A subcutaneous implantable continuous hormone monitoring device for IVF controlled ovarian hyperstimulation cycles

Abstract

The application discloses a subcutaneous implantable continuous hormone monitoring device for an IVF (In Vitro Fertilization) stimulation cycle, which comprises a shell, a tissue fluid flow channel, a plurality of monitoring components and a control system; the shell is provided with a liquid inlet hole and a containing cavity; the tissue fluid flow channel is arranged in the containing cavity and comprises a tissue fluid inflow channel and at least four detection cavities; the liquid inlet hole, the containing cavity, the tissue fluid inflow channel and the at least four detection cavities are sequentially communicated; each monitoring component is one-to-one correspondingly arranged in each detection cavity; the monitoring component comprises a first electrochemical sensor and a specific recognition element; a working electrode of the first electrochemical sensor is arranged in the detection cavity; the specific recognition element is arranged on the working electrode and is used for being specifically combined with a target hormone; the specific recognition elements belonging to different monitoring components are specifically combined with different target hormones; and the plurality of first electrochemical sensors are electrically connected with the control system. The application aims at improving the accuracy of monitoring data.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and in particular to a subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles. Background Technology

[0002] In vitro fertilization-embryo transfer (IVF-ET) is one of the core methods for treating infertility. The ovulation induction stage is a crucial step in IVF treatment, and its success or failure directly affects the overall success rate. Throughout the IVF induction process, the dynamic changes in the levels of key hormones such as estradiol (E2), luteinizing hormone (LH), progesterone (P), and human chorionic gonadotropin (hCG) are fundamental to guiding adjustments to the induction protocol, determining the timing of trigger medication, setting the egg retrieval time, and predicting early pregnancy. Therefore, accurate and continuous monitoring of these hormones is a vital technical support for the entire IVF induction process.

[0003] Currently, clinical monitoring of hormone levels during IVF stimulation cycles mainly relies on daily venous blood sampling and laboratory testing. This method cannot achieve real-time, continuous monitoring and is insufficient to capture instantaneous fluctuations and dynamic trends in hormone levels.

[0004] To overcome the aforementioned shortcomings, implantable monitoring devices have emerged in the prior art. For example, Chinese invention patent CN112168179A discloses an implantable hormone monitoring and assisted secretion device, which uses a sampling needle to actively aspirate tissue fluid and then feed it into an integrated chip for analysis to achieve monitoring. However, this solution has drawbacks in practical applications: it adopts a single-chip mixed detection mode, superimposing signals from multiple hormones into the same monitoring unit, which cannot effectively eliminate cross-interference between multiple hormone monitoring, resulting in insufficient accuracy of the monitoring data. Summary of the Invention

[0005] In order to overcome the shortcomings of the prior art, the purpose of this invention is to provide a subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles, which can improve the accuracy of monitoring data.

[0006] The objective of this invention is achieved through the following technical solution: a subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles, comprising: a shell, a tissue fluid flow channel, multiple monitoring components, and a control system;

[0007] The housing is provided with at least one liquid inlet and a receiving cavity, the liquid inlet penetrating the wall thickness of the housing and communicating with the receiving cavity;

[0008] The tissue fluid flow channel is located within the accommodating cavity. The tissue fluid flow channel includes a tissue fluid inlet channel and at least four detection chambers. The inlet hole, the accommodating cavity, the tissue fluid inlet channel, and the at least four detection chambers are sequentially connected along the tissue fluid flow direction.

[0009] Each of the monitoring components is installed in a corresponding manner on the cavity wall of each of the detection chambers; each monitoring component includes a first electrochemical sensor and a specific recognition element, wherein the working electrode of the first electrochemical sensor passes through the cavity wall of the detection chamber and extends into the detection chamber; the specific recognition element is disposed on the working electrode and is used to specifically bind to the target hormone; any two specific recognition elements belonging to different monitoring components specifically bind to different types of target hormones;

[0010] The control system is installed inside the accommodating cavity, and multiple first electrochemical sensors are electrically connected to the control system.

[0011] Furthermore, the liquid inlet holes are multiple, and the multiple liquid inlet holes are distributed at intervals around the axis of the housing, and some of the liquid inlet holes are distributed at intervals along the radial direction of the housing. The diameter of the liquid inlet holes is slightly larger than the diameter of hormone molecules in the tissue fluid.

