Biological response type memristor for in-vitro embryo monitoring and application of biological response type memristor

Abstract

The invention belongs to the technical field of assisted reproduction, and particularly relates to a biological response type memristor for in-vitro embryo monitoring and application of the biological response type memristor. The memristor comprises a substrate, a bottom electrode, a dielectric layer and a top electrode which are sequentially arranged from bottom to top, the dielectric layer is a double-layer functional layer composed of an Nb2O5 thin film and a barium titanate thin film, the barium titanate thin film is located on the upper layer of the bottom electrode, and the Nb2O5 thin film is located on the upper layer of the barium titanate thin film. The memristor realizes response to biological information by monitoring metabolic byproducts and oxidative stress markers in an embryo in-vitro culture solution in real time, realizes operation by inducing redistribution of surface charges of an interface through ion adsorption, and shows a resistance state transformation characteristic. Besides, the system breaks through the limitation of traditional microscope visual evaluation, realizes direct, sensitive and quantitative electric signal reading of the embryo metabolism state and the oxidative stress level, and solves the problem of embryo development potential evaluation caused by the increase of aneuploid rate in old lying-in women and recurrent implantation failure groups.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of assisted reproductive technology, and particularly relates to a biological response type memristor for in vitro embryo monitoring and application thereof. BACKGROUND

[0002] Current clinical embryo screening still mainly relies on artificial morphological evaluation. Embryologists evaluate development parameters such as cell number, cytoplasmic fragmentation rate and division uniformity through subjective microscopic imaging technology. Although a standardized grading system has been widely used, morphological evaluation still has significant limitations: first, the evaluation indicators (such as the number of blastomeres and the degree of blastocyst expansion) can be observed but change rapidly; second, visual interpretation is greatly influenced by optical resolution and observer subjective experience; third, in older pregnant women and cases of repeated embryo implantation failure, the incidence of embryo aneuploidy increases or the complexity of developmental potential evaluation increases. Therefore, traditional methods are difficult to meet the precision requirements of individualized assisted reproductive technology for embryo screening.

[0003] The core bottleneck in this field at present is the lack of precise detection technology that can monitor the key biochemical activities reflecting embryo vitality in real time, quantitatively and objectively. Static observation has inherent subjectivity and limitations, but the dynamic process of embryo metabolic activity and oxidative stress level cannot be obtained through traditional morphological observation. The lack of this deep functional information hinders clinical decision-making from relying on experience, thereby severely restricting the improvement of embryo selection accuracy. SUMMARY

[0004] The purpose of the present application is to overcome the above technical problems and provide a biological response type memristor for in vitro embryo monitoring and a method of using the same. The sensing and diagnostic functions are realized through a double-layer heterostructure, which can regulate the distribution of oxygen vacancies and the distribution of interface charges. The interface surface charge is redistributed through ion adsorption to realize operation, and the resistance state transition characteristics are exhibited.

[0005] The specific scheme provided by the present application is as follows: The present application provides a biological response type memristor for in vitro embryo monitoring, comprising a substrate, a bottom electrode, a dielectric layer and a top electrode arranged in order from bottom to top; the dielectric layer is a double-layer functional layer composed of a Nb2O5 thin film and a barium titanate thin film, and the barium titanate thin film is located on the upper layer of the bottom electrode, and the Nb2O5 thin film is located on the upper layer of the barium titanate thin film.

[0006] As a preferred embodiment of the present application, the substrate is a glass sheet, the bottom electrode material is FTO, and the top electrode material is Ag.

[0007] As a preferred embodiment of the present application, the bottom electrode, the dielectric layer and the top electrode are deposited by a direct current magnetron sputtering method.

[0008] Further preferably, the deposition thickness of the Nb2O5 film is 280 nm to 320 nm, and the deposition thickness of the barium titanate film is 480 nm to 520 nm.

[0009] Further preferably, when the dielectric layer is deposited by direct current magnetron sputtering, the sputtering power is 60 W to 80 W, and the sputtering time is 40 min to 60 min.

[0010] The application provides an application of the biological response type memristor in in-vitro prediction of embryo grade and embryo development.

[0011] As a preferred embodiment of the application, the embryo development includes the number of blastomeres, fragmentation rate and symmetry.

