CN112690785A

CN112690785A - Oral cavity in-situ flexible detection device and manufacturing method thereof

Info

Publication number: CN112690785A
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: 2021-04-23
Anticipated expiration: 2040-12-10
Also published as: CN112690785B

Abstract

The disclosure relates to an oral cavity in-situ flexibility detection device and a manufacturing method thereof. The first detection module, the second detection module, the processing module and the medicine storage module are organically combined, a detected pressure signal between upper and lower jaw dentitions of the organism is converted into a first electric signal, the medicine storage module is controlled to release the stored medicine under the condition that the voltage value of the first electric signal is determined to exceed a voltage threshold value, target ions in saliva of the organism are detected, a second electric signal is obtained, and the concentration of the target ions is obtained according to the second electric signal. This flexible detection device in oral cavity normal position utilizes integrated into one piece's technology, can closely laminate with the dentition of organism, when realizing the timely early warning of health through the target ion in the monitoring saliva, can realize the release of medicine under emergency, and quick accurate dosing solves the technical problem such as the state of an illness aggravation that the time delay of dosing leads to, sudden death among the prior art.

Description

Oral cavity in-situ flexible 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

The currently adopted in-vitro saliva ion detection mode needs to acquire and store saliva, 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 the collection and storage of saliva samples and the measurement of saliva ion concentration values at a plurality of time points are time-consuming and labor-consuming.

And due to the complexity of the oral environment, space is limited; the moist environment within the oral cavity; lip, cheek, tongue movements caused by chewing and speaking; factors such as swallowing and absorption of saliva generated by organisms increase the difficulty of integrating the biosensor into the oral cavity, and the biocompatibility of the biosensor integrated into the oral cavity requires higher requirements, so that the real-time in-situ detection of the concentration of ion and other biomarkers in the saliva is very challenging. In the related art, only the intraoral biosensor and the oral device are simply assembled together, and after an electrode of the intraoral biosensor is connected with an external device through a wire or an induction coil, the detected signal is further processed and converted, and in the process, the detected signal is easy to have a distortion problem. Moreover, part of oral devices (such as a denture) have large volume, are not well jointed with tissues in the oral cavity and are uncomfortable to wear; the sensors in the mouth need to be supported by large-scale equipment, and are inconvenient to use. On the other hand, the simple assembly of the intraoral biosensor with the oral device also fails to meet the diverse needs of users.

Disclosure of Invention

In view of this, the present disclosure provides an oral cavity in-situ flexibility detection apparatus and a manufacturing method thereof.

According to an aspect of the present disclosure, there is provided an oral cavity in-situ flexibility detection apparatus, the apparatus including:

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

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 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 the processing module;

the second detection module is positioned in a second area, opposite to the salivary gland of the organism, on the flexible substrate and 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;

the processing module is positioned in a third area corresponding to dentition of the organism on the flexible substrate, is connected with the first detection module and the second detection module through connecting leads, and is used for controlling the drug storage module to release the stored drugs under the condition that the voltage value of the first electric signal is determined to exceed 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 quickly and accurately administering the drugs under the emergency condition;

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 leads and is used for supplying power to the device;

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

the medicine storage module is connected with the processing module through a connecting lead, is positioned on the packaging layer in an area corresponding to the oral administration position of the organism, 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 with the power supply module through a connecting lead, the processing module comprises a control sub-module, the packaging layer is also used for packaging the heating module,

the control sub-module starts the heating module under the condition that the voltage value of the first electric signal is determined to exceed a voltage threshold value;

the heating module is used for heating the fuse of the medicine storage module after being started;

the drug 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 the drugs is formed in 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 to release the drugs in the cavity.

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

a channel is arranged in the lower shell, a connecting part is arranged at a first position, corresponding to the opening of the channel, on the upper shell, the fuse is installed 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, opposite to the connecting part, on the upper shell and the lower shell, and fixedly connects the upper shell and the lower shell together at the second position.

In a possible embodiment, the second detection module comprises at least: a working electrode, a reference electrode and a counter electrode, wherein the working electrode, the reference electrode and the counter electrode are flatly laid on the flexible substrate,

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

and 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 a possible embodiment, the surface of the second detection module that is in contact with saliva of a biological body is provided with a first permselective membrane for preventing the materials of the working electrode, the reference electrode and the counter electrode from entering the saliva of the biological body.

