Ti3C2 MXene field effect sensor and preparation and application thereof

Abstract

The invention relates to the technical field of sensing detection, in particular to a Ti3C2MXene field effect sensor as well as preparation and application thereof. The Ti3C2MXene field effect sensor provided by the invention comprises an insulating substrate, a sample introduction groove formed in the upper surface of the insulating substrate, source and drain electrodes which are arranged on the upper surface of the insulating substrate, are symmetrically arranged, extend into the sample introduction groove and are connected with an external electrical test system, and a Ti3C2MXene conducting channel region arranged between the source and drain electrodes, and the bladder cancer characteristic protein aptamer probe is modified in a Ti3C2MXene conducting channel region. According to the invention, a Ti3C2MXene FET preparation technology and a sensing technology are combined, so that low-cost, high-sensitivity, rapid and efficient detection of bladder cancer markers can be realized.

Description

Technical Field

[0001] The present invention relates to the field of sensor detection technology, in particular to a Ti 3 C 2 MXene field effect sensors and their preparation and applications. Background Art

[0002] In recent years, sensors based on field effect transistors (FETs) have gained considerable attention due to their ability to sense target substances by detecting changes in the conductivity of the transistor. Compared with traditional methods, FET-based biosensors have the advantages of simple operation, low cost, small size, and fast response. They have been widely used to detect heavy metal ions, environmental pollutants, and biomolecules. However, the performance of FET sensors is greatly affected by the semiconductor material used as the channel. The channel size of traditional three-dimensional semiconductor materials (10 2 -10 4 The large size of the channel material (nm) leads to low signal transduction efficiency, which limits the carrier modulation at the solid electrolyte interface and the sensor performance. Therefore, the development of stable, efficient and sensitive channel materials is a key strategy to improve the sensing performance of FET sensors.

[0003] Two-dimensional materials have lower material thickness and larger specific surface area, and the conductive interface can be directly exposed to external stimuli or perturbations, making them highly sensitive to target analytes. FET sensors based on two-dimensional materials show unique potential in biomarker analysis and healthcare applications. 3 C 2 T x Discovered in 2011, MXene is a layered two-dimensional material with high specific surface area, excellent conductivity and good biocompatibility, and has promising applications in chemical and biological sensing. The inherent high conductivity of MXene significantly improves the signal-to-noise ratio of the sensor, while its large specific surface area provides different active sites; in addition, its excellent biocompatibility indicates that it has potential application prospects in biosensing. However, the current research and reports on MXene-based FET sensors are very limited, and the excellent performance of MXene has not yet been fully utilized. Summary of the invention

[0004] In order to solve the above problems, the purpose of the present invention is to provide a Ti 3 C 2 MXene field effect sensors and their preparation and applications.

[0005] The purpose of the present invention can be achieved by the following technical solutions:

[0006] The first object of the present invention is to provide a Ti 3 C 2The MXene field effect sensor comprises an insulating substrate, a sampling slot arranged on the upper surface of the insulating substrate, a source-drain electrode arranged on the upper surface of the insulating substrate, symmetrically arranged and extending into the sampling slot for connecting to an external electrical test system, and a Ti arranged between the source-drain electrode. 3 C 2 MXene conductive channel region and modified on Ti 3 C 2 Bladder cancer characteristic protein aptamer probe in the conductive channel region of MXene;

[0007] The bladder cancer characteristic protein aptamer probe is used to bind to the bladder cancer characteristic protein to change Ti 3 C 2 The charge distribution of MXene thus changes the current response of the sensor;

[0008] Specifically, the bladder cancer characteristic protein aptamer probe is a short oligonucleotide sequence or short polypeptide obtained by in vitro screening, which can bind to the selected NMP22 ligand with high affinity and strong specificity; it is fixed on Ti 3 C 2 The probe on the MXene conductive channel will specifically capture and bind to the bladder cancer characteristic protein NMP22. At this time, the charge carried by NMP22 produces an electric field effect, changing the Ti 3 C 2 The charge distribution within the MXene in turn changes the current response of the sensor.

[0009] In one embodiment of the present invention, the insulating substrate is selected from one of silicon dioxide, glass, mica, a silicon wafer covered with an insulating layer, polyethylene terephthalate, polyimide or polydimethylsiloxane.

[0010] In one embodiment of the present invention, the source-drain electrodes are gold film electrodes; the thickness of the gold film electrodes is 20 to 60 nm.

