Method and system for establishing gel observation chamber and determining gel deformation rate
By constructing a gel observation chamber and determining the proportional relationship between gel deformation rate and particle flow velocity, the problem of simultaneously measuring gel deformation behavior and flow field in existing technologies has been solved, enabling quantitative measurement and rapid screening with high spatiotemporal resolution.
Patent Information
- Application Number
- CN202511671633.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-13
- Publication Date
- 2026-02-13
- Estimated Expiration
- 2045-11-13
AI Technical Summary
Existing technologies struggle to achieve simultaneous, high spatiotemporal resolution, and non-destructive quantitative measurement of the deformation behavior and induced flow field of stimulus-responsive gels at the microscale. This makes it difficult to establish stable quantitative mappings and achieve comparable evaluation and rapid screening across different formulations and stimulation conditions.
A gel observation chamber was constructed by stacking a first glass slide, an elastic pad, and a second glass slide, configuring a stimulation module, and injecting a medium containing tracer particles to establish an observable and stable flow field in a two-dimensional gel observation chamber. Two-dimensional time-series gel microscopic images were captured using a microscope to determine the proportional relationship between the gel deformation rate and the particle flow velocity.
It achieves simultaneous, high spatiotemporal resolution, and non-destructive quantitative measurement of stimulus-response gel deformation behavior and induced flow field at the microscale, establishes a stable quantitative mapping, and supports comparable evaluation and rapid screening under different formulations and stimulus conditions.
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Figure CN121521744A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present disclosure relates to the technical field of gel observation and gel deformation rate determination, and particularly relates to a gel observation chamber establishment method, a gel deformation rate determination method and a system. BACKGROUND
[0002] Thermoresponsive hydrogel is a kind of polymer network material that can produce reversible volume phase transition under temperature stimulus. Taking typical PNIPAM (N-isopropyl acrylamide) as a representative, it undergoes hydrophilic-hydrophobic transition near the lower critical solution temperature (LCST), showing macroscopic swelling / shrinking and microscopic network pore, network chain density and solvation state changes. This characteristic constitutes the basis for its application in the fields of smart materials, controlled drug delivery, microfluidic valves, wearable and soft robots, tissue engineering scaffolds, etc. By adjusting the monomer type, crosslinker content (such as MBA, N,N'-methylenebisacrylamide), comonomer ratio, ionic strength and solvent system, etc., the phase transition temperature, response rate, mechanical strength and hysteresis behavior can be controlled within a certain range. Different application scenarios have specific requirements for response characteristics (for example, in vivo drug release requires a specific response speed and amplitude at near body temperature), so in the research and industrialization process, it is necessary to quickly, accurately and repeatedly quantify the key performance of the gel and further understand the relationship between the microstructure and the macro function.
[0003] At present, the characterization methods for the swelling / shrinking behavior and related properties of thermoresponsive hydrogel mainly include the following types of technologies: a. Basic physicochemical indicators Response temperature (LCST / UCST): commonly used transmittance / cloud point method, differential scanning calorimetry (DSC), dynamic light scattering (DLS), etc. This kind of method can determine the phase transition starting, peak or completion temperature interval, which is used for formula screening and application temperature range limitation (ISO 11357-3:2018《Determination of temperature and enthalpy of melting and crystallization》; ASTM D3418-21《Standard Test Method for Transition Temperatures and Enthalpies of Fusion and Crystallization of Polymers by Differential Scanning Calorimetry》).
[0004] Volume / area change vs. swelling ratio: Assessing the size and porosity changes of gels under different temperatures / media by gravimetric method (equilibrium liquid uptake), optical imaging (2D projection / thickness measurement), DLS / PCS (particle size change), SAXS / SANS (nanoscale dimensions and correlation length) (ASTM D570-22 Standard Test Methods for Water Absorption of Plastics; ISO 22412:2017 Particle size analysis — Dynamic light scattering (DLS)).
[0005] Mechanical and viscoelastic parameters: Obtaining linear and nonlinear viscoelastic spectra of gels under controlled stress / strain by rheology (storage modulus G', loss modulus G''), AFM nanomechanics, DMA testing for predicting load-bearing capacity, deformation, and fatigue behavior (ISO 3219-1:2021 Rheology — Part 1: Vocabulary and symbols for rotational and oscillatory rheometry; ISO 14577-1:2015 Metallic materials — Instrumented indentation test for hardness and materials parameters).
[0006] b. Kinetic response indicators Response speed, deformation amplitude, recovery time: Reflecting the time dependence of gels under temperature step or gradient stimuli. Common methods include optical size tracking under temperature jump, recording of mass change over time, DLS time correlation function analysis (ASTM F2900-11 Standard Guide for Characterization of Hydrogels used in Regenerative Medicine).
[0007] Kinetic characteristics: Such as t10-90, half-width, apparent rate constant, equivalent diffusion coefficient, response hysteresis (difference between heating / cooling cycles), cycle durability and fatigue attenuation, temperature ramp-rate dependence, etc.
[0008] 2. Drawbacks of existing technology: Although the above methods constitute the mainstream technical route for the characterization of temperature-sensitive gels, there are still the following common deficiencies in terms of rapid, accurate, dynamic and comparable engineering evaluation: a. Coupling of kinetics and in-situ information is insufficient: Most methods measure equilibrium parameters (such as swelling ratio, LCST) under static or quasi-static conditions, making it difficult to reflect the rapid, non-equilibrium response process.
[0009] b. Mechanical characterization does not match the real working state: Traditional rheological / tensile tests are mostly conducted under controlled strain / stress, closed clamp conditions, which cannot directly reflect the driving force and power output generated by the gel when it is free to swell / shrink under no constraint or partial constraint, and the experimental conditions are seriously disconnected from the real working conditions.
[0010] c. Low flux, lack of quantitative indicators: Many characterization methods (such as SAXS / SANS, AFM, DMA) are time-consuming, expensive and require professional operation, which is not suitable for rapid online / batch detection on the production line. There is currently a lack of uniform, quantifiable performance evaluation standards and reference procedures, which affects the comparability of industrial quality control and intellectual property claims. SUMMARY
[0011] The present disclosure proposes a gel observation chamber establishment method and the corresponding technical solution of a gel deformation rate determination method and system.
[0012] According to an aspect of the present disclosure, a gel observation chamber establishment method is provided, comprising: laminating a first glass slide, an elastic gasket and a second glass slide to construct a quasi-two-dimensional closed observation chamber; wherein the elastic gasket is provided with a target gel placement area; the target gel placement area is configured with a stimulation module corresponding to at least one or several of temperature stimulation, pH stimulation, ion strength stimulation, light stimulation, electric field stimulation, and magnetic field stimulation on any one side of the first glass slide, the elastic gasket and the second glass slide corresponding to the target gel placement area; after injecting a medium containing tracer particles into the quasi-two-dimensional closed observation chamber until it is full without air bubbles, and standing for a set time, a stable flow field two-dimensional gel observation chamber is obtained.
[0013] Preferably, the first glass slide and the second glass slide are configured as quartz sheets of a set size; and / or, the elastic gasket is configured as one or several of silicone, polydimethylsiloxane and polytetrafluoroethylene sheet of a set thickness; and / or, the target gel placement area is configured as a hollow circular window or a rectangular window or a square window; and / or, the tracer particles are configured as one or several of styrene, polymethyl methacrylate and silica microspheres of a set particle size range.
[0014] According to an aspect of the present disclosure, a gel deformation rate determination method is provided, comprising: obtaining a two-dimensional time sequence gel microscopic image corresponding to a two-dimensional stable flow field observable gel observation chamber established by the above-mentioned gel observation chamber establishment method under a set quasi-step temperature stimulus, a k standard curve, and a proportional relationship between a gel deformation rate and a particle flow velocity; extracting the particle flow velocity corresponding to the two-dimensional time sequence gel microscopic image; and determining the gel deformation rate corresponding to the two-dimensional time sequence gel microscopic image based on the particle flow velocity, a proportional coefficient corresponding to the k standard curve, and the proportional relationship.
[0015] Preferably, the set quasi-step temperature stimulus is constructed, comprising: obtaining a first set temperature corresponding to a set temperature range of the set quasi-step temperature and a second set temperature greater than the first set temperature; maintaining the first set temperature and the second set temperature within a set temperature stability in each period of a set temperature regulation period of the set quasi-step temperature; and switching the first set temperature to the second set temperature or the second set temperature to the first set temperature within a set temperature rise and fall rate and a set gradient switching time, so as to construct the set quasi-step temperature stimulus.
[0016] Preferably, the k standard curve is determined, comprising: repeatedly measuring the gel deformation rate and the particle flow velocity corresponding to the standard sample of the target gel with a known formula or crosslinking degree under the same experimental conditions as in the gel deformation rate determination process; and determining the k standard curve by using the proportional relationship between the gel deformation rate and the particle flow velocity corresponding to the standard sample of the target gel with a known formula or crosslinking degree.
