Preparation and application of minimally invasive implantable composite fiber sensor

Abstract

The application relates to a preparation method and application of a minimally invasive implantable composite fiber sensor, which is prepared by means of curling, folding, core curling and the like of a patterned stretchable thin film electrode. The diameter of the sensor is micron level, and the sensor can be implanted in the body in a minimally invasive manner. The sensor has the characteristics of good biocompatibility, long-term implantability, simple preparation, good designability and the like, and can be used in the fields of deep brain electroencephalogram monitoring and electrical stimulation for epilepsy early warning and intervention, implantable electromyography-stress monitoring for bladder closed-loop monitoring and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of flexible electronics, in particular to a preparation and minimally invasive implantation of a soft and stretchable multi-channel electrophysiological recording, multi-point electrical stimulation, stress composite fiber sensor. BACKGROUND

[0002] Implantable devices can accurately monitor the electrical signals and mechanical signals accompanied by physiological activities of the human body, and perform electrical stimulation intervention when necessary, which has important applications in the fields of health monitoring, intelligent prosthesis, human-computer interaction, etc. For example, deep brain electroencephalogram monitoring and electrical stimulation show ideal curative effect in the aspects of epilepsy warning and intervention, Parkinson's disease intervention, severe depression treatment, etc. The monitoring of bladder wall stress and the stimulation of detrusor muscle to achieve assisted urination can be used for the treatment of neurogenic bladder. However, the device will cause damage to the tissue during implantation, resulting in the adsorption of tissue proteins on the surface of the device, triggering immune rejection reaction and inducing fibrous encapsulation layer, thereby reducing the service life of the device. In addition, due to the difference in mechanical properties between the device and the tissue, the micro-damage caused by the friction between the device and the surrounding tissue after implantation will further aggravate the thickness of the fibrous encapsulation layer. Therefore, reducing the implantation wound of the device, improving the softness and stretchability of the device, and realizing the high integration of functions have become the development direction of implantable devices. Compared with thin film devices, fiber devices have smaller implantation wounds, and have become a research hotspot of implantable devices.

[0003] Most of the existing implantable devices are hard devices, and the functions are single. To realize the synchronous monitoring of the electrical signals and mechanical signals generated in the physiological activities, and to perform electrical stimulation intervention for abnormal symptoms, multiple devices need to be implanted at the same time, which will increase the damage to the tissue, easily cause infection, and easily induce the formation of fibrous encapsulation layer around the device after implantation, affecting the service life of the device. SUMMARY

[0004] The purpose of the present application is to solve the above-mentioned problems in the prior art, and to provide a soft and stretchable composite fiber sensor with physiological electrical signal sensing, mechanical sensing and electrical stimulation functions, and to realize its minimally invasive implantation, in order to improve the biocompatibility of the device.

[0005] In order to achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows:

[0006] A preparation of a minimally invasive implantable composite fiber sensor, a conductive pattern is designed on a high molecular thin film substrate to obtain a thin film electrode; the thin film electrode is stacked one or more layers, and then reversely curled, folded or core-curling with the back-end connection site exposed, thereby obtaining the composite fiber sensor.

[0007] The polymer film substrate comprises one or more of polydimethylsiloxane, polyurethane, polystyrene butadiene block copolymer, hydrogenated polystyrene butadiene block copolymer, polyimide, collagen, silk fibroin.

[0008] The thickness of the polymer film substrate is not less than 50 nm, and preferably the thickness is 200-1000 nm.

[0009] The conductive pattern is in the shape of "L", "C", "L" or "C" with one end connected, or a combination of "L" and "C", or a similar pattern.

[0010] In the present application, two adjacent "L" shaped conductive patterns form a capacitive stress sensor and expose the back end connection site; the "L" or "C" shaped conductive pattern with one end connected forms a resistive stress sensor and exposes the back end connection site; the "C" shaped conductive pattern forms a physiological recording electrode or stimulation electrode and exposes the back end connection site.

[0011] In the present application, the width of the conductive pattern is 1 μm-5 mm, and preferably 20 μm-2 mm; the spacing between adjacent conductive patterns is 1 μm-5 mm, and preferably 20 μm-2 mm.

[0012] The diameter of the composite fiber sensor after being curled is determined by the width and thickness of the film substrate, and is not less than 5 μm, and preferably 50 μm-5 mm; the composite fiber sensor is used as a channel for physiological electrical signal sensing and electrical stimulation, and the distribution of the channels can be adjusted according to the needs of the film conductive pattern, and the number of channels in the present application is 1-500 channels, and preferably 2-100 channels.

[0013] The preparation method of the conductive pattern comprises magnetron sputtering, thermal evaporation, electron beam deposition, spray coating or blade coating;

[0014] The metal material for magnetron sputtering, thermal evaporation and electron beam deposition comprises one or a combination of several of gold, silver, platinum, copper, titanium and iridium gold;

[0015] The conditions for magnetron sputtering are as follows: argon partial pressure 3.8 Pa, power 150 W, sputtering thickness 7-20 nm, and preferably 15-18 nm;

[0016] The conditions for thermal evaporation and electron beam deposition are as follows: gas pressure less than 3*10 -3 Pa, evaporation rate 0.1-20 nm / s, and preferably 0.3-0.7 nm / s; conductive layer thickness 20-100 nm, and preferably 30-70 nm;

[0017] The spraying method and the blade coating method use a conductive nanoparticle dispersion liquid as a conductive material, and preferably a metal nanoparticle material, a carbon nanoparticle material, and a conductive polymer water dispersion liquid; the mass concentration of the conductive nanoparticle water dispersion liquid is preferably 0.1-20 mg / mL, and more preferably 0.5-5 mg / mL. The spraying time is 1-20 min, and more preferably 8-10 min.

[0018] The application of the minimally invasive implantable composite fiber sensor is used for minimally invasive implantation in brain, muscle, peripheral nerve, bladder and other parts to realize multi-channel physiological electrical signal monitoring, multi-point electrical stimulation and mechanical signal monitoring; and is especially used for epilepsy early warning and intervention, brain-computer interface and bladder closed-loop monitoring.

[0019] The prepared composite fiber sensor can be fixed to the rear end of a puncture needle and inserted into tissue with the puncture needle to realize minimally invasive implantation. Or a hollow needle is first punctured into the implantation site, and then the composite fiber sensor is inserted into the hollow needle, and after the hollow needle is pulled out, only the composite fiber sensor is left in the tissue to complete the minimally invasive implantation. A soluble core can also be added to improve the bending stiffness, and after being inserted into the tissue, the core is dissolved to complete the implantation. A soluble shell can also be added outside the fiber, and after being inserted into the tissue, the shell is dissolved to complete the implantation.

[0020] Compared with the prior art, the technical scheme of the present application has the following beneficial effects:

[0021] 1. The present application provides a composite sensor integrating multi-channel physiological electrical signal recording, multi-point electrical stimulation and stress monitoring functions on a fiber with a diameter of microns, which can significantly promote the development of minimally invasive implantable devices.

[0022] 2. The device prepared by the present application has a small implantation wound, and the mechanical properties of the device are less different from the tissue, which significantly improves the biocompatibility of the device.

[0023] 3. The strategy provided by the present application can realize the preparation of high-integration functional fibers only by using a mask plate method, which significantly reduces the cost of minimally invasive implantable devices. DETAILED DESCRIPTION

[0024] Figure 1 The figure is a schematic diagram of the preparation method of the dual-channel electromyography-electrical stimulation-capacitance type stress composite fiber sensor in Example 1.

[0025] Figure 2 The figure is a schematic diagram of the preparation and minimally invasive implantation of the high-density soft electrode in Example 2.

[0026] Figure 3 The figure is a schematic diagram of the preparation method of the dual-channel electromyography-electrical stimulation-resistance type stress composite fiber sensor in Example 3. DETAILED DESCRIPTION

[0027] To make the technical problems, technical solutions, and beneficial effects of this invention clearer and more understandable, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. The following embodiments are merely some, not all, of the embodiments of this invention. Therefore, the detailed descriptions of the embodiments provided below are not intended to limit the scope of the claimed invention, but merely represent selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without inventive effort are within the scope of protection of this invention.

[0028] Example 1

[0029] Using a polystyrene-butadiene block copolymer with a thickness of 200 nm and a width of 2 cm as a substrate, gold was magnetron sputtered onto it as an electrode. The sputtering conditions were: argon partial pressure 3.8 Pa, power 150 W, and sputtering time 10 s. Figure 1 As shown, by designing two "L"-shaped and two "C"-shaped patterns, the fabricated conductive patterns have a line width of 2 mm and a spacing of 2 mm. After rolling up the thin-film electrode, a capacitive stress sensor and a two-channel electromyographic electrode are integrated. The fabricated fiber device has a diameter of 200 μm. The fabricated device can be fixed on a puncture needle and sutured into the outer wall of the bladder for minimally invasive implantation. The fabricated device can stably monitor the electromyographic signals of bladder volume, detrusor muscle, and urethral sphincter, and apply electrical stimulation at appropriate times to assist bladder emptying. It can be used in the fabrication of a closed-loop bladder monitoring system for patients with neurogenic bladder.

