Memristor for brain tumor typing detection and preparation method thereof
By using a tungsten trioxide (WO3)-based memristor, using its interaction with tumor biomarkers, the time-consuming and cost-effective classification in brain tumor detection is solved, and high-sensitivity tumor cell typing and real-time analysis is achieved.
Patent Information
- Application Number
- CN202510583395.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-07
- Publication Date
- 2025-08-01
AI Technical Summary
The prior art has the problem of time-consuming and high cost in brain tumor detection, and it is difficult to achieve early rapid and accurate tumor typing.
The memristor based on tungsten trioxide (WO3) is used as the functional layer, and it interacts with tumor biomarkers through biological functionalization. The specific binding of antibodies to antigens is used to cause changes in the resistance of the memristor, and the electrochemical or bioelectric signal characteristics of tumor cells are recorded and analyzed to distinguish different types of tumor cells.
It has achieved high sensitivity tumor cell typing, has the potential for real-time analysis and monitoring, is suitable for high-throughput detection, and can be combined with artificial neural network to improve classification efficiency and accuracy.
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Figure CN120405116A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of in vitro diagnostic devices, and particularly relates to a memristor for brain tumor typing detection and a preparation method thereof. Background Art
[0002] Cancer is a major global challenge in terms of social, public health, and economic impact. Among them, brain tumors are one of the most lethal cancers, the most common type of solid tumor in children and adolescents, and the main cause of cancer-related deaths in men under 40 years old and women under 20 years old. In addition, compared with other cancers, the mortality rate of brain tumors is much higher, and only one-third of patients survive at least five years after diagnosis. Therefore, early and accurate tumor classification plays a crucial role in timely adopting appropriate treatment strategies, thereby greatly improving the survival rate of patients.
[0003] The existing methods for tumor detection and classification are through imaging modalities such as CT and MRI, which can provide preliminary information on tumor characteristics. However, the clear classification of tumors still depends on pathological examinations and immunostaining, and both of these methods are usually time-consuming. Existing technologies also use gene typing or blood tumor markers. Although gene typing can accurately classify, it is costly and time-consuming; while most blood tumor markers can only indicate cancer and do not support typing. Therefore, how to improve the rapid classification of early tumors and thus improve the diagnostic efficiency is an urgent problem to be solved at present, which can promote timely treatment and ultimately improve patient care. Summary of the Invention
[0004] To solve the above problems, the present invention provides a memristor for brain tumor typing detection and a preparation method thereof. The present invention is based on tungsten trioxide (WO3) with memristive effect as the functional layer. Since WO3 can interact with biomolecules (such as antibodies) after contacting with tumor biomarkers, through biofunctionalization, the specific binding between antibodies and antigens can cause changes in the resistance of the memristor, which is further reflected in its memristive behavior, used to record and analyze the electrochemical or bioelectrical signal characteristics of tumor cells. According to the electrical signal differences between tumor cells and normal cells, different types of tumor cells can be effectively distinguished, with obvious effects and good repeatability.
[0005] The present invention solves the above technical problems through the following technical solutions.
[0006] The first object of the present invention is to provide a memristor for brain tumor typing detection, which includes a bottom electrode layer, a metal oxide layer, and an upper electrode layer sequentially formed from bottom to top. The bottom electrode layer is a conductive electrode layer, the metal oxide layer is tungsten trioxide, and the upper electrode layer is a metal single-element electrode layer. The metal single element provides migrating metal ions under the action of an electric field.
[0007] Further, the thickness of the metal oxide layer is 200 nm to 250 nm.
[0008] Further, the bottom electrode layer is a Ti electrode layer with a thickness of 150 nm to 200 nm.
[0009] Further, the top electrode layer is an Ag electrode layer with a thickness of 150 nm to 200 nm.
[0010] The second object of the present invention is to provide a preparation method of the memristor for brain tumor typing detection as described above, including the following steps: S1. By means of magnetron sputtering, deposit a bottom electrode layer on a glass substrate.
[0011] S2. By means of magnetron sputtering, sequentially deposit a metal oxide layer on the bottom electrode layer.
[0012] S3. Cover a metal mask plate with openings on the metal oxide layer, and by means of DC sputtering, deposit a top electrode layer on the metal mask plate, and then remove the metal mask plate to obtain a memristor for brain tumor typing detection.