In one possible embodiment, the working electrode includes a conductive polymer layer for electrochemically reacting with the target ion to generate the second electrical signal.

In one possible embodiment, the working electrode further comprises a second selectively permeable membrane disposed between the first selectively permeable membrane and the conductive polymer layer for passing target ions in saliva of the organism for detection of the target ions by the working electrode.

In a possible embodiment, a projected shape of the working electrode on the plane of the flexible substrate includes a circle, a projected shape of the reference electrode on the plane of the flexible substrate includes a circle, a projected shape of the counter electrode on the plane of the flexible substrate includes a half-ring, 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 apparatus further includes a wireless transmission module, connected to the processing module and the power supply module through connecting wires, for transmitting the concentration of the target ions to a terminal.

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

according to the dental arch curve of a living body, a flexible substrate matched with the shape of the dental arch curve is manufactured, and a first metal layer is deposited 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 used for detecting a pressure signal between an upper jaw dentition and a lower jaw dentition of the organism, converting the pressure signal into a first electric signal and sending the first electric signal 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 a 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 a drug storage module to release the stored drug when the voltage value of the first electric signal is determined to exceed a voltage threshold value;

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

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

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

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 the stored medicines under the control of the processing module.

According to the oral cavity in-situ flexible detection device and the manufacturing method thereof provided by the embodiment of the disclosure, by arranging the flexible substrate, the first detection module, the second detection module, the processing module, the power supply module, the packaging layer and the medicine storage module, the oral cavity in-situ flexible detection device can be tightly attached to dentition of an organism, monitoring of target ions in saliva is realized, and in an emergency situation, release of medicines is realized, so that rapid and accurate medicine delivery is realized, and the technical problems of illness deterioration, sudden death and the like caused by time delay of medicine delivery in the prior art are solved.

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 disclosure and, together with the description, serve to explain the principles of the disclosure.

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

Fig. 2 shows a schematic structural diagram of a connecting wire according to an embodiment of the present disclosure.

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

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

Fig. 5 shows a schematic flow chart of a method for manufacturing an oral cavity in-situ flexibility detection device according to an embodiment of the present disclosure.

List of reference numerals

11 a first detection module; 12 a second detection module; 13 a processing module; 14 a power supply module; 15 an encapsulation layer; 16 a drug storage module; 17 dentition of an organism; 21 connecting a lead; a 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 shell; 402 a lower housing; 403 an elastic connection member; 404 a connecting part; 405 a fuse; 406 resistance wire; 407 cavities; 408 a channel; 409 at an opening; 410 one end of a fuse; 411 the other end of the fuse.

Detailed Description

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

The word "exemplary" is used exclusively 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.

Furthermore, in the following detailed description, numerous specific details are set forth 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 that are well known to those skilled in the art have not been described in detail so as not to obscure the present disclosure.

With the increasing development of economic construction in China, the living standard of people is continuously improved, disease spectrums in cities and rural areas are changing, infectious diseases are reduced, the life of people is prolonged, and the morbidity and mortality of cardiovascular diseases, particularly hypertension, cerebral apoplexy and coronary heart disease are obviously increased 30 years ago. And when the cardiovascular disease is acute, the patient can not be treated in time due to factors such as incorrect administration mode, delayed administration time and the like, and the condition of the patient is affected. How to realize the detection of the concentration of the ion biomarker in the oral in-situ saliva and the targeted drug delivery is a technical problem to be solved urgently.

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

a flexible substrate (not shown in fig. 1, since it is identical in structure to the encapsulation layer 15) having a shape that matches the shape of the dentition 17 of the living being, such that the device is worn on the dentition 17 of the living being.

The first detection module 11 is located in a first area on the flexible substrate corresponding to the surface of the dentition 17 of the living body, and is used for detecting a pressure signal between the upper and lower jaw dentitions of the living body, converting the pressure signal into a first electric signal, and sending the first electric signal to the processing module 13.

