CN112690785B

CN112690785B - Oral cavity in-situ flexibility detection device and manufacturing method thereof

Info

Publication number: CN112690785B
Application number: CN202011454328.2A
Authority: CN
Inventors: 董岩; 董爱玲; 冯雪; 陈颖
Original assignee: Tsinghua University; Institute of Flexible Electronics Technology of THU Zhejiang; Dalian Medical University; Qiantang Science and Technology Innovation Center
Current assignee: Tsinghua University; Institute of Flexible Electronics Technology of THU Zhejiang; Dalian Medical University; Qiantang Science and Technology Innovation Center
Priority date: 2020-12-10
Filing date: 2020-12-10
Publication date: 2023-11-03
Anticipated expiration: 2040-12-10
Also published as: CN112690785A

Abstract

The present disclosure relates to an oral cavity in-situ flexibility detection device and a method of manufacturing the same. The method comprises the steps of converting a detected pressure signal between the upper and lower dentitions of an organism into a first electric signal through organic combination of a first detection module, a second detection module, a processing module and a drug storage module, controlling the drug storage module to release stored drugs under the condition that the voltage value of the first electric signal exceeds a voltage threshold value, detecting target ions in saliva of the organism to obtain a second electric signal, and obtaining the concentration of the target ions according to the second electric signal. The oral cavity in-situ flexible detection device can be tightly attached to the dentition of an organism by utilizing an integrated forming process, realizes timely early warning of the physical condition by monitoring target ions in saliva, can realize release of medicines under emergency conditions, and can rapidly and accurately administer medicines, thereby solving the technical problems of deterioration, sudden death and the like of the state of an illness caused by the delay of administration time in the prior art.

Description

Oral cavity in-situ flexibility detection device and manufacturing method thereof

Technical Field

The disclosure relates to the field of cross research of flexible electronic technology and biomedical engineering, in particular to an oral cavity in-situ flexible detection device and a manufacturing method thereof.

Background

Saliva is acquired and stored in the in vitro saliva ion detection mode adopted at present, so that a reference measured value and an actual value can be different. In addition, the in-vitro saliva ion detection mode mainly adopts an electrochemical principle, but saliva samples are collected and stored, and saliva ion concentration values at a plurality of time points need to be measured, so that time and labor are wasted.

And due to the complexity of the oral environment, the space is limited; a moist environment within the oral cavity; chewing and speaking induced movements of the lips, cheeks and tongue; factors such as swallowing, absorbing saliva generated by organisms into the body increase the difficulty of integrating the biosensor into the oral cavity, and the biocompatibility of the biosensor integrated into the oral cavity needs to be more demanding, so that the real-time in-situ detection of the concentration of the biomarker such as ions in saliva is very challenging. In the related art, only the oral cavity biosensor is simply assembled with the oral cavity device, and after the electrodes of the oral cavity biosensor are connected with external equipment through wires, induction coils or the like, the detected signals are further processed and converted, and in the process, the detected signals are easy to have distortion problems. Moreover, part of the oral devices (such as dental trays) have large volume, poor fit with tissues in the oral cavity and uncomfortable wearing; the intraoral sensor needs large-scale equipment support, and is inconvenient to use. On the other hand, simple assembly of oral biosensors and oral devices also cannot meet the diversified demands of users.

Disclosure of Invention

In view of this, the present disclosure proposes an oral cavity in-situ flexibility detection device and a method of manufacturing the same.

According to an aspect of the present disclosure, there is provided an oral in situ flexibility detection device, the device comprising:

a flexible substrate having a shape that matches the shape of a dentition of a living being such that the device is worn on the dentition of the living being,

the first detection module is positioned in a first area corresponding to the surface of the dentition of the organism on the flexible substrate, and is used for detecting a pressure signal between the maxillary dentition and the mandibular dentition of the organism, converting the pressure signal into a first electric signal and transmitting the first electric signal to the processing module;

the second detection module is positioned in a second area, opposite to the salivary glands of the organisms, of the flexible substrate, is used for detecting target ions in saliva of the organisms to obtain a second electric signal, and sends the second electric signal to the processing module;

the processing module is positioned in a third area corresponding to the dentition of the organism on the flexible substrate, is connected with the first detection module and the second detection module through connecting wires, and is used for controlling the drug storage module to release stored drugs under the condition that the voltage value of the first electric signal exceeds a voltage threshold value, obtaining the concentration of the target ions according to the second electric signal, monitoring the physical condition, realizing timely early warning and quick and accurate drug administration under emergency conditions;

The power supply module is positioned in a fourth area corresponding to the dentition of the organism on the flexible substrate, is connected with the second detection module and the processing module through connecting wires and is used for supplying power to the device;

the shape of the packaging layer is matched with the shape of the dentition of the organism, and the packaging layer is used for packaging the flexible substrate, the connecting wires, the first detection module, the second detection module, the processing module and the power supply module;

and the medicine storage module is connected with the processing module through a connecting wire, is positioned in an area corresponding to the oral administration position of the organism on the packaging layer and is used for releasing the stored medicine under the control of the processing module.

In a possible embodiment, the device further comprises a heating module connected to the power module via connecting wires, the processing module comprises a control sub-module, the encapsulation layer is further configured to encapsulate the heating module,

the control sub-module starts the heating module under the condition that the voltage value of the first electric signal exceeds a voltage threshold value;

the heating module is used for heating the fuse wire of the drug storage module after starting;

The medicine storage module comprises a shell, a fuse and an elastic connecting piece, wherein the shell comprises an upper shell and a lower shell, the upper shell and the lower shell are connected together through the fuse and the elastic connecting piece to form the shell, a cavity for storing medicines is formed inside the shell, and when the fuse is heated and fused by the heating module, the upper shell and the lower shell are disconnected under the action of the elastic connecting piece, so that medicines in the cavity are released.

