A planar extended gate organic field effect transistor and its preparation method and application

Abstract

The present invention discloses a planar extended gate organic field effect transistor and its preparation method and application. The planar extended gate organic field effect transistor comprises an extended gate organic field effect transistor and a planar gate; the planar gate covers the extended gate in the extended gate organic field effect transistor to form a planar capacitor; the extended gate organic field effect transistor comprises a substrate, an aluminum film evaporated on the substrate, an aluminum oxide dielectric layer, an organic film, a source electrode and a drain electrode; the aluminum film or an aluminum film evaporated with a gold film serves as an extended gate; the planar gate comprises a substrate and a gold film evaporated on the substrate. The planar extended gate organic field effect transistor is combined with the extended gate by a planar gold electrode, which is equivalent to connecting a planar capacitor C in series with the OFET gate, thereby changing the gate capacitance. It is applied in biosensors, has higher stability and yield, and reduces the detection limit of low-abundance proteins.

Description

Technical Field

[0001] The present invention relates to the technical field of biosensors, and in particular to a planar extended-gate organic field effect transistor and a preparation method and application thereof. Background Art

[0002] A biosensor is a device that detects chemical or biological compounds using specific biochemical reactions mediated by isolated enzymes, the immune system, tissues, organelles, or whole cells, typically by using electrical, thermal, or optical signals to communicate biological information. Biosensors are promising analytical tools for use in healthcare, monitoring food toxins and pathogens, and environmental screening, with the unique characteristics of being inexpensive, portable, disposable, and simple in construction.

[0003] In the past decade, field effect transistors (FETs) have been intensively studied for biosensing applications because they can be naturally integrated into portable electronic devices and because the field effect is related to capacitance, and this capacitance is very sensitive to surface changes. For example, the presence of guest molecules at one of the gate / dielectric or dielectric / semiconductor interfaces can cause a shift in the semiconductor conductance. Therefore, immobilizing specific bioreceptors at the device gate / electrolyte or semiconductor / electrolyte interface makes the device highly sensitive to interface changes.

[0004] Electrolyte-gated field-effect transistors (EGOFETs) are very different from classical OFETs in that the organic semiconductor layer of an EGOFET is in contact with an electrolyte rather than a traditional dielectric. In an EGOFET, the conductivity of the semiconductor channel is modulated by a solid or liquid electrolyte between the semiconductor and the gate. EGOFETs show higher gate capacitance (up to about 1000) than other types of OFETs that use traditional inorganic or organic non-electrolytic dielectrics. Therefore, the bias voltage used for EGOFETs is typically much smaller than the bias voltage required for OFETs (<1V, compared to >10V or more). This feature makes EGOFETs an ideal candidate for next-generation biosensors, particularly for detecting and quantifying biomolecules in aqueous media. Functionalized gate electrodes with specific molecules or functional groups are able to interact with target molecules present in the electrolyte, giving EGOFETs excellent sensing capabilities.

[0005] The most common architecture of OFET is the top gate, bottom contact structure. The gate electrode is immersed in the electrolyte, and the source and drain are isolated from the electrolyte to provide electrical contact for the channel. Among them, the gate capacitance of OFET has an important influence on the performance of the device, and the size of the gate capacitance can affect the performance stability of OFET. Smaller gate capacitance may lead to more unstable performance, especially under temperature changes or voltage changes. Summary of the invention

[0006] The purpose of the present invention is to provide a planar extended gate organic field effect transistor to address the technical defect in the prior art that the gate capacitance is small and easily causes unstable performance of the organic field effect transistor. The planar extended gate organic field effect transistor is combined with the extended gate through a planar gold electrode, which is equivalent to connecting a planar capacitor C in series with the OFET gate, thereby changing the gate capacitance.

[0007] Another object of the present invention EG is to provide a method for preparing the above-mentioned planar extended gate organic field effect transistor.

[0008] Another object of the present invention is to provide the use of the above-mentioned planar extended gate organic field effect transistor in a biosensor, the biosensor device has higher stability and yield rate, and reduces the detection limit of low-abundance proteins.

[0009] The technical solution adopted to achieve the purpose of the present invention is:

[0010] A planar extended gate organic field effect transistor comprises an extended gate organic field effect transistor and a planar gate; the planar gate covers the extended gate in the extended gate organic field effect transistor to form a planar capacitor;

[0011] The extended gate organic field effect transistor comprises a substrate, an aluminum film evaporated on the substrate, an aluminum oxide dielectric layer, an organic film covering the aluminum oxide dielectric layer as an active layer, and a source electrode and a drain electrode vacuum deposited on the organic film; the aluminum film or the aluminum film evaporated with a gold film serves as an extended gate;

[0012] The planar grid includes a substrate and a gold film evaporated on the substrate.

