CN109222905B - Intracranial wound healing monitoring device, preparation method and application thereof - Google Patents
Intracranial wound healing monitoring device, preparation method and application thereof Download PDFInfo
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Abstract
The invention provides an intracranial wound healing monitoring device, a preparation method and application thereof, wherein the device comprises: flexible electrode arrays and photoacoustic imaging systems. The flexible electrode array based on the liquid metal has high biological safety and lower elastic modulus, can be tightly attached to the surface of a wound of a cortex layer, and detects an electroencephalogram signal with high resolution; the photoacoustic imaging system has high detection precision, no damage to tissues, safety and convenience, and is an important progress of medical imaging auxiliary diagnosis; the flexible brain electrode array and the photoacoustic imaging system are combined, the problem that intracranial wounds cannot be observed is solved, noninvasive monitoring of the intracranial wounds is achieved, and the monitoring accuracy can even meet the requirements of clinical monitoring indexes.
Description
Technical Field
The invention belongs to the field of intracranial wound monitoring, and particularly relates to an intracranial wound healing monitoring device, and a preparation method and application thereof.
Background
At present, an effective monitoring means for intracranial trauma condition is lacked, which is a great problem of clinical treatment. The intracranial wound healing condition is timely and accurately monitored, the intracranial wound change can be found at early stage, the treatment effect is improved, and the method has very important significance for clinical diagnosis and guidance of treatment. The implanted brain electrode can effectively monitor brain tissue electric signals, so that the healing condition of wounds can be judged according to the change of the brain electrical signals. The brain electrode array is an important brain-computer interface for monitoring brain electrical signals, can establish a direct communication channel between the human brain and electronic equipment, and provides important data reference for the wound healing condition. However, although the traditional implantable nerve electrode can obtain a higher signal-to-noise ratio, it is easy to cause some damage to tissue, such as the commercially available Michigan electrode and Utah electrode. In recent years, new flexible brain electrode arrays have become the focus of research in the neuroscience field with their high resolution signal detection and extremely low tissue damage.
Meanwhile, with the continuous development of medical imaging technology, the medical imaging technology provides powerful technical support for intracranial wound monitoring. Common medical imaging techniques include Magnetic Resonance Imaging (MRI), X-ray Computed Tomography (CT), and photoacoustic imaging (PAT). In the practical use process, the MRI imaging needs to be carried out by means of a strong magnetic field, and the time for generating the image is long, so that the real-time imaging of the tissue wound cannot be realized; CT imaging produces a large amount of radiation when used and is not useful for long term viewing. As an emerging non-invasive imaging technology, the photoacoustic imaging technology combines the advantages of optical imaging and ultrasonic imaging, has the excellent characteristics of high contrast and high penetration depth, and can provide clear and continuous monitoring imaging.
Therefore, by combining the flexible brain electrode array and the photoacoustic imaging technology, the method for accurately monitoring the intracranial wound healing condition is researched and developed, and the method has good research and application values.
Disclosure of Invention
Therefore, the invention aims to overcome the defects in the prior art and provide an intracranial wound healing monitoring device, a preparation method and application thereof.
Before setting forth the context of the present invention, the terms used herein are defined as follows:
the term "PDMS" refers to: polydimethylsiloxane.
To achieve the above object, a first aspect of the present invention provides an intracranial wound healing monitoring device, the device comprising: flexible electrode arrays and photoacoustic imaging systems.
The apparatus according to the first aspect of the present invention, wherein the photoacoustic imaging system is a near-infrared photoacoustic imaging system; preferably, the photoacoustic imaging system comprises a pulsed laser, an ultrasonic signal receiver and a data processing and analyzing module.
The apparatus according to the first aspect of the invention, wherein the flexible electrode array comprises: the device comprises a substrate and an interconnection wire formed by converging nano-scale or micro-scale liquid metal particles on the substrate.
The device according to the first aspect of the present invention, wherein the substrate material is selected from one or more of: high polymer materials such as PDMS, Ecoflex, water-soluble polyurethane, polylactic acid, polycaprolactone and the like; preferably PDMS.
The apparatus according to the first aspect of the invention, wherein the liquid metal is selected from one or more of: indium gallium alloy, gallium indium tin alloy, bismuth tin alloy; preferably an indium gallium alloy.
The device according to the first aspect of the present invention, wherein the method for preparing the flexible electrode array comprises the following steps:
(1) adding liquid metal into an organic solvent, and processing the liquid metal into micro-nano particles to obtain liquid metal ink;
(2) drawing an electrode array pattern by using the liquid metal ink prepared in the step (1);
(3) and after the solvent is completely volatilized, casting a pre-cured substrate material on the printed electrode pattern, and obtaining the flexible electrode array after the curing is completely carried out.
