201213541 六、發明說明： 【發明所屬之技術領域】 本發明係關於一種細胞培養系統，尤指一種可即時監 測細胞生長情況之細胞培養系統。 【先前技術】 細胞培養技術是生物科技產業之核心技術，利用人工 培養的方法’在生物體外進行大規模的培養細胞，可以藉 此快速的生產各種生技產品，應用於原料藥、醫藥、疫苗、 生物農藥等各產業。細胞培養的目的，除了可於體外進行 培養以利於短時間内獲得大量目標細胞外，另一個目的， 即在於透過觀察培養過程中細胞之變化，推知活體中各組 織之特性。而於細胞培養過程中加入不同之化合物，亦可 探究化合物對於細胞之影響，包括是否發生細胞毒性或為 可促進細胞生長之物質等。 近年來，隨著技術進步，石英晶體微天平（quartz crysul microbalance，QCM )逐漸被應用於細胞測量。儘管如此， 目前之石英晶體微天平只能透過細胞增殖數量所造成之石 英晶體振盪頻率變化，來觀察細胞生長情況，無法更明確 得知細胞的生長情況，例如無法得知細胞是否有完好的形 成單層膜、是否具有良好的緊密連接（tightjuncti〇n)等， 因此在需要確認細胞單層膜形成良好之情況下才可進行的 實驗中，如腸道上皮細胞吸附實驗、藥物對上皮細胞之穿 透性實驗、細胞表面接合狀態、或者腦血管屏障試驗等， 201213541 便無法利用石英晶體微天平來確認細胞單層膜的形成狀 況。 因此，若可發展出一套細胞培養系統，可達到即時監 測待測細胞生長狀況，同時確保培養系統中各條件恆定狀 況’以確定細胞生長、分化、凋亡變化及緊密連接（ junction)狀況，並可做為藥物刺激結果觀察，亦即建構一 可連續式之細胞研究平臺，將更有利於相關領域發展。 【發明内容】 本發明之主要目的係在提供一種細胞培養系統，其中 整合石英晶體微天平之相關技術，除保有石英晶體微天平 藉由石英晶體振盪之頻率、振幅變化來得知重量變化之原 有功效外，尚整合石英晶體交流阻抗分析、跨細胞阻抗等 技術及特殊細胞培養裝置，並搭配周邊中央控制裝置，控 制培養過程中溫度、濕度及二氧化碳濃度，俾以即時監測 細胞生長情況。 為達上述目的，本發明之一態樣提供一種即時監測之 細胞培養系統，包括：一培養箱；一環境控制裝置，設置 於該培養箱，該環境控制裝置係用以感測該培養箱内之環 境變化；一細胞培養裝置，位於該培養箱中，該細胞測量 裝置包含一細胞培養容器及一石英晶體微天平感測模組， 其中S玄細胞培養容器係用以容納一細胞樣本，該石英晶體 微天平感測模組係用以測量該細胞樣本之跨細胞電阻變 化、以及石英晶體之振盪頻率、振幅及交流阻抗變化；以 201213541 ^一中央㈣裝置’耗合該環境控制裝置以及該細胞培 裝置m英晶體微天平感測模組’且透過控制該環境 控制裝置來調控該培養箱内部之環境變化，並接收及處理 該石英晶體微天平感測模組輸出的該細胞樣本之跨細胞電 炎化以及石英晶體之振盈頻率、振幅及交流阻抗變化。 於本發明即時監測之細胞測量系統中，該環境控制裝 置可L 3 /皿度控制模組、一 2氧化碳控制模組及—濕度 控制模組，該溫度控制模組、該二氧化碳控制模組及該濕 度控制模組係分別感測該培養箱内之溫度變化、二氧化碳 濃度變化及濕度變化。除上述相關環境因子之控制模組之 外，若有需要’該境控制裝置亦可更包含其他模組以調 控其他環境因子^此外，該：氧化碳控制模組的種類沒有 特別限制，舉例可為紅外線二氧化碳感測器、化學二氧化 碳感測器、或超音波二氧化碳感測器。 於本發明即時監測之細胞測量系統中，該細胞培養裝 置可更包含一液體供應模組’以供應一培養基至該細胞培 養容器中，並回收由該細胞培養容器排放之培養基。此外， 該細胞培養容器可具有複數條流道孔，以讓該液體供應模 組經由該些流道孔提供該培養基至該細胞培養容器。再 者’該中央控制裝置可耦合該液體供應模組，以控制該液 體供應模組。具體而言，該液體供應模組可包含幫浦，以 於供應培養基、待測藥劑等液體至該細胞培養容器時，調 控穩定流速進入該細胞培養容器。 201213541 於本發明即時監測之細胞測量系統中，該石英晶體微 天平感測模組可包含一石英晶體振盈單元、一週波產生單 元及一低通濾波單元，該週波產生單元耦合該石英晶體振 盪單元、該低通濾波單元及該中央控制裝置，用以施加一 週波至該細胞樣本。此外，該低通濾波單元可耦合該中央 控制裝置並接收該細胞樣本之跨細胞電阻訊號後傳輸至該 中央控制裝置。再者，該石英晶體微天平感測模組可更包 含一交流阻抗量測單元，該交流阻抗量測單元耦合該石英 晶體振盪單元且用以測量石英晶體之交流阻抗變化。 本發明即時Ji測之細胞測量系統中，該石英晶體微天 平感測模組之石英晶體振盪單元，其結構類似典型的石英 晶體微天平（quartz crystal microbalance，QCM)結構，例 如將兩片金屬做為電極，以三明治方式將石英晶體夾在其 間，於電極上以接近石英晶體之自然諧振頻率施加交替電 壓，使晶體產生機械性振盪。其中一電極做為感測區，測 量細胞樣本，而在細胞生長過程中，觀察因細胞增殖造成 石英晶體振盪的頻率及振幅發生變化，則可以得知細胞樣 本中細胞增殖之情況。 為了使該石英晶體微天平感測模組同時具有測量細胞 增殖數量及跨細胞電阻的雙重功能，因此本發明將該週波 產生單70及該低通濾波單元整合於該石英晶體微天平感測 模組中。其中，該週波產生單元經由一探針電極接觸一細 胞樣本，而產生一週波給該細胞樣本’再利用該石英晶體 振盪單元之感測電極，做為一接收電極，以接收該週波產 201213541 生單元產生之一週波。此時，該低通渡波單元接收傳遞至 該細胞樣本之週波分壓，於此訊號通過時降低其中之高頻 雜訊’因此可以突顯出其中低頻直流訊號，待傳輸至中央 處理裝置則可換算得知跨細胞電阻值。由此可知，若細胞 樣本具有較高的跨細胞電阻值時，表示細胞具有較好的緊 密連接（tight junction)，此係因為細胞膜可以阻隔電流， 而使電流較難通過，因此顯示出較高的跨細胞電阻值。 上述週波產生單元可為定寬度電壓脈衝產生器，而且 • 該週波產生單元之週期舉例可為5秒内施加2 0毫秒至！ 〇 〇毫 秒的電壓脈衝，可以防止該待測樣本在本發明之細胞測量 系統運作期間發生離子化或極化現象。由於，長時間施加 給細胞，會造成細胞生長受到影響，因此本發明之週波產 生器控制在短暫時間内施加電壓，故不會影響細胞生長。 此外，可於該週波產生單元中或該石英晶體微天平感 測模組中設置一位準遷移電路，以偏移該週波產生單元輸 出之週波的電位準，舉例如一 RLC電路，其中之電阻做電 • 壓分壓，電容與電感耦合於該石英晶體振盪單元及該週波 產生單7C，故可耦合前後訊號，並使該週波產生單元輸出 之該第一週波的中線電壓之準位下拉，舉例如將原本〇¥至 5V的電壓範圍下拉至成為-25v至25V的電壓範圍，以防 電壓過大產生過高電流而使細胞樣本發生離子化或極化現 象。 於本發明即時監測之細胞測量系統中，該培養箱係一 加/服|目，且該加溫箱具有風扇以均勻其中氣體濃度。 201213541 上述「環境變化」一詞’係指該培養箱中各種環境因 子之變化’該些環境因子舉例如：溼度、溫度、氣體濃度（如 二氧化碳濃度）、氣壓大小等。上述「頻率變化」一詞，係 指細胞生長過程中，細胞增殖、分泌等造成石英晶體的振 盪頻率、振幅發生改變，以推算出細胞增殖量。上述「跨 細胞電阻」一詞’係指外加的週波通過細胞時，細胞層膜 造成之電位下降，如此則可推算出細胞層膜的電阻值，以 推測細胞層膜的完整性及其緊密連接（tightjuncti〇n)。 