[0011] In one embodiment of the present invention, the material of the injection slot is selected from one of polydimethylsiloxane, Flexdym, and thermoplastic polyurethane elastomer.

[0012] In one embodiment of the present invention, the bladder cancer characteristic protein aptamer probe is an aptamer probe of protein NMP22.

[0013] The second object of the present invention is to provide a Ti 3 C 2 Preparation method of MXene field effect sensor, the Ti 3 C 2 MXene field effect sensor is the above Ti 3 C2 The preparation of MXene field effect sensor includes the following steps:

[0014] (S1) Ti 3 AlC 2 The powder is mixed with the fluorine-containing solution and then post-treated to obtain a mixed solution;

[0015] (S2) using a standard photolithography process to make an electrode pattern on an insulating substrate, and then preparing a gold film electrode as a source and drain electrode by vacuum coating, applying the mixed solution prepared in step (S1) between the source and drain electrodes, and performing a vacuum drying process to obtain Ti 3 C 2 MXene conductive channel region;

[0016] (S3) Modification of bladder cancer characteristic protein aptamer probe to Ti 3 C 2 MXene conductive channel region, and then the injection slot is set on the upper surface of the source and drain electrodes to prepare Ti 3 C 2 MXene field effect sensor.

[0017] In one embodiment of the present invention, in step (S1), Ti 3 AlC 2 Mix the powder with the fluorine-containing solution in small amounts several times.

[0018] In one embodiment of the present invention, in step (S1), Ti 3 AlC 2 The mass ratio of powder to fluorine-containing solution is 1:15-25;

[0019] Preferably, Ti 3 AlC 2 The mass ratio of powder to fluorine-containing solution is 1:21;

[0020] The fluorine-containing solution is selected from one of a hydrofluoric acid solution or a LiF hydrochloric acid solution;

[0021] Preferably, the fluorine-containing solution is a mixed solution of LiF powder and a 9M hydrochloric acid solution;

[0022] Ti 3 AlC 2 The mass ratio of the powder to the LiF powder is 1:1; the amount ratio of the LiF powder to the hydrochloric acid solution is 1 g:20 mL.

[0023] In one embodiment of the present invention, in step (S1), the post-treatment is re-suspension treatment using deionized water after centrifugation;

[0024] The pH of the mixed solution is 6-7.

[0025] In one embodiment of the present invention, in step (S2), during the vacuum drying process, the temperature is 40-70° C. and the time is 0.5-2 h.

[0026] The third object of the present invention is to provide a Ti 3 C 2 Application of MXene field effect sensors in the preparation of kits for detecting and / or preventing bladder cancer.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] The present invention adopts Ti 3 C 2 MXene FET preparation technology is combined with sensing technology to change Ti by using the specific binding of aptamer probes and characteristic proteins. 3 C 2 The charge distribution of MXene can be used to detect bladder cancer specifically by observing the current change of the sensor. 3 C 2 The MXene field effect sensor has a simple preparation process, fast response speed, low cost, and high selectivity. It effectively improves the sensitivity and efficiency of bladder cancer marker detection and has potential application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 is the Ti obtained in Example 1 3 C 2 Scanning electron microscope image of MXene.

[0030] Figure 2 This is an optical microscope image of the field effect crystal sensor channel obtained in Example 1.

[0031] Figure 3 This is a schematic diagram of the structure of the field effect crystal sensor obtained in Example 1; the numbers in the figure are: 1, insulating substrate; 2, Ti 3 C 2 MXene conductive channel area; 3. Electrode; 4. Injection slot.

[0032] Figure 4 The 1×10 -18 M to 1×10 -9 Current response curve of NMP22, a characteristic protein of bladder cancer, at gradient concentrations. DETAILED DESCRIPTION

[0033] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments.

[0034] In the following examples, unless otherwise specified, all reagents used are commercially available reagents, and all detection means and methods used are conventional detection means and methods in the art.

