TWI730503B - Physiological and biochemical monitoring device - Google Patents

Abstract

A physiological and biochemical monitoring device includes a monitoring body and a replaceable component, wherein a physiological sensor for sensing physiological sensing signals is embedded in the monitoring system, and the replaceable component can be combined On the surface of the monitoring body, it is possible to perform micro-invasive sensing at any point on the skin of the animal body, and then to obtain different analyte concentrations based on different sensing microneedles at the same point, and then undergo signal conversion In order to obtain biochemical sensing signals, this project can obtain dynamic information of the body by measuring multiple physiological and biochemical signals at the same time.

Description

Physiological and biochemical monitoring device

The invention relates to a physiological and biochemical monitoring device, in particular to a physiological and biochemical monitoring device capable of simultaneously measuring multiple physiological and biochemical signals.

In recent years, various technological breakthroughs and quantifications have had a more profound impact on human daily life. Wearable devices can achieve movement records and heart rhythm states. Their functions are for exercise volume records, community interaction, heartbeat records, and Sleep records and so on.

In terms of the aforementioned wearable device, it is usually limited to the measurement of pure physiological signals, but if you want to measure pure biochemical signals (such as blood oxygen concentration, uric acid concentration, or lactic acid concentration), you need to use other additional devices to separate However, in the case of animals, many signals on the body may be causal to each other. If the physiological and biochemical signals cannot be recorded at the same time for a long time, errors will occur in the judgment of the animal's condition.

For athletes, pilots, or patients in the intensive care unit, it is very important to know the continuous body state. However, because there are no equipment or devices that can measure physiological and biochemical signals at the same time, it is often impossible to be more accurate. Control diet content and timing, medication content and timing, training content and timing, so if you can measure a variety of physiological and biochemical signals at the same time, you will be able to obtain dynamic information of the body through sensory signal fusion, and provide a variety of health, sports training, and rehabilitation. Real-time adjustment of prescriptions for health, prevention, treatment, etc., as well as individual adjustments.

At present, there are many wearable devices on the market. Because they cannot obtain personalized physiological and biochemical information in real time, they cannot perform big data and deep learning calculations based on this, and they cannot achieve medical-grade prescriptions.

Therefore, this case has developed a device that can continuously measure. In addition to measuring the physiological data of electrocardiogram, blood pressure, and blood oxygen, it can also measure body surface temperature, blood sugar, lactic acid, uric acid, cholesterol, alcohol, and taking drugs. The concentration of biochemical data can measure multiple physiological and biochemical signals at the same time. This device should be the best solution for the application field of animal body posture.

The physiological and biochemical monitoring device of the present invention includes: a monitoring body for combining with the skin of an animal body, a first connection end is arranged on the surface of the monitoring body, and the monitoring body further has: a power supply unit, It is used to provide the power required for the operation of the monitoring body. In addition, an opening is provided on the surface of the monitoring body; a central control unit is electrically connected to the power supply unit and the first connection terminal to control the monitoring body Operation and transmission of data; a physiological sensor is electrically connected to the power supply unit and the central control unit, and the physiological sensor is used to monitor the physiological sensing signal of the animal body, and can monitor the physiological The sensing signal is transmitted to the central control unit; the biochemical sensor is electrically connected with the power supply unit, the central control unit and the first connection terminal, and the biochemical sensor is used to monitor the biochemical of the animal body Signal, wherein the biochemical sensor includes: a detection unit for detecting and obtaining a biochemical concentration change value; a processing unit for converting the detected biochemical concentration change value into a biochemical sensor Signal, and can transmit the biochemical sensing signal to the central control unit; a replaceable component is combined on the surface of the monitoring body, and the replaceable component has an opening, wherein the replaceable component The component system includes: several sensing micro-needle groups, the sensing micro-needle group has two or more sensors Microneedles, and each sensing microneedle is combined with one or more perspiration blocking elements, and the tips of every two or more sensing microneedles in the sensing microneedle group can be inward Gather; a second connection terminal is electrically connected with the first connection terminal, used for two or more sensing micro-needles toward any point on the animal skin for micro-intrusion sensing, the biochemical The detection unit of the sensor is connected to the second connecting end to obtain different biochemical concentration changes at the same point position according to different sensing microneedles; therefore, the replaceable component is integrated on the monitoring body Later, the monitoring body can simultaneously monitor physiological sensing signals and biochemical sensing signals.

More specifically, the physiological sensor can be an optical sensor, and the physiological sensor can be a photoplethysmography sensor, a blood oxygen sensor, or a blood pressure sensor.

More specifically, the physiological sensor can be an electrode contact sensor, and the physiological sensor can be an all-in-one meter impedance sensor, an electrocardiogram (ECG) sensor, and a surface electromyography sensor. Figure (sEMG) sensor, an electroencephalogram (EEG) sensor.

More specifically, the physiological sensor can be a sensor for inertial motion detection, and the physiological sensor is a velocity sensor, an acceleration sensor, an angular velocity sensor, and a An electronic compass, a magnetic field sensor, and a multi-axis motion sensor are used to measure the velocity, acceleration, angular velocity, azimuth angle, etc., and can perform fusion calculations based on the velocity or/and acceleration, angular velocity, and azimuth angle. Judge the movement posture and trajectory.

More specifically, the physiological sensor can be a temperature detecting sensor, and the physiological sensor can be an all-in-one watch temperature sensor.

Furthermore, this physiological and biochemical monitoring device can also add environmental sensors that are not in contact with the body surface but are used to detect environmental variables, including environmental temperature and humidity, illuminance, noise, air quality, etc., to infer environmental sensing Measure the effect of signal changes on the wearer’s physiological and biochemical signal changes.

More specifically, the biochemical sensor is used to measure a blood glucose value, a lactic acid value, a uric acid value, a cholesterol value, a cortisol value, an alcohol value, a gas value, an ion value, and a consumption value. The drug concentration value is either two or more of the above values.

More specifically, the processing unit can electrochemically convert the detected biochemical concentration change value into the biochemical sensing signal.

To be more specific, the said further includes a combining component for fixing the monitoring body on the animal body so that the monitoring body can contact or be micro-invasive to the skin of the animal body.

More specifically, the sensing microneedle of the sensing microneedle is selected from stainless steel, nickel, nickel alloy, titanium, titanium alloy or silicon material, and biocompatible metal is deposited on the surface.

More specifically, one of the sensing microneedles in the sensing microneedle group is connected to the surface-modified sensing polymer and the porous protective layer.

More specifically, the replaceable component includes several microneedle sheets stacked on top of each other, and each microneedle sheet has one or more perforations, and each perforation edge is provided with one or more senses. Micrometer needles, and after a plurality of microneedle sheets are stacked, a sensing microneedle group is formed with a factor of multiple microneedle sheets that are superimposed to pass through the sensing microneedles.

