TWI860571B - Biosensor measurement system and method thereof for detecting human lactic acid - Google Patents
Biosensor measurement system and method thereof for detecting human lactic acid Download PDFInfo
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本發明係關於一種用於〔血液〕乳酸〔lactic acid或乳酸酶,lactate〕檢測之生醫感測器〔biosensor〕之量測系統及其方法;特別是關於一種具有溫度補償電路〔thermal compensation circuit〕之用於乳酸檢測之生醫感測器之量測系統及其方法;更特別是關於一種用於乳酸檢測之生醫感測器之延伸式閘極感測場效電晶體〔EGFET,Extended-Gate Field Effect Transistor〕電阻分壓式量測系統及其方法;更特別是關於一種用於乳酸檢測之二氧化釕〔Ruthenium Dioxide〕薄膜生醫感測器之量測系統及其方法。 The present invention relates to a measurement system and method of a biosensor for detecting lactic acid (lactic acid or lactase, lactate) in blood; in particular, to a measurement system and method of a biosensor for detecting lactic acid with a thermal compensation circuit; more particularly, to an extended-gate field effect transistor (EGFET) resistance-divider measurement system and method of a biosensor for detecting lactic acid; and more particularly, to a measurement system and method of a ruthenium dioxide thin-film biosensor for detecting lactic acid.
舉例而言,習用維生素C生物感測器,如中華民國專利公告第TW-I374267號〝維生素C感測器校正量測系統及其校正方法〞之發明專利,其揭示一種維生素C感測器之校正量測系統,且該維生素C感測器之校正量測系統包含一維生素C感測器、一參考電極、一放大器、一類比數位轉換器及一可程式化邏輯閘陣列模組。 For example, a conventional vitamin C biosensor, such as the invention patent of the Republic of China Patent Publication No. TW-I374267 "Vitamin C sensor calibration measurement system and calibration method thereof", discloses a calibration measurement system for a vitamin C sensor, and the calibration measurement system for the vitamin C sensor includes a vitamin C sensor, a reference electrode, an amplifier, an analog-to-digital converter, and a programmable logic gate array module.
承上,前述第TW-I374267號之該放大器具有一正輸入端、一負輸入端及一輸出端,而該參考電極選擇連接至該放大器之正輸入端,且一感測元件選擇連接至該放大器之負輸入端,且該類比數位轉換器選擇連接至該放大器之輸出端。 As mentioned above, the amplifier of the aforementioned TW-I374267 has a positive input terminal, a negative input terminal and an output terminal, and the reference electrode is selectively connected to the positive input terminal of the amplifier, and a sensing element is selectively connected to the negative input terminal of the amplifier, and the analog-to-digital converter is selectively connected to the output terminal of the amplifier.
承上,前述第TW-I374267號之該可程式化邏輯閘陣列模組選擇連接至該類比數位轉換器,而該可程式化邏輯閘陣列模組包含一控制晶片,且該可程式化邏輯閘陣列模組另包含一控制器、一多段顯示器及一發光二極體燈,且該控制器、多段顯示器及發光二極體燈分別連接至該控制晶片。 As mentioned above, the programmable logic gate array module of the aforementioned TW-I374267 is selectively connected to the analog-to-digital converter, and the programmable logic gate array module includes a control chip, and the programmable logic gate array module further includes a controller, a multi-segment display and a light-emitting diode lamp, and the controller, the multi-segment display and the light-emitting diode lamp are respectively connected to the control chip.
另一習用生物感測元件,如中華民國專利公告第TW-I377342號〝延伸式閘極場效電晶體之感測元件的形成方法與其所形成之感測元件〞之發明專利,其揭示一種延伸式閘極場效電晶體之感測元件,且該延伸式閘極場效電晶體之感測元件包含一基板、一釕摻雜二氧化鈦感測薄膜及一導線。 Another commonly used biosensing element, such as the invention patent of the Republic of China Patent Publication No. TW-I377342 "Method for forming a sensing element of an extended gate field effect transistor and the sensing element formed thereby", discloses a sensing element of an extended gate field effect transistor, and the sensing element of the extended gate field effect transistor includes a substrate, a ruthenium-doped titanium dioxide sensing film and a wire.
承上,前述第TW-I377342號之該釕摻雜二氧化鈦感測薄膜形成於該基底上,而該釕摻雜二氧化鈦感測薄膜為一奈米結晶表面,且該奈米結晶表面之尺寸約為37-61nm,且該導線由該釕摻雜二氧化鈦感測薄膜延伸而出,其作為對外之一電性接點。 As mentioned above, the ruthenium-doped titanium dioxide sensing film of the aforementioned TW-I377342 is formed on the substrate, and the ruthenium-doped titanium dioxide sensing film is a nanocrystalline surface, and the size of the nanocrystalline surface is about 37-61nm, and the wire extends from the ruthenium-doped titanium dioxide sensing film, which serves as an electrical contact to the outside.
承上,前述第TW-I377342號之該延伸式閘極場效電晶體之感測元件另選擇包含一基板、一二氧化鈦、一釕摻雜二氧化鈦或氧化釕感測薄膜、一鈣離子感測薄膜及一導線。 As mentioned above, the sensing element of the extended gate field effect transistor of the aforementioned TW-I377342 may alternatively include a substrate, a titanium dioxide, a ruthenium-doped titanium dioxide or ruthenium oxide sensing film, a calcium ion sensing film and a conductor.
