Physico-chemical determination method for diffusion rate of local anesthetic solution in erector spinae muscle fascia plane

Abstract

The application relates to the cross field of basic research of anesthesiology and physical and chemical property test of materials, and discloses a physical and chemical determination method for diffusion rate of local anesthetic liquid on erector spinae muscle fascia plane, which comprises the following steps: a pre-prepared micron-sized anti-slip array structure piston is used to apply pre-tightening force to a porous medium, a non-slip boundary is formed by embedding the medium surface layer, and anisotropic rearrangement of pores is induced; a composite stress of constant reference and periodic modulation superposition is applied to establish a convection and diffusion coupling environment in the medium; complex impedance data are collected through a surface electrode array; and based on frequency response decoupling, a static diffusion coefficient and a dynamic transmission enhancement factor are calculated. In the application, wall slip artifacts in contact measurement are eliminated through micro-texture locking, and micro-pumping effects are restored through a dynamic field, so that the problem that a static model cannot represent nonlinear transmission behavior of a fluid under dynamic stress is solved.

Description

TECHNICAL FIELD

[0001] The application relates to a physicochemical determination method of diffusion rate of local anesthetic solution in erector spinae plane. BACKGROUND

[0002] In modern clinical anesthesia and regional nerve block technology, the fascial space block therapy such as erector spinae plane block is widely used due to its significant analgesic effect. However, in the research and development of anesthetic drugs and clinical quality control links, how to accurately evaluate the diffusion behavior of local anesthetic solution in these restricted anatomic spaces is a key factor to determine the onset time and block range of anesthesia. In the current research and development and quality control links of local anesthetic drugs, the Franz diffusion cell method and the agarose gel plate method are common means to evaluate the diffusion performance of the drug solution. Such methods are based on the isotropic free diffusion physical model, which assumes that the internal pore structure of the medium to be tested is uniformly distributed, the drug solution migrates in all directions with equal and constant resistance, and the standardized test is characterized by stable performance of uniform solution or simple gel matrix. It is the mainstream way to obtain the basic diffusion coefficient of the drug. When the target diffusion environment is converted into a complex physical interface with structural anisotropy and dynamic stress constraints, the static isotropic model has limitations. The simulation of the physical transport process of the erector spinae muscle fascia plane restricted anatomic space is the free Brownian motion of fluid in a non-open space. The fluid is constrained in the interlayer gap composed of dense fibrous connective tissue. The physical gap has two characteristics: one is structural anisotropy, and the diffusion resistance of the fluid along the interlayer gap extension direction is smaller than that in the vertical penetration direction; the other is stress dependence, and the interlayer gap width and micro-pore morphology are regulated by external normal load. The existing standard test method lacks the dynamic control ability of physical boundary conditions, and cannot reproduce the structural non-uniformity induced by stress in the isotropic consumables.

[0003] The existing engineering solutions, even if they are special instruments optimized for this anatomical site, are mostly limited to mechanically assisted drug administration operations, ignoring the decisive influence of the micro fluid dynamics environment on drug distribution. For example, the Chinese invention patent with publication number CN111035439A discloses a nerve block puncture drug injection device. The scheme solves the single-person operation convenience and controllability of the injection rate through a constant-speed infusion assembly and a mechanical buckle design. The technical concept still stays at the level of regarding the human body tissue as a static receiving container. Such a device can control the drug infusion process, but it cannot sense and simulate the periodic pumping effect of the erector spinae muscle fascia plane due to respiratory movement or muscle tension fluctuations, resulting in a mismatch between the set drug injection parameters and the actual anesthetic dynamic diffusion needs in the body. Simply adding a static load to the existing device cannot solve the measurement distortion problem. Only constant pressure is applied, which cannot simulate the pumping effect caused by periodic mechanical movement in the real physical environment, resulting in the omission of transmission gain under the convection and dispersion coupling mechanism. In high-pressure contact measurement, a low-resistance interface slip channel is easily formed between the flat probe surface and the medium, causing the fluid to preferentially leak along the wall surface rather than into the medium interior, resulting in false high measurement data.

[0004] Therefore, how to construct a physical simulation of the stress state of a restricted gap, eliminate boundary slip interference, and decouple the dynamic anisotropic diffusion rate measurement method has become a technical problem to be solved by the present application. SUMMARY

[0005] To solve the problems raised in the background art, the technical solution of the present application is as follows: a physicochemical measurement method for the diffusion rate of local anesthetic solution in the erector spinae muscle fascia plane, the method comprising the following steps:

[0006] Step 101, construct a mechanically interlocked anisotropic constraint boundary, place a standard isotropic porous conductive medium in an insulating test cavity, apply a pre-tightening force to the porous conductive medium along the normal direction using an actuating piston pre-fabricated with a micron-level anti-slip array structure, make the anti-slip array structure completely embedded in the surface layer of the porous conductive medium, physically cut off the tangential fluid leakage channel along the contact interface between the actuating piston and the porous conductive medium, and use the pre-tightening force to cause the micro-pores inside the porous conductive medium to be flattened and rearranged to form anisotropic diffusion channels;

[0007] Step 102, apply a composite stress load, control the actuating piston to apply a composite mechanical pressure stress to the porous conductive medium along the normal direction, the composite mechanical pressure stress is superimposed by a constant reference pressure stress component for setting the porosity of the medium and a periodic modulation pressure stress component for exciting elastic oscillation of the medium skeleton, and a fluid dynamics environment coupled with convection and dispersion is established inside the porous conductive medium;

[0008] Step 103, collect multi-dimensional impedance response data, quantitatively inject the test liquid into the center of the porous conductive medium while maintaining the composite mechanical pressure stress, and synchronously collect the complex impedance space-time evolution data reflecting the migration front of the test liquid under different stress states using the radially distributed surface electrode array;

[0009] Step 104, decouple the calculation of the physicochemical transport index, based on the frequency characteristics of the periodically modulated pressure stress component, perform frequency domain analysis on the complex impedance space-time evolution data, separate out the static diffusion coefficient dominated by Brownian motion, and the dynamic transport enhancement factor induced by periodic pore deformation.