Preferably, in the step (1), the organic solvent is selected from one or more of: n-decanol, water, alcohol, acetone, N-dimethylformamide, dichloromethane, trichloromethane and tetrahydrofuran; preferably n-decanol.
In the step (1), the processing method is ultrasonic and/or mechanical stirring.
In the step (2), the electrode array pattern drawing method is selected from one or more of the following methods: screen printing, ink jet printing, 3D printing; screen printing is preferred.
A second aspect of the invention provides the use of a device according to the first aspect in the manufacture of a medical product for monitoring wound healing.
The invention aims to overcome the problems in the prior art, and provides a method for monitoring the intracranial wound healing condition aiming at the serious challenge that the intracranial wound healing condition cannot be monitored.
In order to achieve the purpose, the invention adopts the following technical scheme to realize the purpose:
the brain electrical signals of intracranial wound tissues are detected by utilizing the flexible and stretchable brain electrode array, and then the high-resolution images of the wound tissues are obtained by combining the photoacoustic imaging technology, so that the wound healing condition can be accurately monitored in real time.
The flexible and stretchable brain electrode array adopts high-biosafety liquid metal as a conductive matrix and adopts a screen printing technology to prepare the high-stretchability and high-biosafety brain electrode array with Polydimethylsiloxane (PDMS) as a substrate. Compared with traditional gold, silver and conductive polymers, the liquid metal not only has excellent tensile property, but also shows good biological safety. The specific process steps of the flexible brain electrode array are as follows:
(1) adding liquid metal into an organic solvent, and processing the liquid metal into micro-nano particles under the action of ultrasonic or mechanical stirring.
(2) And printing the liquid metal conductive ink into a pre-designed brain electrode array pattern by adopting a screen printing process.
(3) And after the solvent is completely volatilized, casting pre-cured PDMS on the printed electrode pattern, and further completely curing to obtain the flexible and stretchable electroencephalogram array.
The photoacoustic imaging system is a commercial near-infrared photoacoustic imaging system, mainly comprises a pulse laser, an ultrasonic signal receiver and a data processing and analyzing module, can perform high-resolution and high-contrast imaging, and can perform clear dynamic monitoring on the blood vessel and the blood oxygen saturation at a wound.
Compared with the prior art, the invention can have the following beneficial effects but not limited to:
(1) the flexible stretchable brain electrode array based on the liquid metal has high biosafety and low elastic modulus, can be tightly attached to the surface of a wound on a cortex layer, and can detect a high-resolution brain electrical signal.
(2) The photoacoustic imaging system is high in detection precision, free of damage to tissues, safe and convenient, and is an important progress of medical imaging auxiliary diagnosis.
(3) The flexible brain electrode array and the photoacoustic imaging system are combined, the problem that intracranial wounds cannot be observed is solved, noninvasive monitoring of the intracranial wounds is achieved, and the monitoring accuracy can even meet the requirements of clinical monitoring indexes.
Drawings
Embodiments of the invention are described in detail below with reference to the attached drawing figures, wherein:
fig. 1 shows a schematic diagram of a liquid metal-based flexible electroencephalogram array employed by the present invention.
FIG. 2 shows the morphology of rat hippocampal cells observed by confocal laser microscopy after 10 days of culture on liquid metal electrodes.
Detailed Description
The invention is further illustrated by the following specific examples, which, however, are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.
This section generally describes the materials used in the testing of the present invention, as well as the testing methods. Although many materials and methods of operation are known in the art for the purpose of carrying out the invention, the invention is nevertheless described herein in as detail as possible. It will be apparent to those skilled in the art that the materials and methods of operation used in the present invention are well within the skill of the art, provided that they are not specifically illustrated.
The reagents and instrumentation used in the following examples are as follows:
reagent:
indium gallium alloy was purchased from Sigma Aldrich, n-decanol, PDMS (Sylgard 184) from Dow Corning.
The instrument comprises the following steps:
an ultrasonic cell disruptor, available from BINEUTINOIN ULTRASONIC CORPORATION, model S-450D;
photoacoustic imaging system, available from VisualSonics, Canada, model Vevo LAZR.
Example 1
This example is used to illustrate the processing and preparation method of the flexible brain electrode array of the present invention, and includes the following steps:
4 g of liquid metal (indium-gallium alloy, gallium mass fraction 75.5%, indium mass fraction 24.5%) and 1 ml of n-decanol were added to a 5 ml centrifuge tube. And (3) carrying out ultrasonic treatment on the liquid metal micro-nano particles for 2 minutes under the intensity of 20% by using an ultrasonic cell disruptor, adding the prepared liquid metal ink to a screen printing template, and printing to obtain a pattern of the electrode array. Then, pre-cured PDMS (PDMS: curing agent: 10: 1) is cast onto the electrode array pattern, the electrodes are placed in an oven at 80 ℃ for curing for 2 hours, and after the PDMS is completely cured, the PDMS is peeled off from the substrate to obtain the flexible brain electrode array. And pouring PDMS on the PET substrate, and after the PDMS is completely cured, removing the PDMS from the substrate to obtain the PDMS as the substrate of the electrode array.