[0012] As a preferred embodiment of the application, the in-vitro prediction is to evaluate the embryo state after the embryo is cultured in a continuous culture system, and the specific culture process includes: G-1 PLUS™* culture solution is used on the first to third day, and G-2 PLUS™* culture solution is used on the third to fifth day or the third to sixth day, and the culture is carried out for 5 to 6 days under the conditions of 37.0±0.2℃, 6% CO2, 5% O2, 89% N2, humidity >95% and covering with mineral oil, and the culture solution is collected.

[0013] Further preferably, the evaluation of the embryo state includes the following steps: The current value of the culture solution is detected by using the biological response type memristor; The current value is compared with a threshold value, when the current value of the sample is greater than the threshold value, it is determined as a high-quality embryo sample, and when the current value of the sample is less than the threshold value, it is determined as a low-quality embryo sample.

[0014] More preferably, the current threshold value is 0.02 A.

[0015] In order to construct a non-invasive embryo detection platform, the application designs a biological response type resistance memory device with sensing and diagnostic functions based on a heterojunction interface. The memristor uses ordinary glass as a substrate, uses an easy adsorption layer as an intermediate layer to realize the response to biological information, uses Ag as an upper electrode of the device, and uses FTO conductive film as a lower electrode of the device, and is a memristor device sensitive to biological information.

[0016] The biological response type memristor for in-vitro embryo monitoring provided by the application detects culture solution metabolites by using a functional layer to determine whether the embryo development meets the transplantation requirements. When a voltage is applied to the top electrode of the device, the metal silver (Ag) is oxidized at the Ag / Nb2O5 interface, resulting in the formation of Ag + OH- ions. The high-quality embryo culture solution is weakly alkaline, and the surface adsorbs OH- Adsorbed oxidized Ag + , forming an interface layer with good conductivity, and the device shows relatively high current under test voltage; on the contrary, the poor embryo forms a high-resistance interface layer at the interface due to the increase of lactic acid in the culture solution and the decrease of PH value due to the insufficient development, which increases the series resistance of the whole device, and the device shows relatively low current, so as to determine the current threshold of the good and poor embryos, and distinguish the good and poor embryos.

[0017] The memristive sensing technology provided by the application can realize direct, sensitive and quantitative electrical signal reading of embryo metabolic by-products and oxidative stress markers in the culture medium by using its unique interface charge response mechanism, which provides hope for overcoming the current difficulties related to subjective morphological evaluation. This strategy not only realizes real-time and sensitive processing of short-term signals generated by changes in the external environment, but also obtains detection results with extremely low volatility, breaks through the limitations of traditional microscope visual evaluation, and solves the problem of embryo development potential evaluation caused by the increase of aneuploidy rate in high-risk pregnant women and recurrent implantation failure groups. Therefore, the application combines innovative sensing technology and bioelectric resistance medium in the field of reproductive medicine, and fully shows its important application value in embryo screening. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 is the basic performance of the initial state of the memristor. a, resistance state and power consumption distribution diagram; b, uniformity test between devices; c, simulation of synapse-like enhancement / inhibition behavior.

[0019] Figure 2 is the data related to high-quality embryos. a, I-V curve; b, consistency; c, cycle.

[0020] Figure 3 is the data related to poor quality embryos. a, I-V curve; b, consistency; c, cycle.

[0021] Figure 4 is the parameter extracted from the I-V curve of sample 1 and sample 2 for distinguishing and detecting the sample category. a, SET voltage; b, resistance effect.

[0022] Figure 5 is the morphological image (a) of high and low grade embryos and blastocysts, the correlation diagram (b) between ROS level and embryo grade, and the detection principle of memristor (c, d). DETAILED DESCRIPTION

[0023] The application will be further described in detail below in combination with the drawings: To enable those skilled in the art to have a better understanding of the features and effects of the present application, the following is a general description and definition of the terms and phrases mentioned in the specification and claims. Unless otherwise specified, all technical and scientific words used herein have their usual meanings to those skilled in the art of the present application, and in case of conflict, the definition in the specification shall prevail.

[0024] Herein, unless otherwise specified, "comprising", "including", "containing", "having" or similar words encompass the meaning of "consisting of" and "consisting essentially of", for example, "A comprising a" encompasses the meaning of "A comprising a and other" and "A comprising only a".

[0025] The present application will be further described in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present application and not used to limit the scope of the present application. Furthermore, it should be understood that after reading the content taught by the present application, those skilled in the art can make various modifications or changes to the present application, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

[0026] In the following examples, the instruments and equipment of the art are used. In the following examples, the experimental methods not specified with specific conditions are usually carried out according to the conventional conditions, or according to the conditions recommended by the manufacturer. In the following examples, various raw materials are used, unless otherwise specified, the conventional commercially available products are used, and the specifications are the conventional specifications in the art. In the specification of the present application and the following examples, unless otherwise specified, "%" means weight percent, "parts" means weight parts, and the ratio means weight ratio.

[0027] The present application applies the memristor to the field of assisted reproductive technology, and provides a biological response type memristor for in vitro embryo monitoring. The biological response type memristor comprises, from bottom to top, a substrate, a bottom electrode, a dielectric layer and a top electrode; the dielectric layer is an Nb2O5 and BaTiO3 film, the substrate is a glass sheet, the bottom electrode is an FTO film obtained by sputtering, and the top electrode is an Ag electrode.

[0028] In the present application, the substrate serves as a support base, and a rigid material such as glass can be used to achieve mechanical stability. The bottom electrode uses FTO to realize electrical signal conduction by its conductive properties. The top electrode uses silver material to ensure signal acquisition accuracy through its high conductivity. The dielectric layer uses a double heterostructure composed of Nb2O5 and BaTiO3 films to reflect physiological state by using the dielectric property change of metabolites. Resistance difference measurement captures the response difference of the film under the action of different electric fields by comparing high resistance state and low resistance state data.

[0029] This bioresponsive memristor generates an electric field distribution in a thin film by applying an excitation signal through electrodes. When the composition of the embryonic metabolite solution changes, the internal ion mobility and charge storage capacity change, leading to differences in the dielectric layer resistance characteristics. By collecting current and voltage signals, multiple sets of system data maps are established to identify changes in the concentration of biomarkers related to embryo quality in the metabolites.

[0030] The memristor provided by this invention is a nonlinear two-terminal device whose resistance can switch between a high-resistance state (HRS) and a low-resistance state (LRS) in response to input current or voltage, simulating biological synaptic behavior to achieve efficient parallel computing and pattern recognition. This invention is the first to introduce memristors into in vitro embryo monitoring in assisted reproductive technology. Bioresponsive memristors may provide a new, highly sensitive, and specific detection method, contributing to a deeper understanding of pathophysiological mechanisms and providing guidance for clinical treatment.

[0031] The present invention provides a bio-responsive memristor for embryo monitoring, which uses the functional layer of the memristor to distinguish and monitor embryo quality. By collecting the electrical signals of the memristor, it is possible to clearly distinguish between high-quality and low-quality embryos.

[0032] The following description is based on specific embodiments.

[0033] Example 1 A bioresponsive memristor for embryo 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 Nb₂O₅ and BaTiO₃ thin film, the substrate is a glass slide, the bottom electrode is a sputtered FTO thin film, and the top electrode is an Ag electrode. This bioresponsive memristor is prepared according to the following steps:

[0034] Step 1: Clean the substrate containing the FTO conductive film. Place the glass slide in acetone, alcohol and deionized water in sequence and sonicate for 20 minutes for each cleaning agent. After drying with N2, place it in the magnetron sputtering chamber as a substrate. Step 2: BaTiO3 and Nb2O5 are sequentially sputtered onto the substrate using magnetron sputtering to form a bilayer thin film, which serves as the functional layer. The specific process is as follows: a target is mounted on the magnetron sputtering gun, the target-substrate distance is set to 9 cm, the film gauge is maintained at 0.6 Pa during sputtering, the sputtering power is 60 W, and the sputtering time is 40 min; the deposition thickness of the Nb2O5 thin film is 300 nm, and the deposition thickness of the barium titanate thin film is 500 nm. Step 3: Prepare the top electrode Ag on the bilayer thin film using magnetron sputtering. Deposition is performed by DC sputtering for 5 min at a power of 60 W.