In one possible embodiment, the heating module comprises a resistive wire,

the lower shell is internally provided with a channel, a first position on the upper shell corresponding to the opening of the channel is provided with a connecting part, the fuse is arranged in the channel, one end of the fuse is fixed in the channel, the other end of the fuse is fixed on the connecting part, and the resistance wire is wound on the fuse;

the elastic connecting piece is arranged at a second position on the upper shell and the lower shell, which is opposite to the connecting part, and the upper shell and the lower shell are fixedly connected together at the second position.

In one possible embodiment, the second detection module includes at least: the working electrode, the reference electrode and the counter electrode are flatly arranged on the flexible substrate,

the working electrode and the reference electrode form a measuring loop for measuring a second electric signal generated in the electrochemical reaction process of the target ions on the working electrode,

the working electrode and the counter electrode form a polarization loop for stabilizing the measurement process of the second electric signal by the measurement loop.

In one possible embodiment, the surface of the second detection module that contacts the saliva of the organism is provided with a first selectively permeable membrane for preventing the material of the working electrode, reference electrode, counter electrode from entering the saliva of the organism.

In one possible embodiment, the working electrode comprises a conductive polymer layer for electrochemical reaction with the target ions to generate the second electrical signal.

In one possible embodiment, the working electrode further comprises a second permselective membrane disposed between the first permselective membrane and the conductive polymer layer, the second permselective membrane being configured to pass target ions in saliva of the organism for detection of the target ions by the working electrode.

In one possible embodiment, the shape of the projection of the working electrode on the plane of the flexible substrate comprises a circle, the shape of the projection of the reference electrode on the plane of the flexible substrate comprises a circle, the shape of the projection of the counter electrode on the plane of the flexible substrate comprises a semi-circle, the working electrode is located between the reference electrode and the counter electrode, and the counter electrode surrounds the working electrode.

In a possible implementation manner, the device further comprises a wireless transmission module connected with the processing module and the power module through connecting wires and used for sending the concentration of the target ions to a terminal.

According to another aspect of the present disclosure, there is provided a method of manufacturing an oral in situ flexibility testing device for manufacturing the device described above, the method comprising:

according to the dental arch curve of a living body, manufacturing a flexible substrate matched with the shape of the dental arch curve, and depositing a first metal layer on the flexible substrate;

etching the first metal layer according to a preset pattern to form a connecting wire of the device,

a first detection module is arranged in a first area of the flexible substrate and is used for detecting pressure signals between the upper and lower dentitions of the organism, converting the pressure signals into first electric signals and transmitting the first electric signals to a processing module;

Manufacturing a second detection module in a second area of the flexible substrate, wherein the second detection module is used for detecting target ions in saliva of the organism to obtain a second electric signal and sending the second electric signal to the processing module;

installing a processing module in a third area of the flexible substrate, wherein the processing module obtains the concentration of the target ions according to the second electric signal, and controls the drug storage module to release the stored drug under the condition that the voltage value of the first electric signal exceeds a voltage threshold value;

a power module is arranged in a fourth area of the flexible substrate to obtain a device to be packaged, wherein the power module is connected with the second detection module and the processing module through connecting wires and is used for supplying power to the device;

packaging the device to be packaged to form a packaging layer to obtain a device to be formed;

attaching the device to be molded to a plaster model manufactured according to the dentition of the living body, and performing molding treatment to obtain a flexible integrated device attached to the dentition of the living body;

and installing a medicine storage module on the packaging layer in a region corresponding to the oral administration position of the organism to obtain the oral in-situ flexible detection device, wherein the medicine storage module is used for releasing stored medicines under the control of the processing module.

According to the oral cavity in-situ flexible detection device and the manufacturing method thereof, the flexible substrate, the first detection module, the second detection module, the processing module, the power module, the packaging layer and the medicine storage module are arranged, so that the oral cavity in-situ flexible detection device can be tightly attached to the dentition of an organism, the monitoring of target ions in saliva is realized, and the release of medicine is realized under emergency conditions, thereby realizing rapid and accurate medicine administration, and solving the technical problems of state of illness worsening, sudden death and the like caused by medicine administration time delay in the prior art.

Other features and aspects of the present disclosure will become apparent from the following detailed description of exemplary embodiments, which proceeds with reference to the accompanying drawings.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate exemplary embodiments, features and aspects of the present disclosure and together with the description, serve to explain the principles of the disclosure.

Fig. 1 shows a schematic structural view of an oral in-situ flexibility detection device according to an embodiment of the present disclosure.

Fig. 2 illustrates a schematic structure of a connection wire according to an embodiment of the present disclosure.

Fig. 3 illustrates a schematic structural view of a second detection module according to an embodiment of the present disclosure.

Fig. 4 illustrates a schematic structural view of a drug storage module according to an embodiment of the present disclosure.

Fig. 5 shows a flow diagram of a method of manufacturing an oral in situ flexibility detection device, according to an embodiment of the present disclosure.

List of reference numerals

11 a first detection module; a second detection module 12; 13, a processing module; 14 a power module; 15 packaging layers; a 16 drug storage module; 17 dentition of a living organism; 21 connecting wires; 31 potassium ion working electrode; a 32 sodium ion working electrode; 33 potassium ion counter electrode; 34 sodium ion counter electrode; 35 potassium sodium ion common reference electrode; 401 an upper housing; 402 a lower housing; 403 an elastic connection; 404 a connection; a 405 fuse; 406 resistance wire; 407 cavity; 408 channels; 409 opening; 410 one end of the fuse; 411 the other end of the fuse.

Detailed Description

Various exemplary embodiments, features and aspects of the disclosure will be described in detail below with reference to the drawings. In the drawings, like reference numbers indicate identical or functionally similar elements. Although various aspects of the embodiments are illustrated in the accompanying drawings, the drawings are not necessarily drawn to scale unless specifically indicated.

The word "exemplary" is used herein to mean "serving as an example, embodiment, or illustration. Any embodiment described herein as "exemplary" is not necessarily to be construed as preferred or advantageous over other embodiments.

In addition, numerous specific details are set forth in the following detailed description in order to provide a better understanding of the present disclosure. It will be understood by those skilled in the art that the present disclosure may be practiced without some of these specific details. In some instances, methods, means, elements, and circuits well known to those skilled in the art have not been described in detail in order not to obscure the present disclosure.