[0013] Further, during the magnetron sputtering process, the target-substrate distance is 9 cm to 11 cm, the vacuum degree is 3×10 -4 Pa to 4×10 -4 Pa, the working gas is argon, the sputtering gas pressure is 0.7 Pa to 0.8 Pa, the sputtering power is 60 W / cm 2 , and the sputtering time is 40 min to 90 min.
[0014] Further, during the DC sputtering process, the target-substrate distance is 9 cm to 11 cm, the vacuum degree is 2×10 -4 Pa to 3×10 -4 Pa, the working gas is argon, the sputtering gas pressure is 0.7 Pa to 0.8 Pa, the sputtering power is 60 W / cm 2 , and the sputtering time is 25 min to 35 min.
[0015] Further, the metal mask plate is provided with an array of openings, and the top electrode layer is deposited inside all the openings.
[0016] The present invention has the following beneficial effects compared with the prior art: (1) The present invention forms a memristor by sequentially forming a bottom electrode layer, a metal oxide layer and an upper electrode layer from bottom to top. The bottom electrode layer is a conductive electrode layer, and the metal oxide layer is (WO3). The upper electrode layer is a metal single-element electrode layer. WO3 is rich in oxygen vacancies and serves as a dielectric layer for ion migration and conductive channels. The conductive electrode layer can stably transfer electrons and exert its good electrode performance. The interface between WO3 and the conductive electrode layer forms a Schottky barrier, which enhances non-volatility and data retention capabilities. The metal single-element electrode layer serves as an active electrode and is easily electrochemically oxidized under the action of an electric field. Ag atoms are easily oxidized into ions. Through the migration of ions and the movement of oxygen vacancies in WO3, the two work together to form and break conductive filaments, thereby achieving reversible changes in resistance. Based on WO3 with a memristive effect as the functional layer, due to the obvious differences in intracellular fluid and metabolism between different tumor cells and normal cells, their conductivity is different, which is further fed back into their memristive behavior to record and analyze the electrochemical or bioelectric signal characteristics of tumor cells. Based on the differences in electrical signals between tumor cells and normal cells, different types of tumor cells can be effectively distinguished with obvious effects and good repeatability.
[0017] (2) The memristor provided by the present invention is based on the fact that there are differences in the electrical properties (such as capacitance, conductance, etc.) between tumor cells and normal cells. These differences are caused by cell membrane composition, cytoplasmic electrolyte concentration, membrane potential changes, etc. Tumor cells often show abnormal membrane potential and ion channel activity. The memristor is used as a sensor and combined with a detection circuit to capture the electrical signals of tumor cells. The cells are classified according to the differences in the electrical signals between tumor cells and normal cells. It has the following advantages: (1) It has high sensitivity. The memristor is highly sensitive to weak electrical signal changes and is suitable for detecting tiny electrical property differences of tumor cells; (2) It is small in size and has the potential to be combined with microfluidic chips to achieve high-throughput detection; (3) It has the ability to dynamically record signals and has the potential for real-time analysis and monitoring; (4) It can be better combined with artificial neural networks to improve the efficiency and accuracy of tumor cell classification. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Figure 1 Schematic diagram of the structure of the memristor of the present invention.
[0019] Among them, 1. bottom electrode layer, 2. metal oxide layer, 3. top electrode layer.
[0020] Figure 2 This is an analysis of the memristor characteristics of the Ag / WO3 / Ti memristor prepared in Example 1 of the present invention before testing the cell suspension. Figure 2 Figure a is a typical IV curve of the memristor before testing; Figure b is the retention characteristics analysis of the high resistance state (HRS) and low resistance state (LRS) of the memristor after 100 cycles.
[0021] Figure 3 The test response diagram of the Ag / WO3 / Ti memristor prepared in Example 1 of the present invention for different cell suspensions Figure 3 In which, a is the typical I-V curve of the memristor for the DMEM solution; b is the typical I-V curve of the memristor for the LN-18 cell suspension; c is the typical I-V curve of the memristor for the SHG44 cell suspension; d is the typical I-V curve of the memristor for the U251 cell suspension; e is the typical I-V curve of the memristor for the U87 cell suspension; f is the peak current of the memristor's response to different cell suspensions.
[0022] Figure 4 The difference statistical chart of the Ag / WO3 / Ti memristor prepared in Example 1 of the present invention for detecting different tumor cells under repeated experimental conditions. Detailed implementation manners
[0023] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.