承上,前述第TW-I377342號之該導線可另選擇由該二氧化鈦、釕摻雜二氧化鈦或氧化釕感測薄膜感測薄膜延伸而出,其作為對外之一電性接點,且該鈣離子感測薄膜形成於該釕摻雜二氧化鈦或氧化釕感測薄膜上。 As mentioned above, the wire of the aforementioned TW-I377342 can alternatively extend from the titanium dioxide, ruthenium-doped titanium dioxide or ruthenium oxide sensing film as an external electrical contact, and the calcium ion sensing film is formed on the ruthenium-doped titanium dioxide or ruthenium oxide sensing film.
然而,前述中華民國專利公告第TW-I374267號之維生素C感測器及第TW-I377342號之延伸式閘極場效電晶體之感測元件未揭示如何用以血液乳酸檢測或其相關方法,因此其必然存在如何用以血液乳酸檢測或提供其 相關方法之需求。 However, the aforementioned Vitamin C sensor of the Republic of China Patent Publication No. TW-I374267 and the sensing element of the extended gate field effect transistor of No. TW-I377342 do not disclose how to be used for blood lactate detection or related methods thereof, so there must be a need for how to be used for blood lactate detection or provide related methods thereof.
另一習用奈米碳管生物感測器,如美國專利第US-10031102號〝Single-walled carbon nanotube biosensor for detection of glucose,lactate,and urea〞之發明專利,其揭示一種用於檢測血糖〔glucose〕、乳酸〔lactate〕及尿素〔urea〕之單層壁〔single-walled〕奈米碳管〔carbon nanotube〕生物感測器,且該單層壁奈米碳管生物感測器為一基於單層壁奈米碳管微米級〔micron scale〕多重〔multiplex〕生物感測器。 Another commonly used carbon nanotube biosensor is the invention patent of US Patent No. US-10031102 "Single-walled carbon nanotube biosensor for detection of glucose, lactate, and urea", which discloses a single-walled carbon nanotube biosensor for detecting blood glucose, lactate and urea, and the single-walled carbon nanotube biosensor is a micron scale multiplex biosensor based on single-walled carbon nanotubes.
承上,前述第US-10031102號之該單層壁奈米碳管生物感測器為基於以一半導體單層壁奈米碳管材料進行修飾〔modification〕,並採用一連接劑〔linker〕,且其以非共價方式〔non-covalently〕連接於該半導體單層壁奈米碳管材料,且其以共價方式〔covalently〕耦合於一酵素〔enzyme〕。 As mentioned above, the single-walled carbon nanotube biosensor of the aforementioned US-10031102 is based on modification of a semiconductor single-walled carbon nanotube material and the use of a linker, which is non-covalently connected to the semiconductor single-walled carbon nanotube material and covalently coupled to an enzyme.
承上,前述第US-10031102號之該單層壁奈米碳管生物感測器於一生物基板〔physiological substrate〕以該酵素進行反應,並於該單層壁奈米碳管生物感測器內其導致該半導體單層壁奈米碳管材料之一增加阻抗〔increased resistance〕。 As mentioned above, the single-walled carbon nanotube biosensor of the aforementioned US-10031102 reacts with the enzyme on a biological substrate, and causes an increased resistance of one of the semiconductor single-walled carbon nanotube materials in the single-walled carbon nanotube biosensor.
然而,前述美國專利第US-10031102號之單層壁奈米碳管生物感測器僅揭示可用以檢測乳酸,其並未揭示如何增益血液乳酸檢測或其相關方法,因此其必然存在如何增益血液乳酸檢測或提供其相關方法之需求。 However, the aforementioned single-walled carbon nanotube biosensor of US Patent No. US-10031102 only discloses that it can be used to detect lactate, and does not disclose how to enhance blood lactate detection or its related methods. Therefore, there must be a need for how to enhance blood lactate detection or provide its related methods.
簡言之,前述中華民國專利公告第TW-I374267號、第TW-I377342號及美國專利第US-10031102號僅為本發明技術背景之參考及說明目前技術發展狀態而已,其並非用以限制本發明之範圍。 In short, the aforementioned Republic of China Patent Publication No. TW-I374267, No. TW-I377342 and US Patent No. US-10031102 are only references to the technical background of the present invention and illustrate the current state of technical development, and are not intended to limit the scope of the present invention.
