A tellurium oxide thin film transistor biosensor and a preparation method and application thereof

Abstract

The application relates to the field of biotechnology, and in particular to a tellurium oxide thin film transistor biosensor and a preparation method and application thereof. The tellurium oxide thin film transistor biosensor comprises a silicon substrate, a silicon dioxide layer, a source electrode, a drain electrode, a semiconductor channel layer and a biological functional modification layer; the silicon dioxide layer is formed on the surface of the silicon substrate; the source electrode and the drain electrode are arranged on the surface of the silicon dioxide layer at a distance from each other; the semiconductor channel layer is arranged on the surface of the silicon dioxide layer and covers at least a channel region between the source electrode and the drain electrode, and the material of the semiconductor channel layer comprises a tellurium oxide-based material; and the biological functional modification layer is arranged on the surface of the semiconductor channel layer. The tellurium oxide thin film transistor biosensor can realize rapid and real-time detection, has high detection sensitivity, and can meet the requirement of early-stage ultra-low-concentration biomarker detection of myocardial injury.

Description

Technical Field

[0001] This invention relates to the field of biotechnology, and more specifically, to a tellurium oxide thin-film transistor biosensor, its fabrication method, and its application. Background Technology

[0002] Cardiovascular disease (CVD) is a major public health problem threatening human health, with acute myocardial infarction (AMI) being one of the leading causes of cardiovascular death. Patients with AMI often lack typical clinical symptoms and electrocardiographic changes in the early stages of the disease; approximately 25% of patients even have no obvious symptoms such as chest pain, easily leading to missed or misdiagnosis. Cardiac troponin (cTn) is a contractile regulatory protein complex found in cardiomyocytes, comprising three subunits: cardiac troponin C (cTnC), cardiac troponin I (cTnI), and cardiac troponin T (cTnT). cTnI is expressed only in myocardial tissue and has extremely high cardiac specificity. When cardiomyocytes are damaged or necrotic, cTnI can be released from the cardiomyocytes into the bloodstream within approximately 15 minutes and rapidly increases within 3–6 hours; its concentration changes directly reflect the degree of myocardial damage and disease progression.

[0003] In healthy individuals, the concentration of cTnI in the blood is typically below 5 pg / mL, while a concentration exceeding 26 pg / mL can indicate myocardial damage. Elevated serum cTnI levels are closely associated with the risk of future cardiovascular events. cTnI can be used not only for the early diagnosis of acute myocardial infarction but also as an important biomarker for predicting cardiovascular disease risk and assessing prognosis.

[0004] Currently, the main clinical techniques for detecting cardiac troponin I (cTnI) are immunological assays, including enzyme-linked immunosorbent assay (ELISA), chemiluminescent immunoassay, electrochemiluminescent immunoassay, and fluorescence immunoassay. High-sensitivity cTnI detection technology (hs-cTnI) has achieved detection limits down to pg / mL and even fg / mL. To meet the needs of point-of-care testing (POCT), researchers have further developed various novel cTnI biosensors, including electrochemical biosensors, surface plasmon resonance (SPR) sensors, and surface-enhanced Raman scattering (SERS) sensors.

[0005] Despite the high accuracy of existing immunoassay techniques, several limitations remain: Chemiluminescence and electrochemiluminescence analyses typically rely on large, automated instruments, requiring specialized laboratories and personnel. Traditional immunoassays are time-consuming, require large sample volumes and numerous reagents, increasing costs and hindering the detection of minute samples. Traditional methods are mostly endpoint-based, unable to monitor real-time changes in cTnI concentration, thus hindering continuous assessment of patient conditions and prognostic monitoring. Furthermore, miniaturization and integration of existing testing equipment are difficult to achieve.

[0006] Therefore, developing a novel cTnI detection technology with high sensitivity, rapid response, low sample consumption, easy miniaturization and portability is of great significance for the early diagnosis and immediate detection of cardiovascular diseases.

[0007] In view of this, the present invention is hereby proposed. Summary of the Invention

[0008] The purpose of this invention is to provide a tellurium oxide thin-film transistor biosensor, its preparation method, and its application. The tellurium oxide thin-film transistor biosensor can achieve rapid, real-time detection, has high detection sensitivity, and can meet the needs of detecting ultra-low concentration biomarkers in the early stage of myocardial injury.

[0009] In order to achieve the above-mentioned objectives of the present invention, the following technical solution is adopted: A tellurium oxide thin-film transistor biosensor includes: a silicon substrate, a silicon dioxide layer, a source electrode, a drain electrode, a semiconductor channel layer, and a biofunctionalized modification layer; The silicon dioxide layer is formed on the surface of the silicon substrate; the source and the drain are disposed on the surface of the silicon dioxide layer at intervals; the semiconductor channel layer is disposed on the surface of the silicon dioxide layer, at least covering the channel region between the source and the drain, and the material of the semiconductor channel layer includes: tellurium oxide-based material; the biofunctionalized modification layer is disposed on the surface of the semiconductor channel layer.

[0010] A method for fabricating the tellurium oxide thin-film transistor biosensor includes the following steps: (a) Forming a silicon dioxide layer on the surface of a silicon substrate; (b) Preparing a source and a drain on the surface of the silicon dioxide layer; (c) Preparing a semiconductor channel layer on the surface of the silicon dioxide layer; (d) Preparing a biofunctionalized modification layer on the semiconductor channel layer.

[0011] A method for detecting cardiac troponin I, using the aforementioned tellurium oxide thin-film transistor biosensor to detect the sample to be tested.

[0012] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) This invention uses non-stoichiometric tellurium oxide thin film as the channel material for field-effect transistors, utilizing its semiconductor properties and high sensitivity to changes in surface charge. Compared with traditional detection methods that rely on fluorescence, enzyme labeling, or chemiluminescence signal amplification, this invention can directly convert biomarker events into electrical signals without additional labeling, achieving rapid and real-time detection. Experimental results show that this invention can produce a stable and recognizable electrical response to cTnI at a concentration of 100 fg / mL, indicating that this technical solution has high detection sensitivity and can meet the needs of detecting ultra-low concentration biomarkers in the early stage of myocardial injury.

[0013] (2) This invention expands the application scope of tellurium oxide semiconductor materials in the field of biosensing, provides a new technical route for the design and development of novel field-effect transistor biosensors based on tellurium oxide thin films, and provides a reference technical platform for the detection of other protein biomarkers. Attached Figure Description

[0014] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0015] Figure 1 This is a flowchart of the sensor fabrication process; Figure 2 The images show a comparison of Raman spectra before and after tellurium oxide growth. The left image shows the result before tellurium oxide growth, and the right image shows the result after tellurium oxide growth. Figure 3 The images show XPS characterizations of tellurium oxide growth; the left image represents Te 3d, and the right image represents O 1s. Figure 4 Electrode pattern design and actual product photos; Figure 5 Output / transfer characteristic curve; Figure 6 The graphs show the transfer characteristics of cTnI at different concentrations (left) and the bar charts showing the signal response (right). Figure 7 The left figure shows the fitting results of the cTnI response linearity parameter test (left figure) and the response histogram of the four pairs of electrodes (right figure). Figure 8 This is a specific detection result. Detailed Implementation

[0016] The technical solution of the present invention will be clearly and completely described below with reference to the accompanying drawings and specific embodiments. However, those skilled in the art will understand that the embodiments described below are some embodiments of the present invention, but not all embodiments, and are only used to illustrate the present invention, and should not be regarded as limiting the scope of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall be followed. Where the manufacturers of reagents or instruments are not specified, they are all conventional products that can be purchased commercially.

