A programmable waveform sequence intelligent layered delivery needle-free injection system based on bioimpedance spectrum technology

Abstract

The application provides a programmable waveform sequence intelligent layered delivery needle-free injection system based on a bioimpedance spectrum technology, and belongs to the technical field of needle-free injection, and comprises a bioimpedance spectrum sensing front end integrated on a skin contact ring at the front end of a nozzle of a needle-free injection device, has a four-electrode symmetric layout, two outer electrodes are current injection electrodes, two inner electrodes are voltage pickup electrodes, an excitation signal with a frequency range of 100 Hz to 10 MHz and a current amplitude of ≤100 mu A is output to the skin of an injection site in a sweep frequency mode, and a wide-band impedance spectrum containing impedance modulus and phase angle at each frequency is output; compared with the method of applying a fixed pressure waveform to all individuals by the existing needle-free injector, the amplitude, duration and interval of each injection pulse are customized in real time according to the actual skin state of the part of the subject, the problem of too shallow or too deep penetration caused by individual age, part and physiological state difference is solved, and the hit rate of drug liquid reaching the target level is improved.

Description

Technical Field

[0001] This invention belongs to the field of needle-free injection technology, specifically relating to a programmable waveform sequence intelligent layered delivery needle-free injection system based on bioimpedance spectroscopy technology. Background Technology

[0002] Needle-free injection technology, as an alternative to traditional needle-based drug delivery, has gained widespread attention in recent years in the fields of mass vaccination, self-administration of chronic diseases, and cosmetic medicine. Its core principle is to use high pressure to drive the drug solution into a high-speed jet with a diameter of micrometers, directly penetrating the skin surface and delivering the drug to the target subcutaneous layer, thus avoiding the pain, infection risk, and needle prick injuries associated with needle insertion. Existing needle-free injection devices mainly use a single power source, such as spring energy storage and release, high-pressure gas expansion, or micro-explosive detonation. A fixed pressure waveform is generated at the moment of triggering to drive the plunger movement. The injection speed, duration, and pulse pattern of the drug jet are entirely determined by the inherent parameters of the mechanical structure or pneumatic components and cannot be adjusted after leaving the factory.

[0003] Since the advent of vaccination, traditional needle-based injections have long dominated, relying on needles for subcutaneous injections. This method often carries high safety risks, potentially leading to the transmission of various pathogens such as viruses, bacteria, fungi, and parasites, as well as non-infectious adverse reactions like abscesses and toxic reactions. With technological advancements, needle-free injection technology has gradually become a research hotspot in modern medicine and animal disease control. Due to its advantages such as reduced pain, lower infection risk, and improved efficiency, needle-free injection technology has attracted attention and favor from human and veterinary medicine. The immunomodulatory effects of needle-free injection are influenced by a combination of factors, including jet parameters, drug physical properties, and skin mechanical properties. Current mainstream technologies mainly fall into three categories: spring-driven, laser-driven, and energy-driven. Energy-driven technologies further include Lorentz force-driven, shock wave-driven, and pneumatic-driven methods. However, existing needle-free injection technology has the problem of uncontrollable injection depth. Most existing needle-free injectors are designed for a fixed depth, and the same jet pressure and duration are applied regardless of the age of the recipient and the injection site. This leads to two problems: First, the same parameters can produce a difference of several millimeters in the penetration depth among different individuals, resulting in some patients receiving drugs that are injected too shallowly or too deeply; Second, for treatment plans that require layered delivery, multiple injections are the only way to complete the procedure, which is cumbersome and the positioning accuracy is uncontrollable. Summary of the Invention

[0004] The purpose of this invention is to provide a programmable waveform sequence intelligent layered delivery needle-free injection system based on bioimpedance spectroscopy technology. It aims to solve the following problems in the prior art: firstly, the same parameter can produce a difference of several millimeters in the penetration depth among different individuals, resulting in some patients receiving drugs that are injected too shallowly or too deeply; secondly, for treatment plans that require layered delivery, it can only be completed through multiple injections, which is cumbersome and the positioning accuracy is uncontrollable.

[0005] To achieve the above objectives, the present invention provides the following technical solution: A programmable waveform sequence intelligent hierarchical delivery needle-free injection system based on bioimpedance spectroscopy technology includes: The bioimpedance spectrum sensing front end is integrated on the skin contact ring at the front end of the nozzle of the needleless injection device. It has a four-electrode symmetrical layout. The two outer electrodes are current injection electrodes and the two inner electrodes are voltage pickup electrodes. It outputs an excitation signal with a frequency range of 100Hz to 10MHz and a current amplitude ≤100μA to the skin at the injection site in a frequency sweep mode. The output is a broadband impedance spectrum containing the impedance modulus and phase angle at each frequency. The processing module, whose input is coupled to the output of the bioimpedance spectrum sensing front end, pre-stores a skin layer equivalent circuit model. In the model, the stratum corneum is a parallel branch of resistor R_sc and capacitor C_sc, the active epidermis is a parallel branch of resistor R_ep and capacitor C_ep, and the dermis and subcutaneous tissue are a branch of resistor R_de. The processing module adjusts the model parameters through an optimization algorithm to minimize the error between the model impedance spectrum and the measured impedance spectrum in order to extract the values ​​of R_sc, C_ep, and R_de. Based on the values ​​of R_sc, C_ep, and R_de and the target delivery layer, the processing module calculates the pulse parameters in the driving current waveform using the following formula: D = k·ρ·v²·τ / E, v = C_d·sqrt[2(P_c - P_0) / ρ], I = P_c·A / (BL), R_sc is mapped to the first pulse current amplitude adjustment coefficient, and C_ep is mapped to the second pulse duration or current amplitude adjustment coefficient, generating a drive current waveform sequence containing at least two pulses with a time interval between adjacent pulses; The drive module includes a programmable servo driver, which receives the drive current waveform sequence as a current command and controls the output current to track the command through a closed-loop current loop control. A voice coil motor has a permanent magnet stator and a moving coil, wherein the moving coil generates an axial Lorentz force when current is applied to it. The transmission rod connects the mover of the voice coil motor to the plunger; The injection chamber contains the plunger, which slides within it to form a sealing pair, and its front end is connected to the nozzle. The nozzle has a converging internal flow channel and an outlet orifice diameter of 50μm to 300μm, and the skin contact ring is located at the front end of the nozzle; The locking module includes a mechanical locking mechanism and an electronic safety interlock circuit. The input terminal of the electronic safety interlock circuit is connected to a contact ring compression sensor, an inclination sensor, the effective data output terminal of the bioimpedance spectrum sensing front end, and the calculation completion flag output terminal of the processing module. When any locking condition is not met, the mechanical locking mechanism is controlled to be in a locked state.

[0006] As a preferred embodiment of the present invention, the processing module extracts R_sc, C_ep, and R_de using the following objective function: ; Where n is the number of sweep frequency points, ωi is the i-th sweep angular frequency, Zm(ωi) is the measured impedance magnitude, and Ze(ωi) is the theoretical impedance magnitude of the equivalent circuit model; the processing module also includes a feedforward neural network classifier, which takes the impedance magnitude, phase angle, real impedance, and imaginary reactance of the broadband impedance spectrum after time difference as input, and outputs skin layer classification labels to set the initial values ​​of the optimization algorithm.

[0007] In a preferred embodiment of the present invention, in the driving current waveform sequence, the current amplitude of the first pulse is higher than that of the second pulse, the duration of the first pulse is shorter than that of the second pulse, and the time interval between the two pulses is 0.5ms to 5ms; the numerical value of R_sc is linearly mapped to the multiplication factor of the current amplitude of the first pulse, and the numerical value of C_ep is linearly mapped to the multiplication factor of the duration of the second pulse.

[0008] As a preferred embodiment of the present invention, the locking conditions include: the output value of the contact ring compression sensor is lower than the fit threshold, the output value of the tilt sensor exceeds the preset angle range, the valid data output terminal is in an invalid state, and the calculation completion flag output terminal is in an incomplete state; when any one of the conditions is met, the electronic safety interlock circuit controls the mechanical locking mechanism to lock the trigger button.

[0009] As a preferred embodiment of the present invention, the bioimpedance spectrum sensing front end is restarted after injection to output the frequency sweep excitation signal to the injection area and generate a broadband impedance spectrum after injection; the processing module calculates the change in impedance modulus between the impedance spectrum after injection and the impedance spectrum before injection at characteristic frequency points as a delivery depth deviation value and stores it as a delivery depth deviation value, and superimposes the deviation value onto the target penetration depth during the next injection to adjust the amplitude of each pulse current.