[0030] Example 2

[0031] A high-density, flexible electrode with 60 channels was fabricated using a polydimethylsiloxane substrate with a thickness of 500 nm and a width of 1.5 cm as the substrate, and platinum nanowire dispersion as the electrode. Spraying conditions: platinum nanowire dispersion concentration of 1 mg / mL, spraying time of 8 min. A "C"-shaped pattern was used, with channels 200 μm wide and spaced at 200 μm. Soluble silk protein fibers were used as the core of the folded thin-film electrode. Figure 2 The fabricated fiber device has a diameter of 200 μm. The electrode was directly inserted into the brain, and minimally invasive implantation was achieved after the core dissolved. The fabricated electrode can provide long-term stable monitoring of EEG signals, and when a seizure signal is detected, it can provide electrical stimulation to the brain to inhibit seizures. It can be used in the fabrication of a closed-loop monitoring system for epilepsy monitoring and electrical stimulation intervention.

[0032] Example 3

[0033] Using a 200 nm thick hydrogenated polystyrene-butadiene block copolymer as a substrate, iridium was prepared on it as a conductive layer by thermal evaporation. The evaporation conditions were: gas pressure less than 3*10 -3Pa, evaporation rate of 5 nm / s, gold thickness of 50 nm. Design using a "C" shaped pattern and two "L" shaped patterns connected at one end ( Figure 3 The fabricated conductive pattern has a linewidth of 2 mm and a spacing of 2 mm. By rolling up the thin-film electrode, a resistive stress sensor, an electromyography (EMG) monitoring electrode, and a muscle stimulation electrode are integrated onto a single fiber device. The fabricated fiber device has a diameter of 300 μm. A hollow needle with a diameter of 500 μm is inserted through the bladder wall, through which the fiber device passes. After removing the hollow needle, the minimally invasive implantation of the fiber device into the bladder wall is completed. The fabricated device can stably monitor the EMG signals of the bladder volume, detrusor muscle, and urethral sphincter, and apply electrical stimulation at appropriate times to assist bladder emptying. It can be used in the fabrication of a closed-loop bladder monitoring system for patients with neurogenic bladder.

Claims

1. A preparation of minimally-invasive implantable composite fiber sensor, characterized by: A conductive pattern is designed on a polymer film substrate to obtain a thin film electrode; the thin film electrode is stacked one or more layers and then reversely rolled or folded to obtain a composite fiber sensor; The polymer film substrate has a thickness of 200-1000 nm; the diameter of the rolled composite fiber sensor is 50 μm-5 mm; The conductive pattern is "L" shaped, "C" shaped, "L" shaped with one end connected, "C" shaped with one end connected, or a combination of "L" shaped and "C" shaped. Two adjacent "L" shaped conductive patterns constitute a capacitive stress sensor and expose a rear end connection site; "L" shaped with one end connected or "C" shaped with one end connected conductive patterns constitute a resistive stress sensor and expose a rear end connection site; "C" shaped conductive patterns constitute a physiological recording electrode or a stimulating electrode and expose a rear end connection site.

2. The preparation of a minimally-invasive, implantable composite fiber sensor according to claim 1, characterized in that: The polymer film substrate comprises one or more of polydimethylsiloxane, polyurethane, polystyrene butadiene block copolymer, hydrogenated polystyrene butadiene block copolymer, polyimide, collagen, and silk protein.

3. The preparation of a minimally-invasive, implantable composite fiber sensor according to claim 1, characterized in that: The width of the conductive pattern is 1 μm-5 mm; the distance between adjacent conductive patterns is 1 μm-5 mm.

4. The preparation of a minimally-invasive, implantable composite fiber sensor according to claim 3, characterized in that: The width of the conductive pattern is 20 μm-2 mm; the distance between adjacent conductive patterns is 20 μm-2 mm.

5. The preparation of a minimally-invasive, implantable composite fiber sensor according to claim 1, wherein: The preparation method of the conductive pattern comprises magnetron sputtering, thermal evaporation, electron beam deposition, spray coating, or blade coating.

6. The preparation of a minimally-invasive, implantable composite fiber sensor according to claim 1, wherein: The composite fiber sensor is used for physiological electrical signal sensing and electrical stimulation, and the number of channels is 1-500 channels.

7. The preparation of a minimally-invasive, implantable composite fiber sensor according to claim 6, wherein: The composite fiber sensor is used for physiological electrical signal sensing and electrical stimulation, and the number of channels is 2-100 channels.

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