[0017] One aspect of the present invention relates to a tellurium oxide thin-film transistor biosensor, comprising: a silicon substrate, a silicon dioxide layer, a source electrode, a drain electrode, a semiconductor channel layer, and a biofunctionalized modification layer; The silicon dioxide layer is formed on the surface of the silicon substrate; The source and the drain are disposed at intervals on the surface of the silicon dioxide layer; The semiconductor channel layer is disposed on the surface of the silicon dioxide layer and at least covers the channel region between the source and the drain. The material of the semiconductor channel layer includes tellurium oxide-based materials. The biofunctionalized modification layer is disposed on the surface of the semiconductor channel layer.

[0018] Currently, clinical detection of cTnI mainly relies on enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay (CIA), and electrochemiluminescence immunoassay (ECIA). These methods generally suffer from drawbacks such as large equipment size, complex procedures, long detection times, cumbersome sample pretreatment, and high costs, making them unsuitable for early screening of acute myocardial infarction, point-of-care testing, and portable detection. In ultra-low concentration protein detection, non-specific adsorption of biomolecules at the sensing interface can easily lead to increased background signals and deviations in detection results, thus reducing accuracy and stability. Furthermore, complex biological samples contain numerous non-target proteins, such as high-abundance albumin, whose interference can affect the sensor's ability to recognize target molecules and its detection specificity. Therefore, improving sensor specificity, reducing non-specific adsorption, and achieving highly sensitive detection of ultra-low concentrations of cTnI are key technical problems that urgently need to be solved in the field of biosensing.

[0019] The tellurium oxide thin-film transistor biosensor of the present invention utilizes the excellent electrical properties and surface sensitivity of the semiconductor channel layer composed of tellurium oxide-based materials, combined with the antibody-specific recognition mechanism and the effective shielding of non-specific binding sites by the blocking agent, to achieve rapid, label-free and highly sensitive detection of cardiac troponin I.

[0020] The present invention verifies the excellent selectivity and anti-interference capability of the device through specific verification on non-target proteins such as albumin, and achieves effective response to cTnI at a concentration as low as 100fg / mL, providing a novel detection technical solution for early diagnosis and point-of-care testing of acute myocardial infarction.

[0021] Further, the tellurium oxide-based material includes: non-stoichiometric TeO x thin film, where 1<x<2, and the TeO x Te in the thin film simultaneously exists in Te 0 and Te 4+ two chemical states, forming a non-stoichiometric oxidation network in which a Te-O structure and a Te-enriched structure coexist. A non-stoichiometric TeO x (x<2) tellurium oxide-based material containing both coexisting Te-Te bonds and Te-O bonds is used as the channel layer, and an acceptor level is introduced through oxygen vacancy defects, endowing the thin film with p-type conductivity characteristics and good gate voltage modulation capability. This material property ensures that the interface electric field change caused by the biological binding event can effectively deplete or accumulate channel carriers, realizing a highly sensitive electrical response.

[0022] Further, the semiconductor channel layer has a thickness of 18 to 24nm, including but not limited to any one point value or the range value between any two of 18nm, 19nm, 20nm, 21nm, 22nm, 23nm or 24nm. This thickness not only ensures the continuity and uniformity of the thin film and guarantees the integrity of the carrier transport channel, but also makes the entire channel thickness fall within the Debye screening length range. This design enables the charge effect generated by the surface biorecognition event to fully penetrate and modulate the carrier concentration of the entire channel, overcomes the defect that the bottom of the channel in a thick-film device is weakly modulated by surface charges, and serves as a key structural guarantee for realizing a stable response to an ultra-low concentration target of 100fg / mL.

[0023] Further, the source electrode includes: a chromium adhesion layer located on the silicon dioxide layer and a gold conductive layer located on the surface of the chromium adhesion layer.

[0024] Further, the drain electrode includes: the chromium adhesion layer located on the silicon dioxide layer and a gold conductive layer located on the surface of the chromium adhesion layer.

[0025] Further, the chromium adhesion layer has a thickness of 13 to 18nm, including but not limited to any one point value or the range value between any two of 13nm, 14nm, 15nm, 16nm, 17nm or 18nm. The Cr adhesion layer enhances the adhesion between Au and the Si wafer.