[0035] Example 1

[0036] This embodiment provides a Ti 3 C 2 The preparation method of MXene field effect sensor specifically comprises the following steps:

[0037] (S1) adding 5 g of LiF powder into 100 mL of hydrochloric acid solution (concentration: 9 M), and stirring the mixture on a stirrer for 15 minutes to obtain a primary mixed solution;

[0038] 5g Ti 3 AlC 2 The powder was added to the primary mixed solution obtained above in 6 portions within 5 minutes, and the mixture was placed in a stirrer and stirred continuously for 48 hours to obtain a secondary mixed solution;

[0039] (S2) adding deionized water to the secondary mixed solution, and centrifuging the mixed solution. After the treatment, the precipitate is mixed with deionized water again and centrifuged until the pH of the solution reaches 6.1, thereby obtaining a mixed solution;

[0040] (S3) Using a standard photolithography process to make a patterned electrode on an insulating substrate (made of polydimethylsiloxane), and then using a vacuum coating process to make a gold film electrode with a thickness of 50 nanometers, 1 mL of the mixed solution obtained in step (S2) is applied between the source and drain electrodes, and vacuum dried in a vacuum oven at 60° C. for 1 hour to obtain Ti 3 C 2 MXene conductive channel region (Ti 3 C 2 MXene scanning electron microscopy image Figure 1 As shown, Ti 3 C 2 Microscope images of the conductive channel region of MXene Figure 2 shown);

[0041] (S4) The bladder cancer characteristic protein NMP22 aptamer probe (SEQ ID NO.1: 5'-GCCTATTCCGACTAGAGACCGGCGCACAGAGGCTTCGGAATAGGCTTAAC-3') was modified to Ti 3 C 2 MXene conductive channel area, and then the PDMS injection groove (outer diameter square 6*6mm, inner diameter circular diameter 3mm) was set up on the upper surface of the source and drain electrodes to obtain Ti 3 C2 MXene field effect sensors (such as Figure 3 As shown, it includes an insulating substrate 1, a sampling slot 4 arranged on the upper surface of the insulating substrate 1, electrodes 3 (source-drain electrodes) arranged on the upper surface of the insulating substrate 1 and extending into the sampling slot for connecting to an external electrical test system, and a Ti disposed between the electrodes. 3 C 2 MXene conductive channel region 2, and bladder cancer characteristic protein aptamer probe modified on Ti3C2MXene conductive channel region 2).

[0042] Test process (same as the following embodiments):

[0043] The Ti prepared in this example 3 C 2 The electrode contacts of the MXene field effect sensor were welded to the metal contacts on the PCB board through aluminum wires. The PCB board and the electrical test system were connected using PCB clips. Then, a concentration of 1×10 -18 M to 1×10 -9 Samples of NMP22 (synthesized by Sangon Biotech (Shanghai) Co., Ltd.) with gradient concentrations of bladder cancer characteristic protein were added into the injection slot for testing. The sensor began to respond in about 20 to 100 seconds (the current response curve is shown in Figure 2). Figure 4 shown).

[0044] pass Figure 4 It can be found that the Ti prepared in this embodiment 3 C 2 MXene field effect sensors can detect concentrations as low as 1aM (1×10 -18 M) produced a current response to the characteristic protein NMP22 of bladder cancer, showing high sensitivity to the characteristic protein of bladder cancer, and the response signal gradually increased with the increase of concentration; when the concentration reached 1×10 -9 M, it can still have a large response to the characteristic protein of bladder cancer and respond to all concentration gradients, indicating that the sensor has a wide detection range and strong reliability.

[0045] Example 2

[0046] This embodiment provides a Ti 3 C 2 The preparation method of MXene field effect sensor specifically comprises the following steps:

[0047] (S1) adding 10 g of LiF powder into 200 mL of hydrochloric acid solution (concentration: 9 M), and stirring the mixture on a stirrer for 20 minutes to obtain a primary mixed solution;

[0048] 10g Ti3 AlC 2 The powder was added to the primary mixed solution obtained above in 6 portions within 5 minutes, and the mixture was placed in a stirrer and stirred continuously for 45 hours to obtain a secondary mixed solution;

[0049] (S2) adding deionized water to the secondary mixed solution, and centrifuging the mixed solution. After the treatment, the precipitate is mixed with deionized water again and centrifuged until the pH of the solution reaches 6.0, thereby obtaining a mixed solution;

[0050] (S3) Using a standard photolithography process to make a patterned electrode on an insulating substrate (made of polyimide), and then using a vacuum coating process to make a gold film electrode with a thickness of 60 nanometers, 1 mL of the mixed solution obtained in step (S2) is applied between the source and drain electrodes, and vacuum dried in a vacuum oven at 50° C. for 1.5 hours to obtain Ti 3 C 2 MXene conductive channel region;

[0051] (S4) The bladder cancer characteristic protein NMP22 aptamer probe (SEQ ID NO.1: 5'-GCCTATTCCGACTAGAGACCGGCGCACAGAGGCTTCGGAATAGGCTTAAC-3') was modified to Ti 3 C 2 MXene conductive channel area, and then the PDMS injection groove (outer diameter square 6*6mm, inner diameter circular diameter 3mm) was set up on the upper surface of the source and drain electrodes to obtain Ti 3 C 2 MXene field effect sensor;

[0052] The Ti prepared in this example 3 C 2 The MXene field effect sensor was connected to an electrical test system, and then a concentration of 1×10 -18 M to 1×10 -9 Samples of M gradient concentrations of bladder cancer characteristic protein NMP22 (artificially synthesized) were added to the injection slot in sequence for testing.