More specifically, the replaceable component includes: a first microneedle sheet as a working electrode, and the first microneedle sheet is in the shape of a sheet, and the first microneedle sheet is provided with a first microneedle sheet. A perforation, the edge of the first perforation is provided with a first sensing microneedle; a second microneedle sheet is used as a reference electrode, and the second microneedle sheet is thin, and the second microneedle sheet is A second perforation is provided, and the edge of the second perforation is provided with a second sensing microneedle; wherein the first perforation and the second perforation are in the same vertical position, and the first microneedle sheet and the second microneedle sheet are separated Overlap each other, and the first sensing microneedle and the second sensing microneedle are separated from each other without overlapping.

More specifically, the replaceable component includes: a first microneedle sheet as a working electrode, and the first microneedle sheet is in the shape of a sheet, and the first microneedle sheet is provided with a first microneedle sheet. A perforation, the edge of the first perforation is provided with a first sensing microneedle; a second microneedle sheet is used as a reference electrode, and the second microneedle sheet is thin, and the second microneedle sheet is A second perforation is provided, and the edge of the second perforation is provided with a second sensing microneedle; a third microneedle sheet is used as a counter electrode, and the third microneedle sheet is thin, and the third microneedle The needle sheet is provided with a third perforation, and the edge of the third perforation is provided with a third sensing microneedle; wherein the first perforation and the second perforation are in the same vertical position as the third perforation, and the first microneedle sheet, The second microneedle sheet and the third perforation overlap each other, and the first sensing microneedle, the second sensing microneedle, and the third microneedle sheet are separated from each other without overlapping.

More specifically, the sensing microneedle contacts the skin and partially invades the subcutaneously. During the measurement, the working electrode and the counter electrode or the reference electrode of the conventional microneedle patch are in contact with the skin respectively, resulting in the positive electrode A certain distance from the negative electrode, when using the potentiostat measurement method, the sweat gland between the positive electrode and the negative electrode produces a reverse iontophoresis (reverse iontophoresis), which stimulates the discharge of sweat and affects the concentration of the analyte in the tissue fluid. In order to reduce the effect of biochemical signals, the sensing microneedles are superimposed on each other through the working electrode and the counter electrode/reference electrode, so that the distance between the positive electrode and the negative electrode is zero, so that the sweat glands can avoid the reverse ion penetration effect (reverse ion penetration). iontophoresis). Assuming 100 glands/cm ² and 4 nL/min per gland, when the conventional positive and negative electrodes are separated by 0.5 cm, it is equivalent to 0.25 cm ² of sweat at the skin-electrode interface to produce 100 nL/min. However, the present invention overlaps the positive and negative electrodes, and the microneedle spacing between the positive and negative electrodes is 0.5 mm, which is equivalent to less than 0.0025 cm ^{2 of the} skin-electrode interface where the sweat production is less than 1 nL/min. Basically, it is less than the amount of sweat that hardly affects the results of the subcutaneous microneedle measurement.

More specifically, the sensing microneedle can change the shape of both sides, so that the animal sweat produced around the bottom of the sensing microneedle will not invade the tip of the sensing microneedle to eliminate movement. The interference factor of object sweat on the tip sensing of the sensing microneedle.

More specifically, the bottom of the sensing microneedle can be coated with a non-porous polymer material, so that animal sweat produced around the bottom of the sensing microneedle cannot invade the sensing microneedle. The tip is used to eliminate the interference factors of animal body sweat on the tip sensing of the sensing microneedle.

More specifically, an adsorption structure is designed around the bottom of the sensing microneedle, so that the animal sweat produced around the bottom of the sensing microneedle can be adsorbed, so as to eliminate the influence of the animal sweat on the sensing microneedle. The interference factor of the cutting-edge sensing.

More specifically, a trench structure is designed around the bottom of the sensing microneedle, so that animal body sweat produced around the bottom of the sensing microneedle can be guided to the outside of the sensing microneedle for volatilization. In order to eliminate the interference factor of animal body sweat on the tip sensing of the sensing microneedle.

More specifically, the bottom of the sensing microneedle is designed to be coated with a non-porous polymer layer and then coated with a perspiration inhibitor, such as aluminum chloride (ACH), aluminum chloride hexahydrate ointment (aluminum chloride hexahydrate cream), such as Drysol or anticholinergic medications, such as glycopyrrolate, which makes most of the sweat glands on the part of the microneedle substrate in contact with the skin temporarily be prevented from sweating by the action of antiperspirant , So it will not affect the sensing of the microneedle.

The physiological and biochemical monitoring device in this case includes: a monitoring body for combining with the skin of an animal body, a first connection end is arranged on the surface of the monitoring body, and the monitoring system has: a power supply unit, In order to provide the power required for the operation of the monitoring body, an opening is provided on the surface of the monitoring body; a central control unit is electrically connected to the power supply unit and the first connection terminal to control the operation of the monitoring body And transmission data; a physiological sensor is electrically connected with the power supply unit and the central control unit, and the physiological sensor is used to monitor the physiological sensing signal of the animal body, and can monitor the physiological sense The test signal is sent to the central control unit; a first connection terminal is exposed to the monitoring The opening of the body; a replaceable component is combined on the surface of the monitoring body, and the replaceable component has an opening, wherein the replaceable component includes: a plurality of sensing microneedle sets, The sensing microneedle set has two or more sensing microneedles, and each sensing microneedle is combined with one or more sweat blocking elements, and the sensing microneedle set The tips of every two or more sensing microneedles can be gathered inward; the biochemical sensor is electrically connected with the plurality of sensing microneedle groups to monitor the biochemical signals of the animal body. The biochemical sensor includes: a detection unit for micro-intrusion detection of two or more sensing microneedles towards any point on the skin of the animal body, the detection unit can be in the same A point position obtains different biochemical concentration change values according to different sensing microneedles; a processing unit is used to convert the detected biochemical concentration change value into a biochemical sensing signal; a second connection terminal is connected with The processing unit and the first connection terminal are electrically connected to enable the biochemical sensing signal to be transmitted to the central control unit through the first connection terminal; therefore, after the replaceable component is combined with the monitoring body, the monitoring The main body can monitor physiological sensing signals and biochemical sensing signals at the same time.

1: monitor the body

101: opening

102: open

11: Central control unit

12: Physiological Sensor

13: Biochemical sensor

131: Detection unit

132: Processing Unit

14: power supply unit

15: The first connection terminal

2: Replaceable components

20: Hole

21: The first microneedle sheet

211: First Piercing

212: The first sensing microneedle

213: second connection end

22: The second needle

221: second perforation

222: Second sensing microneedle

223: second connection end

23: The third needle

231: Third Piercing

232: Third sensing microneedle

2321: protrusion

233: third connection

24: Non-porous polymer layer

25: Adsorption structure

26: microneedle sheet

261: Piercing

262: Sense Microneedle

263: connection end

27: microneedle sheet

271: Perforation

272: Sense Microneedle

273: connection end

27’: Microneedle sheet

271’: Piercing

272’: Sensing microneedle

273’: connecting end

3: Subcutaneous tissue

31: Animal body sweat

4: arm

5: calf

6: Combining components

7: Monitor the body

71: Central control unit

72: Physiological Sensor

73: power supply unit

74: The first signal connection terminal

75: The first power connection

8: Replaceable components

80: opening

81: Sensing micro-needle group

82: Biochemical Sensor

821: Detection Unit

822: Processing Unit

83: power supply unit

84: The second signal connection terminal

85: second power connection

[Figure 1A] is a schematic diagram of the three-dimensional structure of the physiological and biochemical monitoring device of the present invention.

[Figure 1B] is a schematic diagram of the overall structure of the physiological and biochemical monitoring device of the present invention.

[Figure 2A] is a schematic diagram of the structure of the monitoring body of the physiological and biochemical monitoring device of the present invention.

[Figure 2B] is a schematic diagram of the structure of the biochemical sensor of the physiological and biochemical monitoring device of the present invention.

[Figure 3A] is a schematic diagram of the first implementation of the sensing microneedle set of the physiological and biochemical monitoring device of the present invention.

[Figure 3B] is a schematic diagram of the first implementation of the sensing microneedle set of the physiological and biochemical monitoring device of the present invention.

[Figure 4] is a schematic diagram of the second implementation of the sensing microneedle set of the physiological and biochemical monitoring device of the present invention.

[Figure 5A] is a schematic diagram of the third implementation of the sensing microneedle set of the physiological and biochemical monitoring device of the present invention.

[Figure 5B] is a schematic diagram of the third implementation of the sensing microneedle set of the physiological and biochemical monitoring device of the present invention.

[Figure 5C] is a schematic diagram of the third implementation of the sensing microneedle set of the physiological and biochemical monitoring device of the present invention.

[Figure 5D] is a schematic diagram of the third implementation of the sensing microneedle set of the physiological and biochemical monitoring device of the present invention.

[Figure 6A] is a schematic diagram of the test structure of the sensing microneedle group of the physiological and biochemical monitoring device of the present invention.

[Figure 6B-1] is a schematic diagram of the first perspiration blocking implementation structure of the physiological and biochemical monitoring device of the present invention.

[Figure 6B-2] is a schematic diagram of the first anti-perspiration implementation and application of the physiological and biochemical monitoring device of the present invention.

[Figure 6C] is a schematic diagram of the second perspiration blocking implementation structure of the physiological and biochemical monitoring device of the present invention.

[Figure 6D] is a schematic diagram of the third implementation structure of sweat blocking of the physiological and biochemical monitoring device of the present invention.

[Figure 7] is a schematic diagram of the wearable application of the physiological and biochemical monitoring device of the present invention.

[Figure 8] is a schematic diagram of the wearable application of the physiological and biochemical monitoring device of the present invention.

[Figure 9A] is a schematic diagram of another implementation structure of the monitoring body of the physiological and biochemical monitoring device of the present invention.

[Figure 9B] is a schematic diagram of another implementation architecture of the replaceable components of the physiological and biochemical monitoring device of the present invention.

[Figure 9C] is a schematic diagram of another implementation of the three-dimensional structure of the physiological and biochemical monitoring device of the present invention.

Other technical content, features and effects of the present invention will be clearly presented in the following detailed description of the preferred embodiment with reference to the drawings.

The physiological and biochemical monitoring device of the present invention, as shown in Figures 1A, 1B, 2A, and 2B, can be combined with the replaceable component 2 on the monitoring body 1, and the monitoring body 1 is used to combine with the skin of an animal body , And the monitoring body 1 is provided with a central control unit 11 and a power supply unit 14. The central control The unit 11 is used to control the operation and data transmission of the monitoring body 1, and the power supply unit 14 is used to provide the power required for the operation of the monitoring body 1; The replaceable component 2 can be snapped onto the monitoring body 1, wherein the monitoring body 1 has a physiological sensor 12 and a biochemical sensor 13 inside, and is specific to the physiological sensor 12 and the biochemical sensor. The position of the sensor 13 is provided with an opening 101, 102 on the surface of the monitoring body 1 to allow the physiological sensor 12 and the biochemical sensor 13 to expose the detection port of the physiological sensor 12 and the first connection end 15 (The first connecting terminal 15 itself is a connecting circuit and will be connected to the biochemical sensor 13, and the first connecting terminal 15 can be directly designed on the biochemical sensor 13), and the replaceable component 2 The opening 20 is capable of exposing the physiological sensor 12 from the opening 20 (the detection port of the physiological sensor 12 can be parallel to the opening 20 or protruding from the opening 20), and the physiological The description of the sensor 12 and the biochemical sensor 13 is as follows:

(1) The physiological sensor 12 is used to monitor the physiological sensing signal of the animal body, and can transmit the monitored physiological sensing signal to the central control unit 11; wherein the physiological sensor 12 can be:

(a1) Optical sensors, such as photoplethysmography sensors, blood oxygen sensors, and blood pressure sensors.

(a2) Electrode micro-invasive sensors, such as body surface impedance sensors, electrocardiogram (ECG) sensors, surface electromyography (sEMG) sensors, and electroencephalogram (EEG) sensors.

(a3) Sensors for inertial motion detection, such as a speed sensor, an acceleration sensor, an angular velocity sensor, an electronic compass, a magnetic field sensor, and a multi-axis motion sensor to enable Measure the velocity, acceleration, angular velocity, azimuth angle, etc. of the movement, and can perform fusion calculations to determine the movement posture and trajectory based on the velocity or/and acceleration, angular velocity, and azimuth angle.

(a4) Sensors for temperature detection, such as body surface temperature sensors.

(2) The biochemical sensor 13 is used to monitor the biochemical signals of the animal body (a blood sugar value, a lactic acid value, a uric acid value, a cholesterol value, a cortisol value, an alcohol value, a gas value, an ion Value, a drug concentration value, or the above two or more values), as shown in Figure 2B, the biochemical sensor 13 includes a detection unit 131 and a processing unit 132, wherein the detection The unit 131 can obtain the biochemical concentration change value through the first connection terminal 15, and then through the processing unit 132, electrochemically convert the detected biochemical concentration change value into the biochemical sensing signal, and then the biochemical sensing signal The measurement signal is sent to the central control unit 11; and the above-mentioned biochemical sensor element can be a semiconductor element that senses the characteristics of chemical substances or their changes and converts them into electrical signals. Through this, the detection of chemical substances, physical, chemical or biochemical changes can be carried out. The chemical substance sensor element, for example, is for ions such as H+, K+, Ca2+, neurotransmitters such as acetylcholine, metabolites produced inside or outside cells, or substances that can be metabolized, etc. A semiconductor sensor element that detects metabolites, specific antigens or antibodies derived from these proteins, etc., and converts the signals derived from the information from the chemical substances that should be detected into electrical signals . Examples of chemical substance sensor components can be ion-sensitive or chemical field-effect transistors, ISFETs, CHEMFETs, and the like.

The types of physiological sensors 12 in this case are:

(1) The light sensor component obtains light information related to the measurement object that should be sensed by this. The so-called light information is information related to some light obtained by irradiating light to the measurement object. The light sensor element can be a semiconductor element that senses optical signals and converts them into electrical signals. The light used for sensing can be visible light, ultraviolet light, red External light, fluorescence, phosphorescence, luminescence, etc. By this, it is possible to obtain information about the morphology of the measurement target, the distribution of the measurement target, and the distribution, concentration, and behavior of the substance related to the measurement target.

(2) The inductance sensor component is a semiconductor component that obtains electrical information about the measurement object. The inductance sensor element can be used to detect potential information such as the activity potential of cells, the degree of cell grounding, the degree of adhesion between cells or the degree of microinvasiveness, and the activation or activation state of measurement objects such as cells. A semiconductor device that senses potential, current value, voltage value, and impedance and generates current or voltage signals. By generating current or voltage signals, it is possible to induce stimulation, activation, or inactivation of the object to be measured. Furthermore, the sensor element may also be a body surface temperature sensor element. The sensing at each component and the conversion of information obtained by sensing into electrical signals, etc., can be performed under the control of the control system. In addition, the system can also include sensor elements for detecting other substances. Examples of inductance sensor components may be semiconductor sensors with electrodes, semiconductor voltage sensors, and the like.

(3) The pressure sensor element can detect the pressure of the blood vessel through the contraction and deformation of the blood vessel wall through the application of the pressure sensor.

The replaceable component 2 is combined with the surface of the monitoring body 1, and the replaceable component 2 contains several microneedle sheets stacked on top of each other, and each microneedle sheet has one or more perforations, wherein Each perforation edge is provided with one or more sensing microneedles, and after a plurality of microneedle sheets are stacked, a sensor with multiple microneedle sheets overlapping and passing through the sensing microneedle is formed Microneedle group.

At least one of the above-mentioned microneedle sheets is a working electrode, and its inner surface is modified with a sensing polymer, which is an aptamer specific to the target drug molecule, and one end is modified with a self-assembled single molecule (SAM) , Can be fixed on the inner surface of the working electrode, and the other end is modified by redox Reporter (redox reporter). More specifically, in an example, the working electrode is first coated with gold, and then various sensing polymers are modified. The sensing polymer is modified with thiol SH at one end, and then an aptamer, and the end of the aptamer is modified. Methyl blue. With square wave voltammetry (SWV) or DPV or chronoamperometry (chronoamperometry), it can continuously detect various inflammations, immune response molecules, or drugs or drugs that can appear in the tissue fluid.

The sensing molecules used in the sensing microneedle of the present invention basically include specific aptamers, antibodies, etc., wherein the universality of aptamers comes from the multifunctional recognition and signal transduction properties of the aptamers, and the nucleic acid is Select the ability to bind to a specific molecular target. By using a sophisticated in vitro selection method (SELEX), aptamers that can bind to a wide range of analytes can be generated, and can be reasonably redesigned to make them large-scale when binding these analytes within any wide or narrow concentration window. The conformational changes.

The biochemical sensor 13 in this case uses this conformational change to generate an easy-to-measure electrochemical signal without the need for target chemical transformation. In order to achieve this signal transduction, the binding of the aptamer is used to induce a conformational change to change the efficiency of the covalently attached redox reporter molecule (here, methylene blue) close to the underlying electrode, which produces a target concentration dependence when the sensor is an electrode. The change in current is interrogated by square wave voltammetry. In accordance with the requirements to support continuous in vivo measurement, sensor signal conduction does not depend on batch processing, such as washing steps or the addition of exogenous reagents.

In addition, since the percutaneous microneedle sensor signal is generated by a specific, binding-induced conformational change, instead of the target being adsorbed to the sensor surface (in the case of SPR, QCM, FET and microcantilever), the platform is relatively Biological fouling (fouling) is not sensitive. For example, previous studies have shown that the percutaneous microneedle sensor performs well within a few hours in flowing, undiluted serum, making it one of the single-step biosensor platforms with the strongest pollution resistance reported to date.

In addition, the structure of the sensing microneedle is further described, wherein the microneedle sheet can be a stainless steel sheet of 0.06-0.1mm, and the height of the protruding array sensing microneedle is 0.6-1.2mm, and the first embodiment described below is a triple stack One (outer layer: reference electrode; middle layer: working electrode; bottom layer: counter electrode), the order of stacking can be selected arbitrarily, and the advantage of such a combined structure is that the area is reduced and the layers can be covered with electrical properties Insulation layer (in addition, the number of microneedles can be reduced to only 2x2, and the corresponding area is reduced to 2mm * 2mm).

The implementation of the first embodiment is shown in Figures 3A and 3B. The replaceable component 2 includes: (1) a first microneedle sheet 21 as a working electrode, and the first microneedle The sheet 21 is a sheet, and the first microneedle sheet 21 is provided with a first perforation 211, the edge of the first perforation 211 is provided with a first sensing microneedle 212, and the edge of the first microneedle sheet 21 has Second connecting end 213; (2) a second microneedle sheet 22 as a reference electrode, and the second microneedle sheet 22 is in the shape of a sheet, and the second microneedle sheet 22 is provided with a second perforation 221 , The second perforation edge 221 is provided with a second sensing microneedle 222, and the edge of the second microneedle sheet 22 has a second connecting end 223; (3) a third microneedle sheet 23 is used as a counter electrode, The third microneedle sheet 23 is thin, and the third microneedle sheet 23 is provided with a third perforation 231, the edge of the third perforation 231 is provided with a third sensing microneedle 232, and the third The edge of the microneedle sheet 23 has a second connecting end 233; (4) where the first perforation 211 and the second perforation 221 are in the same vertical position as the third perforation 231, the first microneedle sheet 21 and the second microneedle sheet 22 and the third microneedle sheet 23 overlap each other, so that the first sensing microneedle 212, the second sensing microneedle 222, and the third microneedle sheet 232 are in a triangular cone shape or form that does not slightly invade each other. A quadrangular pyramid with a missing side to allow the subcutaneous tissue fluid to be effective Enter the inner surface of the protruding thorn to interact with the sensing molecule (the three sensing microneedles are separated from each other without overlapping, wherein the first sensing microneedle 212, the second sensing microneedle 222, and the third microneedle sheet The range of 232 at one point is the sensing micro-needle group).

The aforementioned second connecting end 213, second connecting end 233, and second connecting end 233 are respectively aligned with the first connecting end 15 at different positions to perform micro-intrusion to achieve electrical connection.

Each of the aforementioned microneedle sheets can be packaged to the substrate PCB using SMD. SMD can be combined with room temperature/normal temperature/low temperature conductive silver glue, or UV ultraviolet light curing conductive silver glue, or low temperature riveting Together. When laminating metal sheets, electrical insulation is required between the layers. The preferred stacking sequence for manufacturing is the outermost layer (reference electrode), the intermediate layer (working electrode), and the bottommost layer (counter electrode), because In addition to covering the sensing polymer, the working electrode usually needs to be covered with a porous electrically insulating film for most of the outermost layer. Therefore, if it is placed in the middle layer, it can just electrically isolate the upper layer of the reference electrode from the bottom layer. In this way, the upper reference electrode and the bottom counter electrode do not need to be covered with an electrically insulating film on the outermost layer.

In the assembly, the metal sheet can also be made into the form of DIP, passing through the PCB substrate, and the back side is still combined with room temperature/normal temperature/low temperature conductive silver glue or UV ultraviolet light curing conductive silver glue for fixing. The substrate adopts a PCB double-layer board, so that the assembly can be completed more easily. In order to take into account the biocompatibility, the PCB needs to use a lead-free process. Biocompatible plastic substrates can also be used for production by injection molding.

In addition, as shown in Figure 4, the replaceable component 2 can also only include the first microneedle sheet 21 and the second microneedle sheet 22, wherein the second sensing microneedle 222 passes through the first through hole 211 and The first sensing microneedle 212 is opposite. In addition, the replaceable component 2 in this case is a separate structure, so after use, it can be removed to replace it with a new replaceable component 2.

In addition, this case can also use the microneedle sheet pattern shown in Figures 5A to 5C, as described below:

(1) It can be seen from Figure 5A that the microneedle sheet 26 of the working electrode has four perforations 261, four sensing microneedles 262 and two connecting ends 263;

(2) It can be seen from Figure 5B that the microneedle sheet 27 of the reference electrode (which can also be used as a counter electrode) has two perforations 271, two sensing microneedles 272, and two connecting ends 273;

(3) As shown in Figure 5C, if the microneedle sheet 26 and the microneedle sheet 27 can be stacked, the measurement can be performed, which can be used with different microneedle sheets 27 or multiple layers of microneedle sheets 27. , To achieve three-in-one or even four-in-one biochemical measurement.

(4) As shown in Figure 5D, the working electrode microneedle sheet 26 can be overlapped with the reference electrode microneedle sheet 27, and the counter electrode microneedle sheet 27' (with two perforations 271', two sensing microneedles 272' and the two connecting ends 273') are also stacked on the other side of the working electrode microneedle sheet 26, but are not in contact with the reference electrode microneedle sheet 27, the three-electrode electrochemical measurement can be performed.

In addition, the microneedle sheet is made of biocompatible or medical stainless steel. During manufacturing, only the inner and outer surfaces of the microneedle are coated with gold, while the reference electrode is only coated with a layer of Ag/AgCl on the microneedle, and the working electrode is coated Sensing molecules, such as enzymes, aptamers, etc., need special attention. The coated area only needs to be 3/1 or more of the microneedle height, or even more than 1/2. In addition, insulating parts and preventing biological interference, etc., need to be covered with porous materials. These porous materials can be water glue or HEMA, epoxy-polyurethane formic resin (Epoxy-PU) membrane, semi-permeable membrane, or low oxygen permeability when the sensing polymer is enzyme. membrane. When the sensing polymer is aptamer, it may be polysulfone membrane (polysulfone) or the like.

In the preferred manufacturing implementation of the sensing microneedle in this case, firstly, the sensing microneedle is electrically operated. The electrode is roughened to increase its active area, and then gold-plated to become a gold electrode. Thaw DNA constructs specific to the target analyte, etc., and then reduce them with a 1,000-fold molar excess of tris(2-carboxyethyl)phosphine at room temperature for 1 hour. Then, the freshly roughened gold electrode was rinsed in deionized water, and then immersed in a solution of 200-500 nM of an appropriately reduced DNA construct at room temperature for 1 hour. After that, the microneedle working electrode was covered with a polysulfone fiber membrane. The microneedle working electrode was soaked in a 20mM 6-mercapto-1-hexanol PBS solution overnight for 12 hours at 4°C to cover the remaining gold surface and remove non-specifically adsorbed DNA. After that, the microneedle working electrode was rinsed with deionized water and stored in PBS.

The sensing microneedle in this case can be formed by a stamping or etching process. The material of the sensing microneedles is selected from stainless steel, nickel, nickel alloy, titanium, titanium alloy or silicon material. The materials for the sensing microneedles can also be resins such as polycarbonate, polymethacrylic acid copolymer, ethylene/vinyl acetate copolymer, Teflon or polyester, and deposit on the surface with biocompatibility Metal. The height of the sensing microneedles is 400-1500 microns, and the substrate width is 200-350 microns. The distance between the tip portions of the sensing microneedles is 500-2000 microns.

In addition, in this case, two or more microneedle sheets (not shown in the figure) can be installed in the replaceable assembly 2, so it can be used to make a two-in-one sensing system, such as simultaneous measurement of blood sugar, Insulin; or measure endotoxin, antibiotics, etc. at the same time.

In addition, each microneedle sheet in this case can have a variety of possible application combinations, which can be used to make two two-in-one sensing systems, such as simultaneous measurement of blood sugar and insulin; or a three-in-one sensing system. Simultaneously measure blood sugar, lactic acid, antibiotics, etc. Can do four-in-one sensing. For example, simultaneous measurement of blood glucose, lactic acid, uric acid, antibiotics, etc.

In addition, the implementation of this case is because the electrochemical detection composed of three electrodes can have enzyme-type sensing polymers, and the main detection circuit is biased to the electrochemical measurement of the potentiostat. Way; and the use of such as antibodies, aptamers, or other non-enzyme sensing polymers, may be biased to use square wave voltammetry (SWV), differential pulse voltammetry (DPV), or electrochemical impedance spectroscopy (EIS) Electrochemical reading circuit; if you want to increase the reading efficiency, you can separate the two microneedle layers, corresponding to the enzyme and non-enzyme reading circuits.

In addition, in some implementations of this case, the reading circuit can be multi-functional, and it also has reading circuits for potentiostat, SWV, DPV, and EIS. It only needs to switch between software and hardware switches. In this way, These microneedle groups can use multiplexers in turn to switch to a single electrochemical reading circuit, which can greatly reduce the size of the overall monitoring system, and can simultaneously monitor the concentration of various analytes in the body, which is helpful for the realization of real-time precision medicine. .

And this case can continuously measure pure physiological signals or pure biochemical signals, such as simultaneous measurement of electrocardiogram, blood pressure, blood oxygen, cortisol (CORTISOL) concentration, and lactic acid concentration, which can comprehensively evaluate the athlete's state of coping with competition stress. In addition, this case also provides several additional examples of simultaneous measurement of physiological signals and pure biochemical signals:

(1) Lactic acid sensing + nine-axis IMU: attach the physiological and biochemical monitoring device in this case to various parts of the athlete's body, muscle parts that will be used during exercise, and parts that will not be used. In addition to obtaining lactic acid, It is also possible to know the intensity of the movement of the part through the nine-axis IMU.

(2) Lactic acid sensing + sEMG: The physiological and biochemical monitoring devices in this case can be attached to various parts of the athlete’s body, muscle parts that will be used during exercise, and parts that will not be used. Through sEMG to know the intensity of the movement of the part.

(3) Lactic acid sensing + nine-axis IMU + sEMG: attach the physiological and biochemical monitoring devices in this case to various parts of the athlete's body, muscle parts that will be used during exercise, and parts that will not be used. In addition to being able to obtain lactic acid, the intensity of movement of the part can also be known through the nine-axis IMU and sEMG.

(4) Drug concentration sensing + physiological signal: It will be of great help to the drug-compliant animal body, whether it is a blood pressure lowering drug, analgesic, or various drugs, the blood concentration of which is important to the life of the animal body The influence of the signal can be continuously detected in real time here.

(5) In addition, in this case, various combinations of biochemical and physiological signal detection modules can be designed based on pharmacology, main effects, and side effects. Including drug concentration sensing (such as hypertension drugs, or antithrombotic drugs), main action biochemical marker concentration detection, side effect biochemical marker concentration detection, a total of three, plus basic physiological signals, including heartbeat, blood pressure, blood Oxygen, activity level, etc.

However, if it is applied to the motion sensing of athletes, a large amount of sweat will be produced during exercise. If only the sensing microneedle as shown in Figure 6A is used, it is often because the animal body sweat 31 in the subcutaneous tissue 3 will slightly invade the sensing microneedle. The tip of the needle, and sweat will interfere with the enzyme at the tip of the sensing microneedle. Therefore, as shown in Figures 6B-1 and 6B-2, a sweat blocking element (protruding from the bottom end of the sensing microneedle 232) can be designed as shown in Figures 6B-1 and 6B-2. Part 2321), so that the animal body sweat generated around the bottom of the sensing microneedle 232 does not slightly invade the tip of the sensing microneedle 212, 222, 232, so that it can exclude the animal body sweat 31 from sensing the tip of the sensing microneedle 232. The interference factor of the measurement.

As shown in Figure 6C, the bottom of the sensing microneedles 212, 222, 232 can also be coated with a non-porous polymer layer 24 (or the non-porous polymer layer 24 is coated first and then the sweat inhibitor ( (Not shown)), such as aluminum chloride (ACH), aluminum chloride hexahydrate cream, such as Drysol or anticholinergic medications, such as glycopyrrolate, This move makes the microneedle substrate so that the sensing microneedle Most of the sweat glands around the bottom of the 212, 222, 232 that are in contact with the skin are temporarily prevented from sweating by the action of the antiperspirant, so they will not touch the tip of the sensing microneedle 212, 222, 232 to remove the sweat of the animal from the sensing microneedle. 212,222,232 The interference factors of tip sensing.

As shown in Figure 6D, a sweat blocking element (adsorption structure 25) can also be designed around the bottom of the sensing microneedles 212, 222, 232, so that the animal body sweat produced around the bottom of the sensing microneedles 212, 222, 232 can be absorbed , To eliminate the interference factors of animal body sweat on the tip sensing of the sensing microneedles 212, 222, 232. In addition, the adsorption structure 25 used in this case can be made of polymer materials such as water glue or made of glass fiber materials The filter material.

In addition, the whole of the sensing microneedles 212, 222, 232 or the tip of the sensing microneedles 212, 222, 232 can be made of a sweat blocking element (non-porous polymer material), so that the periphery of the bottom of the sensing microneedles 212, 222, 232 The generated animal body sweat cannot invade the tip of the sensing microneedle 212, 222, 232, so as to eliminate the interference factor of the animal body sweat on the tip sensing of the sensing microneedle 212, 222, 232.

In addition, sweat blocking elements ((ditch structure (not shown)) can also be designed around the bottom of the sensing microneedles 212, 222, 232, so that the animal body sweat produced around the bottom of the sensing microneedles 212, 222, 232 can be It is guided to the outside of the sensing microneedles 212, 222, and 232 for volatilization, so as to eliminate the interference factors of animal body sweat on the tip sensing of the sensing microneedles 212, 222, and 232.

In this case, the monitoring body 1 combined with the replaceable assembly 2 can be worn on an animal body through a joining component 6. As shown in Fig. 7, the monitoring body 1 can be worn on the arm 4 of the animal body. Or, as shown in Fig. 8, the monitoring body 1 can be worn on the lower leg 5 of the animal body.

The technology in this case can be used with new drug testing. Since new drug testing will have very strict test standards, the testees participating in the test must strictly abide by the regulations and regularly measure physiological and biochemical data, but not every testee It’s convenient to be able to arrive in time for measurement, so that the new drug The test will be flawed. In addition, if the test must be expanded, there is no device that can achieve this goal based on the current equipment; however, the device in this case will be able to timely obtain the physiological and biochemical data of the tested person. Returning back to the server will save the testee’s round trip time. In addition, it will be able to measure the desired data more accurately. This will bring great convenience to new drug testing. Can greatly reduce the time spent on new drug testing.

In terms of new drug development, because new drugs have unique development stages, usually referred to as phase I to IV, dose tolerance and dose response exploration studies are carried out in the second or third phase, and pharmacokinetic studies usually involve these Stage, but usually only as a secondary goal; therefore, for new drugs, the usefulness of blood concentration monitoring (TDM) of therapeutic drugs has not been studied. Usually, the need for TDM is discovered only after the drug has been put on the market.

TDM is particularly valuable in the following situations: (1) Is the relationship between drug concentration and action stronger than that between dose and action; (2) Is there no simple, clear clinical parameter that can be used to evaluate the clinical of the drug Efficacy; (3) Whether the treatment window is small; (4) Recording interaction; (5) Monitoring drug compliance; (6) Whether there are large variability and unpredictability of intra- and inter-individual pharmacokinetic parameters. Our recommendation is that randomized concentration controlled trials should be conducted in the early stages of drug development, and the trial must be mandatory for drug licensing.

In a case, when discussing the relationship between the pharmacokinetics (PK) and pharmacodynamics (PD) of TJ301 in patients with active ulcerative colitis, it is usually necessary to monitor the adverse events and vital signs. The method is to use one to two lead ECG for monitoring, except In addition, it is more necessary to measure and record the heartbeat, blood pressure, etc. of the drug user, but unfortunately, it is often time-consuming and not necessarily instantaneous to perform such monitoring with conventional technology. Therefore, the entire drug clinical trial is The time frame will be very long, but if the technology in this case is used, since the medication status of the drug user and the current physiological and biochemical data can be uploaded in real time, it will inevitably be able to shorten the entire drug test under the condition of obtaining large amounts of data. The itinerary.

In addition, when a person who wants to conduct a new drug clinical trial adopts this case, he can synthesize the corresponding drug aptamer by himself or entrust an aptamer professional development company for the new drug tested, and then apply it to the microneedle drug concentration sensing in this case. Device.

In addition, the power supply unit 14 of the monitoring body 1 in this case is a rechargeable battery or a replaceable battery, so if the monitoring body 1 is out of power, it can be wired to charge or replace the lithium battery.

In addition, the monitoring body 1 of this case can further incorporate a screen or/and a miniature microphone (not shown in the figure) on the outer surface.

In addition, as shown in Figures 9A-9C, the replaceable component 8 can be combined with the monitoring body 7. The monitoring body 7 is provided with a central control unit 71, a physiological sensor 72, and a power supply unit 73. The central control unit 11 is electrically connected to a first signal connection terminal 74, and the power supply unit 73 is electrically connected to a first power connection terminal 75, and after being combined, the physiological sensor 72 can be switched on The hole 80 is exposed; and the replaceable component 8 contains:

(1) Several sensing microneedle groups 81, the sensing microneedle group 81 has two or more sensing microneedles, and each sensing microneedle is combined with one or more Anti-sweat element, and the tips of every two or more of the sensing microneedles in the sensing microneedle group can be gathered inward (the same as the above, so the illustration is not repeated);

(2) The biochemical sensor 82 is electrically connected to the plurality of sensing microneedle groups 81 for monitoring the biochemical of the animal body Signal, wherein the biochemical sensor 82 includes: (a) a detection unit 821, which is used to perform micro-invasion sensing after two or more sensing microneedles are directed towards any point on the skin of the animal , The detection unit can obtain different biochemical concentration change values according to different sensing microneedles at the same point position; and the detection unit 821 will be electrically connected with a second signal connection terminal; (b) a process The unit 822 is used to convert the detected biochemical concentration change value into a biochemical sensing signal.

(3) A power supply unit 83 for providing power required for the operation of the biochemical sensor 82;

(4) A second signal connection terminal 84 is electrically connected to the detection unit 821 of the biochemical sensor 82;

(5) A second power connection terminal 85 is electrically connected to the power supply unit 83.

Therefore, when the monitoring body 7 is combined with the replaceable component 8, the first signal connection terminal 74 will be electrically connected to the second signal connection terminal 84, and the first power connection terminal 75 will be connected to the second power supply The connection terminal 85 is electrically connected to provide power to the replaceable component 8 through the power supply unit 73; After that, when the sensing microneedle group 81 performs micro-invasion sensing toward any point on the animal's skin, the detection unit 821 can obtain different analyte concentrations at the same point position according to different sensing microneedles. The processing unit 822 converts the signal to obtain the biochemical sensing signal, and finally transmits the biochemical sensing signal to the central control unit 71 through the second signal connection terminal 84 and the first signal connection terminal 74.

The advantages of the physiological and biochemical monitoring device provided by the present invention when compared with other conventional technologies are as follows:

(1) The present invention can develop a continuous measurement device. In addition to measuring the physiological data of electrocardiogram, blood pressure, and blood oxygen, it can also measure the biochemical data of cortisol concentration and lactic acid concentration. Only in this way can a variety of physiological and biochemical signals be measured at the same time, so the device is suitable for the application field of animal body posture.

(2) The present invention has been disclosed above through the above-mentioned embodiments, but it is not intended to limit the present invention. Anyone familiar with this technical field with ordinary knowledge should understand the aforementioned technical features and embodiments of the present invention without departing from it. Within the spirit and scope of the present invention, some changes and modifications can be made. Therefore, the patent protection scope of the present invention shall be subject to what is defined by the claims attached to this specification.

101: opening

102: open

12: Physiological Sensor

13: Biochemical sensor

15: The first connection terminal

2: Replaceable components

20: Hole

213: second connection end

223: second connection end

233: third connection

Claims (10)

A physiological and biochemical monitoring device includes: a monitoring body for combining with the skin of an animal body, a first connection end is arranged on the surface of the monitoring body, and the monitoring body further has: a power supply unit for In order to provide the power required for the operation of the monitoring body, an opening is provided on the surface of the monitoring body; a central control unit is electrically connected to the power supply unit and the first connection terminal to control the operation of the monitoring body And transmission data; a physiological sensor is electrically connected with the power supply unit and the central control unit, and the physiological sensor is used to monitor the physiological sensing signal of the animal body, and can monitor the physiological sense The measurement signal is sent to the central control unit; the biochemical sensor is electrically connected to the power supply unit, the central control unit and the first connection terminal, and the biochemical sensor is used to monitor the biochemical signal of the animal body , Wherein the biochemical sensor includes: a detection unit for detecting and obtaining a biochemical concentration change value; a processing unit for converting the detected biochemical concentration change value into a biochemical sensing signal , And can transmit the biochemical sensing signal to the central control unit; a replaceable component is combined on the surface of the monitoring body, and the replaceable component has an opening, wherein the replaceable component The system includes: several sensing micro-needle groups, the sensing micro-needle group has two or more sensing micro-needles, and each sensing micro-needle is combined with one or more anti-perspiration Components, and the tips of every two or more of the sensing microneedles in the sensing microneedle group can be gathered inward; A second connecting end is electrically connected to the first connecting end, and is used for the biochemical sensing after two or more sensing microneedles are directed towards any point on the animal's skin. The detection unit of the device can obtain different biochemical concentration change values at the same point position according to different sensing microneedles through the connection with the second connection end; therefore, after the replaceable component is combined with the monitoring body, The monitoring body can simultaneously monitor physiological sensing signals and biochemical sensing signals. The physiological and biochemical monitoring device according to claim 1, wherein the physiological sensor can be an optical sensor, an electrode contact sensor, a sensor for inertial motion detection, or a sensor for temperature detection The sensor, the optical sensor can be a photoplethysmography sensor, a blood oxygen sensor, a blood pressure sensor, and the electrode contact sensor is an all-in-one impedance sensor, An electrocardiogram (ECG) sensor, a surface electromyography (sEMG) sensor, an electroencephalogram (EEG) sensor, and the sensor for inertial motion detection is a speed sensor, An acceleration sensor, an angular velocity sensor, an electronic compass, a magnetic field sensor, and a multi-axis motion sensor are used to measure the speed, acceleration, angular velocity, azimuth angle, etc. of the movement, and can be based on the speed Or/and acceleration, angular velocity, azimuth angle to perform fusion calculation to determine the movement posture and trajectory, and the temperature detection sensor is a body surface temperature sensor. The physiological and biochemical monitoring device according to claim 1, wherein the biochemical sensor is used to measure a blood glucose value, an ion value, a drug concentration value, or two or more of the above values. The physiological and biochemical monitoring device according to claim 1, wherein the processing unit can electrochemically convert the detected biochemical concentration change value into the biochemical sensing signal. The physiological and biochemical monitoring device according to claim 1, which further includes a combining component for fixing the monitoring body on the animal body so that the monitoring body can interact with the animal Body-skin contact or micro-invasion. The physiological and biochemical monitoring device according to claim 1, wherein the sensing microneedle of the sensing microneedle is selected from stainless steel, nickel, nickel alloy, titanium, titanium alloy or silicon material, and is deposited on the surface with biocompatibility In addition, one of the sensing microneedles in the sensing microneedle group may be attached to the surface to modify the sensing polymer and the porous protective layer. The physiological and biochemical monitoring device according to claim 1, wherein the replaceable component includes several microneedle sheets stacked on top of each other, and each microneedle sheet has one or more perforations, and each perforation edge is One or more sensing microneedles are provided, and after a plurality of microneedle sheets are stacked, a sensing microneedle group with multiple microneedle sheets overlapping and passing through the sensing microneedles is formed. The physiological and biochemical monitoring device according to claim 1, wherein the replaceable component includes: a first microneedle sheet as a working electrode, and the first microneedle sheet is in the shape of a sheet, and the first microneedle sheet A microneedle sheet is provided with a first perforation, and the edge of the first perforation is provided with a first sensing microneedle; a second microneedle sheet is used as a reference electrode, and the second microneedle sheet is in the shape of a sheet. And the second microneedle sheet is provided with a second perforation, and the second perforation edge is provided with a second sensing microneedle; wherein the first perforation and the second perforation are in the same vertical position, and the first microneedle The sheet and the second microneedle sheet overlap each other, and the first sensing microneedle and the second sensing microneedle are separated from each other without overlapping; in addition, a third microneedle sheet may be added as a Counter electrode, and the third microneedle sheet is thin, and the third microneedle sheet is provided with a third perforation, the edge of the third perforation is provided with a third sensing microneedle, and the first perforation, The second perforation is at the same vertical position as the third perforation, and the first microneedle The sheet, the second microneedle sheet, and the third perforation overlap each other, and the first sensing microneedle, the second sensing microneedle, and the third microneedle sheet are separated from each other without overlapping. The physiological and biochemical monitoring device according to claim 1, wherein the sensing microneedle can change the shape of both sides, so that the animal body sweat produced around the bottom of the sensing microneedle cannot invade the sensing microneedle. The tip of the sensor is used to eliminate the interference factors of animal sweat on the tip sensing of the sensing microneedle; or the bottom of the sensing microneedle can be coated with a non-porous polymer material, so that the bottom of the sensing microneedle Animal body sweat produced around cannot invade the tip of the sensing microneedle, so as to eliminate the interference factors of animal body sweat on the tip sensing of the sensing microneedle; or there is an adsorption structure designed around the bottom of the sensing microneedle , So that the animal body sweat produced around the bottom of the sensing microneedle can be absorbed, so as to eliminate the interference factor of the animal body sweat on the tip sensing of the sensing microneedle; or the bottom of the sensing microneedle is designed around the bottom There is a trench structure, so that the animal sweat produced around the bottom of the sensing microneedle can be guided to the outside of the sensing microneedle for volatilization, so as to eliminate the interference of animal sweat on the tip sensing of the sensing microneedle factor. A physiological and biochemical monitoring device includes: a monitoring body for combining with the skin of an animal body, a first connection end is arranged on the surface of the monitoring body, and the monitoring system has: a power supply unit, In order to provide the power required for the operation of the monitoring body, an opening is provided on the surface of the monitoring body; a central control unit is electrically connected to the power supply unit and the first connection terminal to control the operation of the monitoring body And transmission data; a physiological sensor is electrically connected with the power supply unit and the central control unit, and the physiological sensor is used to monitor the physiological sensing signal of the animal body, and can monitor the physiological sense The test signal is sent to the central control unit; A first connecting end is exposed at the opening of the monitoring body; a replaceable component is combined with the surface of the monitoring body, and the replaceable component has an opening, wherein the replaceable component The system includes: several sensing micro-needle groups, the sensing micro-needle group has two or more sensing micro-needles, and each sensing micro-needle is combined with one or more anti-perspiration The tip of every two or more sensing microneedles in the sensing microneedle group can be gathered inward; the biochemical sensor is electrically connected to the plurality of sensing microneedle groups , Used to monitor the biochemical signal of the animal body, wherein the biochemical sensor includes: a detection unit for micro-intrusion of two or more sensing microneedles towards any point on the animal body’s skin After sensing, the detection unit can obtain different biochemical concentration change values based on different sensing microneedles at the same point position; a processing unit is used to convert the detected biochemical concentration change value into a lifetime allelopathy Test signal; a second connection terminal is electrically connected to the processing unit and the first connection terminal to enable the biochemical sensing signal to be transmitted to the central control unit through the first connection terminal; therefore, the replaceable After the components are combined on the monitoring body, the monitoring body can simultaneously monitor physiological sensing signals and biochemical sensing signals.

Images