Implantable detection device for tear disease markers

Abstract

The embodiment of the invention provides an implantable detection device for a tear disease marker, and the device is characterized in that a flexible rollable substrate for bearing a wireless transmission module and an electrochemical sensing module is attached to the surface of a punctum plug; the wireless transmission module comprises an antenna coil, the electrochemical sensing module comprises a working electrode, and the surface of the working electrode is modified with an organic probe; after the device is implanted into a lacrimal ductule of a patient, the antenna coil converts radio frequency field energy sent by terminal equipment into an electric signal and sends the electric signal to the working electrode; after the working electrode receives the electric signal, when the organic probe is combined with a target disease marker in tear, the working electrode sends detection information to the antenna coil, and the antenna coil sends the detection information to terminal equipment. The device can detect the disease marker in real time, avoids sampling and component extraction processes, improves the detection efficiency, and reduces the labor cost of sampling; the device is low in equipment cost and easy to process and produce in batches; the device is implanted in a non-invasive mode, and harm to the human body can be avoided.

Description

Technical Field

[0001] The present application relates to the technical field of medical equipment, and in particular to an implantable detection device for tear disease markers. Background Art

[0002] Tears are a complex mixture of proteins, lipids, mucins, water, and salts, and contain numerous disease markers. Through long-term and in-depth studies of the composition and function of the tear film and tears, researchers have demonstrated their crucial role in the metabolic state and homeostasis of the ocular surface. Furthermore, they have discovered that effectively analyzing disease markers using tear composition can provide a reliable detection pathway for a variety of diseases.

[0003] Currently, tear testing primarily relies on non-invasive sampling methods such as Schirmer strips combined with mass spectrometry, enzyme-linked immunosorbent assay (ELISA), or proteomics. For example, proteomics based on Orbitrap high-resolution mass spectrometry can identify thousands of proteins from trace amounts of tear fluid, while exosome isolation technologies such as iTEARS rapidly enrich tear exosomes using nanoporous membranes for analysis of disease markers.

[0004] However, these methods commonly suffer from complex sample processing and high equipment dependence. For example, mass spectrometry analysis requires high-purity samples and is time-consuming, while exosome isolation places stringent demands on nanomaterials and technical conditions. Furthermore, traditional techniques consume large sample volumes (e.g., microliter-level) and rely on laboratory-grade instruments and specialized operators. Existing tear testing solutions suffer from low efficiency and high equipment and labor costs, hindering timely patient detection and diagnosis. Summary of the Invention

[0005] The present application provides an implantable tear disease marker detection device to solve the problem of low detection efficiency and high equipment and labor costs required for detection, which is not conducive to timely detection and diagnosis of patients.

[0006] The present application provides an implantable tear disease marker detection device, comprising: a wireless transmission module, an electrochemical sensing module, a flexible rollable substrate, and a punctal plug, wherein the flexible rollable substrate carrying the wireless transmission module and the electrochemical sensing module is attached to the surface of the punctal plug;

[0007] The wireless transmission module includes an antenna coil, the electrochemical sensing module includes a working electrode, the surface of the working electrode is modified with an organic probe, the organic probe is configured to bind to a target disease marker, and the antenna coil is electrically connected to the working electrode;

[0008] After the device is implanted inside the patient's lacrimal canaliculus, the antenna coil is used to convert the energy of the radio frequency field sent by the terminal device into an electrical signal and send the electrical signal to the working electrode; the working electrode is used to, after receiving the electrical signal, when the organic probe combines with the target disease marker in the patient's tears, the working electrode sends detection information to the antenna coil, and the antenna coil is used to send the detection information to the terminal device.

[0009] In one possible design, the wireless transmission module further includes a near-field communication chip, the antenna coil is electrically connected to the near-field communication chip, and the near-field communication chip is electrically connected to the working electrode;

[0010] The antenna coil is used to convert the energy of the radio frequency field sent by the near field communication reader of the terminal device into an AC voltage signal, and transmit the AC voltage signal to the near field communication chip;

[0011] The near field communication chip is used for:

[0012] modulating the AC voltage signal and transmitting it to the working electrode;

[0013] The detection information sent by the working electrode is received, and the detection information is sent to the near field communication reader through the antenna coil.