由上述可知，本發明保留石英晶體微天平（QCM)原 本可以量測微質量變化的功能，同時整併石英晶體微天平 技術及跨細胞電阻量測技術，即利用石英晶體微天平其中 一電極做為測量跨細胞電阻之接收電極，接收通過細胞之 週波，故可以同時偵測石英晶體頻率、振幅與交流阻抗變 化、及細胞樣本之跨細胞電阻變化。此外，本發明之細胞 培養系統以中央控制裝置監測細胞生長狀況'調控細胞培 養條件、處理培養過程之訊號等，因此本發明之細胞培養 系統可做為一可連續性的細胞研究平臺，進行一連串的細 胞培養、細胞表面接合狀態觀察、藥物穿透實驗、藥物筛 檢、腦血管屏障試驗等，同時達到即時監測及控制的目標。 【實施方式】 以下係藉由特定的具體實施例說明本發明之實施方 式，熟習此技藝之人士可由本說明書所揭示之内容輕易地 了解本發明之其他優點與功效。本發明亦可藉由其他不同 201213541 的具體實施例加以施行或應用，本說明#中的各項細節亦 可基於不同觀點與應用，在不詩本發明之精神下 種修飾與變更。 本發明之實施例中該等圖式均為簡化之示意圖。惟該 等圖示僅顯示與本發明有關之元件，其所顯示之元件非為 實際實施時之態樣’其實際實施時之元件數目、形狀等比 例為it擇性之設計，且其元件佈局型態可能更複雜。 實施例 圖1係本發明之即時監測之細胞培養系統的示意圖。該 細胞培養系統包括··一培養箱10、一環境控制裝置2〇、一 細胞培養裝置30、以及一中央控制裝置4〇。 該環境控制裝置20設置於該培養箱1〇，用以感測該培 養箱10内之環境因子的變化。 該細胞培養裝置30位於該培養箱1〇中，該細胞測量裝 置30包含一細胞培養容器31及一石英晶體微天平感測模組 32，其中’該細胞培養容器3丨係用以容納一細胞樣本該 石英晶體微天平感測模組3 2係用以測量該細胞樣本之跨細 胞電阻變化、以及石英晶體之振盪頻率、振幅及交流阻抗 變化。該細胞培養容器3 1具有複數條流道孔3丨〇，以讓—液 體供應模組33經由該些流道孔3 10提供培養基至該細胞培 養容器3 1。此液體供應模組33可包含幫浦331、332，而可 在供應培養基、待測藥劑等液體至該細胞培養容器3丨時， 提供穩定流速。 201213541 該中央控制裝置40麵合該環境控制裝置2〇 '以及^田 胞培養裝置30之該石英晶體微天平感測模組32，且透過控 制該環境控制裝置2G來調控該培養箱_部之環境因子: 變化，並接收及處理該石英晶體微天平感龍組^輸出的 該細胞樣本之跨細胞電阻變化、以及石英晶體之振錢 率、振幅及交流阻抗變化。 圖2係本發明之即時監測之細胞培養系統中，中央控制 裝置所耦合之元件的系統方塊示意圖。 如圖2所示，該環境控制裝置2〇耦合該中央控制裝置 4〇,該環境控制裝置20包含一溫度控制模組21、:二氧化 碳控制模組22及一濕度控制模組23。該溫度控制模組21、 該二氧化碳控制模組22及該濕度控制模組23係分別感測該 培養箱10内之溫度變化、二氧化碳濃度變化及濕度變化。 於本實施例中，該培養箱1〇係一加溫箱，且其中之二氧化 碳控制模組22連接外部的二氧化碳鋼瓶，因此可透過該中 央控制裝置40調整該培養箱1〇内的二氧化碳濃度。 具體而言’可把該培養箱1 〇内的環境條件設定於溫度 為37°C、二氧化碳濃度為5%且溼度為飽和溼度，亦即提供 細胞恆定的生長環境，使細胞於恆溫、恆二氧化碳濃度、 以及怪濕度下培養生長。除上述相關環境因子之控制模組 之外’若有需要，該環境控制裝置20亦可更包含其他模組 以調控其他環境因子。 該液體供應模組33耦合該中央控制裝置40，以供應一 培養基至該細胞培養容器3 1中。此液體供應模組33可包含 201213541 幫浦、供應槽、及回收槽，以於供應培養基、待測藥劑等 液^該細胞培養容器31時，調控穩定流速進入該細胞培 f容器31 ’同時提供細胞在穩定流速的培養基下培養，亦 疋提供、..田月IL f亙疋的生長環境；另一方面，由於此液體供應 模組33具有时槽，因此若需要分析培養後之培養基亦 可由回收槽中取樣分析。 該石英晶體微天平感測模組32可包含一石英晶體振盪 單元322週波產生單元323、一低通濾波單元324、及一 交流阻抗量測單元321，其中，該週波產生單元323耦合該 石英晶體振盪單元322、該低通濾波單元324及該中央控制 裝置40，利用探針電極施加一週波至細胞樣本，；並由該石 英晶體振盪單元322之感測電極做為接收電極。此時，耦合 該t央控制裝置4 0之該低通濾波單元3 2 4接收傳遞至該細 胞樣本之週波分壓，並降低其中高頻雜訊，而後輸出低頻 直流訊號給該中央控制裝置40，以供其處理計算出該細胞 樣本之跨細胞電阻值。該交流阻抗量測單元321耦合該石英 晶體振盪單元324，用以測量石英晶體之交流阻抗變化。 由上述可知’本發明利用t央控制裝置耦合環境控制 裝置、石英晶體微天平感測模組及液體供應模組，由中央 控制裝置控制培養細胞的環境因子，包括：溫度、二氧化 碳濃度、溼度、培養基供應流速等，再加上即時處理由石 英晶體微天平感測模組測得之石英晶體振盪頻率、振幅大 小、與交流阻抗變化，以及細胞樣本的跨細胞電阻 (Trans-Epithelial Electric Resistance > TEER)，亦即使所 201213541 有資訊皆可透過中央控制裝置進行雙向溝通'處理，因此 可達到即時監測及控制之目的。 上述實施例僅係為了方便說明而舉例而已，本發明所 主張之權利範圍自應以申請專利範圍所述為準而非僅限 於上述實施例。 【圖式簡單說明】 圖1係本發明實施例之即時監測之細胞測量系統的示意圖。 圖2係本發明實施例之即時監測之細胞培養系統中’中央控 制裝置所耦合之元件的系統方塊示意圖。 【主要元件符號說明】 培養箱 10 環境控制裝置 20 細胞培養裝置 30 中央控制裝置 40。 細胞培養容器 31 石英晶體微天平感測模組 32 流道孔 310 液體供應模組 33 溫度控制模組 21 二氧化碳控制模組 22 濕度控制模組 23 石英晶體振盪單元 322 12 201213541201213541 VI. Description of the Invention: [Technical Field] The present invention relates to a cell culture system, and more particularly to a cell culture system capable of monitoring cell growth in real time. [Prior Art] Cell culture technology is the core technology of the biotechnology industry. It uses the artificial culture method to carry out large-scale cultivation of cells outside the organism, so that it can quickly produce various biotechnology products for use in APIs, medicines, and vaccines. , bio-pesticide and other industries. The purpose of cell culture, in addition to being cultured in vitro to facilitate obtaining a large number of target cells in a short period of time, is to infer the characteristics of each tissue