[0013] In the above technical solution, the substrate is a rigid substrate or a flexible substrate; the rigid substrate is a quartz plate or a glass slide; the flexible substrate is polyethylene naphthalate or polymethyl methacrylate.

[0014] In the above technical solution, the material of the organic film is C8-BTBT or C10-DNTT.

[0015] In the above technical solution, a packaging layer is encapsulated on the surface of the gold film, and only a fixed area of ​​the gold film is exposed as a flat gate contact site;

[0016] Preferably, the gold contact sites are in a circular pattern with a diameter of 4-5 mm.

[0017] In the above technical solution, the material of the encapsulation layer is photoresist material, polymethyl methacrylate or polydimethylsiloxane.

[0018] In the above technical solution, the method for preparing the extended gate organic field effect transistor comprises the following steps:

[0019] Step 1: cleaning and drying the substrate; evaporating a layer of aluminum film with a thickness of 70-150 nm on the substrate as an extended gate;

[0020] Step 2: using the substrate with the aluminum film vapor-deposited thereon as an anode and a conductive material as a cathode, respectively, and immersing them in an electrolyte; and applying a constant current between the anode and the cathode to oxidize the aluminum film immersed in the electrolyte to form an aluminum oxide dielectric layer;

[0021] Step 3: Covering the surface of the aluminum oxide dielectric layer with an organic film as an active layer;

[0022] Step 4: attaching a mask plate to the organic film, and vacuum evaporating a layer of silver as a source electrode and a drain electrode to obtain an extended gate organic field effect transistor.

[0023] In the above technical solution, the method for preparing the planar gate is:

[0024] The substrate is cleaned and dried; firstly, a gold film with a thickness of 70-150 nm is evaporated on the substrate; then, a packaging layer is encapsulated on the surface of the obtained gold film by spin coating;

[0025] Preferably, the spin coating speed is 3000-4000 rpm and the time is 30-40 s.

[0026] In the above technical solution, the preparation method of the photoresist material encapsulation layer is to obtain a pattern through a mask during spin coating; then cure at 40-80°C for 1-2 minutes; finally expose and develop for 10-20 seconds, clean and blow dry;

[0027] The preparation method of the polymethyl methacrylate encapsulation layer is as follows: firstly, the gold contact sites to be exposed are protected by a PDMS mask plate or a polyimide tape mask plate; then, spin coating is performed; and finally, the mask plate is removed;

[0028] The preparation method of the polydimethylsiloxane encapsulation layer is as follows: patterning a polydimethylsiloxane film with a thickness of 100-200 um by a puncher; and then adhering the film to a gold film.

[0029] In another aspect of the present invention, the above-mentioned planar extended gate organic field effect transistor is used in a biosensor, and the antigen-antibody complex incubation carrier is located between the extended gate and the planar gate.

[0030] In the above technical solution, the antibody solution is first added to the extended grid, flat grid or nitrocellulose membrane, incubated for 40-50 minutes, then washed and dried; then the antigen solution is added, incubated for 40-50 minutes, then washed and dried;

[0031] The concentration of the antibody solution is 1-10 ng / mL;

[0032] The concentration of the antigen solution is 1pg / mL-1ug / mL.

[0033] Compared with the prior art, the present invention has the following beneficial effects:

[0034] 1. The planar extended gate organic field effect transistor provided by the present invention is combined with the extended gate through a planar gold electrode, which is equivalent to connecting a planar capacitor C in series with the gate, thereby changing the gate capacitance and facilitating the stability of the transistor.

[0035] 2. The flat extended gate organic field effect transistor provided by the present invention has a low detection limit, which is far lower than the threshold of biomarkers and can accurately detect different biomarkers.

[0036] 3. The flat extended gate organic field effect transistor provided by the present invention can measure multiple biomarkers such as D-Dimer (thrombus marker), CEA (carcinoembryonic antigen) and PSA (prostate-specific antigen) with sensitivity below the threshold. At the same time, this method also has a sensitivity below the threshold for sample testing in complex environments (10% FBS, human serum solution). BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 The figure shows the structure schematic diagram of the planar extended gate organic field effect transistor in Example 1;

[0038] Figure 2 The figure shows a physical picture of the planar extended gate organic field effect transistor in Example 1;

[0039] Figure 3 Shown are the transfer (left) and output (right) characteristic curves of the planar extended gate organic field effect transistor in Example 1;

[0040] Figure 4 The threshold voltage and source-drain current offset of the planar extended gate organic field effect transistor under different concentrations of the antigen-antibody complex in Example 1 are shown;

[0041] Figure 5 Shown are the transfer characteristic curve (a) and saturation mobility (b) of the C10DNTT transistor;

[0042] Figure 6 The figure shows the preparation process of the planar grid;

[0043] Figure 7 The D-Dimer △V of the planar extended gate organic field effect transistor in Example 2 is shown. th Response value;