The second detection module 12 is located in a second region of the flexible substrate opposite to the salivary gland of the biological body, and is configured to detect a target ion in saliva of the biological body, obtain a second electrical signal, and send the second electrical 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 lead 21, and is used for controlling the drug storage module 16 to release the stored drugs under the condition that the voltage value of the first electric signal is determined to exceed the voltage threshold, obtaining the concentration of the target ions according to the second electric signal, monitoring the physical condition, realizing timely early warning and quickly and accurately administering the drugs under the emergency condition.

And the power supply module 14 is positioned in a fourth area corresponding to the dentition 17 of the organism on the flexible substrate, is connected with the second detection module 12 and the processing module 13 through connecting leads 21, and is used for supplying power for the device.

An encapsulation layer 15, the shape of the encapsulation layer 15 matching the shape of the dentition 17 of the living being, for encapsulating the flexible substrate, the connecting leads 21, the first detection module 11, the second detection module 12, the processing module 13, the power module 14.

A drug storage module 16 connected to the processing module 13 through a connecting wire 21, located in a region of the encapsulation layer 15 corresponding to the oral administration site of the living body, 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 the shape of the mandibular dentition of the living being, a device that matches the shape of the maxillary dentition of the living being, or a device that matches the shape of the upper and lower mandibular dentitions of the living being.

Wherein, in case that the apparatus is an apparatus which is matched with the shape of the upper and lower dentitions of the living body, respectively, the apparatus may include a first apparatus which is matched with the shape of the upper dentition of the living body and a second apparatus which is matched with the shape of the lower dentition of the living body, and the first apparatus and the second apparatus may be used as an orthodontic appliance. Wherein the first detection module 11 and the drug storage module 16 must be simultaneously provided in the first device matching the maxillary dentition shape of the living body or the second device matching the mandibular dentition shape of the living body, and the second detection module 12 may be separately provided in the first device matching the maxillary dentition shape of the living body or the second device matching the mandibular dentition shape of the living body. The setting positions of the processing module and the power supply module, and the role of the processing module provided in the first device and/or the second device may be determined according to the setting positions of the first detection module 11, the second detection module 12, and the drug storage module 16 (provided in the first device or the second device). For example, in the case where the first detection module 11, the drug storage module 16 and the second detection module 12 are provided in the first device and the second device, respectively, the first device and the second device need to be provided with a power supply module and a processing module. 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 is determined to exceed 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 which are used for obtaining the concentration of the target ions according to the second electric signal in the second device.

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

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

The first region of the first detection module 11 on the flexible substrate corresponding to the face of the dentition 17 of the living body may be any one of the following regions: for example, the first detection module 11 may be located on the flexible base in a region corresponding to a face of one of the teeth in the molars of the living being, the first detection module 11 may be located on the flexible base in a region corresponding to a face of one of the teeth in the premolars of the living being, the first detection module 11 may be located on the flexible base in a region corresponding to a face of a second molar on the right side of the mandible of the living being, and the first detection module 11 may be located on the flexible base in a region corresponding to a face of a second molar on the right side of the living being. The first region on the flexible substrate can be configured by those skilled in the art according to actual needs, and the disclosure is not limited thereto.

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

Wherein, the third region of the processing module 13 corresponding to the dentition 17 of the living body on the flexible substrate may be any region except the first detection module 11 and the second detection module 12 corresponding to the dentition 17 of the living body on the flexible substrate. For example, the treatment module 13 may be located in a region corresponding to a second premolar buccal region on a right side of a mandible of the living being, and a person skilled in the art may set the third region on the flexible substrate according to actual needs, which the present disclosure does not limit.

In a 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 when it is determined that the voltage value of the first electrical signal exceeds the voltage threshold, and the second processing sub-module is configured to obtain the concentration of the target ion according to the second electrical signal. Wherein the first detection module 11, the drug storage module 16, the first processing sub-module must be simultaneously provided in a first device matching the maxillary dentition shape of the living being or in a second device matching the mandibular dentition shape of the living being, and the second detection module 12, the second processing sub-module must be simultaneously provided in the first device matching the maxillary dentition shape of the living being or in the second device matching the mandibular dentition shape of the living being. 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 may be determined according to the setting positions of the first detection module 11, the second detection module 12, and the medicine storage module 16 (whether set in the first device or the second device).