[0014] In one possible design, the wireless transmission module further includes a voltage modulation component, and the voltage modulation component is carried by the flexible rollable substrate;

[0015] The near field communication chip is electrically connected to the voltage modulation component, and the voltage modulation component is electrically connected to the working electrode;

[0016] The voltage modulation component is used to convert the AC voltage signal into a target DC analog voltage signal, and transmit the target DC analog voltage signal to the working electrode.

[0017] In one possible design, the voltage modulation component includes a rectifier, a voltage regulator, a waveform generator, a DAC digital-to-analog converter, an operational amplifier, and a low-pass filter connected in sequence, the rectifier is electrically connected to the near-field communication chip, and the low-pass filter is electrically connected to the working electrode;

[0018] The rectifier is used to convert the AC voltage signal into a DC voltage signal and transmit the DC voltage signal to the voltage stabilizer;

[0019] The voltage stabilizer is used to adjust the DC voltage signal to a DC voltage signal with a target amplitude and transmit the signal to the waveform generator;

[0020] The waveform generator is configured to, after receiving the DC voltage signal having the target amplitude, output a waveform digital sequence signal to the DAC digital-to-analog converter, wherein the waveform digital sequence signal is configured to instruct the generation of a DC analog voltage signal having the target waveform;

[0021] The DAC digital-to-analog converter is used to generate a first DC analog voltage signal having a target waveform according to the waveform digital sequence signal, and transmit the first DC analog voltage signal to the operational amplifier;

[0022] The operational amplifier is used to amplify the first DC analog voltage signal into a second DC analog voltage signal, and transmit the second DC analog voltage signal to the filter;

[0023] The filter is used to filter the second DC analog voltage signal into the target DC analog voltage signal, and transmit the target DC analog voltage signal to the working electrode.

[0024] In one possible design, the wireless transmission module further includes a signal modulation component, the near-field communication chip is carried on the flexible rollable substrate, the near-field communication chip is electrically connected to the signal modulation component, and the signal modulation component is electrically connected to the working electrode;

[0025] The signal modulation component is used to convert the current detection signal sent by the working electrode into a digital detection signal, and transmit the digital detection signal to the near field communication chip. The current detection signal and the digital detection signal carry the detection information.

[0026] In one possible design, the signal modulation component includes a transimpedance amplifier and an ADC analog-to-digital converter, the transimpedance amplifier is electrically connected to the ADC analog-to-digital converter, the transimpedance amplifier is electrically connected to the working electrode, and the ADC analog-to-digital converter is electrically connected to the near-field communication chip;

[0027] The transimpedance amplifier is used to amplify the current detection signal into an analog voltage detection signal, and output the analog voltage detection signal to the ADC analog-to-digital converter;

[0028] The ADC analog-to-digital converter is used to convert the analog voltage detection signal into the digital detection signal.

[0029] In one possible design, the working electrode and the organic probe are constructed so that when the organic probe binds to the target disease marker in the patient's tears, the charge transfer impedance of the working electrode changes to convert the electrical signal input by the working electrode into the current detection signal.

[0030] In one possible design, the working electrode has a gold element layer, and the junction end of the organic probe and the working electrode has a thiol group, so that the organic probe is bonded to the surface of the gold element layer through an Au—S bond.

[0031] In a possible design, after the flexible rollable substrate carrying the wireless transmission module and the electrochemical sensing module is attached to the surface of the punctal plug, the antenna coil is located at the end surface of the punctal plug.

[0032] In one possible design, after the flexible rollable substrate carrying the wireless transmission module and the electrochemical sensing module is attached to the surface of the punctal plug, the portion of the wireless transmission module excluding the antenna coil and the electrochemical sensing module are located on the conical surface of the punctal plug.

[0033] The tear disease marker implantable detection device provided in this application has the following technical effects:

[0034] Compared with existing tear detection solutions, this device can detect disease markers in real time by implanting lacrimal plugs and directly contacting the area where tears flow. The detection information is sent to the terminal device instantly through a wireless transmission module, avoiding the sampling and component extraction process, improving detection efficiency, and reducing the labor cost of sampling. This device uses sampling working electrodes and surface organic probes to achieve detection, with low equipment cost and easy processing and mass production. This device is non-invasively implanted and works by being implanted in the lacrimal canaliculus, which can avoid harm to the human body. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the present application and, together with the description, serve to explain the principles of the present application.