[0012] Furthermore, the working electrode is a micropillar array electrode;

[0013] The specific identification element belonging to the same monitoring component has multiple elements, and each of the multiple specific identification elements is disposed on one of the micropillars of the working electrode. One end of the specific identification element is connected to the micropillar, and the other end extends in a direction away from the axis of the micropillar.

[0014] Furthermore, among the at least four monitoring components, there is at least one estradiol monitoring component, at least one luteinizing hormone monitoring component, at least one progesterone monitoring component, and at least one human chorionic gonadotropin monitoring component.

[0015] The specific recognition element of the estradiol monitoring component is used to specifically recognize estradiol; the specific recognition element of the luteinizing hormone monitoring component is used to specifically recognize luteinizing hormone; the specific recognition element of the progesterone monitoring component is used to specifically recognize progesterone; and the specific recognition element of the human chorionic gonadotropin monitoring component is used to specifically recognize human chorionic gonadotropin.

[0016] Furthermore, the recognition part of the specific recognition element in each of the monitoring components is an aptamer.

[0017] Furthermore, the tissue fluid flow channel also includes multiple one-way valves, each of which is correspondingly located at the connection point of any two adjacent detection chambers.

[0018] Furthermore, the tissue fluid flow channel also includes a waste fluid collection chamber, and the plurality of detection chambers and the waste fluid collection chamber are connected sequentially along the tissue fluid flow direction.

[0019] Furthermore, the tissue fluid flow channel is also provided with a signal verification chamber, and the tissue fluid inflow channel, the signal verification chamber and at least four detection chambers are connected sequentially along the tissue fluid flow direction;

[0020] The subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles further includes a second electrochemical sensor, which is located in the signal verification chamber. The second electrochemical sensor is used to detect non-specific interference signals and is electrically connected to the control system.

[0021] Furthermore, the subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycle also includes magnetic beads, which are disposed in the tissue fluid inflow channel. The magnetic beads vibrate under the drive of an external magnetic field to disturb the tissue fluid inflow channel.

[0022] Furthermore, the shell is made of a biodegradable material that can degrade under external stimuli.

[0023] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0024] 1. The shell size design references existing clinical use standards for subcutaneous implants (such as contraceptive implants) to ensure implantation into the patient's abdominal subcutaneous tissue using commercially available implant needles. As a further design feature, the shell can be designed as a double-layer composite structure, with the outer layer directly contacting the subcutaneous tissue and the inner layer serving as a supporting framework to resist compression from the subcutaneous tissue after implantation. The shell has at least one inlet port and a receiving cavity. The inlet port penetrates the wall thickness of the shell and connects to the receiving cavity. The number of inlet ports can be multiple to ensure that tissue fluid can smoothly enter the receiving cavity inside the shell. The aperture of the inlet port, through specific design, can also screen the components of the tissue fluid: allowing only small molecule hormones in the tissue fluid to pass through, while blocking cells and large molecule proteins outside the shell, thereby increasing the purity of the tissue fluid and reducing interference from impurities on the monitoring components.

[0025] 2. The specific recognition element is located on the working electrode. The specific recognition element is used to specifically bind to the target hormone. The specific recognition element can be an aptamer or an antibody. Specific binding means that the specific recognition element has a three-dimensional structure or chemical affinity complementary to the target hormone molecule, so that the target hormone molecule can selectively bind to the specific recognition element, rather than binding to other non-target components in the tissue fluid. Any two specific recognition elements belonging to different monitoring components specifically bind to different types of target hormones. That is, the specific recognition elements in each monitoring component installed in different detection chambers only recognize one type of target hormone (e.g., estradiol). Therefore, the device can simultaneously acquire the concentration information of multiple target hormones at the same time point, and the specific binding process in each detection chamber is independent and does not interfere with each other, thereby helping to improve the accuracy of the monitoring results.

[0026] 3. After the specific recognition element binds to the target hormone, the concentration of the target hormone in the tissue fluid within the detection chamber decreases accordingly, thus creating a concentration gradient on both sides of the inlet orifice. Driven by this concentration gradient, the tissue fluid outside the shell flows continuously along the flow path of "inlet orifice → accommodating cavity → tissue fluid inflow pipe → multiple detection chambers." Therefore, the tissue fluid can flow uninterruptedly through each detection chamber, enabling continuous and stable monitoring of multiple target hormones within a preset monitoring period (e.g., 30 days) without relying on any external power components. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the structure of a subcutaneous implantable continuous hormone monitoring device for an IVF stimulation cycle according to the present invention.

