A method for preparing a bile function layer-based memristor

Abstract

This invention discloses a method for fabricating a memristor based on a bile functional layer, belonging to the field of bioelectronic device fabrication and in vitro diagnostics of biliary tract diseases. The method sequentially completes FTO substrate pretreatment, bile functional layer preparation, Ag-on-electrode deposition, and memristor detection array fabrication. First, the FTO substrate is physically cleaned and plasma-activated. Then, a 240-260 nm bile functional layer is prepared. Subsequently, an Ag-on-electrode is deposited, and a 5-15 nm Ag atom embedding transition region is constructed. Finally, a 2×2 array is arranged and passivated for isolation. The process parameters of each step are synergistically matched to optimize the interface between the substrate, functional layer, and electrode, fully preserving bile pathological information. The resulting Ag / Bile / FTO structure memristor exhibits high electrical stability and shows significant differences in electrical response to bile samples from normal, gallstone, and gallbladder cancer patients. It enables accurate and rapid in vitro identification of biliary tract diseases, and the process is simple, low-cost, and suitable for clinical application and large-scale production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of bio-electronic device preparation and in vitro diagnosis of biliary tract diseases, and in particular to a preparation method of a memristor based on a bile functional layer. BACKGROUND

[0002] Gallstones and gallbladder cancer are common and highly dangerous biliary tract diseases. The global prevalence of gallstones is about 6.1%, which can easily induce serious complications such as acute cholecystitis, cholangitis, and biliary pancreatitis. Gallbladder cancer has become the sixth most common gastrointestinal tumor threatening human health, with a very poor prognosis, and has brought a heavy health and economic burden to global public health. In the field of clinical diagnosis, the current radiological diagnosis methods for biliary tract diseases mainly rely on upper abdominal X-ray, ultrasound, computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP), and endoscopic retrograde cholangiopancreatography (ERCP). Among them, abdominal ultrasound as a first-line imaging examination method, related studies have shown that its detection sensitivity for early gallbladder tumors is low, and it is difficult to distinguish between benign inflammatory gallbladder wall thickening and malignant infiltration. The images obtained by MRCP lack specificity, and its identification of the causes of biliary obstruction and benign and malignant tumors still needs to be combined with clinical, imaging, and pathological information for comprehensive judgment. Although ERCP is an important means for the diagnosis and treatment of biliary tract diseases, it is inherently invasive and can easily cause postoperative complications such as pancreatitis, cholangitis, and bleeding. The existing diagnosis techniques for biliary tract diseases generally have strong invasiveness, insufficient sensitivity and specificity, and poor timeliness, which cannot meet the clinical needs of precise, rapid, and minimally invasive differential diagnosis of gallstones and gallbladder cancer, and it is also difficult to achieve early prediction of disease progression.

[0003] Memristors, as the fourth basic electronic element after resistors, capacitors, and inductors, have shown significant advantages in the field of nonlinear resistance devices due to their charge storage capacity and unique resistance memory characteristics. The "memory-response" characteristics can convert specific biochemical signals into measurable electrical signals, and have shown application potential in medical clinical detection fields such as biological detection and health monitoring. In existing research, there have been reports on the realization of rapid detection of brain tumor cells based on Ag / WO / Ti structure memristors, high blood sugar and high blood lipid detection based on Ag / blood / Ti / glass structure memristors, and pulmonary arterial hypertension monitoring based on Ag / MnO / BaTiO3 / FTO structure memristors, but none of the above memristors use bile as a functional layer, and none of them are applied to the differential diagnosis of gallstones, gallbladder cancer, and other biliary tract diseases. There is no specific memristor detection scheme for biliary tract diseases.

[0004] The existing memory resistor preparation method is mostly aimed at inorganic functional layer or conventional biological fluid (such as blood), and the film forming process and interface treatment mode cannot adapt to the biological characteristics of bile: on the one hand, the components such as bile acid, cholesterol and phospholipid contained in the bile are prone to phase separation or denaturation due to temperature and operation process, resulting in loss of pathological information of the functional layer. On the other hand, the conventional substrate treatment and electrode deposition process cannot guarantee the interface bonding force and conductivity stability of the FTO substrate-bile functional layer-Ag upper electrode, and problems such as film delamination, disordered growth of conductive wires and large variation coefficient of electrical parameters are prone to occur, which cannot realize accurate conversion of pathological information to electrical signal.