[0010] Preferably, the specific process of separating out the static diffusion coefficient and the dynamic transport enhancement factor in step 104 includes: using a lock-in amplification algorithm to extract the alternating current response component consistent with the frequency of the periodically modulated pressure stress component and the direct current drift component that changes monotonously with time from the complex impedance space-time evolution data; calculating the static diffusion coefficient based on the time-varying slope of the direct current drift component, which represents the molecular diffusion ability of the test liquid in the pore structure defined by the constant reference pressure stress component; calculating the dynamic transport enhancement factor based on the amplitude of the alternating current response component, which represents the convective transport gain of the test liquid in response to the periodic pore deformation.

[0011] Preferably, the anti-slip array structure in step 101 is a rough microstructure formed on the contact end face of the actuating piston by sandblasting process or laser etching process; the arithmetic mean height of the rough microstructure is limited to be greater than the average pore size of the porous conductive medium in the unpressurized state, to ensure that when the pre-tightening force is applied, the skeleton of the porous conductive medium undergoes plastic rheology and fills the gaps of the rough microstructure, forming a fluid-sealed boundary without interfacial slip.

[0012] Preferably, the waveform of the periodically modulated pressure stress component in step 102 is set to a sine wave or a triangle wave, the oscillation frequency is set to a low frequency range of 0.1 Hz to 1.0 Hz, and the oscillation amplitude is controlled to be between 5% and 20% of the constant reference pressure stress component; the combination of the oscillation frequency and the oscillation amplitude is used to induce a periodic volume pumping effect in the anisotropic diffusion channel without damaging the integrity of the skeleton structure of the porous conductive medium.

[0013] Preferably, the surface electrode array in step 103 includes an injection electrode located at the center of the bottom surface of the insulating test chamber, and a plurality of measurement electrodes distributed in concentric circles around the injection electrode; step 103 further includes: measuring the impedance values between electrode pairs at different azimuth angles along the radial direction respectively, and comparing the impedance change rates at different azimuth angles; when the difference in impedance change rate at different azimuth angles is detected to exceed a preset anisotropy threshold, it is determined that a non-uniform stress distribution field has been formed inside the porous conductive medium, and a stress distribution calibration signal is output.

[0014] Preferably, the porous conductive medium is selected from polyacrylamide hydrogel or agarose gel, which has an isotropic pore structure in the unpressurized state; the method further comprises a step of establishing a stress-dependent characteristic curve: by adjusting the magnitude of the constant reference pressure stress component in stages, quantitatively changing the porosity and tortuosity of the porous conductive medium, and recording the corresponding static diffusion coefficient, thereby constructing a functional relationship of the static diffusion coefficient with the external mechanical constraint.

[0015] Preferably, step 104 further comprises calculating an anisotropy ratio , which is calculated as follows: , wherein, is the transverse diffusion coefficient of the drug solution to be tested along the direction perpendicular to the pressure direction of the actuating piston, which is analyzed based on the spatiotemporal evolution data of the complex impedance, is the longitudinal diffusion coefficient of the drug solution to be tested along the direction parallel to the pressure direction of the actuating piston, which is analyzed based on the spatiotemporal evolution data of the complex impedance; is used to quantitatively represent the physical constraint strength of the porous conductive medium on the fluid transmission direction under the action of the composite mechanical pressure stress.

[0016] Preferably, the method for collecting the complex impedance spatiotemporal evolution data in step 103 comprises: using a multi-frequency electrical impedance tomography technology, alternately applying a high-frequency excitation current and a low-frequency excitation current during the injection of the drug solution to be tested; using the impedance response under the high-frequency excitation to represent the volume filling degree of the drug solution to be tested in the pores of the porous conductive medium, using the impedance response under the low-frequency excitation to represent the double-layer polarization effect between the drug solution to be tested and the skeleton of the porous conductive medium, and using the data of the double-layer polarization effect to correct the calculation error of the diffusion rate caused by the interface polarization.

[0017] Preferably, the method further comprises an environmental temperature control step: before step 101 is performed, a constant temperature circulation system integrated in the side wall of the insulation test cavity is started to maintain the temperature environment inside the insulation test cavity at a constant state of 37 degrees Celsius; and during the whole process of steps 102 to 103, the temperature environment is monitored and adjusted in real time to eliminate the thermodynamic influence of temperature fluctuations on the viscosity of the drug solution to be tested and the intensity of diffusion Brownian motion.

[0018] Preferably, the method further comprises a step of establishing a rheological sensitivity fingerprint of the drug solution: for the same drug solution to be tested, steps 102 to 104 are repeatedly performed by changing the frequency and amplitude of the periodically modulated pressure stress component in stages, to construct a response spectrum of the dynamic transmission enhancement factor with the mechanical disturbance parameter; the response spectrum is used to quantitatively represent the nonlinear rheological transmission characteristics of the drug solution to be tested in the dynamic mechanical environment, so as to identify the drug solution formula with specific shear thinning or thixotropic properties.

[0019] Compared with the prior art, the present application has the following advantages:

[0020] 1. In the vertical ridge muscle fascia plane diffusion rate, the standard porous medium surface applies controllable normal compression load, uses mechanical deformation to make the internal micro-pore of the medium flatten and rearrange along the stress direction, does not need to prepare special oriented material, induces specific structural tensor anisotropic diffusion channel in isotropic matrix, physically decouples the influence of medium intrinsic properties and geometric structure on diffusion behavior, makes continuous construction and analysis of vector diffusion model under different compression ratios by adjusting the boundary conditions of external stress field on a single universal test consumable, solves the problem of relying on expensive non-standard pre-prepared microstructure samples for measurement in the prior art when characterizing the fluid transport characteristics in a confined space.

[0021] 2. On the basis of superimposing periodic modulation alternating stress wave on the constant reference stress, a forced vibration and molecular diffusion coexistence complex fluid dynamics environment is constructed in the test domain, the micro-pumping effect is excited in the porous medium skeleton by mechanical wave, the fluid is driven to produce micro-convection migration, the dynamic gain component induced by mechanical disturbance and the static diffusion component driven by concentration gradient are separated from the total impedance signal through frequency domain response analysis, and the nonlinear transmission enhancement characteristics of specific viscosity fluid under the assistance of dynamic mechanical field are identified and quantified.

[0022] 3. A slip-preventing microarray structure is prepared at the stress loading interface, the material elastic-plastic rheological characteristics are used to make the surface layer of the porous medium embedded in the gap between the microarray to form mechanical interlocking, the free fluid leakage channel distributed along the tangential direction of the test probe surface is physically blocked, the fluid tracer line is injected to migrate through the internal pore network of the medium, the wall slip artifact commonly existing in contact rheological or diffusion measurement is eliminated, and the impedance space-time distribution data collected by the electrode array is ensured to reflect the transmission properties of the medium body phase. BRIEF DESCRIPTION OF DRAWINGS

[0023] Fig. 1 The figure is a schematic diagram of the logical flow of the local anesthetic liquid diffusion rate physical and chemical determination method of the application;

[0024] Fig. 2 The figure is a characteristic curve of the dynamic transmission enhancement factor with the change of the modulation frequency and amplitude;

[0025] Fig. 3 The figure is a fishbone principle diagram of the core technical elements and system architecture of the determination method. DETAILED DESCRIPTION

[0026] The detailed description is intended to clearly and completely describe the technical solutions of the application. Obviously, the described embodiments are only part of the embodiments of the application, rather than all the embodiments. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the application.

[0027] This invention provides a physicochemical method for determining the diffusion rate of local anesthetic solutions in the erector spinae fascia plane. It utilizes physical field control technology to reconstruct the structural anisotropy and dynamic stress characteristics of anatomical gaps in an isotropic medium, and combines this with surface array electrode impedance imaging technology to decouple and determine the transport parameters of the anesthetic solution. This method involves constructing mechanically interlocked anisotropic constraint boundaries, placing a standard isotropic porous conductive medium within an insulating test chamber. This porous conductive medium is selected from materials with uniform pore structure under uncompressed conditions, such as agarose gel or polyacrylamide hydrogel with a concentration of 1% to 3%. The insulating test chamber is equipped with an actuating piston, the end face of which in contact with the porous conductive medium has a pre-fabricated micron-level anti-slip array structure, fabricated using sandblasting or laser etching processes. Its arithmetic mean height is limited to being greater than the average pore size of the porous conductive medium, and the arithmetic mean height... The average pore size of the porous conductive medium under unpressurized conditions The ratio is limited to between 1.5 and 2.5 to ensure the mechanical interlock strength while avoiding local shear failure. At the start of the test, the actuating piston is controlled to apply a preload force to the porous conductive medium along the normal direction, causing the surface skeleton of the porous conductive medium to undergo plastic rheology and completely fill the gaps of the anti-slip array structure, forming a fluid closed boundary without interface slippage, physically cutting off the tangential fluid leakage channel along the surface of the actuating piston. At the same time, the preload force causes the micropores inside the porous conductive medium to flatten and rearrange along the direction of force, inducing anisotropic diffusion channels with high diffusion resistance in the vertical direction and low diffusion resistance in the horizontal direction.

[0028] After establishing the aforementioned boundary conditions, the method enters the stage of applying a composite stress load, controlling the actuating piston to apply a composite mechanical compressive stress to the porous conductive medium along the normal direction, based on a constant reference compressive stress component. and periodically modulated compressive stress components It is formed by superposition, among which, Used to simulate basic muscle tension and set the basic porosity of the medium; Used to simulate physiological oscillations caused by breathing or pulsation, in specific implementation, The waveform is set to a sine wave or a triangular wave, with its oscillation frequency set in the low-frequency range of 0.1 Hz to 1.0 Hz, and the oscillation amplitude is controlled within... The composite stress loading between 5% and 20% of the porous conductive medium establishes a convective and diffusive coupled fluid dynamics environment inside the porous conductive medium, utilizes mechanical wave excitation medium skeleton to produce micro pumping effect, eliminates the influence of temperature fluctuation on fluid viscosity and ion mobility, integrates a constant temperature circulation system on the side wall of the insulation test chamber, and maintains the test environment temperature at 37 degrees Celsius; under the condition of maintaining the composite mechanical stress, the local anesthetic liquid to be tested is injected into the center of the porous conductive medium at a constant rate through the micro injection channel penetrating the center of the actuating piston, and the time-space evolution data of the complex impedance are synchronously collected by using the surface electrode array arranged on the bottom surface of the insulation test chamber, the surface electrode array includes an injection electrode at the center and a plurality of measurement electrodes distributed in a concentric circular radial manner around the injection electrode, the collection process adopts a multi-frequency electrical impedance tomography technology, and high-frequency excitation current and low-frequency excitation current are alternately applied to obtain impedance responses reflecting medium body phase resistance and impedance responses reflecting double-layer polarization effect, respectively, and the measurement error caused by electrode interface polarization is corrected by using double-layer polarization data.