[0024] On the one hand, the present invention provides a memristor for brain tumor typing detection, as Figure 1 shown, comprising a bottom electrode layer 1, a metal oxide layer 2, and a top electrode layer 3 that are sequentially formed from bottom to top. Among them, the bottom electrode layer 1 is a conductive electrode layer, the metal oxide layer 2 is tungsten trioxide, and the top electrode layer 3 is a metal single-element electrode layer.
[0025] The present invention forms a memristor with a bottom electrode layer 1, a metal oxide layer 2, and a top electrode layer 3 that are sequentially arranged from bottom to top. The bottom electrode layer 1 is a conductive electrode layer, the metal oxide layer 2 is WO3, and the top electrode layer 3 is a metal elemental electrode layer. WO3 is rich in oxygen vacancies and serves as a dielectric layer for the formation of ion migration and conductive channels. The conductive electrode layer can stably transfer electrons and exhibit its good electrode performance. A Schottky barrier is formed at the interface between WO3 and the conductive electrode layer, enhancing non-volatility and data retention ability. The metal elemental electrode layer serves as an active electrode and is prone to electrochemical oxidation under the action of an electric field. Ag atoms are easily oxidized into ions. Through the migration of ions and the movement of oxygen vacancies in WO3, the two jointly act to form and break conductive filaments, thereby realizing reversible changes in resistance. Based on WO3 with memristive effect as the functional layer, due to the obvious differences in intracellular fluid and metabolism between different tumor cells and normal cells, their conductivity is different, which is further reflected in their memristive behavior, used to record and analyze the electrochemical or bioelectric signal characteristics of tumor cells. According to the electrical signal differences between tumor cells and normal cells, different types of tumor cells can be effectively distinguished, with obvious effects and good repeatability.
[0026] In a specific embodiment, the thickness of the metal oxide layer 2 is 200 nm to 250 nm. The bottom electrode layer 1 is a Ti electrode layer with a thickness of 150 nm to 200 nm. The top electrode layer 3 is an Ag electrode layer, and the thickness of the Ag electrode layer is 150 nm to 200 nm. The memristor provided by the present invention forms an Ag / WO3 / Ti memristor with a Ti electrode layer as the bottom electrode layer 1, tungsten trioxide as the functional layer, and an Ag electrode layer as the top electrode layer 3. Among them, WO3 is rich in oxygen vacancies and serves as a dielectric layer for the formation of ion migration and conductive channels, and can form a Schottky barrier at the interface with the Ti electrode layer, enhancing non-volatility and data retention ability. The Ag electrode layer serves as an active electrode and is prone to electrochemical oxidation under the action of an electric field. Ag atoms are easily oxidized into Ag + ions. Through the migration of Ag + ions and the movement of oxygen vacancies in WO3, the two jointly act to form and break conductive filaments, thereby realizing reversible changes in resistance. The Ag electrode layer is resistant to oxidation and corrosion, improving the long-term reliability of the device and having a low resistivity, reducing the power consumption of the device.
[0027] In the present invention, the performance of the Ti / WO3 / Ag memristor highly depends on the thickness of each layer: by precisely regulating the thickness matching and interface engineering, reversible resistance changes can be achieved. Through biofunctionalization and its unique resistance change characteristics, the specific binding between antibodies and antigens can cause changes in the resistance of the memristor, which is further reflected in its memristive behavior for recording and analyzing the electrochemical or bioelectrical signal characteristics of tumor cells. According to the electrical signal differences between tumor cells and normal cells, different types of tumor cells can be effectively distinguished. For example, if the thickness of the Ti electrode layer is too thin (<150 nm), it may lead to poor contact with the WO3 layer, increase the interface resistance, affect the electron injection efficiency, be prone to local breakdown, and reduce the device stability; if it is too thick (>200 nm), it will increase the overall volume of the device, be unfavorable for high-density integration, and there will also be introduced thermal stress, affecting the crystallization quality of the WO3 layer; if the thickness of the WO3 layer is too thin (<200 nm), the electric field strength is too high, conductive filaments (Ag) are formed rapidly but difficult to control, the distribution of oxygen vacancies is limited, and multi-filament competition is prone to occur, reducing the durability; if it is too thick (>250 nm), the voltage required to drive ion migration increases, the energy consumption increases, the path of the conductive filament is too long, and the on-off ratio decreases; if the thickness of the Ag electrode layer is too thin (<150 nm), the Ag ion source is limited, Ag is depleted after multiple cycles, resulting in device failure, the ion migration rate is limited, and the sensitivity decreases; if it is too thick (>200 nm), it is easy to cause cracking of the WO3 layer, leading to leakage current.
