ISFET

離子敏感場效應電晶體，又稱ISFET （英語：ion-sensitive field-effect transistor ），是用於測量溶液中離子濃度的場效應電晶體。當離子濃度（例如H⁺ ，參見pH值）變化時，流經電晶體的電流也會相應變化。在這裡，溶液被用作柵極。基板和氧化物表面之間的電壓由於離子層而產生。它與MOSFET具有相同的基本結構，是一種特殊類型的MOSFET （金屬氧化物半導體場效應電晶體） ^[1] ，但金屬柵極被離子敏感膜，電解質溶液和參比電極代替。 ^[2] ISFET於1970年發明，是第一款生物傳感器FET（BioFET）。

PH值影響柵極材料的Si–OH基團在水溶液中的界面水解性。典型的柵極材料有 SiO₂, Si₃N₄, Al₂O₃ 和 Ta₂O₅.

可以通過位點結合模型描述負責氧化物表面電荷的機理，該模型描述了溶液中Si-OH表面位點和H⁺離子之間的平衡。覆蓋氧化物表面（例如SiO₂）的羥基可以通過提供或接受質子而表現兩性，如在氧化物-電解質界面發生的以下酸鹼反應：

-Si-OH + H₂O ↔ -Si-O ^- + H₃O⁺

-Si-OH + H₃O⁺ ↔ -Si–OH₂⁺ + H₂O

ISFET的源極和漏極的結構與MOSFET相同。氫離子敏感膜通過對氫離子的選擇透過以改變柵極電壓。即ISFET的閾值電壓取決於與其離子敏感膜接觸的物質的pH值。

參比電極的現實局限

對H⁺濃度敏感的ISFET電極可用作常規的玻璃電極，以測量溶液的pH值。但是，它也需要參比電極才能工作。如果與溶液接觸的參比電極是經典的AgCl或Hg₂Cl₂，則它將遭受與常規pH電極相同的局限性（在凝膠電極的情況下，結電位，KCl洩漏和甘油洩漏）。常規的參比電極也可能體積龐大且易碎，由於體積太大的限制也無法使ISFET電極小型化。電極微型化對於某些生物學或活體臨床分析（一次性微型導管pH探針）是必不可少的。

因此，自20多年來以來，許多研究工作一直致力於片上嵌入式微型參比場效應電晶體（REFET）。它們的功能原理或操作模式可能會有所不同，具體取決於電極生產商，並且通常受專利保護。REFET所需的半導體改良表面也不總是與測試溶液保持熱力學平衡，並且可能對侵蝕性或干擾性溶解物質或未很好表徵的老化現象敏感。如果電極能夠以規則的時間間隔頻繁地重新校準並且在其使用壽命期間易於維護，這些問題都可以避免。但是，如果電極必須長時間保持浸入狀態，或者由於測量層面有關的特定約束而無法使用，則可能會出現問題（地球化學測量在極端的環境如升高的水壓下或缺氧或還原條件下容易受大氣氧進入或壓力變化而被干擾）。

與常規玻璃電極一樣，ISFET電極的關鍵因素仍然是參比電極。在對電極故障進行故障排除時，通常從參比電極入手。

歷史

ISFET的基礎是 MOSFET （金屬氧化物半導體場效應電晶體）， ^[1]最初由埃及工程師Mohamed M. Atalla和韓國工程師Dawon Kahng於1959年發明。 ^[3] 1962年， Leland C. Clark和Champ Lyons發明了生物傳感器。 ^[4] ^[5]

特文特大學的荷蘭工程師Piet Bergveld隨後研究了MOSFET，並意識到可以將其改裝為用於電化學和生物應用的傳感器。 ^[6] ^[1] 這導致了Bergveld在1970年發明ISFET。 ^[7] 他將ISFET描述為「一種具有一定距離的柵極的特殊MOSFET」。它是最早的生物傳感器FET （BioFET）。 ^[4]

ISFET傳感器可以在基於 CMOS（互補MOS）技術的集成電路中實現。ISFET器件廣泛用於生物醫學應用中，例如DNA雜交檢測，血液中生物標誌物檢測，抗體檢測，葡萄糖測量和 pH傳感。ISFET也是後來的生物FET的基礎，例如遺傳技術中使用的DNA場效應電晶體（DNAFET）。^[7]