[0026] Furthermore, the thickness of the gold conductive layer is 47~53 nm, including but not limited to any one of 47 nm, 49 nm, 51 nm, or 53 nm, or a range between any two. This thickness ensures that the source and drain electrodes have low sheet resistance and excellent signal transmission capability, while the high chemical inertness of gold makes it resistant to corrosion or oxidation in PBS buffer and antibody / antigen solutions, maintaining a stable electrical contact interface.

[0027] Furthermore, the biofunctionalized modification layer includes a specific antibody and a blocking agent. The specific antibody and blocking agent are of conventional types in the art and are not specifically limited thereto.

[0028] Furthermore, the specific antibody is immobilized on the surface of the semiconductor channel layer for specifically capturing target biomarkers; the blocking agent covers the sites on the surface of the semiconductor channel layer where the specific antibody has not bound, for blocking non-specific binding sites.

[0029] Another aspect of the present invention relates to a method for fabricating the aforementioned tellurium oxide thin-film transistor biosensor, comprising the following steps: (a) Forming a silicon dioxide layer on the surface of a silicon substrate; (b) Fabricating source and drain electrodes on the surface of the silicon dioxide layer; (c) A semiconductor channel layer is prepared on the surface of the silicon dioxide layer; (d) A biofunctionalized modification layer is prepared on the semiconductor channel layer.

[0030] The method for fabricating the tellurium oxide thin-film transistor biosensor is simple and does not rely on complex processes and equipment. The fabricated sensor has high sensitivity and can achieve rapid, real-time detection, meeting the needs for detection of ultra-low concentration biomarkers in the early stage of myocardial injury.

[0031] Furthermore, the material of the semiconductor channel layer is magnetron sputtered onto the surface of the silicon dioxide layer, covering at least the channel region between the source and the drain, and then annealed.

[0032] Furthermore, the parameters of the magnetron sputtering include: a Te target DC sputtering power of 6~10W (for example, it can be any one of 6W, 7W, 8W, 9W or 10W or any range between any two); and a TeO2 target RF sputtering power of 20~30W (for example, it can be any one of 20W, 22W, 24W, 26W, 28W or 30W or any range between any two). Slightly increasing the Te target sputtering power slightly reduces the on-state current of the device. Considering the overall electrical performance of the device, 8W is currently the optimal Te target sputtering power. Sputtering power; sputtering pressure of 0.3~0.7 Pa (e.g., any one of 0.3 Pa, 0.4 Pa, 0.5 Pa, 0.6 Pa, or 0.7 Pa, or a range between any two); sputtering time of 18~22 s (e.g., any one of 18 s, 19 s, 20 s, 21 s, or 22 s, or a range between any two). Longer sputtering times result in increased film thickness and higher on-state current, but a lower on / off ratio; target spacing of 50~60 mm (e.g., any one of 50 mm, 52 mm, 54 mm, 56 mm, 58 mm, or 60 mm, or a range between any two); sputtering atmosphere including argon. These parameter ranges allow for precise control of the deposition rate and particle energy, resulting in TeO with a moderate and uniform oxygen vacancy concentration. x film.

[0033] Furthermore, air annealing promotes the sputtering process of metallic Te to TeO. x Further oxidation forms a non-stoichiometric oxidation network dominated by the Te–O structure. The annealing atmosphere includes air; annealing under vacuum or N2 atmosphere significantly reduces the conductivity of the device. The annealing temperature is 148~152℃ (e.g., any value or range between 148℃, 149℃, 150℃, 151℃, or 152℃). Annealing at 100℃ slightly reduces the conductivity of the device, and both on-state and off-state currents decrease, with a greater decrease in the off-state current. Annealing in air at 150℃ slightly improves the device mobility. Annealing in air at 200℃ decreases the device mobility. Overall, the optimal temperature is 150℃; the annealing time is 28~32min (e.g., any value or range between 28min, 29min, 30min, 31min, or 32min). Longer annealing times result in more significant leakage current in the device. The above-mentioned annealing process can effectively repair lattice damage and dangling bonds generated during magnetron sputtering, promote atomic rearrangement between Te-Te and Te-O bonds, further improve carrier mobility and device stability, and will not eliminate oxygen vacancy defects due to excessive oxidation of the thin film.

