Puncture depth adaptive microneedle system

Abstract

The present application relates to the technical field of microneedle transdermal drug delivery, and in particular to a microneedle system with self-adaptive penetration depth. The microneedle system comprises: a microneedle array for penetrating the skin, providing a sampling point for detecting the skin impedance at the skin layer touched by the needle tip, and releasing drugs; a detection unit connected with the microneedle array, configured to obtain the skin impedance at the sampling point in a short pulse mode, and output a control signal when judging that the needle tip of the microneedle array has penetrated the stratum corneum according to the skin impedance; and an execution unit connected with the microneedle array and the detection unit respectively, configured to receive the control signal from the detection unit to stop the microneedle array from continuing to penetrate the skin after the detection unit determines the penetration. In this way, the microneedle penetration depth can be actively limited based on the change in the electrical properties of the skin during the microneedle penetration process, effectively addressing the problem of individual differences in the skin, and the system has the active identification ability and automatic adjustment ability of the real-time penetration state.

Description

Technical Field

[0001] This invention relates to the field of microneedle transdermal drug delivery technology, and more particularly to a microneedle system with adaptive puncture depth. Background Technology

[0002] Microneedle transdermal drug delivery technology uses micro-scale needles to pierce the surface structure of the skin, allowing drugs to cross the stratum corneum barrier and enter the skin tissue. It has wide applications in vaccine delivery and cosmetic medicine (topical drug delivery). Existing microneedle devices mainly include patch-type microneedle patches, spring-driven microneedle injectors, and handheld press-type microneedle devices. Microneedle transdermal drug delivery technology is generally based on capillary action. Capillary action (also known as capillary phenomenon) refers to the phenomenon where a liquid flows into a narrow tubular or porous object without external force, due to a combination of adhesion between the liquid and the object and surface tension caused by cohesive forces between liquid molecules.

[0003] In existing technologies, the depth of microneedle insertion is typically controlled in the following ways:

[0004] 1. Fixed needle length limitation method: By pre-designing the length of the microneedle, it can theoretically only penetrate the stratum corneum of the epidermis (the epidermis is divided into 5 layers from the outside to the inside, namely the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum and stratum basale, and the stratum basale is connected to the dermis through the basement membrane) or limit the depth range.

[0005] 2. Mechanical limiting structure control method: A fixed mechanical limiting structure is set in the microneedle device to limit the maximum downward stroke of the entire microneedle;

[0006] 3. Spring or impact force control method: The penetration depth is indirectly controlled by the spring stiffness or the amount of energy released.

[0007] The above-mentioned technical solutions usually rely on passive control based on structural dimensions or mechanical parameters. When the work is carried out by manual force, the force of different operators is different, and the puncture depth will also be different. The puncture depth is uncontrollable, the control precision of the microneedle stroke is low, and there is a lack of active recognition and automatic adjustment capabilities for individual skin differences and real-time puncture status. Summary of the Invention

[0008] To address the aforementioned technical problems, this invention provides a microneedle system with adaptive puncture depth. This system actively limits the microneedle insertion depth based on changes in skin electrophysiological properties during insertion. The microneedle system provided by this invention offers controllable puncture depth, resulting in less discomfort compared to traditional syringes entering the muscle. It minimizes discomfort caused by needle pricks without affecting drug injection efficiency.

[0009] This invention provides a microneedle system with adaptive puncture depth, comprising:

[0010] Microneedle arrays are used to puncture the skin, providing sampling points for detecting skin impedance at the skin layer touched by the needle tip, and for releasing drugs;

[0011] The detection unit, connected to the microneedle array, is configured to acquire the skin impedance at the sampling point using a short pulse method, and output a control signal when it is determined from the skin impedance that the tip of the microneedle array penetrates the stratum corneum;

[0012] An execution unit, connected to both the microneedle array and the detection unit, is configured to receive a control signal from the detection unit to stop the microneedle array from further penetrating the skin after the detection unit determines that the microneedle array has penetrated.

[0013] In one possible implementation, the execution unit includes an execution mechanism and a locking mechanism;

[0014] The actuator is connected to the microneedle array and the locking mechanism respectively;

[0015] The actuator is used to cause the microneedle array to perform a downward motion to puncture the skin;

[0016] The locking mechanism is used to perform a locking action on the actuator when the control signal is received, so as to stop the microneedle array from continuing to penetrate the skin.

[0017] In one possible implementation, the microneedle array includes a plurality of drug delivery microneedles, at least two detection probes, and a needle hub;

[0018] The drug delivery microneedle and the detection probe are evenly disposed on the needle hub;

[0019] The needle hub is connected to the actuator.

[0020] In one possible implementation, the detection unit includes a sampling unit, a processing unit, and a locking drive unit;

[0021] The sampling end of the sampling unit is connected to the detection probe, its voltage input end is connected to the pulse output end of the processing unit, and its voltage output end is connected to the voltage sampling end of the processing unit.

[0022] The trigger output terminal of the processing unit is connected to the input terminal of the locking drive unit;

[0023] The output of the locking drive unit is connected to the locking mechanism.

