CN-121987943-A - Flexible artificial cochlea electrode material with inner ear lymph pressure sensing function and preparation method thereof

Abstract

The invention discloses a flexible artificial cochlea electrode material with an inner ear lymph pressure sensing function, which comprises an electrode body and a miniature piezoresistive pressure sensor integrated on the electrode body, wherein the miniature piezoresistive pressure sensor is arranged at the tip end of the electrode body and the back side of an electrode contact array, the miniature piezoresistive pressure sensor comprises a flexible basal layer, a lower electrode layer, a pressure sensitive layer, a passivation packaging layer, an upper electrode layer and an integral packaging layer which are arranged in a stacked manner, and the miniature piezoresistive pressure sensor is electrically led out through at least three independent metal wires which are connected with a signal processing unit. The invention can monitor the hydrostatic pressure of the fluid in the cochlea in real time, and provides a new scheme for guiding and postoperative evaluation in artificial cochlea implantation.

Inventors

• JIN XIAOQIANG
• Teng Wangsiyuan
• GAO HAN
• XIANG HAIBIN
• Zhou Chenhe
• Yu Zipu
• CHEN JIAYU
• CHEN WENXIN
• ZHAO TENGFEI
• WANG ZHIYI
• JIANG HUIHONG
• YAN YU
• YU JIJUN
• TAN ZHIPING
• LIN ZHAOXUAN
• FU YONG
• LI YAN

Assignees

• 浙江大学

Dates

Publication Date

20260508

Application Date

20260210

Claims (10)