[0034] Furthermore, the method for preparing the biofunctionalized modified layer includes: The semiconductor channel layer was incubated, cleaned, and blocked in a specific antibody solution.

[0035] Furthermore, the incubation temperature is 2~6℃ (for example, it can be any one of 2℃, 3℃, 4℃, 5℃ or 6℃ or a range between any two), and the time is 8~12h (for example, it can be any one of 8h, 9h, 10h, 11h or 12h or a range between any two).

[0036] Furthermore, the sealing temperature is 2~6℃ (for example, it can be any point value of 2℃, 3℃, 4℃, 5℃ or 6℃ or a range between any two), and the time is 1~3h (for example, it can be any point value of 1h, 1.5h, 2h, 2.5h or 3h or a range between any two).

[0037] Another aspect of the present invention relates to a method for detecting cardiac troponin I, using the aforementioned tellurium oxide thin-film transistor biosensor to detect the sample to be tested.

[0038] Furthermore, after immersing the cardiac troponin I test solution in the semiconductor channel layer, a specific biological reaction is carried out, and cardiac troponin I specifically binds to the specific antibody on the biofunctionalized modified layer.

[0039] Furthermore, the temperature of the specific biological reaction is 15~30℃ (for example, it can be any one of 15℃, 20℃, 25℃ or 30℃ or a range between any two), and the time is 15~25min (for example, it can be any one of 15min, 17min, 19min, 21min, 23min or 25min or a range between any two).

[0040] The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of the invention. Unless otherwise specified in the examples, conventional conditions or conditions recommended by the manufacturer are followed. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0041] Example 1 (1) Fabrication process of tellurium oxide thin film transistor biosensor The method for fabricating the tellurium oxide thin-film transistor biosensor provided in this embodiment is completed using standard semiconductor processes, such as... Figure 1 As shown, it includes the following steps: AZ5214 photoresist was spin-coated onto a highly doped (p++) Si / SiO2 substrate (total thickness 525 μm), with the highly doped substrate serving as the bottom gate. Electrode patterns were fabricated using photolithography. Patterned source and drain electrodes were obtained by electron beam evaporation of 15 nm thick Cr and thermal evaporation of 50 nm thick Au followed by metal stripping.

[0042] After the electrodes were fabricated, a tellurium oxide thin film (semiconductor channel layer) with a thickness of 21 nm was grown on the chip using magnetron sputtering and thermal annealing. Longer sputtering times resulted in greater film thickness and increased on-state current, but a decreased on / off ratio. A device with a sputtering time of 60 s achieved a mobility of 4 cm⁻¹. 2 V -1 s -1 The on / off ratio remains >10 3 The optimal sputtering parameters were determined by further testing the effects of sputtering time, sputtering power, annealing time, and annealing temperature on the film itself. Channel layer sputtering parameters: Te (DC) sputtering 8W, TeO2 (RF) sputtering 25W, sputtering pressure 0.5Pa, sputtering time 20s, target spacing 55mm, sputtering atmosphere Ar:O2 = 20:0sccm. Annealing atmosphere was air, annealing temperature 150℃, annealing time 30min. A comparison of Raman spectra before and after tellurium oxide growth is provided. Figure 2 As shown.

[0043] like Figure 2 As shown, in a blank Si / SiO2 substrate, only at approximately 520 cm⁻¹ - A distinct characteristic peak was observed at position ¹, corresponding to the intrinsic vibrational mode of the SiO2 substrate. No other impurity peaks were detected, indicating a clean background in the test system. After depositing the Te-based thin film, its Raman spectrum remained in the low wavenumber region (100–160 cm⁻¹). - ¹) A significantly enhanced characteristic peak appears, especially at 128 cm⁻¹. - ¹and 143 cm - Two distinct vibration peaks were observed at point ¹.