[0024] In one possible implementation, the sampling unit includes a sampling interface, a first resistor, a second resistor, a first ESD protection diode, and a second ESD protection diode;

[0025] The sampling interface serves as the sampling terminal of the sampling unit. Its input pin is connected to the first end of the first resistor, and its output pin is connected to the negative terminal of the first ESD protection diode and the first end of the second resistor, respectively, serving as the voltage output terminal of the sampling unit.

[0026] The second end of the first resistor serves as the voltage input terminal of the sampling unit, and the line containing the first resistor is connected to the negative terminal of the second ESD protection diode.

[0027] The second terminal of the second resistor, the positive terminal of the first ESD protection diode, and the positive terminal of the second ESD protection diode are respectively grounded.

[0028] In one possible implementation, the detection unit further includes a comparison unit;

[0029] The first input terminal of the comparison unit is connected to the voltage output terminal of the sampling unit, its second input terminal is connected to the threshold voltage terminal of the processing unit, and its output terminal is connected to the comparison input terminal of the processing unit.

[0030] In one possible implementation, the comparison unit includes a voltage comparator, a third resistor, and a first capacitor;

[0031] The non-inverting input terminal of the voltage comparator serves as the first input terminal of the comparator unit, its inverting input terminal serves as the second input terminal of the comparator unit, its positive power supply is connected to the working voltage, its negative power supply is grounded, and its output terminal is connected to the first terminal of the third resistor as the output terminal of the comparator unit.

[0032] The second terminal of the third resistor is connected to the operating voltage and then to the grounded first capacitor.

[0033] In one possible implementation, the latch-up drive unit includes an NMOS transistor, a drive interface, a freewheeling diode, a fourth resistor, and a fifth resistor;

[0034] The gate of the NMOS transistor is connected to the first terminal of the fourth resistor and the first terminal of the fifth resistor, respectively. Its drain is connected to the positive terminal of the freewheeling diode and the output pin of the drive interface, respectively. Its source is grounded.

[0035] The drive interface serves as the output terminal of the latching drive unit, and its input pin is connected to the negative terminal of the freewheeling diode and connected to the drive voltage.

[0036] The second end of the fourth resistor serves as the input end of the locking drive unit;

[0037] The second terminal of the fifth resistor is grounded.

[0038] In one possible implementation, the actuator includes a sliding push rod;

[0039] The locking mechanism includes a locking sleeve, a return spring, a mechanism base, a solenoid unit, a chuck housing, and a slotted chuck;

[0040] The sliding push rod passes through the chuck housing from top to bottom, with one end connected to the microneedle array and the other end used to receive the applied force;

[0041] The locking sleeve is fixedly sleeved on the body of the sliding push rod, and its top end is connected to the first end of the return spring;

[0042] The return spring is sleeved on the body of the sliding push rod, and its second end is connected to the bottom of the first end of the mechanism base;

[0043] The bottom of the first end of the mechanism base is also connected to the solenoid unit, the top of the first end is connected to the inside of the top end cap of the chuck housing through an elastic structure, and the second end extends out from the top opening of the chuck housing.

[0044] The magnetic end of the solenoid unit is positioned downwards;

[0045] The slotted chuck is arranged around the bottom opening of the chuck housing;

[0046] The upper end of the slotted chuck is provided with a magnetic suction element;

[0047] When the solenoid unit is powered on, its magnetic end attracts the magnetic element, which drives the slotted chuck and the chuck housing to move upward, so that the blocking surface of the slotted chuck contacts the force-bearing surface of the locking sleeve to limit the sliding push rod to the current position.

[0048] In one possible implementation, the detection unit stops acquiring the skin impedance at the sampling point after determining that the tip of the microneedle array has penetrated the stratum corneum.

[0049] The technical solution provided by this invention has at least the following beneficial effects:

[0050] 1. Active Depth Limitation Based on Skin Impedance Difference (Trigger-Triggered Locking). This invention utilizes the impedance difference between the stratum corneum (high impedance) and the dermis / active epidermis (low impedance) as a criterion. Through pulsed impedance detection and threshold comparison and / or impedance change rate determination, the execution unit is triggered when preset conditions are met to actively limit the further downward travel of the microneedle array, thereby achieving adaptive control of the puncture depth.

[0051] 2. Improve the effectiveness and consistency of transdermal drug delivery. Through the aforementioned active restriction mechanism, this invention can reduce the probability of insufficient or excessive penetration while ensuring the formation of an effective transdermal channel through piercing the stratum corneum, thereby improving the effectiveness and operational consistency of transdermal drug delivery.

[0052] 3. Reduced risk of pain and tissue damage. When the detection result reaches the preset judgment condition corresponding to the impedance of the dermis / active epidermis, the present invention can enable the execution unit to immediately lock the current extension length of the microneedle, preventing further extension / descending, thereby avoiding the microneedle from further penetrating the deep dermis and excessively touching nerve endings, reducing the risk of pain and potential tissue damage.