With the increasing development of economic construction in China, the living standard of people is continuously improved, the disease spectrum of cities and rural areas is changing, infectious diseases are reduced, the life span of people is prolonged, and the incidence and death rate of cardiovascular diseases, particularly hypertension, cerebral apoplexy and coronary heart disease are obviously increased compared with 30 years ago. And when the cardiovascular disease is in an acute attack, the patient can not be treated in time due to the factors of incorrect administration mode, delay of administration time and the like, and the illness state is influenced. How to realize targeted drug delivery while realizing the detection of the concentration of the biomarkers such as ions in the saliva in situ in the oral cavity is a technical problem to be solved.

Fig. 1 shows a schematic structural view of an oral in-situ flexibility detection device according to an embodiment of the present disclosure. Fig. 2 illustrates a schematic structure of a connection wire according to an embodiment of the present disclosure. As shown in fig. 1 and 2, the oral cavity in-situ flexibility detection device comprises:

A flexible substrate (not shown in fig. 1 because the flexible substrate and the encapsulation layer 15 are of the same structure) the shape of which matches the shape of the dentition 17 of the living being so that the device is worn on the dentition 17 of the living being.

The first detection module 11 is located in a first area corresponding to the face of the dentition 17 of the living being on the flexible substrate, and is used for detecting a pressure signal between the maxillary dentition and the mandibular dentition of the living being, converting the pressure signal into a first electrical signal, and sending the first electrical signal to the processing module 13.

The second detection module 12 is located in a second area of the flexible substrate opposite to the salivary glands of the living body, and is used for detecting target ions in saliva of the living body to obtain a second electric signal, and sending the second electric signal to the processing module 13.

The processing module 13 is located in a third area corresponding to the dentition 17 of the living body on the flexible substrate, is connected with the first detection module 11 and the second detection module 12 through a connecting wire 21, and is used for controlling the drug storage module 16 to release the stored drug under the condition that the voltage value of the first electric signal exceeds a voltage threshold value, obtaining the concentration of the target ions according to the second electric signal, monitoring the physical condition, realizing timely early warning and quick and accurate drug administration under emergency conditions.

A power module 14, located in a fourth area of the flexible substrate corresponding to the dentition 17 of the living being, is connected to the second detection module 12, the processing module 13 by means of connection wires 21 for powering the device.

And an encapsulation layer 15, wherein the shape of the encapsulation layer 15 is matched with the shape of the dentition 17 of the organism, and the encapsulation layer is used for encapsulating the flexible substrate, the connecting wires 21, the first detection module 11, the second detection module 12, the processing module 13 and the power module 14.

The drug storage module 16 is connected to the processing module 13 through a connection wire 21 and is located in a region corresponding to the oral administration position of the living body on the encapsulation layer 15, for releasing the stored drug under the control of the processing module 13.

In one possible embodiment, the device may be a device that matches only the shape of the mandibular dentition of a living body, a device that matches only the shape of the maxillary dentition of a living body, or a device that matches the shape of each of the maxillary and mandibular dentitions of a living body.

Where the device is a device that matches the shape of the upper and lower dentition of a living being, respectively, the device may include a first device that matches the shape of the upper dentition of the living being and a second device that matches the shape of the lower dentition of the living being, and the first device and the second device may function as orthodontic appliances. The first detection module 11 and the drug storage module 16 must be simultaneously provided in a first device that matches the shape of the maxillary dentition of the living body or in a second device that matches the shape of the mandibular dentition of the living body, and the second detection module 12 may be separately provided in the first device that matches the shape of the maxillary dentition of the living body or in the second device that matches the shape of the mandibular dentition of the living body. The arrangement positions of the processing module and the power supply module, and the roles of the processing modules provided in the first device and/or the second device may be determined according to the arrangement positions (whether provided in the first device or the second device) of the first detection module 11, the second detection module 12, and the drug storage module 16. For example, in the case where the first detection module 11 and the drug storage module 16 are provided in the first device and the second detection module 12 is provided in the second device, the first device and the second device need to be provided with a power supply module and a processing module, respectively. Wherein the power module in the first device is used for supplying power to the processing module in the first device, which is used for controlling the drug storage module to release the stored drug under the condition that the voltage value of the first electric signal exceeds the voltage threshold value; and the power supply module in the second device is used for supplying power to the processing module and the second detection module in the second device, which are used for obtaining the concentration of the target ions according to the second electric signal.

In one possible embodiment, the material of the flexible substrate may be a flexible material, such as Polydimethylsiloxane (PDMS), silicone, copolyester (PBAT, PBAT is a thermoplastic biodegradable plastic, a copolymer of butylene adipate and butylene terephthalate, such as ecoflex), polyimide (PI), and the like. The flexible material may be provided according to actual needs by those skilled in the art, and this disclosure is not limited thereto.

In one possible embodiment, the first detection module 11 may be a thin film pressure sensor for converting a detected pressure signal between the maxillary and mandibular dentitions of a living being into a first electrical signal and transmitting the first electrical signal to the processing module 13. For example, the film pressure sensor may include DF9-40 pressure sensor, WPE-103-50 pressure sensor, etc., and those skilled in the art may set the film pressure sensor according to actual needs, which is not limited by the present disclosure.

Wherein the first area of the first detection module 11 corresponding to the face of the dentition 17 of the living being on the flexible substrate may be any one of the following areas: the first detection module 11 may be located on the flexible substrate in a region corresponding to a face of one of the teeth in the molar region dentition of the living being, a region corresponding to a face of one of the teeth in the incisor region dentition of the living being, or the first detection module 11 may be located on the flexible substrate in a region corresponding to a face of one of the teeth in the incisor region dentition of the living being. The first region on the flexible substrate may be provided as desired by one skilled in the art, and this disclosure is not limited in this regard.

In one possible implementation, as shown in fig. 2, the shape of the connecting wire 21 may be a serpentine pattern. The shape of the connection wire 21 may also be a fractal pattern or the like, which is not limited by the present disclosure.