[0028] On the other hand, the present invention provides a method for preparing the above-mentioned memristor for brain tumor typing detection, including the following steps: S1. By means of magnetron sputtering, a bottom electrode layer 1 is sputter-deposited on a glass substrate.
[0029] S2. By means of magnetron sputtering, a metal oxide layer 2 is successively deposited on the bottom electrode layer 1.
[0030] S3. A metal mask plate with openings is covered on the metal oxide layer 2. By means of DC sputtering, a top electrode layer 3 is deposited on the metal mask plate, and the metal mask plate is removed to obtain a memristor for brain tumor typing detection.
[0031] The present invention prepares the memristor by sputtering. The prepared bottom electrode layer 1, metal oxide layer 2, and top electrode layer 3 have uniform and dense films, strong adhesion, and high process stability and repeatability.
[0032] Before using the glass substrate, the glass substrate needs to be cleaned. The glass substrate is successively placed in deionized water, ethanol, acetone, ethanol, and deionized water and ultrasonically treated for 30 minutes each to completely clean the surface oil; then it is dried with N2 and reserved for use.
[0033] In a specific embodiment, during the magnetron sputtering process, the target-substrate distance is 9 cm to 11 cm, and the vacuum degree is 3×10 -4 Pa~4×10 -4 Pa, the working gas is argon, the sputtering pressure is 0.7 Pa ~ 0.8 Pa, and the sputtering power is 60 W / cm 2 , the sputtering time is 40 min to 90 min.
[0034] In a specific embodiment, during the DC sputtering process, the target-substrate distance is 9 cm to 11 cm, and the vacuum degree is 2×10 -4 Pa~3×10 -4 Pa, the working gas is argon, the sputtering pressure is 0.7 Pa ~ 0.8 Pa, and the sputtering power is 60 W / cm 2 , the sputtering time is 25 min ~ 35 min.
[0035] In a specific embodiment, the metal mask is provided with an array of openings, and the upper electrode layer is deposited in all the openings. The diameter of the openings may be 0.8 mm to 1.5 mm.
[0036] The memristor provided by the present invention is based on the differences in electrical properties (such as capacitance and conductance) between tumor cells and normal cells. These differences are due to changes in cell membrane composition, cytoplasmic electrolyte concentration, membrane potential, etc. Tumor cells often exhibit abnormal membrane potential and ion channel activity. The memristor is used as a sensor and combined with a detection circuit to capture the electrical signals of tumor cells. The cells are then classified based on the differences in electrical signals between tumor cells and normal cells. The memristor has the following advantages: (1) It has high sensitivity. The memristor is highly sensitive to weak electrical signal changes and is suitable for detecting subtle electrical property differences of tumor cells; (2) It is small in size and has the potential to be combined with microfluidic chips to achieve high-throughput detection; (3) It has the ability to dynamically record signals and has the potential for real-time analysis and monitoring; (4) It can be better combined with artificial neural networks to improve the efficiency and accuracy of tumor cell classification.
[0037] The following is further described through specific examples.
[0038] Example 1 A memristor for brain tumor typing detection includes a Ti electrode layer, a WO3 oxide layer, and an Ag electrode layer sequentially arranged from bottom to top; the thickness of the Ti electrode layer is 175 nm, the thickness of the WO3 oxide layer is 220 nm, and the thickness of the Ag electrode layer is 160 nm.
[0039] The method for preparing the memristor for brain tumor typing detection comprises the following steps: S1. Substrate cleaning: The glass substrate is successively placed in deionized water, alcohol, acetone, alcohol, and deionized water and ultrasonically treated for 30 min to completely clean the surface oil stain. After being dried with N2, the glass substrate is used as a substrate and placed in the magnetron sputtering chamber.
[0040] S2. Depositing a Ti electrode layer on the glass substrate by magnetron sputtering: Install a Ti target on the magnetron sputtering gun, set the target-substrate distance to 9 cm, evacuate the background vacuum of the sputtering chamber to 3×10 -4 Pa, introduce argon with a purity of 99.999% as the working gas, the sputtering pressure is 0.7 Pa, and the sputtering power is 60 W / cm 2 , and the sputtering time is 40 min. Under these parameters, the uniform deposition of Ti can be ensured to reach the best, and a Ti thin film electrode layer with a thickness of 175 nm can be obtained.