[0053] 4. Low power consumption and reduced adverse effects associated with continuous detection (supports shutting down the measurement link after one calibration). This invention uses a microsecond-level short pulse method for impedance detection, avoiding continuous excitation and sampling: on the one hand, it reduces power consumption during the detection phase, and on the other hand, it reduces the risk of skin polarization and other problems caused by continuous detection; and after completing one detection and obtaining a fixed criterion (determining that the needle tip of the microneedle array has penetrated the stratum corneum), the measurement link (sampling unit) can be shut down, so that subsequent stages only perform microneedle drug delivery and necessary locking actions, thereby further reducing system power consumption and the impact of long-term operation of the measurement link. Attached Figure Description

[0054] Figure 1 This is a schematic diagram of the structure of a microneedle system with adaptive puncture depth provided in an embodiment of this application;

[0055] Figure 2 This is a schematic diagram of the structure of the microneedle array provided in the embodiments of this application;

[0056] Figure 3 This is a circuit schematic diagram of the sampling unit provided in the embodiments of this application;

[0057] Figure 4 This is a schematic diagram of another microneedle system with adaptive puncture depth provided in the embodiments of this application;

[0058] Figure 5 This is a circuit schematic diagram of the sampling unit and comparison unit provided in the embodiments of this application;

[0059] Figure 6This is a circuit schematic diagram of the locking drive unit provided in an embodiment of this application;

[0060] Figure 7 This is a schematic diagram of the cooperation structure between the actuator and the locking mechanism provided in the embodiments of this application;

[0061] Figure 8 This is a flowchart of the ADC dynamic baseline acquisition and ΔZ / Δt slope determination algorithm based on anti-polarization pulse provided in the embodiments of this application;

[0062] In the attached diagram: 10, microneedle array; 11, execution unit; 20, execution mechanism; 30, locking mechanism; 40, detection unit; 101, drug delivery microneedle; 102, detection probe; 103, needle seat; 201, sliding push rod; 301, locking sleeve; 302, return spring; 303, mechanism base; 304, solenoid unit; 305, chuck housing; 306, slotted chuck; 307, elastic structure; 308, magnetic suction element. Detailed Implementation

[0063] To enhance understanding of the present invention, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. These embodiments are only used to explain the invention and do not limit the scope of protection of the invention.

[0064] Please refer to Figures 1 to 8 The present invention provides a microneedle system with adaptive puncture depth, comprising:

[0065] The microneedle array 10 is used to puncture the skin, providing sampling points for detecting skin impedance at the skin layer touched by the needle tip, and for releasing drugs;

[0066] The detection unit 40 is connected to the microneedle array 10 and is configured to acquire the skin impedance at the sampling point using a short pulse method, and output a control signal when it is determined that the tip of the microneedle array 10 penetrates the stratum corneum based on the skin impedance.

[0067] The execution unit 11 is connected to the microneedle array 10 and the detection unit 40 respectively, and is configured to receive a control signal from the detection unit 40 to stop the microneedle array 10 from continuing to penetrate the skin after the detection unit 40 determines that the penetration has been achieved.

[0068] In one possible implementation, the execution unit 11 includes an execution mechanism 20 and a locking mechanism 30;

[0069] The actuator 20 is connected to the microneedle array 10 and the locking mechanism 30 respectively;

[0070] The actuator 20 is used to cause the microneedle array 10 to perform a downward motion to puncture the skin;

[0071] The locking mechanism 30 is used to perform a locking action on the actuator 20 when the control signal is received, so as to stop the microneedle array 10 from continuing to pierce the skin.

[0072] It should be noted that the microneedle system of this invention can identify the skin's layer structure in real time, distinguishing between the stratum corneum and the dermis or active epidermis during the insertion of microneedles (including drug delivery microneedles 101 and detection probes 102) on the microneedle array 10, and dynamically adjusting the insertion depth according to changes in skin layers. The microneedle system of this invention has good adaptability to individual differences. Although there are significant differences in skin thickness and mechanical properties among different individuals and at different locations, skin layer identification based on skin impedance is unaffected by these differences, thus balancing safety and drug delivery effectiveness. The microneedle system of this invention can reduce the risk of discomfort or damage caused by excessively deep insertion. In actual operation, the skin impedance changes significantly as soon as the microneedle penetrates the dermis. Locking the actuator 20 via the locking mechanism 30 prevents the microneedle from further contacting nerve endings, reducing the risk of pain or even tissue damage. The microneedle system of this invention, based on feedback control of skin electrical properties, can achieve precise and controllable insertion depth management.

[0073] In practical implementation, the actuator 20 can be driven by a high-precision stroke-controlled cylinder, or it can be passively pushed by a pure spring or by hand. When the cylinder provides the force, it can be driven by a separate drive module. During the process of the microneedles in the microneedle array 10 contacting the skin and descending for puncture, the detection unit 40 detects the skin impedance. Using the difference between the high impedance of the stratum corneum and the low impedance of the dermis / active epidermis as a criterion, when the detected skin impedance reaches a preset threshold and / or the impedance change rate exceeds a set dynamic threshold, the locking mechanism 30 locks the actuator 20, preventing the microneedle array 10 from continuing to descend, thereby achieving adaptive limitation of the puncture depth and preventing further puncture into the deep dermis.

[0074] In one possible implementation, such as Figure 2 The microneedle array 10 includes a plurality of drug delivery microneedles 101, at least two detection probes 102 and a needle hub 103;

[0075] The drug delivery microneedle 101 and the detection probe 102 are uniformly disposed on the needle seat 103;

[0076] The needle holder 103 is connected to the actuator 20.