1. 1. The flexible artificial cochlea electrode material with the inner ear lymph pressure sensing function is characterized by comprising an electrode body and a miniature piezoresistive pressure sensor integrated on the electrode body, wherein the miniature piezoresistive pressure sensor is arranged at the tip end of the electrode body and the back side of an electrode contact array; The miniature piezoresistive pressure sensor comprises a flexible substrate layer, a lower electrode layer, a pressure sensitive layer, a passivation packaging layer, an upper electrode layer and an integral packaging layer which are arranged in a stacked manner; The miniature piezoresistive pressure sensor is electrically led out through at least three independent metal wires, and the metal wires are connected with the signal processing unit so as to realize real-time monitoring of intra-cochlear lymph hydrostatic pressure.
2. 2. The flexible cochlear implant electrode material of claim 1, wherein the flexible substrate layer is a Polyimide (PI) layer with a thickness of 5 μm, the lower electrode layer is a Ti/Au composite film layer, wherein the Ti film layer has an adhesion function and a thickness of 15-25 nm, the Au film layer has a conductive function and a thickness of 100-200 nm, the pressure sensitive layer is a three-dimensional crosslinked gold nanowire network, the passivation packaging layer is a dense insulating film of aluminum oxide (Al 2 O 3 ) with a thickness of 25-30 nm, the surface of the pressure sensitive layer is provided with array through holes, and the integral packaging layer is a parylene layer with a thickness of 4-6 μm.
3. 3. The flexible cochlear implant electrode material according to claim 1, wherein the miniature piezoresistive pressure sensor and the electrode body are integrally molded and packaged, the distance between the miniature piezoresistive pressure sensor and the tip of the electrode body is 0.5-1.5 mm, two of the three independent metal wires are connected to an upper electrode layer, namely a driving wire and an induction wire, and one of the three independent metal wires is connected to a lower electrode layer, namely the driving wire.
4. 4. A method for preparing the flexible cochlear implant electrode material with the function of sensing the fluid pressure of the inner ear according to any one of claims 1 to 3, comprising the steps of: 1) Preparing a sacrificial layer by adopting a spin coating curing process, and preparing a PI flexible substrate layer on the surface of the sacrificial layer by adopting the spin coating process and a two-step curing method; 2) Coating photoresist on the flexible substrate layer by adopting a mask photoetching technology, exposing and developing to photoetching a preset area of a lower electrode layer, wherein the preset area comprises a lower electrode, a lead and a bonding disc area; 3) Depositing a mercaptan layer on the surface of a lower electrode area of a lower electrode layer by adopting a self-assembled monolayer technology to form a self-assembled monolayer seed, and depositing a three-dimensional crosslinked gold nanowire network on the surface of the self-assembled monolayer seed by adopting an electrochemical deposition technology to obtain a pressure-sensitive layer; 4) Adopting an Atomic Layer Deposition (ALD) process, taking Trimethylaluminum (TMA) and deionized water as precursors, and depositing a biocompatible Al 2 O 3 compact insulating film on the surface of the sample obtained in the step 3); 5) Removing Al 2 O 3 films in the bonding disc area of the lower electrode layer and the non-sensor area on the substrate by adopting a mask photoetching technology and a plasma etching technology, and etching a through hole array on the Al 2 O 3 film on the surface of the pressure sensitive layer; 6) Depositing a paraxylene integral packaging layer on the integral surface of the sample obtained in the step 5) by adopting a vapor deposition packaging technology; 7) Removing the parylene packaging layer and the PI flexible basal layer in the non-sensor area by adopting a mask photoetching technology and a plasma etching technology, exposing the sacrificial layer, dissolving, releasing an independent sensor unit, and cleaning to obtain the miniature piezoresistive pressure sensor; 8) The method comprises the steps of removing a parylene packaging layer in a bonding disc area of the miniature piezoresistive pressure sensor by adopting a laser ablation process controlled by a program, exposing the metal surface, welding the bonding disc with an electrode body by adopting a metal wire, fixing a sensor at the tip of the electrode body and the back side of an electrode contact array, and then performing integrated molding packaging to obtain the flexible artificial cochlea electrode material with the inner ear lymph pressure sensing function.
5. 5. The method according to claim 4, wherein the sacrificial layer is prepared by spreading Polystyrene (PS) solution 5-10 s on the surface of monocrystalline silicon wafer or borosilicate glass at a rotation speed of 400-600 rpm/min, spin-drying at a rotation speed of 4000-6000 rpm/min for 30-60 s, and baking at 150deg.C on a hot plate for 5-10 min to form PS film with thickness of 1-2 μm to obtain the sacrificial layer; the preparation method of the PI flexible substrate layer comprises the specific steps of spin-coating PI precursor solution 30 s on the surface of a sacrificial layer at the rotating speed of 2000 rpm/min, then placing the sacrificial layer on a 100 ℃ hot plate for soft baking 3-8 min, placing the sacrificial layer in a nitrogen atmosphere oven for stepped heating and curing, wherein the curing procedure is that the PI precursor solution is cured at 200 ℃ to 40 min, and then cured at 300 ℃ to 50-70 min, and finally the PI flexible substrate layer with the thickness of 5 mu m is formed.
