201202714 六、發明說明： 【發明所屬之技術領域】 [0001] 本發明係有關於一種阻抗量測裝置’尤其是一種用 於分析生物分子及生物之阻抗量測裝置。 【先前技術】 自1962年Clark和Lyon兩人提出酵素電極的觀念以 後’美國YSI(Yellow Spring Instrument Company) 公司於七零年代即積極投入商品化開發與生產，啟開了 第一世代生物感測器於1 979年投入醫檢市場。近年來， 由於科技技術的進步，且在應用市場及商業價值上逐年 大巾田k昇’各方面對於生物威測.器.的研究愈來愈多，現 今的生物感測器多具備攜帶式、自動化與即時測定功能 "Η执# 土个V PW 双里八崎， 由於代謝對溶液的影響’而使電極表面電荷累積改變造 成電雙層電容變〃、，使其整蠢漏大，因電路複雜成 本非常高。 :華民國專利公開號 與待=揭=魏生物檢，藉生_ 電流，以判斷是否存在二:: 貞測生物檢測器 、放大器及參考檢測器，；=’其需要數個電壓源 性分析無法定#分析。_成本較⑥’且僅能定 【發明内容】 種阻抗量測 有鑑於此，本發明之目的就是在提供 099122996 第4頁/共22頁 表單編號Α0101 0992040532-0 [0003] 201202714 、置以提供靈敏度兩且成本低廉的生物研究及健康及 醫療臨床;^測之阻抗量測裝置，解決習知技藝中生物檢 、’J方法方便操作、定性、定量及電路複雜成本較高之問 題。 本發明之阻抗量測裝置包含—感測晶片'一阻抗轉 換元件、—資訊處理元件及一輸出元件。該感測晶片之 表面可供置放待測之—生物細胞，該阻抗感測元件與該 感測晶片相接，量測一阻抗值，該資訊處理元件藉連接 阜與謔阻抗轉換元件連接，用於讀取及傳送該阻抗值， 輸出元件接收該阻抗值並顯示或儲存，當生物細胞濃度 變化時，該感測晶片之電子特性改變，使該阻抗值變化 ’藉此能針對生物細胞做定量分析, 承上所述’因依本發明之阻抗量測裝置，具有以下 功效： (1) 本發明之阻抗量測裝置相較一般電化學阻抗分 析儀’直流偏移訊號較大，所以能針對最佳之訊號增益 度提供交、直流之複合式電壓調整，在生物阻抗量測上 靈敏度較一般電化學阻抗分析翁高。 (2) 本發明之阻抗量測裝置，其電路及元件較簡單 ，且量測資料也數位化，除成本較低外、可量產外，應 用上也更加方便及容易。 (3) 本發明之阻抗量測裝置，已能量測出不同數量 的細胞阻抗及生物分子之變化，其靈敏度可達到定量分 析之效果。 【實施方式】 [0004] 099122996 請參閱第1圖，其係為本發明之阻抗量測裝置之示意 表單編號A0101 第5買/共22頁 0992040532-0 201202714 圖。圖中，阻抗量測裝置（1)包含感測晶片（li)、阻抗轉 換元件（12)、資訊處理元件（13)及輸出元件（14)。其中 感測晶片（11)表面可供置放待測之生物細胞或生物分子 ;阻抗轉換元件（12)與感測晶片（11)之電極相接，根據 感測晶片表面之生物細胞或生物分子變化時造成電雙層 電容的變化，而量測一阻抗值（15);資訊處理元件（13) ，用於讀取及傳送阻抗轉換元件（丨2)所測得之阻抗值 (15)，其與阻抗轉換元件（12)之間的溝通橋樑是以 2 I C(Inter-Integrated Circuit)的溝通方式做為阻 抗值（15)的表現，且藉由連接埠輿談阻抗轉換元件（12) 連接，同時連接埠做為時脈傳送籍資料傳送線與阻抗轉 換几件（12)溝通，輸出元件（14)藉RS232串列通訊與資 訊處理元件（13)連接，用於接收阻抗值（15)顯示或儲存 ，當感測晶片（11)表面的生物細胞變化時，感測晶片 (11)之電雙層電容隨之改變，而使阻抗轉換元件（12)量 測到的阻抗值（15)不同。 本發明之阻抗量測裝置之感測晶片之製作過程包含 基板切割、基板清洗、光阻塗伟、枝烤、曝光、顯影、 蒸鍍金屬'剝離及沉積二氧化矽之步驟。 其中，依本發明之阻抗量測裝置之輸出元件（14)係藉串 列傳輸接收該阻抗值。資訊處理元件（13)較佳為微處理 器輸出元件（14)較佳為電腦。該生物細胞較佳之變化 較佳為生物細胞生長代謝或分裂造成生物細胞的數量變 化0 請參閱第2圖，其係為本發明之阻抗量測裝置之實施 0992040532- 例示意圖。圖中，阻抗量測裝置包含感測晶片（21)、 099122996 表單編號A0101 第6頁/共22頁 201202714 AD5933電路（22)、微處理電路（23)、 電腦（24)、内部 鲨合電路（25)及RS232電路（26)。其中，其中感測晶片 Ο (21)表面可供置放待測之生物細胞；AD5g33電路與 感測晶片（21)之電極相接，根據感測晶片表面之生物細 胞浪度變化時造成電雙層電容的變化，而量測一阻抗值 ’微處理電路（23) ’用於讀取及傳送阻抗轉換元件（12) 所測得之阻抗值（15) ’其與AD5933電路之間的溝通 橋樑是以内部整合電路（25)傳遞阻抗值’且藉由連接埠（ 圖未示）與該AD5933電路（22)連接，同時連接埠（圖未示 )做為時脈傳送籍資料傳送線舆AD5933電路（22 )溝通， 電腦（24)藉RS232電路（26)與微處理電路（23)連接，用 於接收阻抗值並顯示或儲存；當感測晶片（21)表面的生 物細胞濃度變化時，感測晶片（21)之電雙層電容隨之改 變，而使AD5933電路（22)量測到的阻抗值不同。201202714 VI. Description of the Invention: [Technical Field of the Invention] [0001] The present invention relates to an impedance measuring device', particularly an impedance measuring device for analyzing biomolecules and living things. [Prior Art] Since the concept of enzyme electrodes was proposed by Clark and Lyon in 1962, the United States YSI (Yellow Spring Instrument Company) actively engaged in commercial development and production in the 1970s, opening the first generation of biological sensing. The machine was put into the medical examination market in 1979. In recent years, due to the advancement of technology and technology, and in the application market and commercial value, the company has been researching more and more on biometric devices. Today's biosensors are more portable. , automation and real-time measurement function "Η执# soil V PW Shuangli Baqi, due to the influence of metabolism on the solution', the electrode surface charge accumulation changes cause the electric double-layer capacitance to become sinister, making it a whole stupid leak, due to The complexity of the circuit is very high. :Huaguoguo Patent Publication No. and Waiting = Jie = Wei Biometric, Borrowing _ Current to