[0077] In this embodiment, the drug delivery microneedle 101 can be a conventional microneedle used for drug release. The detection probe 102 does not need to release drug; it only serves as a sampling point to detect skin impedance between at least two detection probes 102. The portions of the drug delivery microneedle 101 and the detection probes 102 extending from the needle hub 103 are at the same height. In one specific embodiment, such as Figure 2 In the left figure, there are two detection probes 102. The detection probes 102 and several drug delivery microneedles 101 are arranged in a rectangle with equal spacing. The two detection probes 102 are located at two opposite corners of the rectangle. In another specific embodiment, such as... Figure 2 In the right figure, there are four detection probes 102. The detection probes 102 and several drug delivery microneedles 101 are arranged in a rectangle with equal spacing. The four detection probes 102 are located at the four corners of the rectangle. The two detection probes 102 on the left are collinearly connected, and the two detection probes 102 on the right are also collinearly connected. It should be noted that placing the detection probes 102 at the edge / diagonal positions of the array can maximize the coverage of the effective puncture area of ​​the microneedle array 10, effectively avoiding single-point misjudgments caused by minor skin abrasions or sweat from pores, and improving the overall reliability of impedance change detection.

[0078] In one possible implementation, the detection unit 40 includes a sampling unit, a processing unit, and a locking drive unit;

[0079] The sampling end of the sampling unit is connected to the detection probe 102, its voltage input end is connected to the pulse output end of the processing unit, and its voltage output end is connected to the voltage sampling end of the processing unit.

[0080] The trigger output terminal of the processing unit is connected to the input terminal of the locking drive unit;

[0081] The output of the locking drive unit is connected to the locking mechanism 30.

[0082] In this embodiment, the sampling unit primarily uses the principle of resistor voltage division for sampling. The processing unit can be implemented using a conventional microcontroller, i.e., an MCU (such as a single-chip microcomputer). The ADC input pin of the MCU serves as the voltage sampling terminal of the processing unit, allowing direct reading of the real-time analog voltage value, i.e., the sampling voltage. The pulse output pin of the MCU serves as the pulse output terminal of the processing unit, used to output the pulse signal PULSE_OUT. The MCU is the core of the system, responsible for periodically sending pulses and reading the sampling voltage output by the sampling unit. Based on the sampling voltage, it performs baseline calibration and determines the impedance change rate of the skin impedance. When the impedance change rate exceeds a set dynamic threshold, it controls the locking drive unit to output a large current. The MCU can be a small-package, low-power model. The locking drive unit can be understood as an electronic switch, which can be constructed using MOSFETs, used to implement high-current power supply control for the locking mechanism 30.

[0083] It should be noted that due to significant differences in skin thickness and mechanical properties between individuals (dry or oily skin, and the same person at different ages) and different areas, the absolute impedance value defining the stratum corneum and dermis will inevitably vary from person to person. Therefore, when the microneedle array 10 initially contacts the skin surface, the MCU can first perform baseline calibration (slight pressure, not requiring penetration of the stratum corneum, only extremely close to the dermis). This allows for dynamic prediction of the threshold for determining the boundary (predicting penetration of the stratum corneum to the dermis / active epidermis rich in tissue fluid). After baseline calibration, dynamic slope determination within the MCU program can then determine whether the needle tip of the microneedle array 10 has penetrated the stratum corneum.

[0084] The baseline calibration process is as follows: When the microneedle array 10 just touches the skin surface (before penetrating the stratum corneum), the MCU first sends an initial test pulse through the pulse output pin, and simultaneously uses the ADC input pin to read the analog voltage divider value at this time, i.e., the voltage divider detection signal V_SENSE. This value is recorded by the MCU as the user's "initial stratum corneum impedance baseline". By setting the corresponding lookup table in advance, the preset threshold of skin impedance and the dynamic threshold of impedance change rate can be dynamically set. The lookup table here can include a one-to-one correspondence between the initial stratum corneum impedance baseline, the preset threshold of skin impedance, and the dynamic threshold of impedance change rate.

[0085] The dynamic slope determination process is as follows: The MCU continuously acquires pulsed ADC data, i.e., the voltage divider detection signal V_SENSE, to calculate the impedance change rate. When the microneedle array 10 is extremely close to / just pierces the stratum corneum and comes into contact with the dermis / active epidermis rich in tissue fluid, the impedance will show a steep, precipitous drop. By matching the impedance change rate with the set dynamic threshold, it can be determined whether the needle tip of the microneedle array 10 has penetrated the stratum corneum.

[0086] In practical implementation, the operating voltage VCC and drive voltage VBAT required by the processing unit, latch-up drive unit, etc., can be provided by a conventional power management module. For example, the power management module includes a battery input terminal, a filter circuit, and a low-dropout linear regulator (LDO) to convert the battery output voltage into a stable operating voltage VCC, which can be directly used as the drive voltage VBAT.

[0087] In one possible implementation, such as Figure 3 The sampling unit includes a sampling interface J1, a first resistor R1, a second resistor R2, a first ESD protection diode D1, and a second ESD protection diode D2;

[0088] The sampling interface J1 serves as the sampling terminal of the sampling unit. Its input pin is connected to the first end of the first resistor R1, and its output pin is connected to the negative terminal of the first ESD protection diode D1 and the first end of the second resistor R2, respectively, as the voltage output terminal of the sampling unit.