有鑑於此,本發明為了滿足上述技術問題及需 求,其提供一種用於乳酸檢測之生醫感測器之量測系統及其方法,其利用一乳酸感測元件量測獲得一乳酸量測訊號,並將該乳酸感測元件電性連接於一乳酸訊號處理電路,如此將該乳酸量測訊號經由該乳酸訊號處理電路進行處理,以獲得一已處理乳酸量測訊號,且將該乳酸訊號處理電路電性連接於一訊號讀出電路,如此將該已處理乳酸量測訊號經由該訊號讀出電路進行放大,以獲得一已放大乳酸量測訊號,因此相對於習用乳酸感測元件可達成提供準確量測乳酸、提升感測特性及量測穩定性之目的。 In view of this, in order to meet the above technical problems and needs, the present invention provides a measurement system and method of a biomedical sensor for lactate detection, which uses a lactate sensing element to measure a lactate measurement signal, and electrically connects the lactate sensing element to a lactate signal processing circuit, so that the lactate measurement signal is processed by the lactate signal processing circuit to obtain a processed lactate measurement signal, and the lactate signal processing circuit is electrically connected to a signal readout circuit, so that the processed lactate measurement signal is amplified by the signal readout circuit to obtain an amplified lactate measurement signal, so that compared with the conventional lactate sensing element, the purpose of providing accurate lactate measurement, improving sensing characteristics and measurement stability can be achieved.
本發明之主要目的係提供一種用於乳酸檢測之生醫感測器之量測系統及其方法,其利用一乳酸感測元件量測獲得一乳酸量測訊號,並將該乳酸感測元件電性連接於一乳酸訊號處理電路,如此將該乳酸量測訊號經由該乳酸訊號處理電路進行處理,以獲得一已處理乳酸量測訊號,且將該乳酸訊號處理電路電性連接於一訊號讀出電路,如此將該已處理乳酸量測訊號經由該訊號讀出電路進行放大,以獲得一已放大乳酸量測訊號,以便達成提供準確量測乳酸、提升感測特性及量測穩定性之功效。 The main purpose of the present invention is to provide a measurement system and method of a biomedical sensor for lactate detection, which utilizes a lactate sensing element to measure and obtain a lactate measurement signal, and electrically connects the lactate sensing element to a lactate signal processing circuit, so that the lactate measurement signal is processed by the lactate signal processing circuit to obtain a processed lactate measurement signal, and the lactate signal processing circuit is electrically connected to a signal readout circuit, so that the processed lactate measurement signal is amplified by the signal readout circuit to obtain an amplified lactate measurement signal, so as to achieve the effect of providing accurate measurement of lactate, improving sensing characteristics and measurement stability.
為了達成上述目的,本發明較佳實施例之用於乳酸檢測之生醫感測器之量測方法包含: In order to achieve the above-mentioned purpose, the measurement method of the biomedical sensor for lactate detection in the preferred embodiment of the present invention includes:
利用一乳酸感測元件於一待測乳酸樣本進行量測,以獲得一乳酸量測訊號; Using a lactic acid sensing element to measure a lactic acid sample to be tested to obtain a lactic acid measurement signal;
將該乳酸感測元件電性連接於一乳酸訊號處理電路; Electrically connecting the lactate sensing element to a lactate signal processing circuit;
將該乳酸量測訊號經由該乳酸訊號處理電路進行處理,以獲得一已處理乳酸量測訊號; Processing the lactate measurement signal through the lactate signal processing circuit to obtain a processed lactate measurement signal;
將該乳酸訊號處理電路電性連接於一訊號讀出電路;及 Electrically connecting the lactate signal processing circuit to a signal readout circuit; and
將該已處理乳酸量測訊號經由該訊號讀出電路進行放大,以獲得一已放大乳酸量測訊號。 The processed lactate measurement signal is amplified by the signal readout circuit to obtain an amplified lactate measurement signal.
本發明較佳實施例之該乳酸感測元件為一二氧化釕薄膜乳酸感測元件。 The lactic acid sensing element of the preferred embodiment of the present invention is a ruthenium dioxide thin film lactic acid sensing element.
本發明較佳實施例之該乳酸訊號處理電路包含一延伸式閘極感測場效電晶體及一分壓電阻,以便該延伸式閘極感測場效電晶體形成為一電阻,或該乳酸訊號處理電路包含一NMOS延伸式閘極感測場效電晶體及一分壓電阻,以便該NMOS延伸式閘極感測場效電晶體形成為一電阻。 The lactate signal processing circuit of the preferred embodiment of the present invention includes an extended gate sensing field effect transistor and a voltage divider resistor so that the extended gate sensing field effect transistor forms a resistor, or the lactate signal processing circuit includes an NMOS extended gate sensing field effect transistor and a voltage divider resistor so that the NMOS extended gate sensing field effect transistor forms a resistor.
本發明較佳實施例之該訊號讀出電路連接一溫度補償電路,以便將該已處理乳酸量測訊號經由該溫度補償電路進行溫度補償,以獲得一已補償乳酸量測訊號。 The signal reading circuit of the preferred embodiment of the present invention is connected to a temperature compensation circuit so that the processed lactate measurement signal is temperature compensated through the temperature compensation circuit to obtain a compensated lactate measurement signal.
本發明較佳實施例之該溫度補償電路具有一預定溫度補償範圍,且該預定溫度補償範圍介於25℃至55℃之間。 The temperature compensation circuit of the preferred embodiment of the present invention has a predetermined temperature compensation range, and the predetermined temperature compensation range is between 25°C and 55°C.
本發明較佳實施例之該已放大乳酸量測訊號由一類比訊號轉換為一數位訊號。 The amplified lactate measurement signal of the preferred embodiment of the present invention is converted from an analog signal to a digital signal.