[0028] Figure 2 for Figure 1 The sectional view shown;

[0029] Figure 3 for Figure 2 The front view of the monitoring component shown.

[0030] In the diagram: 1. Shell; 11. Liquid inlet; 12. Receptacle; 2. Tissue fluid flow channel; 21. Tissue fluid inflow channel; 22. Detection chamber; 23. Waste fluid collection chamber; 24. Signal verification chamber; 3. Monitoring component; 31. First electrochemical sensor; 311. Working electrode; 32. Specific recognition element; 4. Control system; 5. One-way valve; 6. Second electrochemical sensor; 7. Magnetic bead. Detailed Implementation

[0031] The present invention will now be further described in conjunction with the accompanying drawings and specific embodiments. It should be noted that, without conflict, the various embodiments or technical features described below can be arbitrarily combined to form new embodiments.

[0032] It should be noted that when an element is described as being "fixed to" another element, it can be directly attached to the other element or there may be an intervening element. When an element is described as being "connected to" another element, it can be directly connected to the other element or there may be an intervening element. The terms "vertical," "horizontal," "left," "right," and similar expressions used herein are for illustrative purposes only and do not represent the only possible implementations.

[0033] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0034] like Figures 1 to 3 As shown, a preferred embodiment of the present invention provides a subcutaneous implantable continuous hormone monitoring device for an IVF stimulation cycle, comprising: a shell 1, a tissue fluid flow channel 2, multiple monitoring components 3, and a control system 4.

[0035] The shell 1 is preferably designed in a capsule shape. The dimensions of the shell 1 are designed with reference to the clinical use standards of existing subcutaneous implants (such as contraceptive implants) to ensure that it can be implanted into the subcutaneous tissue of the patient's abdomen using existing implant needles. As a further design, the shell 1 can be designed as a double-layer composite structure. The outer layer of the shell 1 is in direct contact with the subcutaneous tissue, and the inner layer of the shell 1 serves as a supporting skeleton to resist compression of the subcutaneous tissue after implantation. The shell 1 is provided with at least one inlet hole 11 and a receiving cavity 12. The inlet hole 11 penetrates the wall thickness of the shell 1 and connects to the receiving cavity 12. The number of inlet holes 11 can be set to multiple to ensure that tissue fluid can smoothly enter the receiving cavity 12 inside the shell 1. The pore size of the inlet hole 11 can also play a screening role for the components of the tissue fluid through specific design: that is, only small molecule hormones in the tissue fluid are allowed to pass through, while cells and large molecule proteins are blocked outside the shell 1. By improving the purity of the tissue fluid, the interference of impurities on the monitoring component 3 is reduced. According to the principle of diffusion, the tissue fluid carrying a relatively high concentration of hormones outside the shell 1 flows naturally and enters the accommodating cavity 12 through the inlet hole 11.

[0036] The tissue fluid flow channel 2 is located within the accommodating cavity 12. The tissue fluid flow channel 2 includes a tissue fluid inflow channel 21 and at least four detection chambers 22. The inlet port 11, the accommodating cavity 12, the tissue fluid inflow channel 21, and the at least four detection chambers 22 are sequentially connected along the tissue fluid flow direction. The at least four detection chambers 22 are arranged in series and sequentially connected along the length of the housing 1, allowing the tissue fluid to pass through multiple detection chambers 22 sequentially for subsequent detection of target hormones within each chamber. Specifically, after the device is implanted in the subcutaneous tissue, the tissue fluid enters the accommodating cavity 12 through the inlet port 11 and then sequentially enters each detection chamber 22 via the tissue fluid inflow channel 21. The tissue fluid flow channel 2 can be implemented as a microfluidic channel with a diameter designed to be at the micrometer level. The tissue fluid inflow channel 21 serves as a buffer zone before the tissue fluid enters the first detection chamber 22, ensuring stable flow before the tissue fluid enters the detection chamber 22.