[0005] In addition, the preparation of the existing biological memory resistor is mostly independent operation of each link, and lacks accurate matching of the whole process parameters for the bile functional layer, such as matching of the substrate hydroxyl active site density and the anchoring of the bile phospholipid molecules, matching of the magnetron sputtering parameters and the depth of Ag atom embedding into the bile layer, matching of the spin coating speed and the thickness and uniformity of the bile film, etc., resulting in poor electrical response stability and low accuracy of pathological identification of the prepared bile-based memory resistor, which cannot meet the clinical detection requirements.

[0006] In summary, there is an urgent need to develop a memory resistor preparation method that adapts to the biological characteristics of bile. Through accurate activation of the substrate, non-destructive film formation of the bile functional layer, gradient deposition of the Ag electrode and coordinated matching of the process parameters of each link, the interface of the bile functional layer and the substrate and electrode of the memory resistor is optimized, the complete retention of the bile pathological information and the stable conversion of the electrical signal are guaranteed, and a bile-based memory resistor that can accurately identify gallstones and gallbladder cancer is prepared, solving the technical problems of the existing technology that the bile-based memory resistor cannot be stably prepared and the pathological identification effect is poor. SUMMARY

[0007] The present application aims to overcome the above-mentioned deficiencies of the prior art and provide a preparation method of a memory resistor based on a bile functional layer. The prepared memory resistor has an Ag / Bile / FTO three-layer structure and can realize rapid auxiliary identification and diagnosis of gallstones and gallbladder cancer in vitro. In particular, the present application relates to accurate film forming process of the bile functional layer, interface optimization preparation technology of the substrate and electrode, and integrated preparation process of the whole memory resistor.

[0008] The present application adopts the following technical solutions: A preparation method of a memory resistor based on a bile functional layer, comprising the following steps: S1 FTO substrate pretreatment A physical cleaning + plasma activation two-step process is adopted to construct high-density hydroxyl active sites on the surface of the FTO substrate, guaranteeing the hydrogen bond anchoring combination with the bile functional layer, and removing impurities to guarantee the conductivity of the substrate. Specifically, it includes: S1-1 Physical cleaning: The FTO glass substrate with size of 2x2 cm, thickness of 1.1 mm, and meeting the requirements of square resistance of 10-15 Ω / sq and light transmittance of 85-95% in the wavelength range of 400-800 nm is sequentially immersed in deionized water with resistivity of 18.2-20.0 MΩ·cm, analytical pure anhydrous ethanol with purity of 99.7%, and deionized water, and is ultrasonically cleaned for 10 min at a power of 300 W and water temperature of 25°C by using a KQ-500DE ultrasonic cleaner, so as to remove oil stains, dust and other impurities on the surface of the substrate. After cleaning, the substrate is dried by blowing nitrogen at 0.3 MPa along an angle of 45°, so as to avoid residual water droplets on the surface.

[0009] S1-2 plasma activation: The dried FTO substrate is placed in a sample chamber of a PDC-002 plasma cleaning machine, vacuumized to 30-50 mTorr, and air is introduced and the vacuum degree is maintained. A power of 100 W is turned on for cleaning for 5 min, so as to form hydroxyl active sites with a density of 10¹³-10¹ 5 cm - ² on the surface of the substrate. The substrate is immediately taken out after activation, and subsequent bile functional layer coating is performed within 30 min, so as to avoid re-adsorption of impurities on the surface of the substrate and inactivation of the hydroxyl active sites.

