KR20160013768A - Dual gate ion-sensitive field-effect transistor sensor - Google Patents
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- KR20160013768A KR20160013768A KR1020140096028A KR20140096028A KR20160013768A KR 20160013768 A KR20160013768 A KR 20160013768A KR 1020140096028 A KR1020140096028 A KR 1020140096028A KR 20140096028 A KR20140096028 A KR 20140096028A KR 20160013768 A KR20160013768 A KR 20160013768A
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Abstract
Description
A double gate ion sensing field effect transistor (ISFET) sensor is provided.
Since P. Bergveld proposed a dual-gate ion-sensor field-effect transistor (ISFET) sensor architecture in 1970, ISFETs have been used in high- Has been developed. The ISFET has a structure in which the gate electrode of the conventional MOSFET is replaced by a reference electrode and an electrolyte. Changes in the surface potential of the membrane can be explained by a site-binding model for the amphiphilic reaction of hydrogen ions. In the site-binding model, it is assumed that there are a large number of OH hydroxyl group sites capable of adsorbing or desorbing hydrogen ions on the surface of the sensing membrane. Thus, the hydrogen ions can be desorbed / adsorbed to a plurality of sites existing on the surface. The electrolyte hydrogen ion concentration determines the surface potential and the ISFET senses it as a change in the amount of current. With this principle, ISFET has been implemented in various biosensors by functionalizing various bioelements on the sensing membrane surface.
ISFET sensor application fields are wide ranging such as DNA sensor, antigen antibody sensor, enzyme sensor, water quality sensor, heavy metal sensor, and soil sensor. In 1976, S. Caras and J. Janata first proposed an enzyme sensor that detects the penicillinase-penicillin reaction. Since then, many sensors have been studied using enzymes that react with glucose, urea, maltose, ethanol, lactose, ascorbic acid, etc. (HI Seo Actuators B, 40, pp1-5, 1997. C. Puig-Lleixa et al., Polyurethane-acrylate photocurable polymeric membrane for ion- et al., Application of enzyme-field effect transistor sensor arrays as detectors in a flow-injection analysis system F. Sevilla et al., A bio-FET sensor for lactose based on co-immobilized < RTI ID = 0.0 > β- galactosidase / glucose dehydrogenase, Biosens. Bioelectron., 9, pp 275-281, 1994; V. Volotovsky et al., Ascorbi c acid determination with an ion-sensitive field effect transistor-based peroxidase biosensor, Anal. Chim. Acta, 359, pp 143-148, 1998).
Despite these intensive studies, however, the enzyme sensor has been shown to be an obstacle to commercialization because of the low sensitivity to the reaction, the selective restriction of the enzyme from which the hydrogen ion should come out as a by-product, the slow reaction rate, It was left.
Meanwhile, in 1980, Schenck proposed an antibody sensor that detects an antigen-antibody reaction using an ISFET. However, the sensitivities of the antigen-antibody reactions are very small, about 10 mV per mole in the concentration range of about 10-7 to 10-11 M, reaching the limit of development of the current antigen antibody sensor (MJ Schoning et al., Recent advances in biologically sensitive field-effect transistors "Analyst, 127, pp1137-1151, 2002).
In 1991, P. Fromherz, A. Offenhausser, T. Vetter, and J. Weis implemented a cell-based sensor that sensed neuronal cell activity (P. Fromherz et al., A Neuron-silicon Junction: A Retzius Field of Effect Transistor, Science, 252, pp. 1290-1293, 1991). Cell-based ISFET biosensors are easy to measure for long periods of time, not only neuronal cells but also mammalian olfactory or taste cell activation potentials, because the method of measuring cell activity potential is non-destructive and capable of measuring long-term cell activity. However, since the maximum potential difference of the cells due to the reaction is low, the signal to noise ratio of the sensor is weak.
In conclusion, conventional ISFET-based sensors have been limited to Nernst reactions at about 59 mV / pH, thus exhibiting problems with low signal sensitivity and hence reproducibility. In addition, semiconductor devices are very vulnerable to potassium and sodium, which are essential for living body elements, making it difficult to commercialize and mass-produce ISFET biosensors.