[0041] S3. Depositing a WO3 oxide layer on the Ti electrode layer by magnetron sputtering: Install a WO3 compound target on the magnetron sputtering gun, with the W:O atomic ratio of 1:3, set the target-substrate distance to 9 cm, evacuate the background vacuum of the sputtering chamber to 3×10 - 4 Pa, introduce argon with a purity of 99.999% as the working gas, the sputtering pressure is 0.7 Pa, and the sputtering power is 60 W / cm 2 , and the sputtering time is 90 min to obtain a WO3 oxide layer with a thickness of 220 nm.
[0042] S4. Depositing an Ag electrode layer on the WO3 oxide layer by magnetron sputtering: Cover a metal mask plate with a pore diameter of 1 mm on the surface of the WO3 oxide layer, deposit a circular Ag electrode by DC sputtering, install an Ag metal target on the magnetron sputtering DC target, set the target-substrate distance to 9 cm - 11 cm, evacuate the background vacuum of the sputtering chamber to 2×10 -4 Pa, introduce argon with a purity of 99.999% as the working gas, the sputtering pressure is 0.7 Pa, and the sputtering power is 60 W / cm 2 , and the sputtering time is 30 min to obtain an Ag electrode layer with a thickness of 160 nm. Remove the metal mask plate, and use silver glue to fix silver wires on the Ag electrode layer and the Ti electrode layer respectively to obtain a memristor, named Ag / WO3 / Ti memristor.
[0043] Example 2 A memristor for brain tumor typing detection, comprising a Ti electrode layer, a WO3 oxide layer, and an Ag electrode layer successively from bottom to top; the thickness of the Ti electrode layer is 200 nm, the thickness of the WO3 oxide layer is 250 nm, and the thickness of the Ag electrode layer is 200 nm.
[0044] The preparation method of the memristor for the above-mentioned brain tumor typing detection includes the following steps: S1. Clean the substrate: Put the glass substrate into deionized water, alcohol, acetone, alcohol, and deionized water in sequence and ultrasonically clean for 30 min to completely clean the surface oil stain. After drying the glass substrate with N2, place it as the substrate into the magnetron sputtering chamber.
[0045] S2. Deposit a Ti electrode layer on the glass substrate by magnetron sputtering: Install a Ti target on the magnetron sputtering gun, set the target-substrate distance to 11 m, pump the background vacuum degree of the sputtering chamber to 4×10 -4 Pa, introduce argon with a purity of 99.999% as the working gas, the sputtering pressure is 0.8 Pa, and the sputtering power is 60 W / cm 2 . Under this parameter, it can ensure that the Ti deposition uniformity reaches the best, and a Ti thin film electrode layer with a thickness of 200 nm can be obtained.
[0046] S3. Deposit a WO3 oxide layer on the Ti electrode layer by magnetron sputtering: Install a WO3 compound target on the magnetron sputtering gun, the atomic ratio of W to O is 1:3, set the target-substrate distance to 11 cm, pump the background vacuum degree of the sputtering chamber to 4×10 -4 Pa, introduce argon with a purity of 99.999% as the working gas, the sputtering pressure is 0.8 Pa, and the sputtering power is 60 W / cm 2 . The sputtering time is 90 min to obtain a WO3 oxide layer with a thickness of 250 nm.
[0047] S4. Deposit an Ag electrode layer on the WO3 oxide layer by magnetron sputtering: Cover a metal mask with a pore diameter of 1 mm on the surface of the WO3 oxide layer, deposit a circular Ag electrode by DC sputtering, install an Ag metal target on the magnetron sputtering DC target, set the target-substrate distance to 11 cm, pump the background vacuum degree of the sputtering chamber to 3×10 -4 Pa, introduce argon with a purity of 99.999% as the working gas, the sputtering pressure is 0.8 Pa, and the sputtering power is 60 W / cm 2 . The sputtering time is 35 min to obtain an Ag electrode layer with a thickness of 200 nm. Remove the metal mask, and use silver glue to fix silver wires on the Ag electrode layer and the Ti electrode layer respectively to obtain a memristor, named Ag / WO3 / Ti memristor.
[0048] Example 3 A memristor for brain tumor typing detection, comprising a Ti electrode layer, a WO3 oxide layer, and an Ag electrode layer that are sequentially stacked from bottom to top; the thickness of the Ti electrode layer is 150 nm, the thickness of the WO3 oxide layer is 200 nm, and the thickness of the Ag electrode layer is 150 nm.