[0010] S2 bile functional layer preparation A lossless film forming process of sample pretreatment-gradual spin coating-physiological temperature drying is adopted to prepare a dense bile functional layer with a thickness of 240-260 nm, which completely retains the pathological information in the bile and guarantees the interfacial bonding force with the FTO substrate, and specifically includes the following steps. S2-1 sample pretreatment: Fresh bile samples are collected in clinical operation, and the amount of each sample is 100-200 μL. The samples are treated within 2 h after collection, and are stored in a cold storage at 4°C throughout the process to avoid degradation of bile components. The bile samples are filtered through a 0.22 μm filter membrane to remove particulate impurities such as precipitates and cell fragments, so as to prevent short circuit channels during subsequent electrode deposition. After filtration, 100 μL is taken for standby.

[0011] S2-2 gradual spin coating film forming: Using a 1μL precision pipette, 100μL of filtered bile sample was dropped onto the center of the S1-treated FTO substrate. The substrate with the added bile was fixed on the suction cup of a KW-4A spin coater, and vacuum adsorption was activated to achieve a vacuum level ≥-0.08MPa to prevent substrate misalignment during spin coating. The preset spin-coating program was executed: first, spin-coating at a low speed of 500rpm for 10s with a 2s acceleration time to initially spread the bile and ensure sufficient contact between the bile phospholipid molecules and the hydroxyl groups of the FTO substrate to form hydrogen bonds, covering all micropores of the substrate. Then, spin-coating at a high speed of 2000rpm for 60s with a 5s acceleration time, using centrifugal force to remove excess liquid, allowing the bile components to form a molecularly smooth film on the substrate surface.

[0012] S2-3 Physiological temperature drying: The spin-coated substrate was immediately placed in a 37°C oven for 10 minutes to dry, with humidity controlled at ≤30%. This process slowly removed free moisture from the film, forming a bile pathological fingerprint sensing layer with a thickness of 240-260 nm. Drying at a physiological temperature of 37°C prevented denaturation of biomolecules such as albumin, mucin, and tumor-associated proteins in the bile, while also preventing phase separation of lipid components such as cholesterol and phospholipids due to temperature abrupt changes. This ensured that the structure, content, and spatial arrangement of pathological components in the bile remained consistent with the original sample.

[0013] S3 Ag upper electrode deposition A gradient magnetron sputtering process is used to deposit Ag on the surface of the bile functional layer, and a 5-15 nm Ag atom embedding transition region is constructed at the interface between the electrode and the bile functional layer to guide the directional growth of the conductive filament, reduce the device's cyclic variability coefficient, and ensure the interfacial adhesion between the electrode and the bile functional layer. Specifically, this includes: S3-1 Preparation before sputtering: Place the FTO substrate with the bile functional layer prepared in S2 into the sample stage of a JGP-450 magnetron sputtering coating machine. Adjust the height of the sample stage so that the distance between the substrate and the silver target is 8 cm. The silver target has a purity ≥99.99%, a diameter of 50 mm, a thickness of 5 mm, and a surface roughness of 0.1~0.5 μm. After closing the coating machine chamber, evacuate to 5 × 10⁻⁶. -4 Pa, then introduce argon gas with a purity of 99.999% and adjust the chamber pressure to 1.2 Pa, with a pressure error of ±0.1 Pa.

[0014] S3-2 Gradient Sputtering Deposition: Turn on the magnetron sputtering DC power supply, set the power to 70W with a power error of ±2W, preheat for 30 seconds, and then begin sputtering for 15 minutes. During sputtering, the sample stage rotates at a constant speed of 3 rpm to ensure uniform Ag electrode deposition. Through the coordinated control of low chamber pressure and precise power, Ag atoms partially penetrate into the surface of the bile functional layer, forming an Ag atom embedding transition region with a thickness of 5-15 nm at the electrode-bile functional layer interface. This transition region forms pre-set nucleation sites to guide the directional growth of conductive filaments. After sputtering, allow the device to cool naturally to room temperature in the chamber for approximately 20 minutes before removing it to avoid cracking at the bile functional layer-Ag electrode interface due to sudden temperature changes.

[0015] S4 memristor detection array fabrication Individual Ag / Bile / FTO memristors prepared by S3 were arranged in a 2×2 array to construct a memristor detection unit, with a spacing of 5 mm between adjacent memristors. Hydrophobic polymer / SiN was used in the array. x The passivation layer constructs a dike structure to physically and signal isolate each memristor, preventing lateral diffusion of bile biomolecules and electrical signal crosstalk, thus ensuring the independence and detection accuracy of each memristor.

[0016] Furthermore, the memristor prepared by this invention has an FTO substrate as the bottom electrode, a bile functional layer as the core sensing layer, and an Ag top electrode as the top electrode. The three layers are tightly bonded together to form a complete conductive and sensing system. The bile functional layer is a biomolecular composite membrane composed of a bile liquid matrix and specific pathological functional components. The liquid matrix is ​​a mixture of water, bile acids, cholesterol, phospholipids, bile pigments, electrolyte ions, and trace proteins. The specific pathological functional components exhibit qualitative and quantitative differences depending on the pathological state of the bile sample (normal, gallstones, gallbladder cancer), and these differences are completely preserved in the functional layer through the preparation process of this invention.

[0017] The process parameters for each preparation step in this invention are synergistically matched: the density of hydroxyl active sites prepared in S1 matches the anchoring requirements of bile phospholipid molecules in S2, ensuring the interfacial bonding between the substrate and the functional layer. The 240-260 nm thickness of the bile functional layer prepared in S2 matches the 5-15 nm depth of Ag atom embedding in the transition region in S3, ensuring the directional growth of the conductive wire. The magnetron sputtering parameters in S3 match the array spacing in S4, ensuring the stability of the electrical signal of the memristor detection array.

[0018] This invention prepares a bile functional layer using a non-destructive film-forming process combining gradient spin coating and drying at a physiological temperature of 37°C. This effectively avoids denaturation of biomolecules and phase separation of lipid components within the bile, fully preserving the pathological information of the sample. This results in significant differences in the electrical responses of memristors for normal, gallstone, and gallbladder cancer bile samples, with no overlap in peak currents, greatly improving the accuracy of biliary tract disease identification. Simultaneously, plasma activation treatment of the FTO substrate constructs high-density hydroxyl active sites, and gradient magnetron sputtering forms a 5-15nm Ag atom embedding transition region at the electrode-functional layer interface. This ensures the interfacial bonding between layers and guides the directional growth of conductive wires, resulting in a coefficient of variation of electrical parameters of <5% after 500 cycles of testing, significantly improving the electrical stability and repeatability of the device.

[0019] This invention achieves coordinated matching of process parameters throughout the entire process, from substrate pretreatment, functional layer film formation, electrode deposition, and array fabrication. It constructs an integrated memristor fabrication process adapted to the biological characteristics of bile, solving the problems of incompatibility between traditional processes and bile characteristics, and poor device performance caused by independent operation of each step. The fabrication process is simple, controllable, and suitable for large-scale production. Moreover, all the equipment used are mature equipment in the field of bioelectronic devices, requiring no additional customization. Only 100μL of bile sample is needed. The fabricated memristor can be matched with portable detection devices, which is low-cost and easy to promote. It can also monitor the dynamic changes of electrical parameters based on the non-volatile characteristics of memristors, realizing early warning of the progression of gallstones and the risk of malignant transformation. It has strong functional expandability. Attached Figure Description

[0020] Figure 1 This is a front view of an Ag / Bile / FTO structure memristor.

[0021] Figure 2 This is a top view of an Ag / Bile / FTO structure memristor. Detailed Implementation

[0022] The present invention will be further described in detail below with reference to specific embodiments. The scope of protection of the present invention is not limited to the following embodiments, and all technical solutions based on the present invention are within the scope of protection of the present invention.

[0023] Reference Figure 1 , Figure 2 As shown, 1 represents the Ag top electrode, 2 represents the bile functional layer, and 3 represents the FTO bottom electrode. The structure and dimensional relationships of each layer are clearly illustrated. Ag top electrode: approximately 100 nm thick, deposited on the surface of the bile functional layer by magnetron sputtering. Bile functional layer: 240-260 nm thick, formed from the bile sample to be tested through spin coating and drying. FTO substrate (bottom electrode): A 2×2 cm, 1.1 mm thick FTO glass substrate, serving as the conductive substrate for the device.