[0044] Figure 8 Shown is a schematic structural diagram of a planar gate (a) and a planar extended gate organic field effect transistor (b) in Example 3;

[0045] Fig. 9 The ΔV of the D-Dimer of the planar extended gate organic field effect transistor in Example 3 is shown. th Response value (a) and △I SD Response value (b);

[0046] Fig.10 The figure shows the structure schematic diagram of the planar extended gate organic field effect crystal in Example 4;

[0047] Fig.11 The ΔV of the D-Dimer of the planar extended gate organic field effect transistor in Example 4 is shown. th Response value (a) and △I SD Response value (b);

[0048] Fig.12 The figure shows a schematic diagram of the structure of the planar extended gate organic field effect crystal in Example 5;

[0049] Fig.13 The ΔV of the D-Dimer of the planar extended gate organic field effect transistor in Example 5 is shown. th Response value (a) and △ISD response value (b);

[0050] Fig.14 Shown are the curve of the capacitance of the sensing area of ​​the planar extended gate organic field effect transistor changing with concentration (a) and the test result of multiple switching cycles of 7500s (b);

[0051] Fig.15 The figure shows the structure schematic diagram of the planar extended gate organic field effect crystal in Example 6;

[0052] Fig.16 The ΔV of the D-Dimer of the planar extended gate organic field effect transistor in Example 6 is shown. th Response value (a) and △I SD Response value (b);

[0053] Fig.17 The ΔV of the D-Dimer human serum sample of the planar extended gate organic field effect transistor in Example 7 is shown. th Response value (a) and △I SDResponse value (b);

[0054] Fig.18 The ΔV of the tumor marker CEA in Example 8 is shown. th Response value (a) and △I SD Response value (b);

[0055] Fig.19 The ΔV of the tumor marker HSA in Example 9 is shown. th Response value (a) and △I SD Response value (b).

[0056] Fig. 20 The Vth statistical distribution (a) of Example 1 and Comparative Example 1 and the ΔV of the D-Dimer of the extended gate organic field effect transistor of Comparative Example 1 are shown. th Response value (b). DETAILED DESCRIPTION

[0057] The present invention is further described in detail below in conjunction with specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0058] Example 1

[0059] A planar extended gate organic field effect transistor, such as Figure 1 , Figure 2 As shown, it includes a C8-BTBT extended gate organic field effect transistor and a planar gate; the C8-BTBT extended gate organic field effect transistor includes a glass slide substrate, an aluminum film, an aluminum oxide dielectric layer, a C8-BTBT film, a source electrode and a drain electrode; the planar gate includes a PMMA film substrate and a gold film.

[0060] In the planar extended gate organic field effect transistor:

[0061] The preparation method of the C8-BTBT extended gate organic field effect transistor comprises the following steps:

[0062] Step 1: Prepare a glass slide as a substrate, clean it and blow it dry with nitrogen; evaporate a layer of aluminum film with a thickness of 100nm on the substrate;

[0063] Step 2: The substrate with the aluminum film evaporated is used as the anode; the conductive material graphite is used as the cathode; the anode and cathode are immersed in the electrolyte, and a density of 0.07 mA / cm is applied between the anode and the cathode. 2 When a constant current is applied, the anode immersed in the electrolyte will produce an oxidation reaction, and the aluminum film will oxidize to form aluminum oxide, thus obtaining an aluminum oxide dielectric layer with an aluminum film.

[0064] In this step, part of the aluminum film immersed in the electrolyte is oxidized to form aluminum oxide, and the remaining part of the aluminum film serves as an extended gate.

[0065] Step 3: By solution shearing method, a 27-30 nm thick C8-BTBT film is scraped on the aluminum oxide dielectric layer as the active layer of the organic semiconductor; the structure of C8-BTBT is as follows:

[0066]

[0067] Step 4: A mask is attached to the surface of the C8-BTBT film (the mask is customized by Beijing Xinxing Bairui Technology Co., Ltd., with a width-to-length ratio of 5:1), and a 40nm thick silver layer is vacuum-deposited as the source electrode and drain electrode to obtain a C8-BTBT extended gate organic field-effect transistor.

[0068] The channel width-to-length ratio of the obtained C8-BTBT extended-gate organic field effect transistor is 5:1. The electrical performance of the C8-BTBT extended-gate organic field effect transistor was tested on an electrical performance test instrument Kerthley 4200 CSC. The transfer output characteristic curve of the C8-BTBT extended-gate organic field effect transistor is shown in FIG. Figure 3 As shown, it shows the properties of a typical p-type field effect transistor, and the saturation voltage is as low as 3 volts. The mobility of the C8-BTBT extended gate organic field effect transistor can reach 2cm 2 / (v*s) -1 , the on / off ratio reaches 10 6 .