in the living body by observing changes in cells during the culture. By adding different compounds to the cell culture process, the effects of the compound on the cells, including whether cytotoxicity or substances that promote cell growth, can also be explored. In recent years, with the advancement of technology, quartz crystal microscopy (QCM) has been gradually applied to cell measurement. Despite this, the current quartz crystal microbalance can only observe the cell growth by the change of the oscillation frequency of the quartz crystal caused by the amount of cell proliferation, and it is impossible to know the growth of the cell more clearly. For example, it is impossible to know whether the cell is intact or not. A single-layer membrane, whether it has a good tight junction (tightjuncti〇n), etc., so in experiments where it is necessary to confirm that the cell monolayer membrane is well formed, such as intestinal epithelial cell adsorption experiments, drugs for epithelial cells Penetration test, cell surface junction state, or cerebral vascular barrier test, etc., 201213541 It is impossible to confirm the formation of cell monolayer film by using quartz crystal microbalance. Therefore, if a cell culture system can be developed, it is possible to instantly monitor the growth of the cells to be tested while ensuring constant conditions in the culture system to determine cell growth, differentiation, apoptosis changes and junctional conditions. It can be used as a drug stimulation result observation, that is, constructing a continuous cell research platform, which will be more conducive to the development of related fields. SUMMARY OF THE INVENTION The main object of the present invention is to provide a cell culture system in which a quartz crystal microbalance is integrated, and the weight change of the quartz crystal microbalance is known by the frequency and amplitude change of the quartz crystal oscillation. In addition to the efficacy, it is integrated with quartz crystal AC impedance analysis, trans-cell impedance and other special cell culture equipment, and with the surrounding central control device to control the temperature, humidity and carbon dioxide concentration during the culture process, to monitor cell growth in real time. To achieve the above object, an aspect of the present invention provides an instant monitoring cell culture system, comprising: an incubator; an environmental control device disposed in the incubator, the environmental control device for sensing the inside of the incubator Environmental change; a cell culture device, located in the incubator, the cell measurement device comprises a cell culture container and a quartz crystal microbalance sensing module, wherein the S-cell culture container is for accommodating a cell sample, The quartz crystal microbalance sensing module is used for measuring the transcellular resistance change of the cell sample, and the oscillation frequency, amplitude and AC impedance change of the quartz crystal; and the environmental control device is consumed by the 201213541 ^ a central (four) device The cell culture device m-crystal micro-balance sensing module' controls the environmental control device to control the environmental change inside the incubator, and receives and processes the cross-section of the cell sample output by the quartz crystal microbalance sensing module Cell electro-inflammation and changes in the frequency, amplitude, and AC impedance of quartz crystals. In the cell measurement system for instant monitoring of the present invention, the environmental control device can be a L 3 / dish control module, a carbon dioxide control module and a humidity control module, the temperature control module, the carbon dioxide control module And the humidity control module senses temperature changes, carbon dioxide concentration changes, and humidity changes in the incubator. In addition to the above-mentioned control module of the relevant environmental factors, if necessary, the environment control device may further include other modules to regulate other environmental factors. In addition, the type of the carbon oxide control module is not particularly limited. It is an infrared carbon dioxide sensor, a chemical carbon dioxide sensor, or an ultrasonic carbon dioxide sensor. In the cell measurement system for immediate monitoring of the present invention, the cell culture device may further comprise a liquid supply module ' to supply a medium to the cell culture container, and recover the medium discharged from the cell culture container. Additionally, the cell culture vessel can have a plurality of channel holes for the liquid supply module to provide the medium to the cell culture vessel via the channel holes. Further, the central control device can be coupled to the liquid supply module to control the liquid supply module. Specifically, the liquid supply module may include a pump to adjust a steady flow rate into the cell culture container when supplying a medium such as a medium or a test agent to the cell culture container. 201213541 In the cell measurement system for real-time monitoring of the present invention, the quartz crystal microbalance sensing module can include a quartz crystal oscillation unit, a one-wave generation unit and a low-pass filter unit, and the cycle generation unit couples the quartz crystal oscillation The unit, the low pass filtering unit and the central control device are configured to apply a one-wave wave to the cell sample. In addition, the low pass filtering unit can be coupled to the central control device and receive the transcellular resistance signal of the cell sample and transmitted to the central control device. Furthermore, the quartz crystal microbalance sensing module further includes an AC impedance measuring unit coupled to the quartz crystal oscillation unit and configured to measure an AC impedance change of the quartz crystal. In the instant Ji measurement cell measurement system of the present invention, the quartz crystal oscillation unit of the quartz crystal microbalance sensing module has a structure similar to a typical quartz crystal microbalance (QCM) structure, for example, two pieces of metal are used. For the electrode, a quartz crystal is sandwiched therebetween, and an alternating voltage is applied to the electrode at a natural resonant frequency close to the quartz crystal to cause mechanical oscillation of the crystal. One of the electrodes serves as a sensing region to measure the cell sample, and during the cell growth process, the frequency and amplitude of the quartz crystal oscillation caused by the cell proliferation are observed, and the cell proliferation in the cell sample can be known. In order to make the quartz crystal microbalance sensing module have the dual functions of measuring the cell proliferation quantity and the transcellular resistance, the present invention integrates the cycle generation unit 70 and the low-pass filter unit into the quartz crystal microbalance sensing mode. In the group. Wherein, the cycle generating unit contacts a cell sample via a probe electrode, and generates a one-wave wave to the cell sample to reuse the sensing electrode of the quartz crystal oscillation unit as a receiving electrode to receive the cycle product 201213541 The unit produces a cycle. At this time, the low-pass wave unit receives the partial pressure of the pulse transmitted to the cell sample, and reduces the high-frequency noise when the signal passes. Therefore, the low-frequency DC signal can be highlighted, and can be converted to the central processing device. Know the transcellular resistance value. It can be seen that if the cell sample has a high transcellular resistance value, it means that the cell has a good tight junction. This is because the cell membrane can block the current and make the current difficult to pass, so it shows a higher Transcellular resistance value. The above-mentioned cycle generating unit may be a constant-width voltage pulse generator, and • the cycle of the cycle generating unit may be applied for 20 milliseconds in 5 seconds! A voltage pulse of 〇 〇 can prevent ionization or polarization of the sample to be tested during operation of the cell measurement system of the present invention. Since application of cells to cells for a long period of time causes cell growth to be affected, the cycle generator of the present invention controls the application of voltage for a short period of time, so that cell growth is not affected. In addition, a quasi-migration circuit may be disposed in the cycle generating unit or the quartz crystal microbalance sensing module to offset the potential of the cycle outputted by the cycle generating unit, for example, an RLC circuit, wherein the resistor is The voltage is divided, the capacitor and the inductor are coupled to the quartz crystal oscillating unit and the cycle generating unit 7C, so that the front and rear signals can be coupled, and the level of the first line of the first cycle outputted by the cycle generating unit is pulled down. For example, the voltage range of the original 至¥ to 5V is pulled down to a voltage range of -25v to 25V, in order to prevent the voltage from being too high to generate an excessive current to cause ionization or polarization of the cell sample. In the cell measurement system of the present invention for immediate monitoring, the incubator is added/served, and the warming box has a fan to uniform the concentration of the gas therein. 201213541 The term "environmental change" as used above refers to the change of various environmental factors in the incubator. The environmental factors such as humidity, temperature, gas concentration (such as carbon dioxide concentration), and atmospheric pressure. The term "frequency change" refers to the change in the oscillation frequency and amplitude of the quartz crystal caused by cell proliferation and secretion during cell growth to estimate the amount of cell proliferation. The term "transcellular resistance" refers to the decrease in the potential caused by the cell membrane when the applied cycle passes through the cell, so that the resistance of the cell membrane can be derived to estimate the integrity of the cell membrane and its tight junction. (tightjuncti〇n). It can be seen from the above that the present invention retains the function that the quartz crystal microbalance (QCM) can measure the micro-mass change at the same time, and at the same time, the quartz crystal microbalance technology and the transcellular resistance measurement technology, that is, one of the electrodes of the quartz crystal microbalance is used. In order to measure the cross-cell resistance of the receiving electrode and receive the cycle through the cell, it is possible to simultaneously detect the quartz crystal frequency, amplitude and AC impedance change, and the transcellular resistance change of the cell sample. In addition, the cell culture system of the present invention monitors the cell growth condition by the central control device, regulates the cell culture condition, and processes the signal of the culture process, etc., so that the cell culture system of the present invention can be used as a continuous cell research platform for performing a series of Cell culture, cell surface junction state observation, drug penetration test, drug screening, cerebrovascular barrier test, etc., while achieving the goal of immediate monitoring and control. [Embodiment] The embodiments of the present invention will be described by way of specific examples, and those skilled in the art can readily understand other advantages and effects of the present invention from the disclosure of the present disclosure. The present invention may be embodied or applied by other specific embodiments of the present invention. The details of the present invention can also be modified and changed without departing from the spirit and scope of the invention. The drawings in the embodiments of the present invention are simplified schematic diagrams. However, the drawings show only the components related to the present invention, and the components shown therein are not in actual implementation. The actual number of components in the actual implementation, the shape and the like are designed in an alternative manner, and the component layout thereof. The pattern may be more complicated. EXAMPLES Figure 1 is a schematic representation of a cell culture system for immediate monitoring of the present invention. The cell culture system comprises an incubator 10, an environmental control device 2, a cell culture device 30, and a central control device 4A. The environmental control device 20 is disposed in the incubator 1A for sensing a change in an environmental factor in the culture tank 10. The cell culture device 30 is located in the incubator 1 . The cell measuring device 30 comprises a cell culture container 31 and a quartz crystal microbalance sensing module 32, wherein the cell culture container 3 is used to accommodate a cell. Sample The quartz crystal microbalance sensing module 32 is used to measure the transcellular resistance change of the cell sample, and the oscillation frequency, amplitude and AC impedance change of the quartz crystal. The cell culture vessel 31 has a plurality of channel holes 3 丨〇 to allow the liquid supply module 33 to supply a medium to the cell culture container 31 via the channel holes 3 10 . The liquid supply module 33 may include the pumps 331, 332 to provide a stable flow rate when supplying a medium such as a medium or a test agent to the cell culture container. 201213541 The central control device 40 faces the quartz crystal microbalance sensing module 32 of the environmental control device 2' and the cell culture device 30, and controls the incubator by controlling the environmental control device 2G Environmental factors: change, and receive and process the transcellular resistance change of the cell sample outputted by the quartz crystal microbalance, and the change of the vibration rate, amplitude and AC impedance of the quartz crystal. Figure 2 is a block diagram showing the system of components coupled to the central control unit in the cell culture system for immediate monitoring of the present invention. As shown in FIG. 2, the environmental control device 2 is coupled to the central control device 4, and the environmental control device 20 includes a temperature control module 21, a carbon dioxide control module 22, and a humidity control module 23. The temperature control module 21, the carbon dioxide control module 22, and the humidity control module 23 respectively sense temperature changes, carbon dioxide concentration changes, and humidity changes in the incubator 10. In the present embodiment, the incubator 1 is a heating tank, and the carbon dioxide control module 22 is connected to an external carbon dioxide cylinder, so that the concentration of carbon dioxide in the incubator 1 can be adjusted through the central control unit 40. Specifically, the environmental conditions in the incubator 1 can be set at a temperature of 37 ° C, a carbon dioxide concentration of 5%, and a humidity of saturated humidity, that is, a constant growth environment of the cells, so that the cells are kept at a constant temperature and constant carbon dioxide. Concentration, and culture growth under strange humidity. In addition to the control modules of the relevant environmental factors described above, the environmental control device 20 may further include other modules to regulate other environmental factors. The liquid supply module 33 is coupled to the central control unit 40 to supply a medium to the cell culture vessel 31. The liquid supply module 33 may include a 201213541 pump, a supply tank, and a recovery tank for regulating the steady flow rate into the cell culture container 31 while supplying the culture medium, the reagent to be tested, and the like. The cells are cultured in a medium with a stable flow rate, and the growth environment of the Tianyue IL f亘疋 is also provided. On the other hand, since the liquid supply module 33 has a time slot, the culture medium after the analysis can be analyzed by Sampling analysis in the recovery tank. The quartz crystal microbalance sensing module 32 can include a quartz crystal oscillation unit 322 cycle generation unit 323, a low pass filter unit 324, and an AC impedance measurement unit 321, wherein the cycle generation unit 323 couples the quartz crystal. The oscillating unit 322, the low-pass filtering unit 324, and the central control device 40 apply a one-wave wave to the cell sample by using the probe electrode; and the sensing electrode of the quartz crystal oscillating unit 322 serves as a receiving electrode. At this time, the low-pass filtering unit 324 coupled to the t-th control device 40 receives the partial voltage division transmitted to the cell sample, and reduces the high-frequency noise therein, and then outputs the low-frequency DC signal to the central control device 40. , for its processing to calculate the transcellular resistance value of the cell sample. The AC impedance measuring unit 321 is coupled to the quartz crystal oscillation unit 324 for measuring the AC impedance change of the quartz crystal. It can be seen from the above that the present invention utilizes a t-control device coupling environment control device, a quartz crystal microbalance sensing module and a liquid supply module, and the central control device controls the environmental factors of the cultured cells, including: temperature, carbon dioxide concentration, humidity, The medium supply flow rate, etc., plus the instantaneous processing of the quartz crystal oscillation frequency, amplitude, and AC impedance change measured by the quartz crystal microbalance sensing module, and the trans-Epithelial Electric Resistance of the cell sample (Trans-Epithelial Electric Resistance > TEER), even if the information is available in 201213541, the two-way communication can be handled through the central control unit, so that it can achieve immediate monitoring and control. The above-described embodiments are merely examples for the convenience of the description, and the scope of the claims is intended to be limited to the scope of the claims. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic illustration of a cell monitoring system for immediate monitoring in accordance with an embodiment of the present invention. Fig. 2 is a block diagram showing the system of the components coupled to the central control unit in the immediately monitored cell culture system of the embodiment of the present invention. [Description of main component symbols] Incubator 10 Environmental control device 20 Cell culture device 30 Central control device 40. Cell culture vessel 31 Quartz crystal microbalance sensing module 32 Flow channel 310 Liquid supply module 33 Temperature control module 21 Carbon dioxide control module 22 Humidity control module 23 Quartz crystal oscillation unit 322 12 201213541
週波產生單元 323 低通濾波單元 324 交流阻抗量測單元 321 幫浦 331、332 13Cycle generation unit 323 Low-pass filter unit 324 AC impedance measurement unit 321 Pump 331, 332 13