Wherein the third area of the processing module 13 corresponding to the dentition 17 of the living being on the flexible substrate may be any area of the flexible substrate corresponding to the dentition 17 of the living being other than the first detection module 11, the second detection module 12. For example, the treatment module 13 may be located in an area corresponding to the right mandibular second premolars buccal area of the living being, and a person skilled in the art may set a third area on the flexible substrate as desired, without limitation to the present disclosure.

In one possible implementation, the processing module 13 may include a first processing sub-module corresponding to the first detection module 11, and a second processing sub-module corresponding to the second detection module 12. Wherein the first processing sub-module is configured to control the drug storage module 16 to release the stored drug in case it is determined that the voltage value of the first electrical signal exceeds a voltage threshold value, and the second processing sub-module is configured to obtain the concentration of the target ion from the second electrical signal. The first detection module 11, the drug storage module 16, and the first processing sub-module must be simultaneously provided in a first device that matches the shape of the maxillary dentition of the living body or in a second device that matches the shape of the mandibular dentition of the living body, and the second detection module 12 and the second processing sub-module must be simultaneously provided in the first device that matches the shape of the maxillary dentition of the living body or in the second device that matches the shape of the mandibular dentition of the living body. The setting positions of the first processing sub-module and the second processing sub-module, and the roles of setting the first processing sub-module and the second processing sub-module, can be determined according to the setting positions (set in the first device or the second device) of the first detection module 11, the second detection module 12, and the medicine storage module 16.

In one possible embodiment, where the first detection module 11 is located on the flexible substrate in an area corresponding to the face of the second molar on the left side of the mandible of the living being, and the device is intended to be worn by an adult, the voltage threshold may be set to the voltage value of the electrical signal corresponding to an bite force of 300 newtons. However, since the correspondence between the first electrical signals and the biting forces of the different pressure sensors are different, the biting forces between the upper and lower dentitions of organisms of different ages are also different, and a person skilled in the art can set the voltage threshold of the first electrical signals according to the actual conditions of different organisms, which is not limited in the present disclosure.

The second area of the second detection module 12 opposite to the salivary gland of the living body on the flexible substrate may be any one of the following areas: the region of the flexible substrate opposite the parotid gland of the organism, the region of the flexible substrate opposite the submandibular and sublingual glands of the organism. For example, the second detection module 12 may be located in a region of the organism corresponding to the left side of the upper jaw of the second molar for detecting target ions in saliva produced by the parotid gland of the organism. The second detection module 12 may be located in an intermediate region between the left mandibular central incisor lingual side of the living body and the right mandibular central incisor lingual side of the living body, and is configured to detect target ions in saliva produced by the mandibular and sublingual glands of the living body. The second region on the flexible substrate may be provided as desired by those skilled in the art, and the present disclosure is not limited thereto.

In one possible embodiment, the second detection module 12 may include at least: the working electrode, the reference electrode and the counter electrode are flatly arranged on the flexible substrate.

The working electrode and the reference electrode form a measuring loop for measuring a second electric signal generated in the electrochemical reaction process of the target ions on the working electrode.

The second detection module 12 may include a plurality of working electrodes, a plurality of reference electrodes corresponding to each working electrode, and a plurality of counter electrodes corresponding to each working electrode, where each working electrode is used to implement detection of a different target ion. The second detection module 12 may also include a plurality of working electrodes, a reference electrode, and a plurality of counter electrodes corresponding to each working electrode, where each working electrode is used to implement detection of a different target ion, and the reference electrode may be a common reference electrode for multiple target ions. It should be noted that, those skilled in the art may set the working electrode and the counter electrode according to the target ions to be detected, which is not limited in this disclosure.

In one possible embodiment, the shape of the projection of the working electrode on the plane of the flexible substrate may include a circle, the shape of the projection of the reference electrode on the plane of the flexible substrate includes a circle, the shape of the projection of the counter electrode on the plane of the flexible substrate includes a semi-circle, the working electrode is located between the reference electrode and the counter electrode, and the counter electrode surrounds the working electrode.

Fig. 3 illustrates a schematic structural view of a second detection module according to an embodiment of the present disclosure. As shown in FIG. 3, when the target ion to be detected is potassium ion (K ⁺ ) And sodium ion (Na) ⁺ ) In this case, the second detection module 12 may include a potassium ion working electrode 31, a sodium ion working electrode 32, a potassium ion counter electrode 33, a sodium ion counter electrode 34, and a potassium-sodium ion common reference electrode 35. Wherein, the potassium ion working electrode 31 is positioned between the potassium-sodium ion common reference electrode 35 and the potassium ion counter electrode 33, and the sodium ion working electrode 32 is positioned between the potassium-sodium ion common reference electrode 35 and the sodium ion counter electrode 34. In the projection shape on the plane of the flexible substrate, the potassium ion working electrode 31 is circular, the potassium ion counter electrode 33 is semi-annular with the same center as the potassium ion working electrode 31, and the potassium ion counter electrode 33 surrounds the potassium ion working electrode 31; the sodium ion working electrode 32 is circular, the sodium ion counter electrode 34 is semi-circular with the center of the sodium ion working electrode 32, and the sodium ion counter electrode 34 surrounds the sodium ion working electrode 32.

Through the real-time detection of the sodium and potassium ion concentration in saliva, the organism wearing the device can monitor the physical condition according to the sodium and potassium ion concentration in saliva in real time, evaluate the risk of cardiovascular diseases and play a role in early warning in time.

According to the target ions to be detected, the working electrode, the reference electrode and the counter electrode corresponding to the target ions to be detected are arranged, so that different target ions to be detected can be accurately measured.

In one possible embodiment, the working electrode and the reference electrode may be configured as cylinders having a radius of less than or equal to 1 millimeter and a height of less than or equal to 1 micrometer, and the counter electrode may be configured as half-rings having an inner radius of less than or equal to 1.2 millimeters, an outer radius of less than or equal to 2.5 millimeters, and a height of less than or equal to 1 micrometer around the working electrode at the same center of a circle as the working electrode, wherein the distance between the working electrode and the counter electrode may be greater than 0.2 millimeters and less than 1 millimeter.