[0069] The method for preparing the planar grid is as follows: a PMMA film is prepared as a substrate, which is cleaned and dried, and a gold film with a thickness of 150 nm is evaporated on the substrate as the planar grid.

[0070] Prepare a 10ug / mL OkeyBio K65f1 D-dimer monoclonal antibody solution; prepare OkeyBio C1564 human D-dimer protein antigen solutions with concentration gradients of 1000, 500, 100, 10, 2.5, 1, 0ng / mL respectively.

[0071] A small amount of antibody solution was taken with a pipette and dropped onto the extended gate of the C8-BTBT extended gate organic field effect transistor. After incubation for 45 minutes, it was washed with 0.01X PBS and the excess water was absorbed with dust-free paper. Then, a small amount of antigen solution of different concentrations was taken with a pipette and dropped onto the extended gate incubated with the antibody. After incubation for another 45 minutes, it was washed with 0.01X PBS and the excess water was absorbed with dust-free paper to obtain an incubation carrier with fixed antigen-antibody complexes of different concentrations.

[0072] A small amount of phosphate buffer solution or deionized water is pipetted onto the antigen-antibody complex incubation carrier, and a flat gate is covered on the droplet. The flat gate is used as a gate contact site to test electrical properties on an electrical performance tester Kerthley 4200 CSC.

[0073] Before testing, the transfer curve of the device before the target analyte reaction needs to be repeatedly measured until the three transfer curves overlap perfectly to obtain a stable electrical signal baseline. By testing antigen-antibody complexes of different concentrations, regular threshold voltage and source-drain current offsets can be obtained, such as Figure 4 As shown, the calculated detection limit was 0.1 ng / mL.

[0074] Comparative Example 1

[0075] Use a pipette to draw a small amount of phosphate buffer solution or deionized water droplets on the above antigen-antibody complex incubation carrier, and use the metal needle as the gate contact site to test the electrical performance on the electrical performance test instrument Kerthley4200 CSC. Fig. 20 It can be seen from a that the threshold voltage shift of the traditional Pt electrode extraction reaches 400mV, which is much larger than the 100mV of the flat extended gate organic field effect transistor in Example 1. Based on this, it is difficult to obtain an accurate standard curve, and it is necessary to statistically draw a standard curve graph for multiple data, which undoubtedly increases the difficulty of sensor operation and is not conducive to promotion. The threshold voltage shift response of 20 traditional Pt electrode devices to extract D-Dimer at different concentrations in PBS solution is shown in the figure. Fig. 20 As shown in b, the detection limit was 2.837 pg / mL. Figure 4 and Fig. 20 b It can be seen from the comparison that the error bars of the threshold voltage and source-drain current offset curves in Example 1 are smaller, indicating that the performance of the planar extended gate organic field effect transistor in Example 1 is more stable.

[0076] Example 2

[0077] A planar extended gate organic field effect transistor comprises a C10DNTT extended gate organic field effect transistor and a planar gate; the C10DNTT extended gate organic field effect transistor comprises a glass slide substrate, an aluminum film, an aluminum oxide dielectric layer, a C10DNTT film, a source electrode and a drain electrode; the planar gate comprises a glass slide base and a gold film.

[0078] In the planar extended gate organic field effect transistor:

[0079] The method for preparing a C10DNTT extended gate organic field effect transistor comprises the following steps:

[0080] Step 1: Prepare a substrate, which is a glass slide. After cleaning the substrate, blow dry the substrate with nitrogen gas, and evaporate a layer of aluminum film with a thickness of 100 nm on the substrate as an extended gate.

[0081] Step 2: Use the substrate with the aluminum film as the anode; prepare graphite as the conductive material and the conductive material as the cathode. Soak the anode and cathode in the electrolyte and apply a current with a density of 0.07 mA / cm between the anode and cathode. 2 When a constant current is applied, the anode immersed in the electrolyte will produce an oxidation reaction, oxidizing the aluminum film to form aluminum oxide, thereby obtaining an aluminum oxide dielectric layer with an aluminum film.

[0082] Step 3: By vacuum deposition, a C10DNTT film with a thickness of 40 nm is deposited on the aluminum oxide dielectric layer as an active layer of the organic semiconductor; the structural formula of C10DNTT is as follows:

[0083]

[0084] Step 4: A mask is attached to the surface of the C10DNTT film (the mask is customized by Beijing Xinxing Bairui Technology Co., Ltd., with a width-to-length ratio of 5:1), and 40nm thick silver is vacuum-deposited as the source electrode and drain electrode to obtain a C10DNTT extended-gate organic field-effect transistor.