[0017] Preferably, the proportional relationship between the gel deformation rate and the particle flow velocity is determined, comprising: performing linear regression fitting on the gel deformation rate and the particle flow velocity corresponding to a plurality of standard samples of the target gel with a known formula or crosslinking degree under the same experimental conditions as in the gel deformation rate determination process, to determine the proportional relationship between the gel deformation rate and the particle flow velocity.
[0018] Preferably, determining the gel deformation rate corresponding to the standard sample includes: segmenting the gel region of the two-dimensional time-series gel micrograph to obtain a corresponding two-dimensional time-series gel image; performing edge detection on the two-dimensional time-series gel image to obtain a two-dimensional time-series gel boundary image; projecting the gel micrograph within the two-dimensional time-series gel boundary image to obtain a two-dimensional time-series gel micrograph area projection image; calculating the gel micrograph projection area of the two-dimensional time-series gel micrograph area projection image; and calculating the first derivative of the gel micrograph projection area of the two-dimensional time-series gel micrograph area projection image with time to determine the corresponding gel deformation rate.
[0019] Preferably, before performing linear regression fitting on the gel deformation rate and particle flow velocity corresponding to the standard sample, determining the gel deformation rate corresponding to the standard sample includes: segmenting the gel region of the two-dimensional time-series gel micrograph corresponding to the standard sample, including: segmenting the gel region of the two-dimensional time-series gel micrograph to obtain the corresponding two-dimensional time-series gel image; performing edge detection on the two-dimensional time-series gel image to obtain the two-dimensional time-series gel boundary image; calculating the second first derivative of the selected matching gel boundary feature points in the two-dimensional time-series gel boundary image as a function of time to determine the corresponding gel deformation rate.
[0020] Preferably, the gel deformation rate corresponding to the two-dimensional time-series gel micrograph is determined based on the first gel deformation rate corresponding to the gel microscopic projection area of the two-dimensional time-series gel micrograph and the second gel deformation rate corresponding to the gel boundary feature points of the two-dimensional time-series gel micrograph.
[0021] Preferably, the step of segmenting the gel region of the two-dimensional time-series gel micrograph corresponding to the standard sample to obtain the corresponding two-dimensional time-series gel image includes: obtaining an initial reference region corresponding to a first frame gel micrograph in the two-dimensional time-series gel micrograph; performing binary segmentation on the initial reference region corresponding to the first frame gel micrograph to obtain a first frame gel segmentation micrograph; determining a global exclusion mask based on the first frame gel micrograph in the two-dimensional time-series gel micrograph; processing the first frame gel segmentation micrograph based on the global exclusion mask to obtain a first frame gel target segmentation micrograph corresponding to the two-dimensional time-series gel image; when performing gel region segmentation on a gel micrograph other than the first frame gel micrograph, using the segmentation binary mask corresponding to the previous frame gel target segmentation micrograph as the initial reference region image of the current frame gel micrograph to perform binary segmentation on the current frame gel micrograph grayscale image to obtain the current frame gel segmentation micrograph; and processing the current frame gel segmentation micrograph based on the global exclusion mask to obtain the current frame gel target segmentation micrograph corresponding to the two-dimensional time-series gel image.
[0022] According to one aspect of this disclosure, a gel observation chamber establishment system is provided, comprising: a stacking processing unit for stacking a first glass slide, an elastic pad, and a second glass slide to construct a quasi-two-dimensional sealed observation chamber; wherein the elastic pad is provided with a target gel placement area; a stimulation module unit for arranging stimulation modules corresponding to at least one or more of the following stimuli: temperature stimulation, pH stimulation, ionic strength stimulation, light stimulation, electric field stimulation, and magnetic field stimulation, on any one side of the first glass slide, the elastic pad, and the second glass slide corresponding to the target gel placement area; and an injection and settling unit for injecting a medium containing tracer particles into the quasi-two-dimensional sealed observation chamber until it is filled without air bubbles, and then settling for a set time to obtain an observable stable flow field two-dimensional gel observation chamber.
[0023] According to one aspect of this disclosure, a gel observation chamber establishment system apparatus is provided, comprising: a processor; a memory for storing processor-executable instructions; wherein the processor is configured to invoke the instructions stored in the memory to execute the gel observation chamber establishment method described above.
[0024] According to one aspect of this disclosure, a gel observation chamber establishment system apparatus is provided, comprising: a computer-readable storage medium having stored thereon computer program instructions, which, when executed by a processor, implement the above-described gel observation chamber establishment method.
[0025] According to one aspect of this disclosure, a gel observation chamber establishment system apparatus is provided, comprising: a computer program product, wherein the computer program product is configured with computer programs / instructions, which, when executed by a processor, implement the above-described gel observation chamber establishment method.
[0026] According to one aspect of this disclosure, a gel observation chamber is provided, comprising: a first glass slide, an elastic pad, and a second glass slide; the first glass slide and the second glass slide are respectively disposed on both sides of the elastic pad to construct a quasi-two-dimensional sealed observation chamber; wherein, the elastic pad is provided with a target gel placement area; any one side of the first glass slide, the elastic pad, and the second glass slide corresponding to the target gel placement area is provided with a stimulation module corresponding to at least one or more of the following stimuli: temperature stimulation, pH stimulation, ionic strength stimulation, light stimulation, electric field stimulation, or magnetic field stimulation; the quasi-two-dimensional sealed observation chamber is filled with a medium containing tracer particles after being left to stand for a set time, constructing an observable stable flow field two-dimensional gel observation chamber.
[0027] According to one aspect of this disclosure, a gel deformation rate determination system is provided, comprising: an acquisition unit for acquiring an observable stable flow field two-dimensional gel observation chamber established under a set quasi-step temperature stimulus using the gel observation chamber establishment method described above, or an observable stable flow field two-dimensional gel observation chamber established using the gel observation chamber establishment system described above, or a two-dimensional time-series gel micrograph corresponding to the gel observation chamber, a k-standard curve, and a proportional relationship between gel deformation rate and particle flow velocity; an extraction unit for extracting the particle flow velocity corresponding to the two-dimensional time-series gel micrograph; and a determination unit for determining the gel deformation rate corresponding to the two-dimensional time-series gel micrograph based on the particle flow velocity, the proportionality coefficient corresponding to the k-standard curve, and the proportional relationship.
[0028] According to one aspect of this disclosure, a gel deformation rate determination system is provided, comprising: a processor; a memory for storing processor-executable instructions; wherein the processor is configured to invoke the instructions stored in the memory to perform the gel deformation rate determination method described above.
[0029] According to one aspect of this disclosure, a gel deformation rate determination system is provided, comprising: a computer-readable storage medium having computer program instructions stored thereon, wherein the computer program instructions, when executed by a processor, implement the above-described gel deformation rate determination method.
[0030] According to one aspect of this disclosure, a gel deformation rate determination system is provided, comprising: a computer program product, the computer program product being configured with computer programs / instructions that, when executed by a processor, implement the above-described gel deformation rate determination method. In this disclosure, a technical solution is proposed for establishing a gel observation chamber and determining the gel deformation rate, as well as a corresponding system. This solution addresses the difficulty in achieving synchronous, high spatiotemporal resolution, and non-destructive quantitative measurement of the "deformation behavior" and "induced flow field" of stimulus-responsive gels at the microscale, which makes it difficult to establish a stable quantitative mapping between the two and thus hinders at least one technical problem in achieving comparable evaluation and rapid screening between different formulations and stimulation conditions.
[0031] It should be understood that the above general description and the following detailed description are exemplary and explanatory only, and are not intended to limit this disclosure.
[0032] Other features and aspects of this disclosure will become clear from the following detailed description of exemplary embodiments with reference to the accompanying drawings. Attached Figure Description
[0033] The accompanying drawings, which are incorporated in and form part of this specification, illustrate embodiments consistent with this disclosure and, together with the specification, serve to illustrate the technical solutions of this disclosure.
[0034] Figure 1 A flowchart illustrating a method for establishing a gel observation chamber according to an embodiment of the present disclosure is shown; Figure 2 Fluid velocity profiles according to embodiments of the present disclosure are shown. With the rate of change of gel area Time series comparison and and The linear fitting results; (a) fluid velocity curve With the rate of change of gel area (a) Time series comparison; (b) and The linear fitting results; Figure 3 The diagram illustrates the non-monotonic relationship between the peak gel flow rate, peak area change rate, and peak flow rate area as a function of MBA content, according to embodiments of the present disclosure. Figure 4 The linear calibration relationship between the maximum induced flow rate and the maximum deformation rate of gels with different MBA contents according to embodiments of the present disclosure is shown. Figure 5 A comparison of two-dimensional observation plots and instantaneous flow rate plots of NIPAM-based BZ gel and AAM-based BZ gel according to embodiments of the present disclosure is shown. Figure 6The flow rate and area of NIPAM-based BZ gel and AAM-based BZ gel according to embodiments of the present disclosure are shown as curves over time. Figure 7 The comparison of the peak induced flow rate Vmax, chemical oscillation frequency f, and area change rate Amax of NIPAM-based BZ gel and AAM-based BZ gel according to embodiments of the present disclosure is shown. Figure 8 This is a block diagram illustrating an electronic device 800 according to an exemplary embodiment; Figure 9 This is a block diagram illustrating an electronic device 1900 according to an exemplary embodiment. Detailed Implementation
[0035] Various exemplary embodiments, features, and aspects of this disclosure will now be described in detail with reference to the accompanying drawings. The same reference numerals in the drawings denote elements that have the same or similar functions. Although various aspects of the embodiments are shown in the drawings, they are not necessarily drawn to scale unless specifically indicated otherwise.