[0024] All equipment used in this embodiment was calibrated, and all reagents were analytical grade or specialized reagents that met specifications. The prepared memristor was an Ag / Bile / FTO three-layer structure, consisting of an FTO substrate, a bile functional layer, and an Ag top electrode from bottom to top. The supporting detection device included a detection unit (2×2 memristor detection array), a signal excitation and acquisition unit (Keysight B2901B electrochemical workstation), and a signal processing and output unit (integrated logic circuit + digital pathological feature database).

[0025] Example 1: Fabrication of a memristor based on a normal bile functional layer FTO substrate pretreatment Physical cleaning: Select an FTO glass substrate with dimensions of 2×2cm, thickness of 1.1mm, sheet resistance of 12Ω / sq, and transmittance of 88% in the 400-800nm ​​wavelength band, and immerse it sequentially in a 18.5MΩ immersion solution. The solution was prepared using a KQ-500DE ultrasonic cleaner (300W power, 25℃) in deionized water, 99.8% analytical grade anhydrous ethanol, and deionized water, with each solution being ultrasonically cleaned for 10 minutes. After cleaning, the solution was dried using a 0.3MPa nitrogen gun at a 45° angle, leaving no water droplets.

[0026] S1-2 Plasma Activation: The dried FTO substrate was placed in a PDC-002 plasma cleaner, evacuated to 45 mTorr, and air was introduced to maintain the vacuum. Cleaning was performed at 100W power for 5 minutes, resulting in a substrate surface hydroxyl active site density of 1.2 × 10¹. 4 cm - ². Remove immediately after activation and apply bile within 20 minutes.

[0027] Preparation of normal bile functional layer Sample pretreatment: 250 μL of fresh bile sample was collected from healthy volunteers during surgery, refrigerated at 4°C, and processed within 1 hour. Cell debris was removed by filtration through a 0.22 μm filter, and 100 μL was used for later use.

[0028] Gradient spin coating: A bile sample was dropped onto the center of the FTO substrate using a 1μL precision pipette, with a deviation of 1mm. The substrate was fixed in a KW-4A spin coater with a vacuum adsorption of -0.085MPa. Spin coating was performed at 500rpm (accelerated by 2s) for 10s, followed by spin coating at 2000rpm (accelerated by 5s) for 60s.

[0029] Physiological temperature drying: Immediately place in a constant temperature oven at 37℃ and 25% humidity for 10 minutes to form a bile functional layer with a thickness of 250nm, with an error of ±3nm as measured by a step meter.

[0030] Ag on electrode deposition Preparation before sputtering: Place the bile functional layer / FTO substrate into a JGP-450 magnetron sputtering coating machine, with a distance of 8 cm between the substrate and the silver target (purity 99.995%, Ra 0.3 μm). Evacuate to 4.5 × 10⁻⁶. -4 Pa, introduce 99.999% argon gas, and adjust the chamber pressure to 1.2 Pa.

[0031] Gradient sputtering deposition: DC power supply 70W, preheating for 30s, sputtering for 15min, sample stage rotating at a constant speed of 3rpm. A 10nm Ag atom embedding transition region was formed at the interface. After sputtering, the device was allowed to cool naturally to room temperature for 20min, and then removed. The Ag electrode thickness was 100nm.

[0032] Memristor detection array fabrication The memristor cells were arranged in a 2×2 array with an adjacent spacing of 5 mm, using a hydrophobic polymer / SiN array. x A passivation layer was used to construct a cofferdam structure, completing the fabrication of the detection array. Observation under an optical microscope (200x) revealed no defects such as electrode detachment or bile membrane rupture on the array surface.

[0033] Device performance testing The prepared memristor detection array was connected to the matching detection device, and a scanning voltage of ±2V was applied at a scanning rate of 0.1V / s to collect IV response data. The memristor IV curve exhibited symmetrical resistive switching characteristics. During forward scanning, it switched to a low-resistance state at 1.88V, and during reverse scanning, it switched to a high-resistance state at -1.49V. The peak current was 46.44-50.01mA, and the HRS / LRS ratio was 3.38±0.2. After 500 cycles of testing, the coefficient of variation of the electrical parameters was 3.2%, indicating good stability.