[0036] Figure 1 A schematic diagram of an implantable tear disease marker detection device provided in an embodiment of the present application;

[0037] Figure 2 A schematic diagram of the wireless transmission module structure provided in an embodiment of the present application;

[0038] Figure 3 Schematic diagram of the electrode structure and curling provided in the embodiment of the present application;

[0039] Figure 4 Schematic diagram of probe modification on the working electrode surface provided in the examples of this application.

[0040] Reference numerals:

[0041] 100-wireless transmission module;

[0042] 110-antenna coil;

[0043] 120- signal conversion component;

[0044] 200-electrochemical sensor module;

[0045] 300-flexible rollable substrate;

[0046] 400-punctal plug;

[0047] 500-Tear ductules.

[0048] The above drawings illustrate specific embodiments of the present application, which will be described in more detail below. These drawings and the textual description are not intended to limit the scope of the present application in any way, but rather to illustrate the concepts of the present application to those skilled in the art by reference to specific embodiments. DETAILED DESCRIPTION

[0049] Exemplary embodiments will be described in detail herein, with examples illustrated in the accompanying drawings. In the following description, when referring to the drawings, identical numerals in different figures represent identical or similar elements, unless otherwise indicated. The embodiments described in the following exemplary embodiments are not intended to represent all embodiments consistent with the present application. Rather, they are merely examples of apparatus and methods consistent with certain aspects of the present application, as detailed in the appended claims.

[0050] A recent study identified up to six proteins through proteomics, spurring increased interest in identifying novel tear biomarkers for ocular diseases such as dry eye disease (DED), vernal conjunctivitis, diabetic retinopathy, Graves' ophthalmopathy, ocular tumors, and glaucoma. Furthermore, tear composition can provide valuable information for the diagnosis and treatment of several non-ophthalmic conditions. Over the past two decades, a large number of non-communicable / chronic diseases, such as diabetes, cardiovascular disease, and some malignancies, have reached epidemic proportions worldwide, placing a significant socioeconomic burden on healthcare systems. Studies have demonstrated the presence of tear biomarkers for a variety of diseases, including diabetic retinopathy, cancer, and neurological disorders. Pathological analysis and monitoring of tear composition can be widely used to assess health and disease states and has become a research hotspot in ophthalmology.

[0051] Currently, tear testing primarily relies on non-invasive sampling methods such as Schirmer strips combined with mass spectrometry, enzyme-linked immunosorbent assay (ELISA), or proteomics. For example, proteomics based on Orbitrap high-resolution mass spectrometry can identify thousands of proteins from trace amounts of tear fluid, while exosome isolation technologies such as iTEARS rapidly enrich tear exosomes using nanoporous membranes for analysis of disease markers.

[0052] However, these methods commonly suffer from complex sample processing and high equipment dependence. For example, mass spectrometry analysis requires high-purity samples and is time-consuming, while exosome isolation places stringent demands on nanomaterials and technical conditions. Furthermore, traditional techniques consume large sample volumes (e.g., microliter-level) and rely on laboratory-grade instruments and specialized operators. Existing tear testing solutions suffer from low efficiency and high equipment and labor costs, hindering timely patient detection and diagnosis.

[0053] In order to solve the problems of the above-mentioned prior art, an implantable detection device for tear disease markers can be designed, which includes a wireless transmission module, an electrochemical sensing module, a flexible rollable substrate, and a tear punctum plug. The flexible rollable substrate carries the wireless transmission module and the electrochemical sensing module, and the flexible rollable substrate is attached to the surface of the tear punctum plug. When used, the device is implanted inside the patient's lacrimal canaliculus, thereby achieving non-invasive implantation and avoiding the tear sampling process. The wireless transmission module includes an antenna coil, and the electrochemical sensing module includes a working electrode, and the surface of the working electrode is modified with an organic probe. The antenna coil is electrically connected to the working electrode, and the tear antenna coil captures energy from the radio frequency field sent by the terminal device, and converts the captured energy into an electrical signal and sends it to the working electrode, thereby realizing wireless passive operation of the device. The various probes modified on the surface of the electrochemical sensing electrode can specifically identify the target to be tested. After the working electrode receives the electrical signal, when the organic probes on the surface combine with specific disease markers in the tears, the working electrode sends the detection information to the wireless transmission module, and the wireless transmission module sends the detection information to the terminal device through the antenna coil, thereby saving the cost of sample processing and component extraction.

[0054] In order to make the objects, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below in conjunction with specific embodiments and with reference to the accompanying drawings. It should be noted that the directions mentioned in the embodiments, such as "up", "down", "front", "back", "left", "right", etc., are only directions with reference to the accompanying drawings and are not intended to limit the scope of protection of the present invention. Throughout the accompanying drawings, the same elements are represented by the same or similar figure marks. Conventional structures or constructions will be omitted when they may cause confusion in the understanding of the present invention. In addition, the shapes and sizes of the components in the figures do not reflect the actual size and proportion, but only illustrate the contents of the embodiments of the present invention.

[0055] Example 1

[0056] Figure 1 Schematic diagram of the tear disease marker implantable detection device provided in the embodiment of the present application, as shown in FIG. Figure 1 As shown, the device includes:

[0057] The wireless transmission module 100, the electrochemical sensing module 200, the flexible rollable substrate 300, and the punctal plug 400 are attached to the surface of the punctal plug 400.

[0058] The wireless transmission module 100 includes an antenna coil 110, and the electrochemical sensing module 200 includes a working electrode, the surface of the working electrode is modified with an organic probe, the organic probe is configured to bind to a target disease marker, and the antenna coil 110 is electrically connected to the working electrode;

[0059] After the device is implanted inside the patient's lacrimal canaliculus 500, the antenna coil 110 is used to convert the energy of the radio frequency field sent by the terminal device into an electrical signal and send the electrical signal to the working electrode; the working electrode is used to, after receiving the electrical signal, when the organic probe combines with the target disease marker in the patient's tears, the working electrode sends detection information to the antenna coil 110, and the antenna coil 110 is used to send the detection information to the terminal device.

[0060] Specifically, the terminal device can be, for example, a mobile phone, a tablet computer, a handheld reader, a smart watch, a laptop or desktop computer, a server, a dedicated medical device, a smart home device, a car-mounted smart device, etc. When the external terminal device sends a radio frequency field, the antenna coil 110 is in the radio frequency field and generates an alternating current signal through electromagnetic induction, thereby realizing wireless and power-free operation of the device. The alternating current signal can be transmitted via Figure 1 The signal conversion component 120 in the working electrode converts the impedance to a DC operating voltage. The working electrode and organic probe can be configured so that, when a DC operating voltage is applied, specific target disease markers in tear fluid, such as glucose, bind specifically to the organic probe, causing a change in interfacial charge transfer. This impedance change signal, serving as detection information, can be converted from analog to digital and transmitted back to the terminal device via backscatter modulation from the antenna coil 110, such as frequency offset or phase angle change.

[0061] It should be noted that the punctal plug 400 is a medical device commonly used to treat dry eye. The punctal plug 400 is inserted into the opening of the lacrimal canaliculus 500, i.e., the lacrimal punctum, to partially or completely block tear drainage, thereby increasing tear volume on the ocular surface. In the embodiment of the present application, after a thin, flexible, rollable substrate 300 is attached to the surface of the punctal plug 400, the wireless transmission module 100 and electrochemical sensor module 200 on the flexible, rollable substrate 300 can be implanted within the patient's lacrimal canaliculus 500 along with the punctal plug 400, allowing the electrochemical sensor module 200 to directly contact the patient's tears and detect specific disease markers in the tears. Materials for the flexible, rollable substrate 300 include, but are not limited to, biocompatible, eye-safe materials such as polyglycolide-ε-caprolactone copolymer, medical-grade thermoplastic elastomers, and resin composites.

[0062] After the flexible rollable substrate 300 is attached to the tear point plug 400, the wireless transmission module 100 and the electrochemical sensor module 200 can be Figure 1 As shown, they are all located on the conical surface of the lacrimal plug 400; the antenna coil 110 can also be located at the end surface of the lacrimal plug 400, so that the antenna coil 110 is placed flat to ensure that it can smoothly receive energy from the radio frequency field and transmit signals. Parts of the wireless transmission module 100 other than the antenna coil 110, such as the signal conversion component 120 and the electrochemical sensor module 200, are located on the conical surface of the lacrimal plug 400, so that there is a large enough area for layout and wiring.

[0063] The technical effects of this embodiment are as follows:

[0064] Compared with existing tear detection solutions, this device directly contacts the area where tears flow by implanting a lacrimal plug 400, and can detect disease markers in real time. The detection information is instantly sent to the terminal device through the wireless transmission module 100, avoiding the sampling and component extraction process, improving detection efficiency, and reducing the labor cost of sampling; this device uses sampling working electrodes and surface organic probes to achieve detection, with low equipment cost and easy processing and mass production; this device is non-invasively implanted, and works by being implanted in the lacrimal canaliculus 500, which can avoid harm to the human body.