參照

化學場效應電晶體
離子選擇電極
MISFET：金屬-絕緣體-半導體場效應電晶體
MOSFET：金屬-氧化物-半導體場效應電晶體
pH
pH測量儀
電位法
醌氫醌極
飽和甘汞電極
氯化銀電極
標準氫電極

參考文獻

^ ^1.0 ^1.1 ^1.2 Bergveld, Piet. The impact of MOSFET-based sensors (PDF). Sensors and Actuators. October 1985, 8 (2): 109–127 [2019-12-07]. Bibcode:1985SeAc....8..109B. ISSN 0250-6874. doi:10.1016/0250-6874(85)87009-8. （原始內容存檔 (PDF)於2020-08-04）. 引用錯誤：帶有name屬性「Bergveld」的<ref>標籤用不同內容定義了多次
^ Schöning, Michael J.; Poghossian, Arshak. Recent advances in biologically sensitive field-effect transistors (BioFETs) (PDF). Analyst. 10 September 2002, 127 (9): 1137–1151 [2019-12-07]. Bibcode:2002Ana...127.1137S. ISSN 1364-5528. PMID 12375833. doi:10.1039/B204444G. （原始內容存檔 (PDF)於2020-04-21）.
^ 1960: Metal Oxide Semiconductor (MOS) Transistor Demonstrated. The Silicon Engine: A Timeline of Semiconductors in Computers (Computer History Museum). [August 31, 2019]. （原始內容存檔於2019-10-27）.
^ ^4.0 ^4.1 Park, Jeho; Nguyen, Hoang Hiep; Woubit, Abdela; Kim, Moonil. Applications of Field-Effect Transistor (FET)–Type Biosensors (PDF). Applied Science and Convergence Technology. 2014, 23 (2): 61–71 [2019-12-07]. ISSN 2288-6559. doi:10.5757/ASCT.2014.23.2.61. （原始內容存檔 (PDF)於2019-10-07）. 引用錯誤：帶有name屬性「Park」的<ref>標籤用不同內容定義了多次
^ Clark, Leland C.; Lyons, Champ. Electrode Systems for Continuous Monitoring in Cardiovascular Surgery. Annals of the New York Academy of Sciences. 1962, 102 (1): 29–45. Bibcode:1962NYASA.102...29C. ISSN 1749-6632. PMID 14021529. doi:10.1111/j.1749-6632.1962.tb13623.x.
^ Bergveld, P. Development of an Ion-Sensitive Solid-State Device for Neurophysiological Measurements. IEEE Transactions on Biomedical Engineering. January 1970, BME–17 (1): 70–71. doi:10.1109/TBME.1970.4502688.
^ ^7.0 ^7.1 Chris Toumazou; Pantelis Georgiou. 40 years of ISFET technology: From neuronal sensing to DNA sequencing. Electronics Letters. December 2011 [13 May 2016]. doi:10.1049/el.2011.3231.

參考書目

Bergveld, P. Thirty years of ISFETOLOGY, What happened in the past 30 years and what may happen in the next 30 years. Sensors and Actuators B: Chemical. 2003, 88: 1–20. doi:10.1016/S0925-4005(02)00301-5.
Bergveld, P. ISFET, theory and practice (PDF). IEEE Sensor Conference, October 2003. Toronto: IEEE: 26. 2003 [2019-12-07]. （原始內容存檔 (PDF)於2016-12-21）.
ISFET pH傳感器（頁面存檔備份，存於網際網路檔案館）