[0089] The second end of the first resistor R1 serves as the voltage input terminal of the sampling unit, and the line containing the first resistor R1 is connected to the negative terminal of the second ESD protection diode D2.

[0090] The second terminal of the second resistor R2, the positive terminal of the first ESD protection diode D1, and the positive terminal of the second ESD protection diode D2 are respectively grounded.

[0091] In this embodiment, the sampling unit is equivalent to an anti-polarization pulse sensing interface module, including ESD protection, current-limiting resistors, and a core voltage divider / reference resistor network. The first ESD protection diode D1 and the second ESD protection diode D2 are conventional ESD protection diodes, providing ESD protection. The first resistor R1 is a conventional current-limiting resistor. The second resistor R2 is a conventional type of resistor. The sampling interface J1 can provide skin impedance through the microneedle array 10, forming a voltage divider / reference resistor network with the second resistor R2. Applying microsecond-level short pulses to the skin through the microneedle array 10 via the sampling interface J1 can solve the skin polarization problem caused by continuous voltage application during detection. In specific implementations, a third ESD protection diode D3 can also be placed between the input and output pins of the sampling interface J1. The third ESD protection diode D3 is a conventional ESD protection diode, which can further provide ESD protection.

[0092] In one possible implementation, such as Figure 4 The detection unit 40 further includes a comparison unit;

[0093] The first input terminal of the comparison unit is connected to the voltage output terminal of the sampling unit, its second input terminal is connected to the threshold voltage terminal of the processing unit, and its output terminal is connected to the comparison input terminal of the processing unit.

[0094] In this embodiment, the comparison unit can be implemented based on a conventional voltage comparator. The operating voltage VCC required by the comparison unit can be provided by a conventional power management module. The sampling unit and the comparison unit together constitute an analog detection circuit. The microcontroller can determine the reference threshold V_THRESH, i.e., the preset threshold of skin impedance, based on baseline calibration. The comparison unit compares the voltage divider detection signal V_SENSE with the reference threshold V_THRESH and outputs the comparison result. The microcontroller reads the comparison result output by the comparison unit to determine whether the needle tip of the microneedle array 10 has penetrated the stratum corneum, and determines whether to control the latching drive unit to output a large current based on the determination result. This embodiment achieves a combination of the "zero-delay instantaneous response" of the hardware comparator and the "adaptive" nature of the software algorithm.

[0095] In one possible implementation, such as Figure 5 The comparison unit includes a voltage comparator COMP1, a third resistor R3, and a first capacitor C1;

[0096] The non-inverting input terminal of the voltage comparator COMP1 serves as the first input terminal of the comparator unit, and its inverting input terminal serves as the second input terminal of the comparator unit. Its positive power supply is connected to the working voltage VCC, its negative power supply is grounded, and its output terminal is connected to the first terminal of the third resistor R3 as the output terminal of the comparator unit.

[0097] The second end of the third resistor R3 is connected to the working voltage VCC and then to the grounded first capacitor.

[0098] In this embodiment, the voltage comparator COMP1 is a precision voltage comparator responsible for converting weak analog voltage signals into digital logic signals (high / low levels). The third resistor R3 is a standard type resistor. The first capacitor C1 is a standard type capacitor. At the moment the pulse is emitted, the voltage comparator COMP1 compares the voltage divider detection signal V_SENSE with the reference threshold V_THRESH and outputs a comparison signal COMP_IN to the MCU. The MCU determines whether the skin impedance is lower than the preset threshold (or whether the detection voltage exceeds the threshold) through the comparison signal COMP_IN. When the trigger condition is met, the MCU outputs a trigger signal TRIG_OUT, which drives the locking mechanism 30 by the locking drive unit. This causes the locking mechanism 30 to immediately act on the actuator 20, preventing the microneedle array 10 from continuing to extend / retract and locking the current extension length, thus achieving needle depth locking.

[0099] In one possible implementation, such as Figure 6The latching drive unit includes an NMOS transistor Q1, a drive interface J2, a freewheeling diode D4, a fourth resistor R4, and a fifth resistor R5.

[0100] The gate of the NMOS transistor Q1 is connected to the first terminal of the fourth resistor R4 and the first terminal of the fifth resistor R5, respectively. Its drain is connected to the positive terminal of the freewheeling diode D4 and the output pin of the drive interface J2, respectively. Its source is grounded.

[0101] The drive interface J2 serves as the output terminal of the latching drive unit, and its input pin is connected to the negative terminal of the freewheeling diode D4 and connected to the drive voltage VBAT.

[0102] The second end of the fourth resistor R4 serves as the input end of the locking drive unit;

[0103] The second terminal of the fifth resistor R5 is grounded.

[0104] In this embodiment, NMOS transistor Q1 is a conventional N-type MOS transistor. The drive interface J2 can be a conventional two-pin interface. The freewheeling diode D4 is a conventional model and serves as freewheeling protection. The fourth resistor R4 and the fifth resistor R5 are conventional resistors.

[0105] In one possible implementation, such as Figure 7 The actuator 20 includes a sliding push rod 201;

[0106] The locking mechanism 30 includes a locking sleeve 301, a return spring 302, a mechanism base 303, a solenoid unit 304, a chuck housing 305, and a slotted chuck 306.

[0107] The sliding push rod 201 passes through the chuck housing 305 from top to bottom, with one end connected to the microneedle array 10 and the other end used to receive the applied force;

[0108] The locking sleeve 301 is fixedly sleeved on the body of the sliding push rod 201, and its top end is connected to the first end of the return spring 302;

[0109] The return spring 302 is sleeved on the body of the sliding push rod 201, and its second end is connected to the bottom of the first end of the mechanism base 303;

[0110] The bottom of the first end of the mechanism base 303 is also connected to the solenoid unit 304, and the top of its first end is connected to the inner side of the top end cap of the chuck housing 305 through the elastic structure 307. Its second end extends out from the top opening of the chuck housing 305.

[0111] The magnetic end of the solenoid unit 304 is positioned downwards;

[0112] The slotted chuck 306 is arranged around the bottom opening of the chuck housing 305;

[0113] The upper end of the slotted chuck 306 is provided with a magnetic suction element 308;

[0114] When the solenoid unit 304 is powered on, its magnetic end attracts the magnetic member 308, which drives the slotted chuck 306 and the chuck housing 305 to move upward, so that the blocking surface of the slotted chuck 306 contacts the force-bearing surface of the locking sleeve 301 to limit the sliding push rod 201 to the current position.

[0115] In this embodiment, the sliding push rod 201 mainly controls the up and down movement of the microneedle array 10. The locking mechanism 30 is similar to an electromagnetic brake. The locking sleeve 301 can be a cone with a hollow cylinder inside, with its bottom surface facing upwards and its apex facing downwards, through which the sliding push rod 201 passes. The return spring 302 can limit the maximum up and down stroke of the sliding push rod 201. The mechanism base 303 serves a fixing function; its first end provides a support position for the return spring 302, solenoid unit 304, elastic structure 307, etc., and its second end can be fixedly set in other external positions to provide a support position for the entire locking mechanism 30. The solenoid unit 304 is an electromagnet and can be composed of several conventional solenoids with built-in metal cores. The chuck housing 305 is both an external protective housing and a support component for the slotted chuck 306.

[0116] The slotted chuck 306 can be a single, integral structure, or it can consist of multiple identical sub-chucks arranged in a ring at equal intervals at the bottom opening of the chuck housing 305. The slotted chuck 306 is preferably made of high-performance engineering plastics, such as polyoxymethylene (POM) or polyetheretherketone (PEEK). From a biocompatibility and fatigue resistance perspective, PEEK is a medical-grade polymer material that supports various sterilization processes (high temperature, high pressure, radiation, etc.) and exhibits strong fatigue resistance. In this application, the locking sleeve 301 and the slotted chuck 306 cooperate to form a tapered wedging mechanism. The biggest concern with tapered wedging mechanisms is "jamming" and inability to reset. POM has an extremely low coefficient of friction and excellent self-lubricating properties, ensuring that after the electromagnet is de-energized, the elastic structure 307 can smoothly separate the slotted chuck 306 and the locking sleeve 301. It should be noted that the slotted chuck 306 in this embodiment has a perfect elastic modulus match. The Young's modulus of polymer materials is typically between 2 GPa and 4 GPa, far lower than the 200 GPa of metals. This means that a micro-solenoid (such as solenoid unit 304) requires only a very small force to induce centripetal elastic deformation in the slotted chuck 306 made of POM or PEEK, quickly locking the sliding push rod 201. This significantly reduces the power requirements of the electromagnet in the system.

[0117] The elastic structure 307 can be constructed using a conventional spring. In specific implementation, after the solenoid unit 304 is powered on, it can drive the slotted chuck 306 to move upward toward the locking sleeve 301, so that the inclined surface of the slotted chuck 306 contacts the inclined surface of the locking sleeve 301, preventing the sliding push rod 201 from continuing to descend, thereby locking / stopping the stroke of the sliding push rod 201. This reduces the risk of the microneedle further penetrating deep into the skin and touching nerve endings, and achieves the purpose of reducing pain and improving the effectiveness of transdermal drug delivery.

[0118] It should be noted that in this embodiment, the force-bearing surface of the locking sleeve 301 and the blocking surface of the slotted chuck 306 actually form a pair of matching conical inclined surfaces, which can achieve a tapered fit. When the solenoid unit 304 is powered on and pulls the slotted chuck 306 upward, it is equivalent to forcibly "squeezing / wedging" the slotted chuck 306 (outer sleeve) into the gap between the locking sleeve 301 and the slotted chuck 306, thereby achieving a wedging amplification effect. The inclination angle of the conical inclined surface (i.e., the angle between the contour line of the cone and the axis) can be 1~15 degrees, preferably 3~5 degrees, which can ensure the geometric self-locking property when the downward pressure drives the sliding push rod 201. In specific implementation, the inclination angle of the conical inclined surface is set to be smaller than the friction angle of the material. Due to the physical properties of the conical inclined surface, the greater the downward force applied by the user to the sliding push rod 201, the more the radial (centripetal) locking force / clamping force converted by the conical inclined surface will increase geometrically. The greater the downward pressure, the greater the locking force of the locking sliding push rod 201, thereby achieving self-locking and anti-slip.