[0049] The preparation method of the above-mentioned memristor for brain tumor typing detection includes the following steps: S1. Clean the substrate: Put the glass substrate into deionized water, alcohol, acetone, alcohol, and deionized water in sequence and ultrasonically clean for 30 min to completely clean the surface oil stain. After drying the glass substrate with N2, place it as the substrate into the magnetron sputtering chamber.
[0050] S2. Deposit the Ti electrode layer on the glass substrate by magnetron sputtering: Install a Ti target on the magnetron sputtering target gun, set the target-substrate distance to 10 cm, pump the base vacuum of the sputtering chamber to 3.5×10 -4 Pa, introduce argon with a purity of 99.999% as the working gas, the sputtering pressure is 0.7 Pa, the sputtering power is 60 W / cm 2 , and the sputtering time is 40 min. Under these parameters, the uniform deposition of Ti can be ensured to reach the best, and a Ti thin film electrode layer with a thickness of 150 nm can be obtained.
[0051] S3. Deposit the WO3 oxide layer on the Ti electrode layer by magnetron sputtering: Install a WO3 compound target on the magnetron sputtering target gun, with the W:O atomic ratio of 1:3, set the target-substrate distance to 10 cm, pump the base vacuum of the sputtering chamber to 3.5×10 -4 Pa, introduce argon with a purity of 99.999% as the working gas, the sputtering pressure is 0.7 Pa, and the sputtering power is 60 W / cm 2 , and the sputtering time is 80 min to obtain a WO3 oxide layer with a thickness of 200 nm.
[0052] S4. Deposit the Ag electrode layer on the WO3 oxide layer by magnetron sputtering: Cover a metal mask with a pore size of 1 mm on the surface of the WO3 oxide layer, deposit a circular Ag electrode by DC sputtering, install an Ag metal target on the DC magnetron sputtering target, set the target-substrate distance to 10 cm, pump the base vacuum of the sputtering chamber to 3×10 -4 Pa, introduce argon with a purity of 99.999% as the working gas, the sputtering pressure is 0.7 Pa, and the sputtering power is 60 W / cm 2 , and the sputtering time is 25 min to obtain an Ag electrode layer with a thickness of 150 nm. Remove the metal mask, and use silver glue to fix silver wires on the Ag electrode layer and the Ti electrode layer respectively to obtain a memristor, named Ag / WO3 / Ti memristor.
[0053] The Ag / WO3 / Ti memristor prepared in Example 1 is used for the detection and typing of brain tumors, including the following steps: First, for the culture methods of DMEM cell suspension, LN-18 cell suspension, SHG44 cell suspension, and U251 cell suspension, DMEM cells, LN-18 cells, SHG44 cells, and U251 cells were respectively inoculated in modified Eagle medium. The modified Eagle medium is Dulbecco's modified Eagle medium, and they were cultured in the conventional manner until the cell density reached 5×10 5 cells / mL, obtaining DMEM cell suspension, LN-18 cell suspension, SHG44 cell suspension, and U251 cell suspension respectively.
[0054] The memristor operates in a no-load state. At voltages from -2.8V to 2.8V, the typical current-voltage (I-V) curve of the memristor was tested. When the voltage of the memristor was 2.8V, the current was stable at 2mA - 3mA, and its (I-V) curve was continuously monitored. After the I-V curve of the memristor was stable at a no-load voltage of 2.8V, 2 μL of DMEM cell suspension, 2 μL of LN-18 cell suspension, 2 μL of SHG44 cell suspension, and 2 μL of U251 cell suspension were respectively dropped onto the surface of the memristor to obtain the tested I-V curve.
[0055] Figure 2 is the memristive characteristic analysis of the Ag / WO3 / Ti memristor prepared in Example 1 of the present invention before testing the cell suspension. Among them Figure 2 a is the typical I-V curve of the memristor before testing; b is the retention characteristic analysis of the high resistance state (HRS) and low resistance state (LRS) of the memristor for 100 cycles. As Figure 2 shown, the Ag / WO3 / Ti memristor has very stable memristive characteristics and retention characteristics.