6. 6. The method according to claim 4, wherein in the step 2), the thickness of the photoresist is 1.0-1.5 μm, the exposure condition is that the wavelength is 315-400 nm, the light intensity is 10 mW/cm 2 , the exposure is 8-12 s, the development condition is that 2-4 wt% tetramethyl ammonium hydroxide aqueous solution is adopted to soak 45-60 s at room temperature, and deionized water is used for washing 2-3 times after development; The magnetron sputtering specifically comprises depositing a titanium film layer with a thickness of 15-25 nm in the preset area under the conditions of inert atmosphere, 0.3-0.5 Pa pressure and 200-300W sputtering direct current power, cleaning, depositing a gold film layer with a thickness of 100-200 nm, and keeping the temperature of a substrate below 50 ℃ in the deposition process; the acetone dissolution and ultrasonic assisted stripping treatment specifically comprises immersing a sample in an acetone solution, ultrasonic assisted stripping at 80-120W power for 2-3 min, completely dissolving photoresist and covered metal in an unexposed area, sequentially ultrasonic cleaning each 2-3 min in acetone, isopropanol and deionized water, and drying with nitrogen.
7. 7. The method of claim 4, wherein in step 3), the specific steps of the self-assembled monolayer technique include: Immersing the lower electrode area part of the sample into 5-15 mM (3-mercaptopropyl) trimethoxysilane or 11-mercaptoundecanoic acid ethanol solution, immersing for 30-60 min at room temperature, washing for 1-2 min with absolute ethanol by ultrasonic, and drying with nitrogen; In the electrochemical deposition technology, a three-electrode working system is adopted, a sample is used as a working electrode, a platinum electrode is used as a counter electrode, a silver electrode is used as a reference electrode, an electrolyte solvent is a mixture of deionized water and ethanol, solutes comprise 5-20 mM sodium gold disulfite or 0.5-5 mM chloroauric acid, 0.1-0.3M sodium perchlorate or potassium nitrate, 0.01-0.1M potassium dihydrogen phosphate-dipotassium hydrogen phosphate or boric acid-borax, 0.001-0.01M sodium citrate, 0.0001-0.001% (v/v) Triton X-100, and the electrodeposition time is 30-120 s.
8. 8. The method of claim 4, wherein in step 4), the ALD process has a reaction temperature of 80-100 ℃ and a deposition cycle number of 150-250, and each deposition cycle sequentially comprises TMA pulse 0.1-0.2 s, nitrogen purge 10-15 s, deionized water pulse 0.1-0.2 s, nitrogen purge 10-15 s, and finally Al 2 O 3 film with a thickness of 25-30 nm.
9. 9. The method according to claim 4, wherein the array of through holes in step 5) is a2×2 array of square through holes uniformly distributed in the center of the pressure sensitive layer, each square through hole has a side length of 5-10 μm, the upper electrode layer has a preset area size of 170-320 μm on the side of the upper electrode area, 500-1000 μm on the lead area, 15-25 μm on the width of 15-25 μm on the length of 50-100 μm on the bonding pad area, 50-100 μm on the width of 50-100 μm on the side of the lower electrode area, 150-300 μm on the length of 500-1000 μm on the lead area, 15-25 μm on the width of 15-25 μm on the length of 50-100 μm on the bonding pad area; The specific steps of the plasma etching technology in the step 5) comprise the steps of placing a sample subjected to photoetching in a reactive ion etching chamber, introducing mixed gas of BCl 3 and Cl 2 , wherein the flow rates are 35-45 sccm and 10-20 sccm respectively, maintaining the chamber pressure at 20 mTorr, applying source power at 300-500W and bias power at 80-120W, maintaining a sample stage at 22-25 ℃ through water cooling, and monitoring the intensity of an aluminum characteristic spectral line in real time through an optical emission spectrum to judge the etching end point.
10. 10. The method of claim 4, wherein the specific operations of the vapor deposition packaging technique of step 6) are: sublimating parylene serving as a raw material at 150-160 ℃ and 1-Torr ℃, then cracking the parylene into an active monomer at 680-700 ℃, carrying out gas-phase polymerization on the surface of the sample obtained in the step 5) at 22-27 ℃ and 0.1-Torr, and depositing to form a parylene integral packaging layer with the thickness of 4-6 mu m; step 7) the plasma etching technology has the etching power of 150-250W, the oxygen flow of 40-60 sccm and the time of 8-12 min; The sacrificial layer is dissolved by toluene or xylene at the temperature of 22-25 ℃ for 1-3 h; The specific steps of the laser ablation process controlled by the program in the step 8) comprise the steps of using a nanosecond pulse laser system with the wavelength of 350-360 nm, the pulse energy of 25-35 mu J, the frequency of 25-35 kHz, the spot diameter of 15-25 mu m and the scanning speed of 280-320 mm/s, and starting the real-time monitoring of the coaxial optical reflectivity for end point control; The micro spot welding technology is completed under the substrate temperature of 120-200 ℃ by adopting thermosonic energy and 20-200 ms under the action of 20-100 mW power; The metal wire is a pure gold wire or a platinum iridium alloy wire with the diameter of 15-50 mu m; the distance between the sensor and the tip of the electrode is 0.5-1.5 mm.

Description

Flexible artificial cochlea electrode material with inner ear lymph pressure sensing function and preparation method thereof Technical Field The invention belongs to the field of artificial cochlea and flexible microsensors, and particularly relates to a flexible artificial cochlea electrode material with an inner ear lymph fluid pressure sensing function and a preparation method thereof Background Cochlear implants are currently the most effective biomedical engineering devices for treating severe and extremely severe sensorineural hearing loss. The acoustic signals are converted into electric signals, so that residual acoustic nerve fibers are directly stimulated, and the patient obtains auditory perception. The success or failure of the artificial cochlea implantation operation is highly dependent on the accurate and minimally invasive implantation of the electrode array into the scala tympani in the cochlea. However, current electrode implantation procedures are essentially a "blind-mate" operation. The operator mainly relies on preoperative imaging evaluation and intraoperative hand experience, and lacks perception of real-time mechanical interaction between an implanted electrode and a cochlear fine structure. The cochlea is a closed bone organ filled with lymph fluid, and the insertion of electrodes will inevitably cause severe fluctuations in the hydrostatic pressure in the lumen. Studies have shown that this abrupt change in pressure is one of the important factors that leads to mechanical damage to normal structures within the cochlea (e.g., residual hair cells, supporting cells), and thus to post-operative residual hearing loss, post-operative cochlear inflammation, and fibrosis. At present, no effective means for monitoring the dynamic change of fluid in a cochlea in real time and in situ in the implantation process is clinically available, so that the implantation method is optimized, and objective data support is lacked in the realization of a real soft operation. Meanwhile, long-term postoperative monitoring of intra-cochlear environment is also a clinical difficulty. Local inflammatory responses of the inner ear are often accompanied by hydronephrosis of the inner ear and manifest as abnormally high intra-cochlear hydrostatic pressure. At present, the intra-cochlear environment evaluation after implantation is mostly dependent on indirect clinical symptoms and imaging examination, and pressure data in the cochlea cannot be directly and continuously obtained, so that early and accurate diagnosis and objective evaluation of curative effect of diseases are difficult to realize. In recent years, micro-nano processing and flexible electronic technology have been significantly advanced, and miniaturized and flexible pressure sensors have been widely used in the fields of health monitoring, electronic skin, robot touch and the like. However, the advanced sensing technology is integrated into the artificial cochlea electrode and is used for solving the two challenges of accurate implantation in the operation and long-term monitoring after the operation, and the prior art is still blank. In order to achieve the purpose, the invention designs an intelligent electrode capable of monitoring the intra-cochlear hydrostatic pressure change in real time and in situ in the electrode implantation process. The electrode can sense pressure change of the micro pascal level, and feed data back to an operating doctor or control an operating robot in real time, so that the operating robot can actively adjust an implantation strategy (such as slowing down the implantation speed or slightly withdrawing) when sensing abrupt pressure rise, thereby minimizing the trauma to the cochlear microstructure. In addition, after the electrode is implanted for a long time, the integrated sensor can monitor intra-cochlear pressure as required, and provide direct physiological parameters for judging pathological states such as inner ear inflammatory reaction, endolymphatic hydrops and the like, so that the postoperative starting time is accurately selected or necessary drug treatment is given, and full-period refined management from implantation operation to long-term rehabilitation is realized. Disclosure of Invention The invention aims to realize the monitoring of the hydrostatic pressure of the inner ear during and after the implantation of an artificial cochlea electrode, and provides a flexible artificial cochlea electrode material with an inner ear lymph pressure sensing function and a preparation method thereof. In order to solve the problems, the invention adopts the following technical scheme: The flexible artificial cochlea electrode material with the inner ear lymph pressure sensing function comprises an electrode body and a miniature piezoresistive pressure sensor integrated on the electrode body, wherein the miniature piezoresistive pressure sensor is arranged at the tip end of the electrode body and the back side of a