In a possible embodiment, in case the first detection module 11 is located on the flexible base 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 a voltage value of the electrical signal corresponding to an occlusal force of 300 newtons. However, since the corresponding relationship between the first electrical signal and the occlusal force of different pressure sensors is different, and the occlusal force between the upper and lower jaw dentitions of different ages of living bodies is also different, a person skilled in the art can set the voltage threshold of the first electrical signal according to the actual situation of different living bodies, which is not limited by the present disclosure.

Wherein, the second region of the second detection module 12 opposite to the salivary gland of the organism on the flexible substrate can be any one of the following regions: 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 corresponding to a second molar buccal side on a left maxillary side of the living body, and is used for detecting the target ions in saliva generated by a parotid gland of the living body. The second detection module 12 may also be located in a middle region of the incisor tongue side in the left side of the mandible of the living being and the incisor tongue side in the right side of the mandible of the living being for detecting the target ions in saliva generated by the submandibular and sublingual glands of the living being. The second region on the flexible substrate can be set by those skilled in the art according to actual needs, and the disclosure is not limited thereto.

In a possible embodiment, the second detection module 12 may comprise at least: the device comprises a working electrode, a reference electrode and a counter electrode, wherein the working electrode, the reference electrode and the counter electrode are flatly laid on the flexible substrate.

The working electrode and the reference electrode form a measuring loop for measuring a second electric signal generated in the process that the target ions perform electrochemical reaction 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 different target ions. 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 detect different target ions, and the reference electrode may be a common reference electrode for multiple target ions. It should be noted that, the working electrode and the counter electrode can be set by those skilled in the art according to the target ions to be actually detected, and the disclosure is not limited thereto.

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

Fig. 3 shows a schematic structural diagram 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 a 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 and 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 and 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 in the shape of a semi-ring 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 in the shape of a semi-ring with the same center as the sodium ion working electrode 32, and the sodium ion counter electrode 34 surrounds the sodium ion working electrode 32.

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

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 a cylinder with a radius less than or equal to 1 mm and a height less than or equal to 1 micron, and the counter electrode may be configured as a half-ring surrounding the working electrode and having an inner radius less than or equal to 1.2 mm, an outer radius less than or equal to 2.5 mm and a height less than or equal to 1 micron, wherein the distance between the working electrode and the counter electrode may be greater than 0.2 mm and less than 1 mm.

In a possible embodiment, the surface of the second detection module 12 that is in contact with the saliva of the biological body is provided with a first permselective membrane for preventing the materials of the working electrode, the reference electrode and the counter electrode from entering the saliva of the biological body. Wherein the first selectively permeable membrane may be a medical biocompatible membrane. The medical biocompatible membrane can be a cuprammonium cellulose 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 biocompatible membrane for medical use can be set by those skilled in the art according to actual needs, and the present disclosure does not limit this.

Through setting up first selective permeability membrane, because first selective permeability membrane is biocompatible polymer film, can not cause the injury to the organism to this first selective permeability membrane can also prevent that harmful substance in working electrode, reference electrode, the counter electrode from entering into the saliva of organism, can also avoid harmful substance in working electrode, reference electrode, the counter electrode to cause the injury to the organism.

In one possible embodiment, the working electrode includes a conductive polymer layer for electrochemically reacting with the target ion to generate the second electrical signal. The conductive polymer layer is formed after the solvent in the conductive polymer solution is volatilized, the solute in the conductive polymer solution may include polythiophene, polypyrrole, polyaniline, and the like, and a person 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 by 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 formula,

wherein PEDOT⁺PSS^- _(film)Denotes the poly (3, 4-ethylenedioxythiophene) -poly (styrenesulfonic acid) ion, K, in the conductive polymer layer⁺ _(membrane)Represents potassium ion in saliva of organism, PEDOT⁰PSS^-K⁺ _(film)Represents potassium poly (3, 4-ethylenedioxythiophene) -poly (styrenesulfonate), e^-And represents the charge required by the target ion in the process of electrochemically reacting with the conductive polymer layer, i.e., the second electrical signal.