In one possible embodiment, the surface of the second detection module 12 that contacts the saliva of the living body is provided with a first selectively permeable membrane for preventing the material of the working electrode, the reference electrode, the counter electrode from entering the saliva of the living body. Wherein the first permselective membrane may be a medical biocompatible membrane. The medical biocompatible membrane can be a cuprammocellulose membrane, a saponified cellulose membrane, a polyacrylonitrile membrane, a polymethyl methacrylate membrane, a polysulfone membrane and the like, and has good biocompatibility and high safety. The medical biocompatible film may be provided according to actual needs by those skilled in the art, and the present disclosure is not limited thereto.

By arranging the first selective permeable membrane, the first selective permeable membrane is a biocompatible polymer membrane, so that the damage to organisms can be avoided, and harmful substances in the working electrode, the reference electrode and the counter electrode can be prevented from entering saliva of the organisms, and the damage to the organisms caused by the harmful substances in the working electrode, the reference electrode and the counter electrode can be avoided.

In one possible embodiment, the working electrode comprises a conductive polymer layer for electrochemical reaction with the target ions to generate the second electrical signal. Wherein the conductive polymer layer is formed according to the solvent in the conductive polymer solution volatilized, and the solute in the conductive polymer solution may include polythiophene, polypyrrole, polyaniline, etc., and one skilled in the art may set the solute in the conductive polymer solution according to the target ion setting to be actually detected, which is not limited in the present disclosure.

In one possible embodiment, when the target ion to be detected is potassium ion, the working electrode is a potassium ion working electrode, the reference electrode is a potassium ion reference electrode, and the conductive polymer layer is formed after the solvent in the poly 3, 4-ethylenedioxythiophene solution is volatilized, wherein the target ion and the conductive polymer layer electrochemically react by the following chemical reaction scheme,

Wherein PEDOT ⁺ PSS ^- _(film) Represents poly (3, 4-ethylenedioxythiophene) -poly (styrenesulfonic acid) ions, K, in a conductive polymer layer ⁺ _(membrane) Representing potassium ions in saliva of an organism, PEDOT ⁰ PSS ^- K ⁺ _(film) Represents potassium poly (3, 4-ethylenedioxythiophene) -poly (styrenesulfonate), e ^- Representing the charge required during the electrochemical reaction of the target ions with the conductive polymer layer, i.e. the second electrical signal.

In one possible embodiment, the processing module 13 converts the second electrical signal to a corresponding electrical potential and obtains the concentration of the target ions by the following formula (1):

wherein a represents the concentration of the target ion, z _a The valence state of the target ion is represented by R, the gas constant is represented by T, the temperature is represented by F, the Faraday constant is represented by E _meas Representing the potential generated by all ions in saliva of an organism, E ₀ Representing the potential generated by ions other than the target ions in saliva of the organism. Wherein, in the case that only target ions enter the working electrode to react electrochemically with the conductive polymer layer in the working electrode, E ₀ Is 0.

By arranging the first detection module 11 and the processing module 13, the concentration of target ions in saliva of organisms can be detected, basic values are provided for oral disease prevention and treatment, and references are provided for clinical disease differential diagnosis.

In one possible embodiment, the working electrode may further include a second permselective membrane disposed between the first permselective membrane and the conductive polymer layer, the second permselective membrane configured to pass target ions in saliva of the organism for detection of the target ions by the working electrode. Wherein the second permselective membrane can be determined based on the target ions to be detected. For example, when the target ion to be detected is sodium ion, the second permselective membrane may include sodium ionophore, na-TFPB (sodium tetrakis [3, 5-bis (trifluoromethyl) phenyl ] borate), PVC (Polyvinyl chloride ) and DOS (bis (2-ethylhexyl) sebacate), tetrahydrofuran, and the like. When the target ion to be detected is potassium ion, the second permselective membrane may comprise valomycin (i.e., potassium ionophore), kaTPB (potassium tetrakis [3, 5-bis (trifluoromethyl) phenyl ] borate), PVC and DOS, cyclohexanone, and the like. One skilled in the art can set the second permselective membrane according to the target ion to be detected, which is not limited by the present disclosure.

Through setting up the second selectively permeable membrane, can be selectively through the target ion that needs to detect, and not allow other ions to pass through to make the working electrode detect target ion, can effectively avoid other ions to produce the interference to the second signal of telecommunication in the in-process that the working electrode detected target ion, influence the working electrode to the accuracy of target ion detection.

In one possible embodiment, the processing module 13 may include a voltage buffer, a differential amplifier, a low pass filter, a transimpedance amplifier, an analog-to-digital converter for preprocessing the received first and second electrical signals, controlling the drug storage module 16 to release the stored drug if the voltage value of the first electrical signal exceeds a voltage threshold after preprocessing the first and second electrical signals, and deriving the concentration of the target ions from the second electrical signal.

In a possible embodiment, the fourth area of the flexible substrate corresponding to the dentition 17 of the living being of the power supply module 14 may be any area of the flexible substrate corresponding to the dentition 17 of the living being other than the first detection module 11, the second detection module 12, the processing module 13. For example, the power module 14 may be located on the flexible substrate in an area corresponding to the lingual side of the second premolars on the right mandible of the living being for powering the device. The power module 14 may be a micro battery with a diameter less than or equal to 4.8 mm and a thickness less than or equal to 1.5 mm, such as an SR416 button battery, and one skilled in the art may set the power module 14 according to actual needs, which is not limited in this disclosure.

In one possible embodiment, the encapsulation layer 15 may be a transparent dental laminate. The dental pressure membrane can be made of resin, is safe and nontoxic, can be softened and remolded by heating, has the softening and remolding temperature of 140-160 ℃, and does not cause adverse effect on other modules in the device. Wherein the thickness of the encapsulation layer 15 is less than or equal to 1.5 mm, which is not limited in this disclosure.