[0065] Example 2

[0066] In this embodiment, the signal conversion component 120 of the wireless transmission module 100 may further include a near-field communication chip NFC chip carried by the flexible rollable substrate 300, the antenna coil 110 is electrically connected to the near-field communication chip, and the near-field communication chip is electrically connected to the working electrode;

[0067] The antenna coil 110 is used to convert the energy of the radio frequency field sent by the near field communication reader of the terminal device into an AC voltage signal, and transmit the AC voltage signal to the near field communication chip;

[0068] Near field communication chips are used for:

[0069] Modulating the AC voltage signal and transmitting it to the working electrode;

[0070] Receive the detection information sent by the working electrode, and send the detection information to the near field communication reader through the antenna coil 110.

[0071] Specifically, in this embodiment, the NFC chip's functions include: receiving radio frequency energy emitted by an external terminal, such as a smartphone's NFC reader / writer, to power the electrochemical sensor module 200, achieving completely passive operation; and wirelessly transmitting detection information to the terminal device's NFC reader / writer via backscatter modulation technology. For example, the NFC chip can modulate the AC signal in the following ways:

[0072] Changing the amplitude, frequency or phase of an AC voltage signal;

[0073] Convert analog signals to digital signals.

[0074] In this embodiment, by adopting near field communication technology, the following technical advantages are achieved:

[0075] The device does not require a built-in battery and is driven by radio frequency field energy, avoiding battery life limitations and making it suitable for long-term implantable applications;

[0076] The NFC chip has extremely low power consumption and is small enough to be integrated into a millimeter-scale flexible substrate, adapting to narrow spaces such as the tear duct 500;

[0077] It can communicate directly with common devices such as smartphones and tablets without the need for dedicated readers, lowering the threshold for use;

[0078] It can work stably in humid tear environments, has strong anti-interference capabilities, and meets the reliability requirements of human implants;

[0079] NFC chips have low cost and mature manufacturing technology, making them suitable for large-scale production.

[0080] In this embodiment, the antenna coil 110 can be a resonant coil, and the resonant coil and the parallel resonant capacitor can be configured to match the impedance of the NFC chip port and ensure that the resonant frequency is at 13.56 MHz. The antenna coil 110 can select copper, a highly conductive material, as the conductor to reduce energy loss. The preparation method of the antenna coil 110 is not limited to radio frequency sputtering, physical vapor deposition, chemical vapor deposition, etc. In actual manufacturing, the shape of the antenna coil 110, such as circular, rectangular, etc., and the size can be appropriately changed according to the difference of the tear punctum plug 400. After adjusting the number of turns, width, thickness, side length and other parameters of the antenna coil 110 as needed and obtaining the inductance value of the antenna coil 110, the matching capacitor required for the operating frequency to be at the NFC resonant frequency of 13.56 MHz is selected according to the resonant frequency calculation formula. The resonant frequency calculation formula is:

[0081]

[0082] Where L is the inductance of antenna coil 110, C is the matching capacitor value, and f is the resonant frequency. After connecting a matching capacitor network in parallel or series at both ends of the antenna, it is connected to the port of the NFC chip via micro-nanofabricated copper wire.

[0083] Example 3

[0084] In this embodiment, the signal conversion component 120 of the wireless transmission module 100 may further include a voltage modulation component and a signal modulation component carried by the flexible rollable substrate 300. The near-field communication chip is electrically connected to the voltage modulation component, and the voltage modulation component is electrically connected to the working electrode;

[0085] The voltage modulation component is used to convert the AC voltage signal into a target DC analog voltage signal, and transmit the target DC analog voltage signal to the working electrode.

[0086] Figure 2 The wireless transmission module structure diagram provided in the embodiment of the present application is as follows: Figure 2 As shown, optionally, the voltage modulation component may include a rectifier AC\DC, a voltage regulator LDO, a waveform generator WG, a DAC digital-to-analog converter DAC, an operational amplifier OPA, and a low-pass filter LPF connected in sequence, and the rectifier is electrically connected to the near-field communication chip. Figure 2 In the embodiment, ECS is the electrochemical sensor module 200. The low-pass filter is electrically connected to the working electrode of the electrochemical sensor module 200;

[0087] The rectifier is used to convert the AC voltage signal into a DC voltage signal and transmit it to the voltage regulator;

[0088] The voltage stabilizer is used to adjust the DC voltage signal into a DC voltage signal with a target amplitude and transmit the signal to the waveform generator;

[0089] The waveform generator is used to, after receiving a DC voltage signal with a target amplitude, output a waveform digital sequence signal to a DAC digital-to-analog converter, wherein the waveform digital sequence signal is used to instruct the generation of a DC analog voltage signal with a target waveform;

[0090] The DAC digital-to-analog converter is used to generate a first DC analog voltage signal having a target waveform according to the waveform digital sequence signal, and transmit the first DC analog voltage signal to the operational amplifier;

[0091] The operational amplifier is used to amplify the first DC analog voltage signal into a second DC analog voltage signal, and transmit the second DC analog voltage signal to the filter;

[0092] The filter is used to filter the second DC analog voltage signal into a target DC analog voltage signal, and transmit the target DC analog voltage signal to the working electrode.

[0093] The AC voltage signal input by the antenna coil 110 is ultimately converted into a second DC analog voltage signal having a target waveform required for the working electrode through a voltage modulation component. It should be noted that in this embodiment, the preferred rectifier is a Schottky diode, including but not limited to the BAT54 series, SS12, or SS14. These diodes have the advantages of fast switching speed, low reverse recovery time, and suitability for high-frequency rectification applications. Furthermore, Schottky diodes can significantly improve energy conversion efficiency in low-voltage, low-power applications. The voltage regulator can be a low-power TI TPS7A02, etc. The waveform generator can be a low-power microcontroller integrated with the NFC function on a single chip, such as an ARM Cortex-M0, or a dedicated waveform generation chip, including but not limited to the AD9833. The DAC digital-to-analog converter includes but is not limited to the TI DAC8562. The operational amplifier includes but is not limited to the TI OPA333.

[0094] like Figure 2 As shown, the near field communication chip is electrically connected to the signal modulation component, and the signal modulation component is electrically connected to the ECS, i.e., the working electrode of the electrochemical sensor module 200;

[0095] The signal modulation component is used to convert the current detection signal sent by the working electrode into a digital detection signal, and transmit the digital detection signal to the near-field communication chip. The current detection signal and the digital detection signal carry detection information.

[0096] Optional, such as Figure 2 As shown, the signal modulation component includes a transimpedance amplifier TIA and an ADC analog-to-digital converter ADC, the transimpedance amplifier is electrically connected to the ADC analog-to-digital converter, the transimpedance amplifier is electrically connected to the working electrode of the electrochemical sensor module 200, and the ADC analog-to-digital converter is electrically connected to the near-field communication chip;

[0097] The transimpedance amplifier is used to amplify the current detection signal into an analog voltage detection signal, and output the analog voltage detection signal to the ADC analog-to-digital converter;

[0098] The ADC analog-to-digital converter is used to convert the analog voltage detection signal into a digital detection signal.

[0099] Ultimately, the signal modulation component converts the current detection signal output by the working electrode into a digital detection signal, which is then transmitted by the NFC chip to the NFC reader via antenna coil 110. It should be noted that the transimpedance amplifier includes, but is not limited to, the ADI AD8603, and the ADC is a high-precision ADC, including, but not limited to, the TI ADC1115.

[0100] Example 4

[0101] Figure 3 The electrode structure and curling diagram provided in the embodiment of the present application are as follows: Figure 3 As shown, three circular working electrodes can be designed, each modified with a different organic probe. In practical applications, the number of working electrodes is determined by detection requirements, ranging from 1 to 64, enabling up to 64-channel detection. Reference and comparison electrodes are arranged in a circular pattern around the three working electrodes. The working, reference, and comparison electrodes are connected to the signal modulation component and voltage modulation component, respectively, using copper wires. Figure 3 In the figure, WE1, WE2, and WE3 represent three working electrodes, RE represents the reference electrode, and CE represents the comparison electrode. The function of the reference electrode is to provide a stable potential reference to ensure that the potential measurement of the working electrode WE is not affected by fluctuations in the solution environment. In this embodiment, the reference electrode can be an Ag / AgCl electrode, whose potential remains constant in tear fluid and is used to calibrate the response signal of the working electrode; the function of the comparison electrode is to form a current loop with the working electrode to assist in completing the charge balance of electrochemical reactions such as redox reactions. The comparison electrode can be a platinum Pt electrode, which is suitable as an auxiliary electrode due to its high conductivity and chemical inertness. It should be noted that the preparation methods of the above-mentioned electrodes include but are not limited to laser induction, screen printing, radio frequency sputtering, chemical vapor deposition, etc., and the electrode materials include but are not limited to new nanomaterials such as graphene, carbon paste, gold, etc.

[0102] In this embodiment, the working electrode may have a gold element layer. For example, the working electrode may be a gold working electrode. The working electrode may also be a graphene electrode with nano-gold particles modified on its surface, thereby having a gold element layer. Figure 4 The schematic diagram of the probe modification on the working electrode surface provided in the embodiment of the present application is as follows: Figure 4 As shown, Figure 4 The working electrode surface is modified with a designed aptamer, a single-stranded DNA with a thiol group at one end. This aptamer forms an Au-S bond with the gold layer, anchoring it to the surface. The aptamer specifically recognizes and captures the DNA single strand being tested. The two connect through complementary base pairing, affecting the impedance of the working electrode surface and causing a change in the current signal, thus enabling DNA detection. Figure 4 b. A designed antibody is modified on the working electrode surface. One end of the antibody carries a thiol group, which forms an Au-S bond with the gold layer and becomes fixed to the surface. The antibody specifically recognizes and captures the antigen being tested. The two react to form an antigen-antibody complex, which affects the impedance of the working electrode surface and causes a change in the current signal, thereby achieving antigen detection. Figure 4c. A designed enzyme is modified on the surface of the working electrode. One end of the enzyme carries a thiol group, which can form an Au-S bond with the gold layer and be fixed on the surface of the gold layer. The enzyme can specifically recognize and capture the substance to be tested, affecting the impedance of the working electrode surface, causing changes in the current signal, thereby realizing the function of detecting specific substances. Enzymes modified on the surface of the working electrode are commonly used to detect glucose oxidase, cholesterol oxidase, phenolic compound tyrosinase or laccase, amino acid oxidase, neurotransmitter dopamine oxidase, etc. It should be noted that the target disease markers corresponding to the probe include but are not limited to markers of diseases such as dry eye, spring-like conjunctivitis, diabetic retinopathy, Graves' ophthalmopathy, eye tumors and glaucoma.

[0103] Specifically, when the organic probe binds to its corresponding target disease marker, it will cause the charge transfer impedance of the working electrode to change. Combined with the aforementioned embodiment three, since the working electrode inputs a second DC analog voltage signal with a target waveform, the charge transfer impedance change of the working electrode can cause the waveform of the second DC analog voltage signal to change, so that the working electrode can output a current detection signal to the signal modulation component.

[0104] Finally, it should be noted that those skilled in the art will readily identify other embodiments of the present invention after considering the specification and practicing the invention disclosed herein. The present invention is intended to cover any variations, uses, or adaptations of the present invention that follow the general principles of the present invention and include common knowledge or customary techniques in the art not disclosed herein. The present invention is not limited to the precise structure described above and illustrated in the accompanying drawings, and various modifications and variations may be made without departing from the scope thereof. The scope of the present invention is limited solely by the appended claims.

Claims

1. An implantable detection device for tear disease markers, characterized in that: The device comprises: a wireless transmission module (100), an electrochemical sensing module (200), a flexible rollable substrate (300), and a lacrimal plug (400), wherein the flexible rollable substrate (300) carrying the wireless transmission module (100) and the electrochemical sensing module (200) is attached to the surface of the lacrimal plug (400); The wireless transmission module (100) includes an antenna coil (110), the electrochemical sensing module (200) includes a working electrode, the surface of the working electrode is modified with an organic probe, the organic probe is configured to bind to a target disease marker, and the antenna coil (110) is electrically connected to the working electrode; After the device is implanted inside the patient's lacrimal canaliculus (500), the antenna coil (110) is used to convert the energy of the radio frequency field sent by the terminal device into an electrical signal, and send the electrical signal to the working electrode; the working electrode is used to, after receiving the electrical signal, send detection information to the antenna coil (110) when the organic probe combines with the target disease marker in the patient's tears, and the antenna coil (110) is used to send the detection information to the terminal device.

2. The device according to claim 1, characterized in that The wireless transmission module (100) further comprises a near-field communication chip, the antenna coil (110) is electrically connected to the near-field communication chip, and the near-field communication chip is electrically connected to the working electrode; The antenna coil (110) is used to convert the energy of the radio frequency field sent by the near field communication reader of the terminal device into an AC voltage signal, and transmit the AC voltage signal to the near field communication chip; The near field communication chip is used for: modulating the AC voltage signal and transmitting it to the working electrode; The detection information sent by the working electrode is received, and the detection information is sent to the near field communication reader via the antenna coil (110).

3. The device according to claim 2, characterized in that The wireless transmission module (100) further comprises a voltage modulation component, the voltage modulation component being carried on the flexible rollable substrate (300); The near field communication chip is electrically connected to the voltage modulation component, and the voltage modulation component is electrically connected to the working electrode; The voltage modulation component is used to convert the AC voltage signal into a target DC analog voltage signal, and transmit the target DC analog voltage signal to the working electrode.

4. The device according to claim 3, characterized in that The voltage modulation component includes a rectifier, a voltage stabilizer, a waveform generator, a DAC digital-to-analog converter, an operational amplifier, and a low-pass filter connected in sequence, the rectifier is electrically connected to the near-field communication chip, and the low-pass filter is electrically connected to the working electrode; The rectifier is used to convert the AC voltage signal into a DC voltage signal and transmit the DC voltage signal to the voltage stabilizer; The voltage stabilizer is used to adjust the DC voltage signal to a DC voltage signal with a target amplitude and transmit the signal to the waveform generator; The waveform generator is configured to, after receiving the DC voltage signal having the target amplitude, output a waveform digital sequence signal to the DAC digital-to-analog converter, wherein the waveform digital sequence signal is configured to instruct the generation of a DC analog voltage signal having the target waveform; The DAC digital-to-analog converter is used to generate a first DC analog voltage signal having a target waveform according to the waveform digital sequence signal, and transmit the first DC analog voltage signal to the operational amplifier; The operational amplifier is used to amplify the first DC analog voltage signal into a second DC analog voltage signal, and transmit the second DC analog voltage signal to the filter; The filter is used to filter the second DC analog voltage signal into the target DC analog voltage signal, and transmit the target DC analog voltage signal to the working electrode.

5. The device according to claim 2, characterized in that The wireless transmission module (100) further comprises a signal modulation component, the near-field communication chip is carried on the flexible rollable substrate (300), the near-field communication chip is electrically connected to the signal modulation component, and the signal modulation component is electrically connected to the working electrode; The signal modulation component is used to convert the current detection signal sent by the working electrode into a digital detection signal, and transmit the digital detection signal to the near field communication chip. The current detection signal and the digital detection signal carry the detection information.

6. The device according to claim 5, characterized in that The signal modulation component includes a transimpedance amplifier and an ADC analog-to-digital converter, the transimpedance amplifier is electrically connected to the ADC analog-to-digital converter, the transimpedance amplifier is electrically connected to the working electrode, and the ADC analog-to-digital converter is electrically connected to the near-field communication chip; The transimpedance amplifier is used to amplify the current detection signal into an analog voltage detection signal, and output the analog voltage detection signal to the ADC analog-to-digital converter; The ADC analog-to-digital converter is used to convert the analog voltage detection signal into the digital detection signal.

7. The device according to claim 5, characterized in that The working electrode and the organic probe are constructed so that when the organic probe binds to the target disease marker in the patient's tears, the charge transfer impedance of the working electrode changes, thereby converting the electrical signal input by the working electrode into the current detection signal.

8. The device according to claim 1, characterized in that The working electrode has a gold element layer, and the junction end of the organic probe and the working electrode has a thiol group, so that the organic probe is bonded to the surface of the gold element layer through an Au-S bond.

9. The device according to any one of claims 2 to 8, characterized in that After the flexible rollable substrate (300) carrying the wireless transmission module (100) and the electrochemical sensing module (200) is attached to the surface of the lacrimal plug (400), the antenna coil (110) is located at the end surface of the lacrimal plug (400).

10. The device according to claim 9, characterized in that After the flexible rollable substrate (300) carrying the wireless transmission module (100) and the electrochemical sensing module (200) is attached to the surface of the lacrimal plug (400), the portion of the wireless transmission module (100) other than the antenna coil (110) and the electrochemical sensing module (200) are located on the conical surface of the lacrimal plug (400).

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