[0056] Figure 3 is the test response diagram of the Ag / WO3 / Ti memristor prepared in Example 1 of the present invention to different cell suspensions. Figure 3 Among them, a is the typical I-V curve of the memristor to DMEM solution; b is the typical I-V curve of the memristor to LN-18 cell suspension; c is the typical I-V curve of the memristor to SHG44 cell suspension; d is the typical I-V curve of the memristor to U251 cell suspension; e is the typical I-V curve of the memristor to U87 cell suspension; f is the peak current of the memristor's response to different cell suspensions. As Figure 3 shown, it can be seen that the prepared Ag / WO3 / Ti memristor has obvious differences in response to different cell suspensions, especially in terms of peak current.
[0057] Figure 4 This is a statistical diagram of the difference in the detection of different tumor cells by the Ag / WO3 / Ti memristor prepared in Example 1 of the present invention under repeated experimental conditions. Figure 4 As shown in the figure, it can be seen that the prepared Ag / WO3 / Ti memristor has significant differences in peak current in response to different cell suspensions. It can be used to classify cells based on the differences in electrical signals between tumor cells and normal cells, and has the following advantages: (1) It has high sensitivity. Its memristor is highly sensitive to weak changes in electrical signals and is suitable for detecting small differences in electrical characteristics of tumor cells; (2) It is small in size and has the potential to be combined with microfluidic chips to achieve high-throughput detection; (3) It has the ability to dynamically record signals and has the potential for real-time analysis and monitoring; (4) It can be better combined with artificial neural networks to improve the efficiency and accuracy of tumor cell classification.
[0058] It should be noted that when numerical ranges are mentioned in the present invention, it should be understood that both endpoints of each numerical range and any value between the two endpoints may be selected. Since the steps and methods used are the same as those in the embodiments, in order to avoid redundancy, the present invention describes preferred embodiments. Although preferred embodiments of the present invention have been described, those skilled in the art may make additional changes and modifications to these embodiments once they understand the basic inventive concepts. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.
[0059] Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if such changes and modifications fall within the scope of the claims and their equivalents, the present invention is intended to include such changes and modifications.
Claims
1. A memristor for brain tumor classification detection, characterized in that, It includes a bottom electrode layer (1), a metal oxide layer (2), and a top electrode layer (3) that are sequentially formed from bottom to top. Among them, the bottom electrode layer (1) is a conductive electrode layer, the metal oxide layer (2) is tungsten trioxide, the top electrode layer (3) is a metal elemental electrode layer, and the conductive metal element provides migrating metal ions under the action of an electric field.
2. The memristor for brain tumor typing detection according to claim 1, characterized in that The thickness of the metal oxide layer (2) is 200 nm to 250 nm.
3. The memristor for brain tumor typing detection according to claim 1, wherein The bottom electrode layer (1) is a Ti electrode layer with a thickness of 150 nm to 200 nm.
4. The memristor for brain tumor typing detection according to claim 1, characterized in that, The top electrode layer (3) is an Ag electrode layer with a thickness of 150 nm to 200 nm.
5. A method for preparing a memristor for brain tumor typing detection according to any one of claims 1 to 4, characterized in that, It includes the following steps: By means of magnetron sputtering, the bottom electrode layer (1) is sputter-deposited on a glass substrate; By means of magnetron sputtering, the metal oxide layer (2) is sequentially deposited on the bottom electrode layer (1); A metal mask plate with openings is covered on the metal oxide layer (2). By means of DC sputtering, the top electrode layer (3) is deposited on the metal mask plate, and the metal mask plate is removed to obtain a memristor for brain tumor typing detection.
6. The preparation method of the memristor for brain tumor typing detection according to claim 5, characterized in that, During the magnetron sputtering process, the target-substrate distance is 9 cm to 11 cm, the vacuum degree is 3×10 -4 Pa to 4×10 -4 Pa, the working gas is argon, the sputtering gas pressure is 0.7 Pa to 0.8 Pa, the sputtering power is 60 W / cm 2 , and the sputtering time is 40 min to 90 min.
7. The preparation method of the memristor for brain tumor typing detection according to claim 5, characterized in that, During the DC sputtering process, the target-substrate distance is 9 cm to 11 cm, the vacuum degree is 2×10 -4 Pa to 3×10 -4 Pa, the working gas is argon, the sputtering gas pressure is 0.7 Pa to 0.8 Pa, the sputtering power is 60 W / cm 2 , and the sputtering time is 25 min to 35 min.
8. The preparation method of the memristor for brain tumor typing detection according to claim 5, wherein The metal mask plate is provided with an array of openings, and the top electrode layer (3) is deposited in all the openings.