In one possible embodiment, the area of the drug storage module 16 on the encapsulation layer 15 corresponding to the location of oral administration of the organism may be determined based on the location of actual administration, which is not limiting to the present disclosure. For example, when the living body wearing the device is a heart disease patient, the sublingual nitroglycerin tablet is needed, the nitroglycerin tablet can be placed in the medicine storage module 16 in advance, the medicine storage module 16 with medicine is prevented from being arranged on the packaging layer 15 and in the area between the left middle incisor lingual side of the lower jaw and the right middle incisor lingual side of the lower jaw of the living body, when the heart disease is in an acute attack, the first detection module 11 can convert the sensed pressure signal into the first electric signal by tightly biting the teeth, and under the condition that the voltage value of the first electric signal exceeds the voltage threshold value, the medicine storage module 16 is controlled to release the stored nitroglycerin tablet, so that the quick and accurate administration is realized, and the technical problems of state of illness, sudden death and the like caused by the delay of administration time in the prior art are solved.

In one possible embodiment, the processing module 13 may be further configured to control the drug storage module 16 to release the stored drug if the concentration of the target ion exceeds a concentration threshold after deriving the concentration of the target ion from the second electrical signal. For example, assuming that the concentration of a specific protein in saliva of an organism is related to acute coronary syndrome (Acute Coronary Syndrome, ACS), a drug for treating acute coronary syndrome may be previously placed in the drug storage module 16, and when the acute coronary syndrome patient wears the device, in the case that the processing module 13 determines that the concentration of the specific protein exceeds the concentration threshold value according to the second electrical signal, the drug storage module 16 is controlled to release the stored drug for treating acute coronary syndrome, so that rapid and accurate administration can be achieved, solving the technical problems of deterioration of illness, sudden death, etc. due to a delay of administration time, which exist in the prior art.

According to the oral cavity in-situ flexible detection device provided by the disclosure, through organically combining the first detection module, the second detection module, the processing module and the drug storage module, the monitoring of target ions in saliva can be realized, and simultaneously, the prestored drugs are released, so that organisms wearing the device can timely monitor the physical condition according to the concentration of sodium ions and potassium ions in saliva, the risk of cardiovascular diseases is estimated, the timely early warning effect is achieved, and in an emergency, the release of the prestored drugs can be realized, and thus quick and accurate drug administration is realized, and the technical problems of state of illness worsening, sudden death and the like caused by drug administration time delay in the prior art are solved.

Fig. 4 illustrates a schematic structural view of a drug storage module according to an embodiment of the present disclosure. As shown in fig. 4, the apparatus further includes a heating module connected to the power module 14 through a connection wire 21, and the processing module 13 may include a control sub-module (not shown), and the encapsulation layer 15 is further used to encapsulate the heating module.

The control sub-module starts the heating module when the voltage value of the first electric signal exceeds a voltage threshold. The control submodule is further used for turning off the heating module under the condition that the voltage value of the first electric signal is smaller than or equal to a voltage threshold value. Or the control submodule is further used for turning off the heating module when the time length when the heating module is started exceeds the time length threshold value.

The heating module is used for heating the fuse 405 of the drug storage module 16 after being started.

The drug storage module 16 comprises a housing, a fuse 405 and an elastic connecting piece 403, wherein the housing comprises an upper housing 401 and a lower housing 402, the upper housing 401 and the lower housing 402 are connected together through the fuse 405 and the elastic connecting piece 403 to form the housing, a cavity 407 for storing the drug is formed inside the housing, and when the fuse 405 is heated and fused by the heating module, the upper housing 401 and the lower housing 402 are partially disconnected under the action of the elastic connecting piece 403 to release the drug in the cavity 407.

Wherein, because the oral cavity of organism is moist environment, can play thermal-insulated cooling effect, after the medicine release, the patient stops to bite the tooth tightly, and the voltage value of the first signal of telecommunication that first detection module 11 sensed can be less than voltage threshold value, and control submodule closes heating module, consequently, because heating module's operating time is short and the oral cavity environment has the guard action to the organism for this heating module is less to the influence of oral cavity, and the power consumption is low.

In one possible embodiment, the fuse 405 may be made of a flexible material with a breaking strength greater than 100 newtons and a melting point less than 170 degrees celsius. Wherein the flexible material used to make the fuse 405 is different from the flexible material used to make the flexible substrate, and the melting point of the flexible material used to make the fuse 405 is less than the melting point of the flexible material used to make the flexible substrate, so as to ensure that the fuse 405 is blown without affecting other modules in the device. The flexible material may be provided according to actual needs by those skilled in the art, and this disclosure is not limited thereto.

As shown in fig. 4, the upper housing 401 of the drug storage module 16 may be an upper semi-ellipsoidal housing made of a flexible material, the lower housing 402 may be a lower semi-ellipsoidal housing made of a metal material, and the upper housing 401 and the lower housing 402 form a complete ellipsoidal cavity 407. The three-dimensional shape, cavity shape of the drug storage module 16 may also be provided in other shapes, which is not limiting to the present disclosure.

The elastic connection member 403 may be a buckle, a spring, or the like, which is not limited in this disclosure. The connection portion 404 may be a circular hole in which the upper case 401 and the lower case 402 are connected by fixedly connecting the fuse 405 therein.

Through passing through fuse, elastic connection spare with last casing, lower casing and link together and form the casing, under the circumstances that the fuse was fused by the resistance wire, go up casing and lower casing and partly disconnect under the effect of elastic connection spare, not only can realize releasing the medicine in the medicine storage module, can also keep the partial relation of connection of last casing and lower casing, avoid because last casing breaks away from with lower casing, the circumstances that causes the injury to the organism of wearing the device takes place.

In one possible embodiment, as shown in fig. 4, the heating module may include a resistive wire 406.

A channel 408 is arranged in the lower casing 402, a connecting part 404 is arranged on the upper casing 401 at a first position corresponding to an opening 409 of the channel 408, the fuse 405 is installed in the channel 408, one end 410 of the fuse 405 is fixed in the channel 408, the other end 411 of the fuse 405 is fixed on the connecting part 404, and the resistance wire 406 is wound on the fuse 405;

The elastic connection member 403 is disposed at a second position on the upper housing 401 and the lower housing 402 opposite to the connection portion 404, and fixedly connects the upper housing 401 and the lower housing 402 together at the second position.

