Automatic measurement device for the diameter of the inhibition zone

Abstract

This invention relates to the field of automated microbial antimicrobial susceptibility testing technology, specifically to an automatic device for measuring the diameter of inhibition zones. The device includes an image acquisition module, an antimicrobial susceptibility test strip center positioning module, a radial transmittance profile construction module, a diffusion-MIC inversion module, and a diameter output module. This invention reconstructs the traditional inhibition zone measurement paradigm based on image edge detection and geometric circle fitting into a radial profile inversion paradigm based on a physical model of antimicrobial substance diffusion in agar. It constructs a radial transmittance profile and a family of azimuth profiles with the center of the antimicrobial susceptibility test strip as the polar coordinate origin, inversely infers the local diffusion coefficient field, and uses Fick's second law to nonlinearly invert the minimum inhibitory concentration (MIC) radius. Simultaneously, it separates dual-zone resistant subgroups through residual multi-peak detection and achieves dynamic prediction through temporal differential constraints. This invention achieves a measurement standard deviation better than 0.1 mm, supports dual-zone identification and culture endpoint prediction, and is significantly superior to existing automatic measurement schemes based on edge detection.

Description

Technical Field

[0001] This invention relates to the field of automated microbial drug susceptibility testing technology, specifically to an automatic device for measuring the diameter of inhibition zones, which can be applied to scenarios such as drug susceptibility testing, antibiotic potency evaluation, in vitro antibacterial activity screening, and drug resistance subgroup detection in clinical microbiology laboratories. Background Technology

[0002] The diameter of the inhibition zone is a core quantitative indicator for evaluating the activity of antimicrobial substances using the Kirby-Bauer disk diffusion method. In the traditional Kirby-Bauer disk diffusion test, the tester attaches a disk containing a quantitative amount of antimicrobial substance to the surface of agar inoculated with the test strain. The antimicrobial substance diffuses radially outward in the agar, forming a concentration gradient. Within the region where the concentration exceeds the minimum inhibitory concentration (MIC) of the strain, the test strain cannot grow, thus forming a transparent inhibition zone around the disk. The larger the diameter of the inhibition zone, the stronger the effect of the antimicrobial substance on the strain. In the daily work of clinical microbiology laboratories, a single antimicrobial susceptibility test typically involves dozens to hundreds of petri dishes, each containing six to twelve antimicrobial susceptibility test strips. Testers need to use calipers to measure the diameter of each inhibition zone individually. This manual measurement method has three long-standing unresolved problems: First, measurement accuracy is affected by the observer's subjective judgment; the results from different personnel measuring the same petri dish can vary by more than 2 mm. Second, when the edges of the inhibition zones are blurred or show double or multiple zones, determining the boundary position relies almost entirely on experience, making consistency difficult to guarantee. Third, measurement efficiency is low; measuring a single petri dish typically takes between 2 and 5 minutes, which cannot meet the rapid throughput requirements of large batches of samples.

[0003] To address the aforementioned issues, several automated measurement solutions have been proposed in the industry. Chinese patent application CN108981597A discloses an automatic inhibition zone measuring instrument. This system uses a CMOS camera combined with a dark chamber and supplementary lighting to acquire images of the culture dish. After weighted average grayscale conversion, median filtering, and edge detection through Sobel operator and wavelet transform data fusion, the edge of the inhibition zone is obtained. Finally, the diameter of the inhibition zone is obtained by circle fitting of the edge points using the least squares method. However, the fundamental premise of this solution is the assumption that the inhibition zone has a geometric edge on the image that can be sharpened by the operator. This premise cannot hold true given the physical fact that the boundary of the inhibition zone is essentially a smooth transition zone formed by a radial concentration gradient rather than a grayscale step. The gradient response position obtained by the Sobel and wavelet operators on the smooth transition zone depends on the operator parameters and threshold selection. The diameter obtained under different parameters may differ by more than 1 mm. Furthermore, this solution can only output a meaningless average diameter for double-zone phenomena, losing information about drug-resistant subgroups. Chinese patent application CN110288596A discloses a rapid measurement method, measuring device, and readable storage medium for the diameter of inhibition zones. This method, after image denoising using nonlocal mean filtering and piecewise linear transformation, determines the target circle by selecting three pixels at the edge of the inhibition zone. It then statistically analyzes the proportion of inhibition zone pixels falling inside and outside the target circle. If the proportion of external pixels exceeds 10%, three points are reselected for iterative fitting until the proportion meets a threshold, at which point the diameter is output. While this method improves the robustness of circle fitting to some extent through an iterative mechanism, it is essentially still a geometric paradigm based on "finding edge pixels and then geometrically fitting a circle." The selection of "edge pixels" still relies on the assumption of abrupt grayscale changes in the image. When the edge of the inhibition zone itself presents a smooth transition zone radially tens of pixels wide, the selection of three points is highly random; the diameter fluctuation obtained from different sampling batches of the same inhibition zone can reach 0.8 mm. Furthermore, this method cannot handle situations with double / multiple inhibition zones or uneven culture medium thickness, and it is ineffective for detecting heterogeneous drug-resistant strains commonly found in clinical microbiology laboratories.

[0004] The limitations shared by the aforementioned existing technologies do not stem from the inadequacy of the choice of a specific image processing operator, but rather from a universally accepted yet physically contradictory implicit premise: treating the automatic measurement of inhibition zones as a geometric boundary identification problem in image space. In reality, inhibition zones on petri dishes never exist as geometric boundaries: they are an isoconcentration contour formed by the intersection of a continuous concentration field created by the radial diffusion of antimicrobial substances from the susceptibility testing paper according to Fick's second law and the minimum inhibitory concentration (MIC) of the bacterial strain. The actual colony inhibition rate exhibits a smooth S-shaped curve from 100% to 0% radially, rather than a step function. The so-called "edge blurring" is not image noise, but a direct reflection of the diffusion physical process; the so-called "double rings" are not anomalies, but a physical inevitability of the simultaneous presence of the MICs of the main strain and the resistant subgroup within the same concentration field. Under this cognitive bias, existing technologies treat physical signals as noise to be removed and physical diversity as anomalies to be avoided, thus locking measurement accuracy and functional dimensions to a level far below the upper limit of physical theory. The current technology lacks an automatic measurement system that can directly derive the minimum inhibitory concentration (MIC) contour from the inhibition zone image, which is a technological gap that urgently needs to be filled in the field of automated drug sensitivity testing. Summary of the Invention

[0005] To address the core bottlenecks in existing technologies for automatic measurement of inhibition zone diameter—namely, the limitation in boundary positioning accuracy, unreliable identification of double and multi-zone phenomena, and inability to compensate for physical asymmetries such as uneven culture medium thickness—this invention provides an automatic inhibition zone diameter measurement device. This device constructs a radial transmittance profile with the center of the drug sensitivity paper as the origin of the polar coordinates and performs nonlinear inversion on the profile based on Fick's second law physical model of antibacterial substance diffusion in agar to directly solve for the minimum inhibition concentration isoconcentration radius. This achieves sub-millimeter-level high-precision automatic measurement of inhibition zone diameter and automatic identification of drug-resistant subgroups from the perspective of diffusion physics, without relying on any image geometric edge sharpening assumptions.

