公司
Priority date: 2023-03-23
Filing date: 2023-03-23
Publication date: 2023-06-11

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 medium storage area containing a medium, a first pump, a heating area, and a cell culture area containing a cell solution. The detection unit has a second pump and an observation 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. According to the detection result, the control unit controls the first pump to adjust the addition amount of the culture medium delivered from the culture medium storage area to the heating area for heating, and then to the cell culture area. Therefore, a closed-loop automated cell culture is achieved, reducing the risk of cell contamination caused by manual operations.

Description

Cell Preparation System

本新型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, 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 the 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, it is necessary to add an appropriate amount of new medium. In order to observe the state of the cells and count the number of cells, it is necessary to manually extract the cells in the cell culture device to observe the state of the cells and count the number of cells, and inject an appropriate amount of medium accordingly. However, in the process of culturing cells, the above-mentioned 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，本新型的目的，即在提供一種閉環式自動化細胞培養的細胞製備系統。Therefore, the purpose of the present invention is to provide a closed-loop automatic cell culture cell preparation system.

於是，本新型細胞製備系統，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 novel cell preparation system 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 medium storage area for containing a medium, a first pump, a heating area, and a cell culture area. The first pump is used to transport the medium from the medium storage area to the heating area for heating, and then to the cell culture area. The cell culture area stores a cell fluid containing several cells. The detection unit has a second pump and an observation counting module. The second pump is used to transport the cell liquid in the cell culture area to the observation and counting module, and the observation and counting module observes and counts the cells in the cell liquid 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. The control unit interprets the detection result of the detection signal after receiving the detection signal to generate a control parameter, and sends a control signal containing the control parameter to the first pump of the culture unit to drive the first pump A pump adjusts the addition amount of the culture medium from the culture medium storage area to the heating area for heating according to the control parameters, and then to the cell culture area.

本新型的功效在於：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 function of the present invention is: the at least one preparation device integrates the culture unit and the detection unit, so that the cells cultured in the cell culture area are transported to the observation and counting module through the second pump Observation and counting are carried out to confirm the state and quantity of cells, and then the control unit is used to judge and control the addition amount of the first pump to transport the medium from the medium storage area to the cell culture area, so as to achieve closed-loop automated cell Therefore, it can reduce labor costs and reduce the risk of cell contamination caused by manual operation, so as to improve the stability and yield of cell culture production.

參閱圖1至圖3，本新型細胞製備系統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 FIG. 1 to FIG. 3 , an embodiment of the novel cell preparation system 1 includes three preparation devices 2 , a microinjection unit 3 , a control unit 4 , and a touch screen 5 . Each preparation device 2 is used for culturing a single type of cells, such as NK cells, T cells, and the like.

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 medium storage area 61 has a medium container 611 containing a medium (not shown in the figure). The heating zone 63 has a heating container 631 fluidly connected to the culture medium container 611 for containing 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 solution (not shown in the figure), and a shaking mechanism 642 for the cell culture container 641 to be placed. The cell liquid contains a plurality of 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 ambient temperature of the culture medium storage area 61, and a temperature sensor (not shown) for controlling the environment 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, controlling the cell culture area 64 Another temperature controller (not shown) for ambient temperature, a gas detector (not shown) placed in the cell culture area 64 to detect an ambient _CO2 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 fluid. By controlling the culture environment conditions of the cells in the cell solution by the environment control module 65, the growth curve of the cells can grow exponentially. For example, the ambient temperature of the 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 The concentration is preferably 5%±1%, and the pH value of the cell fluid is preferably pH7.0~pH7.6. The environmental control module 65 can immediately the ambient temperature of the culture medium storage area 61, the ambient temperature of the cell culture area 64, the ambient _CO2 concentration and other gas concentrations of the cell culture area 64, and the cell fluid The numerical information such as the pH value of the cell 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, which is used to transport the medium in the medium container 611 to the heating container 631, and the medium in the heating container 631 is heated by the heating modules, and then passed through the second A pump 62 transports the heated culture medium from the heating vessel 631 to the cell culture vessel 641 of the cell culture area 64 . The cell culture container 641 is shaken by the shaking mechanism 642 to uniformly mix the newly added medium with the original cell liquid, and to distribute the cells evenly 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。2 to 4, the detection unit 7 is electrically connected to the control unit 4 and has a second pump 71, an observation 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 liquid in the cell culture vessel 641 to the observation and counting module 72 for sampling and testing. 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 fluidly connected to the microinjection unit 3 and a third inlet 763, a fluid connected to the waste tank 75 The discharge port 765, and a micro-channel 764 fluidly connected to the first inlet 761, the second inlet 762, the third inlet 763 and the discharge port 765 for circulation of the cell fluid.

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 the fluid connection between the buffer container 731 and the second pump 71 , and 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 should be noted that, in this embodiment, the 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 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 microinjector 31 fluidly connected to the second inlet 762 of the microfluidic chip 76 of each preparation device 2, a fluidically connected to the first microinjector 31 And contain a buffer tank 32 of a buffer (not shown), a second microinjector 33 that is fluidly connected to the third inlet 763 of the microfluidic chip 76 of each preparation device 2, a fluidly connected to the second The microinjector 33 contains a dye tank 34 for a dye (not shown in the figure), and a driving motor 35 electrically connected to the control unit 4 . The driving motor 35 drives the first micro-injector 31 and the second micro-injector 33 to act simultaneously through a screw mechanism, so that the first micro-injector 31 and the second micro-injector 33 respectively use the buffer solution in the buffer tank 32 The dye in the dye tank 34 is delivered into the micro-channel 764 at the same time.

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 liquid from the cell culture container 641 to the microchannel 764 through the first inlet 761 of the microfluidic chip 76 After that, the control unit 4 controls the drive motor 35 to drive the first microinjector 31 to deliver the buffer solution in the buffer tank 32 to the microchannel 764 through the second inlet 762, and in the microchannel 764 Pushing the flow of the cell fluid, the drive motor 35 simultaneously drives the second microinjector 33 to deliver the dye in the dye tank 34 to the micro-channel 764 through the third inlet 763, so that the dye will transfer the dye to the cell fluid. The cells are stained so as to observe the state 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 liquid in the micro-channel 764 through the microscope 771 and generates several 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 of the cell image information by the image processing unit is to observe the state and quantity of the cells in the cell solution in the micro-channel 764, and calculate the survival rate, cell density, The detection result of information such as the number of viable cells.

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。Next, the control unit 4 continues to control the drive motor 35 to drive the first microinjector 31 and the second microinjector 33 to deliver the buffer and the dye to the microchannel 764 at the same time, so as to continue to push the cell solution in the Flow in the micro-channel 764 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。Wherein, by adjusting the speed at which the driving motor 35 drives the first micro-injector 31 and the second micro-injector 33 to deliver the buffer and the dye to the micro-channel 764, the flow of the cell fluid in the micro-channel 764 can be controlled. The flow velocity in 764 makes it convenient for the camera 772 to take pictures of the cell fluid in the micro-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 message containing the control parameter. The signal is sent to the first pump 62 of the corresponding preparation device 2 to drive the first pump 62 to adjust according to the control parameters to transport the culture medium from the medium container 611 to the heating container 631 for heating, and then to the cell culture Addition amount of container 641. The coping mechanism has multiple modes to choose from, wherein a preset data table can be used to calculate the amount of culture medium to be added to the cell culture container 641 , or it can be set by the user according to requirements. The data table can refer to the following table 1. For the convenience of understanding, it is illustrated as follows. If the volume of the cell liquid in the cell culture container 641 is 10ml, and the number of these cells is unknown, the second pump 71 will transfer the cells Part of the cell liquid in the culture container 641 is sent to the observation and counting module 72 for sampling and detection, and when the cell liquid in the cell culture container 641 is calculated to have a detection result of 2,000,000 cells, the control unit 4 interprets the detection result as It is calculated that the cell liquid in the cell culture container 641 needs to be replenished to 20ml, so the additional culture medium that needs to be added to the cell culture container 641 is 10ml, and the first pump 62 is controlled to deliver 10ml of culture medium from the culture medium container 611 to the culture medium. The cell culture container 641 is mixed with the cell liquid currently in the cell culture container 641 . Table 1 number of living 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 transfer the buffer solution from the buffer container 731 through the detection tube valve module 74 is injected into the first inlet 761 of the microfluidic chip 76 , so that the buffer solution flows in the microfluidic channel 764 until it is discharged to the waste liquid tank 75 through the discharge port 765 . Therefore, each preparation device 2 cleans the residual cell fluid in the detection tube valve module 74 and the micro-channel 764 through the buffer solution in the buffer solution container 731 , so as to avoid affecting the test result 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 automatically add medium to the preparation device 2 and clean the detection tube valve module 74 and the micro-channel 764 simultaneously.

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 in the same machine, and these preparation devices 2 share the same culture medium storage area 61 and the same cell culture area 64, so the preparation devices 2 each The culture medium containers 611 are placed in the medium storage area 61 , and the cell culture containers 641 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。In addition to simultaneously cultivating the same type of cells, the three preparation devices 2 in the cell preparation system 1 can also independently cultivate different types of cells, 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 testing, and the other preparation device 2 is performing medium addition and detecting the tube valve module 74 Cleaning with microchannel 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 medium storage area 61 in each preparation device 2, the ambient temperature of the cell culture area 64, the ambient CO _{concentration} and other gas concentrations, and numerical information such as the pH value of the cell liquid in the cell culture container 641, and can display the image information of the cell liquid in the micro-channel 764 captured by the camera 772, so that the user can 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, and set the ambient temperature of the medium storage area 61 and the ambient 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, mobile phone, etc., through the communication network, so that the user can monitor the cell preparation system 1 in real time through the personal device, and immediately receive the abnormal operation of the cell preparation system 1 notification, or predict the state of the cell preparation system 1, the growth curve of the cells, and possible abnormal events, and notify in advance.

綜上所述，本新型細胞製備系統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，故確實能達成本新型的目的。In summary, the new cell preparation system 1 integrates the culture unit 6 and the detection unit 7 by 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 fluid in the cell culture container 641 to the microfluidic chip 76, and controls the cell fluid through the first microinjector 31 and the second microinjector 33 Moving in the micro-channel 764, the camera 772 takes pictures of the cell fluid, and the image processing unit calculates the detection results containing the information of the cells, and then the control unit 4 interprets the detection results And generate the control parameter according to the coping mechanism, so as to control the first pump 62 to adjust the amount of culture medium transported from the culture medium container 611 to the cell culture container 641 according to the control parameter, so as to achieve closed-loop automatic cell culture, so it can The cost of manpower is reduced, and the risk of cell contamination caused by manual operation is reduced, so as 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，僅為本新型的實施例而已，當不能以此限定本新型實施的範圍，凡是依本新型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，皆仍屬本新型專利涵蓋的範圍內。But the above-mentioned person is only the embodiment of the present invention, and should not limit the scope of implementation of the present invention with this, and all simple equivalent changes and modifications made according to the patent scope of the present application and the content of the patent specification are still within the scope of the present invention. Within the scope covered by this patent.

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: Micro injection unit 31: The first microinjector 32: buffer tank 33: Second Microsyringe 34: dye tank 35: Drive motor 4: Control unit 5: Touch screen 6: Culture unit 61: Culture medium storage area 611: Medium container 62: The first pump 63: heating zone 631:Heating container 64: cell culture area 641: cell culture vessel 642: shaking mechanism 65: Environmental 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: The first entrance 762: Second entrance 763: The third entrance 764: Microchannel 765: discharge port 77: Optical components 771:Microscope 772:camera 773: image processor

本新型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是本新型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 implementation manner with reference to the drawings, wherein: Fig. 1 is a perspective view of an embodiment of the novel cell preparation system; Fig. 2 is an incomplete front view of this embodiment; Fig. 3 is a functional block diagram of this embodiment; And Fig. 4 is a schematic diagram of 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: The first pump

63:加熱區 63: heating zone

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 vessel

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

A cell preparation system comprising: at least one preparation device, including a culture unit, and a detection unit, The culture unit has a medium storage area for containing a medium, a first pump, a heating area, and a cell culture area, and the first pump is used to transport the medium from the medium storage area to the After the heating zone is heated, it is transported to the cell culture zone, which stores a cell liquid 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 liquid in the cell culture area to the observation and counting module, and the observation and counting module Observing and counting the cells in the liquid to obtain a detection result, and outputting a detection signal containing the detection result; and A control unit, electrically connected to the culture unit and the detection unit, the control unit receives the detection signal and 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 amount of the cell solution transported from the medium storage area to the heating area for heating and then to the cell culture area according to the control parameters.

The cell preparation system as described in 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 components, the microfluidic chip has a micro flow channel for the flow of the cell fluid, the microinjection unit includes a first micro injector fluidly connected to the micro flow channel, the second pump is used in the cell culture area Part of the cell fluid is transported to the microfluidic chip, and the cell fluid is pushed into the microchannel by the first microinjector, and the optical component is used to observe and calculate the cell fluid in the microfluidic channel the number of the cells in the cytosol.

The cell preparation system according to claim 2, wherein the microinjection unit further comprises a second microinjector fluidly connected to the microfluidic channel, and a dye fluidly connected to the second microinjector and containing a dye The second microinjector delivers the dye to the micro-channel, so that the dye stains the cell fluid in the micro-channel.

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, 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.

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, and 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.

The cell preparation system according to claim 1, wherein the cell culture area of the at least one preparation device has a cell culture container containing the cell liquid, and a shaking mechanism for placing the cell culture container, the shaking mechanism It is used for shaking the cell culture container, so that the cells of the cell solution in the cell culture container are evenly distributed.

The cell preparation system according to claim 1, wherein the medium storage area of the at least one preparation device has a medium container for containing the medium, and the heating area has a heating container for containing the medium to be heated .

The cell preparation system according to claim 1, wherein both the first pump and the second pump are peristaltic pumps.