CN120345867A

CN120345867A - Multi-mode implantable sensor and signal acquisition system

Info

Publication number: CN120345867A
Application number: CN202510592549.2A
Authority: CN
Inventors: 李楠; 祁柯晖; 王军波; 陈健; 陈德勇
Original assignee: Aerospace Information Research Institute of CAS
Current assignee: Aerospace Information Research Institute of CAS
Priority date: 2025-05-06
Filing date: 2025-05-08
Publication date: 2025-07-22

Abstract

The present application discloses a multimodal implantable sensor and a signal acquisition system, which relates to the field of medical device technology. The multimodal implantable sensor includes: two layers of flexible substrates arranged opposite to each other; a multimodal electronic functional layer located between the two layers of flexible substrates, the multimodal electronic functional layer includes at least two sensors for collecting different biometric signals; the flexible substrate has shape memory capability, which enables the multimodal implantable sensor to be converted from a contracted state to an expanded state. The present application can monitor different biometric signals simultaneously through the same multimodal implantable sensor; it can also achieve morphological switching based on a flexible substrate with shape memory capability, so that the multimodal implantable sensor can be implanted in a small-sized contracted state to reduce implantation trauma, and after the implantation is completed, it can be converted from a contracted state to an expanded state to facilitate the collection of multimodal biometric signals.

Description

Multi-mode implantable sensor and signal acquisition system

The present application claims priority from China patent office, application No. 202510578313.3, filed on day 05 and 06 of 2025, entitled "implantable sensor packaging Structure and biometric Signal acquisition System", the entire contents of which are incorporated herein by reference.

Technical Field

The application relates to the technical field of medical instruments, in particular to a multi-mode implantable sensor and a signal acquisition system.

Background

The implanted sensor is miniaturized sensing equipment, can be implanted into a living body, is used for acquiring biological characteristic signals in real time, and transmits the acquired biological characteristic signals to an external monitor in a wired or wireless mode, and has the core value of tracking target indexes for a long time, in situ and dynamically, so as to provide accurate data support for medical diagnosis.

At present, the packaging structure of the conventional implantable sensor is generally a single-mode design scheme of a tubular structure, namely, the packaging structure of the implantable sensor is formed by integrating a sensor chip for collecting single biological characteristic signals on one rigid catheter, the form of the packaging structure of the implantable sensor is fixed, and a multi-catheter implantation scheme is needed in the use process to realize multi-mode biological characteristic signal collection.

Disclosure of Invention

In view of the above, the present application provides a multi-mode implantable sensor and a signal acquisition system, so as to achieve the purposes of automatically switching modes and acquiring multi-mode biological characteristic signals by a single package structure. The specific scheme is as follows:

The present application provides in a first aspect a multi-modal implantable sensor comprising:

Two layers of flexible substrates arranged oppositely;

The multi-mode electronic functional layer is positioned between the two flexible substrates and comprises at least two sensors for collecting different biological characteristic signals;

wherein the flexible substrate has shape memory capability that enables the multi-modal implantable sensor to transition from a contracted state to an expanded state.

Optionally, in the above multi-mode implantable sensor, the method further includes:

The wireless communication functional layer and the multi-mode electronic functional layer are stacked between the two flexible substrates, and the wireless communication functional layer is electrically connected with the sensor and used for carrying out wireless communication with an external circuit.

Optionally, in the above multi-mode implantable sensor, the wireless communication functional layer includes:

The circuit board is provided with a wireless communication function, and the sensor is electrically connected with the circuit board;

and if the multi-mode implantable sensor is unfolded on one plane, the coils are concentric circles.

Optionally, in the multi-mode implantable sensor, the flexible substrate comprises a plurality of radial supporting arms, wherein one end of each radial supporting arm is connected with the same center position;

If the multi-mode implantable sensor is unfolded on a plane, each radial supporting arm is respectively positioned on different radiuses of the same circular area, the center position is the center of the circular area, and two adjacent radial supporting arms are connected through at least two supporting beams.

Optionally, in the multimode implantable sensor, at least two concentric rings are provided in the circular area, and the intersection points of the circumferences of the concentric rings and the radial support arms are sequentially connected with the support beams.

Optionally, in the above-described multimode implantable sensor, the support beam is a serpentine trace connected between two radial support arms.

Optionally, in the above-described multi-modal implantable sensor, the multi-modal electronic functional layer includes a plurality of sensor assemblies;

The sensor assembly comprises at least two sensors for acquiring different biometric signals;

the sensor assembly is positioned between two flexible substrate stacks with opposed radial support arms.

Optionally, in the multi-mode implantable sensor, the sensor assembly comprises a circular detection area, N sensors are arranged in the circular detection area, each sensor is used for collecting different biological characteristic signals, N is a positive integer greater than 1, the circular detection area is opposite to the end part of the radial supporting arm, which is far away from the center position, wherein,

The circular detection area is divided into N+1 sector areas, N of the N+1 sector areas are used for respectively setting one sensor, and the rest sector areas are used for setting signal lines connected with the sensors;

Or, the circular detection area is divided into N concentric ring detection areas, and the N concentric ring detection areas are respectively used for arranging a sensor.

Optionally, in the multi-mode implantable sensor, the flexible substrate automatically changes from a contracted state to an expanded state when the glass transition temperature of the flexible substrate meets the glass transition temperature of the self material, wherein the glass transition temperature of the flexible substrate ranges from 35 ℃ to 45 ℃;

or the multi-mode implantable sensor further comprises a visual marking layer, wherein the visual marking layer is used for displaying the unfolding state of the multi-mode implantable sensor;

or, the thickness of the two layers of flexible substrates is different;

Or, the thickness ratio of the two layers of flexible substrates is not less than 2;

alternatively, the material of the flexible substrate is a biodegradable polymer.

A second aspect of the present application provides a signal acquisition system comprising:

A multi-modal implantable sensor according to any one of the preceding claims;

the external monitor is in communication connection with the multi-mode implantable sensor.

By means of the technical scheme, at least two sensors for collecting different biological characteristic signals are integrated in the multi-mode implanted sensor at the same time, the multi-mode biological characteristic signals can be collected through the same multi-mode implanted sensor, different biological characteristic signals can be monitored through the same multi-mode implanted sensor at the same time, multi-catheter implantation is not needed, and the problems of large implantation wound, high infection risk and the like caused by multi-catheter implantation can be avoided. The multi-mode implantable sensor can be switched from a contracted state to an expanded shape based on a flexible substrate with shape memory capability, so that the multi-mode implantable sensor can be implanted in the contracted state with a small size to reduce implantation trauma, and the multi-mode implantable sensor can be converted from the contracted state to the expanded state by utilizing the shape memory capability of the flexible substrate after implantation is completed, so that acquisition of multi-mode biological characteristic signals is facilitated.

Drawings

In order to more clearly illustrate the embodiments of the present application or the technical solutions in the related art, the drawings required for the description of the embodiments or the prior art will be briefly described below, and it is apparent that the drawings in the following description are only embodiments of the present application, and other drawings may be obtained according to the provided drawings without inventive effort to those skilled in the art.

The structures, proportions, sizes, etc. shown in the drawings are shown only in connection with the present disclosure, and therefore should not be construed as limiting the application, but rather as limiting the scope of the application, so that any structural modifications, proportional changes, or dimensional adjustments should fall within the scope of the application without affecting the efficacy or achievement thereof.

FIG. 1 is a cross-sectional view of a multi-modal implantable sensor according to an embodiment of the present application;

FIG. 2 is a cross-sectional view of another multi-modal implantable sensor according to an embodiment of the present application;

fig. 3 is a top view of a wireless communication functional layer according to an embodiment of the present application;

FIG. 4 is a cross-sectional view of a multi-modal implantable sensor according to an embodiment of the present application;

FIG. 5 is a top view of a flexible substrate according to an embodiment of the present application, and FIG. 5 is a top view of the flexible substrate in an unfolded state;

FIG. 6 is a partial top view of a flexible substrate according to an embodiment of the present application;

FIG. 7 is an exploded view of a sensor package structure according to an embodiment of the present application;

FIG. 8 is a top view of a multi-modal electronic functional layer according to an embodiment of the present application;

FIG. 9 is an enlarged partial top view of a sensor assembly according to an embodiment of the present application;

FIG. 10 is an enlarged partial top view of another sensor assembly provided in accordance with an embodiment of the present application;

Fig. 11 is a schematic structural diagram of a signal acquisition system according to an embodiment of the present application;

FIG. 12 is a schematic diagram of a multi-modal implantable sensor implantation principle of a signal acquisition system prior to signal acquisition according to an embodiment of the present application;

fig. 13 is a schematic diagram of an operating principle of a signal acquisition system according to an embodiment of the present application.