[0036] The term “exemplary” as used herein means “serving as an example, embodiment, or illustration.” Any embodiment illustrated herein as “exemplary” is not necessarily to be construed as superior to or better than other embodiments.
[0037] In this document, the term "and / or" is merely a description of the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent three cases: A alone, A and B simultaneously, and B alone. Furthermore, the term "at least one" in this document means any combination of at least two of any one or more elements. For example, including at least one of A, B, and C can mean including any one or more elements selected from the set consisting of A, B, and C.
[0038] Furthermore, to better illustrate this disclosure, numerous specific details are set forth in the following detailed description. Those skilled in the art will understand that this disclosure can be practiced without certain specific details. In some instances, methods, means, components, and circuits well known to those skilled in the art have not been described in detail in order to highlight the main points of this disclosure.
[0039] It is understood that the various method embodiments mentioned above in this disclosure can be combined with each other to form combined embodiments without violating the principle and logic. Due to space limitations, this disclosure will not elaborate further.
[0040] In addition, this disclosure also provides a gel observation chamber establishment device or system, a gel deformation rate determination device or system, electronic equipment, computer-readable storage medium, and program, all of which can be used to implement any of the gel observation chamber establishment methods and gel deformation rate determination methods provided in this disclosure. The corresponding technical solutions and descriptions are described in the corresponding descriptions in the method section and will not be repeated here.
[0041] Existing technologies struggle to achieve simultaneous, high spatiotemporal resolution, and non-destructive quantitative measurement of the "deformation behavior" and "induced flow field" of stimulus-responsive gels at the microscale. This makes it difficult to establish a stable quantitative mapping between the two, hindering comparable evaluation and rapid screening across different formulations and stimulus conditions. The purpose of this invention is to overcome these shortcomings in existing gel characterization techniques by proposing a technical solution for establishing a gel observation chamber and determining the gel deformation rate, along with a corresponding system.
[0042] Figure 1 A flowchart illustrating a method for establishing a gel observation chamber according to an embodiment of the present disclosure is shown, such as... Figure 1 As shown, the method for establishing the gel observation chamber includes: Step S101: Stacking a first glass slide, an elastic pad, and a second glass slide to construct a quasi-two-dimensional sealed observation chamber; wherein, the elastic pad is provided with a target gel placement area; Step S102: Any one side of the first glass slide, the elastic pad, and the second glass slide corresponding to the target gel placement area is provided with a stimulation module corresponding to at least one or more of the following stimuli: temperature stimulation, pH stimulation, ionic strength stimulation, light stimulation, electric field stimulation, and magnetic field stimulation; Step S103: After injecting a medium containing tracer particles into the quasi-two-dimensional sealed observation chamber until it is filled without bubbles, it is left to stand for a set time to obtain an observable stable flow field two-dimensional gel observation chamber. This method aims to solve at least one technical problem in which it is difficult to achieve synchronous, high spatiotemporal resolution, and non-destructive quantitative measurement of the "deformation behavior" and "induced flow field" of stimulus-responsive gels at the microscale, making it difficult to establish a stable quantitative mapping between the two, and thus making it impossible to achieve comparable evaluation and rapid screening between different formulations and different stimulation conditions.
[0043] In the embodiments of this disclosure and other possible embodiments, a microscope (ordinary binoculars, confocal microscope, or fluorescence wide-field microscope) is used to capture two-dimensional time-series gel micrographs with high spatiotemporal resolution (set spatiotemporal resolution) and non-destructive quantitative measurement corresponding to the deformation behavior and induced flow field of the target gel under a set quasi-step temperature stimulus and a set quasi-step light stimulus.
[0044] In embodiments of this disclosure and other possible embodiments, determining the quasi-step stimulation module corresponding to at least one or more of the quasi-step stimuli selected from quasi-step temperature stimulation, pH stimulation, ionic intensity stimulation, light stimulation, electric field stimulation, and magnetic field stimulation includes: determining the sensitive properties corresponding to the target gel; and configuring the quasi-step stimulation module corresponding to at least one or more of the quasi-step stimuli selected from quasi-step temperature stimulation, pH stimulation, ionic intensity stimulation, light stimulation, electric field stimulation, and magnetic field stimulation based on the sensitive properties. For example, if the sensitive properties corresponding to the target gel are configured as temperature-sensitive and photosensitivity, then a temperature stimulation and light stimulation module is configured on any one side of the first slide, the elastic pad, and the second slide corresponding to the target gel placement area. Some stimuli (signals) may not achieve an ideal step change due to physical limitations or design requirements, but instead change rapidly in a near-step manner; this can be referred to as a "quasi-step" signal.
[0045] In embodiments of this disclosure, the first and second glass slides are configured as quartz sheets of a predetermined size; and / or, the elastic pad is configured as one or more of silicone, polydimethylsiloxane, and polytetrafluoroethylene sheets of a predetermined thickness; and / or, the target gel placement area is configured as a gel placement cavity corresponding to a hollowed-out circular, rectangular, or square window; and / or, the tracer particles are configured as one or more of styrene, polymethyl methacrylate, and silica microspheres within a predetermined particle size range.
[0046] In embodiments of this disclosure and other possible embodiments, determining that the quasi-two-dimensional sealed observation chamber is filled with a medium containing tracer particles until it is (bubble-free) includes: acquiring an image of the interior of the observation chamber corresponding to the quasi-two-dimensional sealed observation chamber and a preset target detection model (bubble target detection model); using the preset target detection model (bubble target detection model) to perform bubble target detection on the image of the interior of the observation chamber; if no bubbles are detected, then determining that the quasi-two-dimensional sealed observation chamber is filled with a medium containing tracer particles until it is bubble-free. The preset target detection model (bubble target detection model) is configured as a target detection network based on a YOLO network. Before performing bubble target detection on the image of the interior of the observation chamber using the preset target detection model (bubble target detection model), multiple images of the interior of the observation chamber and their corresponding bubble target detection label images are acquired for training the target detection network; the target detection network is trained using these multiple images of the interior of the observation chamber and their corresponding bubble target detection label images to obtain the preset target detection model.
[0047] In embodiments of this disclosure and other possible embodiments, determining that the medium containing tracer particles is injected into the quasi-two-dimensional closed observation chamber until it is filled (without bubbles) further includes: if no bubbles are detected, obtaining the volume of the medium containing tracer particles injected into the quasi-two-dimensional closed observation chamber; if the volume of the medium reaches a preset volume, determining that the medium containing tracer particles is injected into the quasi-two-dimensional closed observation chamber until it is filled without bubbles.
[0048] In embodiments of this disclosure and other possible embodiments, a method is proposed to simultaneously measure the deformation behavior of a stimulus-responsive gel and the induced velocity of the surrounding flow field at the microscale, and to establish a quantitative relationship (proportional relationship) between the average particle velocity and the gel response characteristic quantity.
[0049] In the embodiments of this disclosure and other possible embodiments, a quasi-two-dimensional sealed observation chamber is constructed by stacking a glass slide (upper slide, first slide) - an elastic spacer - a glass slide (lower slide, second slide). The upper and lower slides can be conventional glass slides or quartz slides, preferably 5×5 cm (set size) square quartz slides. The elastic spacer is commonly made of silicone, polydimethylsiloxane (PDMS), or polytetrafluoroethylene sheets, with a thickness of 0.1-2 mm to accommodate gels of different thicknesses. The center of the elastic spacer is a circular or square window with a cutout (target gel placement area), preferably a circular window with a radius of 1.5 cm.
[0050] In the embodiments of this disclosure and other possible embodiments, the target gel is placed at the center of a quasi-two-dimensional sealed observation chamber. A medium containing tracer particles (commonly water) is injected into the quasi-two-dimensional sealed observation chamber until it is completely filled without air bubbles. The chamber is then sealed to prevent leakage and allowed to stand for 5-10 minutes (a set time) to eliminate assembly-induced flow, resulting in a stable, observable flow field two-dimensional gel observation chamber. The tracer particles are commonly polystyrene (PS), polymethyl methacrylate (PMMA), or silica microspheres, preferably matched to the medium density. The particle size range is preferably set to 1-5 μm to improve PIV spatial resolution and suppress sedimentation (Stokes sedimentation is negligible). The set concentration of the medium containing tracer particles is configured to be 2-10 mg / mL, preferably 5 mg / mL, to ensure sufficient particle image density without overexposure.