本發明較佳實施例之該乳酸量測訊號與一乳酸量測濃度形成正比。 The lactate measurement signal of the preferred embodiment of the present invention is proportional to a lactate measurement concentration.
為了達成上述目的,本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統包含: In order to achieve the above-mentioned purpose, the measurement system of the biomedical sensor for lactate detection in the preferred embodiment of the present invention includes:
一乳酸感測元件,其包含一基板; A lactic acid sensing element, comprising a substrate;
數個感測電極,其配置於該乳酸感測元件之基板上,且該感測電極用以於一待測乳酸樣本進行量測,以獲得一乳酸量測訊號; A plurality of sensing electrodes are arranged on the substrate of the lactic acid sensing element, and the sensing electrodes are used to measure a lactic acid sample to be tested to obtain a lactic acid measurement signal;
至少一乳酸訊號處理電路,其電性連接於該乳酸感測元件;及 At least one lactate signal processing circuit electrically connected to the lactate sensing element; and
至少一訊號讀出電路,其電性連接於該乳酸訊號處 理電路; At least one signal readout circuit electrically connected to the lactate signal processing circuit;
其中將該乳酸量測訊號經由該乳酸訊號處理電路進行處理,以獲得一已處理乳酸量測訊號,再將該已處理乳酸量測訊號經由該訊號讀出電路進行放大,以獲得一已放大乳酸量測訊號。 The lactate measurement signal is processed by the lactate signal processing circuit to obtain a processed lactate measurement signal, and then the processed lactate measurement signal is amplified by the signal readout circuit to obtain an amplified lactate measurement signal.
本發明較佳實施例之該乳酸感測元件及基板結合至少一微流體系統,以便將該待測乳酸樣本經由該微流體系統進行量測。 The lactic acid sensing element and substrate of the preferred embodiment of the present invention are combined with at least one microfluidic system so that the lactic acid sample to be tested can be measured through the microfluidic system.
本發明較佳實施例之該基板選自一可撓式基板或一非可撓式基板。 The substrate of the preferred embodiment of the present invention is selected from a flexible substrate or a non-flexible substrate.
本發明較佳實施例之該數個感測電極形成一電極陣列,且該電極陣列包含數個感測電極組。 The plurality of sensing electrodes of the preferred embodiment of the present invention form an electrode array, and the electrode array includes a plurality of sensing electrode groups.
本發明較佳實施例之該乳酸訊號處理電路包含一延伸式閘極感測場效電晶體及一分壓電阻,或該乳酸訊號處理電路包含一NMOS延伸式閘極感測場效電晶體及一分壓電阻。 The lactate signal processing circuit of the preferred embodiment of the present invention includes an extended gate sensing field effect transistor and a voltage divider resistor, or the lactate signal processing circuit includes an NMOS extended gate sensing field effect transistor and a voltage divider resistor.
本發明較佳實施例之該訊號讀出電路包含一正端電壓隨耦器、一負端電壓隨耦器及一差動放大器。 The signal reading circuit of the preferred embodiment of the present invention includes a positive voltage follower, a negative voltage follower and a differential amplifier.
1:乳酸感測元件 1: Lactic acid sensing element
10:微流體系統 10: Microfluidic system
11:基板 11: Substrate
12:電路佈局層 12: Circuit layout layer
121:參考電極 121: Reference electrode
122:金屬電極層 122: Metal electrode layer
123:感測電極 123: Sensing electrode
124:感測訊號輸出電極 124: Sensing signal output electrode
13:絕緣圖樣層 13: Insulation pattern layer
100:待測乳酸樣本 100: Lactic acid sample to be tested
101:微流體通道 101: Microfluidic channel
2:乳酸訊號處理電路 2: Lactate signal processing circuit
21:延伸式閘極感測場效電晶體 21: Extended gate sensing field effect transistor
22:分壓電阻 22: Voltage divider resistor
3:訊號讀出電路 3: Signal reading circuit
31:正端電壓隨耦器 31: Positive voltage follower
32:負端電壓隨耦器 32: Negative voltage follower
33:差動放大器 33: Differential amplifier
4:類比轉換數位電路 4: Analog to digital conversion circuit
9:已放大乳酸量測訊號 9: Lactate measurement signal has been amplified
90:溫度補償電路 90: Temperature compensation circuit
a:環氧樹脂層 a: Epoxy resin layer
b:氨丙基三乙氧基矽烷層 b: Aminopropyltriethoxysilane layer
c:第一戊二醛層 c: First glutaraldehyde layer
d:乳酸酶層 d: Lactase layer
e:第二戊二醛層 e: Second glutaraldehyde layer
第1圖:本發明第一較佳實施例之用於乳酸檢測之生醫感測器之量測系統之方塊示意圖。 Figure 1: A block diagram of a measurement system of a biomedical sensor for lactate detection according to the first preferred embodiment of the present invention.
第2圖:本發明較佳實施例之用於乳酸檢測之生醫感測器之量測方法之流程示意圖。 Figure 2: Schematic diagram of the process of the measurement method of the biomedical sensor for lactate detection in the preferred embodiment of the present invention.
第3圖:本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統採用乳酸感測元件之正視示意圖。 Figure 3: A schematic front view of a measurement system of a biomedical sensor for lactate detection using a lactate sensing element in a preferred embodiment of the present invention.