[0010] In a preferred embodiment of the present invention, the nozzle is a gemstone microporous nozzle or a ceramic microporous nozzle, the converging internal flow channel tapers from the inlet end to the outlet end in a conical shape with a cone angle of 30° to 60°, the outlet end is a straight section, and the ratio of the length of the straight section to the outlet diameter is 1:1 to 3:1; the skin contact ring is a flexible medical silicone ring, and its front end face is provided with an annular flange, the electrode surface of the four electrodes is flush with or 0.05mm to 0.2mm higher than the top surface of the annular flange.

[0011] As a preferred embodiment of the present invention, a programmable waveform sequence intelligent layered delivery needle-free injection method based on bioimpedance spectroscopy technology includes: S1: The four-electrode bioimpedance spectrum sensing front end, integrated on the skin contact ring at the nozzle tip, outputs a sweep frequency excitation signal with a frequency range of 100Hz to 10MHz and a current amplitude ≤100μA to the skin at the injection site. It measures the voltage response at each frequency point and calculates the impedance modulus and phase angle to generate a broadband impedance spectrum. S2: The broadband impedance spectrum is input into the processing module. The processing module calls a pre-stored skin layer equivalent circuit model and adjusts the parameter values ​​of the stratum corneum resistance R_sc and capacitance C_sc, active epidermal resistance R_ep and capacitance C_ep, and dermal and subcutaneous tissue resistance R_de in the model through an optimization algorithm to minimize the following objective function: min ∑i=1n[Zm(ωi)−Ze(ωi)]2min∑i=1n[Zm(ωi)−Ze(ωi)]2 Extract the optimized R_sc and C_ep values; S3: Determine the target penetration depth D based on the target delivery level, and sequentially perform the following operations to generate the drive current waveform sequence: D = k·ρ·v²·τ / E, v = C_d·sqrt[2(P_c - P_0) / ρ], I = P_c·A / (BL), Using R_sc as the multiplier coefficient for the amplitude of the first pulse current and C_ep as the multiplier coefficient for the duration of the second pulse, a data packet containing the first pulse, the time interval, and the second pulse is generated. S4: When all locking conditions are met, the unlock trigger button is released. The locking conditions include the contact ring compression being greater than or equal to the fitting threshold, the tilt angle being within a preset range, the processing module having completed waveform calculation, and the system being fault-free. After triggering, the programmable servo driver outputs current to the moving coil of the voice coil motor according to the drive current waveform sequence, causing the moving coil to generate multiple axial thrust pulses in the permanent magnet stator magnetic field in sequence. These pulses are then transmitted through the transmission rod and plunger to eject multiple jet pulses of the liquid from the nozzle in sequence.

[0012] As a preferred embodiment of the present invention, in step S2, before optimization, the processing module first performs time difference analysis on the impedance magnitude, phase angle, real impedance and imaginary reactance of the broadband impedance spectrum and inputs them into the feedforward neural network classifier to obtain skin layer classification labels. Then, based on the classification labels, it reads the initial optimization values ​​of each parameter in the equivalent circuit model from the pre-stored mapping table and executes the optimization algorithm starting from the initial values.

[0013] As a preferred embodiment of the present invention, after step S4, step S5 is further included: the bioimpedance spectrum sensing front end is restarted, outputs the frequency sweep excitation signal to the injection area and generates a broadband impedance spectrum after injection; the processing module calculates the difference in impedance modulus between the impedance spectrum after injection and the impedance spectrum in S1 at characteristic frequency points, extracts a first difference in the low frequency band of 100Hz to 1kHz as an estimate of the total drug volume, extracts a second difference in the high frequency band of 1MHz to 10MHz as an estimate of the drug deposition depth, and weights the first difference and the second difference to convert them into a delivery depth deviation value for storage; when generating the driving current waveform sequence for the next injection, the processing module superimposes the deviation value onto the target penetration depth.

[0014] As a preferred embodiment of the present invention, a programmable waveform sequence intelligent layered delivery needle-free injection control device based on bioimpedance spectroscopy technology includes a digital signal processor and a memory storing firmware programs. The firmware programs include: impedance spectrum acquisition control instructions, used to control the frequency sweep excitation output and voltage response acquisition of the bioimpedance spectroscopy sensing front end, and generate broadband impedance spectrum data including impedance magnitude sequences and phase angle sequences. The equivalent circuit fitting instruction is used to solve for the parameter values ​​of R_sc, C_ep and R_de in the equivalent circuit model by taking the broadband impedance spectrum data as input and using the Levenberg-Marquardt algorithm. In the model, the stratum corneum is represented by R_sc and C_sc in parallel, the active epidermis is represented by R_ep and C_ep in parallel, and the dermis and subcutaneous tissue are represented by R_de. The waveform sequence calculation instruction is used to perform arithmetic operations of D = k·ρ·v²·τ / E, v = C_d·sqrt[2(P_c - P_0) / ρ] and I = P_c·A / (BL) in sequence according to the target delivery level and R_sc, C_ep, and R_de, and map R_sc to the first pulse current amplitude multiplier coefficient and C_ep to the second pulse duration multiplier coefficient to generate drive current waveform sequence data containing at least two pulses; The locking judgment command is used to read the digital values ​​of the contact ring compression sensor, the tilt sensor, and the system fault flag. When the compression is greater than or equal to the contact threshold, the tilt is within the preset angle range, and there is no fault flag, the unlocking level is output to the mechanical locking mechanism. A pulse output command is used to send the drive current waveform sequence data to the programmable servo driver in a time-based manner when a trigger button signal is received and the unlock level has been output.

[0015] Compared with the prior art, the beneficial effects of the present invention are: 1. By acquiring the 100Hz to 10MHz broadband impedance spectrum of the injection site in situ through a bioimpedance spectroscopy sensing front end, and combining the skin layer equivalent circuit model and optimization algorithm, the macroscopic impedance spectrum is decomposed into independent electrical parameters of each layer, such as stratum corneum resistance, active epidermal capacitance, and dermal resistance. Based on this, a quantitative physical mapping from the parameters of each layer to the voice coil motor drive current waveform is established. The stratum corneum resistance is linearly mapped to the first pulse current amplitude multiplier coefficient to overcome the high impedance barrier, and the active epidermal capacitance is linearly mapped to the second pulse duration multiplier coefficient to optimize the electroporation assistance duration. Compared with the existing needle-free injector approach of applying a fixed pressure waveform to all individuals, this method allows the amplitude, duration, and interval of each injection pulse to be customized in real time according to the actual skin condition of the subject at that site. This effectively solves the problem of penetration that is too shallow or too deep due to differences in individual age, location, and physiological state, and significantly improves the hit rate of the drug reaching the target layer.

[0016] 2. By directly integrating the bioimpedance spectroscopy sensing front end onto the skin contact ring at the nozzle tip, the measurement and injection positions are perfectly aligned, eliminating data mismatch errors caused by positional offsets in traditional separate measurement devices. The driving current waveform sequence generated by the processing module contains at least two pulses with different amplitudes, durations, and controllable intervals. In a single trigger operation, multiple thrust pulses with different pressure-time characteristics are sequentially output, delivering the drug solution to different preset skin layers in a time sequence, eliminating the need for multiple punctures or operations. Simultaneously, this invention restarts impedance measurement after injection, extracting the low-frequency difference before and after injection as an estimate of the total drug volume and the high-frequency difference as an estimate of the deposition depth. These two values ​​are weighted and converted into a delivery depth deviation value, which is stored in the system for target depth correction in the next injection. This closed-loop feedback mechanism enables the system to adaptively correct dynamic drift caused by tissue edema, drug accumulation, or tissue fatigue during multiple injections on the same subject—a technical effect completely absent in existing open-loop needle-free injection systems.