[0051] In embodiments of this disclosure, a method for determining gel deformation rate is also proposed, comprising: acquiring a two-dimensional time-series gel micrograph, a k-standard curve, and a proportional relationship between gel deformation rate and particle flow velocity corresponding to an observable stable flow field two-dimensional gel observation chamber established using the above-described gel observation chamber establishment method under a set quasi-step temperature stimulus; extracting the gel deformation rate corresponding to the gel microscopic projection area or gel boundary feature points of the two-dimensional time-series gel (thermosensitive gel) micrograph; and determining the gel deformation rate corresponding to the two-dimensional time-series gel micrograph based on the particle flow velocity, the proportional coefficient corresponding to the k-standard curve, and the proportional relationship.
[0052] In embodiments of this disclosure, constructing the set quasi-step temperature stimulus includes: obtaining a first set temperature corresponding to the set temperature range of the set quasi-step temperature and a second set temperature greater than the first set temperature; maintaining the first set temperature and the second set temperature within the set temperature stability range in each cycle of the set temperature control cycle of the set quasi-step temperature; and switching the first set temperature to the second set temperature or the second set temperature to the first set temperature within a set heating / cooling rate and a set gradient switching time to construct the set quasi-step temperature stimulus.
[0053] In the embodiments of this disclosure and other possible embodiments, the temperature control module is placed on one side of the loading / unloading slide corresponding to the target gel in the stable flow field two-dimensional gel observation chamber. The temperature control module uses a Peltier element to achieve rapid and precise temperature control of the micro-area environment in the stable flow field two-dimensional gel observation chamber. The heating and cooling rate is set to 1-10℃ / s, the temperature stability is set to ±0.5℃, the preferred temperature range is 20-35℃, the preferred temperature control cycle is 5-20min, the gradient switching time is set to ≤10s (to achieve quasi-step temperature stimulation), and the number of temperature cycles is generally more than 5 quasi-step temperature stimulations to ensure the validity of data statistics.
[0054] In the process of achieving quasi-step temperature stimulation, the microscopic platform can select from ordinary binoculars, confocal microscopes (such as Leica SP8), or fluorescence wide-field microscopes according to the gel size and thickness of the target gel in the stable flow field two-dimensional gel observation chamber (the observation instruments can be adjusted according to the gel observation requirements). The time resolution of the microscopic platform is preferably 0.1-5 Hz (one frame every 10 s to every 0.2 s). The pixel calibration of the target gel in the stable flow field two-dimensional gel observation chamber using ordinary binoculars, confocal microscopes, or fluorescence wide-field microscopes depends on the presentation system and the size of the observed target, preferably 0.2-5 μm / px, to obtain two-dimensional time-series gel microscopic images.
[0055] In embodiments of this disclosure, determining the k-standard curve includes: under the same experimental conditions as in the gel deformation rate determination process, repeatedly and independently measuring the gel deformation rate and particle flow velocity of the standard sample corresponding to the target gel with a known formulation or degree of crosslinking; and determining the k-standard curve by utilizing the proportional relationship between the gel deformation rate and particle flow velocity of the standard sample corresponding to the target gel with a known formulation or degree of crosslinking, obtained through repeated and independent measurements.
[0056] In embodiments of this disclosure and other possible embodiments, two-dimensional time-series gel micrographs derived from a microscope are used simultaneously for two-part analysis.
[0057] a. PIV (Particle Image Velocimetry) velocity analysis: PIVlab (or equivalent software) is used to perform particle velocimetry on two-dimensional time-series gel micrographs to obtain the particle flow velocity corresponding to the two-dimensional time-series gel micrographs, such as the average particle flow velocity and the maximum mainstream velocity.
[0058] b. Gel Deformation Analysis: The gel boundary of the two-dimensional time-series gel micrograph is automatically identified by a self-developed image processing code to obtain a two-dimensional time-series gel boundary image; the gel micrograph within the gel boundary is determined using the two-dimensional time-series gel boundary image; the two-dimensional time-series gel micrograph area image is projected to obtain a two-dimensional time-series gel micrograph area projection image; and the gel deformation rate is calculated based on the temporal change of the gel projection area in the two-dimensional time-series gel micrograph area projection image.
[0059] In embodiments of this disclosure, determining the proportional relationship between the gel deformation rate and the particle flow velocity includes: under the same experimental conditions as in the process of determining the gel deformation rate, performing linear regression fitting on the gel deformation rate and particle flow velocity corresponding to multiple standard samples of a target gel with a known formulation or degree of crosslinking, to determine the proportional relationship between the gel deformation rate and the particle flow velocity.
[0060] In embodiments of this disclosure and other possible embodiments, the gel deformation rate ( V g ) and particle velocity (particle flow velocity, V p Linear regression fitting was performed to obtain the proportional relationship between gel deformation rate and particle flow velocity. (in, k (This is the proportionality coefficient).
[0061] In the embodiments of this disclosure and other possible embodiments, at least five target gels with known formulations or degrees of crosslinking are selected as standards. Under the same experimental conditions (quasi-step temperature stimulation of ≥5 cycles per temperature cycle), the gel deformation rate of each standard is independently repeated ≥3 times. V g ) and particle velocity (particle flow velocity, V p Linear regression fitting was performed to obtain the proportional relationship between gel deformation rate and particle flow velocity, and the corresponding relationship between the k value of each standard sample and its structural parameters (such as crosslinking degree, solid content, swelling ratio) was obtained to establish a k standard curve.
[0062] In embodiments of this disclosure and other possible embodiments, determining the gel deformation rate corresponding to the standard sample before performing linear regression fitting on the gel deformation rate and particle flow velocity corresponding to the standard sample includes: segmenting the gel region of the two-dimensional time-series gel micrograph corresponding to the standard sample to obtain the corresponding two-dimensional time-series gel image; performing edge detection on the two-dimensional time-series gel image to obtain the two-dimensional time-series gel boundary image; calculating the gel microscopic area of the two-dimensional time-series gel microscopic area image; calculating the first first derivative of the gel microscopic area of the two-dimensional time-series gel microscopic area image with time or calculating the second first derivative of the selected matching gel boundary feature points in the two-dimensional time-series gel boundary image with time to determine the corresponding gel deformation rate.
[0063] In embodiments of this disclosure, determining the gel deformation rate corresponding to the standard sample before performing linear regression fitting on the gel deformation rate and particle flow velocity corresponding to the standard sample includes: segmenting the gel region of the two-dimensional time-series gel micrograph corresponding to the standard sample to obtain a corresponding two-dimensional time-series gel image; performing edge detection on the two-dimensional time-series gel image to obtain a two-dimensional time-series gel boundary image; projecting the gel micrograph within the two-dimensional time-series gel boundary image according to a set direction to obtain a two-dimensional time-series gel micrograph area projection image; calculating the gel micrograph projection area of the two-dimensional time-series gel micrograph area projection image; and calculating the first derivative of the gel micrograph projection area of the two-dimensional time-series gel micrograph area projection image with time to determine the corresponding gel deformation rate.
[0064] In embodiments of this disclosure, determining the gel deformation rate corresponding to the standard sample before performing linear regression fitting on the gel deformation rate and particle flow velocity corresponding to the standard sample includes: segmenting the gel region of the two-dimensional time-series gel micrograph corresponding to the standard sample to obtain the corresponding two-dimensional time-series gel image; performing edge detection on the two-dimensional time-series gel image to obtain the two-dimensional time-series gel boundary image; and calculating the second first derivative of the selected matching gel boundary feature points in the two-dimensional time-series gel boundary image as a function of time to determine the corresponding gel deformation rate.
[0065] In embodiments of this disclosure and other possible embodiments, the gel deformation rate or gel strain rate is defined as: gel deformation rate based on the area method: ( A This represents the projected area of the gel microscopy. t Representing a time series, g (Representing gel). Gel deformation rate based on the keypoint method: (Displacement rate of selected gel boundary feature point L in a two-dimensional time-series gel boundary image). PIV and deformation data are aligned using timestamps.
[0066] In the embodiments of this disclosure and other possible embodiments, the gel deformation rate corresponding to the two-dimensional time-series gel microscopy image is determined based on the first gel deformation rate corresponding to the gel microscopic projection area of the two-dimensional time-series gel microscopy image and the second gel deformation rate corresponding to the gel boundary feature points of the two-dimensional time-series gel microscopy image.
[0067] In embodiments of this disclosure and other possible embodiments, a technical solution is proposed to improve the accuracy of determining the gel deformation rate corresponding to the two-dimensional time-series gel micrograph. The method for determining the gel deformation rate corresponding to the two-dimensional time-series gel micrograph based on a first gel deformation rate corresponding to the gel microscopic projection area of the two-dimensional time-series gel micrograph and a second gel deformation rate corresponding to the gel boundary feature points of the two-dimensional time-series gel micrograph includes: obtaining a first set weight and a second set weight; multiplying the first set weight by the first gel deformation rate to obtain a first weighted gel deformation rate; multiplying the second set weight by the second gel deformation rate to obtain a second weighted gel deformation rate; calculating the average of the first weighted gel deformation rate and the second weighted gel deformation rate, or selecting the maximum value of the first weighted gel deformation rate and the second weighted gel deformation rate, to determine the gel deformation rate corresponding to the two-dimensional time-series gel micrograph.