第4圖:本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統採用乳酸感測元件之側視示意圖。 Figure 4: A schematic side view of a measurement system of a biomedical sensor for lactate detection using a lactate sensing element in a preferred embodiment of the present invention.
第5圖:本發明第二較佳實施例之用於乳酸檢測之生醫 感測器之量測系統採用乳酸感測元件結合微流體系統之側視示意圖。 Figure 5: A schematic side view of a biomedical sensor measuring system for lactate detection using a lactate sensing element combined with a microfluidic system in accordance with the second preferred embodiment of the present invention.
第6圖:本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統採用乳酸訊號處理電路之電路示意圖。 Figure 6: Circuit diagram of a measurement system of a biomedical sensor for lactate detection using a lactate signal processing circuit in a preferred embodiment of the present invention.
第7圖:本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統採用訊號讀出電路之電路示意圖。 Figure 7: Circuit diagram of a signal readout circuit used in the measurement system of a biomedical sensor for lactate detection in a preferred embodiment of the present invention.
第8圖:本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統及其方法之響應電壓與乳酸濃度關係之示意圖。 Figure 8: Schematic diagram of the relationship between the response voltage and lactic acid concentration of the measurement system and method of the biomedical sensor for lactic acid detection in the preferred embodiment of the present invention.
第9圖:本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統及其方法之平均響應電壓與乳酸濃度關係之示意圖。 Figure 9: A schematic diagram showing the relationship between the average response voltage and lactic acid concentration of the measurement system and method of the biomedical sensor for lactic acid detection in a preferred embodiment of the present invention.
第10圖:本發明第三較佳實施例之用於乳酸檢測之生醫感測器之量測系統之方塊示意圖。 Figure 10: A block diagram of a measurement system of a biomedical sensor for lactate detection according to the third preferred embodiment of the present invention.
第11圖:本發明第四較佳實施例之用於乳酸檢測之生醫感測器之量測系統之方塊示意圖。 Figure 11: A block diagram of a measurement system of a biomedical sensor for lactate detection according to the fourth preferred embodiment of the present invention.
為了充分瞭解本發明,於下文將舉例較佳實施例並配合所附圖式作詳細說明,且其並非用以限定本發明。 In order to fully understand the present invention, the following will give examples of preferred embodiments and provide detailed descriptions with the accompanying drawings, which are not intended to limit the present invention.
本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統及其方法適合應用於各種〔血液〕乳酸生醫感測電路元件之量測作業或比對作業、各種〔血液〕乳酸生醫感測晶片之量測作業或比對作業或各種〔血液〕乳酸生醫感測系統之量測作業及其相關量測作業或比對作業,但其並非用以限制本發明之應用範圍。 The measurement system and method of the biomedical sensor for lactate detection of the preferred embodiment of the present invention are suitable for application in the measurement or comparison of various (blood) lactate biomedical sensing circuit components, the measurement or comparison of various (blood) lactate biomedical sensing chips, or the measurement of various (blood) lactate biomedical sensing systems and related measurement or comparison operations, but they are not intended to limit the scope of application of the present invention.
承上,本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統及其方法適合應用於各種血液輸送系統或其方法、各種血液透析系統或其方法或各種體外血液循環膜肺維生系統或其方法,但其並非用以限制本發明之 應用範圍。 As mentioned above, the measurement system and method of the biomedical sensor for lactate detection in the preferred embodiment of the present invention are suitable for application in various blood delivery systems or methods thereof, various hemodialysis systems or methods thereof, or various extracorporeal blood circulation membrane lung support systems or methods thereof, but they are not intended to limit the scope of application of the present invention.
第1圖揭示本發明第一較佳實施例之用於乳酸檢測之生醫感測器之量測系統之方塊示意圖。請參照第1圖所示,舉例而言,本發明第一較佳實施例之用於乳酸檢測之生醫感測器之量測系統主要包含一乳酸感測元件1、至少一個或數個乳酸〔量測〕訊號處理電路2及至少一個或數個訊號讀出電路〔即乳酸量測訊號讀出電路〕3,如第1圖之左側所示。
FIG. 1 is a block diagram of a measuring system of a biomedical sensor for lactate detection according to the first preferred embodiment of the present invention. Referring to FIG. 1, for example, the measuring system of a biomedical sensor for lactate detection according to the first preferred embodiment of the present invention mainly comprises a
第2圖揭示本發明較佳實施例之用於乳酸檢測之生醫感測器之量測方法之流程示意圖,其對應於第1圖之用於乳酸檢測之生醫感測器之量測系統。請參照第1及2圖所示,本發明較佳實施例之用於乳酸檢測之生醫感測器之量測方法包含步驟S1:舉例而言,首先,利用該乳酸感測元件1〔例如:二氧化釕〔RuO2〕薄膜乳酸感測元件或其它乳酸感測元件〕於一待測乳酸樣本100進行量測一響應電壓〔response voltage〕,例如:高準位或低準位,以獲得一乳酸量測訊號。
FIG. 2 is a schematic flow chart of a measurement method of a biomedical sensor for lactate detection according to a preferred embodiment of the present invention, which corresponds to the measurement system of the biomedical sensor for lactate detection according to FIG. Referring to FIG. 1 and FIG. 2, the measurement method of a biomedical sensor for lactate detection according to a preferred embodiment of the present invention includes step S1: For example, first, a response voltage (response voltage), such as a high level or a low level, is measured on a
第3圖揭示本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統採用乳酸感測元件之正視示意圖。第4圖揭示本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統採用乳酸感測元件之側視示意圖,其對應於第4圖之乳酸感測元件之正視示意圖。 FIG. 3 discloses a front view schematic diagram of a lactic acid sensing element used in a measuring system of a biomedical sensor for lactic acid detection according to a preferred embodiment of the present invention. FIG. 4 discloses a side view schematic diagram of a lactic acid sensing element used in a measuring system of a biomedical sensor for lactic acid detection according to a preferred embodiment of the present invention, which corresponds to the front view schematic diagram of the lactic acid sensing element in FIG. 4.