[0034] Example 2: Fabrication of a memristor based on the bile functional layer of gallstones S1: FTO substrate pretreatment The steps and process parameters are completely consistent with those in Example 1.

[0035] S2: Preparation of the bile functional layer for gallstones S2-1: Sample Pretreatment: Collect 220 μL of fresh bile sample from patients with gallstones during surgery, refrigerate at 4℃, and process within 1.5 h. Filter through a 0.22 μm filter membrane to remove large cholesterol crystals, and use 100 μL for later use.

[0036] S2-2: Gradient spin coating for film formation, S23: Drying at physiological temperature: The steps and process parameters are completely consistent with those in Example 1. The thickness of the prepared bile functional layer is 245 nm, with an error of ±4 nm.

[0037] S3: Ag top electrode deposition The steps and process parameters are completely consistent with those in Example 1, and an 8nm Ag atom embedding transition region is formed at the interface, with an Ag electrode thickness of 100nm.

[0038] S4: Fabrication of Memristor Detection Array The steps and process parameters are completely consistent with those in Example 1.

[0039] Device performance testing Tested using the corresponding testing equipment, the memristor exhibits an asymmetrical IV curve, a forward switching voltage of 1.86V, an HRS resistance of 883.84±50Ω, a peak current of 17.20-28.71mA, and an HRS / LRS ratio of 8.18±0.3. After 500 cycles of testing, the coefficient of variation of the electrical parameters is 4.5%, indicating good stability.

[0040] Example 3: Memristor fabrication based on the bile functional layer of gallbladder cancer S1: FTO substrate pretreatment The steps and process parameters are completely consistent with those in Example 1.

[0041] S2: Preparation of the bile functional layer in gallbladder cancer S2-1: Sample Pretreatment: Collect 200 μL of fresh bile sample from gallbladder cancer patients during surgery, refrigerate at 4℃, and process within 2 hours. Filter through a 0.22 μm filter membrane to remove tumor cell debris, and use 100 μL for later use.

[0042] S2-2: Gradient spin coating for film formation; S23: Drying at physiological temperature: The steps and process parameters are completely consistent with those in Example 1. The thickness of the prepared bile functional layer is 255 nm, with an error of ±3 nm.

[0043] S3: Ag deposition on the upper electrode The steps and process parameters are completely consistent with those in Example 1, and a 12nm Ag atom embedding transition region is formed at the interface, with an Ag electrode thickness of 100nm.

[0044] S4: Fabrication of Memristor Detection Array The steps and process parameters are completely consistent with those in Example 1.

[0045] Device performance testing Tested using the corresponding testing equipment, the memristor's IV curve initially showed a low resistance state. Upon forward scanning at 1.8V, it switched to a high resistance state, with an HRS resistance of 1138.13±80Ω, a peak current of 8.66-13.38mA, and an HRS / LRS ratio of 7.0±0.4. After 500 cycles of testing, the coefficient of variation of the electrical parameters was 4.8%, indicating good stability.

[0046] Example Effect Verification The memristors prepared in Examples 1-3 demonstrated specific electrical responses to bile samples from normal, gallstone, and gallbladder cancer patients, respectively. The peak current ranges of the three groups of samples did not overlap, and the ratios of high and low resistance states differed significantly. Analysis using a matching detection device enabled automated and accurate diagnosis. Furthermore, after 500 cycles of testing, the coefficient of variation of the electrical parameters for all memristors was <5%, indicating that the preparation method of this invention can achieve stable fabrication of bile-based memristors, ensuring the electrical stability of the device and the accuracy of pathological identification.

[0047] The core of the preparation method of this invention lies in the non-destructive film-forming process of the bile functional layer and the coordinated matching of process parameters in each step. The memristor prepared by this method solves the problems of poor interface bonding, loss of pathological information and unstable electrical performance of bile-based memristors in the prior art. It realizes accurate in vitro differentiation between gallstones and gallbladder cancer. Moreover, the preparation process is simple and low in cost, making it suitable for clinical application.