determine whether there is two:: Detecting biodetectors, amplifiers and reference detectors; == It requires several voltage source analysis Unable to set #分析. _ cost is 6' and can only be determined [invention] The impedance measurement is in view of this, the object of the present invention is to provide 099122996 page 4 / total 22 page number Α 0101 0992040532-0 [0003] 201202714, provided The two-sensitivity and low-cost biological research and health and medical clinical; ^ measured impedance measuring device, to solve the problem of biological testing, 'J method convenient operation, qualitative, quantitative and complex circuit cost. The impedance measuring device of the present invention comprises a sensing chip 'an impedance converting element, an information processing element and an output element. The surface of the sensing chip can be used to place a biological cell to be tested, the impedance sensing component is connected to the sensing chip, and an impedance value is measured, and the information processing component is connected to the 谑 impedance conversion component by a connection ,, For reading and transmitting the impedance value, the output component receives the impedance value and displays or stores. When the concentration of the biological cell changes, the electronic characteristic of the sensing chip changes, and the impedance value changes, thereby enabling the biological cell to be made Quantitative analysis, according to the above-mentioned impedance measuring device according to the present invention, has the following effects: (1) The impedance measuring device of the present invention has a larger DC offset signal than the general electrochemical impedance analyzer, so The combination of AC and DC voltage adjustment is provided for the best signal gain, and the sensitivity of the bioimpedance measurement is higher than that of the general electrochemical impedance analysis. (2) The impedance measuring device of the present invention has a simple circuit and components, and the measuring data is also digitized. In addition to low cost and mass production, the application is also more convenient and easy. (3) The impedance measuring device of the present invention has been able to measure different amounts of cell impedance and changes in biomolecules, and the sensitivity thereof can achieve the effect of quantitative analysis. [Embodiment] [0004] 099122996 Please refer to FIG. 1 , which is a schematic diagram of the impedance measuring device of the present invention. Form No. A0101 5th Buy/Total 22 pages 0992040532-0 201202714 Diagram. In the figure, the impedance measuring device (1) comprises a sensing wafer (li), an impedance converting element (12), an information processing element (13) and an output element (14). Wherein the surface of the sensing wafer (11) is capable of placing biological cells or biomolecules to be tested; the impedance converting element (12) is connected to the electrodes of the sensing wafer (11) according to biological cells or biomolecules sensing the surface of the wafer. The change causes an electric double layer capacitance change, and measures an impedance value (15); the information processing component (13) is used for reading and transmitting the impedance value (15) measured by the impedance conversion element (丨2), The communication bridge between the impedance conversion element (12) and the impedance conversion component (12) is represented by the impedance of