[0119] In one possible implementation, the detection unit 40 generates a microsecond-level short pulse signal using a short pulse method.

[0120] In practical implementation, in order to achieve low power consumption and reduce the risk of skin polarization caused by continuous detection, this invention adopts a pulsed impedance detection strategy: the microcontroller generates microsecond-level short pulses to instantaneously excite and sample the skin impedance, and the skin impedance can be equivalent to a variable resistor in detection.

[0121] In one possible implementation, the detection unit 40 stops acquiring the skin impedance at the sampling point after determining that the needle tip of the microneedle array 10 has penetrated the stratum corneum.

[0122] In one specific implementation, reference is made to... Figure 8 In the microneedle system of this invention, during use, an ADC dynamic baseline acquisition and ΔZ / Δt slope (i.e., dynamic slope) determination algorithm based on anti-polarization pulse is employed. The standard procedure of this determination algorithm is as follows:

[0123] Step S101: System initialization and sleep / wake-up.

[0124] In this embodiment, the power management module filters the battery input and regulates it via an LDO to provide a stable 3.3V power supply to the microcontroller (MCU) and analog detection circuit, thereby achieving power supply and voltage regulation. Initially, the MCU powers on and initializes, configuring a PA pin as an ADC input pin, configuring a pulse output pin for digital output to output the pulse signal PULSE_OUT, and configuring a drive pin for digital output to output the trigger signal TRIG_OUT. The system then enters a low-power sleep mode. In a specific implementation, a sensor for detecting pressure or a start button can be set at the force-bearing position of the sliding push rod 201. When the sensor detects pressure or the user presses the start button, the sensor or start button transmits a trigger signal to the MCU, waking the MCU.

[0125] Step S102: Initial contact detection (no-load anti-accidental touch).

[0126] The MCU sends test pulses at a low frequency. If the measured impedance Z > Z open (Extremely high impedance, considered an open circuit) indicates that the microneedle array 10 has not yet contacted the skin, and the cyclic detection continues. If the impedance drops to a reasonable range within the human stratum corneum, it indicates that the microneedle array 10 has adhered to the skin surface and enters the baseline calibration stage.

[0127] Step S103: Dynamic baseline acquisition and calibration.

[0128] In the initial few milliseconds before the microneedles pierce the stratum corneum, the MCU continuously sends N microsecond-level short pulses (N typically needs to be greater than 3), and the corresponding impedance values ​​Z1, Z2, ..., Zn are acquired by the ADC. n .

[0129] Algorithm: After removing outliers, take the average value to calculate the initial stratum corneum impedance baseline Z for that specific user. baseline This step is the foundation for achieving personalized recommendations for each user.

[0130] Step S104: Anti-polarization pulse sampling loop.

[0131] The microneedle moves downwards with the press. The MCU begins a sampling cycle at fixed time intervals Δt (e.g., 1 ms):

[0132] 1. Pull the pulse output pin high to send a transient excitation pulse with a width of 100μs, i.e., the pulse signal PULSE_OUT.

[0133] 2. During the window period when the pulse remains high, the ADC is triggered to sample the current analog voltage, i.e., the voltage divider detection signal V. SENSE And convert it to the current impedance value Z. current .

[0134] 3. Quickly pull down the high pulse output pin to stop applying voltage and prevent electrolytic polarization of the skin tissue.

[0135] Step S105: Calculation of impedance change rate (slope).

[0136] The MCU records the impedance value Z from the last sample. previous .

[0137] Algorithm: The core calculation formula is the dynamic rate of change of impedance (i.e., slope): S = (Z) current -Z previous ) / Δt.

[0138] Step S106: Dual adaptive threshold determination.

[0139] A dual logic is introduced, with slope determination as the primary factor and absolute threshold as a secondary factor, to ensure the absolute reliability of the trigger:

[0140] Condition A (Dynamic Slope Trigger): Determine if the current slope S satisfies S < -S threshold (-S) threshold (This is a preset negative slope threshold). When the needle tip pierces the high-resistivity stratum corneum and comes into contact with the dermis / active epidermis rich in moisture and electrolytes, the resistance drops precipitously, resulting in an extremely negative slope.

[0141] Condition B (Safe Drop Trigger): Determine the current impedance Z current Is it below the initial baseline Z? baseline A specific ratio (e.g., Z) current <0.2×Z baseline ).

[0142] Evaluation logic: If either condition A or condition B is met, the microneedle array 10 is determined to have successfully penetrated the stratum corneum, and the process proceeds to step S107. If neither condition is met, then Z... current Assigned to Z previous Then return to step S104 and continue the loop.

[0143] Step S107: Output a lockout signal and shut down the measurement link.

[0144] The MCU instantly pulls the drive pin high, outputting a trigger signal TRIG_OUT, which drives the solenoid unit 304 within the locking mechanism 30 to actuate, physically locking the sliding push rod 201 via a tapered wedge mechanism. Simultaneously, the MCU permanently stops emitting the PULSE_OUT pulse signal, shuts down the ADC sampling link, and completely eliminates current interference and power consumption during subsequent microneedle drug retention.

[0145] The above embodiments should not limit the present invention in any way. All technical solutions obtained by equivalent substitution or equivalent conversion fall within the protection scope of the present invention.