[0017] 3. Existing needle-free injection devices often rely on single mechanical spring switches or contact pressure sensors for safety interlocking mechanisms. These mechanisms can trigger injection even when the nozzle is not in contact with the target, the device is tilted, or measurement is incomplete, posing safety hazards such as jet deviation, drug leakage, or uncontrolled penetration. This invention constructs a multi-dimensional safety architecture integrating a mechanical locking mechanism and an electronic safety interlock circuit. The locking conditions simultaneously encompass the determination of the skin contact ring compression threshold, the device tilt angle within a safe range, the validity of the bioimpedance spectrum data, the completion of waveform calculation in the processing module, and a system fault flag. If any condition is not met, the electronic safety interlock circuit controls the mechanical locking mechanism to lock the trigger button, unlocking only when all conditions are met simultaneously. This four-level logic and judgment mechanism fundamentally eliminates the possibility of accidental injection under unsafe conditions such as unidentified skin parameters, ungenerated waveforms, improper device posture, or poor contact, significantly improving the operational safety of needle-free injection devices in clinical and personal use scenarios. Attached Figure Description

[0018] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used in conjunction with embodiments of the invention to explain the invention and do not constitute a limitation thereof. In the drawings: Figure 1 This is a system flowchart of the present invention. Detailed Implementation

[0019] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Example 1

[0020] Please see Figure 1 The present invention provides the following technical solutions: A programmable waveform sequence intelligent hierarchical delivery needle-free injection system based on bioimpedance spectroscopy technology includes: The bioimpedance spectrum sensing front end is integrated on the skin contact ring at the front end of the nozzle of the needleless injection device. It has a four-electrode symmetrical layout. The two outer electrodes are current injection electrodes and the two inner electrodes are voltage pickup electrodes. It outputs an excitation signal with a frequency range of 100Hz to 10MHz and a current amplitude ≤100μA to the skin at the injection site in a frequency sweep mode. The output is a broadband impedance spectrum containing the impedance modulus and phase angle at each frequency. The processing module, whose input is coupled to the output of the bioimpedance spectrum sensing front end, pre-stores a skin layer equivalent circuit model. In the model, the stratum corneum is a parallel branch of resistor R_sc and capacitor C_sc, the active epidermis is a parallel branch of resistor R_ep and capacitor C_ep, and the dermis and subcutaneous tissue are a branch of resistor R_de. The processing module adjusts the model parameters through an optimization algorithm to minimize the error between the model impedance spectrum and the measured impedance spectrum in order to extract the values ​​of R_sc, C_ep, and R_de. Based on the values ​​of R_sc, C_ep, and R_de and the target delivery layer, the processing module calculates the pulse parameters in the driving current waveform using the following formula: D = k·ρ·v²·τ / E, v = C_d·sqrt[2(P_c - P_0) / ρ], I = P_c·A / (BL), Then, R_sc is mapped to the first pulse current amplitude adjustment coefficient, and C_ep is mapped to the second pulse duration or current amplitude adjustment coefficient, generating a drive current waveform sequence containing at least two pulses with a time interval between adjacent pulses; The drive module includes a programmable servo driver, which receives the drive current waveform sequence as a current command and controls the output current to track the command through a closed-loop current loop control. A voice coil motor has a permanent magnet stator and a moving coil, wherein the moving coil generates an axial Lorentz force when current is applied to it. The transmission rod connects the mover of the voice coil motor to the plunger; The injection chamber contains the plunger, which slides within it to form a sealing pair, and its front end is connected to the nozzle. The nozzle has a converging internal flow channel and an outlet orifice diameter of 50μm to 300μm, and the skin contact ring is located at the front end of the nozzle; The locking module includes a mechanical locking mechanism and an electronic safety interlock circuit. The input terminal of the electronic safety interlock circuit is connected to a contact ring compression sensor, an inclination sensor, the effective data output terminal of the bioimpedance spectrum sensing front end, and the calculation completion flag output terminal of the processing module. When any locking condition is not met, the mechanical locking mechanism is controlled to be in a locked state.

[0021] In a specific embodiment of the present invention, the frequency sweep excitation and data acquisition process of the bioimpedance spectroscopy sensing front end is as follows: When the operator places the skin contact ring at the front end of the needle-free injection device nozzle against the skin surface of the injection site, the four electrodes on the skin contact ring form a stable electrical contact with the skin; wherein the two outer electrodes serve as current injection electrodes, and the two inner electrodes serve as voltage pickup electrodes. At this time, the processing module generates a frequency sweep control word through its built-in DDS signal generator, driving the current injection electrodes to output an excitation signal with a frequency from 100Hz to 10MHz and a current amplitude not exceeding 100μA to the skin; the frequency sweep process is distributed according to logarithmic frequency intervals, and each frequency point lasts for at least two complete cycles to ensure steady-state response. After the voltage pickup electrode acquires the skin response voltage signal at the corresponding frequency, the signal is processed by the differential amplifier and phase-sensitive detector at the front end to output the impedance magnitude and phase angle at that frequency point. After all frequency points are scanned, the bioimpedance spectrum sensing front end packages the complete multi-frequency impedance spectrum data and transmits it to the input buffer of the processing module. The processing module performs a layered equivalent circuit parameter extraction process based on an optimization algorithm. When the processing module receives the measured impedance spectrum data, it calls the skin layered equivalent circuit model pre-stored in the internal non-volatile memory. In this model, the stratum corneum is represented as a parallel branch of resistance and capacitance, the active epidermis is represented as a parallel branch of resistance and capacitance, and the dermis and subcutaneous tissue are represented as a single resistance branch. At this point, the processing module uses the root mean square error between the theoretical impedance spectrum and the measured impedance spectrum of the model as the objective function, and iteratively adjusts the parameter values ​​of each component in the model using the Levenberg-Marquardt optimization algorithm. When the iteration convergence condition—that is, the relative change of the objective function between two adjacent iterations is less than one-thousandth—is met, the optimization process terminates, and the current parameter values ​​are extracted as R_sc, C_ep, and R_de values ​​representing the skin state of the current injection site. After the above three feature parameters are successfully extracted, the processing module selects the target delivery layer (superficial stratum corneum, active epidermis, or deep dermis / subcutaneous tissue layer) from the preset mapping table according to the operator's pre-set target delivery layer. The desired jet kinetic energy and desired penetration depth are determined. At this point, the processing module calculates the required jet kinetic energy based on the fluid dynamics jet formula D, which is equal to the proportional coefficient k multiplied by the drug density ρ multiplied by the square of the jet velocity v multiplied by the jet duration τ and then divided by the skin elastic modulus E. At the same time, it calculates the theoretical jet velocity based on the electromagnetic drive formula v, which is equal to the voice coil motor force constant C_d multiplied by the current drive current I multiplied by the square root of the equivalent drive stroke and then divided by the square root of the drug density ρ. Furthermore, it determines the drive current amplitude based on the pressure-current relationship formula I, which is equal to the drug pressure P_c in the injection chamber multiplied by the effective area of ​​the plunger A and divided by the product of the motor force constant C_d and the coil resistance R_coil.After the values ​​of R_sc, C_ep, and R_de are mapped to the first pulse current amplitude adjustment coefficient, the second pulse current amplitude adjustment coefficient, and the pulse interval time adjustment coefficient, respectively, the processing module generates a drive current waveform sequence containing at least two pulses according to timing logic. Adjacent pulses in this sequence have a preset time interval, and the amplitude and duration of subsequent pulses are dynamically corrected based on the impedance response prediction result after the previous pulse. This completes the closed-loop current drive process between the drive module and the voice coil motor. When the processing module sends the drive current waveform sequence to the drive module in the form of a digital command, the programmable servo driver inside the drive module immediately converts the digital command into an analog current command value through a digital-to-analog converter. At this time, the closed-loop current control loop of the servo driver uses this analog value as a given input, and simultaneously acquires the actual current feedback value in real time through a high-precision sampling resistor connected in series in the power supply circuit of the voice coil motor's mover coil. The deviation between the given value and the feedback value is sent to a PI regulator, which outputs a pulse width modulation duty cycle to drive the power switching transistor, thereby forcing the actual current to closely track the command. The waveform tracking error is controlled within one percent of the full scale. When the drive current begins to flow through the moving coil of the voice coil motor, the moving coil is subjected to an axial Lorentz force in the constant magnetic field provided by the permanent magnet stator. When the magnitude of this Lorentz force exceeds the static frictional resistance between the plunger and the inner wall of the injection chamber, the plunger begins to move forward axially, accelerating the extrusion of the liquid medicine in the injection chamber through the converging inner cavity flow channel of the nozzle. The outlet orifice diameter of the nozzle is between 50 micrometers and 300 micrometers, at which the liquid medicine is accelerated to tens to hundreds of meters per second, forming a high-speed micro-... The jet penetrates the skin surface; the locking module's multi-condition safety interlock determination process; when the operator places the skin contact ring against the skin surface, the contact ring compression sensor detects the axial displacement of the contact ring relative to the nozzle tip face in real time; the tilt sensor simultaneously detects the tilt angle of the injection device relative to the direction of gravity; the bioimpedance spectrum sensing front end continuously monitors the signal quality at each frequency point during its frequency sweep excitation process, and outputs a valid data flag only when the signal-to-noise ratio at all frequency points exceeds a preset threshold; the processing module outputs a calculation completion flag after completing optimization iterations. At this time, the electronic safety interlock circuit of the locking module simultaneously collects the above four signals—whether the compression is within the preset appropriate contact pressure range, whether the tilt angle is within the range of ±15 degrees from the normal direction of the skin surface, whether the valid data flag is true, and whether the calculation completion flag is true—and performs AND logic determination. When any of the above locking conditions are not met, the electronic safety interlock circuit controls the mechanical locking mechanism to remain locked, preventing the drive module from outputting any current to the voice coil motor; the electronic safety interlock circuit releases the locking state of the mechanical locking mechanism and allows the drive process to start only when all conditions are met simultaneously.During the entire spraying process, if any condition changes abruptly before spraying is completed (e.g., tilt angle exceeding limits due to operator shaking), the locking module immediately restarts locking and interrupts current output, achieving immediate safety interruption of the spraying process. This is based on the pulse correction strategy implemented using C_ep. When the processing module extracts the value of the active epidermal equivalent capacitance C_ep, it compares this value with multiple pre-stored threshold intervals. When the C_ep value falls into the first interval indicating high skin hydration, the processing module reduces the current amplitude of the second pulse to 80% of the original calculated value and extends the duration of the second pulse to 1.2 times the original calculated value to compensate for the deceleration effect of highly hydrated skin on the microjets. When the C_ep value falls into the second interval indicating dry skin, the processing module... The amplitude of the second pulse current is increased to 1.1 times the original calculated value, while the duration remains unchanged. When the C_ep value exceeds the preset normal range, the processing module refuses to generate the driving waveform sequence and sends a "skin condition is abnormal, it is recommended to change the injection site" prompt message to the operator via the human-machine interface. Typical implementation process of the dual-pulse waveform sequence: In a typical implementation scenario, the processing module generates a driving current waveform sequence containing two pulses: the first pulse is a rectangular wave with amplitude I1 and duration τ1, designed to generate kinetic energy sufficient to penetrate the stratum corneum but insufficient to enter the active epidermis; during the time interval Δt after τ1 ends, the processing module does not output any current. At this time, the voice coil motor pulls the plunger back to the initial position by means of a mechanical return spring, and the drug solution in the injection chamber is refilled. After the time interval Δt ends, the processing module dynamically calculates the amplitude I2 and duration τ2 of the second pulse based on the impedance spectrum change after the actual application of the first pulse (obtained by rapid measurement by the bioimpedance spectrum sensing front end within the time interval); the I2 is designed to be greater than I1 to generate kinetic energy sufficient to penetrate the active epidermis and deliver the drug solution to the dermis. After the second pulse is completed, the bioimpedance spectrum sensing front end measures the impedance spectrum at the injection site again, compares it with the baseline value before injection to assess the actual delivery depth, and feeds back the assessment result to the operator through the human-machine interface. This constitutes a complete closed-loop system of "perception-decision-drive-safety".Its overall advantages are as follows: First, through the optimized algorithm of the bioimpedance spectroscopy sensing front-end and processing module, real-time, non-invasive quantitative characterization of the layered electrical properties of the skin at the injection site is achieved, overcoming the shortcomings of traditional single-frequency or few-frequency impedance measurements that cannot distinguish the sublayer structure of the skin, thus providing a dual basis for the adjustment of driving parameters from both anatomical and physical perspectives. Second, by mapping the stratum corneum resistance, active epidermal capacitance, and dermal resistance to the amplitude, duration, and interval of different pulses in the pulse sequence, precise staged control of the penetration process is achieved, ensuring that the first pulse is responsible for breaking through the stratum corneum barrier, and the second and subsequent pulses are responsible for... The system ensures deep delivery, avoiding potential splashing or excessive penetration of medication that might result from a single strong pulse. Furthermore, a multi-condition safety interlock mechanism integrates contact state, posture angle, impedance data validity, and parameter calculation completion into a unified hardware-level enable signal, ensuring that the injection is released only under optimal conditions, fundamentally eliminating false triggering and inappropriate injection. Finally, the entire system operates on a closed-loop control system from impedance acquisition to current output, dynamically adjusting subsequent pulses based on real-time skin response within the same injection action. This significantly improves the consistency and reliability of needle-free injection delivery across different individuals, sites, and skin conditions.