Claims

1. A method for fabricating a memristor based on a bile functional layer, characterized in that, Includes the following steps: S1: FTO substrate pretreatment A two-step process of physical cleaning and plasma activation is used to construct high-density hydroxyl active sites on the surface of FTO substrate, ensuring hydrogen bond anchoring with the bile functional layer, while removing impurities to ensure substrate conductivity. S2 Bile Functional Layer Preparation A non-destructive film-forming process of sample pretreatment-gradient spin coating-physiological temperature drying was adopted to prepare a dense bile functional layer with a thickness of 240-260nm, which fully preserves the pathological information in bile and ensures the interfacial adhesion with the FTO substrate. S3 Ag upper electrode deposition Gradient magnetron sputtering is used to deposit Ag on the surface of the bile functional layer, and a 5-15nm Ag atom embedding transition region is constructed at the interface between the electrode and the bile functional layer to guide the directional growth of the conductive filament, reduce the device cyclic variation coefficient, and at the same time ensure the interfacial bonding between the electrode and the bile functional layer. S4 memristor detection array fabrication Individual Ag / Bile / FTO memristors prepared by S3 were arranged in a 2×2 array to construct memristor detection units, with an adjacent memristor spacing of 5 mm. Hydrophobic polymer / SiN was used in the array. x The passivation layer constructs a dike structure to physically and signal isolate each memristor, preventing lateral diffusion of bile biomolecules and electrical signal crosstalk, thus ensuring the independence and detection accuracy of each memristor.

2. The method for preparing a memristor based on a bile functional layer according to claim 1, characterized in that, The specific steps of S1 are as follows: S1-1 Physical cleaning: FTO glass substrates with dimensions of 2×2cm and a thickness of 1.1mm, and meeting the requirements of sheet resistance of 10~15Ω / sq and transmittance of 85~95% in the 400-800nm ​​wavelength band, were selected. They were then sequentially immersed in deionized water with a resistivity of 18.2~20.0MΩ·cm, analytical grade anhydrous ethanol with a purity of 99.7%, and deionized water. Using a KQ-500DE ultrasonic cleaner, each substrate was ultrasonically cleaned for 10 minutes at a power of 300W and a water temperature of 25℃ to remove oil, dust, and other impurities from the substrate surface. After cleaning, the substrate was dried by blowing it with a 0.3MPa nitrogen gun at a 45° angle to avoid leaving water droplets on the surface. S1-2 Plasma Activation: The dried FTO substrate was placed in the sample chamber of a PDC-002 plasma cleaner, and a vacuum of 30-50 mTorr was created. Air was introduced and the vacuum level was maintained. The cleaning process was performed at 100W power for 5 minutes, forming a layer with a density of 10¹³ - 10¹⁰ on the substrate surface. 5 cm - The hydroxyl active sites are activated, and the substrate is removed immediately after activation. The subsequent bile functional layer is coated within 30 minutes to avoid the substrate surface from adsorbing impurities again, which would cause the hydroxyl active sites to become inactive.