the IC (Inter-Integrated Circuit) and is connected by the impedance conversion component (12). At the same time, the connection port is used as a clock transmission data transmission line to communicate with several pieces of impedance conversion (12), and the output component (14) is connected to the information processing component (13) by RS232 serial communication for receiving the impedance value (15). Displaying or storing, when sensing the biological cell change on the surface of the wafer (11), the electric double layer capacitance of the sensing wafer (11) is changed, and the impedance value measured by the impedance converting element (12) is (15) different. The manufacturing process of the sensing wafer of the impedance measuring device of the present invention comprises the steps of substrate cutting, substrate cleaning, photoresist coating, branch baking, exposure, development, vapor deposition of metal stripping and deposition of cerium oxide. Wherein, the output component (14) of the impedance measuring device according to the present invention receives the impedance value by serial transmission. Preferably, the information processing component (13) is a microprocessor output component (14), preferably a computer. Preferably, the change in the biological cell is a change in the number of biological cells caused by growth or metabolism of the biological cell. See Fig. 2, which is an implementation of the impedance measuring device of the present invention. 0992040532 - A schematic diagram of an example. In the figure, the impedance measuring device comprises a sensing chip (21), 099122996, a form number A0101, a sixth page, a total of 22 pages, a 201202714 AD5933 circuit (22), a microprocessing circuit (23), a computer (24), an internal shark circuit ( 25) and RS232 circuit (26). Wherein, the surface of the sensing wafer Ο (21) can be used for placing the biological cells to be tested; the circuit of the AD5g33 is connected to the electrodes of the sensing wafer (21), and the electrical double is caused according to the change of the biological cell wave amplitude on the surface of the sensing wafer. The change in layer capacitance, and the measurement of an impedance value 'microprocessing circuit (23) 'used to read and transmit the impedance value measured by the impedance conversion component (12) (15) 'the bridge between it and the AD5933 circuit The internal integrated circuit (25) transmits the impedance value ' and is connected to the AD5933 circuit (22) through a connection port (not shown), and the connection port (not shown) is used as a clock transmission data transmission line 舆 AD5933 The circuit (22) communicates, and the computer (24) is connected to the micro-processing circuit (23) via the RS232 circuit (26) for receiving the impedance value and displaying or storing; when sensing the concentration of the biological cell on the surface of the wafer (21), The electric double layer capacitance of the sensing wafer (21) changes accordingly, and the impedance values measured by the AD5933 circuit (22) are different.