Reference numerals:

100-multi-mode implantable sensor, 101-first flexible substrate, 1011-radial support arm, 1012-support arm, 1013-node position, 1014-circular area, 1015-center position, 1016-concentric circular ring, 102-multi-mode electronic function layer, 1020-sensor assembly, 1021-pressure sensor, 1022-temperature sensor, 1023-pH sensor, 1024-passive electrode array, 1025-active electrode array, 1026-signal wire, 103-visual label layer, 104-wireless communication function layer, 1041-coil, 1042-circuit board, 105-second flexible substrate, 106-sensor, 107-circular detection area, 108-trace area, 109-sector area, 110-concentric circular ring detection area, 200-monitor, 201-wireless reading module, 202-cable, 203-display instrument.

Detailed Description

Embodiments of the present application will now be described more fully hereinafter with reference to the accompanying drawings, in which embodiments of the application are shown. As one of ordinary skill in the art can know, with the development of technology and the appearance of new scenes, the technical scheme provided by the embodiment of the application is also applicable to similar technical problems.

The intracranial monitoring technology refers to technology for monitoring intracranial physiological, biochemical or electrophysiological parameters in real time by invasive or non-invasive means, and is mainly used for evaluation of neurological severe and epileptic surgery and brain function research. Clinically, traditional monitoring techniques, such as electroencephalogram (EEG), intracranial pressure (ICP) monitoring, cerebral blood oxygen saturation, cerebral blood flow assessment, etc., provide great assistance to clinicians in clinical decisions and interventions.

Traditional intracranial monitoring relies on invasive ventricular catheters or optical fiber probes, and has the problems of high infection rate (more than 45 percent), easy drifting and the like. The existing wireless implantable sensor has single function, lacks multi-parameter collaborative analysis capability, and the nondegradable material needs to be taken out by secondary operation, so that the risk of a patient is increased. In addition, the existing equipment is difficult to distinguish different encephalopathy characteristics (such as pH difference between cerebral edema and cerebral hemorrhage), and limits the accuracy of clinical decision.

In view of this, the embodiment of the present application provides a multi-mode implantable sensor, which belongs to the fields of biomedical engineering, microelectronic technology and intelligent medical equipment intersection, and the implantable sensor packaging junction includes:

Two layers of flexible substrates arranged oppositely;

In the embodiment of the application, at least two sensors for collecting different biological characteristic signals are integrated in the multi-mode implantable sensor, the multi-mode biological characteristic signals can be collected through the same multi-mode implantable sensor, different biological characteristic signals can be monitored through the same multi-mode implantable sensor, multi-catheter implantation is not needed, and the problems of large implantation wound, high infection risk and the like caused by multi-catheter implantation can be avoided.

The multi-mode implantable sensor can be switched from a contracted state to an expanded shape based on a flexible substrate with shape memory capability, so that the multi-mode implantable sensor can be implanted in the contracted state with a small size to reduce implantation trauma, and the multi-mode implantable sensor can be converted from the contracted state to the expanded state by utilizing the shape memory capability of the flexible substrate after implantation is completed, so that acquisition of multi-mode biological characteristic signals is facilitated.

Furthermore, at least the flexible substrate in the multi-mode implantable sensor can be made of biodegradable materials, and a structural member prepared from the biodegradable materials is not required to be taken out by secondary operation, so that secondary operation wounds can be reduced.

It should be noted that, in the embodiment of the present application, the intracranial biological characteristic signal collection is taken as an example for illustration, and it is easy to know that the multi-mode implantable sensor in the embodiment of the present application is not limited to intracranial biological characteristic signal collection, but can also be used for collecting biological characteristic signals of other parts, such as biological characteristic signal collection of abdominal cavity or thoracic cavity, etc., and the embodiment of the present application does not limit the application scenario of the multi-mode implantable sensor.

In order that the above-recited objects, features and advantages of the present application will become more readily apparent, a more particular description of the application will be rendered by reference to specific embodiments thereof which are illustrated in the appended drawings.

Referring to fig. 1, fig. 1 is a sectional view of a multi-modal implantable sensor in a thickness direction according to an embodiment of the present application, wherein the multi-modal implantable sensor 100 includes:

Two flexible substrates disposed opposite to each other, the flexible substrates may be set to be the first flexible substrate 101 and the second flexible substrate 105, respectively;

A multi-modal electronic functional layer 102 between the two flexible substrates, the multi-modal electronic functional layer 102 comprising at least two sensors 106 for acquiring different biometric signals;

Wherein the flexible substrate has shape memory capability that enables the multi-modal implantable sensor 100 to transition from a contracted state to an expanded state.

As shown in fig. 1, a first flexible substrate 101, a multi-mode electronic function layer 102, and a second flexible substrate 105 are sequentially stacked in the vertical direction in fig. 1. The two layers of flexible substrates not only can realize the form switching of the multi-mode implantable sensor, but also can carry out encapsulation protection on the multi-mode electronic functional layer 102 between the two layers.

At least two sensors for collecting different biological characteristic signals are integrated in the multi-mode implantable sensor 100 at the same time, the multi-mode biological characteristic signals can be collected through the same multi-mode implantable sensor 100, different biological characteristic signals can be monitored through the same multi-mode implantable sensor at the same time, multi-catheter implantation is not needed, and the problems of large implantation wound, high infection risk and the like caused by multi-catheter implantation can be avoided.

The multi-mode implantable sensor 100 can be switched from a contracted state to an expanded state based on a flexible substrate with shape memory capability, so that the multi-mode implantable sensor 100 can be implanted in the contracted state with a small size to reduce implantation trauma, and the multi-mode implantable sensor can be converted from the contracted state to the expanded state by utilizing the shape memory capability of the flexible substrate after implantation is completed, so as to facilitate acquisition of multi-mode biological characteristic signals.

The multi-mode implantable sensor provided by the embodiment of the application can be used for long-term real-time monitoring of intracranial physiological signals, and can provide differential diagnosis support for cerebral trauma, epilepsy and other diseases based on various acquired biological characteristic signals.

Referring to fig. 2, fig. 2 is a cross-sectional view of another multi-mode implantable sensor according to an embodiment of the present application in a thickness direction, and on the basis of other embodiments, the multi-mode implantable sensor 100 shown in fig. 2 further includes a wireless communication functional layer 104, where the wireless communication functional layer 104 and the multi-mode electronic functional layer 102 are stacked between two flexible substrates, and the wireless communication functional layer 104 is electrically connected to the sensor and is used for performing wireless communication with an external circuit.

As shown in fig. 2, a first flexible substrate 101, a multi-mode electronic function layer 102, a wireless communication function layer 104, and a second flexible substrate 105 are sequentially stacked in the vertical direction in fig. 2. Alternatively, the stacking order of the wireless communication functional layer 104 and the multi-mode electronic functional layer 102 between the two flexible substrates may be adjusted according to the requirements, and is not limited to the stacking order shown in fig. 2, and the stacking order of the wireless communication functional layer 104 and the multi-mode electronic functional layer 102 may be adjusted in the structure shown in fig. 2.

The manufacturing method of the wireless communication functional layer 104 comprises the steps of forming a loop antenna by laser etching copper foil on a PDMS substrate, and welding an NFC chip and a packaging capacitor to form a circuit board 1042 for NFC communication. The receiving coil 1041 can be used for preparing a magnesium layer by magnetron sputtering, and is engraved into a planar spiral structure by ultraviolet laser and connected with the sensor layer by conductive silver adhesive.

Referring to fig. 3, fig. 3 is a top view of a wireless communication functional layer according to an embodiment of the present application, and fig. 3 is a top view of the wireless communication functional layer 104 when in an unfolded state, that is, a top view of the wireless communication functional layer 104 when unfolded to a planar state. Based on other embodiments, the wireless communication functional layer 104 shown in fig. 3 includes a circuit board 1042 having a wireless communication function, the sensor is electrically connected to the circuit board 1042, a plurality of coils 1041 surrounding the circuit board 1042, the coils 1041 are used to form an annular magnetic field, and if the multi-mode implantable sensor 100 is deployed on a plane, the plurality of coils 1041 are concentric rings.

The circuit board 1042 in the wireless communication functional layer 104 includes an NFC chip and a ceramic capacitor. The wireless communication functional layer 104 can be coupled with an external wireless reading module to realize wireless energy supply and data return of a near transmission distance. The non-degradable circuit board 1042 can be encapsulated in the PBAT-iodixanol composite layer, and the circuit board 1042 can be taken out through a minimally invasive incision after the biodegradable materials such as the flexible substrate and the like are decomposed in organisms after operation.

Alternatively, the coil 1041 may be a magnesium coil. The magnesium material is not only biocompatible but also biodegradable, so that the magnesium coil can be lowered in vivo after a certain period of use, thereby reducing the volume of the multi-modal implantable sensor 100 removed after use.

The coil 1041 of which the wireless communication function layer 104 has a plurality of concentric ring structures may be set as required, and the number of coils 1041 is not limited to two as shown in fig. 3. Optionally, as described below, the number of coils 1041 in the wireless communication functional layer 104 may correspond to the number of concentric rings in the flexible substrate used to form the support beams 1012, the coils 1041 may be encapsulated and protected based on the concentric rings in the flexible substrate where the support beams 1012 are located, and when the flexible substrate and the coils 1041 are both biodegradable materials, the coils 1041 may be degraded after the flexible substrate is degraded, so that the coils 1041 can complete a signal acquisition cycle of a desired duration.

Referring to fig. 4, fig. 4 is a sectional view of a thickness direction of a multi-mode implantable sensor according to another embodiment of the present application, and on the basis of other embodiments, the multi-mode implantable sensor 100 shown in fig. 4 further includes a visual marker layer 103, where the visual marker layer 103 is used to show an expanded state of the multi-mode implantable sensor 100, and may be used to track an expanded state of a device in real time.

As shown in fig. 4, a first flexible substrate 101, a multi-mode electronic function layer 102, a visual marking layer 103, a wireless communication function layer 104, and a second flexible substrate 105 are sequentially stacked in the vertical direction in fig. 4. Alternatively, the stacking order of the multi-mode electronic functional layer 102, the visual marking layer 103, and the wireless communication functional layer 104 between the two flexible substrates may be adjusted according to the need, and is not limited to the stacking order shown in fig. 4, and the stacking order of the multi-mode electronic functional layer 102, the visual marking layer 103, and the wireless communication functional layer 104 may be arbitrarily adjusted in the structure shown in fig. 4.

The visual marker layer 103 may include an X-ray sensitive material, which has a high absorption and/or scattering effect on X-rays, and under the irradiation of X-rays, the multi-mode implantable sensor 100 may have a significant contrast with the implanted biological tissue, so that the multi-mode implantable sensor 100 may be used to show the unfolded state of the multi-mode implantable sensor 100 after implantation.

The visual marker layer 103 is not limited to exhibiting the deployment state of the multi-modal implantable sensor 100 by an X-ray sensitive material, but may be used to exhibit the deployment state of the multi-modal implantable sensor 100 by other visual marker principles, such as by a terahertz wave sensitive material, to exhibit the deployment state of the multi-modal implantable sensor 100 after implantation based on terahertz waves, or by an ultrasound sensitive material, to exhibit the deployment state of the multi-modal implantable sensor 100 after implantation based on ultrasound, or by a material capable of emitting fluorescence of a specific wavelength band, based on which fluorescence of the multi-modal implantable sensor 100 after implantation.

Alternatively, when the visual marker layer 103 is made of a non-biodegradable material, in order to facilitate the electronic components made of the non-biodegradable material such as the sensor 106 in the multi-mode electronic functional layer 102 and the circuit board 1042 in the wireless communication functional layer 104 to be taken out of the living body together with the visual marker layer 103 after use, the multi-mode electronic functional layer 102 and the wireless communication functional layer 104 may be disposed on one side surface of the visual marker layer 103, that is, the multi-mode electronic functional layer 102, the visual marker layer 103 and the wireless communication functional layer 104 are sequentially stacked, and the positions of the multi-mode electronic functional layer 102 and the wireless communication functional layer 104 may be interchanged.

Referring to fig. 5, fig. 5 is a top view of a flexible substrate according to an embodiment of the present application, and fig. 5 is a top view of the flexible substrate when in an unfolded state, that is, a top view of the flexible substrate when unfolded to a planar state. In other embodiments, the flexible substrate shown in fig. 5 includes a plurality of radial support arms 1011, wherein one end of each radial support arm 1011 is connected to the same central position 1015, the radial support arms 1011 are connected by support beams 1012, if the multi-mode implantable sensor 100 is deployed on a plane, each radial support arm 1011 is located on a different radius of the same circular area 1014, the central position 1015 is the center of the circular area 1014, and two adjacent radial support arms 1011 are connected by at least two support beams 1012.

When integrated with the wireless communication functional layer 104 described above, the multi-modal implantable sensor 100 achieves functional partitioning by the flexible substrate acting as a chassis in combination with mechanical coupling of the support beams 1012 in the flexible substrate. The flexible substrate central region may be used to house a rigid circuit board 1042, the middle loop may be used to house coils 1041, the circular distal ends of the radial support arms 1011 on the outer ring may be used to house pressure sensors 1021, pH sensors 1023, and temperature sensors 1022 for monitoring stress and metabolic indicators, and the circular distal ends are also house a high density passive electrode array 1024 and active electrode array 1025 for capturing neuro-electrical activity. The arcuate design of the support beam 1012 can be used not only to provide a deployment driving force, but also to form a toroidal magnetic field as a carrier for the coil 1041 for optimizing wireless energy transfer efficiency.

Alternatively, the line width of the radial support arm 1011 may be 0.5mm to 2mm, such as 0.51mm, or 0.8mm, or 1mm, or 1.52mm, or 1.69mm, or the like. In the line width range, not only can the effective encapsulation protection of other film layers between two layers of flexible substrates be realized, but also the flexible substrate has good shape memory capability.

Alternatively, the linewidth of the support beams 1012 is less than the linewidth of the radial support arms 1011. The line width of the support beam 1012 may be 100 μm to 500 μm, for example 110 μm, 121 μm, 150 μm, 300 μm, 355 μm, 400 μm, or the like. This approach may provide greater shape memory in the radial direction by radial support arms 1011 of greater linewidth, less shape memory by support beams 1012 of lesser linewidth intersecting the radial direction, and increased tensile strain that each film can withstand when laminated.

The number of the radial support arms 1011 may be set to any number according to the need, and is not limited to six as shown in fig. 5, but may be any number of three, five, 8, or the like, and the number of the radial support arms 1011 is not limited in the embodiment of the present application.

Alternatively, each radial support arm 1011 may be the same length and uniformly distributed within circular region 1014 to facilitate the process preparation of the flexible substrate. In other embodiments, the length of each radial support arm 1011 may be different and/or each radial support arm 1011 may be unevenly distributed within the circular region 1014.

If the multi-modal implantable sensor 100 is deployed in a single plane, in the flexible substrate of the structure shown in fig. 5, each radial support arm 1011 extends from a central location 1015 to the periphery along a different radial direction of the circular region 1014, and two adjacent radial support arms 1011 are connected by at least two support beams 1012. Wherein support beam 1012 and radial support arm 1011 are connected at node location 1013. At node locations 1013 of support beam 1012 and radial support arm 1011, such that radial support arm 1011 may form a grid structure with support beam 1012, the grid structure having the mechanical topology of the tent frame. The mesh structure after deployment may conform to a better conformal coverage over the surface of the biological tissue to be examined based on the flexible and bendable nature.

Optionally, the node locations 1013 are embedded with Polycaprolactone (PCL) fixation rings, which may be integrated with degradable electronics layers (e.g., magnesium coils and magnesium wires, etc.) by a heat sealing process, ensuring mechanical stability. The outer surface of the flexible substrate may be coated with a bio-lubricating layer, the components of which include glyceryl hydrogels, which ensure smooth spreading of the flexible substrate on the tissue surface within the living body by reducing the surface friction coefficient of the flexible substrate, avoiding mechanical damage.

The first flexible substrate 101 and the second flexible substrate 105 have the same pattern structure in plan view and are disposed opposite to each other so that they can be completely overlapped in the plane-spread state. In this way, the first flexible substrate 101 and the second flexible substrate 105 encapsulate and protect other film structures located therebetween by a lamination process.

In the manner shown in fig. 5, the pattern structure of the film layer and the pattern structure of the flexible substrate are encapsulated between two layers of flexible substrates, so that the multi-mode implantable sensor 100 with a grid structure can be formed, the multi-mode implantable sensor 100 is a novel multi-mode heterogeneous encapsulation structure, and synchronous acquisition of multiple biological characteristic signals can be realized on the same base frame (namely, two layers of flexible substrates which are oppositely arranged).

Alternatively, as shown in fig. 5, at least two concentric rings 1016 are provided in the circular region 1014, and support beams 1012 are sequentially connected to the intersections of the circumferences of the concentric rings 1016 and the respective radial support arms 1011. The intersection of the circumference of concentric ring 1016 with each radial support arm 1011 forms node position 1013. Concentric ring 1016 has the same center as circular region 1014. In this way, the radial support arms 1011 are constructed and connected based on the concentric rings 1016 in the circular region 1014, so that the grid structure can be formed, the multi-mode implantable sensor 100 can be better unfolded based on the mechanical topology of the grid structure, and the multi-mode implantable sensor 100 can be better covered and attached on the surface of the biological tissue to be detected based on the self-set flexibility characteristic and the mechanical topology of the grid structure.

In the embodiment of the application, the flexible substrate is made of biodegradable materials, and is integrated with a plurality of different sensors, so that the same kind of different biological characteristic signals can be collected at one time, the advantages of high integration level, small wound surface and the like are achieved, and implantation wounds and infection risks can be remarkably reduced.

In one embodiment, as shown in FIG. 5, each support beam 1012 may be an arc that matches the circumference of the concentric ring 1016.

Referring to fig. 6, fig. 6 is a partial top view of a flexible substrate according to an embodiment of the present application, and fig. 6 is a top view of two adjacent radial support arms 1011 and a connected support beam 1012 when the flexible substrate is in a unfolded state, that is, a top view of two adjacent radial support arms 1011 and a connected support beam 1012 when the flexible substrate 104 is unfolded to a planar state. Unlike the approach shown in fig. 5, in the approach shown in fig. 6, the support beam 1012 is a serpentine trace connected between two radial support arms 1011. The supporting beam 1012 adopts a snake-shaped wiring, and can bear higher tensile strain when being packaged, so that the multi-mode implantable sensor 100 can be packaged in a laminated mode through two layers of flexible substrates after each layer of structures are sequentially laminated, and the problem that the supporting beam 1012 is cracked or broken due to larger tensile strain in the lamination process is avoided.

Referring to fig. 7, fig. 7 is an exploded view of a sensor package structure according to an embodiment of the present application. The multi-modal implantable sensor 100 shown in fig. 7 includes, on the basis of other embodiments, two flexible substrates disposed opposite each other, a multi-modal electronic functional layer 102, a visual marker layer 103, and a wireless communication functional layer 104 laminated in this order between the two flexible substrates.

The two-layer flexible substrate is configured as the base frame of the multi-modal implantable sensor 100. The thickness of the flexible substrate may range from 10 μm to 200 μm, alternatively, the thickness of the flexible substrate may be 30 μm, or 50 μm, or 61 μm, or 100 μm, or 122 μm, or 150 μm, etc. The thickness value of the flexible substrate is set in the thickness range, so that not only can other film structures between the two flexible substrates be effectively packaged and protected through the two flexible substrates, but also the substrate frame has good shape memory capability.

At least the multi-mode electronic function layer 102 may be sealed between the first flexible substrate 101 and the second flexible substrate 105, and further, at least one of the visual marking layer 103 and the wireless communication function layer 104 may be sealed between the first flexible substrate 101 and the second flexible substrate 105. If the multi-mode electronic functional layer 102, the visual marking layer 103 and the wireless communication functional layer 104 are sequentially laminated between the first flexible substrate 101 and the second flexible substrate 105, the lamination order of the multi-mode electronic functional layer 102, the visual marking layer 103 and the wireless communication functional layer 104 between the first flexible substrate 101 and the second flexible substrate 105 can be set according to the requirement, and is not limited to the mode shown in fig. 7.

In the embodiment of the application, the graphic structures of the radial supporting arm 1011 and the supporting beam 1012 can be optimized, so that the flexible substrate has gradual shape memory capability from the central position 1015 to the peripheral edge, for example, the shape memory capability of the flexible substrate can be gradually reduced or gradually increased from the central position 1015 to the peripheral edge, so that the unfolding stress of the flexible substrate can be gradually changed from the central position 1015 to the peripheral edge, and the multi-mode implantable sensor 100 can be enabled to be in a three-dimensional unfolding with a certain bulge or a certain depression instead of a flat plane unfolding, and can be better conformally covered on the surface of biological tissues with curved surfaces in combination with the self flexible attribute.

For the same layer of flexible substrate, the line widths of the support beams 1012 on the concentric rings 1016 can be set to be gradually changed along the radial direction so as to realize that the unfolding stress of the flexible substrate is gradually changed along the radial direction from the central position 1015 to the peripheral edge, or the line widths of the radial support beams 1011 can be set to be gradually changed along the radial direction so as to realize that the unfolding stress of the flexible substrate is gradually changed along the radial direction from the central position 1015 to the peripheral edge, or the line widths of the support beams 1012 on the concentric rings 1016 and the line widths of the radial support beams 1011 are simultaneously set to be gradually changed along the radial direction so as to realize that the unfolding stress of the flexible substrate is gradually changed along the radial direction from the central position 1015 to the peripheral edge.

Optionally, in another embodiment, the flexible substrate is automatically converted from the contracted state to the expanded state when the glass transition temperature of the material of the flexible substrate is satisfied, the glass transition temperature range of the flexible substrate is 35 ℃ to 45 ℃, and the temperature range can be switched by automatically triggering the state through the temperature in the living body. In this manner, the glass transition temperature of the flexible substrate can be automatically switched from the contracted state to the expanded state by exciting the flexible substrate through the body temperature of the living body, that is, the state switching of the multi-mode implantable sensor 100 can be realized through the property that the shape memory capacity of the flexible substrate material is related to the temperature, and the power device for consuming electric energy is not required to be additionally configured, so that the energy consumption can be reduced.

Alternatively, in one embodiment, the two flexible substrates are different in thickness, based on other embodiments. In this way, the thickness of the two flexible substrates can be designed differently, so that the shape memory capacities of the two flexible substrates are different. In this manner, the multi-mode implantable sensor 100 may be configured to be convex toward one of the flexible substrates during state transition based on the difference in shape memory capabilities of the two flexible substrates, so that the deployed state has a curved surface with a specific convex direction, and thus the surface of the biological tissue with the curved surface is covered with a better conformal shape.

Further, when the thicknesses of the two flexible substrates are different, the thickness ratio of the two flexible substrates may be made not less than 2. As may be provided that the first flexible substrate 101 has a first thickness and the second flexible substrate 105 has a second thickness, and the second thickness is at least twice the first thickness. In this way, the multi-modal implantable sensor 100, when switched to the deployed state, may cause the first flexible substrate 101 to form a convex structure on a side surface facing away from the second flexible substrate 105, and the second flexible substrate 105 to form a concave structure on some surfaces facing away from the first flexible substrate 101. When information is collected, the concave structure of the second flexible substrate 105 can cover the surface of the biological tissue with the convex structure, so that the effective contact area between the multi-mode implantable sensor 100 and the surface of the biological tissue can be increased, and the sensitivity and accuracy of information collection can be improved.

Alternatively, in one embodiment, the two flexible substrates may be made of different materials having different shape memory capabilities, such as the first flexible substrate 101 being made of a first material having a first shape memory capability, and the second flexible substrate 105 being made of a geothermal material having a second shape memory capability, the first and second materials being different. When the two flexible substrates have the same pattern structure, the first memory capacity is different from the second memory capacity.

Alternatively, in one embodiment, the material of the flexible substrate is a biodegradable polymer, based on other embodiments. Thus, after information collection is completed, the flexible substrate can be automatically degraded in the organism, so that the volume of the multi-mode implantable sensor 100 after use is reduced, and the postoperative extraction wound can be reduced.

The degradation period of the biodegradable polymer for preparing the flexible substrate can be 6-12 months, the required degradation period is long, long-term monitoring can be realized in the degradation period, and when the biodegradable polymer is used for brain signal acquisition, the time length can meet the signal acquisition period requirement of brain tumors so as to ensure the whole treatment process coverage, and the problem that the conventional multi-mode implanted sensor cannot continuously monitor for a long time is solved.

Alternatively, in one embodiment, the two flexible substrates may be the same material. For example, the flexible substrate material may be polylactic acid-caprolactone copolymer/polylactic acid-glycolic acid copolymer (PLCL-PLGA), thereby forming a base frame of a bilayer PLCL-PLGA. In the embodiment of the application, the materials of the two flexible substrates can also be different. Materials for preparing the degradable flexible substrate include, but are not limited to, PLCL-PLGA, but can also be other polymer materials, which are not limited in this embodiment of the application.

PLCL-PLGA is a biodegradable material, has a shape memory effect, and a flexible substrate prepared based on the material has good shape memory capacity, has a glass transition temperature of 35-45 ℃, and can form a shape memory main body with thermal response characteristics. The flexible substrate prepared based on the material not only has the biodegradability but also has the shape memory capability. Based on the shape memory capability of the flexible substrate, the multi-mode implantable sensor 100 can be implanted in a living body in a contracted state with a small volume, minimally invasive channel implantation can be realized, and the implantation can be automatically switched from the contracted state to an expanded state based on the memory capability of the material after the implantation is completed, so that the surface of biological tissue (such as the surface of cerebral cortex) is covered conformally, and an effective biological characteristic signal is realized by better covering the surface of the tissue to be detected.

In addition, because PLCL-PLGA is a biodegradable material, the degradation period can be matched with the healing period of organism tissues, and signal acquisition in the whole treatment process can be realized.

In an embodiment of the present application, the biodegradable flexible substrate may be prepared by using PLCL-PLGA as a main body and through precise solution blending and spin coating, and the preparation method includes mixing PLGA (lactic acid: glycolic acid=85:15) and PLCL (lactic acid: caprolactone=50:50) in a weight ratio of 1:1, dissolving in a 20wt% chloroform solution, and spin coating at a rotating speed on a glass substrate subjected to silanization treatment (trichlorooctadecylsilane) to form a micrometer thick film. The base frame adopts a double-layer laminated structure, and the two flexible substrates are PLCL-PLGA layers with radial net structures. Through holes can be formed at corresponding positions of the first flexible substrate 101 to realize electrical connection, a polybutylene adipate terephthalate (PBAT) containing 30wt% of iodixanol can be inserted between the two flexible substrates as an X-ray sensitive visual marking layer 103, and three-layer sealing is realized through hot pressing at 80 ℃, namely, the three-layer structure of the two flexible substrates and the visual marking layer 103 seals other film layers.

The method of manufacturing the X-ray sensitive visual marking layer 103 comprises forming a film from a blend of polybutylene adipate-terephthalate (PBAT) and iodixanol (3:1 weight ratio) disposed between the multi-modal electronic functional layer 102 and the wireless communication functional layer 104, the high atomic number of iodixanol causing it to exhibit significant contrast under X-rays.

The multi-mode implantable sensor 100 with the structure shown in fig. 7 can adopt a layered hot-press assembly process, and the multi-layer heterogeneous integration technology ensures the mechanical reliability of the multi-mode implantable sensor 100 when folded and realizes the biodegradation synchronicity control after implantation. In the flexible substrate, the hydrolysis (ester bond fracture) of PLGA chain segments and enzymolysis (lipase catalysis) of PLCL cooperate to realize gradient degradation in matching with tissue healing period, so that the sensor is gradually softened and disintegrated in vivo for 6-8 weeks, after the flexible substrate is degraded, magnesium materials in the sensor can be dissolved in 4 weeks through electrochemical corrosion (Mg & gtMg & lt 2+ & gt & lt 2 & gte-) and the silicon nano-film is hydrolyzed to generate silicic acid, and finally the silicic acid is metabolized to be discharged into urine. The design of the mode breaks through the rigidity limitation of the traditional implanted sensor, realizes full-period intellectualization of implantation-functionalization-disappearance through integration of biomechanics, transient electronics and wireless energy supply technology, and provides a novel product structure with both minimally invasive performance, multi-mode perception and biosafety for in vivo implantation type diagnosis and treatment (such as encephalopathy diagnosis and treatment).

Referring to fig. 8, fig. 8 is a top view of a multi-mode electronic functional layer according to an embodiment of the present application, and fig. 8 is a top view of the multi-mode electronic functional layer 102 when in an unfolded state, that is, a top view of the multi-mode electronic functional layer 102 when unfolded to a planar state. In other embodiments, the multi-modal electronic functional layer 102 includes a plurality of sensor assemblies 1020, and the sensor assemblies 1020 include at least two sensors 106 for acquiring different biometric signals, as shown in FIG. 8.

As shown in connection with fig. 7 and 8, the sensor assembly 1020 is positioned between two opposed radial support arms 1011 of the flexible substrate stack. For example, the first flexible substrate 101 and the second flexible substrate 105 each have six radial support arms 1011, and the radial support arms 1011 in the first flexible substrate 101 and the second flexible substrate 105 are stacked one on top of the other. The sensor assembly 1020 may be disposed between radial support arms 1011 disposed opposite the first flexible substrate 101 and the second flexible substrate 105. In this way, packaging protection for each sensor assembly 1020 is achieved by stacking opposing radial support arms 1011 in two layers of flexible substrate.

Referring to fig. 9, fig. 9 is a partially enlarged top view of a sensor assembly according to an embodiment of the present application, where, based on other embodiments, the sensor assembly 1020 shown in fig. 9 includes a circular detection area 107, where the circular detection area 107 is provided with N sensors 106, each sensor 106 is used to collect different biometric signals, N is a positive integer greater than 1, the circular detection area 107 is opposite to an end of the radial support arm 1011 away from the center, where the circular detection area 107 is divided into n+1 sectors 109, N of the n+1 sectors are used to set one sensor 106 respectively, and the remaining one sector 109 is used to set a signal line 1026 to which each sensor 106 is connected, and fan-out wiring of each sensor 106 is implemented through the sector 109.

Alternatively, the signal line 1026 may be a magnesium wire. The magnesium material is not only biocompatible but also biodegradable, so that the magnesium wire can be reduced in vivo after a certain period of use, thereby reducing the volume of the multi-modal implantable sensor 100 that is removed after use.

The structure of the sensor 106 is not limited to the circular structure shown in fig. 9, and the pattern structure thereof may be designed into a fan-shaped structure having the same or approximately the same shape as the fan-shaped region 109, so as to increase the effective detection area of the sensor 106, increase the intensity of the acquired signal, and increase the detection sensitivity and accuracy.

The sensor assembly 1020 also includes a routing area 108 that is connected to the circular detection area 107. The routing area 108 is located between the radial support arms 1011 opposite to the two layers of flexible substrates, and the routing area 108 is protected by packaging the radial support arms 1011 opposite to the two layers of flexible substrates.

As shown in connection with fig. 7-9, on the surface of the trace area 108, the signal lines 1026 to which the respective sensors 106 are connected may extend along the length of the radial support arm 1011 toward the central region of the multi-mode implantable sensor 100 where they are electrically connected via the conductive vias to the circuit board 1042.

Alternatively, in the manner shown in fig. 9, the sector area 109 for disposing the signal line 1026 and the trace area 108 are disposed directly opposite to each other, that is, a bisector of the central angle of the sector area 109 coincides with a center line parallel to the longitudinal direction in the trace area 108 to which it is connected.

Alternatively, in one embodiment, the at least two sensors 106 in the multi-modal implantable sensor 100 may include at least two of a pressure sensor 1021, a temperature sensor 1022, a pH sensor 1023, a passive electrode array 1024, and an active electrode array 1025, among other embodiments. In other ways, at least two of the sensors 106 in the multimodal implantable sensor 100 may also include other types of sensors, such as at least one of a blood glucose sensor, a lactate sensor, a neurotransmitter sensor, an inflammation marker sensor, and a tumor marker sensor.

Optionally, the pressure sensor 1021 can be formed based on a boron doped silicon nano-film, the pressure sensor 1021 can sense mechanical deformation of tissue (such as brain tissue) in a living body by utilizing a piezoresistance effect, and when the pressure sensor 1021 is used for acquiring intracranial biological characteristic signals, intracranial pressure change or vascular pulsation can be detected, and a linear response range covers 0-15% strain.

The manufacturing method of the pressure sensor 1021 comprises the steps of spin coating photoresist on the surface of an SOI wafer, forming a micropore array through ultraviolet exposure and development, performing reactive ion etching to penetrate through a silicon layer by using mixed gas of sulfur hexafluoride and oxygen, and removing a silicon dioxide release silicon nano film on the bottom layer through hydrofluoric acid wet etching. Transferring the nano film to a Polyimide (PI)/silicon temporary substrate through a Polydimethylsiloxane (PDMS) transfer table, performing magnetron sputtering to deposit a magnesium layer as a signal line 1026 connected with a pressure sensor 1021, forming a strain sensitive area through negative photoresist lithography, and finally coating a PBAT-iodixanol protective layer.

Alternatively, the temperature sensor 1022 may be formed based on a magnesium sheet resistance, and the temperature sensor 1022 may enable short-term body temperature monitoring through oxidative degradation characteristics of magnesium, and may be used to detect local inflammation or metabolic abnormality of the cortex when used for intracranial biological characteristic signal acquisition.

The manufacturing method of the temperature sensor 1022 comprises the steps of performing magnetron sputtering deposition of a high-purity magnesium layer on a PI (polyimide) temporary substrate, and performing micromachining by using an excimer laser to form a serpentine resistor structure. The surface of the sensor is covered with a PBAT packaging layer, and an active area is exposed through laser drilling to improve the thermal response speed, and the thermal sensitivity coefficient reaches 0.35%/DEGC.

Alternatively, the pH sensor 1023 may be formed based on a phosphorus doped silicon nanomembrane modified with 3-aminopropyl triethoxysilane (APTES), and the pH sensor 1023 may measure pH (sensitivity 45 mV/pH) through surface potential changes caused by amino protonation, which may be used to monitor post-operative cerebrospinal acid-base balance when used for intracranial biological signature signal acquisition.

The manufacturing method of the pH sensor 1023 comprises the steps of doping phosphorus element on an SOI wafer through a 1050 ℃ thermal diffusion process to form an n-type semiconductor layer, and performing vapor deposition in aminopropyl triethoxysilane (APTES) vapor to complete surface functionalization. The pH sensor 1023 adopts an interdigital electrode design, is isolated from a bottom layer circuit through a silicon dioxide insulating layer, and is provided with a magnesium lead at the edge to realize impedance signal output.

Alternatively, the passive electrode array 1024 may be formed based on molybdenum (Mo) square electrode units arranged in an array, and the passive electrode array 1024 may be annularly distributed at a distal end of the radial support arm 1011 away from the center position 1015. The passive electrode array 1024 may be connected to the circuit board 1042 by corresponding signal lines 1026, which may be used to collect the cerebral cortex surface brain electrical signals (ECoG). The high conductivity and controllable degradation rate of molybdenum balances signal quality and life requirements.

Optionally, an active electrode array 1025 can be formed based on n-type metal-oxide semiconductor field effect transistors (MOSFETs) arranged in an array and based on silicon nanomembranes, the active electrode array 1025 can realize multichannel signal time-sharing multiplexing through gate voltage switching, the spatial resolution reaches millimeter level, and the active electrode array 1025 can be specially used for space-time positioning of epileptic lesions when being used for intracranial biological characteristic signal acquisition.

The electrode unit comprises a passive manufacturing method and an active manufacturing method. The passive electrode array 1024 of molybdenum material deposits molybdenum layer on PI substrate by radio frequency magnetron sputtering, forms square electrode by positive photoresist photoetching, forms edge impedance by electrochemical polishing, grows silicon dioxide on SOI wafer as doping barrier layer by active electrode array 1025 of metal-oxide semiconductor field effect transistor (MOSFET), forms channel by implementing selective phosphorus diffusion after photoetching window opening, adopts electron beam evaporation to deposit molybdenum metal on source/drain, and forms silicon oxide dielectric layer on grid electrode by atomic layer, finally integrates multichannel array to realize high signal-to-noise ratio.

In one embodiment, each sensor assembly 1020 may be identical in structure, having the same number and type of sensors 106, such as each sensor assembly 1020 including a pressure sensor 1021, a temperature sensor 1022, a pH sensor 1023, a passive electrode array 1024, and an active electrode array 1025. In this manner, the multi-modal implantable sensor 100 can achieve simultaneous acquisition of pressure, pH, temperature, and electrical signals multi-modal signals on the same substrate frame.

Referring to fig. 10, fig. 10 is an enlarged partial top view of another sensor assembly according to an embodiment of the present application, and in the sensor assembly 1020 shown in fig. 10, the circular detection area 107 is divided into N concentric annular detection areas 110, and the N concentric annular detection areas 110 are respectively used for disposing one sensor 106.

In the manner shown in fig. 10, the pattern structure of the sensor 106 is a ring structure with the same or similar shape as the concentric ring detection area 110, so as to increase the effective detection area of the sensor 106, increase the intensity of the acquired signal, and improve the detection sensitivity and accuracy.

Based on the above description, in the multi-mode implantable sensor 100 provided by the embodiment of the application, the base frame is formed by two layers of flexible substrates with specific grid shapes, and the plurality of sensors 106 are integrated on the base frame at the same time, so that the collaborative design of material mechanics and microelectronic technology can be realized, the implantation can be performed based on the contracted state with smaller volume, the minimally invasive implantation can be realized, the implantation can be automatically converted from the contracted state to the expanded state based on the shape memory capability of the flexible substrates, the large-area coverage can be realized with the surface of biological tissues so as to effectively collect various biological characteristic signals, the different biological characteristic signals can be synchronously collected by the plurality of different sensors 106, the multi-mode multi-signal synchronous collection can be realized, the wireless data interaction with the external monitor can be realized by the wireless communication functional layer 104, the structures such as the flexible substrates, the signal lines 1026 and the coils 1041 can adopt biodegradable materials, the required volume can be greatly reduced, the circuit board fixed in the multi-mode visual marker layer 103 and the chip structure of each sensor 106 can be automatically converted into the expanded state based on the shape memory capability of the flexible substrates, the secondary operation can be reduced, and the required volume of the multi-mode implantable sensor 100 can be reduced, and the risk of the secondary operation can be reduced.

It should be noted that, for convenience of illustration, the schematic diagrams of the deployment state of the multi-mode implantable sensor 100 and the internal film layers thereof provided in the embodiments of the present application are illustrated with respect to the deployment state to the planar state, as described above, the embodiments of the present application may optimize the deployment state of the multi-mode implantable sensor 100 by one or more of differentially designing the thickness and/or the material of two flexible substrates, differentially designing the line widths of the supporting beams on different concentric rings 1016 in the same flexible substrate, differentially designing the line widths of the radial supporting arms 1011 in the same flexible substrate, and the like, so that the sensor may be deployed in a planar state or may be deployed in a curved surface with a certain curvature.

In addition to the multi-mode implantable sensor 100 provided in the above embodiment, another embodiment of the present application further provides a signal acquisition system, and the structure of the signal acquisition system is shown in fig. 11.

Referring to fig. 11, fig. 11 is a schematic structural diagram of a signal acquisition system according to an embodiment of the present application, where the signal acquisition system includes a multi-mode implantable sensor 100 according to any one of the foregoing embodiments, and an extracorporeal monitor 200, where the extracorporeal monitor 200 is communicatively connected to the multi-mode implantable sensor 100. The multi-modal implantable sensor 100 is a multi-layered composite structure provided in the above embodiments that can simultaneously acquire a plurality of different biometric signals.

Optionally, the extracorporeal monitor 200 includes a display instrument 203, and image information related to the biometric signals acquired by the multimodal implantable sensor 100 may be displayed by the display instrument 203. When the device is used for acquiring brain biological characteristic signals, the display instrument 203 can display brain electrical signal distribution, intracranial pressure waveforms, temperature trend and pH value in real time, has a built-in threshold alarming function, supports Bluetooth and cloud data transmission, and is accessed by a remote medical platform.

In one embodiment, as shown in fig. 11, the extracorporeal monitor 200 is connected to a wireless reading module 201 via a cable 202. The wireless reading module 201 is a transmitting and receiving coil, and can generate an alternating magnetic field to supply power to the multi-mode implantable sensor 100 and collect signals through electromagnetic induction.

Optionally, the signal acquisition system may prestore in the in vitro monitor an application program capable of executing a pathology specific algorithm according to the biological feature signals acquired by the multiple sensors integrated by the multi-mode implantable sensor 100, and may develop a corresponding feature extraction model and a decision threshold for different encephalopathy when the application program is used for brain disease diagnosis.

Referring to fig. 12, fig. 12 is a schematic diagram illustrating a multi-mode implantation principle of a signal acquisition system before signal acquisition according to an embodiment of the present application. The multi-modal implantable sensor 100 may be implanted through a flexible lead 300. The multi-modal implantable sensor 100 may be in a reduced volume contracted state during implantation and may assume a radially expanded mesh configuration after implantation within a living being. This approach may reduce the diameter of the flexible lead 300 required for implantation, may allow for in vivo implantation using a flexible lead 300 having a diameter of several tens of millimeters, may require a smaller diameter of the flexible lead 300, and may reduce implantation trauma. The diameter of the flexible wire 300 may be 5mm to 80mm, for example, 21mm, 30mm, 33mm, 50mm, 62mm, 75mm, etc.

In clinical operation, the multi-mode implantable sensor 100 can be implanted through a 5mm aperture, and the flexible substrate made of PLCL-PLGA material can be automatically unfolded when being triggered by body temperature, so that the coverage area can be confirmed in an auxiliary manner by utilizing the X-ray sensitive visual marking layer 103. When the device is used for intracranial signal acquisition, the epileptic discharge range can be positioned by utilizing the multichannel electrode array, and data acquired by the pressure sensor 1021 and the pH sensor 1023 can be transmitted to an external system in real time through the wireless communication functional layer 104, so that a closed-loop nerve monitoring network is formed.

Referring to fig. 13, fig. 13 is a schematic diagram illustrating an operating principle of a signal acquisition system according to an embodiment of the present application. The multi-mode electronic functional layer 102 in the multi-mode implantable sensor 100 comprises a multi-mode sensor for acquiring biological characteristic signals such as temperature, pressure, pH, electroencephalogram and the like, and the wireless communication functional layer 104 in the multi-mode implantable sensor 100 comprises an NFC chip for data interaction through the extracorporeal monitor 200. The NFC chip may communicate wirelessly with the wireless reader module 201 via an electromagnetic field to enable data interaction with the extracorporeal monitor 200 and to enable power input of the devices in the multimodal implantable sensor 100. The extracorporeal monitor 200 includes a readout circuit and a display device 203.

Taking a brain implantation scenario as an example, the clinical implantation procedure of the multi-modal implantable sensor 100 includes:

1.1 Pre-operative planning and positioning.

Multi-mode image fusion, namely constructing a three-dimensional model of a target brain region based on preoperative 3T nuclear magnetic MRI and computed tomography CT angiography data through medical image processing software, and planning implantation sites (usually selecting temporal lobe or top lobe non-large blood vessel regions) of the multi-mode implantation sensor 100.

The stereotactic frame calibration is that a stereotactic head frame is used for fixing the head of a patient, and the stereoscopic coordinates (precision +/-0.5 mm) of the implantation path are calculated by combining preoperative image data, so that a functional area and a key blood vessel are avoided.

1.2 Minimally invasive implantation surgery).

Local anesthesia and incision after local infiltration anesthesia is performed at the skull drilling site (diameter 5 mm), skin and periosteum are incised, and the skull is windowed by using a micro trephine to expose the dura mater.

Sensor delivery the multimodal implantable sensor 100 is pre-folded into a custom made flexible catheter 300, maintaining the folded state at low temperature (4 ℃ saline cycle) by the thermal response characteristics (glass transition temperature Tg ≡35 ℃) of the flexible substrate of PLCL-PLGA material.

Catheter guided implantation, the flexible catheter 300 is inserted into the subepidural space through the bone window under guidance of the nerve navigation system, and advanced along a preset path to the target brain area.

Temperature triggered deployment after pushing the multimodal implantable sensor 100 out of the flexible catheter 300 with a syringe, withdrawing the flexible catheter 300 and stopping the low temperature cycle, triggering the glass transition of the flexible substrate made of PLCL-PLGA material by body temperature (37 ℃) and the multimodal implantable sensor 100 can complete radial deployment within 30 seconds, and realizing self-adaptive fitting on the meningeal surface through the elastic release of the serpentine support beam 1012.

And (3) performing functional verification in operation, namely performing X-ray real-time monitoring, and observing the unfolding form of the iodixanol labeling layer by using a C-arm X-ray machine to ensure that the electrode array completely covers a target area (space error is less than 1 mm). Impedance test, namely, measuring impedance values of all channels through the wireless NFC module activation electrode in the wireless communication functional layer, and eliminating wire breakage or poor contact caused by folding.

1.3 Post-operative treatment and recovery.

Incision suturing, namely sealing bone window by absorbable bone wax, suturing subcutaneous tissue and skin layer by layer, and monitoring intracranial pressure (normal value 7-15 mmHg) and local inflammatory response 24 hours after operation.

Degradation component management, 10 weeks after surgery (after the magnesium coil is completely dissolved), taking out the non-degradable chips (PBAT encapsulation layer is softened, and incision only needs to be 3 mm) in the NFC module on the circuit board 1042 and each non-degradable sensor chip in the multi-mode electronic function layer 102 based on the non-degradable visual label layer 103 through a subcutaneous minimally invasive incision. The individual chips are integrally X-ray positioned and removed with the visual marker layer 103.

The data monitoring and intelligent analysis of the multi-modal implantable sensor 100 includes:

2.1 Multi-modal data collection.

The real-time transmission protocol is that the wireless reading module 201 polls the sensor data packet at a frame rate of 100 frames per second, the electrophysiological signals in each frame comprise multichannel electroencephalogram signals ECoG (sampling rate of 1kHz, resolution of 12 bits) covering a frequency band of 0.5-300 Hz, and the biophysical signals comprise three signal parameters of temperature (+ -0.1 ℃), pressure (0.1% resolution) and pH (0.01 precision), and the sampling rate is 10Hz.

Data preprocessing, namely dynamic baseline calibration, elimination of slow-change drift (such as electrode polarization effect) based on a moving average algorithm of a sliding window (10 seconds), power frequency noise suppression, and elimination of environmental interference by an adaptive notch filter (center frequency 50/60Hz, Q=30).

2.2 An intelligent analysis engine.

Feature extraction and fusion, namely time-frequency analysis, continuous wavelet transformation (Morlet basis function, scale 1-100 Hz) is carried out on ECoG signals, and energy duty ratio of gamma wave band (30-80 Hz) is extracted as an epileptic activity sign.

Multi-sensor correlation by establishing a cross-modal correlation matrix of temperature-strain-pH, identifying abnormal metabolic-mechanical coupling events (such as inflammation-induced localized oedema).

And the machine learning model is used for pre-warning epilepsy, training LSTM network learning ECoG time sequence characteristics and combining clinical seizure marking data to realize the epileptic prediction 5-10 minutes in advance. Intracranial pressure anomaly detection, recognizing a deformation mutation mode through feature importance ranking (shape value) based on a gradient lifting decision tree (GBDT) model of data acquired by a pressure sensor. Cloud deep learning, uploading encrypted data to a medical cloud platform, integrating multiple patient data through a graph rolling network (GCN), and mining disease subtype and treatment response modes.

2.3 Clinical interactions and decision support.

The doctor console supports dynamic heat map display, space power spectrum density mapping of multichannel ECoG signals, overlapping of temperature/pressure pseudo-color layers, event backtracking, automatic labeling of abnormal event time axes (such as high-frequency oscillation and pH dip), support of original signal playback and expert labeling, performance attenuation compensation, dynamic correction of influence of electrode impedance drift on signal amplitude through a Recursive Least Squares (RLS) algorithm, life end prediction, prediction of residual time (error + -2 days) of sensor functions based on a magnesium corrosion dynamics model and real-time pH data, and replacement or node taking-out prompt.

Applications of the multimodal implantable sensor 100 in different craniocerebral disorders include:

3.1 Monitoring of brain trauma.

Multimodal dynamic monitoring, namely, intracranial pressure (ICP) real-time tracking, continuously monitoring subdural pressure change through a flexible pressure sensor (resolution 0.1%), inverting ICP fluctuation (error + -2 mmHg) by combining skull deformation data, early warning risk of intracranial high pressure (> 20 mmHg) in real time, detecting metabolic abnormality, capturing lactic acid accumulation of brain tissue through a pH sensor (precision 0.01) (pH <7.2 indicates anaerobic metabolism), and identifying local inflammatory reaction through a temperature sensor (+/-0.1 ℃) (temperature difference >0.5 ℃) indicates infection or hematoma expansion).

And (3) intelligent early warning and decision, namely secondary injury prediction, ICP, pH and temperature time sequence data are analyzed based on an LSTM network (10 minutes of input window), delayed hematoma or brain hernia risk (sensitivity is 95%) is predicted, and cryotherapy or surgical intervention is started in advance.

And optimizing a treatment scheme, namely integrating sensor data and CT perfusion imaging, evaluating brain oxygen uptake fraction through a random forest model, and dynamically adjusting mannitol infusion rate.

3.2 Brain tumor accurate management).

Analysis of tumor microenvironment, monitoring of metabolic state, drawing of an acid region around tumor (pH is 6.5-7.0) through a pH sensor, registration with MRI dynamic enhancement data, definition of tumor infiltration boundary (space matching error <2 mm), capture of electrophysiological markers, multi-channel ECoG identification of peri-tumor cortex high-frequency oscillation, and separation of epileptiform discharge and tumor-related activity through independent component analysis.

Treatment response evaluation and optimization, namely dynamically correcting a radiotherapy target zone, training a Support Vector Machine (SVM) based on real-time pH and temperature data, predicting the risk of radionecrosis, and intraoperatively adjusting the dose of gamma knife isocenter.

Short term monitoring (brain trauma) using a rapidly degrading PLGA encapsulated sensor (4 weeks full absorption) avoiding secondary extraction surgery.

Long-term monitoring (brain tumor) is carried out by preparing flexible substrate (degradation period of 6-12 months) with PLCL-PBAT mixed material, and ensuring whole course coverage of treatment.

The signal acquisition system realizes full-period closed-loop management from 'structural implantation' to 'functional service' to 'safe disappearance' through accurate minimally invasive surgery and intelligent data analysis, and provides a dynamically adaptable solution for brain disease accurate diagnosis and treatment.

The signal acquisition system includes a multi-mode implantable sensor, so that the signal acquisition system provided by the embodiment of the present application has the same or similar technical effects as the multi-mode implantable sensor provided by the above embodiment, and the embodiments of the present application are not repeated.

In the description of the present application, each embodiment is described in a progressive manner, or in parallel manner, or in a combination of progressive and parallel manners, and each embodiment is mainly described as different from other embodiments, and identical and similar parts between the embodiments are all enough to be referred to each other. The embodiments provided by the embodiments of the application can be combined with each other without contradiction.

It is to be noted, however, that the description of the drawings and embodiments are illustrative and not restrictive. Like reference numerals refer to like structures throughout the embodiments of the specification. In addition, the drawings may exaggerate the thicknesses of some layers, films, panels, regions, etc. for understanding and ease of description. It will also be understood that when an element such as a layer, film, region or substrate is referred to as being "on" another element, it can be directly on the other element or intervening elements may be present. In addition, "on" means positioning an element on or under another element, but not essentially on the upper side of the other element according to the direction of gravity.

The terms "upper," "lower," "top," "bottom," "inner," "outer," and the like are used for convenience in describing and simplifying the description based on the orientation or positional relationship shown in the drawings, and do not denote or imply that the devices or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore should not be construed as limiting the application. When an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may also be present.

It is further noted that relational terms such as first and second, and the like are used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Moreover, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that an article or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such article or apparatus. Without further limitation, an element defined by the phrase "comprising one does not exclude the presence of additional like elements in an article or apparatus that comprises such an element.

The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present application. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the application. Thus, the present application is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A multi-modal implantable sensor, comprising:

Two layers of flexible substrates arranged oppositely;

A multi-modal electronic functional layer between the two flexible substrates, the multi-modal electronic functional layer comprising at least two sensors for acquiring different biometric signals;

2. The multi-modal implantable sensor as set forth in claim 1, further comprising:

3. The multi-modal implantable sensor according to claim 2, wherein the wireless communication functional layer comprises:

A plurality of coils surrounding the circuit board, the coils for forming a toroidal magnetic field; if the multi-mode implantable sensor is deployed in a single plane, the coils are concentric rings.

4. The sensor of claim 1, wherein the flexible substrate comprises a plurality of radial support arms, wherein one end of each radial support arm is connected with the same center position;

If the multi-mode implantable sensor is unfolded on a plane, the radial supporting arms are respectively positioned on different radiuses of the same circular area, the center position is the center of the circular area, and two adjacent radial supporting arms are connected through at least two supporting beams.

5. The sensor of claim 4, wherein the circular region has at least two concentric rings inside, and the support beams are connected in sequence at the intersections of the circumferences of the concentric rings and the respective radial support arms.

6. The multi-modal implantable sensor according to claim 4, wherein the support beam is a serpentine trace connected between two of the radial support arms.

7. The multi-modal implantable sensor of claim 4, wherein the multi-modal electronic functional layer includes a plurality of sensor assemblies;

The sensor assembly is positioned between the radial support arms of two layers of the flexible substrate stack opposite each other.

8. The multi-modal implantable sensor as set forth in claim 7, wherein the sensor assembly includes a circular detection zone provided with N of the sensors, each for acquiring a different biometric signal, N being a positive integer greater than 1, the circular detection zone being opposite an end of the radial support arm remote from the central location, wherein,

The circular detection area is divided into N+1 sector areas, N of the N+1 sector areas are used for respectively setting one sensor, and the rest of the sector areas are used for setting signal lines connected with the sensors;

or, the circular detection area is divided into N concentric ring detection areas, and the N concentric ring detection areas are respectively used for arranging one sensor.

9. The multi-modal implantable sensor according to any one of claims 1-8, wherein the flexible substrate automatically transitions from the contracted state to the expanded state upon meeting a glass transition temperature of the self material, the glass transition temperature of the flexible substrate ranging from 35 ℃ to 45 ℃;

or the multi-mode implantable sensor further comprises a visual marking layer, a display layer and a display layer, wherein the visual marking layer is used for displaying the unfolding state of the multi-mode implantable sensor;

Or, the thickness of the two layers of the flexible substrates is different;

or, the thickness ratio of the two layers of the flexible substrate is not less than 2;

10. A signal acquisition system, comprising:

The multi-modal implantable sensor of any one of claims 1-9;

And the external monitor is in communication connection with the multi-mode implanted sensor.