[0037] Each of the monitoring components 3 is installed in a corresponding manner on the cavity wall of each of the detection chambers 22, so that the working electrode 311 of the first electrochemical sensor 31 can extend into the detection chamber 22. The monitoring components 3 can be installed at any position on the cavity wall of the detection chamber 22. When the tissue fluid flow rate is insufficient to fill the detection chamber 22, the tissue fluid accumulates at the bottom of the detection chamber 22 under the action of gravity. Therefore, the monitoring components 3 are preferably installed at the bottom of the detection chamber 22 so that the working electrode 311 of the first electrochemical sensor 31 can continuously contact the tissue fluid. The monitoring components 3 include a first electrochemical sensor 31 and a specific recognition element 32. The working electrode 311 of the first electrochemical sensor 31 passes through the cavity wall of the detection chamber 22 and extends into the detection chamber 22, thereby contacting the tissue fluid. In addition, a sealing structure is provided between the working electrode 311 and the cavity wall of the detection chamber 22 to prevent the tissue fluid from leaking out of the detection chamber 22 along the working electrode 311. The specific recognition element 32 is located at the bottom of the detection chamber 22. Electrode 311, the specific recognition element 32 is used to specifically bind to the target hormone. The specific recognition element 32 may include a base layer and a recognition layer fixed on the base layer. The recognition layer of the specific recognition element 32 may be an aptamer or an antibody. Specific binding means that the specific recognition element 32 has a three-dimensional structure or chemical affinity complementary to the target hormone molecule, so that the target hormone molecule can selectively bind to the specific recognition element 32, rather than binding to other non-target components in the tissue fluid. Any two specific recognition elements 32 belonging to different monitoring components 3 specifically bind to different types of target hormones. That is, the specific recognition elements 32 installed in each monitoring component 3 in different detection chambers 22 only recognize one type of target hormone (e.g., estradiol). Therefore, the device can simultaneously acquire the concentration information of multiple target hormones at the same time point, and the specific binding process in each detection chamber 22 is independent and does not interfere with each other, thereby helping to improve the accuracy of the monitoring results.

[0038] The control system 4 is installed within the accommodating cavity 12, and the plurality of first electrochemical sensors 31 are electrically connected to the control system 4. The control system 4 is packaged in the form of a circuit board within the accommodating cavity 12. The control system 4 may include a microprocessor, signal conditioning circuitry (e.g., potentiostat, amplifier, analog-to-digital converter), and wireless communication module (e.g., near-field communication module or Bluetooth low-power module). The control system 4 receives electrical signals from each of the first electrochemical sensors 31, amplifies, filters, and performs analog-to-digital conversion on the signals, and then transmits the processed data to an external receiving device (e.g., mobile phone, tablet computer, or dedicated reader) via wireless communication. The control system 4 may also include a micro-battery for powering the entire device. Specifically, the specific binding operation process is as follows: First, molecular recognition: When the target hormone molecule diffuses to the surface of the working electrode 311, the hormone molecule interacts with the specific recognition element 32 on the surface of the working electrode 311 (the interaction forms include one or more of hydrogen bonding, hydrophobic interaction, electrostatic attraction, van der Waals forces, or shape complementary matching). These interactions are highly selective, allowing the specific recognition element 32 to bind effectively only to the target hormone molecule among a variety of hormone molecules, while not binding to other non-target molecules with similar structures.

[0039] Second, signal conversion: When the target hormone molecule binds to the specific recognition element 32, the physicochemical properties of the interface between the working electrode 311 and the tissue fluid change (e.g., changes in charge density on the electrode surface, increases in charge transfer resistance, or changes in ion distribution near the electrode surface). The first electrochemical sensor 31 applies an electrical excitation (e.g., constant potential, AC voltage, or potential scan) to the working electrode 311 and measures the electrical parameters (e.g., current, impedance, potential) corresponding to the aforementioned interface changes in real time. Since the change in electrical parameters is positively correlated with the concentration of the target hormone in the corresponding detection chamber 22, the control system 4 can convert the measured electrical signal into a hormone concentration value using a pre-calibrated calibration curve.

[0040] Third, signal output: The control system 4 collects the output signals of multiple first electrochemical sensors 31, calculates the real-time concentration of the target hormone corresponding to each detection chamber 22, and sends the data to the in vitro receiving device through the wireless communication module.

[0041] Furthermore, after the specific recognition element 32 binds to the target hormone, the concentration of the target hormone in the tissue fluid within the detection chamber 22 decreases accordingly, thereby forming a concentration gradient on both sides of the inlet hole 11. Under the diffusion effect driven by the concentration gradient, the tissue fluid outside the shell 1 flows continuously along the flow path of inlet hole 11 → accommodating chamber 12 → tissue fluid inflow pipe 21 → multiple detection chambers 22. Thus, the tissue fluid can flow uninterruptedly through each detection chamber 22, thereby achieving continuous and stable monitoring of multiple target hormones within a preset monitoring period (e.g., 30 days) without relying on any external power components. After monitoring, medical personnel can remove the device from the subcutaneous tissue of the patient's abdomen through a secondary surgery. If the entire device is made of biodegradable materials (e.g., the first electrochemical sensor 31 can be made of PCL / Mo composite film, and the fixation substrate of the specific recognition element 32 can be made of hyaluronic acid hydrogel), the device can also be allowed to degrade naturally in the subcutaneous tissue without the need for secondary surgery.