[0085] The channel width-to-length ratio of the obtained C10DNTT extended-gate organic field effect transistor is 5:1. The electrical performance is tested on an electrical performance test instrument Kerthley 4200 CSC. The transfer characteristic curve of the C10DNTT extended-gate organic field effect transistor is as follows: Figure 5 As shown in the figure, it shows the properties of a typical p-type field effect transistor, and the saturation voltage is as low as 3 volts. The mobility of the prepared flexible low-voltage C10DNTT extended-gate organic field effect transistor can reach 1.33 cm 2 / (v*s) -1 , the on / off ratio reaches 10 6 .

[0086] The method for preparing the planar gate comprises the following steps:

[0087] Step 1: Prepare a substrate, which is a glass slide, clean the substrate, dry the substrate, and evaporate a gold film with a thickness of 150 nm on the substrate.

[0088] Step 2: Use the spin coating method to print a layer of photoresist material on the gold film through the mask. The spin coating speed is 3000rpm and the time is 30s. Make sure the pattern is printed clearly, such as Figure 6As shown, after UV curing at 60° C. for 2 minutes, the planar gate is exposed and developed. The pattern of the photoresist material is a circular photoresist material layer arranged along a rectangular matrix, and the diameter of the circular photoresist material layer is 5 mm.

[0089] Prepare an antibody solution with a concentration of 10ug / mL. In this example, Okey Biotech K65f1 D-dimer monoclonal antibody is used. Prepare an antigen solution with a concentration gradient of 1000, 500, 100, 10, 2.5, 1, 0ng / mL. In this example, Okey Biotech C1564 human D-dimer protein is used.

[0090] According to the same method as in Example 1, the antigen solution and the antibody solution were incubated on the extended gate of the C10DNTT extended gate organic field effect transistor to obtain an extended gate fixed with antigen-antibody complexes of different concentrations.

[0091] 3uL of 0.01X PBS solution was pipetted with a pipette and dropped onto the extended gate fixed with different concentrations of antigen-antibody complexes, and the prepared flat gate was covered on the droplet. The flat gate was used as a gate contact site to test the electrical properties on an electrical performance testing instrument Kerthley4200 CSC.

[0092] Before testing, the transfer curves of the OTFT device before the target analyte reaction need to be repeatedly measured until the three transfer curves overlap perfectly to obtain a stable electrical signal baseline. By testing different concentrations of antigen-antibody complexes, a regular threshold voltage shift can be obtained, such as Figure 7 As shown in the figure, the calculated detection limit was 0.1 ng / mL.

[0093] Example 3

[0094] A planar extended gate organic field effect transistor, such as Figure 8 As shown, it includes a C10DNTT extended gate organic field effect transistor and a planar gate; the C10DNTT extended gate organic field effect transistor is consistent with the C10DNTT extended gate organic field effect transistor in Example 2.

[0095] The method for preparing the planar gate comprises the following steps:

[0096] Step 1: Prepare a substrate, which is a glass slide, clean the substrate, dry the substrate, and evaporate a gold film with a thickness of 150 nm on the substrate.

[0097] Step 2: A PDMS encapsulation layer is encapsulated on the surface of the obtained gold film, exposing only a fixed area of ​​the gold film as a flat gate contact site, and forming a flat capacitor with the extended gate part in the C10DNTT extended gate organic field effect transistor. The PDMS encapsulation layer is directly patterned on the 200um PDMS film through a puncher, and the pattern is a circle with a diameter of 5mm. Then, the PDMS is adsorbed on the gold film with the help of its own viscosity to form a flat gate.

[0098] Antigen solution and antibody solution were prepared in the same manner as in Example 1, and incubated on the extended gate of the C10DNTT extended gate organic field effect transistor to obtain incubation carriers fixed with antigen-antibody complexes of different concentrations.

[0099] 2uL of 1X PBS solution was pipetted with a pipette and dropped onto the antigen-antibody complex incubation carrier, and a flat gate was covered on the droplet. The flat gate was used as a gate contact site to test the electrical properties on an electrical performance tester Kerthley4200 CSC.

[0100] Before testing, the transfer curves of the OTFT device before the target analyte reaction need to be repeatedly measured until the three transfer curves overlap perfectly to obtain a stable electrical signal baseline. By testing different concentrations of antigen-antibody complexes, a regular threshold voltage shift can be obtained, such as Fig. 9 As shown, the calculated detection limit was 0.1 ng / mL.

[0101] from Figure 7 , the difference in error bars can be clearly observed in the standard curve diagram of 9. The smaller the error bar, the more stable the performance of the device. Therefore, it can be determined that the transistor in Example 3 has a more stable test signal. This is because the flat gate is encapsulated with PDMS, which can effectively reduce the variables during performance testing and make the detection more stable.

[0102] Example 4

[0103] A planar extended gate organic field effect transistor, such as Fig.10 As shown, it includes a C10DNTT extended gate organic field effect transistor and a planar gate; the C10DNTT extended gate organic field effect transistor is consistent with the C10DNTT extended gate organic field effect transistor in Example 2. The planar gate is consistent with the planar gate in Example 1.

[0104] The antigen solution and antibody solution were prepared in the same manner as in Example 1.

[0105] Use a pipette to draw 3uL of 10ug / mL antibody solution and drop it on the nitrocellulose membrane NC membrane, incubate for 45 minutes, wash the NC membrane with 0.01X PBS, and absorb excess water with dust-free paper. Use a pipette to draw 3uL of antigen solutions of different concentrations and drop them on the NC membrane, incubate at 37°C for 45 minutes, wash the NC membrane with 0.01X PBS, and absorb excess water with dust-free paper to obtain incubation carriers with fixed antigen-antibody complexes of different concentrations.

[0106] Use a pipette to draw 2uL of 0.01X PBS solution and drop it on the nitrocellulose membrane fixed with different concentrations of antigen-antibody complexes, and cover the prepared flat gate on the nitrocellulose membrane. The flat gate is used as a gate contact site to test the electrical performance on the electrical performance test instrument Kerthley4200 CSC. Before the test, the transfer curve of the OTFT device before the target analyte reacts needs to be repeatedly measured until the three transfer curves overlap perfectly to obtain a stable electrical signal baseline. By testing different concentrations of antigen-antibody complexes, a regular threshold voltage shift can be obtained, such as Fig.11 As shown, the calculated detection limit was 1 pg / mL.

[0107] Using NC membrane as an antigen-antibody complex carrier can make the flat extended gate organic field effect transistor device reused, reduce the error caused by different flat extended gate organic field effect transistor devices, and obtain more stable results.

[0108] Example 5

[0109] A planar extended gate organic field effect transistor, such as Fig.12 As shown, it includes a C10DNTT extended gate organic field effect transistor and a planar gate; the planar gate is consistent with the planar gate in Example 3.

[0110] The method for preparing a C10DNTT extended gate organic field effect transistor and a planar gate comprises the following steps:

[0111] Step 1: Prepare a glass slide as a substrate, clean it and blow it dry with nitrogen; evaporate a 100nm thick aluminum film on the substrate as a gate;

[0112] Step 2: The substrate with the aluminum film evaporated is used as the anode; the conductive material graphite is used as the cathode; the anode and cathode are immersed in the electrolyte, and a density of 0.07 mA / cm is applied between the anode and the cathode. 2 When a constant current is applied, the anode immersed in the electrolyte will produce an oxidation reaction, and the aluminum film will oxidize to form aluminum oxide, thus obtaining an aluminum oxide dielectric layer with an aluminum film.

[0113] On the unoxidized aluminum film, a 60nm gold film is deposited by vacuum deposition as an extended gate.

[0114] Step 3: Vacuum deposition is used to deposit a C10DNTT film with a thickness of 40 nm on the aluminum oxide dielectric layer as an active layer of the organic semiconductor;

[0115] Step 4: A mask is attached to the surface of the C10DNTT film (the mask is customized by Beijing Xinxing Bairui Technology Co., Ltd., with a width-to-length ratio of 5:1), and 40nm thick silver is vacuum-deposited as the source electrode and drain electrode to obtain a C10DNTT extended-gate organic field-effect transistor.

[0116] Antigen solution and antibody solution were prepared in the same manner as in Example 1, and incubated on the flat plate grid to obtain a flat plate grid with antigen-antibody complexes of different concentrations fixed thereon.

[0117] Use a pipette to draw 2uL of 1X PBS solution and drop it on the extended gate fixed with different concentrations of antigen-antibody complexes, and cover the prepared flat gate on the droplet. The flat gate is used as the gate contact site to test the electrical performance on the electrical performance test instrument Kerthley4200 CSC. Before the test, the transfer curve of the OTFT device before the target analyte reaction needs to be repeatedly measured until the three transfer curves overlap perfectly to obtain a stable electrical signal baseline. By testing different concentrations of antigen-antibody complexes, a regular threshold voltage shift can be obtained, such as Fig.13 As shown, the calculated detection limit is 23pg / mL. The capacitance of the flat gate sensing area was tested and it was found that the capacitance value was 50nF, ( Fig.14 a) is much larger than the dielectric layer capacitance, which is beneficial to the stability of the device. Fig.14 As shown in b, the device passed multiple cycle tests and showed high stability.

[0118] Example 6

[0119] A planar extended gate organic field effect transistor is consistent with the planar extended gate organic field effect transistor in embodiment 5.

[0120] Prepare 10ug / mL antibody solution. In this example, Okey Biotech K65f1 D-dimer monoclonal antibody is used. Prepare antigen solution with concentration gradient of 1000, 500, 100, 10, 2.5, 1, 0ng / mL. In this example, Okey Biotech C1564 human D-dimer protein is used. Dilute the antigen solution with 10% FBS solution.

[0121] The antibody solution and the antigen solution were prepared in the same manner as in Example 4, and incubated to obtain nitrocellulose membranes immobilized with antigen-antibody complexes of different concentrations.

[0122] Place the prepared NC membranes of different concentrations, and combine them with C10DNTT extended gate organic field effect transistors and flat gates for sensor testing. The structure diagram is shown in the figure. Fig.15 shown.

[0123] Use a pipette to draw 2uL of 0.01X PBS solution and drop it on the NC membrane. Cover the prepared flat gate on the NC membrane. The flat gate is used as the gate contact site to test the electrical performance on the electrical performance test instrument Kerthley4200 CSC. Before the test, the transfer curve of the OTFT device before the target analyte reaction needs to be repeatedly measured until the three transfer curves overlap perfectly to obtain a stable electrical signal baseline. Testing different concentrations of antigen-antibody complexes can obtain regular threshold voltage shifts, such as Fig.16 As shown, the calculated detection limit was 36 pg / mL.

[0124] Example 7

[0125] A planar extended gate organic field effect transistor is consistent with the planar extended gate organic field effect transistor in embodiment 5.

[0126] Prepare 10ug / mL antibody solution, this example uses Okey Biotech K65f1 D-dimer monoclonal antibody. Prepare antigen solution with concentration gradient of 1000, 500, 100, 10, 2.5, 1, 0ng / mL, this example uses Okey Biotech C1564 human D-dimer protein. Dilute the antigen solution with human serum sample.

[0127] The nitrocellulose membranes were immobilized with antigen-antibody complexes of different concentrations by incubating in the same manner as in Example 4.

[0128] Use a pipette to draw 2uL of 0.01X PBS solution and drop it on the nitrocellulose membrane fixed with different concentrations of antigen-antibody complexes, cover the prepared flat gate on the NC membrane, and cover the prepared flat gate on the droplet. The flat gate is used as the gate contact site to test the electrical performance on the electrical performance test instrument Kerthley4200 CSC. Before the test, the transfer curve of the OTFT device before the target analyte reacts needs to be repeatedly measured until the three transfer curves overlap perfectly to obtain a stable electrical signal baseline. By testing different concentrations of antigen-antibody complexes, a regular threshold voltage shift can be obtained, such as Fig.17 As shown, the calculated detection limit is 480 ng / mL, indicating that the flat extended gate organic field effect transistor still shows good detection effect in the complex environment of human serum samples.

[0129] Example 8

[0130] A planar extended gate organic field effect transistor is consistent with the planar extended gate organic field effect transistor in embodiment 5.

[0131] Prepare 10ug / mL antibody solution, in this example, CEA antibody is used. Prepare antigen solution with concentration gradient of 1000, 100, 10, 2.5, 1, 0ng / mL, in this example, CEA protein is used.

[0132] The nitrocellulose membranes were immobilized with antigen-antibody complexes of different concentrations by incubating in the same manner as in Example 4.

[0133] Use a pipette to draw 2uL of 0.01X PBS solution and drop it on the nitrocellulose membrane fixed with different concentrations of antigen-antibody complexes. Cover the prepared flat gate on the NC membrane. The flat gate is used as the gate contact site to test the electrical performance on the electrical performance test instrument Kerthley4200 CSC. Before the test, the transfer curve of the OTFT device before the target analyte reaction needs to be repeatedly measured until the three transfer curves overlap perfectly to obtain a stable electrical signal baseline. By testing different concentrations of antigen-antibody complexes, a regular threshold voltage shift can be obtained, such as Fig.18 As shown in the figure, the calculated detection limit was 3.6 pg / mL.

[0134] Example 9

[0135] A planar extended gate organic field effect transistor is consistent with the planar extended gate organic field effect transistor in embodiment 5.

[0136] Prepare 10ug / mL antibody solution, in this example, PSA antibody is used. Prepare antigen solution with concentration gradient of 1000, 100, 10, 2.5, 1, 0ng / mL, in this example, PSA protein is used.

[0137] The nitrocellulose membranes were immobilized with antigen-antibody complexes of different concentrations by incubating in the same manner as in Example 4.

[0138] Use a pipette to draw 2uL of 0.01X PBS solution and drop it on the nitrocellulose membrane fixed with different concentrations of antigen-antibody complexes. Cover the prepared flat gate on the NC membrane. The flat gate is used as the gate contact site to test the electrical performance on the electrical performance test instrument Kerthley4200 CSC. Before the test, the transfer curve of the OTFT device before the target analyte reaction needs to be repeatedly measured until the three transfer curves overlap perfectly to obtain a stable electrical signal baseline. By testing different concentrations of antigen-antibody complexes, a regular threshold voltage shift can be obtained, such as Fig.19 As shown in the figure, the calculated detection limit was 0.293 ng / mL.

[0139] The detection limits of the planar extended gate organic field effect transistors in Examples 1-9 are shown in the following table:

[0140]

[0141]

[0142] It can be seen from the above table that the flat extended gate organic field effect transistor prepared by this method has a low detection limit and high sensitivity.

[0143] As can be seen from the table above, the flat extended gate organic field effect transistor prepared by this method has high sensitivity, and can measure multiple biomarkers such as D-Dimer (thrombosis marker), CEA (carcinoembryonic antigen) and PSA (prostate specific antigen) with sensitivity below the threshold. At the same time, this method also has a sensitivity below the threshold for samples tested in complex environments (10% FBS, human serum solution). As can be seen from the table, this method can be used for preliminary screening of diseases such as thrombosis, colorectal cancer and prostate cancer.

[0144] The above is only a preferred embodiment of the present invention. It should be pointed out that, for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A planar extended gate organic field effect transistor, characterized in that: It comprises an extended gate organic field effect transistor and a planar gate; the planar gate covers the extended gate in the extended gate organic field effect transistor to form a planar capacitor; The extended gate organic field effect transistor comprises a substrate, an aluminum film evaporated on the substrate or an aluminum film evaporated on the substrate with a gold film, an aluminum oxide dielectric layer, an organic film covering the aluminum oxide dielectric layer as an active layer, and a source electrode and a drain electrode vacuum deposited on the organic film; the planar gate comprises a base and a gold film evaporated on the base; The material of the organic film is C8-BTBT or C10-DNTT; A packaging layer is packaged on the surface of the gold film evaporated on the substrate in the planar gate, and only a fixed area of ​​the gold film is exposed as a contact site of the planar gate.

2. The planar extended gate organic field effect transistor according to claim 1, characterized in that: The substrate is a rigid substrate or a flexible substrate; the rigid substrate is a quartz plate or a glass slide; the flexible substrate is polyethylene naphthalate or polymethyl methacrylate.

3. The planar extended gate organic field effect transistor according to claim 1, characterized in that: The gold contact sites were in a circular pattern with a diameter of 4-5 mm.

4. The planar extended gate organic field effect transistor according to claim 1, characterized in that: The material of the encapsulation layer is photoresist material, polymethyl methacrylate or polydimethylsiloxane.

5. The planar extended gate organic field effect transistor according to claim 1, characterized in that: The method for preparing the extended gate organic field effect transistor comprises the following steps: Step 1: cleaning and drying the substrate; evaporating a layer of aluminum film with a thickness of 70-150 nm on the substrate as an extended gate; Step 2: using the substrate with the aluminum film vapor-deposited thereon as an anode and a conductive material as a cathode, respectively, and immersing them in an electrolyte; and applying a constant current between the anode and the cathode to oxidize the aluminum film immersed in the electrolyte to form an aluminum oxide dielectric layer; Step 3: Covering the surface of the aluminum oxide dielectric layer with an organic film as an active layer; Step 4: attaching a mask plate to the organic film, and vacuum evaporating a layer of silver as a source electrode and a drain electrode to obtain an extended gate organic field effect transistor.

6. The planar extended gate organic field effect transistor according to claim 5, characterized in that: The method for preparing the flat gate is as follows: The substrate is cleaned and dried; firstly, a gold film with a thickness of 70-150 nm is evaporated on the substrate; then, a packaging layer is encapsulated on the surface of the obtained gold film by spin coating; The spin coating speed is 3000-4000rpm and the time is 30-40s.

7. The planar extended gate organic field effect transistor according to claim 6, characterized in that: The preparation method of the photoresist material encapsulation layer is as follows: obtaining a pattern through a mask during spin coating; then curing at 40-80°C for 1-2 minutes; finally exposing and developing for 10-20 seconds, washing and drying; The preparation method of the polymethyl methacrylate encapsulation layer is as follows: firstly, the gold contact sites to be exposed are protected by a PDMS mask plate or a polyimide tape mask plate; then, spin coating is performed; and finally, the mask plate is removed; The preparation method of the polydimethylsiloxane encapsulation layer is as follows: patterning a polydimethylsiloxane film with a thickness of 100-200 μm by a puncher; and then adhering the film to a gold film.

8. Use of the planar extended gate organic field effect transistor according to any one of claims 1 to 7 in a biosensor, characterized in that: The antigen-antibody complex incubation carrier is located between the extension gate and the flat gate.

9. The use according to claim 8, characterized in that On the extended grid or flat grid, first add the antibody solution, incubate for 40-50 minutes, then wash and dry the water; then add the antigen solution, incubate for 40-50 minutes, then wash and dry the water; The concentration of the antibody solution is 1-10 ng / mL; The concentration of the antigen solution is 1 pg / mL-1 μg / mL.

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