進一步閱讀

Rothberg, Johnathan M. An integrated semiconductor device enabling non-optical genome sequencing. Nature. 2011, 475 (7356): 348–52. ISSN 1476-4687. PMID 21776081. doi:10.1038/nature10242.
Bergveld, P. The impact of MOSFET-based sensors. Sensors and Actuators. 1985, 8 (2): 109–127. Bibcode:1985SeAc....8..109B. ISSN 0250-6874. doi:10.1016/0250-6874(85)87009-8.
Bergveld, P. The development and application of FET-based biosensors. Biosensors. 1986, 2 (1): 15–33. ISSN 0265-928X. PMID 3790175. doi:10.1016/0265-928X(86)85010-6.
Bergveld, P. A critical evaluation of direct electrical protein detection methods. Biosensors and Bioelectronics. 1991, 6 (1): 55–72. ISSN 0956-5663. PMID 2049171. doi:10.1016/0956-5663(91)85009-L.
Bergveld, P. Thirty years of ISFETOLOGY: What happened in the past 30 years and what may happen in the next 30 years. Sensors and Actuators B: Chemical. 2003, 88 (1): 1–20. ISSN 0925-4005. doi:10.1016/S0925-4005(02)00301-5.
Bergveld, P. ISFET, theory and practice (PDF). IEEE Sensor Conference Toronto, October 2003. Toronto: IEEE: 26 pp. 2003 [2019-12-07]. （原始內容 (PDF)存檔於2008-08-20）.
Bergveld, P; A Van den Berg; PD Van der Wal; M Skowronska-Ptasinska; EJR Sudhölter; DN Reinhoudt. How electrical and chemical requirements for REFETs may coincide. Sensors and Actuators. 1989, 18 (3–4): 309–327. ISSN 0250-6874. doi:10.1016/0250-6874(89)87038-6.
Chudy, M; W Wróblewski; Z Brzózka. Towards REFET. Sensors and Actuators B: Chemical. 1999, 57 (1–3): 47–50. ISSN 0925-4005. doi:10.1016/S0925-4005(99)00134-3.
Chudy, Michal; Wojciech Wróblewski; Zbigniew Brzózka. Towards REFET. Sensors and Actuators B: Chemical. 1999, 57 (1–3): 47–50. ISSN 0925-4005. doi:10.1016/S0925-4005(99)00134-3.
Collins, S.D. Practical limits for solid-state reference electrodes. Sensors and Actuators B: Chemical. 1993, 10 (3): 169–178. ISSN 0925-4005. doi:10.1016/0925-4005(93)87002-7.
Duroux, P; C Emde; P Bauerfeind; C Francis; A Grisel; L Thybaud; D Armstrong; C Depeursinge; A L Blum. The ion sensitive field effect transistor (ISFET) pH electrode: a new sensor for long term ambulatory pH monitoring.. Gut. 1991, 32 (3): 240–245. ISSN 0017-5749. PMC 1378826  . PMID 2013417. doi:10.1136/gut.32.3.240.
Errachid, A.; J. Bausells; N. Jaffrezic-Renault. A simple REFET for pH detection in differential mode. Sensors and Actuators B: Chemical. 1999, 60 (1): 43–48. ISSN 0925-4005. doi:10.1016/S0925-4005(99)00242-7.
Ghallab, Y.H.; W. Badawy; K.V.I.S. Kaler. A novel pH sensor using differential ISFET current mode read-out circuit. Proceedings International Conference on MEMS, NANO and Smart Systems. International Conference on MEMS, NANO and Smart Systems. Banff, Alta., Canada: 255–258. doi:10.1109/ICMENS.2003.1222002.
Guth, U; F Gerlach; M Decker; W Oelßner; W Vonau. Solid-state reference electrodes for potentiometric sensors. Journal of Solid State Electrochemistry. 2009, 13 (1): 27–39. ISSN 1432-8488. doi:10.1007/s10008-008-0574-7.
Huang, I-Yu. Chemical sensors research group. [2010-11-01]. （原始內容存檔於2010-11-01）.
Huang, I-Yu; Ruey-Shing Huang; Lieh-Hsi Lo. A new structured ISFET with integrated Ti/Pd/Ag/AgCl Electrode and micromachined back-side P+ contacts. Journal of the Chinese Institute of Engineers. 2002, 25 (3): 327–334 [2010-11-01]. doi:10.1080/02533839.2002.9670707. （原始內容存檔於2011-07-03）.
Kal, S.; Bhanu, P. V. Design and modeling of ISFET for pH sensing. TENCON 2007 - 2007 IEEE Region 10 Conference. Taipei: 1–4. 2007. ISBN 978-1-4244-1272-3. doi:10.1109/TENCON.2007.4428805.
Kisiel, Anna; Agata Michalska; Krzysztof Maksymiuk. Plastic reference electrodes and plastic potentiometric cells with dispersion cast poly(3,4-ethylenedioxythiophene) and poly(vinyl chloride) based membranes. Bioelectrochemistry. September 2007, 71 (1): 75–80. ISSN 1567-5394. PMID 17107827. doi:10.1016/j.bioelechem.2006.09.006.
Lee, YC; BK Sohn. Development of an FET-type reference electrode for pH detection. Journal of the Korean Physical Society. 2002, 40 (4): 601–604. Bibcode:2002JKPS...40..601Y. ISSN 0374-4884. doi:10.3938/jkps.40.601.
Lisdat, F.; W. Moritz. A reference element based on a solid-state structure. Sensors and Actuators B: Chemical. August 1993, 15 (1–3): 228–232. ISSN 0925-4005. doi:10.1016/0925-4005(93)85057-H.
Skowronska-Ptasinska, M; PD Van Der Wal; A Van Den Berg; P Bergveld; EJR Sudhölter; DN Reinhoudt. Reference field effect transistors based on chemically modified ISFETs. Analytica Chimica Acta. 1990, 230: 67–73. ISSN 0003-2670. doi:10.1016/s0003-2670(00)82762-2.
Suzuki, Hiroaki; Taishi Hirakawa; Satoshi Sasaki; Isao Karube. Micromachined liquid-junction Ag/AgCl reference electrode. Sensors and Actuators B: Chemical. 1998-02-15, 46 (2): 146–154. ISSN 0925-4005. doi:10.1016/S0925-4005(98)00110-5.
van den Berg, A.; A. Grisel; H.H. van den Vlekkert; N.F. de Rooij. A micro-volume open liquid-junction reference electrode for pH-ISFETs. Sensors and Actuators B: Chemical. January 1990, 1 (1–6): 425–432. ISSN 0925-4005. doi:10.1016/0925-4005(90)80243-S.
Vonau, W.; W. Oelßner; U. Guth; J. Henze. An all-solid-state reference electrode. Sensors and Actuators B: Chemical. 2010-02-17, 144 (2): 368–373. ISSN 0925-4005. doi:10.1016/j.snb.2008.12.001.

