An implantable multi-parameter biosensor device and multi-parameter monitoring method and use thereof

Abstract

The present invention provides an implantable multi-parameter biosensor device and a multi-parameter monitoring method and use. The implantable multi-parameter biosensor device includes an electrically connected detection unit and a control unit. The detection unit is implanted in the human body for continuous monitoring. The detection unit includes a catheter matrix, a reference electrode and at least two working electrodes. The reference electrode is inserted into the catheter matrix. The outer surface of the catheter matrix is ​​provided with at least two fixed grooves along the axial direction. The working electrode is arranged in the fixed groove. The reference electrode and the working electrode are electrically connected to the control unit respectively. The present invention has a simple structure and is easy to operate. It can realize the simultaneous detection of multiple different biological parameters, and can continuously monitor the fluctuation of the patient's physiological parameters in real time, so that doctors can intervene in patients in a timely manner.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology and relates to a biosensor, in particular to an implantable multi-parameter biosensor device and a multi-parameter monitoring method and application. Background Art

[0002] The management of critically ill patients in the intensive care unit (ICU) requires frequent monitoring of some physiological parameters (such as blood oxygen saturation, blood pressure, temperature, arterial blood gas, glucose, lactose, electrolytes, etc.), which is essential for stabilizing the patient's vital signs and reducing the patient's mortality rate, such as performing arterial blood gas analysis to assess the patient's respiratory and hemodynamic functions. At present, these parameters in the intensive care unit are mostly monitored by bedside monitoring (POCT), however, this method only provides instantaneous test results, and cannot provide long-term dynamic changes and "early warning functions".

[0003] CN210665602U discloses an implantable biosensor, comprising a flexible substrate, wherein the flexible substrate comprises a first base surface and a second base surface, both of which are provided with insulating coatings; a conductive layer is provided on the first base surface of the flexible substrate, and a working electrode area and a reference electrode area are formed, a first conductive band corresponding to the working electrode area and a second conductive band corresponding to the reference electrode area are provided, and a first connection area and a second connection area connected to an external electronic device are provided; an enzyme-containing polymer sensing layer is fixed on the inner surface of the working electrode area.

[0004] CN112294318A discloses an implantable micro biosensor, comprising: a substrate including an implantation end and being implanted under the skin of a living body along an implantation direction, a first electrode disposed on a surface of the substrate and serving as a counter electrode, a second electrode disposed at intervals from the first electrode, a third electrode serving as a working electrode, and a chemical reagent layer. The first electrode comprises a front end portion extending along the implantation direction and located at the implantation end, and the sensing section of the first electrode at least comprises the front end portion. The second electrode comprises a sensing section located at the implantation end and having an area smaller than that of the sensing section of the first electrode, and the third electrode comprises a sensing section located at the implantation end. The chemical reagent layer at least covers the sensing section of the third electrode, so that the third electrode selectively cooperates with the first electrode, or the first electrode and the second electrode for measurement.

[0005] CN10154887U8 discloses an implantable biosensor, which includes a sensor probe composed of a first electrode assembly and a second electrode assembly, the first electrode assembly and the second electrode assembly are connected by a wire, the first electrode assembly is sleeved in a tubular second electrode assembly, and one or more micropores are opened on the tube wall of the second electrode assembly. A reference electrode is installed in the tubular second electrode assembly, a biosensor layer is provided on the outer wall of the first electrode assembly, and a biosensor layer is provided on the inner tube wall of the second electrode assembly.

[0006] How to improve the structure of biosensors so that they can monitor the dynamic changes of biological parameters for a long time and realize early warning functions has become an important research direction. Summary of the invention

[0007] In view of the shortcomings of the prior art, the purpose of the present invention is to provide an implantable multi-parameter biosensor device and a multi-parameter monitoring method and use. The sensor device has a simple structure and is easy to operate. It can simultaneously detect multiple different biological parameters and continuously monitor the fluctuations of the patient's physiological parameters in real time, making it convenient for doctors to intervene in patients in a timely manner.

[0008] To achieve this object, the present invention adopts the following technical solutions:

[0009] In a first aspect, the present invention provides an implantable multi-parameter biosensor device, wherein the implantable multi-parameter biosensor device comprises an electrically connected detection unit and a control unit, and the detection unit is implanted in a human body for continuous monitoring.

[0010] The detection unit includes a catheter matrix, a reference electrode and at least two working electrodes. The reference electrode is inserted into the catheter matrix. The outer surface of the catheter matrix is ​​provided with at least two fixed grooves along the axial direction. The working electrode is located in the fixed grooves. The reference electrode and the working electrode are electrically connected to the control unit respectively.

[0011] The present invention provides an implantable multi-parameter biosensor device, which has a simple structure and is easy to operate. It can detect multiple different biological parameters at the same time and continuously monitor the fluctuation of the patient's physiological parameters in real time, making it convenient for doctors to intervene in patients in a timely manner.

[0012] The implantable multi-parameter biosensor device provided by the present invention can be implanted into a patient's body through an arterial indwelling needle or a sheath tube to achieve the purpose of real-time continuous monitoring.

[0013] As a preferred technical solution of the present invention, a through central cavity is provided in the catheter base, and the reference electrode is inserted into the central cavity.

[0014] Preferably, the reference electrode comprises a first conductive electrode and a first conductive layer coated on a surface of the first conductive electrode.

[0015] Preferably, the working electrode comprises a second conductive electrode and a second conductive layer coated on a surface of a portion of the second conductive electrode.

[0016] Preferably, a section of the reference electrode coated with the first conductive layer extends into the central cavity.

[0017] Preferably, a section of the working electrode coated with the second conductive layer extends into the fixing groove.

[0018] Preferably, the first conductive electrode and the second conductive electrode independently include any one of a silver conductive electrode, a gold conductive electrode or a copper conductive electrode, or a combination of at least two of them.

[0019] Preferably, the first conductive layer and the second conductive layer independently comprise silver chloride.

[0020] Preferably, both the reference electrode and the working electrode are needle-shaped structures.

[0021] As a preferred technical solution of the present invention, a limiting groove is axially provided in the fixing groove, and the working electrode is partially embedded in the limiting groove.

[0022] Preferably, the working electrodes are wrapped with an insulating layer, and the insulating layer is used to prevent mutual interference between the working electrodes.

[0023] Preferably, the fixing groove is filled with a filler to form the insulating layer.

[0024] Preferably, the insulating layer comprises any one of epoxy resin, acrylic resin or polyurethane resin, or a combination of at least two of them.

[0025] It should be noted that the insulating layer formed outside the working electrode in the present invention covers the entire working electrode and is used to shield the remaining components of the sensing device to prevent problems such as short circuits and mutual interference between the working electrodes. It can effectively isolate some interfering substances, improve the accuracy of working electrode detection, shorten the sensor response time, and improve detection efficiency.

[0026] As a preferred technical solution of the present invention, an opening is provided on the surface of the insulating layer to form a sensing area penetrating the insulating layer, and a first sensing film layer and a second sensing film layer are provided in the sensing area, which are sequentially stacked from the surface of the working electrode to the outside.

[0027] Preferably, the sensing areas correspond to the working electrodes one by one, and the distances between two adjacent sensing areas and the corresponding extending ends of the working electrodes are different from each other.

[0028] Preferably, the first sensing membrane layer comprises an ion selective membrane.

[0029] Preferably, the ion selective membrane layer comprises K + Ion selective membrane, Na + Ion selective membrane, Cl - Ion selective membrane, Ca 2+ Ion selective membrane, NH 4 + Ion selective membrane or H + Any one or a combination of at least two of the ion selective membranes.

[0030] Preferably, the second sensing film layer comprises any one of polyethylene, polyethylene glycol, hydroxymethyl cellulose, chitosan, polyvinyl alcohol, polyurethane, polyvinyl pyrrolidone or polyvinyl pyridine.

[0031] Preferably, the sensing area is a quadrilateral structure, and the length of the sensing area is 0.3 to 1 cm, for example, it can be 0.3 cm, 0.4 cm, 0.5 cm, 0.6 cm, 0.7 cm, 0.8 cm, 0.9 cm or 1 cm, but is not limited to the listed values, and other unlisted values ​​within the numerical range are also applicable.

[0032] It should be noted that in the present invention, each working electrode independently corresponds to a sensing area, and the length of the sensing area is less than the length of the working electrode. At the same time, the position of each sensing area is different, which can avoid mutual infection between different working electrodes, improve the accuracy of detection data, and extend the service life of the sensor device. The second sensing film layer in the sensing area can prevent the loss of the first sensing film layer, slow down diffusion, reduce electrode interference, increase the detection linear range of the sensor device, and help improve biocompatibility.

[0033] As a preferred technical solution of the present invention, a substrate is arranged in the central cavity of the catheter base, and the substrate is close to a side of the central cavity away from the reference electrode insertion end.

[0034] Preferably, the substrate comprises porous glass-ceramic.

[0035] Preferably, a sealing member is provided at one end of the catheter base away from the substrate, and a through hole is opened on the surface of the sealing member, and the through hole includes a first through hole and at least two second through holes, the first through hole is located in the middle of the sealing member, and the second through holes are evenly distributed on the surface of the sealing member with the first through hole as the center.

[0036] Preferably, the reference electrode passes through the first through hole and is inserted into the central chamber.

[0037] Preferably, the second through hole is located above the limiting groove, and the working electrode passes through the second through hole and is inserted into the limiting groove.

[0038] Preferably, the sealing element comprises insulating glue.

[0039] Preferably, the central chamber is filled with an inner filling liquid.

[0040] Preferably, the filling liquid comprises KCl.

[0041] Preferably, one end of the reference electrode extending into the catheter base is located below the liquid level of the inner filling liquid.

[0042] As a preferred technical solution of the present invention, the reference electrode and the working electrode are respectively provided with electrode connectors at one end away from the catheter substrate, and the electrode connectors are respectively connected to the control unit.

[0043] Preferably, a connector is further provided between the electrode connector and the control unit.

[0044] Preferably, the control unit includes a storage module and an early warning module. The storage module collects the potential difference change data between the working electrode and the reference electrode, converts the electrical signal into the concentration value of the corresponding indicator through an algorithm, and records and analyzes it. When the concentration value of the substance to be tested exceeds the reference value, the control unit triggers the early warning module.

[0045] In a second aspect, the present invention provides a multi-parameter monitoring method, wherein the method uses the implantable multi-parameter biosensor device of the first aspect for continuous monitoring, and the method comprises:

[0046] The detection unit is implanted in the human body, and the working electrode produces a specific adsorption effect with the corresponding substance to be tested, causing the membrane potential of the working electrode to change. The control unit collects the signal of the voltage difference change between the working electrode and the reference electrode, and converts the electrical signal into a real-time concentration value through an algorithm, thereby realizing dynamic and continuous monitoring of at least two parameters.

[0047] As a preferred technical solution of the present invention, the dynamic continuous monitoring includes:

[0048] The first sensing membrane layer in the sensing area selectively undergoes specific adsorption with the substance to be tested to produce a potential change. The working electrode converts the physical and chemical effects into electrical signals and transmits the generated electrical signals to the storage module. The storage module converts the electrical signals into the corresponding concentration values ​​of the substance to be tested through an algorithm, and records and analyzes them.

[0049] As a preferred technical solution of the present invention, the substance to be tested includes inorganic ions and / or pH.

[0050] Preferably, the inorganic ions include any one of potassium, sodium, calcium, chloride or ammonium, or a combination of at least two thereof.

[0051] Preferably, the detection unit is implanted into the human body via an arterial indwelling needle or sheath.

[0052] In a third aspect, the present invention provides a use of the implantable multi-parameter biosensor device described in the first aspect, wherein the implantable multi-parameter biosensor device is used to continuously monitor dynamic changes in biological parameters in the human body.

[0053] Exemplarily, the assembly method of the implantable multi-parameter biosensor device provided by the present invention includes:

[0054] (I) coating a first conductive layer on a portion of the surface of a first conductive electrode to obtain a reference electrode, and coating a second conductive layer on a portion of the surface of a second conductive electrode to obtain a working electrode, wherein the first conductive electrode and the second conductive electrode independently comprise any one of a silver conductive electrode, a gold conductive electrode or a copper conductive electrode or a combination of at least two thereof, and both the first conductive layer and the second conductive layer comprise silver chloride;

[0055] (II) inserting the substrate into the central cavity from one end of the catheter substrate, and injecting the inner filling liquid into the central cavity, then inserting the reference electrode into the central cavity from the other end of the catheter substrate, extending it below the liquid level of the inner filling liquid, and fixing the reference electrode with a sealing member, wherein the substrate includes porous glass ceramics and the sealing member includes insulating glue;

[0056] (III) passing the working electrode through the sealing member from the end coated with the second conductive layer and embedding it into the limiting groove, injecting a filler into the fixing groove and solidifying it to form an insulating layer, leaving a through blank area on the surface of the insulating layer, dripping a first film liquid into the blank area to form a first sensing film layer, and after the first sensing film layer solidifies, dripping a second film liquid to form a second sensing film layer to obtain the sensing area, wherein the insulating layer comprises any one of epoxy resin, acrylic resin or polyurethane resin or a combination of at least two thereof;

[0057] (IV) Finally, the reference electrode and the working electrode are electrically connected to the control unit respectively to obtain the implantable multi-parameter biosensor device.

[0058] Compared with the prior art, the present invention has the following beneficial effects:

[0059] The present invention provides an implantable multi-parameter biosensor device and a multi-parameter monitoring method and use. The device has a simple structure and is easy to operate. It can detect multiple different biological parameters at the same time and continuously monitor the fluctuations of the patient's physiological parameters in real time, making it convenient for doctors to intervene in the patient in a timely manner. BRIEF DESCRIPTION OF THE DRAWINGS

[0060] Figure 1 A schematic diagram of the structure of an implantable multi-parameter biosensor device provided in Example 1 of the present invention;

[0061] Figure 2 A top view of the implantable multi-parameter biosensor device provided in Example 1 of the present invention;

[0062] Figure 3 A top view of a catheter substrate provided in Example 1 of the present invention;

[0063] Figure 4 A top view of the insulating layer provided in Embodiment 1 of the present invention;

[0064] Figure 5 A schematic diagram of the structure of the first sensing film layer and the second sensing film layer provided in Example 1 of the present invention;

[0065] Figure 6 A schematic diagram of the structure of a sealing member provided in Example 1 of the present invention;

[0066] Figure 7 This is a schematic diagram of the structure of the sensing area provided in Example 1 of the present invention.

[0067] Among them, 1-catheter base; 2-limiting groove; 3-reference electrode; 4-working electrode; 5-insulating layer; 6-sensing area; 7-sealing member; 8-central chamber; 9-first sensing film layer; 10-second sensing film layer; 11-first through hole; 12-second through hole. DETAILED DESCRIPTION

[0068] It should be understood that, in the description of the present invention, the terms "center", "longitudinal", "lateral", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc., indicating the orientation or positional relationship are based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention. In addition, the terms "first", "second", etc. are only used for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Therefore, the features defined as "first", "second", etc. may explicitly or implicitly include one or more of the features. In the description of the present invention, unless otherwise specified, "multiple" means two or more.

[0069] It should be noted that in the description of the present invention, unless otherwise clearly specified and limited, the terms "disposed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood by specific circumstances.

[0070] The technical solution of the present invention is further described below with reference to the accompanying drawings and through specific implementation methods.

[0071] In a specific embodiment, the present invention provides an implantable multi-parameter biosensor device, wherein the implantable multi-parameter biosensor device comprises an electrically connected detection unit and a control unit, and the detection unit is implanted in a human body for continuous monitoring.

[0072] The detection unit includes a catheter matrix 1, a reference electrode 3 and at least two working electrodes 4, the reference electrode 3 is inserted into the catheter matrix 1, the outer surface of the catheter matrix 1 is provided with at least two fixed grooves along the axial direction, the working electrode 4 is located in the fixed groove, and the reference electrode 3 and the working electrode 4 are respectively electrically connected to the control unit.

[0073] The implantable multi-parameter biosensor device provided by the present invention can be implanted into a patient's body through an arterial indwelling needle or a sheath to achieve the purpose of real-time continuous monitoring.

[0074] Furthermore, a through central cavity 8 is provided in the catheter base body 1 , and the reference electrode 3 is inserted into the central cavity 8 .

[0075] The reference electrode 3 comprises a first conductive electrode and a first conductive layer coated on a surface of the first conductive electrode.

[0076] The working electrode 4 includes a second conductive electrode and a second conductive layer coated on a surface of the second conductive electrode.

[0077] A section of the reference electrode 3 coated with the first conductive layer extends into the central chamber 8. A section of the working electrode 4 coated with the second conductive layer extends into the fixing groove.

[0078] The first conductive electrode and the second conductive electrode independently include any one of a silver conductive electrode, a gold conductive electrode or a copper conductive electrode or a combination of at least two thereof. The first conductive layer and the second conductive layer independently include silver chloride.

[0079] The reference electrode 3 and the working electrode 4 are both needle-shaped structures.

[0080] Furthermore, a limiting groove 2 is axially provided at the bottom of the fixing groove, and a portion of the working electrode 4 is embedded in the limiting groove 2 .

[0081] The working electrodes 4 are wrapped with an insulating layer 5 , and the insulating layer 5 is used to prevent mutual interference between the working electrodes 4 .

[0082] The insulating layer 5 is formed by filling the fixing groove with fillers. The insulating layer 5 includes any one of epoxy resin, acrylic resin or polyurethane resin or a combination of at least two of them. The insulating layer 5 formed outside the working electrode 4 in the present invention covers the entire working electrode 4 and is used to shield the remaining components of the sensor device to prevent problems such as short circuits and mutual interference between the working electrodes 4. It can effectively isolate some interfering substances, improve the accuracy of detection of the working electrode 4, shorten the sensor response time, and improve detection efficiency.

[0083] Furthermore, an opening is provided on the surface of the insulating layer 5 to form a sensing area 6 penetrating the insulating layer 5 , and a first sensing film layer 9 and a second sensing film layer 10 are provided in the sensing area 6 , which are sequentially stacked from the surface of the working electrode 4 outward.

[0084] The sensing areas 6 correspond to the working electrodes 4 one by one, and the distances between two adjacent sensing areas 6 and the corresponding extending ends of the working electrodes 4 are different from each other.

[0085] The first sensing membrane layer 9 comprises an ion selective membrane. The ion selective membrane layer comprises K + Ion selective membrane, Na + Ion selective membrane, Cl - Ion selective membrane, Ca 2+ Ion selective membrane, NH 4 + Ion selective membrane or H + Any one or a combination of at least two of the ion selective membranes.

[0086] The second sensing film layer 10 includes any one of polyethylene, polyethylene glycol, hydroxymethyl cellulose, chitosan, polyvinyl alcohol, polyurethane, polyvinyl pyrrolidone or polyvinyl pyridine.

[0087] The sensing area 6 is a quadrilateral structure, and the length of the sensing area 6 is 0.3-1 cm.

[0088] In the present invention, each working electrode 4 independently corresponds to a sensing area 6, and the length of the sensing area 6 is less than the length of the working electrode 4. At the same time, the position of each sensing area 6 is different, which can avoid mutual infection between different working electrodes 4, improve the accuracy of detection data, and extend the service life of the sensor device. The second sensing film layer 10 in the sensing area 6 can prevent the loss of the first sensing film layer 9, slow down diffusion, reduce electrode interference, increase the detection linear range of the sensor device, and help improve biocompatibility.

[0089] Furthermore, a substrate is disposed in the central cavity 8 of the catheter substrate 1, and the substrate is close to a side of the central cavity 8 away from the extended end of the reference electrode 3. The substrate comprises porous glass ceramics.

[0090] A sealing member 7 is provided at one end of the catheter base 1 away from the substrate, and through holes are provided on the surface of the sealing member 7. The through holes include a first through hole 11 and at least two second through holes 12. The first through hole 11 is located in the middle of the sealing member 7, and the second through holes 12 are evenly distributed on the surface of the sealing member 7 with the first through hole 11 as the center.

[0091] The reference electrode 3 passes through the first through hole 11 and is inserted into the central chamber 8. The second through hole 12 is located above the limiting groove 2, and the working electrode 4 passes through the second through hole 12 and is inserted into the limiting groove 2. The sealing member 7 includes insulating glue.

[0092] The central chamber 8 is filled with an internal filling liquid. The internal filling liquid includes KCl. One end of the reference electrode 3 extending into the catheter base 1 is located below the liquid level of the internal filling liquid.

[0093] Furthermore, the reference electrode 3 and the working electrode 4 are both provided with electrode connectors at their ends away from the catheter substrate 1 , and the electrode connectors are respectively connected to the control units.

[0094] A connector is also provided between the electrode connector and the control unit.

[0095] The control unit includes a storage module and an early warning module. The storage module collects the potential difference change data between the working electrode 4 and the reference electrode 3, converts the electrical signal into the concentration value of the corresponding indicator through an algorithm, and records and analyzes it. When the concentration value of the substance to be tested exceeds the reference value, the control unit triggers the early warning module.

[0096] In another specific embodiment, the present invention provides a multi-parameter monitoring method, wherein the method uses an implantable multi-parameter biosensor device provided in a specific embodiment for detection, specifically comprising:

[0097] The detection unit is implanted in the human body, and the working electrode 4 produces a specific adsorption effect with the corresponding substance to be tested, causing the membrane potential of the working electrode 4 to change. The control unit collects the signal of the voltage difference change between the working electrode 4 and the reference electrode 3, and converts the electrical signal into a real-time concentration value through an algorithm, thereby realizing dynamic and continuous monitoring of at least two parameters.

[0098] Furthermore, the dynamic continuous monitoring includes:

[0099] The first sensing film layer 9 in the sensing area 6 selectively undergoes a specific adsorption reaction with the substance to be detected to produce a potential change. The working electrode 4 converts the physicochemical effect into an electrical signal and transmits the generated electrical signal to the storage module. The storage module converts the electrical signal into the corresponding concentration value of the substance to be detected through an algorithm, and records and analyzes it.

[0100] Furthermore, the substance to be tested includes inorganic ions and / or pH. The inorganic ions include any one or a combination of at least two of potassium, sodium, calcium, chloride or ammonium. The detection unit is implanted in the human body through an arterial indwelling needle or sheath.

[0101] Example 1

[0102] This embodiment provides an implantable multi-parameter biosensor device, including a detection unit and a control unit electrically connected, such as Figure 1 and Figure 2 As shown, the detection unit includes a catheter matrix 1, a reference electrode 3 and six working electrodes 4. A through central cavity 8 is provided in the catheter matrix 1, and the reference electrode 3 is inserted into the central cavity 8. Figure 3 As shown, six fixing grooves are evenly arranged along the axial direction on the outer surface of the catheter base 1 , a limiting groove 2 is axially arranged at the bottom of the fixing groove, and a working electrode 4 is partially embedded in the limiting groove 2 .

[0103] The reference electrode 3 and the working electrode 4 are both needle-shaped structures. The reference electrode 3 includes a silver conductive electrode and silver chloride coated on the surface of the silver conductive electrode, and a section of the reference electrode 3 coated with silver chloride extends into the central chamber 8. The central chamber 8 is filled with a KCl solution, and one end of the reference electrode 3 is located below the liquid surface of the KCl solution. The working electrode 4 includes a silver conductive electrode and silver chloride coated on the surface of the silver conductive electrode, and a section of the working electrode 4 coated with silver chloride extends into the limiting groove 2.

[0104] The working electrode 4 is wrapped with Figure 4 The insulating layer 5 shown, Figure 7 As shown, each insulating layer 5 is independently provided with a sensing area 6, and the sensing area 6 corresponds to the working electrode 4 one by one. The length of the six sensing areas 6 is 0.5 cm, and the distance from the corresponding working electrode 4 to the extending end is different. Figure 5 As shown, the first sensing area 6 includes a potassium ion selective membrane layer and a perfluorosulfonic acid layer stacked sequentially from the working electrode 4 to the outside, the second sensing area 6 includes an ammonium ion selective membrane layer and a perfluorosulfonic acid layer stacked sequentially from the working electrode 4 to the outside; the third sensing area 6 includes a sodium ion selective membrane layer and a polytetrafluoroethylene layer stacked sequentially from the working electrode 4 to the outside; the fourth sensing area 6 includes a calcium ion selective membrane layer and a polytetrafluoroethylene layer stacked sequentially from the working electrode 4 to the outside; the fifth sensing area 6 includes a pH buffer layer and a polyethylene glycol layer stacked sequentially from the working electrode 4 to the outside; the sixth sensing area 6 includes a chloride ion selective membrane layer and a cellulose acetate layer stacked sequentially from the working electrode 4 to the outside.

[0105] A substrate is disposed in the central cavity 8 of the catheter base 1. The substrate is close to the side of the central cavity 8 away from the insertion end of the reference electrode 3. The substrate is porous ceramic glass. A sealing member 7 is disposed at one end of the catheter base 1 away from the substrate. The sealing member 7 is an insulating glue, such as Figure 6 As shown, the surface of the insulating glue is provided with a first through hole 11 and six second through holes 12, the first through hole 11 is located at the center of the sealing member 7, and the second through holes 12 are evenly distributed on the surface of the sealing member 7 with the first through hole 11 as the center. The reference electrode 3 passes through the first through hole 11 and is inserted into the central chamber 8, the reference electrode 3 is located in the center, the second through hole 12 is located above the limiting groove 2, and the six working electrodes 4 pass through the second through holes 12 respectively and are inserted into the limiting groove 2.

[0106] The reference electrode 3 and the working electrode 4 are both provided with electrode connectors at their ends away from the catheter substrate 1 . The electrode connectors are respectively connected to the control unit. A connector is also provided between the electrode connector and the control unit.

[0107] Application Example 1

[0108] This application example uses the implantable multi-parameter biosensor device provided in Example 1 to continuously monitor the dynamic changes of multiple biological parameters of the human body, specifically including:

[0109] The detection unit is implanted into the human body through the sheath tube, and the first sensing film layer 9 in the sensing area 6 selectively interacts with the substance to be detected to produce a physical and chemical effect, wherein the first sensing area 6 monitors the potassium ion concentration in the human body, the second sensing area 6 monitors the ammonium ion concentration in the human body, the third sensing area 6 monitors the sodium ion concentration in the human body, the fourth sensing area 6 monitors the calcium ion concentration in the human body, the fifth sensing area 6 monitors the pH value in the human body, and the sixth sensing area 6 monitors the chloride ion concentration in the human body. The working electrode 4 converts the above-mentioned different physical and chemical effects into electrical signals, and transmits the generated electrical signals to the storage module, which analyzes and compares the received electrical signals with the data of the reference electrode 3, and records them.

[0110] The implantable multi-parameter biosensor device provided by the present invention has a simple structure and is easy to operate. It can detect multiple different biological parameters at the same time and monitor the fluctuation of the patient's physiological parameters in real time, making it convenient for doctors to intervene in patients in a timely manner.

[0111] The applicant declares that the above is only a specific implementation mode of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention shall fall within the protection scope and disclosure scope of the present invention.

Claims

1. An implantable multi-parameter biosensor device, characterized in that: The implantable multi-parameter biosensor device comprises a detection unit and a control unit which are electrically connected, and the detection unit is implanted in the human body for continuous monitoring; The detection unit comprises a catheter matrix, a reference electrode and at least two working electrodes, wherein the reference electrode is inserted into the catheter matrix, at least two fixing grooves are provided in the axial direction on the outer surface of the catheter matrix, the working electrode is located in the fixing grooves, and the reference electrode and the working electrode are electrically connected to the control unit respectively; The working electrode is wrapped with an insulating layer, and the insulating layer is used to prevent mutual interference between the working electrodes. The surface of the insulating layer is provided with an opening to form a sensing area that penetrates the insulating layer. The sensing area is provided with a first sensing film layer and a second sensing film layer stacked sequentially from the surface of the working electrode to the outside. The sensing area corresponds to the working electrode one by one, and the distances between two adjacent sensing areas and the corresponding working electrode extension ends are different. The first sensing film layer includes an ion selective film layer, and the second sensing film layer includes any one of polyethylene, polyethylene glycol, hydroxymethyl cellulose, chitosan, polyvinyl alcohol, polyurethane, polyvinyl pyrrolidone or polyvinyl pyridine. The sensing area is a quadrilateral structure, and the length of the sensing area is 0.3~1cm; The control unit includes a storage module and an early warning module. The storage module collects the potential difference change data between the working electrode and the reference electrode, converts the electrical signal into the corresponding concentration value of the substance to be tested through an algorithm, and records and analyzes it. When the concentration value of the substance to be tested exceeds the reference value, the early warning module is triggered.

2. The implantable multi-parameter biosensor device according to claim 1, characterized in that: A through central chamber is arranged in the catheter base, and the reference electrode is inserted into the central chamber.

3. The implantable multi-parameter biosensor device according to claim 1, characterized in that: The reference electrode comprises a first conductive electrode and a first conductive layer coated on a surface of the first conductive electrode.

4. The implantable multi-parameter biosensor device according to claim 3, characterized in that: The working electrode comprises a second conductive electrode and a second conductive layer coated on a surface of the second conductive electrode.

5. The implantable multi-parameter biosensor device according to claim 2, characterized in that: A section of the reference electrode coated with the first conductive layer extends into the central cavity.

6. The implantable multi-parameter biosensor device according to claim 1, characterized in that: A section of the working electrode coated with the second conductive layer extends into the fixing groove.

7. The implantable multi-parameter biosensor device according to claim 4, characterized in that: The first conductive electrode and the second conductive electrode independently include any one of a silver conductive electrode, a gold conductive electrode or a copper conductive electrode, or a combination of at least two thereof.

8. The implantable multi-parameter biosensor device according to claim 4, characterized in that: The first conductive layer and the second conductive layer independently include silver chloride.

9. The implantable multi-parameter biosensor device according to claim 1, characterized in that: The reference electrode and the working electrode are both needle-shaped structures.

10. The implantable multi-parameter biosensor device according to claim 1, characterized in that: A limiting groove is axially provided in the fixing groove, and the working electrode portion is embedded in the limiting groove.

11. The implantable multi-parameter biosensor device according to claim 1, characterized in that: The fixing groove is filled with fillers to form the insulating layer.

12. The implantable multi-parameter biosensor device according to claim 11, characterized in that: The insulating layer comprises any one of epoxy resin, acrylic resin or polyurethane resin or a combination of at least two of them.

13. The implantable multi-parameter biosensor device according to claim 1, characterized in that: The ion selective membrane layer comprises K + Ion selective membrane, Na + Ion selective membrane, Cl - Ion selective membrane, Ca 2+ Ion selective membrane, NH4 + Ion selective membrane or H + Any one or a combination of at least two of the ion selective membranes.

14. The implantable multi-parameter biosensor device according to claim 10, characterized in that: A substrate is arranged in the central cavity of the catheter base body, and the substrate is close to a side of the central cavity away from the reference electrode insertion end.

15. The implantable multi-parameter biosensor device according to claim 14, characterized in that: The substrate comprises porous glass ceramics.

16. The implantable multi-parameter biosensor device according to claim 14, characterized in that: A sealing member is provided at one end of the catheter base away from the substrate, and through holes are provided on the surface of the sealing member. The through holes include a first through hole and at least two second through holes. The first through hole is located in the middle of the sealing member, and the second through holes are evenly distributed on the surface of the sealing member with the first through hole as the center.

17. The implantable multi-parameter biosensor device according to claim 16, characterized in that: The reference electrode passes through the first through hole and is inserted into the central chamber.

18. The implantable multi-parameter biosensor device according to claim 16, characterized in that: The second through hole is located above the limiting groove, and the working electrode passes through the second through hole and is inserted into the limiting groove.

19. The implantable multi-parameter biosensor device according to claim 16, characterized in that: The sealing element comprises insulating glue.

20. The implantable multi-parameter biosensor device according to claim 2, characterized in that: The central chamber is filled with internal filling liquid.

21. The implantable multi-parameter biosensor device according to claim 20, characterized in that: The inner filling liquid includes KCl.

22. The implantable multi-parameter biosensor device according to claim 20, characterized in that: One end of the reference electrode extending into the catheter base is located below the liquid level of the inner filling liquid.

23. The implantable multi-parameter biosensor device according to claim 1, characterized in that: The reference electrode and the working electrode are respectively provided with electrode connectors at one end away from the catheter substrate, and the electrode connectors are respectively connected to the control unit.

24. The implantable multi-parameter biosensor device according to claim 23, characterized in that: A connector is also provided between the electrode connector and the control unit.

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