By winding the resistance wire around the fuse, the contact area between the resistance wire and the fuse can be increased, and the fuse can be quickly fused when the resistance wire is heated.

In one possible embodiment, the channel 408 may be provided in the lower housing 402 or may be provided on an inner wall of the lower housing 402, which is not limited by the present disclosure.

In one possible implementation, one end 410 of the fuse 405 may also be secured to the resilient connector 403. Wherein the passage 408 extends through the entire lower housing 402 to secure one end 410 of the fuse 405 to the resilient connecting element 403.

In one possible embodiment, the control submodule may further include a overheat shutdown switch and the disconnect switch. The overheat closing switch is used for closing the heating module when the voltage value of the first electric signal is smaller than a voltage threshold value. The cut-off switch is used to switch off the heating module in case the time during which the stored drug is released by the drug storage module 16 exceeds a time threshold. For example, when the patient stops biting the teeth after releasing the medicine, the voltage value of the electric signal sensed by the first detection module 11 is made smaller than the voltage threshold value, and the heating module is stopped from heating, so that the medicine is stopped from being released.

In a possible embodiment, the device may further comprise a wireless transmission module located in a fifth area of the flexible substrate corresponding to the dentition 17 of the living being, connected to the processing module 13, the power module 14 by means of a connection wire 21, for transmitting the concentration of the target ions to a terminal. The fifth area of the flexible substrate corresponding to the dentition 17 of the living being may be any area of the flexible substrate corresponding to the dentition 17 of the living being, except for the first detection module 11, the second detection module 12, the processing module 13, and the power module 14. For example, the wireless transmission module may be located on the flexible substrate in an area corresponding to the lingual side of the first premolars on the right mandible of the living being. The terminal can comprise a display panel, and the concentration of the target ions can be displayed in real time through the display panel, so that a prompt can be sent out under the condition that the concentration of the target ions is abnormal. The terminal may include a mobile phone, a computer, etc. of the organism wearing the device. The display panel may include a LCD (liquid crystal display) display, CRT (cathode ray tube) display, to which the present disclosure is not limited.

Fig. 5 shows a flow diagram of a method of manufacturing an oral in situ flexibility testing device for manufacturing the device described above, the method comprising steps S501 to S509, according to an embodiment of the present disclosure.

In step S501, a flexible substrate matching the shape of the arch curve of a living being is fabricated according to the arch curve of the living being, and a first metal layer is deposited on the flexible substrate.

In step S502, etching the first metal layer according to a preset pattern to form a connection wire of the device.

The connecting wire is formed by etching the first metal layer according to a preset pattern by using a photolithography method, an electron beam evaporation method, an acetone stripping method, and the like, wherein the material of the first metal layer may be Au (gold), constantan, nichrome, iron-chromium-aluminum alloy, platinum-tungsten alloy, and the like, which is not limited in this disclosure. The shape of the connection wire may be a serpentine pattern, a fractal pattern, or the like, which is not limited in the present disclosure.

In step S503, a first detection module is installed in a first area of the flexible substrate, and the first detection module is configured to detect a pressure signal between the upper and lower dentitions of the living body, convert the pressure signal into a first electrical signal, and send the first electrical signal to a processing module.

The first detection module and the connecting wire can be connected together in a welding mode such as gold wire ball welding; the first detection module may also be adhered to the first area by conductive gel and connected to the connection wire, and the present disclosure is not limited to the manner in which the first detection module is installed.

In step S504, a second detection module is manufactured in a second area of the flexible substrate, where the second detection module is configured to detect target ions in saliva of the living body, obtain a second electrical signal, and send the second electrical signal to the processing module.

And depositing a second metal layer in the reference electrode area of the second area, depositing a third metal layer in the counter electrode area of the second area, coating a release agent in the second area, and depositing an insulating layer. The second metal layer may be an Ag (silver) layer, etc., the third metal layer may be a Pt (platinum) layer, etc., and the insulating layer may be parylene, etc., which is not limited in this disclosure.

In step S505, a processing module is mounted in a third region of the flexible substrate, the processing module deriving a concentration of the target ions from the second electrical signal, and controlling a drug storage module to release the stored drug if it is determined that the voltage value of the first electrical signal exceeds a voltage threshold.

The processing module and the connecting wires can be connected together in a welding mode such as gold wire ball welding, the processing module can be stuck to the third area through conductive gel, and the mode of installing the processing module is not limited in the present disclosure.

In step S506, a power module is installed in a fourth area of the flexible substrate, so as to obtain a device to be packaged, where the power module is connected with the second detection module and the processing module through connection wires, and is used for supplying power to the device.

The power module and the connecting wires can be connected together in a welding mode such as gold wire ball welding, and the power module can be stuck to the fourth area through conductive gel.

In one possible implementation manner, the method may further include welding the wireless transmission module in a fifth area of the flexible substrate, wherein the wireless transmission module and the connection wire may be connected together by welding such as gold wire ball welding, or the wireless transmission module may be adhered to the fifth area by conductive gel, and the method for installing the wireless transmission module is not limited in this disclosure.

In step S507, the device to be packaged is packaged to form a packaging layer, so as to obtain the device to be formed.

The device to be packaged can be packaged by using a transparent dental pressure film sheet to form a packaging layer, and a layer of gypsum isolating film is attached to the back surface of the device to be packaged to obtain the device to be formed.

In step S508, the device to be molded is attached to a plaster model prepared from the dentition of a living body, and the molding treatment is performed to obtain a flexible integrated device attached to the dentition of the living body.

A plaster model produced from a dentition of a living body is placed on a vacuum chuck of a vacuum molding machine, and a device to be molded is attached to the plaster model produced from the dentition of the living body. Heating the packaging layer by using a vacuum forming machine to soften and deform the packaging layer, vacuumizing the lower part of the packaging layer, and forming the device to be formed by using the pressure difference between the upper part and the lower part of the packaging layer. Wherein, in the process of heating the packaging layer to soften and deform the packaging layer, the device to be packaged is deformed along with the packaging layer. Wherein, when the device to be formed is attached to the gypsum model, the gypsum isolating film of the device to be formed is contacted with the gypsum model, and the attaching position of the device to be formed and the gypsum model can be adjusted according to the second area on the device to be formed, so that the device to be formed corresponds to the gypsum model.