[0029] Based on the collected data, the step of decoupling and calculating the physicochemical transport index is performed. Since the applied stress contains a periodic component of a specific frequency, the migration movement of the liquid contains a fluctuation characteristic corresponding thereto, the time-space evolution data of the complex impedance are analyzed in the frequency domain by the processing unit, and two independent components are separated by using a lock-in amplification algorithm: one is an alternating response component consistent with the frequency of the periodic modulation pressure stress component, and the other is a direct current drift component that changes monotonously with time. Based on the time-varying slope of the direct current drift component, the static diffusion coefficient is calculated by using Fick's second law, which represents the Brownian motion ability of the liquid driven by the concentration gradient in the pore structure defined by the constant reference pressure stress. Based on the amplitude of the alternating response component, a dynamic transport enhancement factor is calculated, which quantitatively represents the convective transport gain of the liquid in response to the periodic pore deformation. In addition, by comparing the impedance change rates measured by the electrode pairs at different azimuth angles along the radial direction, the anisotropy ratio , the calculation formula is , wherein is the transverse diffusion coefficient along the direction perpendicular to the pressure direction of the actuating piston, is the longitudinal diffusion coefficient along the direction parallel to the pressure direction of the actuating piston, which is used to quantitatively represent the physical constraint strength of the simulated fascia plane structure on the fluid transport direction under the action of the current composite mechanical stress, and the characteristic diffusion length L is defined as the radial geometric distance between the geometric center of the injection electrode and the first circle of measurement electrodes closest to the center in the surface electrode array.

[0030] Embodiment 1: In the application scenario of preclinical pharmacological screening of long-acting sustained-release local anesthetic preparations in urgent need of clinical anesthesia, the test system faces the objective working condition of predicting the actual diffusion behavior of high-viscosity drug solution in the dynamic anatomical gap of the erector spinae fascial plane. The traditional standard test method based on the static isotropic assumption cannot simulate the physiological mechanical pumping effect and cannot avoid the interface slip interference in the contact measurement, resulting in a deviation between the measured in vitro diffusion data and the clinical onset time. To solve this engineering problem, the standard isotropic porous conductive medium is loaded in the insulating test cavity, and the actuating piston with a micron-level anti-slip array structure pre-prepared on the contact end face is used to apply a normal pre-tightening force to the medium, so that the anti-slip array structure is completely embedded in the medium surface layer to form a mechanically interlocked closed boundary.

[0031] Under the above boundary constraints, the system controls the actuating piston to apply a composite mechanical pressure stress to the medium, which is composed of a constant reference pressure stress component simulating the basis muscle tension and a periodic modulation pressure stress component simulating the human respiratory frequency of 0.3 Hz. Under this dynamic stress environment, the micro-pores inside the medium are forced to produce periodic volume deformation, which is converted into uniform micro-pumping motion inside the medium under the rigid constraint of the anti-slip array structure instead of invalid slip at the interface, thereby establishing a fluid dynamics environment with convection and dispersion coupling inside the medium based on the dynamic properties of the static pore structure in the time dimension. The test drug solution is injected into the center of the medium while maintaining the state of the composite stress field, and the surface electrode array synchronously collects the complex impedance spatio-temporal evolution data. The processing unit then separates the alternating current response component with the same frequency from the total impedance response using a lock-in amplification algorithm, and the amplitude directly quantifies the convective migration ability of the drug solution molecules in response to mechanical pumping, i.e., the dynamic transmission enhancement factor. Experimental data show that after superimposing the dynamic stress, the equivalent diffusion rate of a specific shear-thinning drug solution is increased by 30% to 50% compared to the simple static compression condition.

[0032] ​Example 2: This example verifies the effectiveness of the technical solution of the present application in restoring the dynamic anisotropic diffusion environment and decoupling the determination of the liquid transport parameters in the standard porous medium through a systematic comparative test, and provides empirical support for the key parameter range defined by the anisotropic diffusion environment construction and physicochemical parameter determination logic; the test platform uses a customized stress-controlled diffusion tester, which integrates a force sensor with a resolution of 0.01 Newton, a multi-channel impedance analyzer with a maximum sampling rate of 100 kilohertz, and a circulating water bath system with a temperature control of 0.1 degrees Celsius. The data is derived from the actual measurement of a set of standardized polyacrylamide hydrogel samples. To ensure the statistical significance of the test results, all tests are repeated 5 times under the same environmental conditions, and the data points are averaged. The test design includes the following three logically progressive steps: perform empirical demonstration of parameter boundaries, to verify the reasonableness of the periodic modulation pressure stress component in the composite mechanical pressure stress modulation range of the present application oscillation amplitude is limited to 5% to 20% of the constant reference pressure stress component , set three groups of tests, with the reference pressure stress uniformly set to 5 kilopascals, respectively applying sinusoidal modulation signals with oscillation amplitudes of 2% (out-of-range control group A), 10% (sample group of the present application), and 30% (out-of-range control group B). Table 1 shows the dynamic transport enhancement factor and gel structure integrity data measured under different modulation amplitudes.

[0033] Table 1: Comparison table of transport characteristics and structural responses under different modulation amplitudes

[0034]

[0035] Data shows that when the modulation amplitude is less than 5% (control group A), the dynamic transmission enhancement factor is only 1.02, indicating that weak mechanical disturbance is not enough to induce convection effect; when the modulation amplitude is within the range defined by the application (application sample group), the enhancement factor reaches 1.45, confirming that moderate mechanical pumping can effectively promote drug diffusion; and when the amplitude exceeds 20% (control group B), the enhancement factor decreases to 1.15, accompanied by damage to the gel structure, indicating that excessive stress causes pore collapse or irreversible damage, which confirms that 5% to 20% is the optimal parameter window for achieving non-destructive and efficient pumping; secondly, explicit demonstration of synergistic effect, to reveal the synergistic mechanism of the anti-slip array structure and dynamic stress modulation, an experimental system including partial deletion control groups is constructed, control group C uses a smooth piston to apply dynamic stress (deletion of anti-slip structure), control group D uses a piston with an anti-slip structure to apply static constant stress (deletion of dynamic modulation), and the application sample group has both anti-slip structure and dynamic stress; in the experiment, an equal amount of ropivacaine simulation liquid is injected into the center of each gel, and the lateral diffusion distance is recorded over time, and Table 2 records the diffusion distance and calculated anisotropy ratio of each group at 30 minutes.

[0036] Table 2: Synergistic effect verification test data table

[0037]

[0038] The results show that when only dynamic stress is applied but without anti-slip structure (control group C), the diffusion distance is large but the anisotropy ratio is low ( ), and interface drug leakage is observed, indicating that the fluid mainly leaks along the interface and does not enter the medium interior; only with anti-slip structure but without dynamic modulation (control group D), a high anisotropy ratio is achieved ( ), but the overall diffusion is slow; while the application sample group maintains a high anisotropy ratio ( ), the diffusion distance is better than that of control group D, and the interface leakage phenomenon of control group C does not occur, proving that the anti-slip structure effectively blocks the interface leakage, making the energy excited by dynamic stress completely used to drive the convection diffusion inside the medium, achieving 1+1>2 synergistic effect; finally, the anti-interference ability is verified, to simulate the electromagnetic noise in the real measurement environment, a Gaussian white noise with a signal-to-noise ratio of 20 decibels is artificially introduced into the acquisition circuit, and Table 3 compares the signal quality before and after processing using the multi-frequency impedance tomography and lock-in amplification algorithm of the application.

[0039] Table 3: Comparison of signal processing effect under noise environment

[0040]

[0041] The data intuitively shows that, after the specific signal decoupling and processing flow of the application, the signal-to-noise ratio is improved from 20 decibels to 55 decibels, and the calculation error of the diffusion coefficient is reduced from 18.5% to 2.1%, which confirms that the method of the application can still stably extract the drug solution transmission characteristics in a complex noise environment. Through comparative tests and data analysis, it is confirmed that the application can reasonably set parameters and cooperate with the structure to restore the dynamic anisotropic diffusion environment of the erector spinae muscle fascia plane in vitro.

[0042] Embodiment 3: This embodiment combines Figs. 1 to 3 a physicochemical determination method for the diffusion rate of a local anesthetic drug solution in the erector spinae muscle fascia plane, as shown in Fig. 1 , step 101 is performed to construct a mechanical interlocking constraint boundary, which covers the embedding of an anti-slip array structure into the surface layer and the anisotropic rearrangement of induced pores, and then step 102 is performed to apply a composite stress load, specifically a constant reference stress and a periodic modulation stress superimposed, to establish a fluid dynamics environment. In this process, an auxiliary environmental temperature control step is implemented in parallel to maintain 37°C through a constant temperature circulation system to eliminate thermodynamic effects. Step 103 is entered to collect complex impedance spatiotemporal evolution data, using a surface electrode array for multi-frequency electrical impedance tomography, and completing double-layer polarization correction. Then step 104 is performed for frequency domain analysis and signal decoupling, using a lock-in amplification algorithm to separate signal components. On the one hand, the static diffusion coefficient representing the ability of Brownian motion driven by concentration gradient is calculated through direct current drift component analysis. On the other hand, the dynamic transport enhancement factor representing the convection transport gain induced by periodic pore deformation is calculated through alternating current response component analysis. Finally, the process points to the output of comprehensive physicochemical indicators, specifically the anisotropy ratio R and the drug solution rheological sensitivity fingerprint spectrum.

[0043] As shown in Fig. 2 , the graph presents the quantitative relationship between the dynamic transport enhancement factor and the modulation parameter, where the horizontal axis represents the modulation frequency, and the scale range covers 0.1Hz, 0.3Hz, 0.5Hz, 0.7Hz to 1Hz. The vertical axis represents the dynamic transport enhancement factor. The legend area marks four different test conditions, which are 5% amplitude, 10% amplitude, 15% amplitude, and 20% amplitude. The four corresponding linear curves in the graph depict the specific numerical trajectory and peak value distribution characteristics of the enhancement factor with frequency under different amplitude settings. As shown in Fig. 3The figure systematically combs the technical elements constituting the physicochemical determination method of the diffusion rate of local anesthetic solution in the form of a fishbone diagram. The right arrow of the figure points to the final determination method target. The main body of the figure is divided into four main branches. The physical boundary constraint branch includes micron-level anti-slip array structure, non-slip fluid closed boundary, and anisotropic diffusion channel rearrangement. The kinetic environment construction branch includes composite mechanical pressure stress loading, periodic volume pumping effect, and 37°C constant temperature circulation temperature control. The impedance data acquisition branch includes complex impedance spatiotemporal evolution data, a radial surface electrode array, and multi-frequency electrical impedance tomography. The signal decoupling and calculation branch includes dynamic transmission enhancement factor (AC component), static diffusion coefficient (DC component), and phase-locked amplification algorithm as a frequency domain analysis method.

[0044] Example 4: This example is directed to the lack of specific algorithm path description for the frequency domain decoupling process of multi-dimensional impedance data in the existing disclosure, and the problem of parameter black box in the calculation procedure of static diffusion coefficient and dynamic transmission enhancement factor. A deterministic data analysis and parameter calculation method is provided. In a typical determination scenario, assuming that the system collects original complex impedance spatiotemporal evolution data containing noise , which reflects the migration behavior of the solution under the action of composite mechanical pressure stress, separates the static diffusion and dynamic enhancement effect, and needs to perform the following standardized data processing procedure to determine the algorithm path of signal decoupling. The discrete time series data collected are input into a digital signal processing unit, and a preset phase-locked amplification algorithm is used to extract the AC response component at the same frequency as the periodic modulation pressure stress component and the DC drift component that changes slowly over time, the dynamic transmission enhancement factor signal extraction adopts a digital quadrature vector demodulation procedure, and the digital signal processing unit uses the periodic modulation pressure stress component driving signal as the clock source to generate a frequency-locked reference sine sequence and a phase-shifted 90-degree orthogonal cosine sequence , the sampling rate of the real-time complex impedance discrete signal is multiplied by the above two reference sequences respectively, and the convolution integral is performed within a sliding Hann window covering modulation periods, and the moving step length of the sliding Hann window is set to 10% of the length of a single window, which suppresses the phase jump interference caused by frequency fluctuations, and outputs the corresponding in-phase component and orthogonal component , the dynamic transmission enhancement factor is directly taken from the vector modulus , and the calculation path uses the low-pass filtering characteristics of the integrator to limit the effective signal bandwidth to the modulation frequency Within the extremely narrow passband, the high-frequency interference caused by fluid thermal noise and the DC drift caused by electrode polarization are directly filtered out, realizing quantitative capture of the pumping effect of micron-sized pores. The specific decoupling process is as follows: the reference signal is set as a sine wave synchronized with the modulated pressure stress The original signal is multiplied by the reference signal and its orthogonal signal respectively, and is integrated through a low-pass filter with a cutoff frequency of The calculated in-phase component and the orthogonal component are used to synthesize the amplitude of the AC response component , which is the required AC response signal. At the same time, a low-pass filter with a cutoff frequency of is used to directly filter the original signal, and the smooth curve obtained is the DC drift component .

[0045] Secondly, the calculation procedure of the static diffusion coefficient is established, which represents the diffusion ability of the drug solution driven only by the concentration gradient in the pore structure defined by the constant reference pressure stress. Based on the extracted DC drift component , it is converted into the corresponding conductivity distribution , and the conductivity distribution is mapped to the drug solution concentration distribution using the Archie formula or the pre-calibrated conductivity-concentration standard curve. The rate of change of the diffusion front position over time is selected, and the analytical solution of Fick's second law in cylindrical coordinates is used for fitting. Specifically, the least squares fitting equation is used to obtain the static diffusion coefficient . In an actual measurement, if the diffusion front is observed to expand 2 millimeters from the center to the outside within 600 seconds, the above fitting can calculate as .

[0046] Finally, the quantitative method of the dynamic transport enhancement factor is defined, which aims to represent the gain of convective transport of the drug solution in response to periodic pore deformation. Based on the amplitude of the extracted AC response component , which reflects the reciprocating displacement amplitude of the drug solution front due to the microscopic pumping effect of the medium skeleton within a single stress modulation period, the displacement amplitude is converted to the equivalent convective velocity through a fluid dynamics model, and the dynamic transport enhancement factor is defined as the ratio of the convective velocity to the static diffusion velocity, i.e. , where The feature diffusion length is 5 microns. If the AC impedance amplitude at a certain position corresponds to a periodic displacement of 5 microns, combined with a modulation frequency of 0.5 Hz, the convection velocity can be calculated, and the dynamic transport enhancement factor under this working condition is 1.45, indicating that the convection effect introduced by dynamic stress makes the transport rate increase by 45%.

[0047] In the standard working condition calibration process for establishing a measurement reference, the system constructs a mapping relationship library of conductivity and concentration by preparing a series of standard hydrogel samples pre-mixed with gradient concentrations of the local anesthetic to be measured. These standard samples are loaded into the insulating test cavity in turn and subjected to a constant reference pressure stress component The temperature is maintained at 37 degrees Celsius, and the corresponding bulk impedance response values are recorded using a surface electrode array. Then, by polynomial fitting of discrete data points from 0.1 mg / mL to 5.0 mg / mL concentration interval, a standard curve of conductivity to concentration is generated for this specific medium batch. In addition, the system needs to extract the drug electrolyte contribution factor X for the specific drug solution before generating the standard conversion curve, and use it as a linear correction term for the polynomial fitting model to eliminate the mapping deviation caused by the difference in dissociation constant of different drug molecules, and as a quantitative basis for converting the DC drift component analyzed in subsequent examples into drug concentration distribution data.

[0048] The system performs a boundary pressure calibration procedure for the mechanical stability of the medium skeleton. The sacrificial sample is subjected to stress sweep test with increasing amplitude under the condition of loading anti-slip array structure, and the energy proportion of high harmonic component in complex impedance response is monitored in real time. The inflection point of sudden increase of this proportion is defined as the yield critical point of the medium microstructure. Accordingly, the maximum amplitude of the periodic modulation pressure stress component in the formal test is locked within 80% of the yield critical point stress value. This preset procedure ensures that all subsequent dynamic measurement processes are limited within the linear viscoelastic interval of the porous medium, ensuring that the measured dynamic transport enhancement factor is purely characterized by reversible elastic pumping effect and completely excludes irreversible structural damage interference caused by skeleton plastic damage or fatigue fracture.

[0049] In the scenario of system initialization and performance benchmarking for batch detection equipment, when the system faces the objective working conditions of measurement baseline drift caused by hardware batch difference or environmental temperature and humidity fluctuation, the method is integrated into the device's power-on self-test process to perform automatic calibration and compensation. In this process, a set of calibration modules with known standard mechanical properties and electrical parameters are sequentially placed in the insulation test cavity. The calibration module is composed of silicone rubber with a hardness of Shore A30 to 70 and conductive gel with a conductivity of 0.1 to 10.0 millisiemens per centimeter, which is used to simulate the mechanical response and electrical impedance characteristics of porous media under different compaction degrees. The system controls the actuator piston to apply a preset step static pressure stress sequence to the calibration module, and records the complex impedance response data collected by the surface electrode array. By comparing the measured impedance spectrum with the standard characteristic curve of the calibration module, a system error compensation matrix is constructed for the current hardware state and stored in the device's non-volatile memory. In the subsequent formal measurement process, the original complex impedance spatio-temporal evolution data is linearly corrected.

[0050] After completing the static calibration, the system further performs adaptive calibration of dynamic response characteristics. The actuator piston is controlled to apply a frequency-swept periodic modulation pressure stress to the calibration module, with a frequency range of 0.1 Hz to 2.0 Hz. The response amplitude-frequency characteristics and phase-frequency characteristics of the system to different frequency excitations are recorded. Based on the frequency response data, the system automatically adjusts the reference signal phase offset and low-pass filter cutoff frequency in the lock-in amplification algorithm to ensure that the weak alternating response component can be extracted with the maximum signal-to-noise ratio in the formal measurement. The medium isotropic reference and decision threshold calibration follow the statistical dispersion analysis logic. Before applying the pre-tightening force, the system controls the surface electrode array to perform omnidirectional impedance scanning on the free-state porous conductive medium with a fixed excitation frequency, and collects a sequence of static impedance values of eight groups of diagonal electrodes uniformly distributed along the radial direction . The coefficient of variation of the sequence , i.e., the ratio of the standard deviation to the mean, is calculated. The system's built-in running logic limits the initial structure of the medium to meet the isotropic test requirements and unlocks the actuator piston's descending authority when . The anisotropic threshold value is set as times the initial value . During the subsequent composite stress application process, once the impedance change rate difference in the orthogonal directions exceeds the dynamic threshold value, it is determined that the internal structure of the medium is rearranged due to stress induction, which has statistical significance. This rule eliminates the anisotropic artifacts caused by uneven medium preparation and locks the measurement object as the mechanical stress-induced structural effect. Finally, the porosity consistency test for the batch difference of the porous medium is performed. Before the formal injection of the liquid medicine, the standard reference pressure stress is applied to the loaded blank hydrogel and measure the baseline resistivity of the central region, if the measured resistivity deviates from the preset standard value by more than then it is determined that the batch of gel has abnormal pore structure and needs to be discarded and replaced; if the deviation is within the allowable range, then the porosity parameter in the subsequent calculation model is fine-tuned according to the measured value.

[0051] It is obvious to those skilled in the art that the present application is not limited to the details of the above exemplary embodiments, and the present application can be implemented in other specific forms without departing from the spirit or essential characteristics of the present application.

[0052] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application and are not limiting. Although the present application is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solutions of the present application can be modified or replaced equivalently without departing from the spirit and scope of the technical solutions of the present application.

Claims

1. A physicochemical method for determining the diffusion rate of a local anesthetic solution in the plane of the erector spinae fascia, characterized in that, The method includes the following steps: Step 101: Construct an anisotropic constraint boundary for mechanical interlocking. Place a standard isotropic porous conductive medium in the insulation test chamber. Use an actuating piston with a prefabricated micron-level anti-slip array structure to apply a pre-tightening force to the porous conductive medium along the normal direction, so that the anti-slip array structure is completely embedded in the surface of the porous conductive medium. Physically cut off the tangential fluid leakage channel along the contact interface between the actuating piston and the porous conductive medium. Use the pre-tightening force to flatten and rearrange the micropores inside the porous conductive medium to form anisotropic diffusion channels. Step 102: Apply a composite stress load and control the actuation piston to apply a composite mechanical compressive stress to the porous conductive medium along the normal direction. The composite mechanical compressive stress is composed of a constant reference compressive stress component used to set the porosity of the medium and a periodic modulated compressive stress component used to excite the elastic oscillation of the medium skeleton, thus establishing a fluid dynamic environment with convection and dispersion coupling inside the porous conductive medium. Step 103: Collect multidimensional impedance response data. While maintaining the composite mechanical compressive stress, quantitatively inject the test drug into the center of the porous conductive medium. Simultaneously collect the complex impedance spatiotemporal evolution data reflecting the migration front of the test drug under different stress states using a radially distributed surface electrode array. Step 104: Decouple the calculation of physicochemical transport indices. Based on the frequency characteristics of the periodically modulated compressive stress components, perform frequency domain analysis on the spatiotemporal evolution data of complex impedance to separate the static diffusion coefficient dominated by Brownian motion and the dynamic transport enhancement factor induced by periodic pore deformation.

2. The physicochemical method for determining the diffusion rate of a local anesthetic solution in the erector spinae fascia plane according to claim 1, characterized in that, The specific process of separating the static diffusion coefficient and the dynamic transport enhancement factor in step 104 includes: using a lock-in amplification algorithm to extract the AC response component with the same frequency as the periodically modulated compressive stress component and the DC drift component that monotonically changes with time from the complex impedance spatiotemporal evolution data; calculating the static diffusion coefficient based on the time-varying slope of the DC drift component, which characterizes the molecular diffusion capability of the test drug in the pore structure defined by the constant reference compressive stress component; and calculating the dynamic transport enhancement factor based on the amplitude of the AC response component, which characterizes the convective transport gain of the test drug in response to periodic pore deformation.

3. The physicochemical method for determining the diffusion rate of a local anesthetic solution in the erector spinae fascia plane according to claim 1, characterized in that, In step 101, the anti-slip array structure is a rough microstructure formed on the contact end surface of the actuating piston by sandblasting or laser etching. The arithmetic mean height of the rough microstructure is limited to be greater than the average pore size of the porous conductive medium under unpressurized conditions, so as to ensure that when a preload is applied, the skeleton of the porous conductive medium undergoes plastic rheology and fills the gaps of the rough microstructure, forming a fluid closed boundary without interface slip.

4. The physicochemical method for determining the diffusion rate of a local anesthetic solution in the erector spinae fascia plane according to claim 1, characterized in that, In step 102, the waveform of the periodically modulated compressive stress component is set to a sine wave or a triangular wave, its oscillation frequency is set to a low frequency range of 0.1 Hz to 1.0 Hz, and its oscillation amplitude is controlled between 5% and 20% of the constant reference compressive stress component. The combination of oscillation frequency and oscillation amplitude is used to induce a periodic volume pumping effect in the anisotropic diffusion channel without destroying the integrity of the porous conductive dielectric skeleton structure.

5. The physicochemical method for determining the diffusion rate of a local anesthetic solution in the erector spinae fascia plane according to claim 1, characterized in that, In step 103, the surface electrode array includes an injection electrode located at the center of the bottom surface of the insulating test chamber, and multiple rings of measuring electrodes distributed concentrically around the injection electrode. Step 103 also includes: measuring the impedance values ​​between electrode pairs at different azimuth angles along the radial direction, and comparing the impedance change rate at different azimuth angles; when the difference in impedance change rate at different azimuth angles exceeds a preset anisotropy threshold, it is determined that a non-uniform stress distribution field has been formed inside the porous conductive medium, and a stress distribution calibration signal is output.

6. The physicochemical method for determining the diffusion rate of a local anesthetic solution in the erector spinae fascia plane according to claim 1, characterized in that, The porous conductive medium is selected from polyacrylamide hydrogel or agarose gel, which has an isotropic pore structure in the uncompressed state; the method also includes the step of establishing a stress-dependent characteristic curve: by adjusting the magnitude of the constant reference compressive stress component step by step, the porosity and tortuosity of the porous conductive medium are quantitatively changed, and the corresponding static diffusion coefficient is recorded, thereby constructing a functional relationship between the static diffusion coefficient and the external mechanical constraint.

7. The physicochemical method for determining the diffusion rate of a local anesthetic solution in the erector spinae fascia plane according to claim 1, characterized in that, Step 104 also includes calculating the anisotropy ratio, which characterizes the transport properties of the anisotropic diffusion channel. The calculation formula is as follows: ,in, The lateral diffusion coefficient of the test drug solution along the direction perpendicular to the pressure applied by the actuating piston is obtained from the spatiotemporal evolution data of complex impedance. The longitudinal diffusion coefficient of the test drug solution along the direction of pressure applied by the actuating piston is the result of the analysis. The value is used to quantitatively characterize the physical constraint strength of porous conductive media on the fluid transport direction under the action of composite mechanical compressive stress.

8. The physicochemical method for determining the diffusion rate of a local anesthetic solution in the erector spinae fascia plane according to claim 1, characterized in that, The method for acquiring complex impedance spatiotemporal evolution data in step 103 includes: using multi-frequency impedance tomography, alternating high-frequency excitation current and low-frequency excitation current during the injection of the drug solution to be tested; using the impedance response under high-frequency excitation to characterize the volume filling degree of the drug solution to be tested in the pores of the porous conductive medium; using the impedance response under low-frequency excitation to characterize the double-layer polarization effect between the drug solution to be tested and the porous conductive medium framework; and using the data of the double-layer polarization effect to correct the diffusion rate calculation error caused by interface polarization.

9. The physicochemical method for determining the diffusion rate of a local anesthetic solution in the erector spinae fascia plane according to claim 1, characterized in that, The method also includes an environmental temperature control step: before performing step 101, the constant temperature circulation system integrated into the side wall of the insulation test chamber is started to maintain the temperature environment inside the insulation test chamber at a constant 37 degrees Celsius; and throughout the entire process of performing steps 102 to 103, the temperature environment is monitored and adjusted in real time.

10. The physicochemical method for determining the diffusion rate of a local anesthetic solution in the erector spinae fascia plane according to claim 1, characterized in that, The method also includes the step of establishing a rheological sensitivity fingerprint spectrum of the drug solution: for the same drug solution to be tested, by gradually changing the frequency and amplitude of the periodically modulated compressive stress component, steps 102 to 104 are repeated to construct a response spectrum of the dynamic transport enhancement factor as a function of mechanical disturbance parameters; the response spectrum is used to quantitatively characterize the nonlinear rheological transport properties of the drug solution to be tested under dynamic mechanical environment, so as to identify drug formulations with specific shear thinning or thixotropic properties.

Images