[Bergveld-1] 1.0 ^1.1 ^1.2 Bergveld, Piet. The impact of MOSFET-based sensors (PDF). Sensors and Actuators. October 1985, 8 (2): 109–127 [2019-12-07]. Bibcode:1985SeAc....8..109B. ISSN 0250-6874. doi:10.1016/0250-6874(85)87009-8. （原始內容存檔 (PDF)於2020-08-04）. 引用錯誤：帶有name屬性「Bergveld」的<ref>標籤用不同內容定義了多次

[Schoning-2] Schöning, Michael J.; Poghossian, Arshak. Recent advances in biologically sensitive field-effect transistors (BioFETs) (PDF). Analyst. 10 September 2002, 127 (9): 1137–1151 [2019-12-07]. Bibcode:2002Ana...127.1137S. ISSN 1364-5528. PMID 12375833. doi:10.1039/B204444G. （原始內容存檔 (PDF)於2020-04-21）.

[computerhistory-3] 1960: Metal Oxide Semiconductor (MOS) Transistor Demonstrated. The Silicon Engine: A Timeline of Semiconductors in Computers (Computer History Museum). [August 31, 2019]. （原始內容存檔於2019-10-27）.

[Park-4] 4.0 ^4.1 Park, Jeho; Nguyen, Hoang Hiep; Woubit, Abdela; Kim, Moonil. Applications of Field-Effect Transistor (FET)–Type Biosensors (PDF). Applied Science and Convergence Technology. 2014, 23 (2): 61–71 [2019-12-07]. ISSN 2288-6559. doi:10.5757/ASCT.2014.23.2.61. （原始內容存檔 (PDF)於2019-10-07）. 引用錯誤：帶有name屬性「Park」的<ref>標籤用不同內容定義了多次

[5] Clark, Leland C.; Lyons, Champ. Electrode Systems for Continuous Monitoring in Cardiovascular Surgery. Annals of the New York Academy of Sciences. 1962, 102 (1): 29–45. Bibcode:1962NYASA.102...29C. ISSN 1749-6632. PMID 14021529. doi:10.1111/j.1749-6632.1962.tb13623.x.

[Bergveld1970-6] Bergveld, P. Development of an Ion-Sensitive Solid-State Device for Neurophysiological Measurements. IEEE Transactions on Biomedical Engineering. January 1970, BME–17 (1): 70–71. doi:10.1109/TBME.1970.4502688.

[Toumazou-7] 7.0 ^7.1 Chris Toumazou; Pantelis Georgiou. 40 years of ISFET technology: From neuronal sensing to DNA sequencing. Electronics Letters. December 2011 [13 May 2016]. doi:10.1049/el.2011.3231.

[1]

[2]

[3]

[4]

[5]

[6]

[7]