[0042] The working principle of this invention is as follows: Medical personnel use an implantation needle to implant a subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles, as described in this invention, into the subcutaneous tissue of the patient's abdomen. The tissue fluid surrounding the housing 1 diffuses under the influence of a concentration gradient, entering the receiving cavity 12 through the inlet port 11. After entering the receiving cavity 12, the tissue fluid flows sequentially along the tissue fluid flow channel 2, through the tissue fluid inflow channel 21, and through multiple detection chambers 22 arranged in series. When the tissue fluid flows through the detection chamber 22, the specific recognition element 32 of the working electrode 311 of the first sensor selectively binds to the target hormone molecules in the tissue fluid. After the target hormone molecules bind to the specific recognition element 32, the interface between the working electrode 311 and the tissue fluid changes. The first electrochemical sensor 31 measures the electrical parameters such as current, impedance, or potential corresponding to the aforementioned interface change in real time. Since the change in electrical parameters is positively correlated with the concentration of the target hormone in the corresponding detection chamber 22, the control system 4 converts the electrical signal into a hormone concentration value through a pre-calibrated calibration curve. The control system 4 collects the output signals of multiple first electrochemical sensors 31, calculates the real-time concentration of the target hormone corresponding to each detection chamber 22, and transmits the data to an in vitro receiving device via a wireless communication module. Because the specific recognition elements 32 within different detection chambers 22 target different hormones, and each detection chamber 22 is independent of the others, the detection of the four hormones does not interfere with each other in time and space, thereby improving the accuracy of the monitoring data. Based on long-term continuous monitoring, medical personnel can capture the dynamic fluctuation trends of hormone levels, providing reliable data support for precise decision-making throughout the entire clinical process.

[0043] Preferably, there are multiple inlet holes 11, which are distributed at intervals around the axis of the housing 1, and some of the inlet holes 11 are distributed at intervals along the radial direction of the housing 1. The pore size of the inlet holes 11 is slightly larger than the diameter of hormone molecules in the tissue fluid. Specifically, with the central axis of the housing 1 as a reference, the multiple inlet holes 11 are arranged uniformly or non-uniformly in the circumferential direction to form one or more rings of inlet hole 11 arrays around the axis of the housing 1. In addition, the pore size range of the inlet holes 11 is preferably 50 nanometers to 100 nanometers, which allows small molecule hormones in the tissue fluid to pass smoothly through the inlet holes 11 into the interior of the housing 1, and allows cells (e.g., fibroblasts, macrophages) and large molecule proteins (e.g., albumin, globulin) in the tissue fluid to enter the housing 1. It should be noted that, depending on the specific application scenario and the molecular size of the hormone to be tested, the pore size range of the inlet holes 11 can also be set to other size ranges that can achieve the above-mentioned screening function.

[0044] Preferably, the working electrode 311 is a micropillar array electrode; a micropillar array electrode refers to a plurality of columnar protrusions formed on an electrode substrate, which are distributed on the surface of the electrode substrate according to a preset array arrangement rule (e.g., rectangular array, hexagonal array, etc.). The height, diameter, and spacing between adjacent micropillars can be appropriately adjusted according to specific detection sensitivity requirements and manufacturing process conditions. The advantage of using a micropillar array electrode is that its effective working area is much larger than that of a planar electrode with the same projected area, that is, it can provide more fixed sites for specific recognition elements 32, thereby enhancing the material exchange efficiency between the working electrode 311 and the tissue fluid, and thus improving the monitoring sensitivity of the monitoring component 3.

[0045] Multiple specific recognition elements 32 belonging to the same monitoring component 3 are respectively disposed on one of the micropillars of the working electrode 311. One end of each specific recognition element 32 is connected to the micropillar, and the other end extends in a direction away from the axis of the micropillar. Specifically, at least one specific recognition element 32 is fixed on the top surface or sidewall surface of each micropillar. Each micropillar in the micropillar array serves as an independent fixed site, causing the specific recognition elements 32 to be distributed in a three-dimensional space, forming a tree-like structure. This facilitates the full contact of target hormone molecules in the tissue fluid with the specific recognition elements 32, thereby improving the binding efficiency.

[0046] Preferably, among the at least four monitoring components 3, there is at least one estradiol monitoring component 3, at least one luteinizing hormone monitoring component 3, at least one progesterone monitoring component 3, and at least one human chorionic gonadotropin monitoring component 3;

[0047] The specific recognition element 32 of the estradiol monitoring component 3 is used to specifically recognize estradiol. When tissue fluid flows through the detection chamber 22 where the monitoring component 3 is located, estradiol molecules in the tissue fluid selectively bind to the specific recognition element 32 fixed on the surface of the working electrode 311, generating an electrochemical signal corresponding to the estradiol concentration. The specific recognition element 32 of the luteinizing hormone monitoring component 3 is used to specifically recognize luteinizing hormone. When tissue fluid flows through the detection chamber 22 where the monitoring component 3 is located, luteinizing hormone molecules in the tissue fluid selectively bind to the specific recognition element 32 fixed on the surface of the working electrode 311, generating an electrochemical signal corresponding to the luteinizing hormone concentration. The progesterone... The specific recognition element 32 of the monitoring component 3 is used to specifically recognize progesterone. When tissue fluid flows through the detection chamber 22 where the monitoring component 3 is located, progesterone molecules in the tissue fluid selectively bind to the specific recognition element 32 fixed on the surface of the working electrode 311, generating an electrochemical signal corresponding to the progesterone concentration. Similarly, the specific recognition element 32 of the human chorionic gonadotropin (hCG) monitoring component 3 is used to specifically recognize human chorionic gonadotropin (hCG). When tissue fluid flows through the detection chamber 22 where the monitoring component 3 is located, hCG molecules in the tissue fluid selectively bind to the specific recognition element 32 fixed on the surface of the working electrode 311, generating an electrochemical signal corresponding to the hCG concentration. It can be understood that the device can simultaneously acquire concentration data of four hormones—estradiol, luteinizing hormone (LH), progesterone, and hCG—within the same monitoring cycle, providing comprehensive data support for adjusting the stimulation protocol, determining the trigger timing, determining the egg retrieval time, and predicting early pregnancy throughout the entire IVF stimulation process.

[0048] Preferably, the recognition portion of the specific recognition element 32 in each of the monitoring components 3 is an aptamer. The aptamer can be a DNA aptamer or an RNA aptamer. Compared with antibodies, aptamers have the following advantages: First, aptamers can be prepared in large quantities through chemical synthesis and have relatively stable quality, which is beneficial to ensuring the stability of the device's detection performance; second, aptamers have good thermal and chemical stability, and can maintain their binding activity for a long time at body temperature, thus meeting the needs of long-term continuous monitoring.

[0049] Preferably, the tissue fluid flow channel 2 further includes multiple one-way valves 5 (e.g., cantilever beam one-way valve 5, diaphragm one-way valve 5, or ball seat one-way valve 5), each of the one-way valves 5 being disposed one-to-one at the connection point of any two adjacent detection chambers 22 to prevent tissue fluid backflow.

[0050] Preferably, the tissue fluid flow channel 2 further includes a waste fluid collection chamber 23. The plurality of detection chambers 22 and the waste fluid collection chamber 23 are connected sequentially along the tissue fluid flow direction. That is, the waste fluid collection chamber 23 is located at the tail end of the tissue fluid flow channel 2. After the tissue fluid completes the detection of the corresponding hormone in each detection chamber 22, it flows into the waste fluid collection chamber 23. Since the waste fluid collection chamber 23 continuously receives tissue fluid from the detection chambers 22, the tissue fluid outside the housing 1 can continuously replenish the tissue fluid flow channel 2 and update the tissue fluid in each detection chamber 22, so that the sensor in each detection chamber 22 is always in contact with fresh tissue fluid, thereby truly reflecting the target hormone concentration at the current moment.

[0051] Preferably, the tissue fluid flow channel 2 is further provided with a signal verification chamber 24, and the tissue fluid inflow channel 21, the signal verification chamber 24 and at least four detection chambers 22 are connected in sequence along the tissue fluid flow direction; that is, the signal verification chamber 24 is set before multiple detection chambers 22 to build a calibration basis for the subsequent second sensor.

[0052] The subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles also includes a second electrochemical sensor 6, which is disposed within the signal verification chamber 24. The second electrochemical sensor 6 is used to detect non-specific interference signals and is electrically connected to the control system 4. Specifically, the signal detected by the second electrochemical sensor 6 originates from the electrochemical response caused by non-target components in the tissue fluid (e.g., non-specifically adsorbed proteins, temperature fluctuations, pH changes, ionic strength changes, etc.), rather than from the specific binding of the target hormone to the specific recognition element 32. Since the signal verification chamber 24 does not contain a specific recognition element 32 (or contains a blank recognition layer that is not targeted at any hormone), the output signal of the second electrochemical sensor 6 mainly reflects the influence of non-specific interference factors on electrochemical detection. The control system 4 receives the non-specific interference signal from the second electrochemical sensor 6 and uses it as a calibration reference signal. When the tissue fluid flows through the signal verification chamber 24, the second electrochemical sensor 6 measures the non-specific signal under the current tissue fluid state. Subsequently, the tissue fluid flows sequentially through each detection chamber 22. The signal measured by the first electrochemical sensor 31 in each detection chamber 22 contains the same interfering components as the non-specific background signal. Since the non-specific interfering factors (such as temperature, pH, ionic strength, etc.) of the tissue fluid change very little during the time interval between flowing through the signal verification chamber 24 and each detection chamber 22, the output signal of the second electrochemical sensor 6 can be used as a calibration reference and subtracted from the output signals of each first electrochemical sensor 31, thereby eliminating interference such as temperature drift and non-specific adsorption and improving the accuracy of the monitoring data.

[0053] Preferably, the subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles further includes magnetic beads 7. The magnetic beads 7 are disposed within the tissue fluid inflow channel 21, and their size is designed to be smaller than the diameter of the tissue fluid inflow channel 21 to ensure free movement within the channel. The magnetic beads 7 vibrate under the drive of an external magnetic field to disturb the tissue fluid within the tissue fluid inflow channel 21. The external magnetic field is generated by an external device (e.g., a handheld reading device or a dedicated magnetic field generator). When the external magnetic field is applied to the implantation site, the magnetic beads 7 move under the action of the magnetic force. By controlling the frequency, intensity, and direction of the external magnetic field, the movement mode of the magnetic beads 7 can be adjusted, including but not limited to reciprocating vibration, rotation, oscillation, or combinations thereof. The movement of the magnetic bead 7 has two effects: First, the movement of the magnetic bead 7 causes the tissue fluid to generate eddies, enhancing the local convection of the tissue fluid and accelerating the flow of the target hormone molecules into the detection cavity 22, thereby improving the response speed of the first sensor; Second, the vibration of the magnetic bead 7 causes the tissue fluid to generate fluid shear force, causing the tissue fluid to flush the tissue fluid into the pipe 21 and the cavity wall of the detection cavity 22, thereby peeling the conjugate formed after the specific recognition element 32 and the target hormone molecules combine from the working electrode 311, thereby preventing the conjugate from accumulating excessively on the working electrode 311, thus ensuring that the first sensor can work normally.

[0054] Preferably, the shell 1 is made of a biodegradable material, including biodegradable polymers (e.g., polylactic acid-glycolic acid copolymer, polylactic acid, polycaprolactone), biodegradable metals (e.g., magnesium, zinc and their alloys), or a composite of both. The shell 1 is designed to degrade under external stimuli, which may include, but are not limited to, one or more of the following: light irradiation (e.g., near-infrared light, ultraviolet light), ultrasound irradiation, alternating magnetic fields, radio frequency electric fields, temperature changes, or combinations thereof. Specifically, taking the shell 1 material containing photothermal conversion substances (e.g., molybdenum, gold nanoparticles, etc.) as an example, when the monitoring task is completed and the shell 1 needs to be degraded, the doctor brings the near-infrared light irradiation device close to the implantation site (e.g., place it on the skin surface). The near-infrared light irradiation causes the temperature of the shell 1 to rise, thereby triggering a depolymerization or hydrolysis reaction in the shell 1 material, accelerating the decomposition of the shell 1. The advantages of using a biodegradable material for the shell 1 are: firstly, no secondary surgery is required for removal; secondly, the degradation timing is controllable, and the degradation time can be flexibly adjusted according to the actual monitoring situation; thirdly, it does not rely on the material's own natural degradation, the degradation speed is fast, and adverse reactions to patients due to excessively long device degradation time are avoided.

[0055] In the description of this specification, references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this application. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of those different embodiments or examples.

[0056] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this application, "a plurality of" means two or more, unless otherwise explicitly specified.

[0057] The above description is merely a specific embodiment of this application, but the scope of protection of this application is not limited thereto. Any person skilled in the art can easily conceive of various variations or substitutions within the technical scope disclosed in this application, and these should all be included within the scope of protection of this application. Therefore, the scope of protection of this application should be determined by the scope of the claims.

Claims

1. A subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles, characterized in that, include: The housing (1) is provided with at least one liquid inlet (11) and a receiving cavity (12). The liquid inlet (11) penetrates the wall thickness of the housing (1) and communicates with the receiving cavity (12). Tissue fluid flow channel (2), the tissue fluid flow channel (2) is located in the accommodating cavity (12), the tissue fluid flow channel (2) includes a tissue fluid inflow channel (21) and at least four detection chambers (22), the inlet hole (11), the accommodating cavity (12), the tissue fluid inflow channel (21) and the at least four detection chambers (22) are connected sequentially along the tissue fluid flow direction; Multiple monitoring components (3) are installed one-to-one on the cavity wall of each detection chamber (22); each monitoring component (3) includes a first electrochemical sensor (31) and a specific recognition element (32); the working electrode (311) of the first electrochemical sensor (31) passes through the cavity wall of the detection chamber (22) and extends into the detection chamber (22); the specific recognition element (32) is disposed on the working electrode (311) and is used to specifically bind to the target hormone; any two specific recognition elements (32) belonging to different monitoring components (3) specifically bind to different types of target hormones; The control system (4) is installed in the accommodating cavity (12), and a plurality of the first electrochemical sensors (31) are electrically connected to the control system (4).

2. The subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles according to claim 1, characterized in that: The liquid inlet (11) has a plurality of holes, which are distributed at intervals around the axis of the housing (1), and some of the liquid inlet (11) are distributed at intervals along the radial direction of the housing (1). The diameter of the liquid inlet (11) is slightly larger than the diameter of hormone molecules in the tissue fluid.

3. The subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles according to claim 2, characterized in that: The working electrode (311) is a micropillar array electrode; The specific identification element (32) belonging to the same monitoring component (3) has multiple components, and the multiple specific identification elements (32) are respectively disposed on one of the micropillars of the working electrode (311). One end of the specific identification element (32) is connected to the micropillar, and the other end extends in a direction away from the axis of the micropillar.

4. A subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles according to claim 3, characterized in that: Of the at least four monitoring components (3), at least one estradiol monitoring component (3), at least one luteinizing hormone monitoring component (3), at least one progesterone monitoring component (3) and at least one human chorionic gonadotropin monitoring component (3). The specific recognition element (32) of the estradiol monitoring component (3) is used to specifically recognize estradiol; the specific recognition element (32) of the luteinizing hormone monitoring component (3) is used to specifically recognize luteinizing hormone; the specific recognition element (32) of the progesterone monitoring component (3) is used to specifically recognize progesterone; the specific recognition element (32) of the human chorionic gonadotropin monitoring component (3) is used to specifically recognize human chorionic gonadotropin.

5. A subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles according to claim 1, characterized in that: The identification part of the specific identification element (32) in each of the monitoring components (3) is an aptamer.

6. A subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles according to claim 2, characterized in that: The tissue fluid flow channel (2) also includes multiple one-way valves (5), each of which is located at the connection point of any two adjacent detection chambers (22).

7. A subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles according to claim 1, characterized in that: The tissue fluid flow channel (2) also includes a waste fluid collection chamber (23), and the plurality of detection chambers (22) and the waste fluid collection chamber (23) are connected sequentially along the tissue fluid flow direction.

8. A subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles according to claim 1, characterized in that: The tissue fluid flow channel (2) is also provided with a signal verification chamber (24), and the tissue fluid inflow channel (21), the signal verification chamber (24) and at least four detection chambers (22) are connected in sequence along the tissue fluid flow direction; The subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycle further includes a second electrochemical sensor (6), which is located in the signal verification chamber (24). The second electrochemical sensor (6) is used to detect non-specific interference signals and is electrically connected to the control system (4).

9. A subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycles according to claim 1, characterized in that: The subcutaneous implantable continuous hormone monitoring device for IVF ovulation induction cycle also includes magnetic beads (7), which are disposed in the tissue fluid inflow channel (21). The magnetic beads (7) vibrate under the drive of an external magnetic field to disturb the tissue fluid in the tissue fluid inflow channel (21).

10. A subcutaneous implantable continuous hormone monitoring device for an IVF stimulation cycle according to claim 1, characterized in that: The shell (1) is made of a biodegradable material and is capable of degrading under external stimuli.

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