[0044] Based on the spectral peak distribution characteristics, it can be seen that the Te element in this thin film material is mainly in a low-valence state dominated by Te–Te bonds or a Te-rich non-stoichiometric oxidation state (Te… 0 / TeO x Te exists in the form of ) rather than being completely oxidized. 4+ State (TeO2). Additionally, approximately 520 cm -The SiO2 substrate signal can still be observed at ¹, indicating that the Te-based film is thin (nanometer-scale) and contributes to laser penetration.

[0045] Raman spectroscopy results indicate that the Te element in the prepared Te-based thin film was not completely transformed into the TeO2 structure, but rather consisted mainly of low-valence Te-Te bonds or TeO enriched with oxygen vacancies. x It exists in amorphous / nanostructure form.

[0046] Further characterization was performed using XPS, and the Te 3d X-ray photoelectron spectroscopy results are as follows: Figure 3 As shown, the spectrum can be decomposed into four main peak components, corresponding to the spin-orbit splitting signals of the two tellurium-related chemical states. Among them, the bimodal components located at approximately 572.5–573.5 eV and 582.8–583.8 eV correspond to the 3d5 / 2 and 3d3 / 2 signals of low-binding-energy tellurium species and can be attributed to Te. 0 The relevant chemical environment; the bimodal components located at approximately 575.5–577.0 eV and 586.0–587.5 eV correspond to the 3d5 / 2 and 3d3 / 2 signals of high-binding-energy tellurium species, and can be attributed to Te in the Te–O-related chemical environment. 4+ Or TeO x Composition. The simultaneous presence of four peak components indicates that tellurium in the sample exists in multiple chemical coordination environments, and its electronic structure is characterized by the combined contribution of Te-Te and Te-O bond-related chemical states. The O 1s high-resolution spectrum, after peak fitting, can be divided into two components. The main peak near 530.5 eV corresponds to Te–O lattice oxygen, indicating the formation of a stable TeO2 structure in the sample; the secondary peak at approximately 532.3 eV belongs to surface-adsorbed oxygen and oxygen-containing species such as hydroxyl groups, mainly originating from adsorbed moisture, hydroxyl groups, and the surface oxide layer formed by air exposure on the sample surface. The lattice oxygen peak area is significantly larger than the high binding energy peak, indicating that oxygen in the sample mainly exists in the form of Te–O bonds.

[0047] After completing all the above steps, the four-inch silicon wafer is cut into smaller pieces according to the smallest electrode assembly unit to obtain the physical biosensor device. A photograph of the actual device is shown below. Figure 4 As shown in the figure. The upper row of square electrode regions is the source and drain external probe region, and the area below the external probe region is used for modification with biological antibodies and specific biological reactions.

[0048] The transfer and output characteristics of the tellurium oxide thin-film transistor were measured, such as... Figure 5As shown in the figure, the output characteristic curve and the transfer characteristic curve show that the device belongs to the p-type transistor. The drain-source current increases with the increase of the negative gate voltage, which shows that the response of the tellurium oxide TFT device is sensitive to the gate voltage and can achieve good gate control, proving that the device can work normally.

[0049] (2) Construction of cTnI reaction system and verification of sensing performance Preparation of bottom gate structure tellurium oxide (TeO) x After thin-film transistor devices are developed, initial electrical performance tests are performed to screen devices with good transistor characteristics for subsequent biofunctionalization modifications. After testing, each device is placed in an independent container for later use to avoid cross-contamination.

[0050] A 100 μg / mL solution of cardiac troponin I (cTnI) monoclonal antibody was prepared using phosphate-buffered saline (PBS). Tellurium oxide (TeO2) was then added... x Thin-film transistor devices were placed in separate test tubes, and an appropriate amount of cTnI monoclonal antibody solution was added to completely immerse the channel region of the device in the antibody solution (excluding the external probe region). The devices were incubated overnight at 4°C to allow the antibody to be fully adsorbed and fixed on the surface of the tellurium oxide film.

[0051] After antibody incubation, the device was removed and washed twice with PBS buffer for about 30 seconds each time to remove free antibodies that were not bound to the surface of the tellurium oxide film.

[0052] The device was placed in 0.05% Tween-20 blocking solution, ensuring full contact between the channel region and the blocking solution. It was incubated at 4°C for 2 hours to block unbound sites on the device surface, reducing non-specific protein adsorption during subsequent detection. After blocking, the device was washed twice with PBS buffer for approximately 30 seconds each time to remove unbound Tween-20.

[0053] Different concentration gradients of cardiac troponin I (cTnI) antigen solutions were prepared using PBS buffer, ranging from 1 fg / mL to 1 ng / mL. Each device was placed in its respective antigen solution, ensuring the channel region was fully submerged (excluding the external probe region). Incubation was performed at room temperature for approximately 20 minutes to allow for specific binding of the antigen to the antibody immobilized on the tellurium oxide film surface. After incubation, the devices were removed and washed twice with PBS buffer for approximately 30 seconds each time to remove unbound antigen molecules. The test results are as follows: Figure 6 As shown, the device exhibits good response performance.

[0054] Example 2: High Specificity Detection To verify the specific recognition ability of the constructed tellurium oxide thin-film transistor biosensor for cardiac troponin I (cTnI), human serum albumin (ALB) was selected as a non-target protein for control experiments. The albumin detection process was consistent with the cTnI detection process. To more accurately evaluate the device response, the gate voltage position with a large drain-source current and a significant difference in response between different concentrations was selected as a characteristic test point based on the transfer characteristic curve. The corresponding drain-source current values ​​were extracted, and the change in current response at different concentrations was calculated to evaluate the device's response characteristics to target and non-target proteins.

[0055] Experimental results show that, under the same concentration conditions, cTnI can significantly reduce the drain-source current of the device, and the current changes of different electrode pairs show a good concentration-dependent relationship with increasing cTnI concentration. Figure 7 As shown in the figure. When albumin was tested, only a slight increase in leakage current was observed, and the current change was much smaller than that of cTnI. No obvious regular changes were observed between different concentrations.

[0056] These results indicate that there is no specific immune binding between albumin and the cTnI antibody immobilized on the tellurium oxide film surface. The weak current change caused by albumin mainly originates from factors such as a small amount of non-specific adsorption of albumin on the device surface, changes in the interfacial ionic environment, and alterations in the liquid dielectric environment. These factors cause slight perturbations to the channel carrier transport, thus manifesting as only small-amplitude current changes. In contrast, cTnI can specifically bind to the surface-immobilized antibody, forming a stable biorecognition layer on the device surface. This causes significant changes in local charge distribution and interfacial electric field, thereby modulating the channel carrier concentration and leading to significant changes in the drain-source current.

[0057] Depend on Figure 8 It can be seen that the current response signal caused by the non-specific adsorption of albumin is much smaller than that caused by the specific binding of the target molecule cTnI and cTnI monoclonal antibody. Therefore, the detection results for albumin indicate that the tellurium oxide thin-film transistor biosensor has good target recognition ability, high detection specificity, and good anti-interference performance.

[0058] This invention uses tellurium oxide (TeO) xThis invention utilizes a tellurium oxide thin film as the channel material for a field-effect transistor (FET) to construct a bottom-gate biosensor, enabling the electrical detection of cardiac troponin I (cTnI). Compared to existing FET biosensors using silicon, graphene, MoS2, and other materials, this invention leverages the excellent semiconductor properties and surface sensitivity of tellurium oxide thin films to effectively convert biorecognition events into electrical signals, achieving the detection of ultra-low concentrations of cTnI. Experimental results show that this invention can produce a stable electrical response to cTnI at a concentration of 100 fg / mL, exhibiting high detection sensitivity, and providing a new technical solution for early screening of acute myocardial infarction.

[0059] Although the present invention has been illustrated and described with specific embodiments, it should be understood that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; those skilled in the art should understand that modifications can be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein, without departing from the spirit and scope of the present invention; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A tellurium oxide thin-film transistor biosensor, characterized in that, include: Silicon substrate, silicon dioxide layer, source electrode, drain electrode, semiconductor channel layer, and biofunctionalized modification layer; The silicon dioxide layer is formed on the surface of the silicon substrate; The source and the drain are disposed at intervals on the surface of the silicon dioxide layer; The semiconductor channel layer is disposed on the surface of the silicon dioxide layer and at least covers the channel region between the source and the drain. The material of the semiconductor channel layer includes tellurium oxide-based materials. The biofunctionalized modification layer is disposed on the surface of the semiconductor channel layer.

2. The tellurium oxide thin-film transistor biosensor according to claim 1, characterized in that, The tellurium oxide-based material comprises: non-stoichiometric TeO x thin film, where 1<x<2, and in the TeO x thin film, Te exists simultaneously in Te 0 and Te 4+ two chemical states, forming a non-stoichiometric oxide network in which a Te-O structure and a Te-enriched structure coexist; And / or, the thickness of the semiconductor channel layer is 18~24nm.

3. The tellurium oxide thin-film transistor biosensor according to claim 1, characterized in that, The source electrode includes: a chromium adhesion layer located on the silicon dioxide layer and a gold conductive layer located on the surface of the chromium adhesion layer; And / or, the drain electrode includes: a chromium adhesion layer located on the silicon dioxide layer and a gold conductive layer located on the surface of the chromium adhesion layer.

4. The tellurium oxide thin-film transistor biosensor according to claim 3, characterized in that, The thickness of the chromium adhesion layer is 13~18 nm; And / or, the thickness of the gold conductive layer is 47~53nm.

5. The tellurium oxide thin-film transistor biosensor according to claim 1, characterized in that, The biofunctionalized modification layer includes: a specific antibody and a blocking agent; And / or, the specific antibody is immobilized on the surface of the semiconductor channel layer for specifically capturing target biomarkers; the blocking agent covers the sites on the surface of the semiconductor channel layer where the specific antibody is not bound, for blocking non-specific binding sites.

6. The method for fabricating the tellurium oxide thin-film transistor biosensor according to any one of claims 1 to 5, characterized in that, Includes the following steps: (a) Forming a silicon dioxide layer on the surface of a silicon substrate; (b) Fabricating source and drain electrodes on the surface of the silicon dioxide layer; (c) A semiconductor channel layer is prepared on the surface of the silicon dioxide layer; (d) A biofunctionalized modification layer is prepared on the semiconductor channel layer.

7. The method for fabricating the tellurium oxide thin-film transistor biosensor according to claim 6, characterized in that, The material of the semiconductor channel layer is magnetron sputtered onto the surface of the silicon dioxide layer, covering at least the channel region between the source and the drain, and then annealed.

8. The method for fabricating a tellurium oxide thin-film transistor biosensor according to claim 7, characterized in that, The parameters of the magnetron sputtering include: DC sputtering power of 6~10W for Te target; RF sputtering power of 20~30W for TeO2 target; sputtering pressure of 0.3~0.7Pa; sputtering time of 18~22s; target spacing of 50~60mm; and sputtering atmosphere of argon.

9. The method for fabricating a tellurium oxide thin-film transistor biosensor according to claim 7, characterized in that, Includes at least one of the following technical features: (1) The atmosphere for the annealing treatment includes: air; (2) The annealing temperature is 148~152℃; (3) The annealing time is 28~32 min.

10. A method for detecting cardiac troponin I, characterized in that, The tellurium oxide thin-film transistor biosensor according to any one of claims 1 to 5 is used to detect the sample to be tested.

Images