Claims

1. A microneedle system with adaptive puncture depth, characterized in that, include: Microneedle arrays are used to puncture the skin, providing sampling points for detecting skin impedance at the skin layer touched by the needle tip, and for releasing drugs; The detection unit, connected to the microneedle array, is configured to acquire the skin impedance at the sampling point using a short pulse method, and output a control signal when it is determined from the skin impedance that the tip of the microneedle array penetrates the stratum corneum; An execution unit, connected to both the microneedle array and the detection unit, is configured to receive a control signal from the detection unit after the detection unit determines that the microneedle array has penetrated the skin, thereby stopping the microneedle array from continuing to penetrate the skin. The execution unit includes an execution mechanism and a locking mechanism; the execution mechanism is connected to the microneedle array and the locking mechanism respectively; the execution mechanism is used to cause the microneedle array to perform a downward movement to puncture the skin; the locking mechanism is used to perform a locking action on the execution mechanism when the control signal is received to stop the microneedle array from continuing to puncture the skin; The actuator includes a sliding push rod; the locking mechanism includes a locking sleeve, a return spring, a mechanism base, a solenoid unit, a chuck housing, and a slotted chuck; the sliding push rod passes through the chuck housing from top to bottom, with one end connected to the microneedle array and the other end used to receive force; the locking sleeve is fixedly sleeved on the body of the sliding push rod, with its top end connected to the first end of the return spring; the return spring is sleeved on the body of the sliding push rod, with its second end connected to the bottom of the first end of the mechanism base; the bottom of the first end of the mechanism base is also connected to the solenoid unit, with its top end connected to the inside of the top end cap of the chuck housing via an elastic structure, and its second end extending from the top opening of the chuck housing; the magnetic end of the solenoid unit is positioned downwards; the slotted chuck is arranged around the bottom opening of the chuck housing; a magnetic element is provided at the upper end of the slotted chuck; When the solenoid unit is powered on, its magnetic end attracts the magnetic element, causing the slotted chuck to move upward, so that the blocking surface of the slotted chuck contacts the force-bearing surface of the locking sleeve to limit the sliding push rod to the current position.

2. The microneedle system according to claim 1, characterized in that, The microneedle array includes several drug delivery microneedles, at least two detection probes, and a needle hub; The drug delivery microneedle and the detection probe are evenly disposed on the needle hub; The needle hub is connected to the actuator.

3. The microneedle system according to claim 2, characterized in that, The detection unit includes a sampling unit, a processing unit, and a locking drive unit; The sampling end of the sampling unit is connected to the detection probe, its voltage input end is connected to the pulse output end of the processing unit, and its voltage output end is connected to the voltage sampling end of the processing unit. The trigger output terminal of the processing unit is connected to the input terminal of the locking drive unit; The output of the locking drive unit is connected to the locking mechanism.

4. The microneedle system according to claim 3, characterized in that, The sampling unit includes a sampling interface, a first resistor, a second resistor, a first ESD protection diode, and a second ESD protection diode; The sampling interface serves as the sampling terminal of the sampling unit. Its input pin is connected to the first end of the first resistor, and its output pin is connected to the negative terminal of the first ESD protection diode and the first end of the second resistor, respectively, serving as the voltage output terminal of the sampling unit. The second end of the first resistor serves as the voltage input terminal of the sampling unit, and the line containing the first resistor is connected to the negative terminal of the second ESD protection diode. The second terminal of the second resistor, the positive terminal of the first ESD protection diode, and the positive terminal of the second ESD protection diode are respectively grounded.

5. The microneedle system according to claim 3, characterized in that, The detection unit further includes a comparison unit; The first input terminal of the comparison unit is connected to the voltage output terminal of the sampling unit, its second input terminal is connected to the threshold voltage terminal of the processing unit, and its output terminal is connected to the comparison input terminal of the processing unit.

6. The microneedle system according to claim 5, characterized in that, The comparison unit includes a voltage comparator, a third resistor, and a first capacitor; The non-inverting input terminal of the voltage comparator serves as the first input terminal of the comparator unit, its inverting input terminal serves as the second input terminal of the comparator unit, its positive power supply is connected to the working voltage, its negative power supply is grounded, and its output terminal is connected to the first terminal of the third resistor as the output terminal of the comparator unit. The second terminal of the third resistor is connected to the operating voltage and then to the grounded first capacitor.

7. The microneedle system according to claim 3, characterized in that, The latching drive unit includes an NMOS transistor, a drive interface, a freewheeling diode, a fourth resistor, and a fifth resistor; The gate of the NMOS transistor is connected to the first terminal of the fourth resistor and the first terminal of the fifth resistor, respectively. Its drain is connected to the positive terminal of the freewheeling diode and the output pin of the drive interface, respectively. Its source is grounded. The drive interface serves as the output terminal of the latching drive unit, and its input pin is connected to the negative terminal of the freewheeling diode and connected to the drive voltage. The second end of the fourth resistor serves as the input end of the locking drive unit; The second terminal of the fifth resistor is grounded.

8. The microneedle system according to claim 1, characterized in that, The detection unit stops acquiring the skin impedance at the sampling point after determining that the tip of the microneedle array has penetrated the stratum corneum.

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