G 請參閱第3圖，其係為本發明之阻抗量測裝置之感測 晶片之指叉電極之示意圖。圖中指叉電極（3)包含一第一 梳狀電極（31)及一第二梳狀電極（π)，第一梳狀電極 (31)及第二梳狀電極（32)係以交錯方式排列。其中本發 明之阻抗量測裝置之感測晶片之電極較佳可選用單一式 指叉電極或陣列式指叉電極。此處選用指叉電極是因為 指叉電極的幾何面積不同於傳統電極，因此在有限的空 間下，可以整齊排列出的感娜面積優於普通傳統電極， 使得指又電極具有將感測訊號放大的功能，靈敏度提高 。且指叉電極採用阻抗形式的觀察方法，在生物分子感 測上可免除使用放射物、螢光劑、生化酵素或電化學標 定等判別方式。 099122996 表單編號A0101 第7頁/共22頁 0992040532-0 201202714 指叉電極數目大於一對以上時可使其並聯做為陣列 式指叉電極’而電容計算如下式（A)所示。由公式中可知 ，電容值（Capacitance)主要由一些相關參數決定， 分別為η :指又電極數目；1 :指叉電極長度；ε :介電 係數；K(k):第一完全橢圓積分式函數；评：指又電極寬 度；s :指又電極間距。而此式在電極寬度（w)與電極 間距（S)相同情況下’可進一步簡化為下式（B)。 K C=nlS- 2Κ / 細、 2(奸 / C sin V 7m 2^+w)^ (A) 為了製程上的容易實現及符合式（Β)的理論計算，設 計的電極寬度及電極間距目前换固宅為相同尺寸，而單 —式指叉電極完整的設計參^1^^表|所示。 [表1〕 電極寬度（Width，W) 8 /z m 電極間距（Space，S) 8 ^ m 電極長度（Length，L) 500 ^ m 電極厚度（Thickness) Cr ( 2 nm) /Au ( 50 nm) 電極數目（Number) 450 pairs 099122996 表單蝙號Α0101 第8頁/共22頁 0992040532-0 201202714 [0006] [0007] 請參閱第4圖’其係為本發明之阻抗量測裝置之資訊 處理70件之控制流程圖資訊處理元件的_程式以〇語 言程式編輯工具keil C撰寫，在一開始韌體程式的初始 化串列通訊埠上，在串列傳輸設定其相關傳送速率及資 訊處理兀件所需使用的計數器等。在串列通訊埠完成設 定後進打資料傳送，資料傳送及接收可以依據 資訊處理 ❹ 元件内的特定暫存器判斷資料是否接收（傳送）結束，如 資訊處理几件内的串列埠控制暫存器（Serial p〇rt Control Register)内的布林值（TI)來辦別傳送資料是 否完成’而串列埠控制暫存器（Serial P〇rt C〇ntr〇i Register)内的布林值（R1)可以用來判斷接收資料是否 成功。無論接收或傳送資料，資料值皆被放置在串列資 料緩衝器（Serial Buffer ; SBUF)内以供下一步處理。 Ο 在結束串列埠設定後就是關於阻抗轉換元件内部參數設 定，其設定參數為交流訊號的起始量測頻率、頻率增幅 大小、掃描頻率數目及對於量測前系統重置等，在設定 結束後便等待由PC端傳送過來的執行訊號，等接收到執 行訊號後’裝置便開始進行阻抗量測。 請參閱第5圖，其係為本發明之阻抗量測裝置之電路 示意圖。本實施例中阻抗量測裝置（4)組成主要分成五個 部份.阻抗轉換器 Impedance converter AD5933(41 ) 、指叉電極感測晶片（42)、微控制器AT89c51(43)、 及串列傳輸準位轉換元件ΜΑΧ232(44)及電腦（圖未示） 。其中微控制器AT89c51(43)作為阻抗量測裝置的中央 099122996 表單編號A0101 第9頁/共22頁 0992040532-0 201202714 控制元件，包含與阻抗轉換器Impedance converter AD5933(41 )溝通、指令下達及資料讀取的功能，再藉由 串列傳輸準位轉換元件MAX232(44)與電腦（圖未示）做 串列傳輸與溝通；阻抗轉換器Impedance converter AD5933C41)與指叉電極感測晶片（42)結合後進行阻抗量 測；串列傳輸準位轉換元件MAX232C44)則是進行將TTL 準位轉換為標準的RS232規格方能與電腦（圖未示）端連 接；指叉電極感測晶片（42)則由一個四通道的指撥開關 (45)再加上晶片的載具組成，而指撥開關（45)主要用來 選擇量測時的指叉電極。 請參閱第6圖，其係為本發明之阻抗量測裝置之阻抗 量測結果圖。利用本發明之阻抗量測裝置進行初始濃度 為7xl02個細胞/毫升（cells/ml)、3xl04個細胞/毫升 (cells/ml)、6xl06個細胞/毫升（cells/ml)的生物細 胞吸附之阻抗量測，其量測結果如第6圖所示。本發明之 阻抗量測裝置對於不同細胞濃度生長的阻抗變化可以被 區分出來，由於此阻抗量測裝置其直流偏移訊號約為 0.28 Volt較大於市售阻抗分析器（AD5933 Evaluation Board約 0. 2 Vo 11 )， 所以對於貼附 於感測 晶片表 面的細胞，表面電雙層電容的影響更加靈敏，這是由於 加入直流電場愈大，對於電極與以感測環境之電荷極化 能力較好所致。由於本發明之阻抗量測裝置的直流偏移 較大，所以造成細胞濃度及其生長特性對於電雙層電容 的極化影響較大，所以也能直接依照細胞吸附的數量與 其生長情況來準確區分出不同的細胞生長特性。 請參閱第7圖，其係為本發明之阻抗量測裝置監控細 099122996 表單編號A0101 第10頁/共22頁 0992040532-0 201202714 胞培養結果圖。本圖為本發明之阻抗量測裝置監控初始 濃度為8χ102個細胞/毫升（cells/ml)的老鼠纖維組織細 胞（L929)在生物感測晶片表面培養小時的結果，縱座 標為阻抗值改變量，橫坐標為細胞培養時間。細胞培養 可分為緩慢期、培養期、穩定期、死亡期四個階段，在 前2個階段（約前36小時），細胞代謝及增殖急速增加使陴 抗值變化量隨著大幅改變，第7圖同時證實本量測系統可 以對於細胞生長過程進行即時監控。G. Referring to Fig. 3, it is a schematic diagram of the finger electrode of the sensing chip of the impedance measuring device of the present invention. In the figure, the interdigitated electrode (3) comprises a first comb electrode (31) and a second comb electrode (π), and the first comb electrode (31) and the second comb electrode (32) are arranged in a staggered manner. . Preferably, the electrodes of the sensing wafer of the impedance measuring device of the present invention are preferably a single finger electrode or an array finger electrode. The finger electrode is used here because the geometric area of the finger electrode is different from that of the conventional electrode. Therefore, in a limited space, the area of the sensor can be arranged neatly better than the conventional electrode, so that the finger has a signal to amplify the sensing signal. The function is improved in sensitivity. Moreover, the finger electrode is observed by an impedance method, and the method for discriminating the use of radiation, a fluorescent agent, a biochemical enzyme or an electrochemical calibration can be eliminated in the biomolecule sensing. 099122996 Form No. A0101 Page 7 of 22 0992040532-0 201202714 When the number of fingers is greater than one pair, the parallel connection can be made as an array finger electrode' and the capacitance is calculated as shown in the following equation (A). It can be seen from the formula that the capacitance value (Capacitance) is mainly determined by some related parameters, namely η: the number of electrodes and the number of electrodes; 1: the length of the finger electrode; ε: the dielectric coefficient; K(k): the first complete elliptic integral Function; Comment: refers to the electrode width; s: refers to the electrode spacing. On the other hand, in the case where the electrode width (w) is the same as the electrode pitch (S), it can be further simplified to the following formula (B). KC=nlS- 2Κ / Fine, 2 (( / C sin V 7m 2^+w)^ (A) For the easy implementation of the process and the theoretical calculation of the conformance (Β), the designed electrode width and electrode spacing are currently changed. The fixed house is the same size, and the complete design of the single-finger finger electrode is shown in the table. [Table 1] Electrode width (Width, W) 8 / zm Electrode spacing (Space, S) 8 ^ m Electrode length (Length, L) 500 ^ m Electrode thickness (Thickness) Cr ( 2 nm) / Au ( 50 nm) Number of electrodes (Number) 450 pairs 099122996 Form bat number Α 0101 Page 8 / Total 22 pages 0992040532-0 201202714 [0006] [0007] Please refer to Figure 4, which is the information processing of the impedance measuring device of the present invention 70 pieces The control flow chart information processing component _ program is written by the 〇 language program editing tool keil C, in the initial serial communication of the firmware program, in the serial transmission to set its relevant transfer rate and information processing software required Counters used, etc. After the serial communication is completed, the data transmission is carried out. The data transmission and reception can be judged according to the specific temporary storage device in the information processing unit. Whether the data is received or transmitted is ended. For example, the serial processing of the information processing is temporarily controlled. Boolean value (TI) in the Serial p〇rt Control Register to determine whether the transfer of data is complete or not, and the Boolean value in the Serial P〇rt C〇ntr〇i Register (R1) can be used to judge whether the received data is successful. Regardless of the data received or transmitted, the data values are placed in the Serial Buffer (SBUF) for further processing. Ο After the serial port is set, it is about the internal parameter setting of the impedance conversion component. The setting parameters are the initial measurement frequency of the AC signal, the frequency amplification, the number of scanning frequencies, and the system reset before the measurement. After that, it waits for the execution signal transmitted by the PC, and after receiving the execution signal, the device starts impedance measurement. Please refer to Fig. 5, which is a circuit diagram of the impedance measuring device of the present invention. In this embodiment, the impedance measuring device (4) is mainly divided into five parts. Impedance converter AD5933 (41), finger electrode sensing chip (42), microcontroller AT89c51 (43), and serial The level conversion element ΜΑΧ 232 (44) and the computer (not shown) are transmitted. The microcontroller AT89c51 (43) is used as the center of the impedance measuring device. 099122996 Form No. A0101 Page 9 of 22 0992040532-0 201202714 Control element, including communication with the impedance converter Impedance converter AD5933 (41), command release and data The function of reading is serially transmitted and communicated with the computer (not shown) by the serial transmission conversion component MAX232 (44); the impedance converter Impedance converter AD5933C41) and the interdigitated electrode sensing chip (42) After the combination, the impedance measurement is performed; the serial transmission conversion component MAX232C44) is connected to the computer (not shown) by converting the TTL level to the standard RS232 specification; the finger electrode sensing chip (42) It is composed of a four-channel dip switch (45) plus a carrier for the wafer, and the dip switch (45) is mainly used to select the finger electrode during the measurement. Please refer to Fig. 6, which is a graph showing the impedance measurement results of the impedance measuring device of the present invention. The impedance of the biological cells adsorbed by the impedance measuring device of the present invention at an initial concentration of 7×10 2 cells/ml (cells/ml), 3×10 4 cells/ml (cells/ml), and 6×10 6 cells/ml (cells/ml) The measurement results are shown in Fig. 6. The impedance measurement device of the present invention can be distinguished from the impedance change of the growth of different cell concentrations, because the impedance measurement device has a DC offset signal of about 0.28 Volt larger than the commercially available impedance analyzer (AD5933 Evaluation Board about 0. 2 Vo 11 ), so the effect of surface electric double layer capacitance is more sensitive for cells attached to the surface of the sensing wafer, which is due to the larger the DC electric field, the better the charge polarization for the electrode and the sensing environment. To. Since the DC offset of the impedance measuring device of the present invention is large, the cell concentration and its growth characteristics have a great influence on the polarization of the electric double layer capacitor, so it can be accurately distinguished according to the amount of cell adsorption and its growth. Different cell growth characteristics. Please refer to Fig. 7, which is a monitoring device for the impedance measuring device of the present invention. 099122996 Form No. A0101 Page 10 of 22 0992040532-0 201202714 Cell culture results. This figure is the result of monitoring the initial concentration of 8χ102 cells/ml (cells/ml) of mouse fibroblasts (L929) on the surface of the biosensing wafer for the impedance measuring device of the present invention, and the ordinate is the impedance value change amount. The abscissa is the cell culture time. Cell culture can be divided into four phases: slow phase, culture phase, stable phase and death phase. In the first two phases (about 36 hours before), the rapid increase of cell metabolism and proliferation makes the change of 陴 resistance value change greatly. Figure 7 also confirms that the measurement system can monitor the cell growth process in real time.
請參閱第8圖，其係為本發明之阻抗量測裝置與市售 阻抗光譜分析儀比較圖》_中，顯示本#明之阻抗量測 裝置與市售阻抗分析儀針對老鼠纖維組織細胞L929在生 物感測晶片表面培養48小時的結果比較，兩裝置在〇~9小 時低濃度都有相似的阻抗值改變趨勢，斧9〜36小時，因 為細胞代謝及增殖，阻抗值持續增加，.36〜48小時細胞生 長達到飽和量時不再影響阻抗值，由於本發明之阻抗量 測裝置加入直流電場較大，對於電極與以感測環境之電 荷極化能力較好’所以整體阻抗值變化較大，對於貼附 於感測晶片表面的細胞而言，在<阻抗量測上更加靈敏。 以上所述僅為舉例性，而非為限制性者。任何未脫 離本發明之精神與料，而對其進行之等效修改或變更 ，均應包含於後附之申請專利範圍中。 【圖式簡單說明】 [0008] 第1圖係為本發明之阻抗量測裝置之示意圖； 第2圖係為本發明之阻抗量測裝置之實施例示意圖； 第3圖係為本發明之阻抗量測震置中之之感測晶片之 指叉電極之示意圖； 099122996 表單編號A0101 第11頁/共22頁 0992040532-0 201202714 第4圖係為本發明之阻抗量測裝置之資訊處理元件之 控制流程圖； 第5圖係為本發明之阻抗量測裝置之電路示意圖； 第6圖係為本發明之阻抗量測裝置之阻抗量測結果圖 9 第7圖係為本發明之阻抗量測裝置監控細胞培養結果 圖； 第8圖係為本發明之阻抗量測裝置與市售阻抗光譜分 析儀比較圖。 【主要元件符號說明】 [0009] 099122996 (1 )、（ 4):阻抗量測裝置 (1 1 ) 、（ 2 1 ):感測晶片 (1 2):阻抗轉換元件 (13):資訊處理元件 (1 4):輸出元件 (15):阻抗值 (2 2) : AD 5 9 3 3 電癟 (2 3):微處理電路 (2 4):電腦 (25):内部整合電路 (2 6) : R S 2 3 2 電路 (3):指叉電極 (3 1 ):第一梳狀電極 (3 2) ·第二梳狀電極 (41):阻抗轉換器 (4 2):指又電極感測晶片 0992040532-0 表單編號A0101 第12頁/共22頁 201202714 (4 3):微控制器 (44):串列傳輸準位轉換元件 (4 5):指撥開關Please refer to FIG. 8 , which is a comparison diagram of the impedance measuring device of the present invention and a commercially available impedance spectrum analyzer. The impedance measuring device of the present invention and the commercially available impedance analyzer are directed to the mouse fiber tissue cell L929. Comparing the results of biosensing wafer surface culture for 48 hours, the two devices have similar impedance values in the low concentration of 〇~9 hours. The axe is 9~36 hours. Because of cell metabolism and proliferation, the impedance value continues to increase, .36~ When the 48-hour cell growth reaches saturation, the impedance value is no longer affected. Since the impedance measuring device of the present invention has a large DC electric field, the polarization of the electrode and the sensing environment is better, so the overall impedance value changes greatly. For cells attached to the surface of the sensing wafer, it is more sensitive to <impedance measurement. The above is intended to be illustrative only and not limiting. Any equivalent modifications or alterations of the present invention are intended to be included in the scope of the appended claims. BRIEF DESCRIPTION OF THE DRAWINGS [0008] Fig. 1 is a schematic view of an impedance measuring device of the present invention; Fig. 2 is a schematic view of an embodiment of an impedance measuring device of the present invention; and Fig. 3 is an impedance of the present invention Schematic diagram of the finger electrode of the sensing wafer in the seismic measurement; 099122996 Form No. A0101 Page 11 of 22 0992040532-0 201202714 Figure 4 is the control of the information processing component of the impedance measuring device of the present invention Figure 5 is a circuit diagram of the impedance measuring device of the present invention; Figure 6 is the impedance measurement result of the impedance measuring device of the present invention. Figure 9 is a impedance measuring device of the present invention. The cell culture result chart is monitored; Fig. 8 is a comparison chart of the impedance measuring device of the present invention and a commercially available impedance spectrum analyzer. [Description of main component symbols] [0009] 099122996 (1), (4): Impedance measuring device (1 1 ), ( 2 1 ): sensing wafer (12): impedance conversion element (13): information processing component (1 4): Output component (15): Impedance value (2 2) : AD 5 9 3 3 Electrical (2 3): Micro processing circuit (2 4): Computer (25): Internal integrated circuit (2 6) : RS 2 3 2 circuit (3): finger electrode (3 1 ): first comb electrode (3 2) · second comb electrode (41): impedance converter (4 2): finger electrode sensing Wafer 0992040532-0 Form No. A0101 Page 12 of 22 201202714 (4 3): Microcontroller (44): Serial transmission level conversion component (4 5): DIP switch
❹ 099122996 表單編號A0101 第13頁/共22頁 0992040532-0❹ 099122996 Form No. A0101 Page 13 of 22 0992040532-0