Example 2
The experimental example is used for illustrating that the flexible electrode array is combined with a photoacoustic imaging system to monitor the condition of intracranial wounds, and comprises the following steps:
rats are used as experimental objects, and brain tissue wounds in specific areas of the rats are monitored. After anesthetizing the rat, a 2 cm × 2 cm opening was made in the skull, the dura was removed and the surface layer was completely exposed, the flexible electrode prepared in example 1 was attached to the cerebral cortex, and the flexible electrode was connected to a commercial EEG system to monitor changes in the brain electrical signal in this area. Meanwhile, a photoacoustic imaging system is used for accurately imaging a monitored part in real time, a probe of the photoacoustic imaging system is aligned to the middle area of brain tissue, an electrode array detects peripheral electroencephalogram signals, and the photoacoustic imaging system is used for imaging wounds of the brain tissue in real time. And judging the trauma condition of the brain tissue by comparing the electroencephalogram signal with the photoacoustic image.
Although the present invention has been described to a certain extent, it is apparent that appropriate changes in the respective conditions may be made without departing from the spirit and scope of the present invention. It is to be understood that the invention is not limited to the described embodiments, but is to be accorded the scope consistent with the claims, including equivalents of each element described.
Claims (11)
1. An intracranial wound healing monitoring device, the device comprising: flexible electrode arrays and photoacoustic imaging systems; the flexible electrode array is tightly attached to the surface of the brain tissue wound, so that high-resolution electroencephalogram signals are detected, and meanwhile, the photoacoustic imaging system performs real-time imaging on the brain tissue wound; judging the trauma condition of the brain tissue by comparing the electroencephalogram signal with the photoacoustic image;
wherein the flexible electrode array comprises: the flexible electrode array comprises a substrate and an interconnected lead formed by converging liquid metal particles on the substrate, and is prepared by a method comprising the following steps:
(1) adding liquid metal into an organic solvent, and processing the liquid metal into micro-nano particles to obtain liquid metal ink;
(2) drawing an electrode array pattern by using the liquid metal ink prepared in the step (1), wherein the drawing method of the electrode array pattern is screen printing;
(3) and after the solvent is completely volatilized, casting a pre-cured substrate material on the printed electrode pattern, and obtaining the flexible electrode array after the curing is completely carried out.
2. The apparatus of claim 1, wherein the photoacoustic imaging system is a near-infrared photoacoustic imaging system.
3. The apparatus of claim 2, wherein the photoacoustic imaging system comprises a pulsed laser, an ultrasonic signal receiver, and a data processing and analysis module.
4. The device of claim 1, wherein the substrate material is selected from one or more of the following: PDMS, Ecoflex, water-soluble polyurethane, polylactic acid and polycaprolactone.
5. The device of claim 4, wherein the substrate material is PDMS.
6. The apparatus of claim 1, wherein the liquid metal is selected from one or more of the following: indium gallium alloy, gallium indium tin alloy, bismuth tin alloy.
7. The device of claim 6, wherein the liquid metal is an indium gallium alloy.
8. The device of claim 1, wherein the organic solvent is selected from one or more of: n-decanol, alcohol, acetone, N-dimethylformamide, dichloromethane, trichloromethane and tetrahydrofuran.
9. The apparatus of claim 8, wherein the organic solvent is n-decanol.
10. The apparatus of claim 1, wherein in step (1), the processing is ultrasonic and/or mechanical agitation.
11. Use of a device according to any one of claims 1 to 10 in the manufacture of a medical product for monitoring wound healing.
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| CN110251125A (en) * | 2019-07-12 | 2019-09-20 | 南方科技大学 | A kind of flexible extensible nerve electrode and its preparation method and application |
| CN112120696B (en) * | 2020-09-29 | 2022-04-26 | 中国科学院上海微系统与信息技术研究所 | Method for implanting deep flexible brain electrode combined with drug delivery |
| CN112535531B (en) * | 2020-11-27 | 2022-08-19 | 广东省医疗器械研究所 | Biological tissue welding effect detection device |
| CN112530626B (en) * | 2020-12-04 | 2023-01-06 | 南方科技大学 | Degradable flexible wire and preparation method and application thereof |
| CN114010163B (en) * | 2021-12-02 | 2023-12-19 | 中国中医科学院医学实验中心 | Epidermis cell migration positioning system and method based on optical imaging |
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