3. The method for preparing a memristor based on a bile functional layer according to claim 1, characterized in that, S2 includes the following steps: S2-1 Sample Preprocessing: Fresh bile samples were collected intraoperatively, 100-200 μL per case. Processing was performed within 2 hours of collection, and the samples were refrigerated at 4°C throughout the process to prevent degradation of bile components. The bile samples were filtered through a 0.22 μm filter membrane to remove precipitates, cell debris, and other particulate impurities, preventing short-circuit paths during subsequent electrode deposition. 100 μL of the filtered sample was reserved for later use. S2-2 Gradient spin coating for film formation: Using a 1μL precision pipette, 100μL of filtered bile sample was dropped onto the center of the S1-treated FTO substrate. The substrate with the added bile was fixed on the suction cup of a KW-4A spin coater. Vacuum adsorption was activated to achieve a vacuum level ≥-0.08MPa to prevent substrate misalignment during spin coating. The preset spin-coating program was executed: first, spin-coating at a low speed of 500rpm for 10s with a 2s acceleration time to initially spread the bile and ensure sufficient contact between the bile phospholipid molecules and the hydroxyl groups of the FTO substrate to form hydrogen bonds and cover all micropores of the substrate; then, spin-coating at a high speed of 2000rpm for 60s with a 5s acceleration time. Excess liquid was then removed using centrifugal force, allowing the bile components to form a molecularly smooth film on the substrate surface. S2-3 Physiological temperature drying: The spin-coated substrate was immediately placed in a 37°C constant temperature oven for 10 minutes to dry. The humidity of the oven was controlled to ≤30%. Free water in the film was slowly removed to form a bile pathological fingerprint sensing layer with a thickness of 240-260 nm. Drying at a physiological temperature of 37°C was used to avoid denaturation of biomacromolecules such as albumin, mucin, and tumor-associated proteins in bile. At the same time, it prevented phase separation of lipid components such as cholesterol and phospholipids due to temperature abrupt changes, ensuring that the structure, content, and spatial arrangement of pathological components in bile were consistent with the original sample.

4. The method for preparing a memristor based on a bile functional layer according to claim 1, characterized in that, The specific steps of S3 are as follows: S3-1 Preparation before sputtering: Place the FTO substrate with the bile functional layer prepared in S2 into the sample stage of a JGP-450 magnetron sputtering coating machine. Adjust the height of the sample stage so that the distance between the substrate and the silver target is 8cm. The silver target has a purity ≥99.99%, a diameter of 50mm, a thickness of 5mm, and a surface roughness of 0.1~0.5μm. After closing the coating machine chamber, evacuate to 5×10⁻⁶. -4 Pa, then introduce 99.999% pure argon gas and adjust the chamber pressure to 1.2 Pa, with a pressure error of ±0.1 Pa. S3-2 Gradient sputtering film deposition: Turn on the magnetron sputtering DC power supply, set the power to 70W, power error ±2W, preheat for 30s and start sputtering for 15min. During sputtering, the sample stage rotates at a constant speed of 3rpm to ensure uniform deposition of Ag electrode. After sputtering, allow the device to cool naturally to room temperature in the chamber for about 20min before removing the device to avoid sudden temperature changes that could cause cracking at the interface between the bile functional layer and the Ag electrode.

5. The method for preparing a memristor based on a bile functional layer according to claim 4, characterized in that, Ag atoms partially penetrate the surface of the bile functional layer, forming an Ag atom embedding transition region with a thickness of 5-15 nm at the interface between the electrode and the bile functional layer. This transition region forms pre-set nucleation sites to guide the directional growth of the conductive wire.

6. The method for preparing a memristor based on a bile functional layer according to claim 1, characterized in that, The fabricated memristor uses an FTO substrate as the bottom electrode, a bile functional layer as the core sensing layer, and an Ag top electrode as the top electrode. The three layers are tightly bonded together to form a complete conductive and sensing system.

7. The method for preparing a memristor based on a bile functional layer according to claim 6, characterized in that, The bile functional layer is a biomolecular composite membrane composed of a bile liquid matrix and specific pathological functional components. The liquid matrix is ​​a mixture of water, bile acids, cholesterol, phospholipids, bile pigments, electrolyte ions, and trace proteins.

8. The method for preparing a memristor based on a bile functional layer according to claim 1, characterized in that, The density of hydroxyl active sites prepared in S1 matches the anchoring requirements of bile phospholipid molecules in S2.

9. The method for preparing a memristor based on a bile functional layer according to claim 1, characterized in that, The 240-260 nm bile functional layer thickness prepared in S2 matches the 5-15 nm depth of the Ag atom embedding transition region in S3, ensuring the directional growth of the conductive wire.

10. The method for preparing a memristor based on a bile functional layer according to claim 1, characterized in that, The magnetron sputtering parameters in S3 are matched with the array spacing in S4 to ensure the stability of the electrical signal of the memristor detection array.

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