TWI656218B - Method and device for generating adaptive cell culture parameters and storage medium thereof - Google Patents

Method and device for generating adaptive cell culture parameters and storage medium thereof Download PDF

Info

Publication number
TWI656218B
TWI656218B TW106139303A TW106139303A TWI656218B TW I656218 B TWI656218 B TW I656218B TW 106139303 A TW106139303 A TW 106139303A TW 106139303 A TW106139303 A TW 106139303A TW I656218 B TWI656218 B TW I656218B
Authority
TW
Taiwan
Prior art keywords
cell
basic control
control factor
adaptive
culture
Prior art date
Application number
TW106139303A
Other languages
Chinese (zh)
Other versions
TW201918561A (en
Inventor
李元發
廖智菁
賴豊文
黃智宏
Original Assignee
財團法人工業技術研究院
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 財團法人工業技術研究院 filed Critical 財團法人工業技術研究院
Priority to TW106139303A priority Critical patent/TWI656218B/en
Application granted granted Critical
Publication of TWI656218B publication Critical patent/TWI656218B/en
Publication of TW201918561A publication Critical patent/TW201918561A/en

Links

Landscapes

  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

一種適應性細胞培養參數產生的方法,用以培養第一細胞為目標細胞,上述方法包括:根據上述第一細胞之一第一細胞種類及一目標細胞特性由一資料庫中搜尋一般化細胞培養參數,以建立一基本控制因子序列表;根據上述第一細胞種類、上述目標細胞特性及上述基本控制因子序列表產生適應性細胞培養參數;根據上述適應性細胞培養參數培養上述第一細胞,並產生一培養結果;以及根據上述培養結果調整上述適應性細胞培養參數。 A method for producing adaptive cell culture parameters for culturing a first cell as a target cell, the method comprising: searching for a generalized cell culture from a database according to a first cell type and a target cell characteristic of the first cell; a parameter to establish a basic control factor sequence table; generating adaptive cell culture parameters according to the first cell type, the target cell characteristics, and the basic control factor sequence table; and cultivating the first cell according to the adaptive cell culture parameter, and A culture result is produced; and the above adaptive cell culture parameters are adjusted according to the above culture results.

Description

適應性細胞培養參數產生的方法、裝置及其儲存 媒體 Method, device and storage for adaptive cell culture parameter generation media

本揭露係涉及一種屬於生物工程技術領域的細胞工程技術,且更加具體地說係有關於一種適應性細胞培養參數產生的方法、裝置及其儲存媒體。 The present disclosure relates to a cell engineering technique pertaining to the field of bioengineering technology, and more particularly to a method, apparatus and storage medium for the production of adaptive cell culture parameters.

細胞培養的過程受到充滿許多變數的影響,例如環境控制參數(腔體溫度、培養箱CO2或低氧濃度、濕度、…)、細胞培養控制參數(pH濃度、培養基及生長因子添加種類及液量、更換液時間、細胞培養時間、胰蛋白處理時間、汙染檢測結果、細胞接種數量及密度、細胞生長數目不如預期、…)等參數。 The process of cell culture is affected by many variables, such as environmental control parameters (cavity temperature, incubator CO2 or hypoxic concentration, humidity, ...), cell culture control parameters (pH concentration, medium and growth factor addition type and amount) Parameters such as replacement time, cell culture time, trypsin treatment time, contamination detection results, cell inoculation number and density, cell growth number not as expected, ...).

不同種類之細胞培養,其控制參數亦不盡相同。當參數控制不當時,將導致培養出來的細胞之細胞特性不符預期或發生細胞死亡。此外,周遭環境因素的變化也會影響細胞生長之結果。由於細胞取自母體的條件不同且外在培養環境改變,皆可能發生同樣培養參數卻無法使用之問題。 Different types of cell culture have different control parameters. When the parameters are not properly controlled, the cell characteristics of the cultured cells will be inconsistent with the expected or cell death. In addition, changes in environmental factors around the environment can also affect the results of cell growth. Since the conditions in which the cells are taken from the mother are different and the external culture environment is changed, the same culture parameters may occur but cannot be used.

因此,有必要提供一種適應性細胞培養參數產生的方法、裝置及其儲存媒體,除了培養參數產生外,能夠避免細胞 死亡,提高細胞生長之特性以符合預期。 Therefore, it is necessary to provide a method, a device and a storage medium for the production of adaptive cell culture parameters, which can avoid cells in addition to the culture parameters. Death, improving the characteristics of cell growth in line with expectations.

以下揭露的內容僅為示例性的,且不意指以任何方式加以限制。除所述說明方面、實施方式和特徵之外,透過參照附圖和下述具體實施方式,其他方面、實施方式和特徵也將顯而易見。即,以下揭露的內容被提供以介紹概念、重點、益處及本文所描述新穎且非顯而易見的技術優勢。所選擇,非所有的,實施例將進一步詳細描述如下。因此,以下揭露的內容並不意旨在所要求保護主題的必要特徵,也不意旨在決定所要求保護主題的範圍中使用。 The disclosures below are merely exemplary and are not meant to be limiting in any way. Other aspects, embodiments, and features will be apparent from the description and drawings. That is, the following disclosure is provided to introduce concepts, advantages, benefits, and novel and non-obvious technical advantages described herein. Selected, not all, embodiments will be described in further detail below. Therefore, the following disclosure is not intended to be an essential feature of the claimed subject matter, and is not intended to be used in the scope of the claimed subject matter.

本揭露提供一種適應性細胞培養參數產生的方法、裝置及其儲存媒體。 The present disclosure provides a method, apparatus, and storage medium for the production of adaptive cell culture parameters.

本揭露提出一種適應性細胞培養參數產生的方法,用以培養第一細胞為目標細胞,上述方法包括:根據上述第一細胞之一第一細胞種類及一目標細胞特性由一資料庫中搜尋一般化細胞培養參數,以建立一基本控制因子序列表;根據上述第一細胞種類、上述目標細胞特性及上述基本控制因子序列表產生適應性細胞培養參數;根據上述適應性細胞培養參數培養上述第一細胞,並產生一培養結果;以及根據上述培養結果調整上述適應性細胞培養參數。 The present disclosure proposes a method for generating adaptive cell culture parameters for culturing a first cell as a target cell, the method comprising: searching for a general database according to a first cell type and a target cell characteristic of the first cell; The cell culture parameters are used to establish a basic control factor sequence table; the adaptive cell culture parameters are generated according to the first cell type, the target cell characteristics, and the basic control factor sequence table; and the first cell is cultured according to the above adaptive cell culture parameters. The cells are produced and a culture result is produced; and the above adaptive cell culture parameters are adjusted according to the above culture results.

本揭露再提出一種適應性細胞培養參數產生的裝置,用以培養第一細胞為目標細胞,上述裝置包括:一控制電路;一處理器,安裝至上述控制電路中;以及一記憶體,安裝至上述控制電路中並且耦接至上述處理器;其中上述處理器配置用以執行 儲存於上述記憶體中之一程式碼以執行:根據上述第一細胞之一第一細胞種類及一目標細胞特性由一資料庫中搜尋一般化細胞培養參數,以建立一基本控制因子序列表;根據上述第一細胞種類、上述目標細胞特性及上述基本控制因子序列表產生適應性細胞培養參數;根據上述適應性細胞培養參數培養上述第一細胞,並產生一培養結果;以及根據上述培養結果調整上述適應性細胞培養參數。 The present disclosure further provides a device for generating adaptive cell culture parameters for culturing a first cell as a target cell, the device comprising: a control circuit; a processor mounted to the control circuit; and a memory mounted to The above control circuit is coupled to the processor; wherein the processor is configured to execute Storing a code in the memory to perform: searching a generalized cell culture parameter from a database according to the first cell type and a target cell characteristic of the first cell to establish a basic control factor sequence table; Obtaining adaptive cell culture parameters according to the first cell type, the target cell characteristics, and the basic control factor sequence table; cultivating the first cell according to the adaptive cell culture parameter, and generating a culture result; and adjusting according to the culture result The above adaptive cell culture parameters.

本揭露又提出一種儲存媒體,經由一裝置讀取上述儲存媒體所儲存之程式碼後以執行一適應性細胞培養參數產生方法,用以培養第一細胞為目標細胞,其中上述方法包括以下步驟:根據上述第一細胞之一第一細胞種類及一目標細胞特性由一資料庫中搜尋一般化細胞培養參數,以建立一基本控制因子序列表;根據上述第一細胞種類、上述目標細胞特性及上述基本控制因子序列表產生適應性細胞培養參數;根據上述適應性細胞培養參數培養上述第一細胞,並產生一培養結果;以及根據上述培養結果調整上述適應性細胞培養參數。 The disclosure further provides a storage medium for reading a code stored in the storage medium via a device to perform an adaptive cell culture parameter generation method for cultivating the first cell as a target cell, wherein the method comprises the following steps: Generating a generalized cell culture parameter from a database according to the first cell type and a target cell characteristic of the first cell, to establish a basic control factor sequence table; according to the first cell type, the target cell characteristics, and the above The basic control factor sequence table generates adaptive cell culture parameters; the first cells are cultured according to the above adaptive cell culture parameters, and a culture result is produced; and the above adaptive cell culture parameters are adjusted according to the above culture results.