[0068] In embodiments of this disclosure and other possible embodiments, before calculating the second first derivative of the time-varying gel boundary feature points selected in the two-dimensional time-series gel boundary image and determining the corresponding gel deformation rate, the method includes: registering the two-dimensional time-series gel image to obtain multiple deformation fields; selecting gel boundary feature points in fixed gel images within the two-dimensional time-series gel image; and using the multiple deformation fields to determine the gel boundary feature points in the fixed gel image that match the selected gel boundary feature points in their registered floating gel images.
[0069] In embodiments of this disclosure and other possible embodiments, before calculating the second first derivative of the time-varying gel boundary feature points selected and matched in the two-dimensional time-series gel boundary image to determine the corresponding gel deformation rate, the method includes: registering the gel target segmentation microscopic image corresponding to the two-dimensional time-series gel image to obtain multiple deformation fields; selecting gel boundary feature points in the fixed gel image of the two-dimensional time-series gel image respectively; and using the multiple deformation fields to determine the gel boundary feature points in the fixed gel image and the gel boundary feature points in the registered floating gel image that match the selected gel boundary feature points.
[0070] For unknown gels, it is only necessary to measure the induced particle flow rate (particle flow velocity). V p The gel deformation rate can then be inferred using the k-value corresponding to the proportionality coefficient. V g This allows for the evaluation of stimulus response performance (such as response sensitivity and oscillation intensity). Multiple chambers can be arranged in parallel on a high-throughput platform to enable rapid formulation screening and quality consistency monitoring. The temperature control module can also be replaced / overlaid with pH, light, electrical, magnetic, or chemical modules to achieve multi-stimuli adaptation.
[0071] In embodiments of this disclosure, the step of segmenting the gel region of the two-dimensional time-series gel micrograph corresponding to the standard sample to obtain the corresponding two-dimensional time-series gel image includes: obtaining an initial reference region corresponding to a first frame gel micrograph in the two-dimensional time-series gel micrograph; performing binary segmentation on the initial reference region corresponding to the first frame gel micrograph to obtain a first frame gel segmentation micrograph; determining a global exclusion mask based on the first frame gel micrograph in the two-dimensional time-series gel micrograph; processing the first frame gel segmentation micrograph based on the global exclusion mask to obtain a first frame gel target segmentation micrograph corresponding to the two-dimensional time-series gel image; when performing gel region segmentation on a gel micrograph other than the first frame gel micrograph, using the segmentation binary mask corresponding to the previous frame gel target segmentation micrograph as the initial reference region image of the current frame gel micrograph to perform binary segmentation on the current frame gel micrograph grayscale image to obtain the current frame gel segmentation micrograph; and processing the current frame gel segmentation micrograph based on the global exclusion mask to obtain the current frame gel target segmentation micrograph corresponding to the two-dimensional time-series gel image.
[0072] In embodiments of this disclosure and other possible embodiments, the step of segmenting the gel region of the two-dimensional time-series gel micrograph corresponding to the standard sample to obtain the corresponding two-dimensional time-series gel image includes: acquiring a preset gel region segmentation model; using the preset gel region segmentation model to segment the gel region of the two-dimensional time-series gel micrograph corresponding to the standard sample to obtain the corresponding two-dimensional time-series gel mask image to be processed; processing the two-dimensional time-series gel mask image to be processed according to the global exclusion mask to obtain multiple gel target segmentation micrograph images that do not contain the global exclusion mask; and extracting the gel region of the two-dimensional time-series gel micrograph using the multiple gel target segmentation micrograph images to obtain gel target segmentation micrograph images corresponding to all frames of the two-dimensional time-series gel image. The network trained using the two-dimensional time-series gel image and its corresponding two-dimensional time-series gel mask label image (the network corresponding to the preset gel region segmentation model) can be configured as one of Enet, U-Net, U-Net++, MagNet, CDSegNet, and DECS-Net.
[0073] In embodiments of this disclosure and other possible embodiments, the steps for automatically identifying the gel area are as follows: 1. Data preparation for two-dimensional time-series gel microscopy images The system reads image files from a specified directory, supporting common formats such as .jpg, .png, or .tif. The system automatically scans the directory to obtain a list of all matching image files. To ensure images are processed in chronological order, the system sorts them according to the numerical identifiers in their filenames; if no valid numbers are found, they are sorted in their original order. The final result is a sequence of image files arranged in ascending chronological order.
[0074] 2. Initialization of the result storage structure The system pre-allocates data structures for storing analysis results, including: the gel microscopic projection area A corresponding to each frame of the two-dimensional time-series gel microscopy image; the gel boundary (gel boundary contour) in the two-dimensional time-series gel boundary image; the corresponding time point array (time series); and the area change rate (i.e., the area increment per unit time, gel deformation rate based on the area method). Simultaneously, the system prompts the user whether they need to save the intermediate processing result image for each frame. If "yes" is selected, a dedicated subfolder is created for output.
[0075] 3. Manual region selection for the initial frame For the first frame of a two-dimensional time-series gel microscopy image, the system loads and displays it in the interactive interface. The user draws a rectangular selection area using the mouse, roughly enclosing the gel region. The system records the position coordinates of this rectangle (top-left corner coordinates and width and height) and generates a binary mask based on this, which serves as the initial reference area for subsequent automatic tracking. This step allows the user to flexibly define the region of interest, avoid background interference, and improve the accuracy of the analysis.
[0076] 4. Timestamp region exclusion mechanism In certain experimental scenarios, two-dimensional time-series gel microscopy images may contain fixed-position timestamps or other irrelevant markers, which may interfere with image segmentation. To address this, the system supports manual labeling of regions to be excluded: users can sequentially select multiple rectangular regions containing timestamps or other irrelevant markers on the first frame (first frame) of the gel microscopy image; the system merges these rectangular regions into a global exclusion mask, which is used to mask the pixels corresponding to the global exclusion mask in subsequent two-dimensional time-series gel microscopy image processing; the location information of all excluded regions corresponding to the global exclusion mask is recorded for later tracking or adjustment.
[0077] 5. Automated frame-by-frame processing workflow Using the active contour model (Chan-Vese model), the first frame of the gel microscopic image is converted to grayscale to obtain the first frame of the gel microscopic grayscale image; the initial reference region image corresponding to step 3 in the first frame of the gel microscopic grayscale image is binary segmented to obtain the first frame of the gel segmented microscopic image; the "global exclusion mask" obtained in step 4 is applied to the first frame of the gel segmented microscopic image corresponding to the segmentation result, and the corresponding position is forcibly set to non-target to obtain the first frame of the gel target segmented microscopic image; the gel area corresponding to the first frame of the gel target segmented microscopic image is calculated.
[0078] Starting from the second frame of the gel microscopy image, the system enters the automated loop processing stage, performing the following operations on each frame of the gel microscopy image: (a) reading the current frame of the gel microscopy image and performing grayscale processing on the current frame of the gel microscopy image to obtain the current frame of the gel microscopy grayscale image; (b) using the segmentation binary mask of the previous frame of the gel microscopy image as the initial reference region image of the current frame of the gel microscopy image, performing binary segmentation on the current frame of the gel microscopy grayscale image to obtain the current frame of the gel segmented microscopy image; (c) applying a "global exclusion mask" to remove gel microscopy images from the current frame of the gel microscopy image. (d) Extract the gel contour of the current frame gel target segmentation micrograph after removing the interference region from the current frame gel segmentation micrograph and calculate the gel area of the current frame; (e) If the segmentation process encounters an anomaly or fails, roll back to use the area and contour results of the previous frame (fault tolerance mechanism) and continue processing the next frame; (f) Generate and save the current frame result image with visual annotations of the segmentation boundary and excluded region according to user options; output the processing progress periodically (every 10 frames).
[0079] 6. Calculation and Output of Dynamic Parameters After processing all frames, the system further calculates the following kinetic indices: Area change rate: the discrete first derivative of the gel area is calculated as the ratio of the gel area difference between adjacent time points to their corresponding time differences; Area change rate acceleration: the second-order change index of the gel area is obtained by performing discrete gradient calculations on the sequence corresponding to the area change rate over time points; Result visualization: gel area-time curves, area change rate-time curves, and area change rate acceleration-time curves are plotted; a comprehensive analysis graph is saved; all analysis results, including time points, areas, boundaries, rates, accelerations, and exclusion region information, are uniformly saved as a .mat format data file for subsequent statistical analysis or use by third-party software.
[0080] 7. Graphical result display The system automatically generates multiple charts to visually display the analysis results. The gel area-time curve shows the trend of gel area evolution over time; the area change rate graph reflects the fluctuations in the rate of gel growth or recession; and the area change rate acceleration graph reveals the speed of rate change, helping to identify key phase transition moments. These charts are saved locally as high-resolution PNG images.
[0081] The execution entity for the gel observation chamber establishment and gel deformation rate determination method can be a gel observation chamber establishment and gel deformation rate determination device or system. For example, the gel observation chamber establishment and gel deformation rate determination method can be executed by a terminal device, server, or other processing device. The terminal device can be a user equipment (UE), mobile device, user terminal, terminal, cellular phone, cordless phone, personal digital assistant (PDA), handheld device, computing device, vehicle-mounted device, wearable device, etc. In some possible implementations, the gel observation chamber establishment and gel deformation rate determination method can be implemented by a processor calling computer-readable instructions stored in memory.