[0006] The technical solution of this invention is: an automatic measurement device for the diameter of the inhibition zone, comprising an image acquisition module, a drug sensitivity test strip center positioning module, a radial transmittance profile construction module, a diffusion-MIC inversion module, and a diameter output module. The image acquisition module is used to acquire images of the inhibition zone of a petri dish with pixel-physical size calibration. The drug sensitivity test strip center positioning module is connected to the image acquisition module and is used to locate the center of the drug sensitivity test strip in the inhibition zone image of the petri dish as the polar coordinate origin for subsequent radial sampling. The radial transmittance profile construction module is connected to the drug sensitivity test strip center positioning module and is used to construct a normalized radial transmittance profile along the radial direction with the polar coordinate origin as the center, and further divide the profile by azimuth angle to obtain an azimuth profile family and a local diffusion coefficient field distributed along the azimuth angle. The diffusion-MIC inversion module is connected to the radial transmittance profile construction module. It converts the normalized radial transmittance profile into an inhibition rate profile using a Hill-type dose-response relationship. Using the radial analytical solution of Fick's second law as a forward model, and with drug loading, local diffusion coefficient, and minimum inhibitory concentration (MIC) as the inversion parameters, it iterates nonlinear least squares to find the MIC isoconcentration radii in each direction. Further, based on multi-peak detection of the fitting residuals, it separates the multilayer MIC isoconcentration profiles corresponding to the master strain and resistant subgroups, and achieves time-consistent inversion based on diffusion kinetics temporal differential constraints. The diameter output module, connected to the diffusion-MIC inversion module, outputs the inhibition zone diameter based on the obtained MIC isoconcentration radii.

[0007] The beneficial effects of this invention include the following aspects. First, this invention completely reconstructs the problem of antibacterial zone measurement from geometric boundary identification in image space to physical profile inversion in radial signal space through a radial transmittance profile construction module. The mechanism is that the essence of the antibacterial zone is a smooth isoconcentration profile formed by the intersection of the diffusion concentration field and the minimum antibacterial concentration. The S-shaped curve presented by the radial transmittance profile completely preserves all the information of this physical process. Compared with the Sobel operator and wavelet transform edge detection used in the prior art CN108981597A, this invention does not rely on any gradient threshold assumption, thereby completely eliminating the systematic error of sub-pixel edge positioning. Under the same imaging conditions, the standard deviation of diameter measurement of this invention is reduced from about 0.5 mm in the prior art to less than 0.1 mm. Secondly, this invention upgrades the output of the traditional system from a single geometric diameter to a multidimensional output that includes the minimum inhibitory concentration value, the diameter of the primary and secondary inhibition zones, and the azimuth diffusion coefficient field through the diffusion-MIC inversion module. The mechanism is that the radial analytical solution of Fick's second law makes the mathematical derivation of the concentration field and the minimum inhibitory concentration from the transmittance profile a well-defined nonlinear least squares problem. Compared with the three-point fixed circle iterative scheme of CN110288596A, which can only output a scalar of diameter, the output dimension improvement of this invention brings about a functional leap from "measurement system" to "efficacy evaluation system". Furthermore, the multi-layer profile separation unit and the temporal constraint inversion unit of this invention form a deep coupling: multi-layer separation identifies drug-resistant subgroups on the inversion residuals at a single time step, while temporal constraint constrains the temporal evolution of the primary and secondary MIC concentration radii at each time step to the diffusion kinetic differential equation. After the two are combined, the system's prediction error for the final 24-hour culture endpoint after 18 hours of culture does not exceed 0.2 mm. This synergistic effect cannot be achieved by any single-layer or single-time inversion. The mechanism is that temporal physical constraint upgrades the data-driven statistical residual detection to the kinetic verification of physical constraints, eliminating random false positives of multi-peak detection. Meanwhile, multi-layer separation provides multiple temporal trajectories that need to be tracked independently for temporal constraint. The two form a nonlinear synergistic effect of 1+1>2. Finally, this invention transforms the physical asymmetries that are unavoidable sources of error in the petri dish preparation process, such as levelness deviation, uneven agar thickness, and air bubbles and dirt, which are considered error sources in the prior art, into signals that can be reversed and compensated by inversely deducing the cross-correlation coefficients of the cross-correlation coefficients between different orientations. The mechanism is that the cross-correlation coefficient distribution of the cross-correlation coefficients between different orientations directly characterizes the differences in the local diffusion environment. The prior art is completely powerless to address this, while this invention can not only compensate for such asymmetries, but also output the variance of the cross-correlation coefficients as an online quality control index for the quality of petri dish preparation. Attached Figure Description

[0008] Figure 1 This is a schematic diagram of the overall architecture of the automatic measurement system for the diameter of the inhibition zone provided in an embodiment of the present invention.

[0009] Figure 2 This is a schematic diagram of the radial transmittance profile construction module and its internal azimuth partitioning unit and diffusion coefficient field inversion unit provided in the embodiments of the present invention.

[0011] Figure 3 This is a schematic diagram of the structure of the diffusion-MIC inversion module and its internal forward model fitting unit, multi-layer contour separation unit and temporal constraint inversion unit provided in the embodiments of the present invention.

[0012] Figure 4 This is a schematic diagram of the diameter output module and the drug sensitivity classification alarm module provided in the embodiment of the present invention. Detailed Implementation

[0013] The specific embodiments of the present invention will now be described in detail with reference to the accompanying drawings. Those skilled in the art should understand that the following embodiments are for illustrative purposes only and should not be construed as limiting the scope of protection of the present invention.

[0014] like Figure 1 As shown in the figure, the automatic measurement system for the diameter of the inhibition zone provided in this embodiment of the invention mainly consists of five core modules: an image acquisition module 1, a drug sensitivity test strip center positioning module 2, a radial transmittance profile construction module 3, a diffusion-MIC inversion module 4, and a diameter output module 5. It also includes a drug sensitivity classification and alarm module and a touchscreen human-machine interaction module as auxiliary functional units. The image acquisition module 1 is communicatively connected to the drug sensitivity test strip center positioning module 2, the drug sensitivity test strip center positioning module 2 is communicatively connected to the radial transmittance profile construction module 3, the radial transmittance profile construction module 3 is communicatively connected to the diffusion-MIC inversion module 4, the diffusion-MIC inversion module 4 is communicatively connected to the diameter output module 5, and the diameter output module 5 is simultaneously communicatively connected to the drug sensitivity classification and alarm module and the touchscreen human-machine interaction module. There is not only a forward data flow from the profile to the inversion between the radial transmittance profile construction module 3 and the diffusion-MIC inversion module 4, but also a feedback data flow from the inversion residual back to the azimuth partition unit. That is, when the fitting residual obtained by the diffusion-MIC inversion module 4 in a certain azimuth exceeds a preset threshold, the feedback signal is sent back to the radial transmittance profile construction module 3 so that it can further subdivide the azimuth sector in that azimuth and reconstruct the profile, thereby forming a deeply coupled closed-loop structure between the radial transmittance profile construction module 3 and the diffusion-MIC inversion module 4.

[0015] The image acquisition module 1 is used to acquire images of the inhibition zones of petri dishes with pixel-to-physical size calibration. Its overall structure includes a darkroom, an LED ring coaxial light source, a CMOS camera, a pixel-to-physical size calibration plate, and a stage. The darkroom is a monolithic metal box with its inner walls covered in matte black paint to eliminate interference from ambient light reflection and secondary reflections from the inner walls. The darkroom has a double-track sliding door on the front, ensuring that the ambient light intensity inside the box does not exceed 0.1 lux when the door is closed. The stage is located at the bottom of the darkroom. The top surface of the stage has an embedded groove that matches the outer diameter of a standard 90mm petri dish. The groove is 3mm deep, and four elastic positioning posts are provided on the bottom surface of the groove to ensure the petri dish is placed horizontally. After placement, the height deviation between the bottom surface of the petri dish and the top surface of the stage does not exceed 0.2mm.

[0016] The LED ring-shaped coaxial light source is fixed to the top of the light-shielding dark chamber, located 260mm directly above the stage, and has an overall ring structure. The inner diameter of the LED ring-shaped coaxial light source is 80mm, and the outer diameter is 140mm. Several cool white LED beads are evenly distributed within the ring. The color temperature of the LED ring-shaped coaxial light source is adjustable within the range of 5300K to 5700K. The uniformity of illuminance across the entire ring-shaped illumination area on the stage plane does not exceed 5%, effectively avoiding grayscale gradients in the background of the culture dish image caused by uneven light source illumination. The emission angle of the LED ring-shaped coaxial light source is optically shaped so that its main light direction is perpendicular to the stage plane, avoiding projection artifacts near the edge of the antibacterial zone caused by tilted illumination. An optical diffuser plate, made of matte polycarbonate material and 2mm thick, is placed below the LED ring-shaped coaxial light source to further diffuse the LED point light source into a surface light source, eliminating the graininess of the LED beads.

[0017] The CMOS camera is mounted in the central through-hole of the LED ring coaxial light source, with its optical axis vertically downward and precisely aligned with the geometric center of the stage groove. The image sensor of the CMOS camera is a C-Mos chip with a diagonal size of 11.3mm, an effective pixel count of no less than 20Mpixel, and a corresponding single pixel physical size of approximately 2.4um. The CMOS camera is equipped with a fixed-focus industrial lens with a focal length of 25mm and a minimum working distance of 260mm. At this working distance, the actual spatial resolution of the CMOS camera for the 90mm culture dish on the stage is approximately 23um per pixel, which fully meets the imaging resolution requirements for measuring the sub-millimeter diameter of the inhibition zone. The CMOS camera is connected to the system main control unit via a USB 3.0 interface, with an image data acquisition frame rate of 30fps, and supports both manual triggering and timed triggering modes.

[0018] The pixel-physical size calibration plate is an aluminized glass substrate with concentric circle calibration patterns of known diameter etched on it. The diameter accuracy of the calibration patterns is ±5µm. The system automatically executes a pixel-physical size calibration process once during each power-on initialization: the CMOS camera captures an image of the pixel-physical size calibration plate; the drug-sensitive paper center positioning module 2 detects the center and edge pixel coordinates of the concentric circle calibration patterns; calculates the actual physical size scaling factor k corresponding to each pixel under the current imaging conditions; and stores the scaling factor k in the system parameter register for use by the diameter output module 5. The typical value range of the scaling factor k is 20µm to 25µm per pixel, and its non-uniformity deviation within the entire imaging field of view does not exceed 0.3% after lens distortion correction.

[0019] The image acquisition module 1 also includes a lens distortion correction subunit and a white balance correction subunit. During the factory calibration phase, the lens distortion correction subunit acquires multiple images of different poses based on a checkerboard calibration board. It then uses the Zhang Zhengyou calibration algorithm to fit the intrinsic parameter matrix and radial and tangential distortion coefficients of the CMOS camera, storing these parameters in the system's non-volatile memory. During routine measurements, the lens distortion correction subunit performs inverse distortion mapping on each acquired raw image to obtain a distortion-free image before transmitting it to the downstream processing module, ensuring consistent geometric accuracy from the center to the edge of the field of view. The white balance correction subunit calculates the white balance gain coefficient based on the average RGB components of the blank culture medium area during each power-on initialization. This compensates for color temperature drift caused by aging of different batches of LED chips, ensuring long-term stability of the normalized transmittance benchmark. The overall imaging repeatability of the image acquisition module 1 drifts by no more than 0.05 mm between 40°C and room temperature, meeting the stringent long-term stability requirements of clinical microbiology laboratories.

[0020] The drug sensitivity test strip center positioning module 2 is connected to the image acquisition module 1. Its core function is to locate the center coordinates of each drug sensitivity test strip in the inhibition zone image of the culture dish, providing the polar coordinate sampling origin for the subsequent radial transmittance profile construction module 3. The drug sensitivity test strip center positioning module 2 includes a preprocessing subunit, a Hough circle transform detection subunit, and a manual-assisted positioning subunit.

[0021] The preprocessing subunit performs conventional preprocessing on the original culture dish inhibition zone image output by the image acquisition module 1, including grayscale conversion, histogram equalization, and Gaussian filtering, to obtain a grayscale image that facilitates subsequent circular target detection. Grayscale conversion uses a weighted average method to merge the RGB three channels into a single-channel grayscale value. Histogram equalization enhances the grayscale contrast between the antimicrobial susceptibility test strip and the agar background. The Gaussian filter has a kernel size of 5×5 and a standard deviation of 1.0 to suppress high-frequency image noise without significantly blurring the edges of the test strip.

[0022] The Hough circle transform detection subunit performs a standard Hough circle transform on the preprocessed grayscale image to detect the center coordinates and radius of circular targets. Considering that the standard diameter of commercially available drug-sensitive paper is 6mm, its corresponding pixel diameter under the imaging conditions of this invention is approximately 260 pixels. The Hough circle transform detection subunit limits the search radius range to 120 to 140 pixels to improve detection efficiency and avoid misdetecting the inhibition zone itself as a drug-sensitive paper. The Hough circle transform detection subunit also employs an accumulator threshold adaptive mechanism: when the number of detected centers is less than the expected number of drug-sensitive papers at a preset accumulator threshold, the accumulator threshold is automatically lowered and re-detection is performed until the number of detected centers reaches the expected value or the accumulator threshold drops to the lower limit. For each detected center, the Hough circle transform detection subunit outputs its pixel coordinates as the center coordinates of the drug-sensitive paper and outputs its radius for the radial transmittance profile construction module 3 to determine the starting position of radial sampling.

[0023] The manual-assisted positioning subunit is activated as a backup mechanism for the Hough circle transformation detection subunit. When the Hough circle transformation detection subunit fails to detect a sufficient number of circle centers after the accumulator threshold drops to the lower limit, the system switches to manual-assisted positioning mode. The system displays the inhibition zone image of the petri dish to the operator via the touchscreen human-machine interface module and prompts the operator to manually click on the approximate center position of each drug sensitivity test strip. After receiving the operator's click coordinates, the manual-assisted positioning subunit performs a local Hough circle transformation within a 30-pixel local neighborhood centered on the clicked position for precise positioning, obtaining the final center coordinates of the drug sensitivity test strip. This manual-assisted positioning mechanism ensures that the system can still complete measurements under abnormal conditions such as extreme light exposure or petri dish contamination, avoiding the invalidation of the entire petri dish measurement results due to positioning failure.

[0024] The radial transmittance profile construction module 3 is the first core module that fundamentally distinguishes this invention from existing technologies. In existing automated measurement systems, the next step after acquiring the petri dish image involves edge detection or geometric circle fitting. However, the radial transmittance profile construction module 3 of this invention does not involve any edge detection. Its core idea is to transform the inhibition zone image of the petri dish from a Cartesian coordinate system to a polar coordinate system with the center of the drug sensitivity paper as the origin, and then sample the transmittance radially in the polar coordinate system to construct a radial transmittance profile. The overall structure of the radial transmittance profile construction module 3 is as follows: Figure 2 As shown, it includes polar coordinate transformation units, azimuth partitioning units, and diffusion coefficient field inversion units.

[0025] The polar coordinate transformation unit receives the center pixel coordinates of the drug sensitivity paper from the drug sensitivity paper center positioning module 2. With the pixel radius of the drug sensitivity paper and with Using the antibacterial zone image of the culture dish as the origin, with the antimicrobial sensitivity paper as the center and a radius of [missing information], [missing information]. The circular region is subjected to polar coordinate transformation. The polar coordinate transformation unit is along the radial direction. Step size, along the azimuth direction Equal-interval sampling is performed with a step size to obtain brightness data in polar coordinates. Further, the polar coordinate transformation unit converts the brightness data according to the culture medium background brightness pre-acquired during the power-on initialization of the image acquisition module 1. After normalization, the normalized radial transmittance profile is obtained: , in: The normalized radial transmittance profile is represented by a one-dimensional scalar function, taking values ​​between 0 and 1 (where 0 indicates complete colony obscuration and 1 indicates the same transmittance as the culture medium background). It is dimensionless and obtained by integrating and averaging the brightness data after polar coordinate transformation along the azimuth angle, characterizing the average transmittance distribution of the inhibition zone in the radial direction with the center of the drug-sensitive disc as the origin. r is the radial distance independent variable, a scalar, taking values ​​ranging from... to The unit is pixels, and it is formed by the polar coordinate transformation unit along the radial direction. The step size is discretized to represent the distance from the sampling point to the center of the drug sensitivity paper. Let be the azimuth integral variable, and let be a scalar, with a value range of 0 to 1. Unitless (radians are dimensionless), obtained by discretizing the polar coordinate transformation unit at equal intervals along the azimuth angle, representing the direction angle in the polar coordinate system; The grayscale function of the antibacterial zone image of the culture dish in the Cartesian coordinate system is a two-dimensional scalar field with integer values ​​ranging from 0 to 255 (8-bit grayscale image). It is dimensionless and is directly output by the CMOS camera, representing the grayscale brightness of each pixel. The pixel coordinates of the center of the drug sensitivity paper are given as a pair, with values ​​ranging from integers within the image size range and in pixels. They are output by the drug sensitivity paper center positioning module 2 and represent the origin of the radial sampling polar coordinates. The background brightness reference value for the culture medium is a scalar value, ranging from 100 to 220 (depending on the brightness of the light source). It is dimensionless and is obtained by averaging samples from the blank culture medium area during the system's initialization phase. It represents the denominator reference for normalization.

[0026] The azimuth partitioning unit obtains the above-mentioned omnidirectional integral average. This is further expanded into a family of azimuth partition profiles. Specifically, the azimuth partition unit will... The azimuth range is divided into equal parts. Each sector in one direction, with typical values. or For the k-th directional sector The azimuth partitioning unit performs azimuth averaging of the normalized luminance data along the radial direction within the sector to obtain the radial transmittance profile corresponding to that sector. Thus, the azimuth partition profile family is obtained. The physical significance of the aforementioned azimuth profile family lies in the fact that, under ideal conditions—ideal petri dish levelness, completely uniform agar thickness, and absence of air bubbles and contaminants—each They should overlap; however, under actual experimental conditions, each There must be differences between them, and these differences directly reflect the asymmetry of the diffusion environment in terms of azimuth.

[0027] The diffusion coefficient field inversion unit takes the azimuth profile family as input and inverts the local diffusion coefficient field distributed along the azimuth angle by calculating the cross-correlation coefficient between any two azimuth sector profiles. Specifically, the diffusion coefficient field inversion unit calculates the cross-correlation coefficient of the profiles for azimuth sectors k and l: , in: Let be the normalized cross-correlation coefficient between the k-th azimuth sector profile and the l-th azimuth sector profile. It is a scalar, a dimensionless real number ranging from -1 to 1, calculated by this formula, and characterizes the similarity of the shapes of the two azimuth profiles. k and l are the azimuth sector numbers, integers ranging from 1 to... Unitless, determined by the sector division of the azimuth partition unit, representing two comparison sectors; r is the radial distance summation variable, an integer, with a value range of... to (Unit: pixel), determined by radial sampling of the polar coordinate transformation unit, characterizing the radial position of the summation traversal; The radial starting value corresponding to the outer edge of the drug sensitivity paper is a scalar value, typically between 120 and 140 pixels, and is output by the drug sensitivity paper center positioning module 2, representing the lower bound of the radial integral. The upper bound of radial sampling is a scalar value, typically between 450 and 600 pixels, in pixels, set by the user according to the size of the petri dish, representing the upper bound of the radial integral; and The k-th and l-th azimuth sector profiles are respectively located in The mean within the range is a scalar, dimensionless, obtained from the arithmetic mean of the corresponding profile, and represents the centered benchmark. Indicates radial from arrive Discrete summation, Both represent the arithmetic square root operation and are mathematical operators.

[0028] Based on the above cross-correlation matrix The diffusion coefficient field inverse calculation unit further inversely calculates the local diffusion coefficient of each sector using a perturbation model of the local diffusion coefficient field. Under Fick's diffusion theory, if the profile shapes of two azimuth sectors are completely similar, their diffusion coefficients are equal; the deviation in the cross-correlation coefficients of the profiles corresponds to the relative deviation in the diffusion coefficients. Specifically, the sector with the highest cross-correlation coefficient is used as the reference sector. And assume that its local diffusion coefficient is the nominal value. The local diffusion coefficients of the remaining sectors can be inferred from the following relationship: , in: Let be the local diffusion coefficient of the k-th azimuth sector, and be a scalar with a value range of . to The unit is m² / s (typical order of magnitude in...). The agar diffusion rate of the antibacterial substance at this location is calculated using this formula. The nominal diffusion coefficient of the reference sector is denoted as σ, which is a scalar value typically taken as the known diffusion coefficient of antibacterial substances in standard agar (e.g., cephalosporin antibiotics are approximately σ). (Unit: m) 2 / s, pre-stored in the system parameter database, serves as a benchmark for inverse diffusion coefficient estimation; The diffusion coefficient-cross-correlation sensitivity coefficient is a positive scalar with a value ranging from 0.3 to 0.6 (0.5 in this embodiment). It is dimensionless and is determined by the system during the factory calibration stage using calibration experiments on culture dishes with known thickness gradients. It characterizes the conversion ratio from cross-correlation deviation to diffusion coefficient deviation. Too small a size will result in insufficient compensation for uneven thickness. If it is too large, it will introduce back-propagation noise; Let be the cross-correlation coefficient between the k-th sector and the reference sector, defined as in the aforementioned formula. The diffusion coefficient field back-calculation unit will back-calculate the obtained... As a local diffusion coefficient field, it is output to the diffusion-MIC inversion module 4, and simultaneously... The variance of the matrix is ​​output as an online quality control indicator for the preparation quality of petri dishes.

[0029] The diffusion-MIC inversion module 4 is the core innovative module of this invention. Its physical basis is that the diffusion process of antibacterial substances in agar strictly follows Fick's second law. Ignoring the approximation of agar adsorption and degradation, this diffusion process has a good radial analytical solution. The overall structure of the diffusion-MIC inversion module 4 is as follows: Figure 3 As shown, it includes a forward model fitting unit, a multi-layer contour separation unit, and a time-constrained inversion unit.

[0030] The forward model fitting unit first uses the radial transmittance profile construction module 3 to generate the omnidirectional zonal profiles. Converted into an inhibition rate profile using the Hill-type dose-response relationship. The closer the normalized transmittance is to 0, the more vigorous the colony growth, i.e., the lower the inhibition rate; the closer the normalized transmittance is to 1, the less colony growth occurs in the region, i.e., the higher the inhibition rate. The Hill-type transformation relationship serves as the biological premise of antibacterial physics, establishing only a monotonic mapping between transmittance and inhibition rate for subsequent physical inversion. An inhibition rate profile is obtained. Subsequently, the forward model fitting unit uses the analytical solution of Fick's second law in the case of radial diffusion from a point source as the forward physical model of the antibacterial substance concentration field: , in: The concentration of the antimicrobial substance at a radial distance r at incubation time t is a scalar function, ranging from 0 to... The positive real number between 0 and 1, with units of mol / m³, is calculated by this formula and characterizes the spatial distribution of the diffusion concentration field; r is the radial distance from the center of the drug sensitivity paper disc, a positive scalar, ranging from 0 to 1. The unit is m (converted from pixel × k), representing spatial location; t is the incubation time calculated from the moment the antimicrobial substance is released from the drug-sensitive paper disc, which is a positive scalar, typically ranging from 18h to 24h, i.e., 64800s to 86400s, in seconds, determined by the system clock, representing the time of diffusion evolution. The initial drug loading of the drug sensitivity test strip is denoted as , which is a positive scalar value ranging from 1 μg to 50 μg (depending on the drug) and is expressed in mol (converted from mass / molar mass). , is the parameter to be inverted, which characterizes the total amount of antibacterial substance. is the local diffusion coefficient of the k-th sector, defined as in the aforementioned formula, with units of m² / s; h is the thickness of the agar medium, a positive scalar, ranging from 3 mm to 5 mm, with units of m, determined by the petri dish preparation process and used as a known constant input, representing a one-dimensional thickness constraint for diffusion; is the natural exponential function, and is a mathematical operator; Circumference constant Four times that, is a dimensionless constant.

[0031] Based on the above positive physical model, the inhibition rate profile With concentration field The inhibition rate is linked through a Hill-type dose-response relationship: when the concentration of the antimicrobial substance equals the minimum inhibitory concentration (MIC) of the strain, the inhibition rate is 50%; when the concentration is much higher than the MIC, the inhibition rate approaches 1; and when the concentration is much lower than the MIC, the inhibition rate approaches 0. The positive model fitting unit is defined as follows: inhibition rate model: , in: Let be the theoretical inhibition rate model prediction value of radial position r in the k-th sector. , is a scalar function, a real number between 0 and 1, dimensionless, calculated by this formula, and characterizes the inhibition rate jointly determined by the Fick concentration field and the strain sensitivity. The minimum inhibitory concentration of the strain against the current antimicrobial substance is a positive scalar value, the range of which is determined by the actual sensitivity of the strain to the drug (typically between 0.01 mg / L and 128 mg / L), and the unit is mol / m³. The parameter to be retrieved is the threshold of sensitivity of the strain to the antimicrobial substance. The definition is the same as the aforementioned analytical solution formula for Fick diffusion, and the unit is mol / m³; Hill coefficient is a positive scalar value, ranging from 2 to 6 (this example applies to most β-lactam drugs). (Dimensionless, pre-stored in a drug pharmacology database, characterizing the steepness of the dose-response curve) When the inhibition rate is too small, the transition from 0 to 1 is too wide, leading to insensitivity of the inversion function to the MIC. If the size is too large and the transition is too narrow, it will amplify the measurement noise. This is the exponentiation operator.

[0032] The forward model fitting unit will , and As parameters to be inverted (where The initial value is provided by the diffusion coefficient field inverse calculation unit, so that... With observation profile The sum of squared residuals is used as the cost function, and the optimal values ​​of the parameters to be inverted are obtained through the Levenberg-Marquardt nonlinear least squares iterative algorithm. After the iteration converges, the forward model fitting unit calculates the radial position corresponding to the inhibition rate of exactly 50% in that azimuth sector, i.e., the radius of the minimum antibacterial concentration, based on the obtained optimal parameters. , in: Let be the radial position corresponding to the concentration of the antibacterial substance in the k-th sector being exactly MIC, and be a positive scalar with a value range of . to The range converted to physical dimensions (typically 3mm to 30mm), in meters, is calculated using this formula and represents the radius of MIC isoconcentration at that location. ,t, The definitions of h and MIC are the same as those in the aforementioned formula; is the natural logarithm function, and is a mathematical operator; Pi is a dimensionless constant; 4 is a numerical constant.

[0033] The multi-layer contour separation unit performs multi-peak detection on the radial sequence of the fitting residuals obtained by the forward model fitting unit under the unimodal Hill model. The fitting residuals are defined as follows: , in: is the residual function between the observed suppression rate and the model predicted suppression rate of the k-th sector. is a scalar function, a real number between -1 and 1, dimensionless, calculated by this formula, and represents the profile bias that the unimodal Hill model fails to explain. To observe the inhibition rate profile, the same formula as above is defined; The suppression rate is predicted for the unimodal Hill model, defined as in the aforementioned formula.

[0034] The multi-layer contour separation unit performs residual function Continuous wavelet transform peak detection is performed on the radial axis, and... For the criterion (where) For residuals in The standard deviation within the range is used to determine whether a systematic multimodal structure exists. If significant multimodality is detected, Gaussian mixture fitting is initiated to decompose the observed suppression rate profile into several component profiles: , in: To observe the inhibition rate profile, the same formula as above is defined; is the Gaussian mixture component number (i.e., the number of different MIC profile layers detected), a positive integer, typically ranging from 2 to 3, dimensionless, determined by the peak detection count of the multi-layer profile separation unit, characterizing the number of drug-resistant subgroups; j is the component number summation variable, an integer, ranging from 1 to No unit; Let be the mixing weight of the j-th component, which is a positive scalar with a value between 0 and 1 and satisfies . , dimensionless, estimated by Gaussian mixture fitting EM algorithm, characterizing the proportion of this subpopulation in the overall population; The Hill-Fick composite inhibition rate model for the j-th component is as described above. Same but with and These are independent parameters; is the minimum inhibitory concentration corresponding to the j-th component, is a positive scalar with units of mol / m³, and is the parameter to be inverted, characterizing the sensitivity of the j-th subgroup; Let be the equivalent drug loading corresponding to the j-th component, be a positive scalar in mol, and be the parameter to be inverted. The definition is the same as the aforementioned formula. The multi-layer contour separation unit iteratively solves all parameters of the above hybrid model using the EM algorithm, and finally outputs the minimum inhibitory concentration of the main strain. and corresponding isoconcentration radius Minimum inhibitory concentration for secondary drug-resistant subgroups and corresponding isoconcentration radius .

[0035] The temporal constraint inversion unit is described in the image acquisition module 1 when the same culture dish is examined at multiple times within the culture period (typically...) , , It starts when images are repeatedly acquired. The time-constrained inversion unit inverts the images obtained at each time step separately. As a time-series observation, the diffusion dynamics differential relation is used as a physical regularization constraint. This physical constraint is derived from the time-series differential relation obtained by differentiating the aforementioned Fick diffusion radial analytical solution with respect to time: , in: Let be the square of the MIC isoconcentration radius of the k-th sector at time t, and be a positive scalar function with a range of values ​​of . to The interval converted to the square of the physical size, in m², is reconstructed by integrating the derivative of the left side of this formula with respect to time, and characterizes the evolution of the square of the isoconcentration radius over time. The first derivative operator with respect to time t; , , h, t, , The definition is the same as the previous formula; 4 is a numerical constant.

[0036] Based on the above differential relationship, the time-constrained inversion unit constructs a time-series consistency cost function and jointly optimizes it with the single-time nonlinear least squares residual: , in: is the total cost function of time-constrained inversion, which is a positive scalar with a range of non-negative real numbers and is dimensionless (after normalization). It is calculated by this formula and represents the objective value of joint optimization. The total number of image acquisition moments during the cultivation cycle is a positive integer, typically 3, and has no unit, determined by the acquisition settings of image acquisition module 1; i is a summation variable for moment numbers, an integer, ranging from 1 to... Unitless; k is the summation variable for the azimuth sector number, which is an integer ranging from 1 to... No unit; and They are time points The observed suppression rate profile and the model suppression rate profile of the k-th sector are defined as described in the aforementioned formula; This represents the L2 norm, which is the root mean square of the radial discrete summation. This is the time-series consistency regularization weight coefficient, a positive scalar with a value ranging from 0.1 to 10 (1.0 in this embodiment), dimensionless, and determined by the user based on a trade-off between the observation noise level and the confidence level of the physical constraints. Physical constraints fail when too small. When the value is too large, it excessively suppresses the information in the observed data; The time interval between adjacent moments is a positive scalar in seconds, obtained from the difference in acquisition time. The midpoint between adjacent moments is a positive scalar with units of seconds (s). Let be the value of the right-hand side of the aforementioned differential relation at the midpoint time, be a scalar function with units of m² / s, and substitute it into the aforementioned differential relation. The calculated derivative predictions characterizing discrete time series are obtained. The first term, within the L2 norm, represents the dimensionless difference in suppression rates, which becomes dimensionless after squaring; the second term, within the L2 norm, represents... difference and of The difference is After squaring, it becomes The two quantities have different dimensions, so normalization is required (in actual implementation, the second term is divided by...). Normalization makes it dimensionless; after normalization, the dimensions are consistent. The time-constrained inversion unit solves the above equation by joint optimization to obtain the final inversion parameters with consistent time series and predicts the culture endpoint accordingly. .

[0037] The diameter output module 5 is connected to the diffusion-MIC inversion module 4, and is used to receive the minimum antibacterial concentration radius of each sector and calculate and output the diameter of the antibacterial zone. For the case of a single-layer MIC profile, the diameter output module 5 will output the diameter of each sector. The arithmetic mean is used to obtain the average MIC isoconcentration radius, which is then multiplied by 2 to obtain the pixel value of the inhibition zone diameter. This value is then converted to a physical diameter in mm using the pixel-to-physical size ratio coefficient k calibrated by the image acquisition module 1. For multi-layer MIC contours, the diameter output module 5 outputs the diameter for each layer... Perform the above calculations independently and output the diameters of the primary inhibition zone and the secondary inhibition zone, respectively.

[0038] The diameter output module 5 also performs an abnormal orientation rejection mechanism when calculating the average MIC isoconcentration radius: for all orientation sectors, the obtained... The sequence is first calculated by taking the absolute deviation of the median from the median. Any azimuth sector deviating from the median by more than three times the absolute deviation of the median is considered an abnormal azimuth (usually caused by air bubbles, dirt, or uneven paper adhesion in that area), and is removed from the mean calculation. Only the remaining valid azimuth sectors are used to calculate the final diameter. This abnormal azimuth removal mechanism avoids the significant drag of a single local contamination on the overall measurement results. In actual clinical measurements, if there is a single air bubble on a culture dish, the measurement error can be reduced from 0.4 mm to 0.08 mm after abnormal azimuth removal, demonstrating excellent robustness.

[0039] The output of the diameter output module 5 is simultaneously sent to the drug susceptibility classification and alarm module and the touchscreen human-machine interaction module. The drug susceptibility classification and alarm module incorporates a database of sensitivity-intermediate-resistance breakpoints for various common antibiotics against various common pathogens from the CLSIM100 standard. It classifies and marks antibiotics based on the output MIC values ​​and inhibition zone diameters. When the classification result indicates resistance, it triggers an audible and visual alarm and generates a special report on heterogeneous resistance if a resistant subgroup is identified. The touchscreen human-machine interaction module graphically displays the original image of the culture dish, the inverted radial transmittance profile curve, the azimuthal section profile family heatmap, the inversion parameter table, and the classification results. It allows operators to zoom in on any azimuthal profile for viewing and manual verification. The touchscreen human-machine interaction module also supports exporting measurement reports in PDF format and raw data in CSV format via a USB interface or the laboratory information management system communication interface, facilitating data archiving and subsequent statistical analysis in clinical laboratories.

[0040] To verify the measurement accuracy and robustness of this invention, Staphylococcus aureus ATCC25923 was used as the test strain and ceftazidime as the test drug. Measurements were performed on 20 MH agar plates prepared in the same batch using the system described in this invention, manual measurement with vernier calipers, and a reproducible measurement based on the scheme disclosed in CN108981597A. Comparison of the measurement results showed that the standard deviation of the diameter measurement using the system described in this invention was 0.08 mm, significantly better than the 0.52 mm of manual measurement with vernier calipers and the 0.34 mm of the reproducible measurement using the CN108981597A scheme. Furthermore, measurements were performed on 10 plates with intentionally introduced uneven agar thickness (thickness gradient of 2 mm). On the culture dish, the measurement error of the system described in this invention does not exceed 0.15 mm, while the measurement error of the CN108981597A scheme reaches more than 0.9 mm. On 10 culture dishes pre-inoculated with drug-resistant subgroups, the system described in this invention successfully identified the double-ring structure on all 10 culture dishes and output the diameters of the primary and secondary inhibition zones and the corresponding MIC values, while the existing technology can only output a single average diameter and cannot provide information on drug-resistant subgroups. In the time-constrained inversion mode, the system's prediction error for the diameter of the inhibition zone at the 24-hour culture endpoint is an average of 0.18 mm after 18 hours of culture, providing clinical microbiology laboratories with the possibility of shortening the testing cycle from 24 hours to 18 hours.

[0041] This invention further extends the validation experiments on more than ten common antibiotics using two reference strains, *Escherichia coli* ATCC25922 and *Pseudomonas aeruginosa* ATCC27853. In a total of 240 independent measurements across all strain-drug combinations, the classification consistency rate between the system described in this invention and human standard measurements reached 98.7%, significantly higher than the 91.2% consistency rate under the same conditions achieved by the three-point circle iterative scheme disclosed in CN110288596A. Addressing the common "double circle" challenge in clinical laboratories, this invention specifically selected 15 cases of heterogeneous vancomycin-resistant intermediate strains of *Staphylococcus aureus* for blind testing. The system successfully identified all heterogeneous drug-resistant subgroups and provided classification conclusions consistent with human expert interpretations, while 12 cases in existing technologies were misclassified as sensitive. Regarding single measurement time, the total time from image acquisition to final output of the measurement report for the system described in this invention is less than 5 seconds, significantly lower than the average time of over 3 minutes for manual measurement of a single culture dish using existing vernier calipers. The above embodiments demonstrate that the present invention has achieved significant technical progress in four aspects compared with the prior art: measurement accuracy, robustness, functional dimensions, and measurement efficiency.

[0042] The present invention has been described in detail above with reference to specific embodiments. However, the embodiments are only used to illustrate the technical solutions of the present invention and should not be regarded as limiting the scope of protection of the present invention. Any modifications, equivalent substitutions, and improvements made by those skilled in the art to the above embodiments without departing from the spirit and principles of the present invention should fall within the scope of protection of the present invention.

Claims

1. An automatic measuring device for the diameter of the inhibition zone, characterized in that, include: The image acquisition module is used to acquire images of the inhibition zone of a petri dish with pixel-physical size calibration; A drug sensitivity test strip center positioning module, connected to the image acquisition module, is used to locate the center of the drug sensitivity test strip as the origin of polar coordinates in the inhibition zone image of the petri dish; a radial transmittance profile construction module, connected to the drug sensitivity test strip center positioning module, is used to construct a normalized radial transmittance profile by sampling radially with the origin of polar coordinates as the center; a diffusion-MIC inversion module, connected to the radial transmittance profile construction module, is used to convert the normalized radial transmittance profile into an inhibition rate profile, and perform nonlinear inversion on the inhibition rate profile based on the physical model of antibacterial substance agar diffusion to solve for the minimum inhibitory concentration isoconcentration radius; a diameter output module, connected to the diffusion-MIC inversion module, is used to output the diameter of the inhibition zone according to the minimum inhibitory concentration isoconcentration radius.

2. The automatic measurement system for the diameter of the inhibition zone according to claim 1, characterized in that, The radial transmittance profile construction module is specifically configured as follows: taking the center of the drug sensitivity paper as the origin, the antibacterial zone image of the culture dish is transformed from the Cartesian coordinate system to the polar coordinate system, and the transmittance is sampled radially with a preset step size in the polar coordinate system to obtain a radial transmittance profile with radial distance as the independent variable; the radial transmittance profile starts at the edge of the drug sensitivity paper and increases radially to the transmittance of the culture medium background, and its radial shape is an S-shaped smooth curve rather than a step function.

3. The automatic measurement system for the diameter of the inhibition zone according to claim 2, characterized in that, The radial transmittance profile construction module further includes an azimuth partitioning unit and a diffusion coefficient field inversion unit. The azimuth partitioning unit divides the polar coordinate space into several azimuth sectors, and independently constructs the radial transmittance profile in each azimuth sector to obtain an azimuth partition profile family. The diffusion coefficient field inversion unit inverts the local diffusion coefficient field distributed along the azimuth angle based on the cross-correlation between any two azimuth profiles in the azimuth partition profile family. The local diffusion coefficient field is used to characterize the diffusion asymmetry caused by deviations in the levelness of the culture dish, uneven agar thickness, air bubbles, or dirt. The cross-correlation coefficient distribution among the azimuth partition profile families is further output as an online quality control indicator for the quality of culture dish preparation.

4. The automatic measurement system for the diameter of the inhibition zone according to claim 3, characterized in that, The diffusion-MIC inversion module is specifically configured as follows: Each radial transmittance profile in the azimuth partition profile family is converted into an inhibition rate profile using a Hill-type dose-response relationship; the radial analytical solution of Fick's second law is used as the forward physical model, with drug loading, local diffusion coefficient, and minimum inhibitory concentration (MIC) as the inversion parameters, and the inhibition rate profile as the observed value; the inversion parameters are solved using the Levenberg-Marquardt nonlinear least squares iterative algorithm; the MIC isoconcentration radius is calculated for each azimuth based on the solved inversion parameters; the diameter of the inhibition zone output by the diameter output module is twice the mean of the MIC isoconcentration radius for each azimuth.

5. The automatic measurement system for the diameter of the inhibition zone according to claim 4, characterized in that, The diffusion-MIC inversion module further includes a multi-layer profile separation unit; the multi-layer profile separation unit performs multi-peak detection along the radial sequence of the fitting residuals after the convergence of the nonlinear least squares iterative algorithm; when the fitting residuals exhibit a systematic multi-peak structure, it is determined that a drug-resistant subgroup exists and Gaussian mixture fitting is initiated to decompose the inhibition rate profile into several component profiles corresponding to different minimum inhibitory concentrations; the inversion process described in the claims is executed independently for each component profile to solve for the minimum inhibitory concentration of the main strain and its isoconcentration radius, and the minimum inhibitory concentration of the secondary drug-resistant subgroup and its isoconcentration radius; the diameter output module outputs the diameter of the main inhibition zone and the diameter of the secondary inhibition zone accordingly.

6. The automatic measurement system for the diameter of the inhibition zone according to claim 5, characterized in that, The diffusion-MIC inversion module also includes a time-constrained inversion unit; the image acquisition module acquires multiple images of the same culture dish at multiple times during the culture cycle to obtain a multi-time inhibition zone image sequence; the time-constrained inversion unit uses the square of the minimum inhibition concentration radius obtained at each time as the time-series observation, and uses the diffusion kinetic differential relationship as a regularization constraint to construct a time-consistency cost function; by jointly optimizing the time-consistency cost function and the single-time nonlinear least squares residual, the time-consistent diffusion parameters and minimum inhibition concentration are obtained; the diameter output module predicts the diameter of the inhibition zone at the final culture endpoint in the early stage of culture based on the time-series inversion results.

7. The automatic measurement system for the diameter of the inhibition zone according to claim 1, characterized in that, The image acquisition module includes an LED ring coaxial light source, a CMOS camera, a light-shielding dark box, and a pixel-physical size calibration plate; the color temperature of the LED ring coaxial light source is 5300K to 5700K, and the illuminance uniformity deviation does not exceed 5%; the effective pixel count of the CMOS camera is not less than 20Mpixel.

8. The automatic measurement system for the diameter of the inhibition zone according to claim 1, characterized in that, The drug sensitivity paper center positioning module is specifically configured to detect the circular outline of the drug sensitivity paper in the inhibition zone image of the culture dish based on the Hough circle transform algorithm and extract its center coordinates; when the Hough circle transform algorithm fails to detect, the drug sensitivity paper center positioning module switches to the manual auxiliary positioning subunit, where the operator manually specifies the center coordinates.

9. The automatic measurement system for the diameter of the inhibition zone according to claim 1, characterized in that, It also includes a drug susceptibility classification and alarm module, which compares the concentration radius of the minimum inhibitory concentration with the susceptibility-intermediate-resistance determination threshold of the corresponding drug in the clinical breakpoint database, classifies and marks the measurement results as sensitive (S), intermediate (I), or resistant (R), and triggers an audible and visual alarm when the drug is classified as resistant.

10. The automatic measurement system for the diameter of the inhibition zone according to claim 1, characterized in that, It also includes a touch screen human-computer interaction module and a data export interface; the touch screen human-computer interaction module displays the antibacterial zone image of the petri dish, the radial transmittance profile, the inversion results and the measurement report; the data export interface includes a USB interface and a communication interface with the laboratory information management system.

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