In 2000, C. Li-Lun proposed an extended-gate field-effect transistor to develop a technology close to commercialization, and reported a technique for separating a commercial field effect transistor from a sensing part. (C. Li-Lun et al., Study on extended gate field effect transistor with tin oxide sensing membrane, Materials Chemistry and Physics 63, pp19-23, 2000). The proposed SnO 2 sensing part is thoroughly separated from commercially available transistors, and when applied to a biosensor, deterioration of the device due to chemical elements such as potassium and sodium can be prevented, and only the inexpensive sensing part can be used Therefore, the possibility of commercialization of an ISFET-based biosensor has been greatly increased. However, since the proposed device was also limited to a maximum of about 59 mV / pH at room temperature by the Nernst reaction, the original problem of low sensitivity was not solved.
In 2010 Mark-Jan Spijkman developed a sensor that surpasses the Nernst limit detection by proposing an ISFET with a double gate structure by adding an additional lower electrode to the existing ISFET (Mark-Jan Spijkman et al., Dual-Gate Organic Field- Effect Transistors as Potentiometric Sensors in Aqueous Solution, Adv. Funct. Mater., 20, pp898-905, 2010). The core of the research is to implement a sensor that exceeds the theoretical limit of about 59 mV / pH due to the electrostatic coupling generated in the upper and lower electrodes. However, since leakage current due to electrostatic coupling and isolation between the sensing part and the thin film transistor are not formed, damage of the transistor due to various ions occurs.
One embodiment of the present invention is to provide a sensor that has a sensitivity that exceeds the theoretical limit of about 59 mV / pH and that is highly stable.
In addition, one embodiment of the present invention is to provide a sensor with reduced leakage current due to super electrostatic coupling, improved sensitivity, linear response to surface potential, hysteresis, and drift characteristics.
In addition, one embodiment of the present invention is to provide a sensor that can be replaced by a sensing unit including a sensing film which continuously uses a measuring unit including a transistor having a high process unit cost and a process unit price is relatively low.
In addition, one embodiment of the present invention provides a new sensor platform for a DNA sensor, an antigenic antibody sensor, an enzyme sensor, a water quality sensor, a heavy metal sensor, or a soil sensor field, Sensor.
Embodiments according to the present invention can be applied to achieve other tasks not specifically mentioned other than the above-mentioned problems.
In one embodiment of the present invention, a lower gate electrode, a lower insulating film located on the lower gate electrode, a source and a drain located on the lower insulating film and spaced apart from each other, a channel layer located between the source and the drain, And a top gate electrode located on the top insulating layer, the channel layer thickness being less than about 10 nm, and a double gate ion sensing field effect transistor (ISFET) sensor using ultra- Lt; / RTI >
The equivalent oxide thickness of the upper insulating layer may be thinner than the equivalent oxide thickness of the lower insulating layer.
The double gate ion sensing field effect transistor (ISFET) sensor may further include an interchangeable sensor coupled to the top gate electrode.
The interchangeable sensor may include a metal electrode connected to the top gate electrode, and a sensing film positioned over the metal electrode and sensing ions.
A double gate ion sensing field effect transistor (ISFET) sensor can have a pH sensitivity of greater than or equal to about 59 mV / pH.
The channel layer may include at least one of an oxide semiconductor, an organic semiconductor, polycrystalline silicon, or monocrystalline silicon.
The sensing film of the upper, lower insulating film or sensor may include at least one of SiO 2 , HfO 2 , Al 2 O 3 , Ta 2 O 5 , ZrO 2 , or TiO 2 .
The sensing film of the upper, lower insulating film or the sensor may include at least one of a single, double, or triple laminated structure.
The double gate ion sensing field effect transistor (ISFET) sensor can be used to diagnose at least one of the following diseases: hepatitis B, avian influenza, foot and mouth disease, pancreatic cancer, prostate cancer, cervical cancer, , a pH sensor, or an enzyme sensor.
The double gate ion sensing field effect transistor (ISFET) sensor according to an embodiment of the present invention has a sensitivity that exceeds the theoretical limit of about 59 mV / pH and is excellent in stability. In addition, the double gate ion sensing field effect transistor (ISFET) sensor according to an embodiment of the present invention reduces the leakage current of the upper channel due to super electrostatic coupling and exhibits high sensitivity, linear response to surface potential, hysteresis, drift characteristic Can be improved. Furthermore, the measuring unit including the transistor having a high process unit cost is continuously used, and the sensor unit including the sensing film having a relatively low process unit price can provide a sensor that can be replaced. In addition, the double gate ion sensing field effect transistor (ISFET) sensor according to an embodiment of the present invention provides a new sensor platform for DNA sensor, antigen antibody sensor, enzyme sensor, water quality sensor, heavy metal sensor, or soil sensor field , And particularly, a sensor for diagnosing a precise detection confirmed disease capable of quick and simple early detection can be provided.
1 is a simplified cross-sectional view of a double gate ion sensing field effect transistor (ISFET) sensor coupled with a sensor in accordance with an embodiment of the present invention.
Figure 2 shows a schematic diagram of a coupling technique of a double gate ion sensing field effect transistor (ISFET) and a sensor in accordance with an embodiment of the present invention.
FIG. 3 is a photograph of a double gate ion sensing field effect transistor (ISFET), interchangeable sensor, and double gate ion sensing field effect transistor (ISFET) according to an embodiment of the present invention, .
4 shows a transfer curve according to the upper gate voltage of the double gate ion sensing field effect transistor (ISFET) according to Comparative Example 1 of the present invention.
5 is a graph showing a relationship between an upper gate voltage extracted in Comparative Example 1 of the present invention and a threshold voltage of a double gate ion sensing field effect transistor (ISFET).
6 shows a transfer curve according to the upper gate voltage of the double gate ion sensing field effect transistor (ISFET) according to
7 is a graph showing the relationship between the upper gate voltage extracted in
FIG. 8 is a graph showing sensitivity and amplification evaluation results of an electrostatic-coupling double gate ion sensing field effect transistor (ISFET) according to a channel layer thickness for Examples 1 to 3 and Comparative Example 1. FIG.
9 is a graph showing distribution of hysteresis and drift characteristics according to channel thickness in Experimental Example 1 of the present invention.
10 is a graph showing pH sensing characteristics of the sensor manufactured in Experimental Example 2 of the present invention.
11 is a graph showing the hepatitis B detection characteristic through the sensor manufactured in Experimental Example 3 of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS The above and other features and advantages of the present invention will be more apparent from the following detailed description taken in conjunction with the accompanying drawings, in which: FIG.
The present invention may be embodied in many different forms and is not limited to the embodiments described herein. In order to clearly explain the present invention in the drawings, parts not related to the description are omitted, and a detailed description of well-known known technologies will be omitted.
Hereinafter, one embodiment of the present invention will be described in detail. However, it should be understood that the present invention is not limited thereto, and the present invention is only defined by the scope of the following claims.
Figure 1 is a simplified cross-sectional view of a double gate ion sensing field effect transistor (ISFET)
Referring to FIG. 1, a double gate ion sensing field effect transistor (ISFET)
Hereinafter, a description of commonly known portions of each component of the double gate ion sensing field effect transistor (ISFET)
The small surface potential voltage difference generated by the
The
Due to the strong electric field of the
The
The
The equivalent oxide thickness of the upper insulating
Sensing membrane of the upper insulating
2 illustrates a schematic diagram of a coupling technique of a double gate ion sensing field effect transistor (ISFET) 120 and a
2, a double gate ion sensing field effect transistor (ISFET)
A double gate ion sensing field effect transistor (ISFET) 120 according to an embodiment of the present invention includes an electric field transistor including an upper
A double gate ion sensing field effect transistor (ISFET) sensor in accordance with an embodiment of the present invention may have a pH sensitivity of greater than or equal to about 59 mV / pH.
In addition, the double gate ion sensing field effect transistor (ISFET) sensor can be used to diagnose at least one disease of hepatitis B, avian influenza, pandemic, pancreatic, prostate, cervical, or liver cancer, A heavy metal sensor, a pH sensor, or an enzyme sensor.
EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples. However, the following Examples are merely examples of the present invention, but the present invention is not limited to the following Examples.
< Example 1> Channel layer Thickness - 4.3 nm
Double gate ion detection Field Effect transistor ISFET ) Production
The substrate is made of silicon-on-insulator (SOI) having a resistivity of about 10 to 20 ohm-cm in the (100) direction, the thickness of silicon as the lower gate electrode is about 107 nm, and the buried SiO 2 oxide film The substrate is fabricated at 224 nm. After performing the standard RCA cleaning, the top silicon is etched with about 2.38 wt% tetramethylammonium hydroxide (TMAH) solution to form an ultra thin film, and a channel region is formed by photolithography. The length and width of the formed channel are about 20 um and 20 um, respectively. The thickness of the formed channel layer is about 4.3 nm. Subsequently, n-type polycrystalline silicon was deposited using a CVD apparatus to form a source and a drain. Thereafter, an upper insulating film is formed on the source and the drain by oxidizing silicon dioxide to a thickness of about 23 nm. Thereafter, an Al thin film layer having a thickness of about 150 nm is deposited using an E-beam evaporator to form an upper gate electrode. Next, a heat treatment performed in a gas atmosphere comprising about 450˚C, and N 2 and H 2 to produce a double-gate ion sensing field effect transistor (ISFET) for eliminating the defects to improve the interface state between them.
Manufacture of interchangeable detectors
The substrate uses a (100) direction p-type silicon in which
Double gate ion detection Field Effect transistor ISFET ) Manufacture of sensor
We fabricate a double gate ion sensing field effect transistor (ISFET) sensor with interchangeable sensors coupled by connecting the metal electrode of the fabricated interrogative sensor to the top gate electrode of a double gate ion sensing field effect transistor (ISFET).
< Comparative Example 1> Channel layer Thickness - 85 nm
In Example 1, a double gate ion sensing field effect transistor (ISFET), interchangeable sensor, interchangeable sensor was fabricated in the same manner as in Example 1 except that the thickness of the channel layer was formed to about 85 nm Coupled double gate ion sensing field effect transistor (ISFET) sensor.
< Comparative Example 2> Channel layer Thickness - 61 nm
In Example 1, a double gate ion sensing field effect transistor (ISFET), interchangeable sensor, interchangeable sensor was fabricated in the same manner as in Example 1 except that the thickness of the channel layer was formed to be about 61 nm Coupled double gate ion sensing field effect transistor (ISFET) sensor.
< Comparative Example 3> Channel layer Thickness - 31 nm
In Example 1, a double gate ion sensing field effect transistor (ISFET), interchangeable sensor, interchangeable sensor was fabricated in the same manner as in Example 1, except that the thickness of the channel layer was formed to about 31 nm Coupled double gate ion sensing field effect transistor (ISFET) sensor.
< Experimental Example 1> Channel layer Evaluation of properties according to thickness
For Example 1 and Comparative Examples 1 to 3, the following experiment is performed to evaluate the characteristics of the double gate ion sensing field effect transistor (ISFET) sensor according to the channel layer thickness. To induce sensitivity amplification using electrostatic coupling, Ag / AgCl is grounded on the upper electrode, and measurement is performed using the lower gate electrode of the double gate ion sensing field effect transistor.
4 shows a transfer curve according to the upper gate voltage of the double gate ion sensing field effect transistor (ISFET) according to Comparative Example 1 of the present invention.
5 is a graph showing a relationship between an upper gate voltage extracted in Comparative Example 1 of the present invention and a threshold voltage of a double gate ion sensing field effect transistor (ISFET).
6 shows a transfer curve according to the upper gate voltage of the double gate ion sensing field effect transistor (ISFET) according to
7 is a graph showing the relationship between the upper gate voltage extracted in
Referring to FIG. 4, when operated in the double gate operation mode, the upper channel interface has electrons or holes depending on the upper gate voltage VF. Here, the carriers induced at the upper gate interface prevent the influence of the electric field of the lower gate from reaching the upper gate, and the upper and lower electrostatic coupling can not be achieved. As a result, a change in the threshold voltage of the lower field transistor due to the upper gate voltage
) Is blocked. Also, when the upper gate interface enters the inversion region, a phenomenon that the leakage current also becomes large can be confirmed. Referring to FIG. 5, it can be seen that, in the thick channel layer of about 85 nm, the amplification phenomenon is allowed only in a limited range where the top gate interface is completely depleted, and the threshold change in the depletion region is not uniform. The slope in the depletion region is the amplification factor of the double gate thin film transistor. Depending on the interfacial state of the upper gate, the slope changes, which, when applied to the sensor, is a factor that hinders the linear response to surface potential.On the other hand, referring to FIG. 6, in the transistor transfer characteristic curve including the about 4.3 nm ultra thin film channel layer, the threshold voltage of the lower field transistor by VF is kept constant, and in the upper interface shown in FIGS. And does not allow the inversion and accumulation regions of the < RTI ID = 0.0 > That is, electrons and holes induced in the upper gate interface are also completely controlled, and the leakage current can be completely shut off. This phenomenon is based on the phenomenon that occurs due to the strong electric field of the lower electrode induced in the ultra-thin body, and super electrostatic coupling that can be controlled under all conditions up to the upper interface. Unlike FIG. 4 of the thick channel layer, FIG. 6 shows that the electrostatic coupling phenomenon is generated in the entire region while allowing a stable inclination.
FIG. 8 is a graph showing sensitivity and amplification evaluation results of an electrostatic-coupling double gate ion sensing field effect transistor (ISFET) according to a channel layer thickness for Examples 1 to 3 and Comparative Example 1. FIG.
Referring to FIG. 8, it can be seen that the thinner the channel, the greater the sensitivity can be obtained. Also, due to the thick channel, the upper interfacial leakage current seen in the approximately 85 nm channel element inherently containing electrons at the upper gate interface can also be largely controlled in the ultra thin film transistor of about 4.3 nm. Ultra-thin channels also increase the linear response for each pH. This is because super electrostatic coupling allows a stable amplification factor.
9 is a graph showing hysteresis and drift characteristic distribution according to channel thickness. Hysteresis is an evaluation of deterioration of the device in accordance with rapid pH change when the device is measured in the order of
< Experimental Example 2> pH Evaluation of Sensing Characteristics
For Example 1, the following experiment was performed to evaluate the pH sensing characteristics of a double gate ion sensing field effect transistor (ISFET) sensor. The interrogative sensor is connected to the field effect transistor, and the Ag / AgCl reference electrode is grounded at the upper electrode of the interrogative sensor. Then, pH solution is injected into the interchangeable sensor, and a pH sensitivity measurement is performed by applying a bias to the lower electrode of the field effect transistor.
Referring to FIG. 10, the sensitivity of the double gate ion sensing field effect transistor (ISFET) sensor is greatly increased to about 2.037 V / pH without increasing the leakage current, and can have a high sensitivity sensor characteristic of about 0.4% error. This is about 35 times the amplified sensitivity of the existing Nernst reaction. Since biosensors are completely isolated from the sensing part and the semiconductor device, they provide a stable platform to prevent damage due to potassium and sodium in the chamber. .
< Experimental Example 3> Evaluation of hepatitis B detection characteristics
The following experiment is performed to evaluate the hepatitis B detection characteristics using the sensor manufactured in Example 1. [ Prepare an interchangeable sensor immobilizing a biomaterial for detection of the first biomarker. Next, the interrogator is inserted into the ion-sensing field-effect transistor and the measurement is performed by injecting the biomarker.
Specifically, an OH group is formed on the surface of the first sensing film by using O 2 plasma so as to immobilize the antibody on the surface of the sensing film. Then, about 5% of (3-aminopropyl) trimethoxysilane diluted in ethanol was reacted for about one hour to form an amino group on the surface, and about 1 M of succinic anhydride Succinic anhydride is injected and reacted at about 37 ° C for about 4 hours to form a carboxyl group on the surface. Next, about 0.4 M of N-hydroxysuccinimide and about 0.1 M of ethyl (dimethylaminopropyl) carbodiimide are reacted for about 15 minutes Next, approximately 100 ng / mL of anti-HBs are injected into the chamber and reacted for 4 hours. Next, HBs viruses at each concentration are injected at approximately 30-minute intervals to detect the signal.
The results are shown in Fig. FIG. 11 is a graph showing the hepatitis B detection characteristic through the manufactured sensor. Referring to FIG. 11, since the super electrostatic coupling phenomenon occurring in the double gate ultra thin film transistor can greatly amplify the reaction of the surface potential of the interchangeable type sensing film, it can be understood that the amount of minute hepatitis B virus can be absolutely quantified can do. Therefore, the sensor platform of the present invention can provide a stable early screening system for diseases, including diseases such as pancreatic cancer, cervical cancer, and avian influenza, which are difficult to be quickly screened.
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments,
Various modifications may be made by those skilled in the art.
100: Detector coupled double-gate ion-sensing field-effect transistor (ISFET) sensor
101: lower gate electrode 102: lower insulating film
103: drain 104: source
105: channel layer 106: upper insulating film
107: upper gate electrode
108: metal electrode
109: Sensing membrane
110: chamber 111: reference electrode, upper electrode
120: Double Gate Ion Sensing Field Effect Transistor (ISFET)
130: Detector
Claims (9)
A lower insulating film located on the lower gate electrode,
A source and a drain disposed on the lower insulating film and spaced apart from each other,
A channel layer located above the lower insulating layer and positioned between the source and the drain,
An upper insulating layer disposed on the source, the drain, and the channel layer, and
The upper gate electrode
/ RTI >
Wherein the channel layer has a thickness of 10 nm or less. ≪ RTI ID = 0.0 > 16. < / RTI >
Wherein the equivalent oxide thickness of the upper insulating layer is thinner than the equivalent oxide thickness of the lower insulating layer.
The double gate ion sensing field effect transistor (ISFET)
Further comprising a replaceable sensor coupled to the top gate electrode. ≪ Desc / Clms Page number 20 >
The interchangeable sensor includes a metal electrode connected to the upper gate electrode,
A sensing electrode disposed on the metal electrode and sensing ions
(ISFET) sensor. ≪ / RTI >
Wherein the sensing film comprises at least one of SiO 2 , HfO 2 , Al 2 O 3 , Ta 2 O 5 , ZrO 2 , or TiO 2 ,
(ISFET) sensor comprising at least one of a single, double, or triple stacked structure.
The double gate ion sensing field effect transistor (ISFET)
Double gate ion sensing field effect transistor (ISFET) sensor with pH sensitivity above 59 mV / pH.
Wherein the channel layer comprises at least one of oxide semiconductor, organic semiconductor, polycrystalline silicon, or monocrystalline silicon.
Wherein the upper insulating film or the lower insulating film includes:
At least one of SiO 2 , HfO 2 , Al 2 O 3 , Ta 2 O 5 , ZrO 2 , or TiO 2 ,
(ISFET) sensor comprising at least one of a single, double, or triple stacked structure.
The double gate ion sensing field effect transistor (ISFET)
Diagnosing a disease of at least one of hepatitis B, avian flu, foot and mouth disease, pancreatic cancer, prostate cancer, cervical cancer, or liver cancer,
Wherein the sensor is used as at least one of a cell-based sensor, a water quality sensor, a heavy metal sensor, a pH sensor, or an enzyme sensor.
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WO2019048059A1 (en) * | 2017-09-08 | 2019-03-14 | Ecole Polytechnique Federale De Lausanne (Epfl) | Double-gate field-effect-transistor based biosensor |
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WO2018016896A1 (en) * | 2016-07-20 | 2018-01-25 | 한국과학기술연구원 | Field effect sensor for colon cancer |
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KR102093659B1 (en) | 2019-07-25 | 2020-03-26 | 광운대학교 산학협력단 | A high-performance biosensor based on a ion-sensitive field effect transistor having a capacitive type coplannar structure |
KR20210012454A (en) | 2019-07-25 | 2021-02-03 | 광운대학교 산학협력단 | A high-performance biosensor based on a ion-sensitive field effect transistor having a triple gate structure |
KR20210012452A (en) | 2019-07-25 | 2021-02-03 | 광운대학교 산학협력단 | A high-performance biosensor based on a ion-sensitive field effect transistor having a resistive type coplannar structure |
KR20210060932A (en) * | 2019-11-19 | 2021-05-27 | 한국전자기술연구원 | Bio sensor using fet element and extend gate, and operating method thereof |
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