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

wherein a represents the concentration of target ions, z_aTo representValence of target ion, R represents gas constant, T represents temperature, F represents Faraday constant, E_measRepresenting the potential generated by all ions in the saliva of an organism, E₀Representing the potential generated by ions other than the target ion in saliva of the organism. Wherein E is a condition where only the target ion enters the working electrode and electrochemically reacts with the conductive polymer layer in the working electrode₀Is 0.

By arranging the first detection module 11 and the processing module 13, the concentration of the target ions in the saliva of the organism can be detected, a basic value is provided for preventing and treating oral diseases, and reference is provided for differential diagnosis of clinical diseases.

In one possible embodiment, the working electrode may further include a second selectively permeable film disposed between the first selectively permeable film and the conductive polymer layer, the second selectively permeable film for passing 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 according to the target ion to be detected. For example, when the target ion to be detected is sodium ion, the second permselective membrane may include sodium ion carrier, 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 include valinomycin (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 arrange the second permselective membrane according to the target ion to be detected, and the present disclosure is not limited thereto.

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

In one possible embodiment, the processing module 13 may include a voltage buffer, a differential amplifier, a low-pass filter, a transimpedance amplifier, and an analog-to-digital converter, and is configured to preprocess the received first and second electrical signals, control the drug storage module 16 to release the stored drug if it is determined that the voltage value of the first electrical signal exceeds a voltage threshold after the preprocessing of the first and second electrical signals, and obtain the concentration of the target ion according to the second electrical signal.

In one possible embodiment, the fourth region of the power module 14 on the flexible substrate corresponding to the dentition 17 of a living being may be any region on the flexible substrate corresponding to the dentition 17 of a living being except for the first detection module 11, the second detection module 12, and the processing module 13. For example, the power module 14 may be located on the flexible base in an area corresponding to the lingual side of the second premolar on the right side of the 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 a person skilled in the art may set the power module 14 according to actual needs, which is not limited by the disclosure.

In one possible embodiment, the encapsulation layer 15 may be a transparent dental laminate film. The dental film pressing sheet can be made of resin, is safe and non-toxic, can be softened and reshaped by heating, has the softening and reshaping temperature of 140-160 ℃, and cannot cause adverse effects on other modules in the device. Wherein the thickness of the encapsulation layer 15 is less than or equal to 1.5 millimeters, which is not limited by the present disclosure.

In one possible embodiment, the area of the drug storage module 16 on the encapsulation layer 15 corresponding to the oral administration site of the living body may be determined according to the actual administration site, which is not limited by the present disclosure. For example, when the organism wearing the device is a heart disease patient, and the nitroglycerin tablet needs to be sublingually taken, the nitroglycerin tablet can be placed in the medicine storage module 16 in advance, the medicine storage module 16 for preventing medicines is arranged in the area between the packaging layer 15 and the incisor tongue side in the left side of the lower jaw and the incisor tongue side in the right side of the lower jaw of the organism, when the heart disease is in acute attack, the first detection module 11 can convert the sensed pressure signal into a first electric signal by tightly biting the teeth, and the medicine storage module 16 is controlled to release the stored nitroglycerin tablet under the condition that the voltage value of the first electric signal exceeds the voltage threshold value, so that the rapid and accurate administration is realized, and the technical problems of disease deterioration, sudden death and the like caused by administration time delay in the prior art are solved.

In a 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 the concentration of the target ion is obtained according to the second electrical signal. For example, assuming that the concentration of a specific protein in saliva of a living body is related to Acute Coronary Syndrome (ACS), a drug for treating Acute Coronary Syndrome may be placed in the drug storage module 16 in advance, and when the device is worn by a patient with Acute Coronary Syndrome, the drug storage module 16 is controlled to release the stored drug for treating Acute Coronary Syndrome in case that the processing module 13 determines that the concentration of the specific protein exceeds a concentration threshold according to the second electric signal, so as to achieve rapid and accurate drug delivery, and solve technical problems of disease deterioration, sudden death and the like caused by drug delivery time delay in the prior art.