100‧‧‧細胞培養系統 100‧‧‧ cell culture system

110‧‧‧管理裝置 110‧‧‧Management device

120‧‧‧培養箱 120‧‧‧ incubator

122‧‧‧培養皿 122‧‧‧ Petri dishes

124‧‧‧細胞培養基 124‧‧‧ cell culture medium

126‧‧‧培養細胞 126‧‧‧Cultivated cells

130‧‧‧儲存裝置 130‧‧‧Storage device

200‧‧‧電子裝置 200‧‧‧Electronic devices

202‧‧‧輸入裝置 202‧‧‧ Input device

204‧‧‧輸出裝置 204‧‧‧Output device

206‧‧‧控制電路 206‧‧‧Control circuit

208‧‧‧中央處理器 208‧‧‧Central Processing Unit

210‧‧‧記憶體 210‧‧‧ memory

212‧‧‧執行程式碼 212‧‧‧Executing code

214‧‧‧收發器 214‧‧‧ transceiver

300‧‧‧方法 300‧‧‧ method

S305、S310、S315、S320‧‧‧步驟 S305, S310, S315, S320‧‧‧ steps

400‧‧‧方法 400‧‧‧ method

S405、S410、S415‧‧‧步驟 Steps S405, S410, S415‧‧

600‧‧‧方法 600‧‧‧ method

S605、S610、S615、S620‧‧‧步驟 S605, S610, S615, S620‧‧‧ steps

900‧‧‧方法 900‧‧‧ method

S905、S910、S915、S920‧‧‧步驟 S905, S910, S915, S920‧‧‧ steps

1200‧‧‧方法 1200‧‧‧ method

S1205、S1210、S1215、S1220、S1225‧‧‧步驟 S1205, S1210, S1215, S1220, S1225‧‧‧ steps

附圖被包括以提供本揭露進一步理解且被合併並組成本揭露的一部分。附圖係說明本揭露的實施例且連同描述一起用以解釋本揭露的原理。其可理解附圖不一定按比例描繪,一些元件可以超過在實際實施方式的大小來顯示,以清楚地說明本揭露的概念。 The figures are included to provide a further understanding of the disclosure and are incorporated in and constitute a part of the disclosure. The drawings illustrate the embodiments of the disclosure and, together with the description, illustrate the principles of the disclosure. It is understood that the drawings are not necessarily to scale,

第1圖係顯示根據本揭露一實施例中適應性細胞培養參數產生之細胞培養系統的示例性示意圖。 1 is an exemplary schematic diagram showing a cell culture system for producing adaptive cell culture parameters in accordance with an embodiment of the present disclosure.

第2圖係以一方式表示根據本揭露一實施例所述之電子裝置之簡化功能方塊圖。 FIG. 2 is a simplified functional block diagram of an electronic device according to an embodiment of the present disclosure.

第3圖係顯示根據本揭露一實施例中一種適應性細胞培養參數產生的方法之流程圖。 Figure 3 is a flow chart showing a method of generating adaptive cell culture parameters in accordance with an embodiment of the present disclosure.

第4圖係顯示根據本揭露一實施例中建立基本控制因子序列表的方法之流程圖。 Figure 4 is a flow chart showing a method of establishing a basic control factor sequence table in accordance with an embodiment of the present disclosure.

第5圖係根據本揭露一實施例中第一細胞種類為A1之第一細胞的基本控制因子序列表。 Figure 5 is a table showing the basic control factor sequence of the first cell of the first cell type A1 according to an embodiment of the present disclosure.

第6圖係顯示根據本揭露一實施例中產生適應性細胞培養參數的方法之流程圖。 Figure 6 is a flow chart showing a method of generating adaptive cell culture parameters in accordance with an embodiment of the present disclosure.

第7圖係顯示根據本揭露一實施例中已知細胞(細胞種類為A1)的基本控制因子序列表。 Figure 7 is a table showing the basic control factor sequence of known cells (cell type A1) according to an embodiment of the present disclosure.

第8圖係顯示根據本揭露一實施例中被培養為目標細胞(細胞種類為B11)之第三細胞(細胞種類為A11)的基本控制因子序列表。 Fig. 8 is a table showing the basic control factor sequence of the third cell (cell type A11) cultured as a target cell (cell type B11) according to an embodiment of the present disclosure.

第9圖係顯示根據本揭露一實施例中根據培養結果調整適應性細胞培養參數的方法之流程圖。 Figure 9 is a flow chart showing a method of adjusting adaptive cell culture parameters based on culture results in accordance with an embodiment of the present disclosure.

第10圖係顯示根據本揭露一實施例中第一細胞之基本控制因子序列表。 Figure 10 is a table showing the basic control factor sequence of the first cell in accordance with an embodiment of the present disclosure.

第11圖係顯示根據本揭露一實施例中第一細胞被培養成第二細胞之基本控制因子序列表。 Figure 11 is a table showing the basic control factor sequence of the first cell being cultured into a second cell in accordance with an embodiment of the present disclosure.

第12圖係顯示根據本揭露一實施例中對第一細胞執行一pH 濃度預測機制的方法之流程圖。 Figure 12 is a diagram showing the execution of a pH on a first cell in accordance with an embodiment of the present disclosure. Flow chart of the method of concentration prediction mechanism.

在下文中將參考附圖對本揭露的各方面進行更充分的描述。然而,本揭露可以具體化成許多不同形式且不應解釋為侷限於貫穿本揭露所呈現的任何特定結構或功能。相反地,提供這些方面將使得本揭露周全且完整,並且本揭露將給本領域技術人員充分地傳達本揭露的範圍。基於本文所教導的內容,本領域的技術人員應意識到,無論是單獨還是結合本揭露的任何其它方面實現本文所揭露的任何方面,本揭露的範圍旨在涵蓋本文中所揭露的任何方面。例如,可以使用本文所提出任意數量的裝置或者執行方法來實現。另外,除了本文所提出本揭露的多個方面之外,本揭露的範圍更旨在涵蓋使用其它結構、功能或結構和功能來實現的裝置或方法。應可理解,其可透過申請專利範圍的一或多個元件具體化本文所揭露的任何方面。 Various aspects of the disclosure will be more fully described below with reference to the drawings. However, the disclosure may be embodied in many different forms and should not be construed as being limited to any particular structure or function presented. Rather, these aspects are provided so that this disclosure will be thorough and complete, and the disclosure will fully convey the scope of the disclosure. Based on the teachings herein, those skilled in the art will appreciate that the scope of the present disclosure is intended to cover any aspect disclosed herein, either alone or in combination with any other aspect disclosed herein. For example, any number of devices or methods of implementation presented herein can be used. In addition, the scope of the present disclosure is intended to cover an apparatus or method that is implemented using other structures, functions, or structures and functions, in addition to the various aspects disclosed herein. It should be understood that any aspect disclosed herein may be embodied by one or more elements of the patent application.

詞語「示例性」在本文中用於表示「用作示例、實例或說明」。本揭露的任何方面或本文描述為「示例性」的設計不一定被解釋為優選於或優於本揭露或設計的其他方面。此外,相同的數字在所有若干圖示中指示相同的元件,且除非在描述中另有指定,冠詞「一」和「上述」包含複數的參考。 The word "exemplary" is used herein to mean "serving as an example, instance or description." Any aspect of the disclosure or a design described herein as "exemplary" is not necessarily to be construed as preferred or preferred. In addition, the same numerals indicate the same elements in all the figures, and the articles "a" and "an"

第1圖係顯示根據本揭露一實施例中適應性細胞培養參數產生之細胞培養系統100的示例性示意圖。 1 is a schematic diagram showing a cell culture system 100 in which adaptive cell culture parameters are generated in accordance with an embodiment of the present disclosure.

細胞培養系統100可至少包括一培養箱120以及一管理裝置110,其中管理裝置110可以有線或無線傳輸方式連接至培養箱120。無線傳輸方式像是,區域網路、網際網路、藍牙 (Bluetooth)、Wi-Fi、Wi-Fi Direct、Zigbee等傳輸方式。 The cell culture system 100 can include at least one incubator 120 and a management device 110, wherein the management device 110 can be connected to the incubator 120 by wire or wireless transmission. Wireless transmission is like regional network, internet, Bluetooth (Bluetooth), Wi-Fi, Wi-Fi Direct, Zigbee and other transmission methods.

在一實施例中,管理裝置110可透過網路連接至一儲存裝置130,其中,網路可以是本領域技術人員所熟悉任何類型的網路,其可使用各種通訊上可用協定中的任一種來支援數據通訊,包括但不侷限於TCP/IP等等。舉例來說,網路可為一本地區域網路(Local Area Network,LAN),像是乙太網路等等、一虛擬網路,包括但不侷限於網際網路(Internet)、無線網路和/或這些和/或其他網路之任何組合。儲存裝置130可儲存一資料庫,其用以儲存所有一般化細胞培養參數以及細胞相關之資訊。 In one embodiment, the management device 110 can be connected to a storage device 130 via a network, wherein the network can be any type of network familiar to those skilled in the art that can use any of a variety of communication-available protocols. To support data communications, including but not limited to TCP/IP and more. For example, the network can be a local area network (LAN), such as Ethernet, etc., a virtual network, including but not limited to the Internet, wireless network And/or any combination of these and/or other networks. The storage device 130 can store a database for storing all generalized cell culture parameters as well as cell related information.

在培養箱120中可容納一或多個培養皿122(或其他形式的培養容器)。培養箱120本身係為習知,且培養箱120內的環境可由管理裝置110控制。管理裝置110可為雲端裝置、個人電腦、筆記型電腦、行動裝置等裝置,其可用以控制培養箱120內溫度、濕度pH濃度、二氧化碳、氧氣和其他氣體成分等。 One or more culture dishes 122 (or other forms of culture vessels) may be contained in the incubator 120. The incubator 120 itself is conventional and the environment within the incubator 120 can be controlled by the management device 110. The management device 110 can be a cloud device, a personal computer, a notebook computer, a mobile device, etc., which can be used to control the temperature, humidity, pH concentration, carbon dioxide, oxygen, and other gas components in the incubator 120.

培養皿122在商業上被廣泛用於各種標準尺寸,通常由透明塑膠(有時是玻璃)所製成。培養皿122內通常充滿細胞培養基124。細胞培養基124例如可以包含各種營養素凝膠的形式,其中營養素的數量和成分適應於將在培養容器中培養細胞126的特定類型。本領域之技術人士應可了解培養皿122和細胞培養基124並不侷限於本揭露之內容。 Petri dishes 122 are widely used commercially in a variety of standard sizes, typically made of clear plastic (sometimes glass). The culture dish 122 is typically filled with cell culture medium 124. The cell culture medium 124 can, for example, comprise a variety of nutrient gels in which the amount and composition of nutrients are adapted to the particular type of cells 126 that will be cultured in the culture vessel. Those skilled in the art will appreciate that the culture dish 122 and cell culture medium 124 are not limited to the disclosure.

此外,在本揭露實施方式的細胞培養系統100中,更可包括一或多個感測設備(圖未顯示),其可安裝在每個培養皿122中,用以偵測細胞狀態或其周圍之環境狀態。在一實施例中,感測設備可包括多個用於監測與細胞生長相關參數的感測器,包括 誘導分化參數(如,蛋白質)感測器、環控參數(如,溫度)感測器和監控參數(如,pH濃度)感測器。感測設備還可以包括其他與被繁殖特定細胞生長相關的感測器,例如包括鈉和/或鉀離子感測器。感測設備還可具有用於測量與細胞生長相關或指示細胞培養活性的氣態環境參數(特別是二氧化碳和/或氧氣)的感測器。感測設備更可被提供以測量培養皿中的濕度和其他氣體成分。感測設備可優選地被配置成以定期地、週期性地或在使用者透過管理裝置110發起請求時進行測量。感測設備在測量後可無線輸出上述測量值至管理裝置110,供管理裝置110分析。 In addition, in the cell culture system 100 of the disclosed embodiment, one or more sensing devices (not shown) may be further included, which may be installed in each of the culture dishes 122 to detect the state of the cells or the surroundings thereof. The state of the environment. In an embodiment, the sensing device can include a plurality of sensors for monitoring parameters related to cell growth, including Differentiation parameters (eg, protein) sensors, environmental parameters (eg, temperature) sensors, and monitoring parameters (eg, pH concentration) sensors are induced. The sensing device may also include other sensors associated with the growth of specific cells being propagated, including, for example, sodium and/or potassium ion sensors. The sensing device can also have a sensor for measuring gaseous environmental parameters (particularly carbon dioxide and/or oxygen) associated with or indicative of cell growth activity. A sensing device can be provided to measure humidity and other gas components in the culture dish. The sensing device may preferably be configured to make measurements periodically, periodically, or when the user initiates a request through the management device 110. The sensing device can wirelessly output the above measured value to the management device 110 after the measurement, for analysis by the management device 110.

第2圖係以一方式表示根據本揭露一實施例所述之電子裝置200之簡化功能方塊圖。如第2圖所示,電子裝置200可以是第1圖細胞培養系統100中之管理裝置110。電子裝置200可包括一輸入裝置202、一輸出裝置204、一控制電路206、一中央處理器(Central Processing Unit,CPU)208、一記憶體210、一程式碼212、一收發器214。控制電路206在記憶體210中透過中央處理器208執行程式碼212,並以此控制在電子裝置200中所進行之作業。電子裝置200可利用輸入裝置202,(例如,鍵盤、數字鍵、觸碰螢幕或麥克風(聲音輸入))接收使用者輸入訊號;也可由輸出裝置204(例如螢幕或喇叭)輸出圖像及聲音。收發器214在此用作接收及發送無線訊號,將接收之訊號送往控制電路206,以及以無線方式輸出控制電路206所產生之訊號。 FIG. 2 is a simplified functional block diagram of an electronic device 200 according to an embodiment of the present disclosure. As shown in FIG. 2, the electronic device 200 may be the management device 110 in the cell culture system 100 of Fig. 1. The electronic device 200 can include an input device 202, an output device 204, a control circuit 206, a central processing unit (CPU) 208, a memory 210, a code 212, and a transceiver 214. The control circuit 206 executes the program code 212 in the memory 210 through the central processing unit 208, and thereby controls the operations performed in the electronic device 200. The electronic device 200 can receive the user input signal by using the input device 202 (for example, a keyboard, a numeric keypad, a touch screen, or a microphone (sound input); and the output device 204 (such as a screen or a speaker) can also output images and sounds. The transceiver 214 is here used to receive and transmit wireless signals, send the received signals to the control circuit 206, and wirelessly output the signals generated by the control circuit 206.

第3圖係顯示根據本揭露一實施例中一種適應性細胞培養參數產生的方法300之流程圖。此方法可用於第1圖細胞培養系統100中之管理裝置110,用以培養第一細胞為目標細胞。 3 is a flow chart showing a method 300 of adaptive cell culture parameter generation in accordance with an embodiment of the present disclosure. This method can be applied to the management device 110 in the cell culture system 100 of Fig. 1 to culture the first cell as a target cell.

在步驟S305中,管理裝置根據第一細胞之一第一細胞種類及一目標細胞特性由一資料庫中搜尋一般化細胞培養參數,以建立一基本控制因子序列表,其中研究人員可預先在資料庫中儲存所有一般化細胞培養參數,以供管理裝置搜尋。接著,在步驟S310中,管理裝置根據第一細胞種類、目標細胞特性及基本控制因子序列表產生適應性細胞培養參數。再來,在步驟S315中,管理裝置根據適應性細胞培養參數培養第一細胞,並產生一培養結果。在步驟S320中,管理裝置根據培養結果調整適應性細胞培養參數。 In step S305, the management device searches for a generalized cell culture parameter from a database according to the first cell type and a target cell characteristic of the first cell, to establish a basic control factor sequence table, wherein the researcher can pre-inform the data. All generalized cell culture parameters are stored in the library for management device search. Next, in step S310, the management device generates adaptive cell culture parameters based on the first cell type, the target cell characteristics, and the basic control factor sequence table. Further, in step S315, the management device cultures the first cells according to the adaptive cell culture parameters and produces a culture result. In step S320, the management device adjusts the adaptive cell culture parameters based on the culture results.

關於管理裝置如何建立基本控制因子序列表及如何產生及調整適應性細胞培養參數的示例性操作流程將在以下進行詳細描述。 An exemplary operational flow for managing how the device establishes a basic control factor sequence table and how to generate and adjust adaptive cell culture parameters will be described in detail below.

第4圖係顯示根據本揭露一實施例中建立基本控制因子序列表的方法400之流程圖。此方法400可由第1圖細胞培養系統100中之管理裝置110所執行,用以建立第一細胞的建立基本控制因子序列表。 4 is a flow chart showing a method 400 of establishing a basic control factor sequence listing in accordance with an embodiment of the present disclosure. This method 400 can be performed by the management device 110 in the cell culture system 100 of FIG. 1 to establish a basic control factor sequence listing for the first cell.

在流程開始前,管理裝置可先確認第一細胞的第一細胞種類以及欲培養第一細胞為目標細胞的目標細胞特性。在步驟S405中,管理裝置根據第一細胞種類判斷第一細胞是否為已知細胞。在此步驟中,管理裝置可比對第一細胞種類與資料庫中所有細胞的細胞種類。當管理裝置有比對到與第一細胞種類相同的細胞時,則判定第一細胞係為已知細胞。 Before the start of the process, the management device may first confirm the first cell species of the first cell and the target cell characteristics of the target cell to be cultured. In step S405, the management device determines whether the first cell is a known cell based on the first cell type. In this step, the management device can align the first cell type with the cell type of all cells in the database. When the management device has aligned the same cells as the first cell species, it is determined that the first cell line is a known cell.

接著,當管理裝置判斷第一細胞為已知細胞時(在步驟S405中的「是」),在步驟S410中,管理裝置由資料庫中取得 對應已知細胞之基本控制因子,設定對應基本控制因子之權重及優先權順序,並儲存基本控制因子、對應基本控制因子之權重及優先權順序於上述第一細胞的基本控制因子序列表中。 Next, when the management device determines that the first cell is a known cell (YES in step S405), in step S410, the management device is obtained from the database. Corresponding to the basic control factors of the known cells, the weights and priority orders corresponding to the basic control factors are set, and the basic control factors, the weights of the corresponding basic control factors, and the priority order are stored in the basic control factor sequence table of the first cell.

當管理裝置判斷第一細胞不為已知細胞時(在步驟S405中的「否」),在步驟S415中,管理裝置儲存預設基本控制因子及對應預設基本控制因子之權重及優先權順序於第一細胞的基本控制因子序列表中。需注意的是,此預設基本控制因子及對應預設基本控制因子之權重及優先權順序可由使用者預先儲存於資料庫中。 When the management device determines that the first cell is not a known cell (NO in step S405), in step S415, the management device stores the weight and priority order of the preset basic control factor and the corresponding preset basic control factor. In the basic control factor sequence table of the first cell. It should be noted that the weight and priority order of the preset basic control factor and the corresponding preset basic control factor may be pre-stored in the database by the user.

此外,在另一實施例中,當管理裝置建立第一細胞的基本控制因子序列表後,仍可不斷搜尋資料庫中之資料,以更新基本控制因子序列表。舉例來說,第5圖係顯示為第一細胞種類為A1之第一細胞的基本控制因子序列表。如圖所示,背景白色部份係為管理裝置前次所建立之基本控制因子序列表,而背景灰色部份係為管理裝置再次搜尋資料庫後更新並建立新控制項以及新控制因子。每個控制因子之控制項可預先由研究人員賦予基本權重。被賦予的權重越高,其意義表示此控制因子的控制項越接近細胞穩定生長的情況。第5圖中的上半部份係為第一細胞在不同控制因子(誘導分化參數、環控參數、監控參數)下的所對應之權重。第5圖中的下半部份係為每一控制因子所對應的優先權,其中優先權也可預先由研究人員所賦予。優先權值越小,其意義表示控制因子的優先調整權越高(即具有最小優先權排序)。如第5圖所示,由於對應誘導分化參數的優先權值為0(即誘導分化參數的優先調整權最高),所以誘導分化參數的權重將優先被調整。 In addition, in another embodiment, after the management device establishes the basic control factor sequence table of the first cell, the data in the database can be continuously searched to update the basic control factor sequence table. For example, Figure 5 is a table showing the basic control factor sequence for the first cell of the first cell type A1. As shown in the figure, the background white portion is the basic control factor sequence table established by the management device, and the background gray portion is updated after the management device searches the database again to establish new control items and new control factors. The control items for each control factor can be given basic weights by the researcher in advance. The higher the weight given, the meaning that the control of this control factor is closer to the steady growth of the cells. The upper part of Fig. 5 is the corresponding weight of the first cell under different control factors (inducing differentiation parameters, environmental control parameters, monitoring parameters). The lower half of Figure 5 is the priority corresponding to each control factor, and the priority can also be given in advance by the researcher. The smaller the priority value, the higher the priority of the priority adjustment of the control factor (ie, the least priority order). As shown in Fig. 5, since the priority value corresponding to the induced differentiation parameter is 0 (i.e., the priority of the differentiation parameter is the highest), the weight of the induced differentiation parameter will be preferentially adjusted.

第6圖係顯示根據本揭露一實施例中產生適應性細胞培養參數的方法600之流程圖。此方法可由第1圖細胞培養系統100中之管理裝置110所執行,用以根據第一細胞之第一細胞種類、目標細胞特性及基本控制因子序列表產生適應性細胞培養參數。 Figure 6 is a flow diagram showing a method 600 of generating adaptive cell culture parameters in accordance with an embodiment of the present disclosure. This method can be performed by the management device 110 in the cell culture system 100 of Figure 1, for generating adaptive cell culture parameters based on the first cell type of the first cell, the target cell characteristics, and the basic control factor sequence listing.

在流程開始前,管理裝置可先確認第一細胞的第一細胞種類以及欲培養第一細胞為目標細胞的目標細胞特性。在步驟S605中,管理裝置根據第一細胞之第一細胞種類判斷第一細胞是否為已知細胞。在此步驟中,管理裝置可比對第一細胞種類與資料庫中所有細胞的細胞種類。當管理裝置有比對到與第一細胞種類相同的細胞時,則判定第一細胞係為已知細胞。 Before the start of the process, the management device may first confirm the first cell species of the first cell and the target cell characteristics of the target cell to be cultured. In step S605, the management device determines whether the first cell is a known cell based on the first cell type of the first cell. In this step, the management device can align the first cell type with the cell type of all cells in the database. When the management device has aligned the same cells as the first cell species, it is determined that the first cell line is a known cell.

當管理裝置判斷第一細胞為已知細胞時(在步驟S605中的「是」),在步驟S610中,管理裝置由資料庫中取得對應已知細胞之基本控制因子。在步驟S615中,管理裝置由每一基本控制因子中選取具有最高權重之基本控制因子作為適應性細胞培養參數。舉例來說,請參考第7圖,假設第7圖係為已知細胞(細胞種類為A1)的基本控制因子序列表,則管理裝置將由各基本控制因子中選取具有最高權重的參數作為適應性細胞培養參數。當權重相同時,則管理裝置則選取表格中排序較高之參數作為適應性細胞培養參數。如第7圖所示,在基本控制因子為誘導分化參數的表格中,由於所有誘導分化參數之權重皆為255,因此管理裝置可選擇表格中排序較高之誘導分化參數v1作為適應性細胞培養參數。在基本控制因子為環控參數的表格中,管理裝置可選擇具有最高權重257之環控參數v3作為適應性細胞培養參數。在基本控制因子為監控參數的表格中,管理裝置可選擇具有最高權重257之監 控參數v3作為適應性細胞培養參數。 When the management device determines that the first cell is a known cell (YES in step S605), in step S610, the management device acquires a basic control factor corresponding to the known cell from the database. In step S615, the management device selects the basic control factor having the highest weight from each of the basic control factors as the adaptive cell culture parameter. For example, please refer to Figure 7, assuming that Figure 7 is a basic control factor sequence table of known cells (cell type A1), the management device will select the parameter with the highest weight among the basic control factors as the adaptability. Cell culture parameters. When the weights are the same, the management device selects the higher ranked parameters in the table as the adaptive cell culture parameters. As shown in Fig. 7, in the table in which the basic control factor is the induced differentiation parameter, since all the differentiation parameter parameters have a weight of 255, the management device can select the higher-order induced differentiation parameter v1 in the table as the adaptive cell culture. parameter. In a table in which the basic control factor is the environmental control parameter, the management device can select the environmental control parameter v3 having the highest weight 257 as the adaptive cell culture parameter. In the table where the basic control factor is the monitoring parameter, the management device can select the supervisor with the highest weight 257 The parameter v3 was controlled as an adaptive cell culture parameter.

當管理裝置判斷第一細胞不為已知細胞時(在步驟S605中的「否」),在步驟S620中,管理裝置由資料庫中取得與第一細胞的第一細胞種類類似之第三細胞,複製對應第三細胞之基本控制因子作為對應第一細胞之基本控制因子。接著,在步驟S615中,管理裝置由每一基本控制因子中選取具有最高權重之基本控制因子作為適應性細胞培養參數。舉例來說,請參考第8圖,假設第8圖係為培養為目標細胞(細胞種類為B11)之第三細胞(細胞種類為A11)的基本控制因子序列表,則管理裝置直接複製第三細胞的基本控制因子序列表作為對應第一細胞之基本控制因子序列表,再由各基本控制因子中選取具有最高權重的參數作為適應性細胞培養參數。 When the management device determines that the first cell is not a known cell (NO in step S605), in step S620, the management device acquires a third cell similar to the first cell type of the first cell from the database. The basic control factor corresponding to the third cell is replicated as a basic control factor corresponding to the first cell. Next, in step S615, the management device selects the basic control factor having the highest weight from each of the basic control factors as the adaptive cell culture parameter. For example, please refer to Figure 8. If the figure 8 is the basic control factor sequence table for the third cell (cell type A11) cultured as the target cell (cell type B11), the management device directly copies the third. The basic control factor sequence table of the cells is used as the basic control factor sequence table corresponding to the first cell, and the parameter with the highest weight is selected from the basic control factors as the adaptive cell culture parameter.

第9圖係顯示根據本揭露一實施例中根據培養結果調整適應性細胞培養參數的方法900流程圖。此方法可由第1圖細胞培養系統100中之管理裝置110所執行,用以根據培養結果調整適應性細胞培養參數,其中上述培養結果係為第一細胞被培養為第二細胞。 Figure 9 is a flow diagram showing a method 900 for adjusting adaptive cell culture parameters based on culture results in accordance with an embodiment of the present disclosure. This method can be performed by the management device 110 in the cell culture system 100 of Fig. 1 to adjust the adaptive cell culture parameters based on the culture results, wherein the culture results are that the first cells are cultured as the second cells.

在流程開始前,管理裝置可先確認細胞培養結果。在步驟S905中,管理裝置判斷第二細胞之一第二細胞種類是否與目標細胞種類相同。當第二細胞之一第二細胞種類是否與目標細胞種類相同時(在步驟S905中的「是」),在步驟S910中,管理裝置判斷第二細胞之一第二細胞特性是否與目標細胞特性相符合。 The management device can confirm the cell culture results before the process begins. In step S905, the management device determines whether the second cell type of one of the second cells is the same as the target cell type. When the second cell type of one of the second cells is the same as the target cell type (YES in step S905), in step S910, the management device determines whether the second cell characteristic of one of the second cells is different from the target cell characteristic Compatible.

當第二細胞之第二細胞特性與目標細胞特性相符合時(在步驟S910中的「是」),則管理裝置判斷第二細胞即為目標 細胞,無須調整適應性細胞培養參數,結束此流程。 When the second cell characteristic of the second cell matches the target cell characteristic ("Yes" in step S910), the management device determines that the second cell is the target The cells do not need to adjust the adaptive cell culture parameters to end the process.

當第二細胞之第二細胞特性與目標細胞特性不符合時(在步驟S910中的「否」),在步驟S915中,管理裝置調整第一細胞之基本控制因子序列表中基本控制因子之權重及優先權順序,以作為下階段培養相同細胞時重新選擇具有最高權重之基本控制因子作為上述適應性細胞培養參數。舉例說明,第10圖係顯示根據本揭露一實施例中第一細胞之基本控制因子序列表,並參考第7圖。假設第7圖係為未調整前之第一細胞之基本控制因子序列表。管理裝置在判斷第二細胞之第二細胞特性與目標細胞特性不符合時,調低具有優先權最高者之基本控制因子的權重。在第7圖中,優先權最高者之基本控制因子係為誘導分化參數。而當初所選取作為適應性細胞培養參數的誘導分化參數係為誘導分化參數v1,因此將誘導分化參數v1的權重從255調低為254,如第10圖所示。此外,管理裝置也調降此基本控制因子之優先權值。如第10圖所示,誘導分化參數之優先權值從0調降至1。當優先權相同時,管理裝置則以表格中之順序決定優先權之排序。因此,誘導分化參數、環控參數及監控參數的優先權排序變為2、1、3。下次調整時,管理裝置則依優先權排序選擇優先權排序為1之環控參數作為適應性細胞培養參數。 When the second cell characteristic of the second cell does not match the target cell characteristic (NO in step S910), in step S915, the management device adjusts the weight of the basic control factor in the basic control factor sequence table of the first cell. And the priority order, as the basic control factor with the highest weight is reselected as the above adaptive cell culture parameter when the same cell is cultured in the next stage. For example, FIG. 10 shows a basic control factor sequence table of a first cell according to an embodiment of the present disclosure, and refers to FIG. Assume that Figure 7 is a list of basic control factor sequences for the first cell before unadjustment. The management device lowers the weight of the basic control factor having the highest priority when determining that the second cell characteristic of the second cell does not match the target cell characteristic. In Figure 7, the basic control factor for the highest priority is the induced differentiation parameter. The induced differentiation parameter selected as the adaptive cell culture parameter was the induced differentiation parameter v1, so the weight of the induced differentiation parameter v1 was lowered from 255 to 254, as shown in FIG. In addition, the management device also lowers the priority value of this basic control factor. As shown in Figure 10, the priority value of the induced differentiation parameter was adjusted from 0 to 1. When the priorities are the same, the management device determines the ordering of the priorities in the order in the table. Therefore, the order of priority for inducing differentiation parameters, environmental control parameters, and monitoring parameters becomes 2, 1, and 3. At the next adjustment, the management device selects the environmental control parameters with priority order 1 as the adaptive cell culture parameters according to the priority order.

當第二細胞之一第二細胞種類與目標細胞種類不相同時(在步驟S905中的「否」),在步驟S920中,管理裝置複製基本控制因子序列表作為第二細胞之基本控制因子序列表,並儲存第二細胞之基本控制因子序列表至資料庫中,以供下次管理裝置可根據第二細胞之基本控制因子序列表培養第二細胞。第11圖係 顯示根據本揭露一實施例中第一細胞被培養成第二細胞之基本控制因子序列表。如圖所示,第一細胞已被培養成細胞種類為B2之第二細胞。因此,管理裝置可儲存第11圖中的基本控制因子序列表至資料庫。待下次使用者欲培養第一細胞為第二細胞時,則可透過管理裝置從資料庫中取得此基本控制因子序列表來進行第二細胞之培養。 When the second cell type of the second cell is different from the target cell type (NO in step S905), in step S920, the management device copies the basic control factor sequence table as the basic control factor sequence of the second cell. List and store the basic control factor sequence table of the second cell into the database for the next management device to culture the second cell according to the basic control factor sequence table of the second cell. Figure 11 A basic control factor sequence listing in which a first cell is cultured into a second cell in accordance with an embodiment of the present disclosure is shown. As shown, the first cell has been cultured into a second cell of cell type B2. Therefore, the management device can store the basic control factor sequence table in FIG. 11 to the database. When the next time the user wants to train the first cell as the second cell, the basic control factor sequence table can be obtained from the database through the management device to culture the second cell.

簡而言之,權重與優先權的調整規則可由下列表格1表示。 In short, the adjustment rules for weights and priorities can be represented by Table 1 below.

舉例來說,管理裝置比對由第一細胞所培養成的第二細胞及目標細胞。當第二細胞與目標細胞為不同細胞時,管理裝置可複製基本控制因子,以建立培養第二細胞的新資料。當第二細胞與目標細胞為相同細胞且特性相符時,管理裝置可維持目前的權重以及優先權。在另一實施例中,管理裝置可累加權重以及優先權,以表示此參數越接近細胞穩定生長情況。當第二細胞與目標細胞為相同細胞且特性不符時,管理裝置可將對應參數之權重值降到 最低,並將對應參數之優先權降低一階,以避免短時間內此參數再度被參考使用,如第10圖所示。當第一細胞在培養過程中死亡時,管理裝置可將對應參數之權重值降到最低,並將對應參數之優先權降低一階,以減低選擇此參數作為適應性細胞培養參數之機率。 For example, the management device aligns the second cells and target cells cultured by the first cells. When the second cell and the target cell are different cells, the management device can replicate the basic control factor to establish new data for culturing the second cell. When the second cell is the same cell as the target cell and the characteristics are consistent, the management device can maintain the current weight and priority. In another embodiment, the management device may weight the weight and priority to indicate that the closer the parameter is to the steady growth of the cell. When the second cell and the target cell are the same cell and the characteristics do not match, the management device can reduce the weight value of the corresponding parameter to The lowest, and the priority of the corresponding parameter is reduced by first order, so as to avoid this parameter being used again for reference in a short time, as shown in Fig. 10. When the first cell dies during the culture process, the management device can minimize the weight value of the corresponding parameter and lower the priority of the corresponding parameter by one step to reduce the probability of selecting the parameter as an adaptive cell culture parameter.

第12圖係顯示根據本揭露一實施例中對第一細胞執行一pH濃度預測機制的方法1200之流程圖。此方法可由第1圖細胞培養系統100中之管理裝置110所執行。此機制係在培養第一細胞時所執行。 Figure 12 is a flow diagram showing a method 1200 of performing a pH concentration prediction mechanism for a first cell in accordance with an embodiment of the present disclosure. This method can be performed by the management device 110 in the cell culture system 100 of FIG. This mechanism is performed when the first cell is cultured.

在步驟S1205中,管理裝置可根據第一細胞之第一細胞種類計算一pH預測值,其中pH預測值(pH predict )可表示如下:pH predict =pH base -Coef×T 2 In step S1205, the management device may calculate a pH predicted value according to the first cell type of the first cell, wherein the pH predictor ( pH predict ) may be expressed as follows: pH predict = pH base - Coef × T 2

其中pH base 表示為培養基之起始pH濃度、Coef係為一係數及T係為單位為小時(hr)之一時間值。 The pH base is expressed as the initial pH concentration of the medium, the Coef system is a coefficient, and the T system is a time value in hours (hr).

接著,在步驟S1210中,管理裝置判斷感測裝置所偵測第一細胞之一pH實際值是否小於一閥值。在一實施例中,此閥值係可由使用者預先設定。當第一細胞之pH實際值小於閥值時(在步驟S1210中的「是」),在步驟S1215中,管理裝置調整在第一細胞之基本控制因子序列表中之基本控制因子。 Next, in step S1210, the management device determines whether the actual pH value of one of the first cells detected by the sensing device is less than a threshold. In an embodiment, the threshold can be preset by the user. When the actual pH value of the first cell is less than the threshold (YES in step S1210), in step S1215, the management device adjusts the basic control factor in the basic control factor sequence table of the first cell.

當第一細胞之pH實際值不小於閥值時(在步驟S1210中的「否」),在步驟S1220中,管理裝置判斷第一細胞之pH實際值是否小於pH預測值。當第一細胞之pH實際值小於pH預測值時(在步驟S1220中的「是」),在步驟S1225中,管理裝置可執行更 換第一細胞之培養液,以避免細胞死亡。在另一實施例中,在步驟S1225中,管理裝置可調整pH濃度回報之頻率(例如,提高pH濃度回報之頻率)。此外,管理裝置更可計數pH實際值小於pH預測值之次數。當次數累計至一預設值以上時,則管理裝置啟動更換第一細胞之培養液,以避免細胞死亡。 When the actual pH value of the first cell is not less than the threshold (NO in step S1210), in step S1220, the management device determines whether the actual pH value of the first cell is smaller than the pH predicted value. When the actual pH value of the first cell is less than the pH predicted value (YES in step S1220), the management device may perform more in step S1225. Change the culture medium of the first cell to avoid cell death. In another embodiment, in step S1225, the management device can adjust the frequency of the pH concentration return (eg, increase the frequency of the pH concentration return). In addition, the management device can count the number of times the actual pH value is less than the predicted pH value. When the number of times is accumulated to a predetermined value or more, the management device starts the replacement of the culture medium of the first cell to avoid cell death.

當第一細胞之pH實際值不小於pH預測值時(在步驟S1220中的「否」),回到步驟S1220,管理裝置持續偵測判斷第一細胞之pH實際值是否小於pH預測值。 When the actual pH value of the first cell is not less than the pH predicted value (NO in step S1220), the process returns to step S1220, and the management device continuously detects whether the actual pH value of the first cell is smaller than the pH predicted value.

此外,中央處理器208可執行程式碼212以執行上述實施例所述之動作和步驟,或其它在說明書中所描述之內容。 In addition, central processor 208 can execute program code 212 to perform the acts and steps described in the above-described embodiments, or otherwise described in the specification.

如上所述,藉由本揭露所提出之一種適應性細胞培養參數產生的方法、裝置及其儲存媒體,可動態產生適應性細胞培養製程參數,並在培養細胞的過程中對細胞的培養基執行pH濃度預測,降低細胞培養死亡的問題,以提高細胞生長之特性符合預期。 As described above, the method, the device and the storage medium for the adaptive cell culture parameter production proposed by the present disclosure can dynamically generate adaptive cell culture process parameters, and perform pH concentration on the cell culture medium during the process of culturing the cells. It is predicted that the problem of cell culture death will be reduced to improve the characteristics of cell growth in line with expectations.

以上實施例使用多種角度來描述。顯然這裡的教示可以多種方式呈現,而在範例中揭露之任何特定架構或功能僅為一代表性之狀況。根據本文之教示,任何熟知此技藝之人士應理解在本文呈現之內容可獨立利用其他某種型式或綜合多種型式作不同呈現。 The above embodiments are described using a variety of angles. It will be apparent that the teachings herein may be presented in a variety of ways, and that any particular structure or function disclosed in the examples is merely representative. In light of the teachings herein, anyone skilled in the art will appreciate that the content presented herein can be independently rendered in various different types or in a variety of different forms.

熟知此技藝之人士將了解訊息及訊號可用多種不同科技及技巧展現。舉例,在以上描述所有可能引用到之數據、指令、命令、訊息、訊號、位元、符號、以及晶片可以伏特、電流、電磁波、磁場或磁粒、光場或光粒、或以上任何組合所呈現。 Those skilled in the art will understand that messages and signals can be presented in a variety of different technologies and techniques. For example, all of the data, instructions, commands, messages, signals, bits, symbols, and wafers that may be referenced above may be volts, currents, electromagnetic waves, magnetic fields or magnetic particles, light fields or light particles, or any combination thereof. Presented.

熟知此技術之人士更會了解在此描述各種說明性之邏輯區塊、模組、處理器、裝置、電路、以及演算步驟與以上所揭露之各種情況可用的電子硬體(例如用來源編碼或其他技術設計之數位實施、類比實施、或兩者之組合)、各種形式之程式或與指示作為連結之設計碼(在內文中為方便而稱作「軟體」或「軟體模組」)、或兩者之組合。 Those skilled in the art will appreciate that various illustrative logic blocks, modules, processors, devices, circuits, and logic steps are described herein for use with the electronic hardware (eg, source coded or Digital implementation of other technical designs, analogy implementation, or a combination of both), various forms of programming or design codes linked to instructions (referred to as "software" or "software modules" for convenience in the text), or a combination of the two.

此外,多種各種說明性之邏輯區塊、模組、及電路以及在此所揭露之各種情況可實施在積體電路(Integrated Circuit,IC)、存取終端、存取點;或由積體電路、存取終端、存取點執行。 In addition, various illustrative logic blocks, modules, and circuits, and various aspects disclosed herein may be implemented in an integrated circuit (IC), an access terminal, an access point, or an integrated circuit. , access terminal, access point execution.

在此所揭露程序之任何具體順序或分層之步驟純為一舉例之方式。基於設計上之偏好,必須了解到程序上之任何具體順序或分層之步驟可在此文件所揭露的範圍內被重新安排。伴隨之方法申請專利範圍以一示範例順序呈現出各種步驟之元件,也因此不應被本揭露說明書所展示之特定順序或階層所限制。 Any specific sequence or layering of the procedures disclosed herein is by way of example only. Based on design preferences, it must be understood that any specific order or hierarchy of steps in the program may be rearranged within the scope of the disclosure. The accompanying claims are intended to be illustrative of the embodiments of the invention

本揭露之說明書所揭露之方法和演算法之步驟,可以直接透過執行一處理器直接應用在硬體以及軟體模組或兩者之結合上。 The method and algorithm steps disclosed in the specification of the present disclosure can be directly applied to a hardware and a software module or a combination of the two directly by executing a processor.

因此本揭露亦可提出一種儲存媒體,經由一電子裝置讀取上述儲存媒體所儲存之程式碼後以執行適應性細胞培養參數產生的方法,其中,該方法步驟如前所述,因此不再贅述。 Therefore, the present disclosure may also provide a storage medium, which reads a code stored in the storage medium via an electronic device to perform an adaptive cell culture parameter generation method, wherein the method steps are as described above, and therefore no further description is provided. .

在申請專利範圍中用以修飾元件之「第一」、「第二」、「第三」等序數詞之使用本身未暗示任何優先權、優先次序、各元件之間之先後次序、或方法所執行之步驟之次序,而僅用作標識來區分具有相同名稱(具有不同序數詞)之不同元件。 The use of ordinal numbers such as "first", "second", "third", etc., used to modify elements in the scope of the patent application does not imply any priority, prioritization, prioritization between elements, or method The order of the steps performed, and used only as an identifier to distinguish between different elements having the same name (with different ordinal numbers).

雖然本揭露已以實施範例揭露如上,然其並非用以限定本案,任何熟悉此項技藝者,在不脫離本揭露之精神和範圍內,當可做些許更動與潤飾,因此本案之保護範圍當視後附之申請專利範圍所界定者為準。 Although the disclosure has been described above by way of example, it is not intended to limit the scope of the present invention, and the scope of protection of the present invention can be made without departing from the spirit and scope of the disclosure. This is subject to the definition of the scope of the patent application.

Claims (12)

一種適應性細胞培養參數產生的方法,用以培養第一細胞為目標細胞,上述方法包括以下步驟:根據上述第一細胞之一第一細胞種類及一目標細胞特性由一資料庫中搜尋一般化細胞培養參數,以建立一基本控制因子序列表,其中上述基本控制因子序列表係至少包括基本控制因子,以及對應上述基本控制因子之權重及優先權順序;根據上述第一細胞種類、上述目標細胞特性及上述基本控制因子序列表產生適應性細胞培養參數;根據上述適應性細胞培養參數培養上述第一細胞,並產生一培養結果;以及根據上述培養結果調整上述適應性細胞培養參數;其中上述培養結果係為上述第一細胞被培養為第二細胞,根據上述培養結果調整上述適應性細胞培養參數的步驟更包括:判斷上述第二細胞之一第二細胞種類是否與上述目標細胞種類相同且判斷上述第二細胞之一第二細胞特性是否與上述目標細胞特性相符合;當上述第二細胞種類與上述目標細胞種類相同且上述第二細胞特性與上述目標細胞特性相符合時,判斷上述第二細胞即為上述目標細胞; 當上述第二細胞種類與上述目標細胞種類相同且上述第二細胞特性與上述目標細胞特性不符合時,調整上述基本控制因子序列表中之上述基本控制因子之上述權重及上述優先權順序,以重新選取具有最高權重之基本控制因子作為上述適應性細胞培養參數;或當上述第二細胞種類與上述目標細胞種類不相同且上述第二細胞特性與上述目標細胞特性不符合時,複製上述基本控制因子序列表作為將上述第一細胞培養成上述第二細胞之基本控制因子序列表,並儲存上述基本控制因子序列表至上述資料庫中。 A method for producing adaptive cell culture parameters for culturing a first cell as a target cell, the method comprising the steps of: searching for a generalization according to a first cell type and a target cell characteristic of the first cell; a cell culture parameter to establish a basic control factor sequence table, wherein the basic control factor sequence form comprises at least a basic control factor, and a weight and a priority order corresponding to the basic control factor; according to the first cell type, the target cell Characterization and the above-mentioned basic control factor sequence table generate adaptive cell culture parameters; cultivating said first cells according to said adaptive cell culture parameters, and producing a culture result; and adjusting said adaptive cell culture parameters according to said culture results; wherein said culture The result is that the first cell is cultured as a second cell, and the step of adjusting the adaptive cell culture parameter according to the culture result further comprises: determining whether the second cell type of the second cell is the same as the target cell type and determining The second fine Whether the second cell characteristic is consistent with the characteristics of the target cell; when the second cell species is the same as the target cell species and the second cell characteristic is consistent with the target cell characteristic, the second cell is determined as Target cell Adjusting the weight of the basic control factor in the basic control factor sequence table and the priority order when the second cell type is the same as the target cell type and the second cell characteristic does not match the target cell characteristic Re-selecting the basic control factor with the highest weight as the above adaptive cell culture parameter; or copying the above basic control when the second cell species is different from the target cell species and the second cell characteristic does not match the target cell characteristics The factor sequence table serves as a basic control factor sequence table for culturing the above first cells into the above second cells, and stores the above basic control factor sequence table into the above database. 如申請專利範圍第1項所述之適應性細胞培養參數產生的方法,其中根據上述第一細胞之上述第一細胞種類及上述目標細胞特性由上述資料庫中搜尋上述一般化細胞培養參數,以建立上述基本控制因子序列表的步驟更包括:根據上述第一細胞種類判斷上述第一細胞是否為已知細胞;當判斷上述第一細胞為上述已知細胞時,由上述資料庫中取得對應上述已知細胞之基本控制因子,設定對應上述基本控制因子之權重及優先權順序,並儲存上述基本控制因子、對應上述基本控制因子之權重及優先權順序於上述基本控制因子序列表中;或當判斷上述第一細胞不為上述已知細胞時,儲存預設基 本控制因子及對應上述預設基本控制因子之權重及優先權順序於上述基本控制因子序列表中。 The method for producing an adaptive cell culture parameter according to claim 1, wherein the generalized cell culture parameter is searched for from the above-mentioned database according to the first cell type of the first cell and the target cell characteristic. The step of establishing the basic control factor sequence table further includes: determining whether the first cell is a known cell according to the first cell type; and determining that the first cell is the known cell, obtaining the corresponding data from the database Knowing the basic control factor of the cell, setting a weight and a priority order corresponding to the basic control factor, and storing the basic control factor, the weight corresponding to the basic control factor, and the priority order in the basic control factor sequence table; or Predetermining the storage base when the first cell is not the above known cell The control factor and the weight and priority order corresponding to the preset basic control factor are in the above basic control factor sequence table. 如申請專利範圍第1項所述之適應性細胞培養參數產生的方法,其中根據上述第一細胞之上述第一細胞種類、上述目標細胞特性及上述基本控制因子序列表產生上述適應性細胞培養參數的步驟更包括:根據上述第一細胞之上述第一細胞種類判斷上述第一細胞是否為已知細胞;當判斷上述第一細胞為上述已知細胞時,由上述資料庫中取得對應上述已知細胞之基本控制因子,由每一基本控制因子中選取具有最高權重之基本控制因子作為上述適應性細胞培養參數;或當判斷上述第一細胞不為上述已知細胞時,由上述資料庫中取得與上述第一細胞的上述第一細胞種類類似之第三細胞,複製對應上述第三細胞之基本控制因子作為對應上述第一細胞之基本控制因子,由每一基本控制因子中選取具有最高權重之基本控制因子作為上述適應性細胞培養參數。 The method for producing an adaptive cell culture parameter according to claim 1, wherein the adaptive cell culture parameter is generated according to the first cell type of the first cell, the target cell characteristic, and the basic control factor sequence table. The step further includes: determining whether the first cell is a known cell according to the first cell type of the first cell; and determining that the first cell is the known cell, and obtaining the corresponding known from the database The basic control factor of the cell, wherein the basic control factor having the highest weight is selected as the adaptive cell culture parameter from each of the basic control factors; or when it is determined that the first cell is not the above known cell, obtained from the above database a third cell similar to the first cell species of the first cell, replicating a basic control factor corresponding to the third cell as a basic control factor corresponding to the first cell, and selecting the highest weight from each of the basic control factors The basic control factor serves as the above adaptive cell culture parameter. 如申請專利範圍第1項所述之適應性細胞培養參數產生的方法,其中根據上述適應性細胞培養參數培養上述第一細胞,並產生上述培養結果的步驟更包括:對上述第一細胞執行一pH濃度預測機制;其中上述pH濃度預測機制係包括: 根據上述第一細胞之上述第一細胞種類計算一pH預測值;判斷所偵測上述第一細胞之一pH實際值是否小於一閥值及上述pH預測值;以及當上述pH實際值大於上述閥值且小於上述pH預測值時,執行更換上述第一細胞之培養液。 The method for producing an adaptive cell culture parameter according to claim 1, wherein the step of cultivating the first cell according to the adaptive cell culture parameter and generating the culture result further comprises: performing a first cell on the first cell. pH concentration prediction mechanism; wherein the above pH concentration prediction mechanism includes: Calculating a pH predicted value according to the first cell type of the first cell; determining whether the actual pH value of one of the first cells detected is less than a threshold value and the pH prediction value; and when the actual pH value is greater than the valve When the value is less than the above-described pH prediction value, the culture solution for replacing the first cell described above is performed. 一種適應性細胞培養參數產生的裝置,用以培養第一細胞為目標細胞,上述裝置包括:一控制電路;一處理器,安裝於上述控制電路中;以及一記憶體,安裝於上述控制電路中並且耦接至上述處理器;其中上述處理器配置用以執行儲存於上述記憶體中之一程式碼以執行:根據上述第一細胞之一第一細胞種類及一目標細胞特性由一資料庫中搜尋一般化細胞培養參數,以建立一基本控制因子序列表,其中上述基本控制因子序列表係至少包括基本控制因子,以及對應上述基本控制因子之權重及優先權順序;根據上述第一細胞種類、上述目標細胞特性及上述基本控制因子序列表產生適應性細胞培養參數;根據上述適應性細胞培養參數培養上述第一細胞,並產 生一培養結果;以及根據上述培養結果調整上述適應性細胞培養參數;其中上述培養結果係為上述第一細胞被培養為第二細胞,而上述處理器根據上述培養結果調整上述適應性細胞培養參數更包括:判斷上述第二細胞之一第二細胞種類是否與上述目標細胞種類相同且判斷上述第二細胞之一第二細胞特性是否與上述目標細胞特性相符合;當上述第二細胞種類與上述目標細胞種類相同且上述第二細胞特性與上述目標細胞特性相符合時,判斷上述第二細胞即為上述目標細胞;當上述第二細胞種類與上述目標細胞種類相同且上述第二細胞特性與上述目標細胞特性不符合時,調整上述基本控制因子序列表中之上述基本控制因子之上述權重及上述優先權順序,以重新選取具有最高權重之基本控制因子作為上述適應性細胞培養參數;或當上述第二細胞種類與上述目標細胞種類不相同且上述第二細胞特性與上述目標細胞特性不符合時,複製上述基本控制因子序列表作為將上述第一細胞培養成上述第二細胞之基本控制因子序列表,並儲存上述基本控制因子序列表至上述資料庫中。 A device for generating adaptive cell culture parameters for culturing a first cell as a target cell, the device comprising: a control circuit; a processor mounted in the control circuit; and a memory mounted in the control circuit And coupled to the processor; wherein the processor is configured to execute a code stored in the memory to perform: according to the first cell type of the first cell and a target cell characteristic from a database Searching for generalized cell culture parameters to establish a basic control factor sequence listing, wherein the basic control factor sequence list includes at least a basic control factor, and a weight and a priority order corresponding to the basic control factor; The above target cell characteristics and the above basic control factor sequence table generate adaptive cell culture parameters; the first cell is cultured according to the above adaptive cell culture parameters, and the first cell is produced. Producing a culture result; and adjusting the above adaptive cell culture parameter according to the above culture result; wherein the culture result is that the first cell is cultured as a second cell, and the processor adjusts the adaptive cell culture parameter according to the culture result The method further includes: determining whether the second cell type of one of the second cells is the same as the target cell species, and determining whether the second cell characteristic of the second cell is consistent with the target cell characteristic; when the second cell type is When the target cell type is the same and the second cell characteristic is consistent with the target cell characteristic, the second cell is determined to be the target cell; when the second cell species is the same as the target cell species and the second cell characteristic is the same as the above When the target cell characteristics are not met, the above-mentioned weights of the above basic control factors in the basic control factor sequence table and the above priority order are adjusted to re-select the basic control factor having the highest weight as the above adaptive cell culture parameter; or when Second cell type and above When the standard cell types are different and the second cell characteristic does not conform to the target cell characteristic, the basic control factor sequence table is copied as a basic control factor sequence table for culturing the first cell into the second cell, and the basic form is stored. The control factor sequence listing is included in the above database. 如申請專利範圍第5項所述之適應性細胞培養參數產 生的裝置,其中上述處理器根據上述第一細胞之上述第一細胞種類及上述目標細胞特性由上述資料庫中搜尋上述一般化細胞培養參數,以建立上述基本控制因子序列表更包括:根據上述第一細胞種類判斷上述第一細胞是否為已知細胞;當判斷上述第一細胞為上述已知細胞時,由上述資料庫中取得對應上述已知細胞之基本控制因子,設定對應上述基本控制因子之權重及優先權順序,並儲存上述基本控制因子、對應上述基本控制因子之權重及優先權順序於上述基本控制因子序列表中;或當判斷上述第一細胞不為上述已知細胞時,儲存預設基本控制因子及對應上述預設基本控制因子之權重及優先權順序於上述基本控制因子序列表中。 Adaptation cell culture parameters as described in item 5 of the patent application scope And the above-mentioned processor, wherein the above-mentioned generalized cell culture parameters are searched from the above-mentioned database according to the first cell type of the first cell and the target cell characteristics, to establish the basic control factor sequence table further includes: Determining, by the first cell type, whether the first cell is a known cell; and when determining that the first cell is the known cell, obtaining a basic control factor corresponding to the known cell from the database, and setting the basic control factor a weight and priority order, and storing the basic control factor, the weight and priority order corresponding to the basic control factor in the basic control factor sequence table; or when determining that the first cell is not the above known cell, storing The preset basic control factor and the weight and priority order corresponding to the preset basic control factor are in the above basic control factor sequence table. 如申請專利範圍第5項所述之適應性細胞培養參數產生的裝置,其中上述處理器根據上述第一細胞之上述第一細胞種類、上述目標細胞特性及上述基本控制因子序列表產生上述適應性細胞培養參數更包括:根據上述第一細胞之上述第一細胞種類判斷上述第一細胞是否為已知細胞;當判斷上述第一細胞為上述已知細胞時,由上述資料庫中取得對應上述已知細胞之基本控制因子,由每一基本控制因子中選取具有最高權重之基本控制因子作為上述適應性細 胞培養參數;或當判斷上述第一細胞不為上述已知細胞時,由上述資料庫中取得與上述第一細胞的上述第一細胞種類類似之第三細胞,複製對應上述第三細胞之基本控制因子作為對應上述第一細胞之基本控制因子,由每一基本控制因子中選取具有最高權重之基本控制因子作為上述適應性細胞培養參數。 The apparatus for producing adaptive cell culture parameters according to claim 5, wherein the processor generates the adaptability according to the first cell type of the first cell, the target cell characteristic, and the basic control factor sequence table. The cell culture parameter further comprises: determining whether the first cell is a known cell according to the first cell type of the first cell; and when determining that the first cell is the known cell, obtaining the corresponding data from the database Knowing the basic control factor of the cell, selecting the basic control factor with the highest weight from each of the basic control factors as the above-mentioned adaptive fineness a cell culture parameter; or when it is determined that the first cell is not the above-mentioned known cell, the third cell similar to the first cell species of the first cell is obtained from the database, and the copy corresponds to the basic of the third cell The control factor is used as a basic control factor corresponding to the first cell, and the basic control factor having the highest weight is selected from each of the basic control factors as the adaptive cell culture parameter. 如申請專利範圍第5項所述之適應性細胞培養參數產生的裝置,當根據上述適應性細胞培養參數培養上述第一細胞時,上述處理器更執行上述程式碼以執行:對上述第一細胞執行一pH濃度預測機制;其中上述pH濃度預測機制係包括:根據上述第一細胞之上述第一細胞種類計算一pH預測值;判斷所偵測上述第一細胞之一pH實際值是否小於一閥值及上述pH預測值;以及當上述pH實際值大於上述閥值且小於上述pH預測值時,執行更換上述第一細胞之培養液。 The apparatus for producing adaptive cell culture parameters according to claim 5, wherein when the first cell is cultured according to the adaptive cell culture parameter, the processor further executes the above code to execute: the first cell Performing a pH concentration prediction mechanism; wherein the pH concentration prediction mechanism comprises: calculating a pH prediction value according to the first cell type of the first cell; and determining whether the actual pH value of one of the first cells detected is less than a valve And a value predicted by the pH; and when the actual value of the pH is greater than the threshold and less than the predicted value of the pH, the culture solution for replacing the first cell is performed. 一種儲存媒體,經由一裝置讀取上述儲存媒體所儲存之程式碼後以執行一適應性細胞培養參數產生方法,用以培養第一細胞為目標細胞,其中上述方法包括以下步驟:根據上述第一細胞之一第一細胞種類及一目標細胞特性由一資料庫中搜尋一般化細胞培養參數,以建立一基本控制 因子序列表,其中上述基本控制因子序列表係至少包括基本控制因子,以及對應上述基本控制因子之權重及優先權順序;根據上述第一細胞種類、上述目標細胞特性及上述基本控制因子序列表產生適應性細胞培養參數;根據上述適應性細胞培養參數培養上述第一細胞,並產生一培養結果;以及根據上述培養結果調整上述適應性細胞培養參數;其中上述培養結果係為上述第一細胞被培養為第二細胞,根據上述培養結果調整上述適應性細胞培養參數更包括:判斷上述第二細胞之一第二細胞種類是否與上述目標細胞種類相同且判斷上述第二細胞之一第二細胞特性是否與上述目標細胞特性相符合;當上述第二細胞種類與上述目標細胞種類相同且上述第二細胞特性與上述目標細胞特性相符合時,判斷上述第二細胞即為上述目標細胞;當上述第二細胞種類與上述目標細胞種類相同且上述第二細胞特性與上述目標細胞特性不符合時,調整上述基本控制因子序列表中之上述基本控制因子之上述權重及上述優先權順序,以重新選取具有最高權重之基本控制因子作為上述適應性細胞培養參數;或當上述第二細胞種類與上述目標細胞種類不相同且上述 第二細胞特性與上述目標細胞特性不符合時,複製上述基本控制因子序列表作為將上述第一細胞培養成上述第二細胞之基本控制因子序列表,並儲存上述基本控制因子序列表至上述資料庫中。 A storage medium, after reading a code stored in the storage medium via a device, to perform an adaptive cell culture parameter generation method for cultivating the first cell as a target cell, wherein the method comprises the following steps: One of the first cell types and a target cell characteristic of a cell is searched for by a database of generalized cell culture parameters to establish a basic control a sequence sequence table, wherein the basic control factor sequence table comprises at least a basic control factor, and a weight and a priority order corresponding to the basic control factor; generating according to the first cell type, the target cell characteristic, and the basic control factor sequence table; An adaptive cell culture parameter; cultivating the first cell according to the above adaptive cell culture parameter, and producing a culture result; and adjusting the adaptive cell culture parameter according to the culture result; wherein the culture result is that the first cell is cultured For the second cell, adjusting the adaptive cell culture parameter according to the culture result further includes: determining whether the second cell type of one of the second cells is the same as the target cell species, and determining whether the second cell characteristic of the second cell is Corresponding to the characteristics of the target cell; when the second cell species is the same as the target cell species and the second cell characteristic is consistent with the target cell characteristic, the second cell is determined to be the target cell; Cell type and upper When the target cell species are the same and the second cell characteristic does not match the target cell characteristic, the weight of the basic control factor in the basic control factor sequence table and the priority order are adjusted to reselect the basic control with the highest weight. a factor as the above adaptive cell culture parameter; or when the second cell species are different from the above target cell species and the above When the second cell characteristic does not conform to the above target cell characteristic, the above basic control factor sequence table is copied as a basic control factor sequence table for culturing the first cell into the second cell, and the basic control factor sequence table is stored to the above data. In the library. 如申請專利範圍第9項所述之儲存媒體,其中根據上述第一細胞之上述第一細胞種類及上述目標細胞特性由上述資料庫中搜尋上述一般化細胞培養參數,以建立上述基本控制因子序列表更包括:根據上述第一細胞種類判斷上述第一細胞是否為已知細胞;當判斷上述第一細胞為上述已知細胞時,由上述資料庫中取得對應上述已知細胞之基本控制因子,設定對應上述基本控制因子之權重及優先權順序,並儲存上述基本控制因子、對應上述基本控制因子之權重及優先權順序於上述基本控制因子序列表中;或當判斷上述第一細胞不為上述已知細胞時,儲存預設基本控制因子及對應上述預設基本控制因子之權重及優先權順序於上述基本控制因子序列表中。 The storage medium according to claim 9, wherein the generalized cell culture parameter is searched from the database according to the first cell type of the first cell and the target cell characteristic to establish the basic control factor sequence. The list further includes: determining whether the first cell is a known cell according to the first cell type; and determining that the first cell is the known cell, obtaining a basic control factor corresponding to the known cell from the database, Setting a weight and a priority order corresponding to the basic control factor, and storing the basic control factor, a weight corresponding to the basic control factor, and a priority order in the basic control factor sequence table; or when determining that the first cell is not the above When the cell is known, the preset basic control factor and the weight and priority order corresponding to the preset basic control factor are stored in the above basic control factor sequence table. 如申請專利範圍第9項所述之儲存媒體,其中根據上述第一細胞之上述第一細胞種類、上述目標細胞特性及上述基本控制因子序列表產生上述適應性細胞培養參數更包括:根據上述第一細胞之上述第一細胞種類判斷上述第一細 胞是否為已知細胞;當判斷上述第一細胞為上述已知細胞時,由上述資料庫中取得對應上述已知細胞之基本控制因子,由每一基本控制因子中選取具有最高權重之基本控制因子作為上述適應性細胞培養參數;或當判斷上述第一細胞不為上述已知細胞時,由上述資料庫中取得與上述第一細胞的上述第一細胞種類類似之第三細胞,複製對應上述第三細胞之基本控制因子作為對應上述第一細胞之基本控制因子,由每一基本控制因子中選取具有最高權重之基本控制因子作為上述適應性細胞培養參數。 The storage medium according to claim 9, wherein the obtaining the adaptive cell culture parameter according to the first cell type of the first cell, the target cell characteristic, and the basic control factor sequence table further comprises: according to the above The first cell type of the above cell determines the first fine Whether the cell is a known cell; when it is judged that the first cell is the above known cell, the basic control factor corresponding to the known cell is obtained from the above database, and the basic control having the highest weight is selected from each of the basic control factors a factor as the above adaptive cell culture parameter; or when it is determined that the first cell is not the above-mentioned known cell, the third cell similar to the first cell type of the first cell is obtained from the database, and the copy corresponds to the above The basic control factor of the third cell is used as a basic control factor corresponding to the first cell, and the basic control factor having the highest weight is selected from each of the basic control factors as the adaptive cell culture parameter. 如申請專利範圍第9項所述之儲存媒體,其中根據上述適應性細胞培養參數培養上述第一細胞更包括:對上述第一細胞執行一pH濃度預測機制;其中上述pH濃度預測機制係包括:根據上述第一細胞之上述第一細胞種類計算一pH預測值;判斷所偵測上述第一細胞之一pH實際值是否小於一閥值及上述pH預測值;以及當上述pH實際值大於上述閥值且小於上述pH預測值時,執行更換上述第一細胞之培養液。 The storage medium according to claim 9, wherein the cultivating the first cell according to the adaptive cell culture parameter further comprises: performing a pH concentration prediction mechanism on the first cell; wherein the pH concentration prediction mechanism comprises: Calculating a pH predicted value according to the first cell type of the first cell; determining whether the actual pH value of one of the first cells detected is less than a threshold value and the pH prediction value; and when the actual pH value is greater than the valve When the value is less than the above-described pH prediction value, the culture solution for replacing the first cell described above is performed.
TW106139303A 2017-11-14 2017-11-14 Method and device for generating adaptive cell culture parameters and storage medium thereof TWI656218B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
TW106139303A TWI656218B (en) 2017-11-14 2017-11-14 Method and device for generating adaptive cell culture parameters and storage medium thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
TW106139303A TWI656218B (en) 2017-11-14 2017-11-14 Method and device for generating adaptive cell culture parameters and storage medium thereof

Publications (2)

Publication Number Publication Date
TWI656218B true TWI656218B (en) 2019-04-11
TW201918561A TW201918561A (en) 2019-05-16

Family

ID=66995926

Family Applications (1)

Application Number Title Priority Date Filing Date
TW106139303A TWI656218B (en) 2017-11-14 2017-11-14 Method and device for generating adaptive cell culture parameters and storage medium thereof

Country Status (1)

Country Link
TW (1) TWI656218B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116926241A (en) * 2023-06-30 2023-10-24 广东美赛尔细胞生物科技有限公司 Immune cell culture control method and system
US11835441B2 (en) 2020-11-20 2023-12-05 Industrial Technology Research Institute Sample classification device, sample classification system, and sample classification method

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0544887A1 (en) * 1991-06-17 1993-06-09 Life Technologies Inc. Media concentrate technology
CN103459584A (en) * 2011-01-14 2013-12-18 科学与技术学院里斯本新大学 A functional enviromics method for cell culture media engineering

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0544887A1 (en) * 1991-06-17 1993-06-09 Life Technologies Inc. Media concentrate technology
CN103459584A (en) * 2011-01-14 2013-12-18 科学与技术学院里斯本新大学 A functional enviromics method for cell culture media engineering

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11835441B2 (en) 2020-11-20 2023-12-05 Industrial Technology Research Institute Sample classification device, sample classification system, and sample classification method
CN116926241A (en) * 2023-06-30 2023-10-24 广东美赛尔细胞生物科技有限公司 Immune cell culture control method and system

Also Published As

Publication number Publication date
TW201918561A (en) 2019-05-16

Similar Documents

Publication Publication Date Title
TWI656218B (en) Method and device for generating adaptive cell culture parameters and storage medium thereof
CN110276470B (en) Search device, search method, and plasma processing device
Bray et al. Computer-based analysis of the binding steps in protein complex formation
CN112513989B (en) Codon optimization
Habibi et al. A review of machine learning methods to predict the solubility of overexpressed recombinant proteins in Escherichia coli
KR20210106357A (en) Information processing system and simulation method
CN1808412A (en) Bus arbitration method and semiconductor apparatus
WO2021197136A1 (en) Page rendering detection method and apparatus
JPH10301979A (en) Method and device for extracting model parameter
CN112529301A (en) Power consumption prediction method, equipment and storage medium
Nghe et al. Sign epistasis caused by hierarchy within signalling cascades
Jackson et al. Computational prediction of the tolerance to amino-acid deletion in green-fluorescent protein
Chen et al. Histopathological images and multi-omics integration predict molecular characteristics and survival in lung adenocarcinoma
Iyer et al. Difference contact maps: From what to why in the analysis of the conformational flexibility of proteins
CN115034369A (en) Fault diagnosis method and device, storage medium and electronic equipment
Wang et al. AI-assisted food enzymes design and engineering: A critical review
CN112785000A (en) Machine learning model training method and system for large-scale machine learning system
CN112084753B (en) Method and system for assisting in editing document
JP2005266866A (en) Document classifying device and classification system generating device and method for document classifying device
Jin et al. Integration Strategy Is a Key Step in Network‐Based Analysis and Dramatically Affects Network Topological Properties and Inferring Outcomes
CN1114877C (en) Information searching apparatus for searching text to retrieve character streams agreeing with key word
CN116469498B (en) Material removal rate prediction method and device, terminal equipment and storage medium
US20230348837A1 (en) Calculation device, control device, culture system, and method for designing culture system
JP2023174450A (en) Information processing method and program
CN113033876B (en) Artificial culture aquatic product growth prediction method and system based on MapReduce and BP neural network