[0035] Example 2 A bioresponsive memristor for embryo 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 Nb₂O₅ and BaTiO₃ thin film, the substrate is a glass slide, the bottom electrode is a sputtered FTO thin film, and the top electrode is an Ag electrode. This bioresponsive memristor is prepared according to the following steps:

[0036] Step 1: Clean the substrate containing the FTO conductive film. Place the glass slide in acetone, alcohol and deionized water in sequence and sonicate for 20 minutes for each cleaning agent. After drying with N2, place it in the magnetron sputtering chamber as a substrate. Step 2: BaTiO3 and Nb2O5 films are sequentially sputtered and deposited on the substrate using magnetron sputtering to form a bilayer film as the functional layer. The specific process is as follows: a target is installed on the magnetron sputtering gun, the target-substrate distance is set to 9 cm, the film gauge is maintained at 0.6 Pa during sputtering, the sputtering power is 80 W, and the sputtering time is 60 min; the deposition thickness of the Nb2O5 film is 280 nm, and the deposition thickness of the barium titanate film is 480 nm. Step 3: Prepare the top electrode Ag on the bilayer thin film using magnetron sputtering. Deposition is performed by DC sputtering for 10 min at a power of 60 W.

[0037] Example 3 A bioresponsive memristor for embryo 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 Nb₂O₅ and BaTiO₃ thin film, the substrate is a glass slide, the bottom electrode is a sputtered FTO thin film, and the top electrode is an Ag electrode. This bioresponsive memristor is prepared according to the following steps:

[0038] Step 1: Clean the substrate containing the FTO conductive film. Place the glass slide in acetone, alcohol and deionized water in sequence and sonicate for 20 minutes for each cleaning agent. After drying with N2, place it in the magnetron sputtering chamber as a substrate. Step 2: BaTiO3 and Nb2O5 are sequentially sputtered onto the substrate using magnetron sputtering to form a bilayer thin film, which serves as the functional layer. The specific process is as follows: a target is mounted on the magnetron sputtering gun, the target-substrate distance is set to 9 cm, the film gauge is maintained at 0.6 Pa during sputtering, the sputtering power is 60 W, and the sputtering time is 40 min. The deposition thickness of the Nb2O5 thin film is 320 nm, and the deposition thickness of the barium titanate thin film is 520 nm. Step 3: Prepare the top electrode Ag on the bilayer thin film using magnetron sputtering. Deposition is performed by DC sputtering for 5 min at a power of 60 W.

[0039] Experimental Example 1 Cyclic durability test The memristor prepared in Example 1 (the performance of the memristors prepared in Examples 1-3 is basically the same, so this invention only uses Example 1 as an example for illustration) is connected to the top and bottom electrodes with a source meter to ensure a good and stable connection. A voltage is applied to the top and bottom electrodes of the memristor as an excitation signal. The parameters of the voltage signal (such as amplitude, width, frequency, etc.) are selected and adjusted according to specific test requirements and memristor characteristics; for example, to verify its basic resistive switching characteristics, evaluate reliability and lifetime, and analyze dynamic switching speed. To meet these requirements, the parameters of the voltage excitation signal applied to the electrodes are adjusted: first, a slow DC voltage scan (0→2.5 V→0→-2.5 V→0) is used to obtain the current-voltage curve to accurately measure the switching voltage and switching ratio; then, a continuous pulse sequence (SET / RESET pulses with an amplitude of ±2 V and a width of 100 ns) is used for cyclic endurance testing.

[0040] Histogram of changes in resistance and SET power ( Figure 1 In Figure a), a clear Gaussian fitting trend can be observed, and the resistance distribution of the device is approximately 30Ω.

[0041] Furthermore, this invention extracted the current change rate of multiple devices, with the observed value calculated to be approximately 0.279%. This result confirms the overall consistency of the resistance switching behavior across multiple cycles and different devices. Figure 1 (b)

[0042] In addition, ten positive pulses (+1 V, 0.2 s) are applied, followed by a negative pulse (-2 V, 0.2 s), causing the current level to gradually increase or decrease, thereby simulating synaptic enhancement or inhibition, indicating that the device possesses potential biological behavior. Figure 1 (c)

[0043] Using the initial state test results of the aforementioned devices as a threshold, a precise benchmark reference point is established for the entire detection process. By setting a clear initial state as the threshold, the system is placed at a known "zero point," providing a unified starting point and a clear system boundary for all subsequent data measurement and interpretation.

[0044] Experiment Example 2 Application of bioresponsive memristors in in vitro prediction of embryo grade and embryonic development The criteria for evaluating high-quality / low-quality embryos were based on parameters such as morphology, cell division, and a low aneuploidy rate. This study recruited women aged 25–38 years who underwent IVF / ICSI cycles and received GnRH antagonist ovarian stimulation, excluding cases of severe endometriosis, uterine abnormalities, or parental chromosomal abnormalities. All participants provided written informed consent according to the protocol approved by the Institutional Review Committee of the First Affiliated Hospital of Xi'an Jiaotong University (No.: XJTU1AF2025LSYY-628).

[0045] 0. Biological sample preparation: Twenty ex vivo embryo samples were collected and cultured for 6 days using G-1 PLUS™* culture medium on days 1-3 and G-2 PLUS™* culture medium on days 3-6. All samples were cultured at 37.0±0.2℃, 6% CO2, 5% O2, 89% N2, humidity >95%, and covered with mineral oil. The culture media were then collected. The G-1 PLUS™* culture medium (catalog number 10128) and the G-2 PLUS™* culture medium (catalog number 10132) were both purchased from Vitrolife.

[0046] 2. Testing At room temperature, a microdroplet of 1 μL of culture medium from different samples is added to the top electrode and the surface of the exposed functional layer of the memristor using a pipette, thereby actively changing the interfacial chemical environment of the device. The droplet rapidly wets and penetrates into the electrode gaps or grain boundaries inside the device, and modulates the electrical characteristics of the memristor in real time and significantly by inducing chemical doping and ion migration effects at the interface.

[0047] A slow DC voltage scan (0→2.5 V→0→-2.5 V→0) is used to acquire the current-voltage curve for accurate measurement of the switching voltage and switching ratio. When the same voltage scan is applied, the device's switching threshold voltage, high-to-low impedance ratio, and IV curve shape will all exhibit controllable, visually perceptible abrupt changes or drifts. These changes in response signals, including real-time voltage, current, and device resistance, are monitored using a source meter or electrochemical workstation. The memristor curve is then plotted using data processing software or plotting tools, with current on the ordinate and voltage on the abscissa.

[0048] The specific parameters detected include the reset voltage directly read from the IV curve, the switching ratio obtained by calculating the current at the reading point, nonlinearity, and peak current. Among these, the SET voltage is the transition voltage from high resistance to low resistance; the nonlinearity is the dynamic change of the current / voltage differential (…). In a specific bio-responsive memristor, the upper and lower electrodes are connected to a source surface. By applying a varying voltage signal, the dielectric layer is excited, causing it to switch between a high-resistivity state and a low-resistivity state. The response signal is continuously acquired and used to generate a current-voltage data graph.

[0049] Figure 2 This is data related to high-quality embryos (sample 1). Figure 2 Figure a shows the RS IV curves, including the original test curve (shown in black) and the subsequent droplet scan of sample 1 (shown in blue). Four particles were randomly selected from 10 groups for analysis. The peak currents of the selected samples were all in the range of 0.03–0.04 A, slightly higher than the initial state current value (i.e., the threshold), and were therefore identified as high-quality embryos. Figure 2 Figure b shows the significant uniformity of the sampling interval. Figure 2 Three memristor devices were used to test the group of samples, and all of them showed consistency.

[0050] Figure 3 This is data related to poor-quality embryos (sample 2). Figure 3 Figure a shows the IV curve, characterized by the original test curve (shown in black) and the subsequent droplet scan of sample 2 (shown in red). Three particles were randomly selected from 10 samples for analysis. The peak current of this embryo sample was much less than 0.02 A, much less than the initial current value (i.e., the threshold), and it was determined to be a poor-quality embryo. Figure 3 As shown in Figure b, the research results indicate significant consistency among the samples. When the input signal strength is 2.5V, the memristor cells exhibit highly consistent response characteristics. Figure 3 (c)

[0051] Figure 4 Parameters such as SET voltage (the voltage at which the device transitions from a high-resistance state to a low-resistance state), peak current, and linear parameters were extracted from the IV curves of Sample 1 and Sample 2 to distinguish between different sample categories. The SET voltage of the original device was -1.7 V, which changed to +1.47 V after adding biological samples. A linear correlation evaluation model for the first-order differential parameter was also established. The change in SET voltage and the negative differential effect (dV / dI < 0) indicate that the device can be used for detection and differentiation. It is easy to see that the peak current value of high-quality embryo samples is above 0.02 A, while the current value of low-quality embryo samples is below 0.02 A. Therefore, a current value of 0.02 A was used as the boundary (i.e., the threshold).

[0052] Figure 5Morphological images of high- and low-grade embryos and blastocysts (a) and a correlation diagram between ROS levels and embryo grade (b) are shown. The culture medium for high-grade embryos showed significantly lower levels of reactive oxygen species and higher levels of pluripotency marker mRNA; while the culture medium for low-grade embryos showed increased ROS levels (230.7 ± 82.23 nM), increased lactate production (28.5 ± 2.4 µM / hr vs 15.1 ± 1.9 µM / hr), and decreased glucose consumption (18.7 ± 2.8% vs 35.2 ± 3.1%). A schematic diagram of interfacial physical adsorption and H+ adsorption at the interface under positive and negative bias were also provided. + / OH - The adsorption / release process and ion movement. Changes in glycolytic activity during cultivation affect lactic acid accumulation, which in turn affects the pH of the liquid (H2O). + / OH - The mechanism of the memristor device provided by this invention is as follows: when a voltage is applied to the top electrode of the device, metallic silver (Ag) is oxidized at the Ag / Nb2O5 interface, causing Ag to... + Formation of ions. High-quality embryo culture medium is weakly alkaline, and OH- ions are adsorbed on the surface. - Adsorption and oxidation of Ag + A high-quality embryo, due to insufficient development, forms a highly conductive interface layer, resulting in a relatively high current under the test voltage. Conversely, a poor-quality embryo, due to underdevelopment, exhibits increased lactic acid and decreased pH in the culture medium, forming a high-resistivity interface layer at the interface. This increases the series resistance of the entire device, leading to a significant decrease in current and a relatively low current output. Figure 4 The analysis uses 0.02A as the dividing line, with high-quality samples having a current value higher than this value and low-quality samples having a current value lower than this value, in order to distinguish between high-quality and low-quality embryo samples.

[0053] 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 bioresponsive memristor for in vitro embryo monitoring, comprising a substrate, a bottom electrode, a dielectric layer, and a top electrode arranged sequentially from bottom to top, characterized in that, The dielectric layer is a bilayer functional layer composed of an Nb2O5 thin film and a barium titanate thin film, with the barium titanate thin film located on top of the bottom electrode and the Nb2O5 thin film located on top of the barium titanate thin film.

2. The bio-responsive memristor according to claim 1, characterized in that, The substrate is a glass sheet, the bottom electrode material is FTO, and the top electrode material is Ag.

3. The bio-responsive memristor according to claim 1, characterized in that, The bottom electrode, the dielectric layer, and the top electrode are all deposited using a DC magnetron sputtering method.

4. The bio-responsive memristor according to claim 3, characterized in that, The Nb2O5 film has a deposition thickness of 280 nm to 320 nm, and the barium titanate film has a deposition thickness of 480 nm to 520 nm.

5. The bio-responsive memristor according to claim 3, characterized in that, The dielectric layer is deposited by DC magnetron sputtering with a sputtering power of 60W~80W and a sputtering time of 40min~60min.

6. The application of the bioresponsive memristor according to any one of claims 1 to 5 in in vitro prediction of embryo grade and embryo development.

7. The application according to claim 6, characterized in that, The embryonic development status includes the number of blastomeres, fragmentation rate, and symmetry.

8. The application according to claim 6, characterized in that, The in vitro prediction involves assessing the embryo's status after culturing the embryo in a continuous culture medium. The specific culturing process includes: G-1 PLUS™* culture medium was used for days 1-3, and G-2 PLUS™* culture medium was used for days 3-6. Both were cultured for 5-6 days at 37.0±0.2℃, 6% CO2, 5% O2, 89% N2, humidity >95%, and covered with mineral oil. The culture medium was then collected.

9. The application according to claim 8, characterized in that, Assessing embryo status includes the following steps: The current value of the culture medium is detected using the bio-responsive memristor. The current value is compared with a threshold. When the current value of the sample is greater than the threshold, it is determined to be a high-quality embryo sample; when the current value of the sample is less than the threshold, it is determined to be a low-quality embryo sample.

10. The application according to claim 9, characterized in that, The current threshold is 0.02A.

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