[0022] Please refer to the details. Figure 1 The processing module extracts R_sc, C_ep, and R_de using the following objective function: ; Where n is the number of sweep frequency points, ωi is the i-th sweep angular frequency, Zm(ωi) is the measured impedance magnitude, and Ze(ωi) is the theoretical impedance magnitude of the equivalent circuit model; the processing module also includes a feedforward neural network classifier, which takes the impedance magnitude, phase angle, real impedance, and imaginary reactance of the broadband impedance spectrum after time difference as input, and outputs skin layer classification labels to set the initial values ​​of the optimization algorithm.

[0023] In this embodiment: during the extraction of stratum corneum resistance, active epidermal capacitance, and dermal resistance values ​​by the processing module, the processing module constructs the following objective function based on all frequency point data obtained from frequency sweep measurement: minimizing the sum of the squares of the differences between the measured impedance magnitude and the theoretical impedance magnitude of the equivalent circuit model over all scanned frequency points, where the theoretical impedance magnitude is calculated by the skin layer equivalent circuit model based on the currently adjusted resistance and capacitance parameters; by iteratively optimizing this objective function to its minimum value, the optimal stratum corneum resistance, active epidermal capacitance, and dermal resistance values ​​can be obtained. Simultaneously, the processing module also integrates a feedforward neural network classifier. This classifier takes the impedance magnitude, phase angle, real impedance, and imaginary reactance from the broadband impedance spectrum (after time-difference processing) as input, and outputs a skin layer classification label after forward propagation calculation. This classification label is used to set the initial iteration value of the above optimization algorithm, allowing the optimization algorithm to start searching from an initial point closer to the true solution, thereby accelerating the convergence speed and avoiding getting trapped in local minima.

[0024] Please refer to the details. Figure 1 In the driving current waveform sequence, the current amplitude of the first pulse is higher than that of the second pulse, the duration of the first pulse is shorter than that of the second pulse, and the time interval between the two pulses is 0.5ms to 5ms; the numerical value of R_sc is linearly mapped to the multiplication factor of the current amplitude of the first pulse, and the numerical value of C_ep is linearly mapped to the multiplication factor of the duration of the second pulse.

[0025] In this embodiment: In the specific construction of the driving current waveform sequence, the waveform sequence generated by the processing module includes at least a first pulse and a second pulse. The current amplitude of the first pulse is set to be higher than that of the second pulse, and the duration of the first pulse is set to be shorter than that of the second pulse. The time interval between the first pulse and the second pulse is set to be within the range of 0.5 milliseconds to 5 milliseconds. Regarding the quantitative mapping relationship between amplitude and time, the processing module maps the extracted stratum corneum resistance value to a multiplier of the first pulse current amplitude according to a linear proportional relationship. That is, the higher the stratum corneum resistance value, the larger the multiplier, enabling the first pulse to drive the voice coil motor with a stronger instantaneous current to generate a greater impact force, thereby effectively penetrating the high-impedance stratum corneum barrier. Simultaneously, the processing module maps the extracted active epidermal capacitance value to a multiplier of the second pulse duration according to a linear proportional relationship. That is, the larger the active epidermal capacitance value, the larger the multiplier, enabling the second pulse to maintain the electroporation effect for a longer duration, ensuring that the microjets fully penetrate the active epidermal layer and are accurately deposited to the target delivery layer.

[0026] Please refer to the details. Figure 1The locking conditions include: the output value of the contact ring compression sensor is lower than the contact threshold, the output value of the tilt sensor exceeds the preset angle range, the valid data output terminal is invalid, and the calculation completion flag output terminal is incomplete; when any condition is met, the electronic safety interlock circuit controls the mechanical locking mechanism to lock the trigger button.

[0027] In this embodiment: when the locking module performs a safety interlock determination, the electronic safety interlock circuit has multiple preset independent criteria. The locking conditions specifically include: when the compression value output by the contact ring compression sensor is lower than a pre-stored skin adhesion threshold, it indicates that the skin contact ring and the injection site have not formed an effective fit; when the device attitude angle output by the tilt sensor exceeds a preset safe injection angle range, it indicates that the tilt of the injection device relative to the skin normal is too large, which may lead to jet deflection or delivery depth deviation; when the effective data output terminal of the bioimpedance spectrum sensing front end is invalid, it indicates that the current impedance spectrum data has not been effectively acquired or the data quality is unreliable; when the calculation completion flag output terminal of the processing module is incomplete, it indicates that the driving current waveform sequence has not been fully generated or the parameter extraction process is still in progress. When any of the above four conditions is determined to be met by the electronic safety interlock circuit, the electronic safety interlock circuit immediately outputs a locking control signal to the mechanical locking mechanism. The mechanical locking mechanism then mechanically jams the pressing stroke of the trigger button, preventing the operator from starting the injection sequence by pressing the trigger button. Only when all of the above conditions are not met simultaneously will the electronic safety interlock circuit release the lock on the trigger button, allowing the operator to press the trigger button to start the drive module to perform current output.

[0028] Please refer to the details. Figure 1 The bioimpedance spectrum sensing front end is restarted after injection, outputting the frequency sweep excitation signal to the injection area and generating a broadband impedance spectrum after injection; the processing module calculates the change in impedance modulus at characteristic frequency points between the impedance spectrum after injection and the impedance spectrum before injection as a delivery depth deviation value and stores it, and superimposes the deviation value onto the target penetration depth during the next injection to adjust the amplitude of each pulse current.

[0029] In this embodiment: After the needle-free injection system completes an injection operation, the processing module sends a post-injection frequency sweep start command to the bioimpedance spectrum sensing front end. The bioimpedance spectrum sensing front end again outputs a frequency sweep excitation signal with a frequency range of 100 Hz to 10 MHz to the skin in the injection area, and collects the response voltage at each frequency. After internal analog front end conditioning and analog-to-digital conversion, a post-injection broadband impedance spectrum is generated. After receiving the post-injection broadband impedance spectrum, the processing module calculates the difference between the post-injection impedance spectrum and the impedance spectrum stored before injection at preset characteristic frequency points. The change in impedance magnitude is quantified by the processing module as a delivery depth offset. The difference, i.e., when the change in impedance modulus is large, indicates that the actual deposition depth of the drug solution is offset from the target depth. This offset is stored in the non-volatile memory inside the processing module in numerical form. When calculating parameters for the next injection operation, the processing module automatically incorporates the stored delivery depth deviation value into the final value of the target penetration depth by superimposing it when calling the physical formula to calculate the target penetration depth. Based on the corrected target penetration depth, the current amplitude of each pulse in the driving current waveform sequence is readjusted, thereby realizing closed-loop compensation for the delivery depth drift caused by tissue fatigue, local edema, or drug accumulation effect during multiple injections of the same subject.

[0030] Please refer to the details. Figure 1 The nozzle is a gemstone microporous nozzle or a ceramic microporous nozzle. The converging internal flow channel tapers from the inlet end to the outlet end in a conical shape with a cone angle of 30° to 60°. The outlet end is a straight section with a length of straight section to outlet diameter ratio of 1:1 to 3:1. The skin contact ring is a flexible medical silicone ring with an annular flange on its front end face. The electrode surfaces of the four electrodes are flush with or 0.05 mm to 0.2 mm higher than the top surface of the annular flange.

[0031] In this embodiment: the nozzle is a sapphire microporous nozzle or a ceramic microporous nozzle. Its internal converging inner cavity flow channel tapers from the inlet end to the outlet end in a conical shape with a cone angle of 30 to 60 degrees, so that the liquid can be accelerated smoothly and efficiently during the flow process, avoiding energy loss caused by turbulence; the outlet end is set as a straight hole section, and the ratio of the length of the straight hole section to the outlet hole diameter is set to 1:1 to 3:1. This ratio range ensures the flow stream shaping effect of the high-speed microjet before it is ejected, so that it has better focusing and penetration consistency. Meanwhile, the skin contact ring is made of flexible medical silicone, with an annular flange on its front end. When pressed, the annular flange preferentially contacts the skin and deforms, achieving a tight fit with the skin surface and increasing sealing and comfort. The electrode surfaces of the four electrodes are configured to be flush with the top surface of the annular flange, or 0.05 mm to 0.2 mm higher than the top surface. This height difference ensures that the electrodes can still stably penetrate the superficial keratin layer of the skin surface and establish reliable electrical contact after the skin contact ring is deformed by pressure. This avoids poor contact caused by the electrodes sinking too deeply into the silicone, and also prevents discomfort or scratch risk caused by electrodes that are too high.

[0032] Please refer to the details. Figure 1 A programmable waveform sequence intelligent layered delivery needle-free injection method based on bioimpedance spectroscopy technology includes: S1: A four-electrode bioimpedance spectroscopy sensing front end integrated on the skin contact ring at the nozzle front end outputs a swept frequency excitation signal with a frequency range of 100Hz to 10MHz and a current amplitude ≤100μA to the skin at the injection site, measures the voltage response at each frequency point and calculates the impedance modulus and phase angle to generate a broadband impedance spectrum; S2: The broadband impedance spectrum is input into the processing module. The processing module calls a pre-stored skin layer equivalent circuit model and adjusts the parameter values ​​of the stratum corneum resistance R_sc and capacitance C_sc, active epidermal resistance R_ep and capacitance C_ep, and dermal and subcutaneous tissue resistance R_de in the model through an optimization algorithm to minimize the following objective function: min ∑i=1n[Zm(ωi)−Ze(ωi)]2min∑i=1n[Zm(ωi)−Ze(ωi)]2 Extract the optimized R_sc and C_ep values; S3: Determine the target penetration depth D based on the target delivery level, and sequentially perform the following operations to generate the drive current waveform sequence: D = k·ρ·v²·τ / E, v = C_d·sqrt[2(P_c - P_0) / ρ], I = P_c·A / (BL), Using R_sc as the multiplier coefficient for the amplitude of the first pulse current and C_ep as the multiplier coefficient for the duration of the second pulse, a data packet containing the first pulse, the time interval, and the second pulse is generated. S4: When all locking conditions are met, the unlock trigger button is released. The locking conditions include the contact ring compression being greater than or equal to the fitting threshold, the tilt angle being within a preset range, the processing module having completed waveform calculation, and the system being fault-free. After triggering, the programmable servo driver outputs current to the moving coil of the voice coil motor according to the drive current waveform sequence, causing the moving coil to generate multiple axial thrust pulses in the permanent magnet stator magnetic field in sequence. These pulses are then transmitted through the transmission rod and plunger to eject multiple jet pulses of the liquid from the nozzle in sequence.

[0033] In this embodiment: Step S1 involves frequency sweeping excitation and impedance spectrum acquisition. When the operator presses the four-electrode bioimpedance spectrum sensing front end integrated on the skin contact ring at the nozzle tip onto the skin surface of the injection site, the bioimpedance spectrum sensing front end automatically starts the frequency sweeping excitation program. This program outputs frequency sweeping excitation signals with a frequency range of 100 Hz to 10 MHz and a current amplitude not exceeding 100 microamps to the outer current injection electrode on the skin contact ring according to a preset logarithmic frequency sequence. During the output at each frequency point, the bioimpedance spectrum sensing front end continuously acquires the response voltage signal of the skin surface through the inner voltage pickup electrode, and calculates the impedance modulus and phase angle at that frequency point after internal differential amplification, filtering, and analog-to-digital conversion. After all preset frequency points have been scanned and measured, the bioimpedance spectrum sensing front end organizes the impedance modulus and phase angle corresponding to each frequency point into broadband impedance spectrum data for subsequent steps. Step S2 involves the extraction of parameters from the skin layer equivalent circuit model. After receiving the broadband impedance spectrum data, the processing module calls the internally stored skin layer equivalent circuit model. This model is composed of parallel branches of stratum corneum resistance and capacitance, parallel branches of active epidermal resistance and capacitance, and branches of dermal and subcutaneous tissue resistance. The processing module aims to minimize the difference between the theoretical impedance spectrum of the model and the impedance spectrum obtained by actual measurement in step S1. It constructs an objective function to minimize the sum of squares of the differences between the measured impedance magnitude and the theoretical impedance magnitude at all scanning frequency points, and uses an iterative optimization algorithm to optimize and adjust the parameter values ​​of each component in the model. When the objective function converges to the minimum value, the processing module extracts the stratum corneum resistance value and active epidermal capacitance value from the optimization result as the core basis for subsequent waveform customization. Step S3 is the process of generating the drive current waveform sequence. After the processing module obtains the stratum corneum resistance value and the active epidermal capacitance value, it determines the corresponding target penetration depth based on the target delivery layer pre-selected by the user. Subsequently, the processing module performs the following calculations in sequence: First, it determines the required jet velocity based on the relationship between the target penetration depth, drug density, jet velocity, pulse duration, and jet kinetic efficiency coefficient. Second, it calculates the theoretical driving pressure difference corresponding to the jet velocity based on the voice coil motor driving pressure difference and drug density. Then, it calculates the required base current value based on the driving pressure difference, voice coil motor thrust constant, and effective coil length. After completing the above basic parameter calculations, the processing module uses the extracted stratum corneum resistance value as the multiplier coefficient of the first pulse current amplitude and the extracted active epidermal capacitance value as the multiplier coefficient of the second pulse duration. It then multiplies these two coefficients by the base current value and the base duration value, respectively, to finally generate a complete driving current waveform sequence containing the first pulse, time interval, and second pulse. This sequence is then packaged into a data package for later use. Step S4: Determining the locking condition and the multi-pulse driven injection process; Before triggering the injection action, the electronic safety interlock circuit monitors and logically determines multiple locking conditions in real time: If the compression value fed back by the contact ring compression sensor is greater than or equal to a pre-stored contact threshold, the contact condition is deemed satisfied; otherwise, it is not satisfied. If the device tilt angle fed back by the tilt sensor is within a preset safety angle range, the attitude condition is deemed satisfied; otherwise, it is not satisfied. If the processing module has completed the waveform calculation in step S3 and the internal self-test status register indicates that the system is fault-free, the calculation and status conditions are deemed satisfied; otherwise, they are not satisfied. Only when all the above locking conditions are simultaneously satisfied will the electronic safety interlock circuit release the trigger button. Locked, allowing the operator to press the trigger button to start the injection; after triggering, the programmable servo driver outputs current of corresponding waveforms to the moving coil of the voice coil motor in sequence according to the instructions of the drive current waveform sequence data packet. The moving coil sequentially generates multiple axial thrust pulses in the magnetic field provided by the permanent magnet stator. The thrust pulses are transmitted to the plunger through the transmission rod, pushing the plunger forward in the injection chamber in sequence, so that the liquid medicine is ejected from the nozzle in multiple jet pulses in sequence. The first pulse breaks through the stratum corneum with a higher amplitude but a shorter duration. After a time interval, the second pulse delivers the liquid medicine to the target layer with a lower amplitude but a longer duration, completing intelligent layered delivery.

[0034] Please refer to the details. Figure 1In step S2, before optimization, the processing module first performs time difference analysis on the impedance magnitude, phase angle, real impedance and imaginary reactance of the broadband impedance spectrum and inputs them into the feedforward neural network classifier to obtain skin layer classification labels. Then, based on the classification labels, it reads the initial optimization values ​​of each parameter in the equivalent circuit model from the pre-stored mapping table and executes the optimization algorithm starting from the initial values.

[0035] In this embodiment: during the parameter extraction process in step S2, before initiating iterative optimization, the processing module first performs feature preprocessing on the broadband impedance spectrum data: the processing module calculates the first-order difference values ​​of impedance magnitude, phase angle, real impedance, and imaginary reactance between adjacent frequency points, forming a feature vector containing the difference features; this feature vector is input to a pre-trained feedforward neural network classifier inside the processing module, and after forward propagation calculation through the input layer, several hidden layers, and the output layer, the classifier outputs a skin layer classification label, which indicates the stratum corneum thickness level and active epidermal electrical property category of the skin at the current injection site; subsequently... The processing module retrieves a pre-stored mapping table based on the classification label. This mapping table pre-stores recommended combinations of optimized initial values ​​for each parameter in the equivalent circuit model, including stratum corneum resistance, stratum corneum capacitance, active epidermal resistance, active epidermal capacitance, and dermal resistance, for each skin layer classification label. After reading this set of initial values, the processing module uses them as the starting point for the iteration of the optimization algorithm. It then performs subsequent iterations to minimize the sum of squared errors between the measured impedance spectrum and the theoretical impedance spectrum of the model. This allows the optimization process to start searching from a region closer to the true solution, significantly reducing the number of iterations and avoiding the risk of getting trapped in local minima due to excessive deviation of the initial values.

[0036] Please refer to the details. Figure 1 Following step S4, step S5 is further included: the bioimpedance spectrum sensing front-end is restarted, outputting the frequency sweep excitation signal to the injection area and generating a broadband impedance spectrum after injection; the processing module calculates the difference in impedance modulus between the post-injection impedance spectrum and the impedance spectrum in S1 at characteristic frequency points, extracts the first difference in the low-frequency band of 100Hz to 1kHz as an estimate of the total drug volume, extracts the second difference in the high-frequency band of 1MHz to 10MHz as an estimate of the drug deposition depth, and weights the first difference and the second difference to convert them into a delivery depth deviation value for storage; when generating the driving current waveform sequence for the next injection, the processing module superimposes the deviation value onto the target penetration depth.

[0037] In this embodiment: after the injection action in step S4 is completed, the method further includes the post-injection impedance spectrum feedback and delivery depth deviation correction process in step S5. When the injection is completed and the plunger stops advancing, the processing module sends a restart command to the bioimpedance spectrum sensing front end. The bioimpedance spectrum sensing front end outputs the frequency sweep excitation signal with a frequency range of 100 Hz to 10 MHz and a current amplitude of no more than 100 microamps to the skin of the injected area again, and collects the response voltage at each frequency point. After conditioning and analog-to-digital conversion by the internal analog front end, a broadband impedance spectrum after injection is generated. The processing module calculates the impedance modulus difference between the post-injection broadband impedance spectrum and the pre-injection broadband impedance spectrum stored in step S1 at the same set of characteristic frequency points. Based on this, the processing module performs hierarchical analysis of the impedance modulus difference according to the frequency dimension: in the low-frequency band of 100 Hz to 1 kHz, since the low-frequency current mainly flows along the extracellular fluid path and is sensitive to changes in the total amount of fluid in the tissue, the processing module extracts a first difference from this frequency band as an estimate of the total drug volume, reflecting the total volume of drug injected into the skin; in the high-frequency band near 10 MHz, since the high-frequency current mainly penetrates the cell membrane and is affected by the tissue dielectric properties, it is sensitive to the depth and location of drug deposition, the processing module extracts a second difference from this frequency band as an estimate of the drug deposition depth, reflecting the actual depth of the drug jet. Subsequently, the processing module multiplies the first and second differences by preset weighting coefficients and sums them to convert them into a delivery depth deviation value. This weighting coefficient is obtained through prior ex vivo skin experiments and is used to balance the contributions of both total volume and depth dimensions to the deviation estimation. This delivery depth deviation value is stored in the non-volatile memory within the processing module and associated with the current subject's identity. When generating the driving current waveform sequence for the next injection, the processing module automatically adds the stored delivery depth deviation value to the target penetration depth when calculating the target penetration depth using physical formulas. This adjusts the pulse amplitude and duration of the next injection accordingly, thereby achieving closed-loop adaptive compensation for dynamic changes such as local tissue edema, drug accumulation, or tissue fatigue caused by multiple injections in the same subject, ensuring that the delivery depth of subsequent injections always remains consistent with the target layer.

[0038] Please refer to the details. Figure 1 A programmable waveform sequence intelligent hierarchical delivery needle-free injection control device based on bioimpedance spectroscopy technology includes a digital signal processor and a memory storing firmware programs. The firmware programs include: impedance spectrum acquisition control instructions, used to control the frequency sweep excitation output and voltage response acquisition of the bioimpedance spectroscopy sensing front end, and generate broadband impedance spectrum data containing impedance magnitude sequences and phase angle sequences. The equivalent circuit fitting instruction is used to solve for the parameter values ​​of R_sc, C_ep and R_de in the equivalent circuit model by taking the broadband impedance spectrum data as input and using the Levenberg-Marquardt algorithm. In the model, the stratum corneum is represented by R_sc and C_sc in parallel, the active epidermis is represented by R_ep and C_ep in parallel, and the dermis and subcutaneous tissue are represented by R_de. The waveform sequence calculation instruction is used to perform arithmetic operations of D = k·ρ·v²·τ / E, v = C_d·sqrt[2(P_c - P_0) / ρ] and I = P_c·A / (BL) in sequence according to the target delivery level and R_sc, C_ep, and R_de, and map R_sc to the first pulse current amplitude multiplier coefficient and C_ep to the second pulse duration multiplier coefficient to generate drive current waveform sequence data containing at least two pulses; The locking judgment command is used to read the digital values ​​of the contact ring compression sensor, the tilt sensor, and the system fault flag. When the compression is greater than or equal to the contact threshold, the tilt is within the preset angle range, and there is no fault flag, the unlocking level is output to the mechanical locking mechanism. A pulse output command is used to send the drive current waveform sequence data to the programmable servo driver in a time-based manner when a trigger button signal is received and the unlock level has been output.

[0039] In this embodiment: the execution process of the impedance spectrum acquisition control command; After the digital signal processor is powered on, reset, and initialized, the impedance spectrum acquisition control command first sends a sweep parameter configuration word to the bioimpedance spectrum sensing front end. This configuration word includes a start frequency of 100 Hz, an end frequency of 10 MHz, a frequency stepping mode of logarithmic stepping, and an excitation duration for each frequency point. Subsequently, the impedance spectrum acquisition control command starts a sweep output loop, synchronously triggering the analog-to-digital converter to acquire the response signal of the voltage pickup electrode at each frequency point, and calling the internal complex number operation unit to calculate the impedance magnitude and phase angle at that frequency point. After all frequency points are scanned, the impedance spectrum acquisition control command arranges the impedance magnitudes of each frequency point into an impedance magnitude sequence according to frequency order, and arranges each phase angle into a phase angle sequence. The two together constitute broadband impedance spectrum data and are stored in the data buffer in the memory. The execution process of the equivalent circuit fitting instruction; When valid broadband impedance spectrum data already exists in the data buffer, the equivalent circuit fitting instruction reads the impedance magnitude sequence and the corresponding frequency sequence from the data buffer. Simultaneously, it calls the internally stored structural parameters of the skin layer equivalent circuit model. In this model, the stratum corneum is defined as a parallel branch of resistance and capacitance, the active epidermis is defined as a parallel branch of resistance and capacitance, and the dermis and subcutaneous tissue are defined as a single resistance branch. The equivalent circuit fitting instruction aims to minimize the sum of squared residuals between the theoretical and measured impedance magnitudes of the model. It uses the Levenberg-Marquardt algorithm to iteratively optimize the parameters of each component in the model. Each iteration requires recalculating the theoretical impedance spectrum of the model under the current parameter combination and comparing it with the measured spectrum. When the iteration converges, the equivalent circuit fitting instruction extracts the stratum corneum resistance value, the active epidermal capacitance value, and the dermal resistance value from the optimal parameter combination and stores these three values ​​in a designated register for use by subsequent instructions. The execution process of waveform sequence calculation instructions; Once the stratum corneum resistance value, the active epidermal capacitance value, and the dermal resistance value are all effectively stored in the register, the waveform sequence calculation instruction reads the user-preset target delivery layer parameters and calls the internal arithmetic logic unit to perform the following operations in sequence: calculate the required jet velocity based on the physical relationship between the target penetration depth, drug density, jet velocity, pulse duration, and jet kinetic efficiency coefficient; calculate the theoretical driving pressure difference corresponding to the jet velocity based on the voice coil motor driving pressure difference and drug density; then calculate the required basic current value based on the driving pressure difference, voice coil motor thrust constant, and effective coil length; after completing the above basic operations, the waveform sequence calculation instruction uses the stratum corneum resistance value as the multiplier coefficient of the first pulse current amplitude and the active epidermal capacitance value as the multiplier coefficient of the second pulse duration, multiplying them by the basic current value and the basic duration value respectively, and finally generating a driving current waveform sequence data containing the first pulse, time interval, and second pulse, and packing the sequence data into a data packet and storing it in the waveform output buffer; The execution process of the lock-in judgment instruction; During and after the execution of the waveform sequence calculation instruction, the locking judgment instruction cyclically reads the digital output of the contact ring compression sensor, the digital output of the tilt sensor, and the status bit of the system fault flag register at a fixed time period. The locking judgment instruction compares the digital value of the compression with the internally stored contact threshold. When the compression is greater than or equal to the contact threshold, the contact condition is determined to be true. The tilt digital value is compared with the internally stored upper and lower limits of the safe angle range. When the tilt is within the preset angle range, the attitude condition is determined to be true. The system fault flag is read. When no fault flag is set, the system status condition is determined to be true. Only when all three conditions are true, the locking judgment instruction outputs an unlocking level to the drive port of the mechanical locking mechanism, causing the mechanical latch of the trigger button to release. If any condition is not met, the locking judgment instruction continues to output a locking level to maintain the mechanically locked state of the trigger button. The execution process of the pulse output command; When the trigger button is pressed by the operator to generate a trigger button signal, the pulse output command first checks whether the unlock level of the lock judgment command has been effectively output. If the unlock level is effective, the pulse output command, according to the time beat parameters in the drive current waveform sequence data packet, sequentially sends the digital value of the current amplitude of each pulse to the input register of the programmable servo driver in chronological order at a preset timer interrupt beat. The transmission time of each data point is strictly aligned with the time axis coordinates in the waveform sequence. After the complete sequence is sent, the pulse output command sends an output enable signal to the programmable servo driver, driving it to execute closed-loop current output according to the received current command sequence, thereby driving the voice coil motor to generate a corresponding axial thrust pulse sequence, completing the precise time-domain output of the drive current waveform sequence.

[0040] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A programmable waveform sequence intelligent layered delivery needle-free injection system based on bioimpedance spectroscopy, characterized in that: include: The bioimpedance spectrum sensing front end is integrated on the skin contact ring at the front end of the nozzle of the needleless injection device. It has a four-electrode symmetrical layout. The two outer electrodes are current injection electrodes and the two inner electrodes are voltage pickup electrodes. It outputs an excitation signal with a frequency range of 100Hz to 10MHz and a current amplitude ≤100μA to the skin at the injection site in a frequency sweep mode. The output is a broadband impedance spectrum containing the impedance modulus and phase angle at each frequency. The processing module, whose input is coupled to the output of the bioimpedance spectrum sensing front end, pre-stores a skin layer equivalent circuit model. In the model, the stratum corneum is a parallel branch of resistor R_sc and capacitor C_sc, the active epidermis is a parallel branch of resistor R_ep and capacitor C_ep, and the dermis and subcutaneous tissue are a branch of resistor R_de. The processing module adjusts the model parameters through an optimization algorithm to minimize the error between the model impedance spectrum and the measured impedance spectrum in order to extract the values ​​of R_sc, C_ep, and R_de. Based on the values ​​of R_sc, C_ep, and R_de and the target delivery layer, the processing module calculates the pulse parameters in the driving current waveform using the following formula: D = k·ρ·v²·τ / E, v = C_d·sqrt[2(P_c - P_0) / ρ], I = P_c·A / (BL), R_sc is mapped to the first pulse current amplitude adjustment coefficient, and C_ep is mapped to the second pulse duration and current amplitude adjustment coefficient, generating a drive current waveform sequence containing at least two pulses with a time interval between adjacent pulses; The drive module includes a programmable servo driver, which receives the drive current waveform sequence as a current command and controls the output current to track the command through a closed-loop current loop control. A voice coil motor has a permanent magnet stator and a moving coil, wherein the moving coil generates an axial Lorentz force when current is applied to it. The transmission rod connects the mover of the voice coil motor to the plunger; The injection chamber contains the plunger, which slides within it to form a sealing pair, and its front end is connected to the nozzle. The nozzle has a converging internal flow channel and an outlet orifice diameter of 50μm to 300μm, and the skin contact ring is located at the front end of the nozzle; The locking module includes a mechanical locking mechanism and an electronic safety interlock circuit. The input terminal of the electronic safety interlock circuit is connected to a contact ring compression sensor, an inclination sensor, the effective data output terminal of the bioimpedance spectrum sensing front end, and the calculation completion flag output terminal of the processing module. When any locking condition is not met, the mechanical locking mechanism is controlled to be in a locked state.

2. The programmable waveform sequence intelligent hierarchical delivery needle-free injection system based on bioimpedance spectroscopy technology according to claim 1, characterized in that: The processing module extracts R_sc, C_ep, and R_de using the following objective function: ； Where n is the number of sweep frequency points, ωi is the i-th sweep angular frequency, Zm(ωi) is the measured impedance magnitude, and Ze(ωi) is the theoretical impedance magnitude of the equivalent circuit model; the processing module also includes a feedforward neural network classifier, which takes the impedance magnitude, phase angle, real impedance, and imaginary reactance of the broadband impedance spectrum after time difference as input, and outputs skin layer classification labels to set the initial values ​​of the optimization algorithm.

3. The programmable waveform sequence intelligent hierarchical delivery needle-free injection system based on bioimpedance spectroscopy technology according to claim 2, characterized in that: In the driving current waveform sequence, the current amplitude of the first pulse is higher than that of the second pulse, the duration of the first pulse is shorter than that of the second pulse, and the time interval between the two pulses is 0.5ms to 5ms; the numerical value of R_sc is linearly mapped to the multiplication factor of the current amplitude of the first pulse, and the numerical value of C_ep is linearly mapped to the multiplication factor of the duration of the second pulse.

4. The intelligent layered delivery needle-free injection system based on bioimpedance spectroscopy technology with programmable waveform sequences, as described in claim 3, is characterized in that: The locking conditions include: the output value of the contact ring compression sensor is lower than the contact threshold, the output value of the tilt sensor exceeds the preset angle range, the valid data output terminal is in an invalid state, and the calculation completion flag output terminal is in an incomplete state; when any one of the conditions is met, the electronic safety interlock circuit controls the mechanical locking mechanism to lock the trigger button.

5. The intelligent layered delivery needle-free injection system based on bioimpedance spectroscopy technology with programmable waveform sequences, as described in claim 4, is characterized in that: The bioimpedance spectrum sensing front end is restarted after injection, outputting the frequency sweep excitation signal to the injection area and generating a broadband impedance spectrum after injection; the processing module calculates the change in impedance modulus at characteristic frequency points between the impedance spectrum after injection and the impedance spectrum before injection as a delivery depth deviation value and stores it, and superimposes the deviation value onto the target penetration depth during the next injection to adjust the amplitude of each pulse current.

6. The programmable waveform sequence intelligent hierarchical delivery needle-free injection system based on bioimpedance spectroscopy technology according to claim 5, characterized in that: The nozzle is a gemstone microporous nozzle or a ceramic microporous nozzle. The converging internal flow channel tapers from the inlet end to the outlet end in a conical shape with a cone angle of 30° to 60°. The outlet end is a straight section with a length of straight section to outlet diameter ratio of 1:1 to 3:

1. The skin contact ring is a flexible medical silicone ring with an annular flange on its front end face. The electrode surfaces of the four electrodes are flush with and 0.05 mm to 0.2 mm higher than the top surface of the annular flange.

7. A programmable waveform sequence intelligent layered delivery needle-free injection method based on bioimpedance spectroscopy, characterized in that, include: S1: The four-electrode bioimpedance spectrum sensing front end, integrated on the skin contact ring at the nozzle tip, outputs a sweep frequency excitation signal with a frequency range of 100Hz to 10MHz and a current amplitude ≤100μA to the skin at the injection site. It measures the voltage response at each frequency point and calculates the impedance modulus and phase angle to generate a broadband impedance spectrum. S2: The broadband impedance spectrum is input into the processing module. The processing module calls a pre-stored skin layer equivalent circuit model and adjusts the parameter values ​​of the stratum corneum resistance R_sc and capacitance C_sc, active epidermal resistance R_ep and capacitance C_ep, and dermal and subcutaneous tissue resistance R_de in the model through an optimization algorithm to minimize the following objective function: min∑i=1n[Zm(ωi)−Ze(ωi)]2min∑i=1n[Zm(ωi)−Ze(ωi)]2 Extract the optimized R_sc and C_ep values; S3: Determine the target penetration depth D based on the target delivery level, and sequentially perform the following operations to generate the drive current waveform sequence: D = k·ρ·v²·τ / E, v = C_d·sqrt[2(P_c - P_0) / ρ], I = P_c·A / (BL), Using R_sc as the multiplier coefficient for the amplitude of the first pulse current and C_ep as the multiplier coefficient for the duration of the second pulse, a data packet containing the first pulse, the time interval, and the second pulse is generated. S4: When all locking conditions are met, the unlock trigger button is released. The locking conditions include the contact ring compression being greater than or equal to the fitting threshold, the tilt angle being within a preset range, the processing module having completed waveform calculation, and the system being fault-free. After triggering, the programmable servo driver outputs current to the moving coil of the voice coil motor according to the drive current waveform sequence, causing the moving coil to generate multiple axial thrust pulses in the permanent magnet stator magnetic field in sequence. These pulses are then transmitted through the transmission rod and plunger to eject multiple jet pulses of the liquid from the nozzle in sequence.

8. The intelligent layered delivery needle-free injection method based on programmable waveform sequences using bioimpedance spectroscopy technology according to claim 7, characterized in that, include: In step S2, before optimization, the processing module first performs time difference analysis on the impedance magnitude, phase angle, real impedance and imaginary reactance of the broadband impedance spectrum and inputs them into the feedforward neural network classifier to obtain skin layer classification labels. Then, based on the classification labels, it reads the initial optimization values ​​of each parameter in the equivalent circuit model from the pre-stored mapping table and executes the optimization algorithm starting from the initial values.

9. The intelligent layered delivery needle-free injection method based on programmable waveform sequences using bioimpedance spectroscopy technology according to claim 7, characterized in that, include: Following step S4, step S5 is further included: the bioimpedance spectrum sensing front-end is restarted, outputting the frequency sweep excitation signal to the injection area and generating a broadband impedance spectrum after injection; the processing module calculates the difference in impedance modulus between the post-injection impedance spectrum and the impedance spectrum in S1 at characteristic frequency points, extracts the first difference in the low-frequency band of 100Hz to 1kHz as an estimate of the total drug volume, extracts the second difference in the high-frequency band of 1MHz to 10MHz as an estimate of the drug deposition depth, and weights the first difference and the second difference to convert them into a delivery depth deviation value for storage; when generating the driving current waveform sequence for the next injection, the processing module superimposes the deviation value onto the target penetration depth.

10. A programmable waveform sequence intelligent layered delivery needle-free injection control device based on bioimpedance spectroscopy technology, characterized in that, The device includes a digital signal processor and a memory for storing firmware, the firmware containing: impedance spectrum acquisition control instructions for controlling the frequency sweep excitation output and voltage response acquisition of the bioimpedance spectrum sensing front end, generating broadband impedance spectrum data containing impedance magnitude sequences and phase angle sequences; The equivalent circuit fitting instruction is used to solve for the parameter values ​​of R_sc, C_ep and R_de in the equivalent circuit model by taking the broadband impedance spectrum data as input and using the Levenberg-Marquardt algorithm. In the model, the stratum corneum is represented by R_sc and C_sc in parallel, the active epidermis is represented by R_ep and C_ep in parallel, and the dermis and subcutaneous tissue are represented by R_de. The waveform sequence calculation instruction is used to perform arithmetic operations of D = k·ρ·v²·τ / E, v = C_d·sqrt[2(P_c - P_0) / ρ] and I = P_c·A / (BL) in sequence according to the target delivery level and R_sc, C_ep, and R_de, and to map R_sc to the first pulse current amplitude multiplier coefficient and C_ep to the second pulse duration multiplier coefficient, thereby generating drive current waveform sequence data containing at least two pulses; The locking judgment command is used to read the digital values ​​of the contact ring compression sensor, the tilt sensor, and the system fault flag. When the compression is greater than or equal to the contact threshold, the tilt is within the preset angle range, and there is no fault flag, the unlocking level is output to the mechanical locking mechanism. A pulse output command is used to send the drive current waveform sequence data to the programmable servo driver in a time-based manner when a trigger button signal is received and the unlock level has been output.

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