[0053] The results show that the Ti prepared in this example 3 C 2 MXene field effect sensors can detect concentrations as low as 1aM (1×10 -18 M) The bladder cancer signature protein NMP22 produces a current response.

[0054] Example 3

[0055] This embodiment provides a Ti 3 C 2The preparation method of MXene field effect sensor specifically comprises the following steps:

[0056] (S1) adding 1 g of LiF powder into 20 mL of hydrochloric acid solution (concentration: 9 M), and stirring the mixture on a stirrer for 30 minutes to obtain a primary mixed solution;

[0057] 1g Ti 3 AlC 2 The powder was added to the primary mixed solution obtained above in 6 portions within 5 minutes, and the mixture was placed in a stirrer and stirred continuously for 40 hours to obtain a secondary mixed solution;

[0058] (S2) adding deionized water to the secondary mixed solution, and centrifuging the mixed solution. After the treatment, the precipitate is mixed with deionized water again and centrifuged until the pH of the solution reaches 6.0, thereby obtaining a mixed solution;

[0059] (S3) Using a standard photolithography process to make a patterned electrode on an insulating substrate (made of mica), and then using a vacuum coating process to make a gold film electrode with a thickness of 40 nanometers, 1 mL of the mixed solution obtained in step (S2) is applied between the source and drain electrodes, and vacuum dried in a vacuum oven at 70° C. for 0.5 hours to obtain Ti 3 C 2 MXene conductive channel region;

[0060] (S4) The bladder cancer characteristic protein NMP22 aptamer probe (SEQ ID NO.1: 5'-GCCTATTCCGACTAGAGACCGGCGCACAGAGGCTTCGGAATAGGCTTAAC-3') was modified to Ti 3 C 2 MXene conductive channel area, and then the PDMS injection groove (outer diameter square 6*6mm, inner diameter circular diameter 3mm) was set up on the upper surface of the source and drain electrodes to obtain Ti 3 C 2 MXene field effect sensor;

[0061] The Ti prepared in this example 3 C 2 The MXene field effect sensor was connected to an electrical test system, and then a concentration of 1×10 -18 M to 1×10 -9 Samples of M gradient concentrations of bladder cancer characteristic protein NMP22 (artificially synthesized) were added to the injection slot in sequence for testing.

[0062] The results show that the Ti prepared in this example 3 C 2 MXene field effect sensors can detect concentrations as low as 1aM (1×10-18 M) The bladder cancer signature protein NMP22 produces a current response.

[0063] Example 4

[0064] This embodiment provides a Ti 3 C 2 The preparation method of MXene field effect sensor specifically comprises the following steps:

[0065] (S1) adding 10 g of LiF powder into 200 mL of hydrochloric acid solution (concentration: 9 M), and stirring the mixture on a stirrer for 20 minutes to obtain a primary mixed solution;

[0066] 10g Ti 3 AlC 2 The powder was added to the primary mixed solution obtained above in 6 portions within 5 minutes, and the mixture was placed in a stirrer and stirred continuously for 45 hours to obtain a secondary mixed solution;

[0067] (S2) adding deionized water to the secondary mixed solution, and centrifuging the mixed solution. After the treatment, the precipitate is mixed with deionized water again and centrifuged until the pH of the solution reaches 6.0, thereby obtaining a mixed solution;

[0068] (S3) Using a standard photolithography process to make a patterned electrode on an insulating substrate (made of silicon dioxide), and then using a vacuum coating process to make a gold film electrode with a thickness of 60 nanometers, 1 mL of the mixed solution obtained in step (S2) is applied between the source and drain electrodes, and vacuum dried in a vacuum oven at 40° C. for 2 hours to obtain Ti 3 C 2 MXene conductive channel region;