According to the flexible detection device of oral cavity normal position that this disclosure provides, through with first detection module, the second detection module, the processing module, the organic combination of medicine storage module, can be when realizing the monitoring to the target ion in the saliva, release the medicine of prestoring, thereby can make the organism of wearing the device can be in time according to sodium in the saliva, potassium ion concentration real-time supervision health, the risk of cardiovascular disease takes place in the aassessment, play the effect of timely early warning, and, under emergency, can realize the release of the medicine of prestoring, thereby realize quick accurate dosing, solve exist among the prior art because the time delay of dosing leads to the state of an illness to worsen, technical problem such as sudden death.

Fig. 4 shows a schematic structural diagram 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 via a connecting wire 21, the processing module 13 may include a control sub-module (not shown), and the packaging layer 15 is further used for packaging the heating module.

The control submodule starts the heating module when the voltage value of the first electric signal is determined to exceed a voltage threshold value. Wherein the control sub-module is further configured to turn off the heating module if it is determined that the voltage value of the first electrical signal is less than or equal to the voltage threshold. Or the control sub-module is further used for closing the heating module when the time length for which the heating module is started is determined to exceed the time length threshold value.

The heating module is configured to heat the fuse 405 of the drug storage module 16 after activation.

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 by the elastic connecting piece 403 to release the drug in the cavity 407.

Wherein, because the oral cavity of organism is the 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 sensing to can be less than the voltage threshold, and the control submodule piece closes the heating module, consequently, because the operating time of heating module is short and the oral cavity environment has the guard action to the organism for this heating module is less to the influence in oral cavity, and consumes energy lowly.

In one possible embodiment, the fuse 405 may be made of a flexible material with a breaking force greater than 100 newtons and a melting point less than 170 degrees celsius. The flexible material used for manufacturing the fuse 405 is different from the flexible material used for manufacturing the flexible substrate, and the melting point of the flexible material used for manufacturing the fuse 405 is smaller than that of the flexible material used for manufacturing the flexible substrate, so as to ensure that other modules in the device are not affected when the fuse 405 is fused. The flexible material can be configured by those skilled in the art according to actual needs, and the present 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 and cavity shape of the drug storage module 16 may be configured in other shapes, which is not limited by the present disclosure.

Wherein, the elastic connection 403 may be a buckle, a spring, etc., which is not limited by the present disclosure. The connection portion 404 may be a circular hole in which the fuse 405 is fixedly connected, thereby connecting the upper case 401 and the lower case 402 together.

Through with last casing, lower casing pass through the fuse, elastic connecting piece links together and forms the casing, under the condition that the fuse was fused by the resistance wire, go up casing and lower casing disconnection part under elastic connecting piece's effect, not only can realize releasing the medicine in the medicine storage module, can also keep the partial connection relation of casing and lower casing, avoid because last casing breaks away from with lower casing, the condition emergence that causes the injury to the organism of wearing the device.

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

A channel 408 is arranged inside the lower shell 402, a connecting part 404 is arranged at a first position on the upper shell 401 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 connecting member 403 is disposed on the upper housing 401 and the lower housing 402 at a second position opposite to the connecting portion 404, and fixedly connects the upper housing 401 and the lower housing 402 at the second position.

The resistance wire is wound on the fuse, so that the contact area of the resistance wire and the fuse can be increased, and the fuse can be rapidly fused under the condition that the resistance wire is heated.

In one possible embodiment, the channel 408 may be disposed in the lower housing 402, or may be disposed 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 fixed to the elastic connector 403. Wherein the channel 408 extends through the entire lower housing 402 such that one end 410 of the fuse 405 is secured to the resilient connector 403.

In one possible embodiment, the control submodule may further include an overheat shutdown switch and the cut-off switch. The overheating closing switch is used for closing the heating module under the condition that the voltage value of the first electric signal is smaller than a voltage threshold value. The cut-off switch is used to turn off the heating module if the time for the drug storage module 16 to release the stored drug exceeds a time threshold. For example, when the patient stops biting the teeth after the drug is released, the voltage value of the electrical signal sensed by the first detection module 11 is smaller than the voltage threshold, the heating of the heating module is stopped, and the drug is stopped being released.