And after the device to be molded is heated and molded, removing the gypsum isolating film, and polishing the molded device to obtain the flexible integrated device attached to the dentition of the living body.

The device for forming the soft integrated device comprises a soft substrate, a first detection module, a second detection module, a processing module, a power module and a packaging layer, wherein the device for forming the soft integrated device comprises a soft substrate, a first detection module, a second detection module, a processing module, a power module and a packaging layer.

In step S509, a drug storage module is mounted on the encapsulation layer in a region corresponding to the oral administration position of the living body, so as to obtain the oral in-situ flexible detection device, where the drug storage module is used to release the stored drug under the control of the processing module.

The drug storage module can be fixed by direct bonding and clamping, and the drug storage module is not limited in this disclosure. The drug storage module can be fixed by adding a wire mesh, so that the drug storage module is firmer.

In one possible embodiment, where the heating module is a resistance wire, the resistance wire may be connected with the fuse wrap in the drug storage module in a channel of the lower housing of the drug storage module.

Wherein, after step S508, further comprises:

and (3) carrying out windowing treatment on the area, corresponding to the second detection module area, on the flexible integrated device, taking out the insulating layer and the release agent on the second area, cleaning stains on the second area, dripping a conductive polymer solution corresponding to the target ions on the working electrode area of the second area, forming a conductive polymer layer after the solvent in the conductive polymer solution corresponding to the target ions volatilizes, dripping the pre-prepared second selectively permeable membrane solution on the conducting wire polymer layer, and forming a second selectively permeable membrane after the solvent in the second selectively permeable membrane solution volatilizes, thus obtaining the working electrode. Wherein the wire polymer solution may be PEDOT: PSS solution, the second permselective membrane solution may be Na ⁺ Permselective membrane solution, K ⁺ Selective permeable membrane solutions, etc., which may be determined based on the target ions to be detected, the disclosure is not limited in this regard.

After the second metal layer of the reference electrode area is subjected to chlorination treatment, a pre-prepared reference liquid is dripped on the second metal layer after the chlorination treatment, and the reference electrode is formed after the solvent in the reference liquid is volatilized. Wherein, the second metal layer can be subjected to chlorination treatment by adopting a method of dripping 0.1mol/L (mol/L) ferric chloride solution on the second metal layer and washing the second metal layer cleanly after 1 hour, and the mode of the chlorination treatment of the second metal layer is not limited in the disclosure.

And (3) dripping a pre-prepared first selectively permeable membrane solution on the surface of the second area, which is in contact with saliva of the organism, and forming a first selectively permeable membrane after the solvent in the first selectively permeable membrane solution volatilizes, so as to obtain a second detection module.

The foregoing description of the embodiments of the present disclosure has been presented for purposes of illustration and description, and is not intended to be exhaustive or limited to the embodiments disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the various embodiments described. The terminology used herein was chosen in order to best explain the principles of the embodiments, the practical application, or the technical improvement of the technology in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

1. An oral in situ flexibility testing device, the device comprising:

a first detection module located on the flexible substrate and in contact with the dentition of the living being The first area corresponding to the surface is used for detecting a pressure signal between the upper and lower jaw dentitions of the organism, converting the pressure signal into a first electric signal and sending the first electric signal to a processing module, and the first area comprises any one of the following areas: a region on the flexible substrate corresponding to a face of a molar region dentition of a living being, a region on the flexible substrate corresponding to a face of a premolaring region dentition of a living being, a region on the flexible substrate corresponding to a face of an incisor region dentition of a living being;

the processing module is positioned in a third area corresponding to the dentition of the organism on the flexible substrate, is connected with the first detection module and the second detection module through connecting wires, and is used for controlling the drug storage module to release the stored drug under the condition that the voltage value of the first electric signal exceeds a voltage threshold value and obtaining the concentration of the target ions according to the second electric signal;

the medicine storage module is connected with the processing module through a connecting wire, is positioned in an area corresponding to the oral administration position of the organism on the packaging layer and is used for releasing the stored medicine under the control of the processing module;

wherein the device also comprises a heating module connected with the power module through a connecting wire, the processing module comprises a control sub-module, the packaging layer is also used for packaging the heating module,

2. The apparatus of claim 1, wherein the heating module comprises a resistive wire,

3. The apparatus of claim 1, wherein the second detection module comprises at least: the working electrode, the reference electrode and the counter electrode are flatly arranged on the flexible substrate,

4. A device according to claim 3, wherein the surface of the second detection module that is in contact with saliva of a living being is provided with a first selectively permeable membrane for preventing material of the working electrode, reference electrode, counter electrode from entering into saliva of the living being.

5. The apparatus of claim 4, wherein the working electrode comprises a conductive polymer layer for electrochemically reacting with the target ions to generate the second electrical signal.

6. The device of claim 5, wherein the working electrode further comprises a second permselective membrane disposed between the first permselective membrane and the conductive polymer layer, the second permselective membrane configured to pass target ions in saliva of the living being for detection of the target ions by the working electrode.

7. The device of claim 3, wherein the shape of the projection of the working electrode onto the plane of the flexible substrate comprises a circle, the shape of the projection of the reference electrode onto the plane of the flexible substrate comprises a circle, the shape of the projection of the counter electrode onto the plane of the flexible substrate comprises a semi-circle, the working electrode is positioned intermediate the reference electrode and the counter electrode, and the counter electrode surrounds the working electrode.

8. The apparatus of claim 1, further comprising a wireless transmission module connected to the processing module and the power module by a connection wire for transmitting the concentration of the target ions to a terminal.

9. A method of manufacturing an oral in situ flexibility testing device, for use in manufacturing the device of any one of claims 1-8, the method comprising: