Blood memristor and method for tinnitus monitoring

Abstract

The invention discloses a blood memristor and a method for tinnitus monitoring, and belongs to the technical field of blood biomedical detection memristor devices, the memristor realizes response to biological information by measuring a blood film, and obtains a high-resistance-state resistance value and a low-resistance-state resistance value of a detected blood sample; the hearing condition of the detected object is determined by judging whether the difference between the high-resistance-state resistance value and the low-resistance-state resistance value belongs to a set threshold value range or not, the application of the method can greatly improve the early diagnosis rate and the treatment success rate of the hearing condition, and the method has great significance in improving the life quality of a patient and is worthy of popularization and application. Discomfort of the patient to white noise masking treatment and secondary damage to hearing can be avoided, and the method is of great significance to improvement of the life quality of the patient.

Description

Technical Field

[0001] This invention belongs to the field of memristor technology for biomedical detection of blood, and relates to a blood memristor for tinnitus monitoring and its preparation method. Background Technology

[0002] Tinnitus is a common ear condition characterized by the perception of abnormal sounds in the ear or skull in the absence of an external sound source. It not only affects hearing but can also be accompanied by decreased attention, sleep disturbances, and negative emotions such as anxiety and depression, severely impacting a patient's quality of life. Because the mechanisms of tinnitus are not fully understood, various treatment methods exist, but their effectiveness varies.

[0003] With technological advancements, tinnitus detection techniques are constantly evolving. Traditional tinnitus detection methods have certain limitations, such as large intervals for measuring frequency and loudness, leading to a high error rate in auditory assessment of tinnitus patients. In recent years, more refined detection methods have begun to be applied clinically, aiming to provide more accurate auditory assessment and intervention information. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide a blood memristor for tinnitus monitoring and its usage method, so as to solve the problem that the traditional tinnitus detection interval and measurement response interval are large, resulting in a large error rate in the auditory assessment of tinnitus patients.

[0005] To achieve the above objectives, the present invention employs the following technical solution: A blood memristor for mouse monitoring includes a substrate, a bottom electrode, a dielectric layer, and a top electrode arranged sequentially from bottom to top; the dielectric layer is a thin film of dried serum. The blood memristor is used to measure resistance values, thereby obtaining the resistance difference between high-resistance and low-resistance resistance values.

[0006] A further improvement of the present invention is that: Preferably, the substrate is a glass sheet, the bottom electrode is made of Ti, and the top electrode is made of Ag.

[0007] Preferably, the bottom electrode and the top electrode are prepared by magnetron sputtering.

[0008] Preferably, the dielectric layer is prepared by spin coating.

[0009] The above-mentioned method of using the blood memristor for tinnitus monitoring includes the following steps: S1, the high-resistivity resistance value and low-resistivity resistance value of the blood sample being tested are obtained through the blood memristor; S2, calculate the difference between the resistance value in the high resistance state and the resistance value in the low resistance state; S3, compare the difference with the set threshold to obtain the comparison result.

[0010] Preferably, in S1, the process of obtaining the high-resistivity resistance value and the low-resistivity resistance value is as follows: S11, connect the upper and lower electrodes of the blood memristor to the source meter and apply an excitation signal; S12, obtain the response signal of the dielectric layer after being excited by the excitation signal through the source table; S13, repeat S11 and S12, collect the response signal, and obtain the high-resistivity and low-resistivity data maps of the blood sample acquired by the blood memristor.

[0011] Preferably, in S11, the excitation signal is a voltage signal, and the excitation signal is a variable value.

[0012] Preferably, in S12, the response signal is a resistance signal.

[0013] Preferably, in S2, if the difference between the high-resistivity data and the low-resistivity data is ≥2.75, the hearing condition of the tested blood sample does not meet the requirements; if the difference between the high-resistivity data and the low-resistivity data is ≤0.75, the hearing condition of the tested blood sample meets the requirements.

[0014] Compared with the prior art, the present invention has the following beneficial effects: This invention discloses a blood-based memristor for tinnitus monitoring. The memristor uses a common glass substrate and a thin blood film as an intermediate layer to respond to biological information. Ag is used as the upper electrode and Ti as the lower electrode, making it a biosensitive memristor device. This invention utilizes blood directly as the functional layer of the memristor to detect the blood of the tested subject, determining whether the subject's hearing meets the requirements, i.e., whether they have tinnitus. Characterization of different memristors can clearly distinguish between mice without tinnitus and those with tinnitus after noise modeling. This contributes to a deeper understanding of the pathophysiological mechanisms of tinnitus and provides guidance for clinical treatment. Developing blood-based memristor detection technology for mice can not only advance tinnitus pathology research but also provide new therapeutic targets for clinical practice. The application of this method will significantly improve the early diagnosis rate and treatment success rate of tinnitus, which is of great significance for improving patients' quality of life. Furthermore, memristor technology can avoid the discomfort and secondary hearing damage experienced by patients undergoing white noise masking therapy; this reduced discomfort is crucial for improving patient acceptance and treatment effectiveness. The application of memristors in neuromorphic computing and brain-computer interfaces has also provided new avenues for tinnitus treatment, contributing to the development of more advanced tinnitus treatment technologies. Developing blood memristor detection technology for mice can not only advance tinnitus pathology research but also provide new therapeutic targets for clinical practice. The application of this technology will significantly improve the early diagnosis rate and treatment success rate of tinnitus, which is of great significance for improving patients' quality of life. Attached Figure Description

[0015] Figure 1 This is an analysis of the Ag / Blood / Ti / Glass memristor curves prepared from the blood of mice that developed tinnitus after noise modeling according to the present invention.

[0016] Figure 2 This is an analysis of the Ag / Blood / Ti / Glass memristor curves prepared from the blood of mice that did not develop tinnitus after noise modeling according to the present invention.

[0017] Figure 3 This is the Ag / Blood / Ti / Glass memristor curve analysis prepared from the blood of untreated mice prepared in this invention, i.e., the control group.

[0018] Figure 4 This is a comparison diagram of the high and low resistance states of the three groups of Ag / Blood / Ti / Glass memristors prepared in this invention. Detailed Implementation

[0019] The present invention will now be described in further detail with reference to the accompanying drawings: To enable those skilled in the art to understand the features and effects of the present invention, the terms and expressions used in the specification and claims are explained and defined in general below. Unless otherwise specified, all technical and scientific terms used herein have the ordinary meaning understood by those skilled in the art regarding the present invention, and in case of conflict, the definitions in this specification shall prevail.

[0020] In this article, unless otherwise specified, “contains,” “includes,” “containing,” “has,” or similar terms cover the meanings of “composed of” and “mainly composed of,” for example, “A contains a” covers the meanings of “A contains a and others” and “A contains only a.”

[0021] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0022] The following examples use instruments and equipment conventional in the art. Experimental methods in the following examples, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. All raw materials used in the following examples are conventional commercially available products with specifications conventional in the art. In this specification and the following examples, unless otherwise specified, "%" refers to weight percentage, "parts" refers to parts by weight, and "ratio" refers to weight proportion.

[0023] This invention discloses a blood memristor for tinnitus monitoring, which is the first time that a memristor has been applied to the field of tinnitus monitoring technology. The blood memristor for tinnitus monitoring of this invention includes a substrate, a bottom electrode, a dielectric layer, and a top electrode arranged sequentially from bottom to top; the dielectric layer is a thin film of dried mouse serum, the substrate is a glass substrate, and the dielectric layer is the blood sample to be tested.

[0024] The substrate is a glass sheet; the bottom electrode is a Ti thin film obtained by sputtering, and the top electrode is an Ag electrode.

[0025] In this invention, the substrate serves as the supporting base, and rigid materials such as glass can be used to achieve mechanical stability. The bottom electrode is made of titanium, utilizing its biocompatibility and conductivity to conduct electrical signals. The top electrode is made of silver, whose high conductivity ensures accurate signal acquisition. The dielectric layer is a thin film structure formed from dried serum, utilizing changes in the dielectric properties of proteins and metabolites in the serum to reflect physiological states. Resistance difference measurement captures the difference in the serum film's response under different electric fields by comparing data from high-resistivity and low-resistivity states.

[0026] This device applies an excitation signal through electrodes to create an electric field distribution within a serum film. Changes in serum composition alter the internal ion mobility and charge storage capacity, leading to differences in the dielectric layer's resistance characteristics. By acquiring resistance signals under different voltage conditions, data maps of high-resistance and low-resistance states are established. The system then identifies changes in the concentration of tinnitus-related biomarkers in the serum sample by calculating the resistance difference between the two states.

[0027] The memristor disclosed in this invention is a nonlinear two-terminal device whose resistance can switch between a high-resistance state (HRS) and a low-resistance state (LRS) depending on the input current or voltage, simulating biological synaptic behavior to achieve efficient parallel computing and pattern recognition. This invention is the first to introduce memristors, particularly in small animal models such as mice, for tinnitus detection. Blood memristors may provide a new, highly sensitive, and specific detection method, contributing to a deeper understanding of the pathophysiological mechanisms of tinnitus and providing guidance for clinical treatment.

[0028] The method for preparing a blood memristor for tinnitus monitoring includes the following steps: Step 1: Clean the substrate. Place the glass slide in deionized water, alcohol, acetone, alcohol, and deionized water in sequence and sonicate for 20-30 minutes. After drying the glass slide with N2, place it in the magnetron sputtering chamber as the substrate. Step 2: A Ti thin film is deposited on a glass substrate using magnetron sputtering as a conductive film and also as the bottom electrode. Specifically, a Ti metal target is mounted on the magnetron sputtering gun, with a target-substrate distance of 9-11 cm. The base vacuum in the sputtering chamber is then evacuated to 3 × 10⁻⁶. -4 Argon gas with a purity of 99.999% was introduced as the working gas. During sputtering, the argon gas flow rate was 7 sccm, the sputtering atmosphere control position was set to 20%, the sputtering pressure was 0.6 Pa, and the sputtering power was 60 W / cm. 2 The sputtering time was 40 minutes.

[0029] Step 3: Five-week-old C57 mice were selected. Before modeling, hearing and startle reflex were tested and found to be normal. The selected mice were randomly divided into experimental and control groups. The experimental group mice received specific noise treatment, while the control group was not exposed to noise, serving as the baseline for the experiment. Then, a 16kHz narrowband noise model was established in one ear of the experimental group mice. One week after modeling, hearing and startle reflex were re-examined to determine the presence or absence of tinnitus. Based on the results, the experimental group mice were divided into those with tinnitus and those without. Fresh blood was collected from the eyes of all three groups of mice (including the control group), and the blood was anticoagulated in anticoagulant tubes before centrifugation to obtain serum.

[0030] Step 4: Using the Ti-coated glass slide obtained in Step 2 as a substrate, spin-coat the fresh mouse serum obtained in Step 3 onto the substrate as a dielectric layer. The spin-coating speed is set to 700 rpm and the spin-coating time is 20 s.

[0031] Step 5: Place the spin-coated glass slide in an oven and dry it at 40 °C for 10 min to obtain a mouse serum film.

[0032] Step 6: Prepare the top electrode Ag on the mouse serum film using magnetron sputtering. Cover the surface of the mouse serum film with a metal mask with circular holes, and deposit the top electrode Ag using DC sputtering.

[0033] The process parameters for preparing the Ag electrode are as follows: An Ag metal target is mounted on a DC magnetron sputtering target, the target-substrate distance is set to 9-11 cm, and the background vacuum of the sputtering chamber is evacuated to 2 × 10⁻⁶. -4 Argon gas with a purity of 99.999% was introduced as the working gas. During sputtering, the argon gas flow rate was 9 sccm, the sputtering atmosphere control position was set to 20%, the sputtering pressure was 0.5 Pa, and the sputtering power was 60 W / cm. 2 The sputtering time was 12 minutes.

[0034] The method for preparing a blood memristor for tinnitus monitoring utilizes blood directly as the functional layer of the memristor to detect whether mice have tinnitus. By characterizing different memristors, mice without tinnitus and mice with tinnitus after noise modeling can be clearly distinguished.

[0035] A second aspect of the present invention discloses a method of using a blood memristor for tinnitus monitoring, the method comprising the following steps: Step 1: Connect the top and bottom electrodes of the blood-phase memristor to the source meter, ensuring a good and stable connection. Apply voltage to the top and bottom electrodes of the memristor as an excitation signal, applying a voltage range of 0 V → 1.5 V → -1.5 V → 0 V. The parameters of the voltage signal (such as amplitude, width, frequency, etc.) need to be selected and adjusted according to the specific test requirements and the characteristics of the memristor; for example, you can start with a small voltage amplitude and gradually increase it to observe the response of the memristor.

[0036] Step 2: Use a source meter to measure the response signal of the memristor film after being subjected to an excitation signal voltage. The response signal may include changes in current, resistance, etc. For blood-borne memristors, due to their potentially complex characteristics, it is necessary to carefully measure and record the signal changes at different times and under different excitation conditions.

[0037] Step 3: During the testing process, continuously collect relevant data, including real-time voltage, current, and device resistance. Use data processing software or plotting tools to plot the memristor curve with current as the vertical axis and voltage as the horizontal axis. For example, a common approach is to plot the current versus voltage (IV) curve. By observing the shape and characteristics of the curve, one can understand the memristor's memory characteristics and switching behavior. Simultaneously, plot the high-resistance and low-resistance conductance states using the collected resistance values.

[0038] The high-resistivity data map refers to the data set of blood memristors exhibiting a high-resistivity state when a specific excitation signal is applied. This can be achieved by adjusting the voltage signal amplitude to trigger the dielectric layer to form a high-resistivity state, reflecting the distribution characteristics of specific components in the blood sample. The low-resistivity data map refers to the data set of the dielectric layer transitioning to a low-resistivity state after a change in the excitation signal. This can be achieved by reducing the voltage signal amplitude to alter the charge migration path, capturing the dynamic response characteristics of the blood sample. The difference value refers to the amount of difference between the high-resistivity and low-resistivity resistance data, calculated using a numerical calculation module. This parameter quantifies changes in the electrical properties of the blood sample. The set threshold is a predefined judgment standard value, determined through clinical data statistics or experimental calibration. This threshold is used to distinguish between normal and abnormal samples.

[0039] Step 4: Calculate the resistance difference between the high-resistance state resistance value and the low-resistance state resistance value, and compare the difference with the set threshold.

[0040] Specifically, if the difference between the high-resistivity and low-resistivity values ​​is greater than 2.75, the hearing condition of the tested blood sample is deemed unsatisfactory, indicating tinnitus. If the difference is less than 0.75, the hearing condition of the tested blood sample is deemed satisfactory, indicating no tinnitus. If the difference is between 0.75 and 2.75, further testing using other methods is required.

[0041] After the upper and lower electrodes of the specific blood memristor are connected to the source surface, a changing voltage signal is applied to excite the dielectric layer, causing it to switch between a high-resistivity state and a low-resistivity state. The response signal is continuously acquired and a data graph of the high-resistivity state and the low-resistivity state is formed. The resistance difference between the two states is quantified by a calculation module. This difference is then compared with a preset threshold. If it exceeds the threshold, it is determined that there are tinnitus-related biomarkers; otherwise, it is determined to be a normal sample.

[0042] In some specific implementations, the threshold can be dynamically adjusted according to the sensitivity of different detection devices. For example, 2.75 can be used as the standard threshold in precision laboratory equipment, while it can be appropriately relaxed to 2.5 in portable detection devices. In addition, the threshold can also be optimized for different blood sample types, such as setting grading criteria for the differences between venous blood and finger-prick blood.

[0043] The following description, in conjunction with specific embodiments, provides further details.

[0044] Example 1 In one embodiment, such as Figures 1 to 4 As shown, a method for preparing and testing a blood memristor for tinnitus monitoring includes the following steps: The preparation process involves the following steps: S11, clean the substrate. Place the glass slide in deionized water, alcohol, acetone, alcohol, and deionized water in sequence and sonicate for 20-30 minutes. After drying the glass slide with N2, place it in the magnetron sputtering chamber as a substrate. S12, Ti electrodes are deposited on a glass substrate by magnetron sputtering for later use; S13, five-week-old C57 mice were randomly divided into experimental group and control group. The experimental group mice were subjected to 16kHz narrowband noise modeling in one ear. After modeling, tinnitus behavior was retested. The experimental group mice were divided into those with tinnitus and those without tinnitus. Fresh blood was collected from the eyeballs of the three groups of mice, including the control group mice. After anticoagulation in anticoagulant tubes, the serum was collected by centrifugation. S14, using the Ti-coated glass slide obtained in step S12 as a substrate, the fresh mouse serum obtained in step 3 is spin-coated onto the substrate as a dielectric layer using a spin-coating method. S15, dried, to obtain mouse serum film; S16, an upper electrode Ag is prepared on the mouse serum film using magnetron sputtering. A metal mask with holes is covered on the surface of the mouse serum film, and the upper electrode Ag is deposited using DC sputtering.

[0045] The testing process is as follows: S21. Connect the upper and lower electrodes of the three sets of blood-related memristors to the source meter, ensuring a good and stable connection. Apply a voltage signal to the top and bottom electrodes of the memristor in the following order: 0 V → 1.5 V → -1.5 V → 0 V. The parameters of the voltage signal (such as amplitude, width, frequency, etc.) need to be selected and adjusted according to the specific test requirements and the characteristics of the memristor; for example, you can start with a small voltage amplitude and gradually increase it to observe the response of the memristor.

[0046] S22, use a source meter to measure the response signal of the memristor thin film after being subjected to an excitation signal voltage. The response signal may include changes in current, resistance, etc. For blood-borne memristors, due to their potentially complex characteristics, it is necessary to carefully measure and record the signal changes at different times and under different excitation conditions.

[0047] S23. During the testing process, relevant data is continuously collected, including real-time voltage, current, and device resistance. Using data processing software or plotting tools, a memristor curve is plotted with current as the vertical axis and voltage as the horizontal axis. For example, a common approach is to plot the curve of current versus voltage. By observing the shape and characteristics of the curve, one can understand the memory characteristics and switching behavior of the memristor.

[0048] S24. Typical IV curves and semi-logarithmic IV curves of blood memristors were plotted for the control group, the group without tinnitus, and the group with tinnitus, respectively, and compared. Figures 1-3 To make the comparison clearer, three sets of histograms were plotted for the high-resistance state (HRS) and low-resistance state (LRS) of the memristor at a voltage of 1 V. The difference between the high and low resistance states was calculated, as shown below. Figure 4 .

[0049] Figure 1 Figure 1 shows the curve analysis of Ag / Blood / Ti / Glass memristors prepared from the blood of mice that developed tinnitus after noise modeling, as prepared in this invention. Figure (a) shows the typical IV curve of the device; Figure (b) shows the semi-logarithmic IV curve of the device. Figure 2 shows the curve analysis of Ag / Blood / Ti / Glass memristors prepared from the blood of mice that did not develop tinnitus after noise modeling, as prepared in this invention. Figure (a) shows the typical IV curve of the device; Figure (b) shows the semi-logarithmic IV curve of the device. Figure 3 shows the curve analysis of Ag / Blood / Ti / Glass memristors prepared from the blood of untreated mice prepared in this invention, i.e., the control group. Figure (a) shows the typical IV curve of the device; Figure (b) shows the semi-logarithmic IV curve of the device. It can be clearly seen from the figures that the IV curves and semi-logarithmic IV curves of the memristors prepared from the blood of mice that developed tinnitus and those that did not are significantly different, with the window of the IV curve and semi-logarithmic I-curve for mice that developed tinnitus being significantly larger.

[0050] Figure 4This is a comparison of the high and low resistance states of the three groups of Ag / Blood / Ti / Glass memristors prepared in this invention. Figure (a) is a bar chart showing the high resistance state (HRS) and low resistance state (LRS) of the three groups of memristors at a voltage of 1 V; Figure (b) is a bar chart showing the difference in conductance between the high and low resistance states of the three groups of memristors at a voltage of 1 V. It can be clearly seen from the figures that the difference in the high and low resistance states of the blood memristors in mice with tinnitus is larger, while the difference in the high and low resistance states in mice without tinnitus is smaller. Based on this, tinnitus monitoring in mice can be performed.

[0051] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A blood memristor for monitoring mice, characterized in that, It includes a substrate, a bottom electrode, a dielectric layer, and a top electrode arranged sequentially from bottom to top; the dielectric layer is a thin film after the serum has been dried; The blood memristor is used to measure resistance values, thereby obtaining the resistance difference between high-resistance and low-resistance resistance values.

2. The blood memristor for tinnitus monitoring according to claim 1, characterized in that, The substrate is a glass sheet, the bottom electrode is made of Ti, and the top electrode is made of Ag.

3. The blood memristor for tinnitus monitoring according to claim 1, characterized in that, The bottom electrode and top electrode are prepared by magnetron sputtering.

4. The blood memristor for tinnitus monitoring according to claim 1, characterized in that, The dielectric layer is prepared by spin coating.

5. The method of using the blood memristor for tinnitus monitoring as described in claim 1, characterized in that, Includes the following steps: S1, the high-resistivity resistance value and low-resistivity resistance value of the blood sample being tested are obtained through the blood memristor; S2, calculate the difference between the resistance value in the high resistance state and the resistance value in the low resistance state; S3, compare the difference with the set threshold to obtain the comparison result.

6. The method of using the blood memristor for tinnitus monitoring according to claim 5, characterized in that, In S1, the process of obtaining the high-resistivity resistance value and the low-resistivity resistance value is as follows: S11, connect the upper and lower electrodes of the blood memristor to the source meter and apply an excitation signal; S12, obtain the response signal of the dielectric layer after being excited by the excitation signal through the source table; S13, repeat S11 and S12, collect response signals, and obtain high-resistivity and low-resistivity data maps of the blood sample acquired by the blood memristor.

7. The method of using the blood memristor for tinnitus monitoring according to claim 6, characterized in that, In S11, the excitation signal is a voltage signal, and the excitation signal is a variable value.

8. The method of using the blood memristor for tinnitus monitoring according to claim 7, characterized in that, In S12, the response signal is a resistance signal.

9. The method of using the blood memristor for tinnitus monitoring according to claim 5, characterized in that, In S2, the difference between the high-resistivity data and the low-resistivity data is ≥ 2.75, the hearing condition of the blood sample being tested does not meet the requirements.

10. The method of using the blood memristor for tinnitus monitoring according to claim 5, characterized in that, In S2, the difference between the high-resistivity data and the low-resistivity data is ≤0.75, and the hearing condition of the blood sample being tested meets the requirements.

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