In a possible embodiment, the apparatus may further comprise a wireless transmission module, located on a fifth region of the flexible substrate corresponding to the dentition 17 of the living being, connected to the processing module 13 and the power supply module 14 through connecting wires 21, for transmitting the concentration of the target ions to a terminal. Wherein, the fifth area of the wireless transmission module corresponding to the dentition 17 of the living body on the flexible substrate may be any area of the flexible substrate corresponding to the dentition 17 of the living body except for the first detection module 11, the second detection module 12, the processing module 13 and the power supply module 14. For example, the wireless transmission module may be located on the flexible base in a region corresponding to the lingual side of the first premolar on the right side of the 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 when the concentration of the target ions is abnormal. Wherein, the terminal can comprise a mobile phone, a computer and the like of the organism wearing the device. The display panel may include an lcd (liquid crystal display) display, a crt (cathode ray tube) display, and the disclosure is not limited thereto.

Fig. 5 is a schematic flow chart illustrating a method for manufacturing an oral cavity in-situ flexibility detection device according to an embodiment of the present disclosure, the method being used for manufacturing the device and including steps S501 to S509.

In step S501, a flexible substrate is fabricated to match the shape of an arch curve of a living body, and a first metal layer is deposited on the flexible substrate.

In step S502, the first metal layer is etched according to a predetermined pattern to form a connection wire of the device.

The connection lead 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, or the like, where the material of the first metal layer may be Au (gold), constantan, nichrome, iron-chromium-aluminum alloy, platinum-tungsten alloy, or the like, which is not limited in this disclosure. Wherein, the shape of the connecting wire may be a serpentine pattern, a fractal pattern, etc., which is not limited by the present disclosure.

In step S503, a first detection module is installed on a first region of the flexible substrate, and the first detection module is configured to detect a pressure signal between upper and lower jaw 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 lead can be connected together in a welding mode such as gold wire ball bonding; the first detection module may also be attached to the first region by a conductive gel, and connected to the connecting wires, and the present disclosure is not limited to the manner of mounting the first detection module.

In step S504, a second detection module is manufactured in a second region of the flexible substrate, and 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 a processing module.

Wherein a second metal layer is deposited on the reference electrode area of the second region, a third metal layer is deposited on the counter electrode area of the second region, a release agent is applied to the second region, and an insulating layer is deposited. 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 a parylene, etc., which is not limited in the present disclosure.

In step S505, a processing module is installed in a third region of the flexible substrate, the processing module obtains the concentration of the target ions according to the second electrical signal, and controls a drug storage module to release the stored drug when it is determined that the voltage value of the first electrical signal exceeds a voltage threshold.

The processing module and the connecting wire can be connected together by welding such as gold wire ball bonding, and the processing module can be adhered to the third area by the conductive gel.

In step S506, a power module is installed in a fourth region of the flexible substrate to obtain a device to be packaged, wherein the power module is connected to the second detection module and the processing module through connecting wires and is used for supplying power to the device.

The power module and the connecting wire can be connected together by welding such as gold wire ball bonding, and the power module can be adhered to the fourth area by the conductive gel.

In a possible implementation manner, the method may further include welding a wireless transmission module on a fifth area of the flexible substrate, wherein the wireless transmission module and the connecting wires may be connected together by welding such as gold wire ball bonding, and the wireless transmission module may also be adhered to the fifth area by a conductive gel, and the disclosure does not limit the manner of installing the wireless transmission module.

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

The device to be packaged can be packaged by utilizing a transparent dental film to form a packaging layer, and a gypsum isolation film is attached to the back 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 produced from the dentition of the living body, and a flexible integrated device attached to the dentition of the living body is obtained after the molding process.

A plaster model produced from the dentition of a living body is placed on a vacuum chuck of a vacuum forming machine, and a device to be formed is attached to the plaster model produced from the dentition of the living body. And 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 utilizing 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 can deform along with the packaging layer. Wherein, will treat the forming device laminating according to the in-process at the gypsum model, treat that forming device's gypsum barrier film contacts with this gypsum model, can treat the laminating position of forming device and gypsum model according to treating the regional adjustment of second on the forming device to make and treat that forming device and gypsum model are corresponding.

And after the device to be formed is heated and formed, removing the gypsum isolation film, and polishing the formed device to obtain the flexible integrated device which is attached to the dentition of the organism.

Through the integrated into one piece's technique realization "wait to form device → flexible integrated device", can make the integrated into one piece of flexible basement, first detection module, second detection module, processing module, power module, encapsulation layer for the flexible integrated device after the shaping closely laminates with the dentition of organism, and the pleasing to the eye degree is high, and foreign matter feels little.

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

The drug storage module may be fixed by direct bonding or clamping, which is not limited by the present disclosure. Wherein, can also fix medicine storage module through the mode that adds the wire mesh to it is more firm to make medicine storage module.

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

After step S508, the method further includes:

and carrying out windowing treatment on the region, corresponding to the second detection module region, on the flexible integrated device, taking out the insulating layer and the release agent on the second region, cleaning stains on the second region, dripping a conductive polymer solution corresponding to target ions on the working electrode region of the second region, forming a conductive polymer layer after the solvent in the conductive polymer solution corresponding to the target ions is volatilized, dripping a pre-modulated second selective permeable film solution on the conductive polymer layer, and forming a second selective permeable film after the solvent in the second selective permeable film solution is volatilized to obtain the working electrode. The lead polymer solution may be PEDOT: the PSS solution and the second selectively permeable membrane solution may be Na⁺Selectively permeable Membrane solution, K⁺The selective permeable membrane solution, etc., may be determined according to the target ion to be detected, and the present disclosure does not limit this.

After the second metal layer of the reference electrode region is chloridized, a reference solution prepared in advance is dripped on the second metal layer after the chlorination, and after a solvent in the reference solution is volatilized, the reference electrode is formed. The second metal layer may be subjected to chlorination treatment by a method of dropping 0.1mol/L (mol per liter) ferric chloride solution on the second metal layer and washing the second metal layer after 1 hour, and the present disclosure does not limit the manner of chlorination treatment of the second metal layer.

And (3) dripping a first selective permeability membrane solution prepared in advance on the surface of the second area, which is in contact with the saliva of the organism, and forming a first selective permeability membrane after the solvent in the first selective permeability membrane solution is volatilized to obtain a second detection module.

Having described embodiments of the present disclosure, the foregoing description is intended to be exemplary, not exhaustive, and not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The terms used herein were chosen in order to best explain the principles of the embodiments, the practical application, or technical improvements to the techniques in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

1. An oral cavity in-situ flexibility detection device, the device comprising:

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

2. The device of claim 1, further comprising a heating module connected to the power module via a connecting wire, wherein the processing module comprises a control sub-module, and wherein the encapsulation layer is further configured to encapsulate the heating module,

3. The device of claim 2, wherein the heating module comprises a resistive wire,

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

5. The device of claim 4, wherein the surface of the second detection module in contact with the saliva of the biological subject is provided with a first selectively permeable membrane for preventing the material of the working, reference and counter electrodes from entering the saliva of the biological subject.

6. The device of claim 5, wherein the working electrode comprises a conductive polymer layer configured to electrochemically react with the target ion to generate the second electrical signal.

7. The device of claim 6, wherein the working electrode further comprises a second selectively permeable membrane disposed between the first selectively permeable membrane and the conductive polymer layer, the second selectively permeable membrane for passage of target ions in saliva of the organism for detection of the target ions by the working electrode.

8. The apparatus of claim 4, wherein the projected shape of the working electrode on the plane of the flexible substrate comprises a circle, the projected shape of the reference electrode on the plane of the flexible substrate comprises a circle, the projected shape of the counter electrode on the plane of the flexible substrate comprises a half-circle, the working electrode is located between the reference electrode and the counter electrode, and the counter electrode surrounds the working electrode.

9. The device of claim 1, further comprising a wireless transmission module connected to the processing module and the power supply module via connecting wires for transmitting the concentration of the target ions to a terminal.

10. A method of manufacturing an oral cavity in-situ flexibility detection device, for manufacturing the device of any one of claims 1-9, the method comprising: