Animal ambulatory vital signs monitoring platform for hypoxia-related diseases

Abstract

The application provides an animal dynamic vital sign monitoring platform for hypoxia-related diseases, and relates to the technical field of animal vital sign monitoring. The animal dynamic vital sign monitoring platform for hypoxia-related diseases comprises an implantable micro blood oxygen sensor, an external wireless power supply module and an external data processing terminal. The overall size of the implantable micro blood oxygen sensor is not more than 3 mm*3 mm*1 mm. The implantable micro blood oxygen sensor adopts a three-layer stacked structure, and the three layers are an optical sensing layer, a flexible circuit layer and a wireless power supply and control layer from top to bottom. The outer side is entirely coated with a biocompatible packaging layer. The optical sensing layer comprises a microvessel directional reflective optical sensing component. Through the implantable wireless architecture, directional optical sensing, hypoxia compensation algorithm and biocompatible packaging, the problems of data distortion, hypoxia instability, human stress and high cost in the prior art are solved, and the stress-free, continuous and accurate high-throughput monitoring of animals in a hypoxic environment is realized.

Description

Technical Field

[0001] This invention relates to the field of animal vital sign monitoring technology, specifically to a dynamic vital sign monitoring platform for animals with hypoxia-related diseases. Background Technology

[0002] Hypoxia-related diseases encompass a wide range of serious threats to human health, including altitude sickness (acute / chronic mountain sickness, acute pulmonary edema, acute cerebral edema, etc.), respiratory diseases (such as chronic obstructive pulmonary disease, acute lung injury / acute respiratory distress syndrome, severe pneumonia, etc.), cardiopulmonary and vascular diseases (such as pulmonary hypertension, heart failure), sleep-related diseases (such as obstructive sleep apnea), and cerebral ischemic diseases (such as stroke, brain injury), as well as hypoxia caused by acute physical and chemical factors. Their common pathological basis is the imbalance between oxygen supply and demand and multi-organ damage caused by hypoxia exposure. With the deepening of major national strategies such as construction, plateau resource development, manned spaceflight, and ocean navigation, the number of people rapidly venturing to high altitudes, staying there for extended periods, and working in special environments continues to expand, creating an urgent need for elucidating the pathogenesis of hypoxia-related diseases, developing preventive drugs, and optimizing treatment plans.

[0003] In basic research on hypoxic diseases, small animal models are core tools for elucidating the pathological mechanisms of the disease and evaluating the effectiveness of interventions. Blood oxygen saturation (SpO2), as a core indicator for assessing the body's oxygenation status, directly reflects the proportion of hemoglobin binding sites occupied by oxygen. It can accurately evaluate the efficiency of pulmonary gas exchange and the oxygen delivery capacity of peripheral tissues, and is a key quantitative endpoint for the early diagnosis of hypoxemia and the evaluation of drug intervention effects. However, existing blood oxygen monitoring technologies for laboratory animals have many insurmountable limitations when applied to animal models of hypoxic diseases.

[0004] Currently, mainstream small animal blood oxygen monitoring technologies are mainly divided into four categories: The first category is the traditional small animal finger-clip pulse oximeter, which uses miniature LEDs and light sensors. It is suitable for monitoring parts such as paws and ears of animals under anesthesia, but it cannot measure animals that are awake and moving freely, and it suffers from severe motion artifacts and poor signal quality under low perfusion conditions. The second category is the second-generation pulse oximeter, represented by MouseOxPlus. It can be used for multi-site monitoring in awake animals and has better adaptability to low perfusion than traditional devices. However, it still uses an external fixation method, and blood flow fluctuations caused by animal movement, scratching, and stress can seriously interfere with data quality and cannot... The third category is novel wearable and implantable sensors, including locally wearable photoacoustic detectors and miniature implantable sensors. The former is prone to device displacement due to changes in animal body size under low pressure, and the photoacoustic signal-to-noise ratio decreases significantly under severe hypoxia. The latter is not optimized for extreme hypoxic environments, and low pressure may affect its sealing performance and electromagnetic coupling efficiency. Moreover, it is still in the prototype stage, with high cost and biocompatibility to be verified. The fourth category is remote control operating system inside the hypoxia chamber, which realizes blood oxygen measurement through internal and external devices. However, it has a complex structure, high manufacturing cost, and cumbersome operation, and cannot be widely used in large low-pressure hypoxia chambers.

[0005] In summary, existing technologies suffer from four major drawbacks: First, they cannot achieve in-situ, real-time, and continuous monitoring; removing animals from hypoxic environments for measurement leads to "oxygen-enrichment shift," causing severe data distortion. Second, monitoring stability is poor under extreme hypoxic conditions, and signals are easily affected by motion artifacts, low perfusion, and environmental factors. Third, the detection procedure itself can induce stress in animals, causing changes in physiological parameters and reducing the reliability and reproducibility of research results. Fourth, some novel devices are complex in structure and expensive, making large-scale application in conventional laboratories difficult. Therefore, there is an urgent need to develop a platform capable of in-situ, real-time, continuous, and accurate monitoring of vital signs in small animals in various hypoxic environments under conscious, free-moving, and stress-free conditions. This would overcome existing technological bottlenecks and advance basic research and drug development for hypoxic diseases. Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention provides a dynamic vital sign monitoring platform for animals with hypoxia-related diseases, which solves the problems of data distortion, unstable hypoxia, artificial stress, and high cost in existing blood oxygen monitoring technologies.

[0007] To achieve the above objectives, the present invention provides the following technical solution: a dynamic vital sign monitoring platform for animals with hypoxia-related diseases, comprising an implantable miniature pulse oximeter, an external wireless power supply module, and an external data processing terminal, wherein the overall size of the implantable miniature pulse oximeter does not exceed [a certain value]. It adopts a three-layer stacked structure, from top to bottom: an optical sensing layer, a flexible circuit layer, and a wireless power supply and control layer, with an overall biocompatible encapsulation layer on the outside. The optical sensing layer includes a microvascular directional reflective optical sensing component for acquiring photoplethysmography (PPG) signals from subcutaneous target blood vessels in experimental animals. The flexible circuit layer integrates an analog signal conditioning component and a main control and blood oxygen calculation component. The analog signal conditioning component is used to convert optical signals into electrical signals and perform amplification and filtering. The main control and blood oxygen calculation component has a built-in dynamic compensation model for hypoxia environment, which is used to calculate and obtain blood oxygen saturation, heart rate and tissue perfusion index parameters. The wireless power supply and control layer includes a wireless power supply component, a wireless communication component, and an electromagnetic isolation component. The wireless power supply component is connected to an external wireless power supply module via magnetic coupling to achieve battery-free power supply. The wireless communication component is used to wirelessly transmit the calculated physiological parameters to an external data processing terminal. The electromagnetic isolation component is used to eliminate the interference of the wireless power supply magnetic field on the optical detection signal. The external wireless power supply module is arranged around the activity area of ​​the experimental animals to provide stable wireless power for the implantable miniature blood oxygen sensor. The external data processing terminal is used to receive, display, and store physiological parameters, and generate dynamic change curves and abnormal warnings.

[0008] Preferably, the microvascular directional reflective optical sensing component includes a first light-emitting device LED1, a second light-emitting device LED2, a photodetector PD, an optical isolation wall, and a transparent optical window; The LED1 emits a wavelength of 620–680 nm. The LED2 emits red light with a wavelength of 850–940 nm. Near-infrared light, wherein the PD has a photosensitive area of ​​0.5–1 High-sensitivity silicon photodetectors with dark current ≤1nA; LED1 and LED2 are located on the same side of the PD, forming a reflective detection structure. The center distance between the LEDs and the PD is controlled between 1.0 and 3.5. The corresponding light penetration depth is 0.5–2.5. It matches the vascular scale of the mouse common carotid artery and femoral artery; The optical isolation wall is black. Made of carbon-doped light-absorbing polymers or metal light-shielding layers, with a height higher than The light-emitting surface is used to block light. Direct light enters The resulting crosstalk.

[0009] Preferably, the biocompatible encapsulation layer adopts a double-layer composite structure, with the inner layer being a barrier layer with a thickness of 5-20 mm. of thin film or / Composite film, water vapor permeability ≤ g / It is used to block the penetration of body fluids and ions; The outer layer is a flexible buffer layer with a thickness of 100-1000 mm. medical grade Or silicone, with a Shore hardness of 20-30. It is used to reduce mechanical friction between devices and tissues, and to alleviate fiber encapsulation and foreign body reaction; The transparent optical window area has a high light transmittance with a thickness ≤10μm. Encapsulation, with a light transmittance ≥92%.

[0010] Preferably, the analog signal conditioning component includes, in sequence, a transimpedance amplifier, a low-noise amplifier, a bandpass filter, an automatic gain control circuit, and an analog-to-digital converter; The gain of the transimpedance amplifier is , used to Output The photocurrent is converted into a voltage signal; The bandpass filter is a second-order Butterworth filter with a passband frequency range of [frequency range missing]. It covers the heart rate range of mice and rats; The automatic gain control circuit dynamically adjusts the gain range to: It adapts to changes in signal strength under low perfusion conditions; the analog-to-digital converter has a 12-bit resolution and a sampling rate of .

[0011] Preferably, the input parameters of the hypoxic environment dynamic compensation model include a dual-wavelength ratio parameter. Perfusion index Environmental pressure Ambient temperature and animal heart rate The compensation relationship is ; The model can automatically correct the blood oxygen calibration curve according to changes in environmental pressure and temperature, eliminating the impact of multiple disturbances such as low pressure, low oxygen, low temperature and low perfusion on the accuracy of blood oxygen calculation.

[0012] Preferably, the wireless power supply component includes a planar helical microcoil and a power management circuit; The planar spiral microcoil is arranged at the tail of the flexible substrate, with a line width of 50μm, a line spacing of 50μm, 15 to 20 turns, an outer diameter of 6mm × 4mm, and an operating frequency of 13.56MHz. The power management circuit integrates a rectifier bridge, filter capacitors, and a low-dropout linear regulator, with a rectification efficiency of ≥80% and an output stable DC voltage of 3.3V. The external wireless power supply module has a power supply distance of 20-100mm, a power supply efficiency of ≥15%, and covers the range of a standard mouse cage.

[0013] Preferably, the electromagnetic isolation component adopts a triple isolation mechanism: spatial isolation, with the wireless power supply coil arranged at the rear of the sensor and the optical detection unit arranged at the head of the sensor, with a distance of ≥5mm between the two; Grounding shielding: A copper foil grounding shielding layer is set below the analog signal area to cover the entire optical sensing and signal conditioning circuitry; Time isolation is achieved by using a time-division multiplexing mechanism. Sampling is paused during power supply and high-frequency power supply excitation is turned off during sampling. The switching frequency is 1kHz.

[0014] Preferably, the implantable micro-blood oxygen sensor is implanted in the subcutaneous tissue area within 0.5 to 2 mm above the common carotid artery of the experimental animal, or in the subcutaneous superficial blood vessel area beside the femoral artery, beside the axillary artery, and on the back. The procedure employs a minimally invasive subcutaneous implantation method with an incision length of 5–10 mm. Subcutaneous fixation is achieved using absorbable sutures. Post-implantation continuous monitoring is conducted for at least 72 hours. The working pressure range is 30–101 kPa, and the working temperature range is -10℃–40℃.

[0015] Preferably, the wireless communication component adopts 433 Low-power radio frequency communication in the frequency band with a data rate of 1 The data packet is 32 bytes long and contains the device ID, blood oxygen saturation value, heart rate, perfusion index, and status information. Data packet loss rate Communication distance It can simultaneously support parallel communication of 16 implantable miniature blood oxygen sensors; The external data processing terminal has a built-in 32 Flash memory, capable of storing It supports multi-channel synchronous display of monitoring data, data export, and audible and visual alarms for low blood oxygen, abnormal heart rate, and signal loss.

[0016] A method for monitoring dynamic vital signs in animals with hypoxia-related diseases includes the following steps: S1. The implantable miniature blood oxygen sensor is implanted subcutaneously in the area adjacent to the target blood vessel of the experimental animal through a minimally invasive method. After the operation, anti-infection and analgesia treatments are given until the animal recovers to a normal activity state. S2. Activate the external wireless power supply module to provide stable wireless power to the implantable miniature blood oxygen sensor through magnetic coupling. S3, the main control chip controls the red light. and near-infrared The light is emitted in pulses in sequence. The light signal irradiates the target blood vessel through the subcutaneous tissue. The oxygenated hemoglobin and deoxygenated hemoglobin in the blood produce differential absorption. The reflected light after being scattered by the tissue returns to the photodetector and is converted into a photocurrent signal. S4, the analog signal conditioning component amplifies, filters, and performs analog-to-digital conversion on the photocurrent signal, outputting a high signal-to-noise ratio photoplethysmography (PPG) signal; S5. The main control chip extracts the waveform characteristics of the photoplethysmography (PPG) wave and calculates the red and infrared light. Ratio, to obtain the dual-wavelength ratio parameter By combining perfusion index, environmental pressure, environmental temperature and heart rate parameters, real-time blood oxygen saturation, heart rate and tissue perfusion index are obtained through a dynamic compensation model for hypoxic environment. S6. The wireless communication component transmits the calculated physiological parameters to an external data processing terminal in real time. The terminal displays the values ​​and dynamic change curves of multiple physiological parameters, stores the monitoring data, and issues an early warning when the parameters are abnormal.

[0017] This invention provides a dynamic vital sign monitoring platform for animals with hypoxia-related diseases. It has the following beneficial effects: 1. This invention achieves in-situ real-time continuous monitoring of animals in a state of free movement throughout the entire process by using a subcutaneous implantation monitoring method without physical connection, combined with a fully wireless magnetic coupling power supply and data transmission architecture. This completely solves the problems of blood oxygenation reversal and data distortion caused by the need to remove the animal in traditional technologies.

[0018] 2. This invention achieves stable signal acquisition and accurate calculation under complex extreme conditions by using a blood oxygen calculation model optimized for hypoxic extreme environments, combined with a directional optical sensing structure and multiple electromagnetic anti-interference designs, thus overcoming signal failure and measurement deviation caused by low perfusion and environmental disturbances.

[0019] 3. This invention, through sub-centimeter-scale miniaturized device design, combined with minimally invasive implantation technology and biocompatible packaging structure, achieves the monitoring effect of postoperative stress-free natural activity in animals, eliminating physiological parameter fluctuations caused by human operations such as grasping and restraint, and improving the authenticity of experimental data.

[0020] 4. This invention achieves high-throughput, low-cost large-scale animal experimental monitoring through a modular, split system architecture, combined with standardized implantable devices and multi-node parallel communication design, reducing equipment investment and operational complexity, and facilitating its application in conventional laboratories. Attached Figure Description

[0021] Figure 1 This is a diagram showing the overall architecture of the monitoring platform of the present invention; Figure 2 This is a cross-sectional view of the layered structure of the implantable sensor of the present invention; Figure 3 This is a top view of the optical sensing component of the present invention; Figure 4 This is a partial cross-sectional view of the biocompatible packaging of the present invention; Figure 5 This is a plan view of the wireless power supply and electromagnetic isolation structure of the present invention; Figure 6 This is a flowchart of the monitoring method of the present invention; Figure 7 This is a schematic diagram of the preferred implantation location of the sensor according to the present invention; Figure 8 This is a comparison chart of the core performance of the present invention. Detailed Implementation

[0022] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0023] Example 1: like Figure 1-8 As shown, this embodiment of the invention provides an animal dynamic vital sign monitoring platform for hypoxia-related diseases, including an implantable miniature pulse oximeter, an external wireless power supply module, and an external data processing terminal. The overall size of the implantable miniature pulse oximeter does not exceed [a certain value]. It adopts a three-layer stacked structure, consisting of an optical sensing layer, a flexible circuit layer, and a wireless power supply and control layer from top to bottom. The entire outer layer is covered by a biocompatible encapsulation layer, which uses a double-layer composite structure with an inner barrier layer of 5–20 mm thickness. of thin film or / Composite film, water vapor permeability ≤ g / It is used to block the penetration of body fluids and ions, with an outer flexible buffer layer of 100-1000 mm thickness. medical grade Or silicone, with a Shore hardness of 20-30. To reduce mechanical friction between devices and tissues, and to mitigate fiber encapsulation and foreign body reactions, the transparent optical window area uses a high transmittance with a thickness ≤10μm. The encapsulation has a light transmittance of ≥92%. The implantable miniature pulse oximeter is preferably implanted in the subcutaneous tissue area within 0.5 to 2 mm above the common carotid artery of the experimental animal, or in the subcutaneous superficial blood vessel area beside the femoral artery, axillary artery, and back. It adopts a minimally invasive subcutaneous implantation method with an incision length of 5 to 10 mm. Subcutaneous fixation is completed by absorbable sutures. The continuous monitoring time after implantation is not less than 72 hours. The working pressure range is 30 to 101 kPa, and the working temperature range is -10℃ to 40℃. Specifically, the aforementioned monitoring platform is primarily designed for basic research and drug evaluation of hypoxia-related diseases. It is compatible with commonly used laboratory animals such as mice and rats, and supports various simulated environments including normobaric hypoxia, hypobaric hypoxia, and intermittent hypoxia. It comprehensively covers the monitoring needs of animal models for diseases such as altitude sickness, chronic obstructive pulmonary disease, pulmonary hypertension, and ischemic brain injury. The platform consists of three collaborative components: an implantable miniature pulse oximeter, an external wireless power module, and an external data processing terminal. It enables long-term continuous monitoring of animals in a free-moving state without physical wiring, completely solving the core pain points of traditional technologies that require animal handling and disrupting the hypoxic environment.

[0024] Example 2: The microvascular directional reflective optical sensing component includes a first light-emitting device (LED1), a second light-emitting device (LED2), a photodetector (PD), an optical isolation wall, and a transparent optical window. LED1 emits light at a wavelength of 620–680 nm. The red light emitted by LED2 has a wavelength of 850–940 nm. Near-infrared light, PD is a photosensitive area of ​​0.5-1 A high-sensitivity silicon photodetector with dark current ≤1nA, LED1 and LED2 are located on the same side of the PD, forming a reflective detection structure, and the center distance between the LEDs and the PD is controlled between 1.0 and 3.5. The corresponding light penetration depth is 0.5–2.5. The optical isolation wall is black, matching the vascular scale of the mouse common carotid artery and femoral artery. Made of carbon-doped light-absorbing polymers or metal light-shielding layers, with a height higher than The light-emitting surface is used to block light. Direct light enters The resulting crosstalk; Specifically, the overall size of the implantable miniature pulse oximeter is strictly controlled within 10mm × 8mm × 3mm to fit the physiological scale of subcutaneous implantation in mice. For rats, the size can be appropriately adjusted to 15mm × 10mm × 4mm. All models employ a top-down, three-layer stacked integrated design. The outer layer is entirely encapsulated by a double-layer composite biocompatible encapsulation structure. The inner barrier layer is prepared using a 10μm thick Parylene-C film through chemical vapor deposition, or a reinforced structure combining a 5μm Al2O3 film and a 5μm Parylene-C film. The water vapor permeability can be as low as 8 × 10⁻⁶. -7 g / (m 2 ·day The system effectively blocks the penetration of body fluids and ions, protecting internal electronic components. The outer flexible buffer layer uses medical-grade PDMS with a Shore A hardness of 25A and a thickness controlled at 500μm. It is encapsulated on the outside of the barrier layer using a molding and curing process, significantly reducing mechanical friction between the device and subcutaneous tissue and mitigating postoperative fibrous encapsulation and foreign body reactions. The optical window area is encapsulated separately with a high-transmittance Parylene-C layer with a thickness of 8μm, achieving a transmittance of over 94%, ensuring efficient transmission of red and near-infrared light. The sensor is preferably implanted via a minimally invasive procedure in the subcutaneous tissue region 0.5–2 mm above the common carotid artery in experimental animals. This area has sufficient blood perfusion and a stable anatomical position, allowing for the acquisition of high-quality pulse oximetry signals. Alternatively, implantation can be performed in the subcutaneous superficial vascular region beside the femoral artery, axillary artery, or on the back, depending on experimental requirements. The implantation surgery involved a tiny skin incision of 5–10 mm. After blunt dissection to create a subcutaneous cavity, the sensor was placed along the blood vessel, ensuring the optical sensing component was aligned with the target vessel. Subcutaneous fixation and incision closure were then completed using 6-0 absorbable sutures. Postoperatively, animals received intraperitoneal injections of penicillin for infection control and buprenorphine for analgesia for three consecutive days. Incision healing, weight changes, and food and water intake were continuously monitored. Animals typically resumed normal activity within seven days postoperatively, meeting the requirements for subsequent experiments.

[0025] Example 3: The optical sensing layer contains microvascular directional reflective optical sensing components for acquiring photoplethysmography (PPG) signals from target blood vessels under the skin of experimental animals. The flexible circuit layer integrates an analog signal conditioning component and a main control and pulse oximetry calculation component. The analog signal conditioning component converts the optical signal into an electrical signal and performs amplification and filtering. The main control and pulse oximetry calculation component incorporates a dynamic compensation model for hypoxic environments to calculate and obtain parameters such as pulse oximetry saturation, heart rate, and tissue perfusion index. The analog signal conditioning component includes, in sequence, a transimpedance amplifier, a low-noise amplifier, a bandpass filter, an automatic gain control circuit, and an analog-to-digital converter. The transimpedance amplifier has a gain of [value missing]. , used to Output The photocurrent is converted into a voltage signal, and the bandpass filter is a second-order Butterworth filter with a passband frequency range of [missing information]. It covers the heart rate range of mice and rats, and the automatic gain control circuit dynamically adjusts the gain range. It adapts to changes in signal strength under low perfusion conditions; the analog-to-digital converter has 12-bit resolution and a sampling rate of The input parameters of the dynamic compensation model for hypoxic environments include the dual-wavelength ratio parameter. Perfusion index Environmental pressure Ambient temperature and animal heart rate The compensation relationship is The model can automatically correct the blood oxygen calibration curve according to changes in environmental pressure and temperature, eliminating the impact of multiple disturbances such as low pressure, low oxygen, low temperature and low perfusion on the accuracy of blood oxygen calculation. Specifically, the core microvascular directional reflective optical sensing component of the sensor has been optimized for the subcutaneous blood vessel scale in small animals. It integrates a red LED, a near-infrared LED, a high-sensitivity silicon photodetector, and an optical isolation wall on the same plane. The red LED emits monochromatic light with a wavelength of 660nm, the near-infrared LED emits monochromatic light with a wavelength of 905nm, and the photodetector has a photosensitive area of ​​0.8mm². 2 With a dark current ≤0.8nA, it can accurately detect weak reflected light signals after tissue scattering. The LED and photodetector are arranged on the same side and in the same plane, with a center-to-center distance controlled at 2.0mm, corresponding to a light penetration depth of approximately 1.5mm. This precisely matches the diameter and burial depth of the mouse common carotid artery, forming a directional reflected light path from LED to the target blood vessel to the scattered light returning to the photodetector. A 0.2mm high black PDMS optical isolation wall is set between the LED and the photodetector to completely block crosstalk caused by direct LED light, effectively improving the signal-to-noise ratio of the photoplethysmography (PPG) signal. The raw light signal collected by the optical sensing layer is transmitted to the flexible circuit layer for processing. The analog signal conditioning component sequentially passes through a gain of 10... 7A V / A transimpedance amplifier converts nA-level photocurrent into a voltage signal. After amplification by a two-stage low-noise amplifier, high-frequency noise is filtered out by a second-order Butterworth filter with a passband of 0.5–20Hz. An automatic gain control circuit then dynamically adjusts the gain within the range of 20–40dB to adapt to signal intensity changes under low perfusion conditions. Finally, a 12-bit, 100Hz sampling rate analog-to-digital converter converts the signal into a digital signal. The main control and blood oxygen calculation components incorporate a dynamic compensation model for hypoxic environments. Input parameters include the dual-wavelength ratio R, perfusion index PI, ambient pressure P, ambient temperature T, and animal heart rate HR. Real-time blood oxygen saturation, heart rate, and tissue perfusion index are calculated using a pre-calibrated nonlinear compensation relationship. The calibration curve can be automatically corrected according to ambient pressure and temperature, ensuring measurement accuracy even under extreme conditions of 30–101 kPa and -10℃–40℃.

[0026] The wireless power supply and control layer includes a wireless power supply component, a wireless communication component, and an electromagnetic isolation component. The wireless power supply component achieves battery-free power supply by magnetic coupling with an external wireless power supply module. The wireless communication component is used to wirelessly transmit the calculated physiological parameters to an external data processing terminal. The electromagnetic isolation component is used to eliminate interference from the wireless power supply magnetic field on the optical detection signal. The wireless power supply component includes a planar spiral microcoil and a power management circuit. The planar spiral microcoil is arranged at the tail of the flexible substrate, with a line width of 50μm, a line spacing of 50μm, 15-20 turns, an outer diameter of 6mm×4mm, and an operating frequency of 13.56MHz. The power management circuit integrates a rectifier bridge, filter capacitors, and a low-dropout line. The voltage regulator has a rectification efficiency of ≥80% and outputs a stable 3.3V DC voltage. The external wireless power supply module has a power supply distance of 20-100mm and a power supply efficiency of ≥15%, covering the standard mouse cage area. The electromagnetic isolation component adopts a triple isolation mechanism: spatial isolation, with the wireless power supply coil placed at the rear of the sensor and the optical detection unit placed at the head of the sensor, with a distance of ≥5mm between them; grounding shielding, with a copper foil grounding shield layer placed below the analog signal area, covering the entire optical sensing and signal conditioning circuit; and time isolation, using a time-division multiplexing mechanism, pausing sampling during power supply and shutting off the high-frequency power supply excitation during sampling, with a switching frequency of 1kHz. The wireless communication component uses 433... Low-power radio frequency communication in the frequency band with a data rate of 1 The data packet is 32 bytes long and contains the device ID, blood oxygen saturation value, heart rate, perfusion index, and status information. The data packet loss rate is... Communication distance It can simultaneously support parallel communication of 16 implantable miniature pulse oximeters, and has a built-in external data processing terminal with 32... Flash memory, capable of storing The system can display monitoring data from the past year, support multi-channel synchronous display, data export, and audible and visual alarms for low blood oxygen, abnormal heart rate, and signal loss. Example 4: An external wireless power module is placed around the area where the experimental animals are active to provide stable wireless power for the implantable miniature blood oxygen sensor. The external data processing terminal is used to receive, display, and store physiological parameters, and generate dynamic change curves and abnormal warnings.

[0027] Specifically, the wireless power supply and control layer enables long-term battery-free power supply and low-interference data transmission. A planar spiral micro-coil is positioned at the tail of the flexible substrate, employing an 18-turn design with a linewidth of 50μm and a spacing of 50μm. It has an outer diameter of 6mm × 4mm and an operating frequency of 13.56MHz, forming a magnetically coupled resonant system with an external power supply coil located at the bottom of the animal cage. The induced energy is converted into a stable 3.3V DC voltage via a rectifier bridge, filter capacitor, and low-dropout linear regulator. The efficiency reaches over 18% within a power supply distance of 20–100mm, meeting the sensor's continuous operation requirements for over 72 hours. To address the interference of the wireless power supply magnetic field on the optical detection signal, the platform employs a triple electromagnetic isolation mechanism: a 6mm distance is set between the wireless power supply coil and the front-end optical detection unit for spatial isolation; a full-area copper foil grounding shield is placed below the analog signal area; and a 1kHz time-division multiplexing mechanism is used, pausing signal sampling during power supply and shutting off high-frequency power supply excitation during sampling, thus eliminating magnetic field coupling noise at its source. The wireless communication component employs a low-power RF solution in the 433MHz ISM band, with a data rate of 1kbps and a data packet length of 32 bytes, containing device ID, physiological parameters, and status information. In a low-pressure, low-oxygen chamber environment, the data packet loss rate is less than 0.8%, and the communication distance reaches 1.5m. A single external terminal can simultaneously support parallel communication from 16 sensor nodes. The external data processing terminal has a built-in 32GB flash memory, capable of storing over two years of monitoring data. It supports real-time display of multi-channel physiological parameters, dynamic curve plotting, historical data export, and abnormal audible and visual alarm functions. When blood oxygen saturation falls below a set threshold or a signal is lost, it automatically triggers an alarm and records the abnormal time point, providing complete evidence for experimental data analysis.

[0028] Example 5: A method for monitoring dynamic vital signs in animals with hypoxia-related diseases includes the following steps: S1. The implantable miniature blood oxygen sensor is implanted subcutaneously in the area adjacent to the target blood vessel of the experimental animal through a minimally invasive method. After the operation, anti-infection and analgesia treatments are given until the animal recovers to a normal activity state. S2. Activate the external wireless power supply module to provide stable wireless power to the implantable miniature blood oxygen sensor through magnetic coupling. S3, the main control chip controls the red light. and near-infrared The light is emitted in pulses in sequence. The light signal irradiates the target blood vessel through the subcutaneous tissue. The oxygenated hemoglobin and deoxygenated hemoglobin in the blood produce differential absorption. The reflected light after being scattered by the tissue returns to the photodetector and is converted into a photocurrent signal. S4, the analog signal conditioning component amplifies, filters, and performs analog-to-digital conversion on the photocurrent signal, outputting a high signal-to-noise ratio photoplethysmography (PPG) signal; S5. The main control chip extracts the waveform characteristics of the photoplethysmography (PPG) wave and calculates the red and infrared light. Ratio, to obtain the dual-wavelength ratio parameter By combining perfusion index, environmental pressure, environmental temperature and heart rate parameters, real-time blood oxygen saturation, heart rate and tissue perfusion index are obtained through a dynamic compensation model for hypoxic environment. S6. The wireless communication component transmits the calculated physiological parameters to an external data processing terminal in real time. The terminal displays the values ​​and dynamic change curves of multiple physiological parameters, stores the monitoring data, and issues an early warning when the parameters are abnormal.

[0029] Specifically: Before sensor implantation, experimental animals are anesthetized with inhaled isoflurane or intraperitoneal sodium pentobarbital. After the animals are in a stable anesthetized state, the target implantation area is shaved, prepared, and disinfected three times with iodine. A minimally invasive subcutaneous implantation method is used. A 5-10 mm incision is made in the skin surface, and the loose subcutaneous tissue is bluntly dissected using hemostatic forceps to create a cavity. The encapsulated implantable miniature pulse oximeter is then implanted along the blood vessel, preferably in the subcutaneous tissue area 0.5-2 mm above the common carotid artery, so that the optical sensing component is directly facing the target blood vessel to obtain optimal signal quality. Alternatively, the area near the femoral artery, axillary artery, or superficial subcutaneous blood vessels on the back can be selected according to experimental needs. After implantation, the sensor is fixed to the subcutaneous fascia layer with 6-0 absorbable sutures to prevent displacement due to animal movement. The skin incision is then sutured layer by layer. For three consecutive days after surgery, animals were given intraperitoneal injections of penicillin for infection control and buprenorphine for analgesia. The wound healing, animal weight changes, and feeding and drinking status were continuously monitored. Generally, animals can recover to normal activity levels 7 days after surgery, and formal monitoring experiments can begin.

[0030] Before the experiment, the external wireless power supply module was placed flat at the bottom of the animal cages to ensure complete coverage of the entire animal activity area. After activating the power supply module, the system automatically outputs a 13.56MHz alternating magnetic field, providing wireless power to the implanted sensors via magnetic coupling resonance. The power supply distance was controlled within the range of 20–100 mm, with a power supply efficiency of no less than 15%. After power activation, the external data processing terminal automatically scans and wakes up the implanted sensors, checking their operating voltage, communication connections, and optical component status one by one. Once all nodes are confirmed to be normal, continuous monitoring mode is entered.

[0031] Once in monitoring mode, the sensor's internal main control chip controls the red LED and near-infrared LED to emit light sequentially in pulses, with a pulse duty cycle ≤1% to minimize overall device power consumption. The red LED emits monochromatic light with a wavelength of 620–680 nm, while the near-infrared LED emits monochromatic light with a wavelength of 850–940 nm. The light signal penetrates subcutaneous tissue and illuminates the target blood vessel. Oxyhemoglobin and deoxyhemoglobin in the blood absorb the two wavelengths of light differently. The reflected light, after being scattered by the tissue, returns to a high-sensitivity silicon photodetector and is converted into a corresponding photocurrent signal. An optical isolation barrier between the LED and the photodetector completely blocks crosstalk caused by direct LED light, ensuring the purity of the reflected light signal.

[0032] The weak nA-level photocurrent signal output by the photodetector is first transmitted to an analog signal conditioning unit for multi-stage processing. The signal then passes through a gain of 10... 6 ~10 7 The V / A transimpedance amplifier converts the signal into a voltage signal, which is then amplified in two stages by a low-noise amplifier. Subsequently, a second-order Butterworth filter with a passband frequency of 0.5–20 Hz filters out high-frequency electromagnetic noise and baseline drift. An automatic gain control circuit dynamically adjusts the gain within the range of 20–40 dB to accommodate signal strength attenuation caused by insufficient peripheral perfusion under hypoxic conditions. Finally, the conditioned analog signal is converted into a digital signal by a 12-bit resolution, 100 Hz sampling rate analog-to-digital converter, outputting a high signal-to-noise ratio photoplethysmography (PPG) signal to the main control chip.

[0033] The main control chip performs moving average preprocessing on the received PPG signal, extracting the peaks, troughs, and DC component characteristics of the waveform. It then calculates the ratio of the AC to DC components of the red and infrared signals, respectively, to obtain the dual-wavelength ratio parameter R. This is combined with the real-time perfusion index PI, the ambient pressure P and temperature T synchronously transmitted by the built-in sensors in the hypoxic chamber, and the animal heart rate HR calculated from the PPG waveform interval. These data are then input into the built-in hypoxic environment dynamic compensation model for calculation. The model automatically corrects the blood oxygen calibration curve based on changes in ambient pressure and temperature, eliminating the impact of multiple disturbances such as low pressure, hypoxia, low temperature, and low perfusion on measurement accuracy. Ultimately, it outputs a real-time blood oxygen saturation value with an error ≤3% within a pressure range of 30–101 kPa, while simultaneously calculating the heart rate and tissue perfusion index parameters.

[0034] After computation, the wireless communication component uses low-power radio frequency communication in the 433MHz ISM band to transmit 32-byte data packets containing device ID, blood oxygen saturation, heart rate, perfusion index, and device status information to an external data processing terminal in real time. A single terminal can simultaneously support parallel communication of 16 implanted sensors, with a data packet loss rate of less than 1% in a hypobaric hypoxic chamber environment. The terminal displays the physiological parameter values ​​and dynamic change curves of multi-channel animals in real time, and all monitoring data is automatically stored in the built-in 32GB flash memory, which can store at least one year of continuous experimental data. When blood oxygen saturation is detected to be below a set threshold, heart rate is outside the normal range, or signal loss exceeds 5 seconds, the terminal automatically triggers an audible and visual alarm and records the time of the anomaly and related parameters, facilitating timely handling and subsequent data analysis by experimental personnel.

[0035] Example 6: This invention discloses a dynamic vital sign monitoring platform for animals with hypoxia-related diseases. Addressing the core challenge of existing technologies' inability to accurately monitor the free movement of small animals under low-pressure, low-oxygen conditions, it employs a split architecture consisting of an implantable miniature sensor, external wireless power supply, and a data terminal. The sensor, with dimensions ≤10mm×8mm×3mm, integrates microvascular directional reflection optics, triple electromagnetic isolation, and a hypoxia dynamic compensation algorithm. It can continuously monitor for ≥72 hours in environments ranging from 30 to 101 kPa, with a blood oxygen measurement error ≤3%. This platform completely eliminates human stress and "oxygen-enrichment shift," and a single terminal supports parallel monitoring of 16 animals, providing accurate and reliable technical support for the study of the pathological mechanisms and drug evaluation of diseases such as altitude sickness and COPD.

[0036] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A dynamic vital signs monitoring platform for animals with hypoxia-related diseases, comprising an implantable miniature blood oxygen sensor, an external wireless power supply module, and an external data processing terminal, characterized in that: The overall size of the implantable miniature pulse oximeter sensor does not exceed [a certain value]. It adopts a three-layer stacked structure, from top to bottom: an optical sensing layer, a flexible circuit layer, and a wireless power supply and control layer, with an overall biocompatible encapsulation layer on the outside. The optical sensing layer includes a microvascular directional reflective optical sensing component for acquiring photoplethysmography (PPG) signals from subcutaneous target blood vessels in experimental animals. The flexible circuit layer integrates an analog signal conditioning component and a main control and blood oxygen calculation component. The analog signal conditioning component is used to convert optical signals into electrical signals and perform amplification and filtering. The main control and blood oxygen calculation component has a built-in dynamic compensation model for hypoxia environment, which is used to calculate and obtain blood oxygen saturation, heart rate and tissue perfusion index parameters. The wireless power supply and control layer includes a wireless power supply component, a wireless communication component, and an electromagnetic isolation component. The wireless power supply component is connected to an external wireless power supply module via magnetic coupling to achieve battery-free power supply. The wireless communication component is used to wirelessly transmit the calculated physiological parameters to an external data processing terminal. The electromagnetic isolation component is used to eliminate the interference of the wireless power supply magnetic field on the optical detection signal. The external wireless power supply module is arranged around the activity area of ​​the experimental animals to provide stable wireless power for the implantable miniature blood oxygen sensor. The external data processing terminal is used to receive, display, and store physiological parameters, and generate dynamic change curves and abnormal warnings.

2. The animal dynamic vital signs monitoring platform for hypoxia-related diseases according to claim 1, characterized in that: The microvascular directional reflective optical sensing component includes a first light-emitting device LED1, a second light-emitting device LED2, a photodetector PD, an optical isolation wall, and a transparent optical window; The LED1 emits a wavelength of 620–680 nm. The LED2 emits red light with a wavelength of 850–940 nm. Near-infrared light, wherein the PD has a photosensitive area of ​​0.5–1 High-sensitivity silicon photodetectors with dark current ≤1nA; LED1 and LED2 are located on the same side of the PD, forming a reflective detection structure. The center distance between the LEDs and the PD is controlled between 1.0 and 3.

5. The corresponding light penetration depth is 0.5–2.

5. It matches the vascular scale of the common carotid artery and femoral artery in mice; The optical isolation wall is black. Made of carbon-doped light-absorbing polymers or metal light-shielding layers, with a height higher than The light-emitting surface is used to block light. Direct light enters The resulting crosstalk.

3. The animal dynamic vital signs monitoring platform for hypoxia-related diseases according to claim 1, characterized in that: The biocompatible encapsulation layer adopts a double-layer composite structure, with the inner layer being a barrier layer with a thickness of 5–20 mm. of thin film or / Composite film, water vapor permeability ≤ g / It is used to block the penetration of body fluids and ions; The outer layer is a flexible buffer layer with a thickness of 100-1000 mm. medical grade Or silicone, with a Shore hardness of 20-30. It is used to reduce mechanical friction between devices and tissues, and to alleviate fiber encapsulation and foreign body reaction; The transparent optical window area has a high light transmittance with a thickness ≤10μm. Encapsulation, with a light transmittance ≥92%.

4. The animal dynamic vital signs monitoring platform for hypoxia-related diseases according to claim 1, characterized in that: The analog signal conditioning components sequentially include a transimpedance amplifier, a low-noise amplifier, a bandpass filter, an automatic gain control circuit, and an analog-to-digital converter. The gain of the transimpedance amplifier is , used to Output The photocurrent is converted into a voltage signal; The bandpass filter is a second-order Butterworth filter with a passband frequency range of [frequency range missing]. It covers the heart rate range of mice and rats; The automatic gain control circuit dynamically adjusts the gain range to: It adapts to changes in signal strength under low perfusion conditions; the analog-to-digital converter has a 12-bit resolution and a sampling rate of .

5. The animal dynamic vital signs monitoring platform for hypoxia-related diseases according to claim 1, characterized in that: The input parameters of the hypoxic environment dynamic compensation model include the dual-wavelength ratio parameter. Perfusion index Environmental pressure Ambient temperature and animal heart rate The compensation relationship is ; The model can automatically correct the blood oxygen calibration curve according to changes in environmental pressure and temperature, eliminating the impact of multiple disturbances such as low pressure, low oxygen, low temperature and low perfusion on the accuracy of blood oxygen calculation.

6. The animal dynamic vital signs monitoring platform for hypoxia-related diseases according to claim 1, characterized in that: The wireless power supply component includes a planar spiral microcoil and a power management circuit. The planar spiral microcoil is arranged at the tail of the flexible substrate, with a line width of 50μm, a line spacing of 50μm, 15 to 20 turns, an outer diameter of 6mm × 4mm, and an operating frequency of 13.56MHz. The power management circuit integrates a rectifier bridge, filter capacitors, and a low-dropout linear regulator, with a rectification efficiency of ≥80% and an output stable DC voltage of 3.3V. The external wireless power supply module has a power supply distance of 20-100mm, a power supply efficiency of ≥15%, and covers the range of a standard mouse cage.

7. The animal dynamic vital signs monitoring platform for hypoxia-related diseases according to claim 1, characterized in that: The electromagnetic isolation component adopts a triple isolation mechanism: spatial isolation, with the wireless power supply coil arranged at the rear of the sensor and the optical detection unit arranged at the head of the sensor, with a distance of ≥5mm between the two. Grounding shielding: A copper foil grounding shielding layer is set below the analog signal area to cover the entire optical sensing and signal conditioning circuitry; Time isolation is achieved by using a time-division multiplexing mechanism. Sampling is paused during power supply and high-frequency power supply excitation is turned off during sampling. The switching frequency is 1kHz.

8. The animal dynamic vital signs monitoring platform for hypoxia-related diseases according to claim 1, characterized in that: The implantable miniature blood oxygen sensor is preferably implanted in the subcutaneous tissue area within 0.5 to 2 mm above the common carotid artery of the experimental animal, or in the subcutaneous superficial blood vessel area beside the femoral artery, beside the axillary artery, and on the back. The procedure employs a minimally invasive subcutaneous implantation method with an incision length of 5–10 mm. Subcutaneous fixation is achieved using absorbable sutures. Post-implantation continuous monitoring is conducted for at least 72 hours. The working pressure range is 30–101 kPa, and the working temperature range is -10℃–40℃.

9. The animal dynamic vital signs monitoring platform for hypoxia-related diseases according to claim 1, characterized in that: The wireless communication component adopts 433 Low-power radio frequency communication in the frequency band with a data rate of 1 The data packet is 32 bytes long and contains the device ID, blood oxygen saturation value, heart rate, perfusion index, and status information. Data packet loss rate Communication distance It can simultaneously support parallel communication of 16 implantable miniature blood oxygen sensors; The external data processing terminal has a built-in 32 Flash memory, capable of storing It supports multi-channel synchronous display of monitoring data, data export, and audible and visual alarms for low blood oxygen, abnormal heart rate, and signal loss.

10. A method for monitoring dynamic vital signs in animals with hypoxia-related diseases, characterized in that, The application of the animal dynamic vital signs monitoring platform for hypoxia-related diseases as described in any one of claims 1 to 9 includes the following steps: S1. The implantable miniature blood oxygen sensor is implanted subcutaneously in the area adjacent to the target blood vessel of the experimental animal through a minimally invasive method. After the operation, anti-infection and analgesia treatments are given until the animal recovers to a normal activity state. S2. Activate the external wireless power supply module to provide stable wireless power to the implantable miniature blood oxygen sensor through magnetic coupling. S3, the main control chip controls the red light. and near-infrared The light is emitted in pulses in sequence. The light signal irradiates the target blood vessel through the subcutaneous tissue. The oxygenated hemoglobin and deoxygenated hemoglobin in the blood produce differential absorption. The reflected light after being scattered by the tissue returns to the photodetector and is converted into a photocurrent signal. S4, the analog signal conditioning component amplifies, filters, and performs analog-to-digital conversion on the photocurrent signal, outputting a high signal-to-noise ratio photoplethysmography (PPG) signal; S5. The main control chip extracts the waveform characteristics of the photoplethysmography (PPG) wave and calculates the red and infrared light. Ratio, to obtain the dual-wavelength ratio parameter By combining perfusion index, environmental pressure, environmental temperature and heart rate parameters, real-time blood oxygen saturation, heart rate and tissue perfusion index are obtained through a dynamic compensation model for hypoxic environment. S6. The wireless communication component transmits the calculated physiological parameters to an external data processing terminal in real time. The terminal displays the values ​​and dynamic change curves of multiple physiological parameters, stores the monitoring data, and issues an early warning when the parameters are abnormal.

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