請再參照第1、2、3及4圖所示,舉例而言,該乳酸感測元件1包含一基板11、一電路佈局層〔印刷電路層〕12及一絕緣圖樣層〔例如:環氧樹脂層〕13,而該基板〔例如:聚對苯二甲酸乙二醇酯或其它可撓式或非可撓式材料〕11選自一可撓式基板或一非可撓式基板,且該電路佈局層12包含數個參考電極〔L型圖案,其可選擇由銀或其它金屬材料製成〕121、數個金屬電極層〔感測金屬
薄膜層〕122、數個感測電極〔工作電極,I型圖案〕123及數個感測訊號輸出電極124,以便用於後續乳酸量測訊號處理。
Please refer to FIGS. 1, 2, 3 and 4 again. For example, the lactic
請再參照第1、3及4圖所示,舉例而言,該金屬電極層122選擇由二氧化釕材料或其它材料製成,而該感測電極123選擇由一複合材料〔例如:複合乳酸酶及銀奈米粒子材料或其它複合材料〕製成,且數個該感測電極123形成一電極陣列或一電極陣列式感測窗口,且該電極陣列或電極陣列式感測窗口包含數個感測電極組,以便同時將多個乳酸量測訊號用於後續訊號處理作業。
Please refer to Figures 1, 3 and 4 again. For example, the
請再參照第1、3及4圖所示,舉例而言,該感測電極123另包含一環氧樹脂層a、一氨丙基三乙氧基矽烷層〔APTES layer,可選擇為酵素固定層〕b、一第一戊二醛層〔可選擇為酵素固定層〕c、一乳酸酶層〔lactate layer,其可選擇採用交聯法之固定方式〕d及一第二戊二醛層〔可選擇為酵素固定層〕e,且該環氧樹脂層a、氨丙基三乙氧基矽烷層b、第一戊二醛層c、乳酸酶層d及第二戊二醛層e依序成型於該感測電極123。
Please refer to Figures 1, 3 and 4 again. For example, the
請再參照第1、2、3及4圖所示,本發明較佳實施例之用於乳酸檢測之生醫感測器之量測方法包含步驟S2:舉例而言,接著,以適當技術手段將該乳酸感測元件1〔例如:感測訊號輸出電極124〕形成電性連接〔electrically connection〕於該乳酸訊號處理電路2或其它相關電路,以便進行一乳酸訊號處理作業。
Please refer to Figures 1, 2, 3 and 4 again. The measurement method of the biomedical sensor for lactate detection of the preferred embodiment of the present invention includes step S2: For example, then, the lactate sensing element 1 (for example: the sensing signal output electrode 124) is electrically connected to the lactate
第5圖揭示本發明第二較佳實施例之用於乳酸檢測之生醫感測器之量測系統採用乳酸感測元件結合微流體系統之側視示意圖。請參照第5圖所示,相對於第一實施例,本發明第二較佳實施例之用於乳酸檢測之生醫感測器之量測系統包含至少一微流體系統10,且該微流體系統
10可選擇連接於至少一周邊設備〔例如:流體驅動單元、自動控制單元或其它功能單元,未繪示〕。
FIG. 5 shows a schematic side view of a biomedical sensor for lactate detection in the second preferred embodiment of the present invention, which uses a lactate sensing element combined with a microfluidic system. Referring to FIG. 5, relative to the first embodiment, the biomedical sensor for lactate detection in the second preferred embodiment of the present invention includes at least one
請再參照第1及5圖所示,舉例而言,該微流體系統10包含數個微流體通道101,以便將該待測乳酸樣本100可分別流經數個該微流體通道101,且該乳酸感測元件1及基板11結合該微流體系統10,以便將該待測乳酸樣本100經由該微流體系統10之數個微流體通道101進行一量測作業〔例如:不同流速量測或其它量測〕。
Please refer to Figures 1 and 5 again. For example, the
第6圖揭示本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統採用乳酸訊號處理電路之電路示意圖。請參照第1及6圖所示,舉例而言,該乳酸訊號處理電路2包含一延伸式閘極感測場效電晶體21〔或可選擇NMOS延伸式閘極感測場效電晶體〕及一分壓電阻〔例如:可選擇可變電阻或具可變電阻功能之元件〕22,以便該延伸式閘極感測場效電晶體21形成為一電阻,而該乳酸訊號處理電路2具有一正供應電壓VDD、一負供應電壓VSS及一輸出電壓VEG,且該輸出電壓VEG輸出自該分壓電阻22。本發明較佳實施例可選擇採用該輸出電壓VEG之計算式如下:
FIG. 6 is a schematic circuit diagram showing a measurement system of a biomedical sensor for lactate detection using a lactate signal processing circuit according to a preferred embodiment of the present invention. Please refer to FIGS. 1 and 6 , for example, the lactate
其中VDD為正供應電壓,VSS為負供應電壓,REGFET為延伸式閘極感測場效電晶體所形成的電阻及RD為分壓電阻。 Where VDD is the positive supply voltage, VSS is the negative supply voltage, REGFET is the resistance formed by the extended gate sense field effect transistor and RD is the voltage divider resistor.
請再參照第1、3、4及6圖所示,舉例而言,該乳酸感測元件1之乳酸量測訊號具有一感測電壓,且該感測電壓可導致改變該乳酸訊號處理電路2之延伸式閘極感測場效電晶體21之一電阻值,如此可改變該分壓電阻22所產生的該輸出電壓VEG。
Please refer to Figures 1, 3, 4 and 6 again. For example, the lactate measurement signal of the
請再參照第1、2及6圖所示,本發明較佳實施例之用於乳酸檢測之生醫感測器之量測方法包含步驟S3:舉例而言,接著,舉例而言,接著,將該乳酸量測訊號經由該乳酸訊號處理電路2進行適當處理,以獲得一已處理乳酸量測訊號,並將該已處理乳酸量測訊號適當輸出至一個或數個其它電路,以便適當進行其它後續訊號處理作業〔例如:訊號讀出作業、訊號放大作業、訊號校正作業或其它訊號處理作業〕。
Please refer to Figures 1, 2 and 6 again. The measurement method of the biomedical sensor for lactate detection of the preferred embodiment of the present invention includes step S3: for example, then, for example, then, the lactate measurement signal is appropriately processed by the lactate
請再參照第1、2及6圖所示,本發明較佳實施例之用於乳酸檢測之生醫感測器之量測方法包含步驟S4:以適當技術手段將一個或數個該乳酸訊號處理電路2形成電性連接於一個或數個該訊號讀出電路3,以便進行一訊號放大作業,如第1圖之右側所示。另外,該訊號讀出電路3可達成降低該已處理乳酸量測訊號之雜訊干擾〔例如:雜訊濾除電路〕。
Please refer to Figures 1, 2 and 6 again. The measurement method of the biomedical sensor for lactate detection of the preferred embodiment of the present invention includes step S4: using appropriate technical means to electrically connect one or more lactate
第7圖揭示本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統採用訊號讀出電路之電路示意圖。請參照第1及7圖所示,舉例而言,該訊號讀出電路3包含一正端電壓隨耦器31、一負端電壓隨耦器32及一差動放大器33,而該訊號讀出電路3具有一正端輸入電壓V+、一負端輸入電壓V-及一輸出電壓VOUT,且該輸出電壓VOUT輸出自該訊號讀出電路3之差動放大器33,如第7圖之右側所示。
FIG. 7 is a circuit diagram of a measurement system of a biomedical sensor for lactate detection according to a preferred embodiment of the present invention using a signal readout circuit. Referring to FIGS. 1 and 7, for example, the
請再參照第1及7圖所示,舉例而言,該正端電壓隨耦器31、負端電壓隨耦器32及差動放大器33適當連接形成該訊號讀出電路3,而該正端電壓隨耦器31、負端電壓隨耦器32及差動放大器33適當連接形成一二級運算放大器裝置,且將該乳酸訊號處理電路2及訊號讀出電路3可選擇整合製成一單一晶片或一單一電路裝置,且其
可選擇結合至少一個或數個CMOS積體電路,以改善其電路特性。
Please refer to Figures 1 and 7 again. For example, the
請再參照第7圖所示,舉例而言,該正端電壓隨耦器31包含一第一運算放大器及一第一隨耦器之電阻〔如第7圖之左下側所示〕,而該負端電壓隨耦器32包含一第二運算放大器及一第二隨耦器之電阻〔如第7圖之左上側所示〕,且該差動放大器33包含一第三運算放大器及四個差動放大器之電阻〔如第7圖之右側所示〕。
Please refer to FIG. 7 again. For example, the
請再參照第1、2及7圖所示,本發明較佳實施例之用於乳酸檢測之生醫感測器之量測方法包含步驟S5:舉例而言,接著,以適當技術手段將該已處理乳酸量測訊號經由一個或數個該訊號讀出電路3進行適當讀出及放大,以獲得一已放大乳酸量測訊號〔即,已放大響應電壓〕9,並將該已放大乳酸量測訊號9可選擇適當輸出至外界〔exterior〕或進行訊號轉換〔例如:類比轉換數位〕。
Please refer to Figures 1, 2 and 7 again. The measurement method of the biomedical sensor for lactate detection of the preferred embodiment of the present invention includes step S5: For example, then, the processed lactate measurement signal is appropriately read and amplified through one or more
第8圖揭示本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統及其方法之響應電壓與乳酸濃度之示意圖。請參照第1、2及8圖所示,舉例而言,該乳酸量測訊號與一乳酸量測濃度形成正比,而該乳酸量測濃度包含0.2mM、0.7mM、1.3mM、2mM、3mM及5mM。該乳酸感測元件1、乳酸訊號處理電路2及訊號讀出電路〔LT1167〕3之線性度〔linearity〕為0.997,且該乳酸感測元件1、乳酸訊號處理電路2及訊號讀出電路3之靈敏度〔sensitivity〕為53.41mV/mM,但其並非用以限制本發明之應用範圍。
FIG8 is a schematic diagram of the response voltage and lactate concentration of the measurement system and method of the biomedical sensor for lactate detection of the preferred embodiment of the present invention. Please refer to FIGS. 1, 2 and 8, for example, the lactate measurement signal is proportional to a lactate measurement concentration, and the lactate measurement concentration includes 0.2mM, 0.7mM, 1.3mM, 2mM, 3mM and 5mM. The linearity of the
第9圖揭示本發明較佳實施例之用於乳酸檢測之生醫感測器之量測系統及其方法之平均響應電壓與乳酸濃度之示意圖。請參照第1、2及9圖所示,舉例而言,該乳酸感測元件〔EGFET CSA〕1、乳酸訊號處理電路2之
線性度為0.996,且該乳酸訊號處理電路2之平均靈敏度〔average sensitivity〕為32.93mV/mM,但其並非用以限制本發明之應用範圍。
FIG. 9 shows a schematic diagram of the average response voltage and lactate concentration of the measurement system and method of the biomedical sensor for lactate detection of the preferred embodiment of the present invention. Please refer to FIGS. 1, 2 and 9. For example, the linearity of the lactate sensing element [EGFET CSA] 1 and the lactate
第10圖揭示本發明第三較佳實施例之用於乳酸檢測之生醫感測器之量測系統之方塊示意圖。請參照第10圖所示,相對於第一實施例,本發明第三較佳實施例之用於乳酸檢測之生醫感測器之量測系統包含一溫度補償電路90,以便補償該乳酸感測元件1、乳酸訊號處理電路2或訊號讀出電路3之環境溫度。
FIG. 10 is a block diagram of a measuring system of a biomedical sensor for lactate detection according to the third preferred embodiment of the present invention. Referring to FIG. 10, relative to the first embodiment, the measuring system of a biomedical sensor for lactate detection according to the third preferred embodiment of the present invention includes a
請參照第10圖所示,舉例而言,該訊號讀出電路3可電性連接於該溫度補償電路90,以便將該已處理乳酸量測訊號經由該溫度補償電路90進行溫度補償,以獲得一已補償乳酸量測訊號,且該溫度補償電路90具有一預定溫度補償範圍,且該預定溫度補償範圍介於25℃至55℃之間,以減少生醫感測器之溫度效應。
Please refer to FIG. 10 , for example, the
第11圖揭示本發明第四較佳實施例之用於乳酸檢測之生醫感測器之量測系統之方塊示意圖。請參照第11圖所示,相對於第一實施例,本發明第四較佳實施例之用於乳酸檢測之生醫感測器之量測系統包含一類比轉換數位電路4,並利用該類比轉換數位電路4將該已放大乳酸量測訊號9由一類比訊號轉換為一數位訊號。
FIG. 11 is a block diagram of a measurement system of a biomedical sensor for lactate detection according to the fourth preferred embodiment of the present invention. Referring to FIG. 11, relative to the first embodiment, the measurement system of a biomedical sensor for lactate detection according to the fourth preferred embodiment of the present invention includes an analog-to-
上述實驗數據為在特定條件之下所獲得的初步實驗結果,其僅用以易於瞭解或參考本發明之技術內容而已,其尚需進行其他相關實驗。該實驗數據及其結果並非用以限制本發明之權利範圍。 The above experimental data are preliminary experimental results obtained under specific conditions, which are only used to facilitate understanding or reference of the technical content of the present invention. Other related experiments are still required. The experimental data and its results are not used to limit the scope of rights of the present invention.
前述較佳實施例僅舉例說明本發明及其技術特徵,該實施例之技術仍可適當進行各種實質等效修飾及/或替換方式予以實施;因此,本發明之權利範圍須視後附申請專利範圍所界定之範圍為準。本案著作權限制使用於 中華民國專利申請用途。 The above preferred embodiments are only examples to illustrate the present invention and its technical features. The technology of the embodiments can still be appropriately implemented in various substantially equivalent modifications and/or replacement methods; therefore, the scope of rights of the present invention shall be subject to the scope defined by the attached patent application scope. The copyright of this case is limited to the use of patent applications in the Republic of China.
1:乳酸感測元件 1: Lactic acid sensing element
100:待測乳酸樣本 100: Lactic acid sample to be tested
2:乳酸訊號處理電路 2: Lactate signal processing circuit
3:訊號讀出電路 3: Signal reading circuit
9:已放大乳酸量測訊號 9: Lactate measurement signal has been amplified
Claims (10)
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| CN101101272A (en) * | 2006-07-07 | 2008-01-09 | 中国科学院电子学研究所 | A biochemical micro-sensing integrated chip, its production and mold preparation method |
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