[0069] (S4) The bladder cancer characteristic protein NMP22 aptamer probe (SEQ ID NO.1: 5'-GCCTATTCCGACTAGAGACCGGCGCACAGAGGCTTCGGAATAGGCTTAAC-3') was modified to Ti 3 C 2 MXene conductive channel area, and then the PDMS injection groove (outer diameter square 6*6mm, inner diameter circular diameter 3mm) was set up on the upper surface of the source and drain electrodes to obtain Ti 3 C 2 MXene field effect sensor;

[0070] The Ti prepared in this example 3 C 2 The MXene field effect sensor was connected to an electrical test system, and then a concentration of 1×10 -18 M to 1×10 -9Samples of M gradient concentrations of bladder cancer characteristic protein NMP22 (artificially synthesized) were added to the injection slot in sequence for testing.

[0071] The results show that the Ti prepared in this example 3 C 2 MXene field effect sensors can detect concentrations as low as 1aM (1×10 -18 M) The bladder cancer signature protein NMP22 produces a current response.

[0072] The above description of the embodiments is to facilitate the understanding and use of the invention by those skilled in the art. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative work. Therefore, the present invention is not limited to the above embodiments, and improvements and modifications made by those skilled in the art based on the explanation of the present invention without departing from the scope of the present invention should be within the scope of protection of the present invention.

Claims

1. A Ti3C2 MXene field effect sensor, characterized in that: It includes an insulating substrate, a sampling slot arranged on the upper surface of the insulating substrate, source and drain electrodes arranged on the upper surface of the insulating substrate, symmetrically arranged and extending into the sampling slot for connecting to an external electrical test system, a Ti3C2 MXene conductive channel region arranged between the source and drain electrodes, and a bladder cancer characteristic protein aptamer probe modified on the Ti3C2 MXene conductive channel region; The bladder cancer characteristic protein aptamer probe is used to bind to the bladder cancer characteristic protein to change the charge distribution of Ti3C2MXene and thus change the current response of the sensor.

2. A Ti3C2 MXene field effect sensor according to claim 1, characterized in that: The insulating substrate is selected from one of silicon dioxide, glass, mica, a silicon wafer covered with an insulating layer, polyethylene terephthalate, polyimide or polydimethylsiloxane.

3. A Ti3C2 MXene field effect sensor according to claim 1, characterized in that: The source and drain electrodes are gold film electrodes; the thickness of the gold film electrodes is 20-60 nm.

4. A Ti3C2 MXene field effect sensor according to claim 1, characterized in that: The material of the injection slot is selected from one of polydimethylsiloxane, Flexdym, and thermoplastic polyurethane elastomer.

5. A Ti3C2 MXene field effect sensor according to claim 1, characterized in that: The bladder cancer characteristic protein aptamer probe is an aptamer probe of protein NMP22.

6. A method for preparing a Ti3C2 MXene field effect sensor, characterized in that: The Ti3C2 MXene field effect sensor is the Ti3C2 MXene field effect sensor according to any one of claims 1 to 5, and its preparation comprises the following steps: (S1) mixing Ti3AlC2 powder and fluorine-containing solution, and post-treating to obtain a mixed solution; (S2) using a standard photolithography process to make an electrode pattern on an insulating substrate, and then preparing a gold film electrode as a source and drain electrode by vacuum coating, applying the mixed solution prepared in step (S1) between the source and drain electrodes, and performing a vacuum drying process to obtain a Ti3C2 MXene conductive channel region; (S3) The bladder cancer characteristic protein aptamer probe is modified into the Ti3C2 MXene conductive channel region, and then the injection slot is set on the upper surface of the source and drain electrodes to prepare the Ti3C2 MXene field effect sensor.

7. The method for preparing a Ti3C2 MXene field effect sensor according to claim 6, characterized in that: In step (S1), the mass ratio of Ti3AlC2 powder to fluorine-containing solution is 1:15-25; The fluorine-containing solution is selected from a hydrofluoric acid solution or a hydrochloric acid solution of LiF.

8. The method for preparing a Ti3C2 MXene field effect sensor according to claim 6, characterized in that: In step (S1), the post-treatment is re-suspending with deionized water after centrifugation; The pH of the mixed solution is 6-7.

9. The method for preparing a Ti3C2 MXene field effect sensor according to claim 6, characterized in that: In step (S2), during the vacuum drying process, the temperature is 40 to 70° C. and the time is 0.5 to 2 h.

10. Use of the Ti3C2 MXene field effect sensor according to any one of claims 1 to 5 in preparing a kit for detecting and / or preventing bladder cancer.

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