[0082] Those skilled in the art will understand that in the above-described method for establishing a gel observation chamber and determining the gel deformation rate in the specific implementation, the order in which each step is written does not imply a strict execution order and does not constitute any limitation on the implementation process. The specific execution order of each step should be determined by its function and possible internal logic.
[0083] According to one aspect of this disclosure, a gel observation chamber establishment system is provided, comprising: a stacking processing unit for stacking a first glass slide, an elastic pad, and a second glass slide to construct a quasi-two-dimensional sealed observation chamber; wherein the elastic pad is provided with a target gel placement area; a stimulation module unit for arranging stimulation modules corresponding to at least one or more of the following stimuli: temperature stimulation, pH stimulation, ionic strength stimulation, light stimulation, electric field stimulation, and magnetic field stimulation, on any one side of the first glass slide, the elastic pad, and the second glass slide corresponding to the target gel placement area; and an injection and settling unit for injecting a medium containing tracer particles into the quasi-two-dimensional sealed observation chamber until it is filled without air bubbles, and then settling for a set time to obtain an observable stable flow field two-dimensional gel observation chamber.
[0084] According to one aspect of this disclosure, a gel observation chamber establishment system apparatus is provided, comprising: a processor; a memory for storing processor-executable instructions; wherein the processor is configured to invoke the instructions stored in the memory to execute the gel observation chamber establishment method described above.
[0085] According to one aspect of this disclosure, a gel observation chamber establishment system apparatus is provided, comprising: a computer-readable storage medium having stored thereon computer program instructions, which, when executed by a processor, implement the above-described gel observation chamber establishment method.
[0086] According to one aspect of this disclosure, a gel observation chamber establishment system apparatus is provided, comprising: a computer program product, wherein the computer program product is configured with computer programs / instructions, which, when executed by a processor, implement the above-described gel observation chamber establishment method.
[0087] According to one aspect of this disclosure, a gel observation chamber is provided, comprising: a first glass slide, an elastic pad, and a second glass slide; the first glass slide and the second glass slide are respectively disposed on both sides of the elastic pad to construct a quasi-two-dimensional sealed observation chamber; wherein, the elastic pad is provided with a target gel placement area; any one side of the first glass slide, the elastic pad, and the second glass slide corresponding to the target gel placement area is provided with a stimulation module corresponding to at least one or more of the following stimuli: temperature stimulation, pH stimulation, ionic strength stimulation, light stimulation, electric field stimulation, or magnetic field stimulation; the quasi-two-dimensional sealed observation chamber is filled with a medium containing tracer particles after being left to stand for a set time, constructing an observable stable flow field two-dimensional gel observation chamber.
[0088] According to one aspect of this disclosure, a gel deformation rate determination system is provided, comprising: an acquisition unit for acquiring an observable stable flow field two-dimensional gel observation chamber established under a set quasi-step temperature stimulus using the above-described gel observation chamber establishment method, or an observable stable flow field two-dimensional gel observation chamber established using the above-described gel observation chamber establishment system, or a two-dimensional time-series gel micrograph corresponding to the gel observation chamber, a k-standard curve, and a proportional relationship between gel deformation rate and particle flow velocity; an extraction unit for extracting the particle flow velocity corresponding to the two-dimensional time-series gel micrograph; and a determination unit for determining the gel deformation rate corresponding to the two-dimensional time-series gel micrograph based on the particle flow velocity, the proportionality coefficient corresponding to the k-standard curve, and the proportional relationship.
[0089] According to one aspect of this disclosure, a gel deformation rate determination system is provided, comprising a processor and a memory for storing processor-executable instructions; wherein the processor is configured to invoke the instructions stored in the memory to execute the gel deformation rate determination method described above.
[0090] According to one aspect of this disclosure, a gel deformation rate determination system is provided, comprising: a computer-readable storage medium having computer program instructions stored thereon, wherein the computer program instructions, when executed by a processor, implement the above-described gel deformation rate determination method.
[0091] According to one aspect of this disclosure, a gel deformation rate determination system is provided, comprising: a computer program product, the computer program product being configured with computer programs / instructions that, when executed by a processor, implement the above-described gel deformation rate determination method. In some embodiments, the functions or modules of the apparatus provided in this disclosure can be used to perform the gel observation chamber establishment and gel deformation rate determination methods described in the above method embodiments. The specific implementation can be referred to the description of the above method embodiments, and for the sake of brevity, it will not be repeated here.
[0092] Specifically, this invention utilizes a standardized quasi-two-dimensional chamber, density-matched tracing and optimized PIV procedures, programmable rapid stimulation and high-resolution imaging, and... The calibration model with gel deformation rate as the core (the proportional relationship between gel deformation rate and particle flow velocity) systematically solves the above problems, enabling rapid, synchronous, and non-destructive quantitative evaluation of gel response performance. It is especially suitable for performance characterization in miniaturization, high-throughput screening, and dynamic response process research.
[0093] This method not only possesses high spatiotemporal resolution, enabling it to reveal local and transient behaviors that traditional methods cannot observe, but also achieves dynamic, non-destructive, and continuous characterization of gel properties under real-world conditions without disturbing the sample environment. It provides a reliable testing and analysis tool for the design and optimization of smart gel materials in high-performance applications such as microfluidics, biomimetic actuation, and controlled drug release.
[0094] This invention proposes a method and system for simultaneously measuring the deformation behavior of stimulus-responsive gels and the induced surrounding flow velocity at the microscale, and establishing a quantitative relationship between the average particle velocity and gel response characteristic quantities. The specific steps are as follows: 1. Construction of the flow field observation chamber A quasi-two-dimensional sealed observation chamber is constructed by stacking slides (upper slide, first slide), elastic spacers, and lower slides (lower slide, second slide). The upper and lower slides can be conventional glass slides or quartz slides, preferably 5×5 cm (defined size) square quartz slides. The elastic spacers are commonly made of silicone, polydimethylsiloxane (PDMS), or polytetrafluoroethylene (PTFE), with a thickness of 0.1-2 mm to accommodate gels of different thicknesses. The center of the elastic spacer is a hollowed-out circular or square window (for the quasi-two-dimensional sealed observation chamber), preferably a circular window with a radius of 1.5 cm.
[0095] The target gel is placed at the center of a quasi-two-dimensional sealed observation chamber. The chamber is then filled with a medium containing tracer particles (usually water) until it is completely air-free. The chamber is sealed to prevent leakage and allowed to stand for 5-10 minutes (a set time) to eliminate assembly-induced flow, resulting in a stable, observable flow field in the two-dimensional gel observation chamber. The tracer particles are commonly polystyrene (PS), polymethyl methacrylate (PMMA), or silica microspheres, preferably matched to the medium density. A particle size range of 1-5 μm is preferred to improve PIV spatial resolution and suppress sedimentation (Stokes sedimentation is negligible). The medium containing tracer particles is prepared at a concentration of 2-10 mg / mL, preferably 5 mg / mL, to ensure sufficient particle image density without overexposure.
[0096] 2. Stimulation and Imaging System The temperature control module is placed on one side of the loading / unloading slide corresponding to the target gel in the stable flow field two-dimensional gel observation chamber. The temperature control module uses a Peltier element to achieve rapid and precise temperature control of the micro-area environment in the stable flow field two-dimensional gel observation chamber. The heating and cooling rate is set to 1-10℃ / s, the temperature stability is set to ±0.5℃, the preferred temperature range is 20-35℃, the preferred temperature control cycle is 5-20 min, and the gradient switching time is set to ≤10 s (to achieve quasi-step temperature stimulation). The number of temperature cycles is generally more than 5 quasi-step temperature stimulations to ensure the validity of data statistics.
[0097] In the process of achieving quasi-step temperature stimulation, the microscopic platform can select from ordinary binoculars, confocal microscopes (such as Leica SP8), or fluorescence wide-field microscopes according to the gel size and thickness corresponding to the target gel in the stable flow field two-dimensional gel observation chamber (the observation instruments can be adjusted according to the gel observation requirements). The time resolution of the microscopic platform is preferably 0.1-5 Hz (one frame every 10 s to every 0.2 s). The pixel calibration of the target gel in the stable flow field two-dimensional gel observation chamber using ordinary binoculars, confocal microscopes, or fluorescence wide-field microscopes depends on the presentation system and the size of the observed target, preferably 0.2-5 μm / px, to obtain two-dimensional time-series gel microscopic images.
[0098] 3. Data Processing Two-dimensional time-series gel micrographs derived from the microscope were used simultaneously for two parts of the analysis: a. PIV (Particle Image Velocimetry) velocity analysis: PIVlab (or equivalent software) is used to perform particle velocimetry on two-dimensional time-series gel micrographs to obtain the particle flow velocity corresponding to the two-dimensional time-series gel micrographs, such as the average particle flow velocity and the maximum mainstream velocity.
[0099] b. Gel Deformation Analysis: The gel boundary of the two-dimensional time-series gel micrograph is automatically identified by a self-developed image processing code to obtain a two-dimensional time-series gel boundary image; the gel micrograph within the gel boundary is determined using the two-dimensional time-series gel boundary image; the two-dimensional time-series gel micrograph area image is projected to obtain a two-dimensional time-series gel micrograph area projection image; and the gel deformation rate is calculated based on the temporal change of the gel projection area in the two-dimensional time-series gel micrograph area projection image.
[0100] This invention introduces PIV technology into the dynamic performance characterization of smart gels, achieving a paradigm shift from the traditional static, indirect, and macroscopic characterization mode to a dynamic, direct, and micro / nano-scale mode. Specifically, it has the following outstanding advantages: This invention enables global and non-destructive measurement of the dynamic response process of gels: Through non-invasive optical measurement, it can continuously and in real time capture complete fluid dynamic information of the entire observation area (including the outer boundary layer and internal pores of the gel) without interfering with the interaction between the gel and the environment, thus completely overcoming the inherent defects of traditional discrete sampling methods, such as sparse data points and the introduction of environmental interference.
[0101] A simple and feasible quantitative evaluation model was established: This invention overcomes the limitations of traditional qualitative or semi-quantitative descriptions of gel response performance by establishing a linear quantitative relationship model between gel deformation rate and induced flow field particle velocity (the proportional relationship between gel deformation rate and particle flow velocity) through data analysis. This model transforms gel deformation kinetic parameters, which are difficult to measure directly and quickly, into flow field velocity parameters that are easy to measure accurately using particle image velocimetry, making the evaluation of gel response sensitivity, oscillation intensity, and other performance characteristics simple, objective, and quantifiable.
[0102] This method improves measurement efficiency and applicability by simplifying the complex performance evaluation process into a standard image acquisition and software analysis workflow. Once a standard curve with a proportionality coefficient k is obtained through calibration with known samples, for unknown gel samples, only the induced flow field velocity needs to be measured to quickly infer their deformation properties, eliminating the complex step of directly measuring deformation. This significantly improves detection efficiency and is particularly suitable for applications requiring high-throughput screening of gel materials (such as those with different formulations and degrees of crosslinking). Furthermore, this method has relaxed requirements on gel size, making it suitable for research at the micrometer scale and expanding its application range.
[0103] High degree of technological integration and ease of implementation and promotion: This invention cleverly integrates mature commercial components (such as confocal microscopes, Peltier temperature control devices, and Matlab / PIVlab software), eliminating the need for custom development of special or expensive core hardware. The steps described in the solution are clear, and the parameters are well-defined, lowering the technical threshold and facilitating promotion and application in laboratories with conventional microscopic imaging conditions, thus promoting the widespread adoption of this method.
[0104] This invention provides direct data support for the design and optimization of gel devices: In applications such as microfluidics and soft robotics, the function of gel devices ultimately manifests in their manipulation of fluids or their actuation of external forces. This invention measures the hydrodynamic performance of this ultimate function, thus the obtained data has direct guiding significance for predicting and optimizing the performance of gel devices under actual operating conditions, greatly shortening the development cycle from materials research to device application.
[0105] The key technical point of this invention lies in solving the core challenge of simultaneously and quantitatively characterizing the response performance of microscale gels through an innovative integrated measurement scheme. This is specifically reflected in the following three aspects: 1. Key Design for System Integration and Synchronous Observation: A specific structure and experimental environment, the "quasi-two-dimensional sealed observation chamber," was constructed. This design (slide-pad-slide) not only ensures the stability and observability of the flow field (quasi-two-dimensional), but also achieves efficient integration of gel samples, tracer particles, and external temperature-controlled stimuli, laying the foundation for synchronous measurement.
[0106] "Spatiotemporal synchronization of image acquisition and external stimulus application" was achieved. By precisely matching the frequency of microscope image acquisition with the stimulation cycle (such as temperature cycling) of the Peltier temperature control device, it was ensured that each frame of the image accurately corresponded to the deformation and flow field information of the gel under specific stimulation conditions, which is a prerequisite for establishing a reliable quantitative relationship.
[0107] 2. Core Algorithm for Data Analysis and Model Building: A physical model is proposed that "linearly correlates the gel deformation rate with the induced flow field particle velocity" (the proportional relationship between the gel deformation rate and the particle flow velocity). This model is the core idea of this invention. It transforms a parameter (gel deformation rate) that is difficult to measure directly and quickly into a parameter (flow field velocity) that is easy to measure accurately using standard PIV technology, thus simplifying and quantifying the detection method.
[0108] 3. Innovative Performance Evaluation Process: A two-step performance evaluation process of "calibration-application" was established. First, a calibration curve (k-standard curve) was established using standard gel samples with known properties to correlate the proportionality coefficient k with gel performance parameters (such as crosslinking degree). Then, for unknown samples, only the gel deformation rate needs to be measured to quickly deduce the gel deformation rate corresponding to its response performance using the calibrated k value. This process elevates the method from a measurement technique to a practical performance evaluation tool.
[0109] This disclosure also proposes a computer-readable storage medium storing computer program instructions, which, when executed by a processor, implement the aforementioned methods for establishing a gel observation chamber and determining the gel deformation rate. The computer-readable storage medium may be a non-volatile computer-readable storage medium.
[0110] This disclosure also proposes an electronic device, including: a processor; and a memory for storing processor-executable instructions; wherein the processor is configured for the above-described methods for establishing a gel observation chamber and determining the gel deformation rate. The electronic device can be provided as a terminal, a server, or other type of device. Example 1: Verification of the linear relationship between the gel area change rate and the flow velocity at the vertex near the boundary center under a fixed MBA content.
[0111] 1. Sample Preparation: A thermosensitive gel with NIPAM monomer and MBA crosslinking agent was selected. The mass of MBA was set at 2.30 mg, dissolved in 0.60 mL of solvent (0.3 mL methanol, 0.06 mL dimethyl sulfoxide, and 0.24 mL water). The initiation system and solvent were prepared according to conventional methods. The precursor solution was injected into a capillary tube for thermal polymerization to form the gel. After gelation, post-treatment was performed to wash away residual solution, and the gel was equilibrated with deionized water for 48 h.
[0112] 2. Observation chamber and tracer configuration: A glass slide-silicone pad (1 mm thick)-glass slide configuration was used, clamped together. The circular window diameter was 3 cm. Deionized water was selected as the liquid medium, and 2 μm PS microspheres were selected as the tracer particles. The effective projected side length of the observation gel was approximately 1 mm, and the gel thickness was approximately 1 mm.
[0113] 3. Stimulation and imaging parameters: Temperature range 20-35℃, cycle 10 min, switching time ≤10 s, number of cycles 7. Confocal microscope (Leica SP8) was used for imaging, 5× objective lens, pixel calibration 3.9 μm / px, sampling interval 3 s.
[0114] 4. Data Processing: In PIVlab, a cascading window setting (64→32 px, 50% overlap) was used to improve the spatial resolution of the flow velocity measurement. To accurately reflect the bulk volume exchange behavior and avoid the influence of shape inhomogeneity caused by end-face cutting, fluid velocities were selected at fixed points within approximately 100-200 μm from the center of the left and right boundaries of the gel. The average flow rate at two points was exported to obtain the curves of change over time. Simultaneously, based on self-developed code in MATLAB, the gel area was accurately calculated over time by segmenting the gel region using an active contour model, thus determining the rate of area change. During the periodic temperature change, the gel expansion stage induced a more significant flow rate peak. Considering the irreversible micro-damage to the gel, this study focuses on analyzing the flow rate peak induced during the first expansion process and establishing its correspondence with deformation parameters. To obtain robust linear calibration, five representative points were selected at equal intervals after the extreme point of the first expansion peak for linear fitting, yielding the slope k and its 95% confidence interval.
[0115] 5. Results: such as Figure 2 As shown in the comparison results, the rate of change of gel area is... Slightly lags behind the fluid velocity The delay time ∆t ≈ 3 s, the two main frequencies are consistent and show a strong correlation. Linear fitting of the selected representative points yielded a linear relationship with a slope of 0.00216 (95% CI: 0.00202 - 0.00229) and an intercept of 0.00184 (95% CI: 0.0012 - 0.00248). This indicates that under a fixed degree of crosslinking, there is a stable mapping relationship between the gel deformation rate and the fixed-point flow velocity near the boundary center; therefore, the fixed-point flow velocity can be used as an effective surrogate for inferring the gel deformation rate.
[0116] Example 2: Screening of gel performance and non-monotonicity under different MBA contents 1. Sample Preparation: The mass gradient of crosslinking agent MBA was 1.38, 1.84, 2.30, 2.76, 3.22, 3.68, 4.14, and 5.52 mg; all were dissolved in 0.60 mL of solvent (0.3 mL methanol, 0.06 mL dimethyl sulfoxide, and 0.24 mL water). Except for MBA, the formulation was the same as in Example 1.
[0117] 2. Test conditions and data processing: The apparatus, medium, tracer, stimulus, and imaging were the same as in Example 1. For each gradient, the average peak fluid velocity between two fixed points within a range of approximately 100-200 μm from the center of the left and right boundaries of the gel was calculated. Peak rate of change of gel area The velocity peak area ∆S (both analyzed for velocity peaks induced during the first expansion process) was calculated. The three sets of data were independently normalized: each value within each group was divided by the maximum value of that group; longitudinal comparisons between different groups do not represent absolute magnitudes, only trends within the groups can be compared.
[0118] 3. Results: such as Figure 3 As shown, as the MBA content increased from 1.38 mg to 2.3 mg, and The concentration increased synchronously; it gradually decreased from 2.76 mg to 5.52 mg, exhibiting a non-monotonic relationship of "increasing first and then decreasing". This result reflects the optimal window of crosslinking degree between "mechanical constraint-swelling drive-percolation coupling", which is a key window for process optimization.
[0119] Example 3: Take the MBA content of each sample from Example 2 and Establish such Figure 4 The linear model shown: Where c is the zero-point bias, a linear relationship was obtained with a slope of 0.00325 (95% CI: 0.00222 - 0.00428) and an intercept of 0.00635 (95% CI: 0.00137 - 0.00734). This result indicates that there is a robust linear mapping between the peak deformation rate of the gel and the peak induced flow rate under different crosslinking conditions. Therefore, the flow rate value can be simplified as an effective surrogate for inferring the extreme value of the gel deformation rate.
[0120] Example 4: Comparison of the differences in chemical kinetic behavior between N-isopropylacrylamide (NIPAM)-based and acrylamide (AAM)-based BZ gels in the Belousov-Zhabotinsky (BZ) reaction system, and demonstration of the effectiveness of the method of the present invention in characterizing their driving performance and mass transfer direction.
[0121] 1. Sample Preparation and Test Environment Construction. Cylindrical NIPAM-based BZ gels and AAM-based BZ gels with uniform dimensions (approximately 5 mm in length) were prepared. A circular jacketed reaction cell with an open top was used. A single gel sample was placed in the center of the reaction cell. The prepared BZ reaction solution, which also served as the tracer fluid for PIV rate measurement, was injected into the reaction cell. This solution contained: 5 mg / ml polystyrene fluorescent microspheres (5 μm in diameter), 80 mmol / L malonic acid (MA), 120 mmol / L sodium bromate (NaBrO3), and 700 mmol / L nitric acid (HNO3). The jacket inlet and outlet of the reaction cell were connected to a constant-temperature water bath circulation system to precisely control the temperature of the entire reaction system at (22±0.5)℃ to eliminate the interference of ambient temperature fluctuations on the BZ reaction and gel behavior.
[0122] 2. Image Data Acquisition and Processing. Using a camera system equipped with a CCD lens of appropriate magnification, observations were made from above the reaction cell. The focus was on the gel sample and the surrounding fluid region with a width greater than 1 mm to ensure simultaneous and clear capture of gel deformation and tracer particle movement. After starting the BZ reaction, image acquisition software automatically captured a sequence of images at 3-second intervals, continuously recording for 1 hour. After the recording was completed, the complete image sequence was exported for subsequent analysis. In PIVlab, the cascade window was set to 256→128 px with an overlap of 50%. Other processing methods were consistent with Example 2, and the time series of fluid velocity V and gel area A were exported. Furthermore, in BZ gels, the structural loss of the gel is relatively small with each oscillation; therefore, five peak values of flow velocity oscillation and area oscillation were repeatedly taken and averaged to make the results more reliable.
[0123] 3. Results and Analysis. A comparison of the two-dimensional instantaneous velocity fields of NIPAM-based BZ gels and AAM-based BZ gels clearly shows that the deformation and induced velocity of the NIPAM-based gel are greater. Figure 5 Comparing the flow rate and area change curves of NIPAM-based BZ gel and AAM-based BZ gel, it was found that they exhibited completely opposite kinetic modes. Figure 6 NIPAM-based BZ gel: When the catalyst is in the oxidized state, the gel expands, while the surrounding fluid flows at an average peak velocity of V. 1,max =4.14 ×10 -6 The fluid flows into the gel at a speed of m / s; when the catalyst is reduced, the gel shrinks, and the fluid flows out from the gel. The area change amplitude of the gel in each cycle is recorded, with an average area change amplitude ∆S = 0.88 mm. 2 / s. AAM-based BZ gel: exhibits a coupling mode completely opposite to that of NIPAM-based gel: when the catalyst is in the oxidized state, the gel shrinks while fluid flows out from the inside of the gel, with an average peak flow rate of only V. 2,max =4.15 × 10 -7 m / s; In the reduced state, the gel swells, and fluid flows in. Its average area change amplitude ∆S = 0.23 mm. 2 / s. Meanwhile, under the same conditions, AAM-based BZ gels exhibit a longer oscillation period than NIPAM-based BZ gels, i.e., a smaller oscillation frequency f( Figure 7 ).
[0124] 5. Conclusion. This embodiment clearly demonstrates that the method described in this invention can intuitively and accurately determine the opposite swelling / drainage behaviors of different types of BZ gels during a chemical oscillation cycle by measuring the direction of fluid inflow / outflow from the gel. The peak flow rate of the induced flow is directly related to the deformation scale of the gel; therefore, this peak flow rate can serve as a key indicator for quantitatively characterizing and comparing the chemimechanical driving capabilities of different gels.
[0125] Figure 8 This is a block diagram illustrating an electronic device 800 according to an exemplary embodiment. For example, the electronic device 800 may be a mobile phone, computer, digital broadcasting terminal, messaging device, game console, tablet device, medical device, fitness equipment, personal digital assistant, or other terminal.
[0126] Reference Figure 8 The electronic device 800 may include one or more of the following components: a processing component 802, a memory 804, a power supply component 806, a multimedia component 808, an audio component 810, an input / output (I / O) interface 812, a sensor component 814, and a communication component 816.
[0127] Processing component 802 typically controls the overall operation of electronic device 800, such as operations associated with display, telephone calls, data communication, camera operation, and recording operations. Processing component 802 may include one or more processors 820 to execute instructions to complete all or part of the steps of the methods described above. Furthermore, processing component 802 may include one or more modules to facilitate interaction between processing component 802 and other components. For example, processing component 802 may include a multimedia module to facilitate interaction between multimedia component 808 and processing component 802.
[0128] Memory 804 is configured to store various types of data to support the operation of electronic device 800. Examples of such data include instructions for any application or method operating on electronic device 800, contact data, phonebook data, messages, pictures, videos, etc. Memory 804 can be implemented by any type of volatile or non-volatile storage device or a combination thereof, such as static random access memory (SRAM), electrically erasable programmable read-only memory (EEPROM), erasable programmable read-only memory (EPROM), programmable read-only memory (PROM), read-only memory (ROM), magnetic storage, flash memory, magnetic disk, or optical disk.
[0129] Power supply component 806 provides power to various components of electronic device 800. Power supply component 806 may include a power management system, one or more power supplies, and other components associated with generating, managing, and distributing power to electronic device 800.
[0130] Multimedia component 808 includes a screen that provides an output interface between the electronic device 800 and the user. In some embodiments, the screen may include a liquid crystal display (LCD) and a touch panel (TP). If the screen includes a touch panel, the screen may be implemented as a touchscreen to receive input signals from the user. The touch panel includes one or more touch sensors to sense touches, swipes, and gestures on the touch panel. The touch sensors may sense not only the boundaries of the touch or swipe action but also the duration and pressure associated with the touch or swipe operation. In some embodiments, multimedia component 808 includes a front-facing camera and / or a rear-facing camera. When the electronic device 800 is in an operating mode, such as a shooting mode or a video mode, the front-facing camera and / or the rear-facing camera may receive external multimedia data. Each front-facing camera and rear-facing camera may be a fixed optical lens system or have focal length and optical zoom capabilities.
[0131] Audio component 810 is configured to output and / or input audio signals. For example, audio component 810 includes a microphone (MIC) configured to receive external audio signals when electronic device 800 is in an operating mode, such as call mode, recording mode, and voice recognition mode. The received audio signals may be further stored in memory 804 or transmitted via communication component 816. In some embodiments, audio component 810 also includes a speaker for outputting audio signals.
[0132] I / O interface 812 provides an interface between processing component 802 and peripheral interface modules, such as keyboards, click wheels, buttons, etc. These buttons may include, but are not limited to, home buttons, volume buttons, power buttons, and lock buttons.
[0133] Sensor assembly 814 includes one or more sensors for providing state assessments of various aspects of electronic device 800. For example, sensor assembly 814 can detect the on / off state of electronic device 800, the relative positioning of components such as the display and keypad of electronic device 800, changes in position of electronic device 800 or a component of electronic device 800, the presence or absence of user contact with electronic device 800, orientation or acceleration / deceleration of electronic device 800, and temperature changes of electronic device 800. Sensor assembly 814 may include a proximity sensor configured to detect the presence of nearby objects without any physical contact. Sensor assembly 814 may also include a light sensor, such as a CMOS or CCD image sensor, for use in imaging applications. In some embodiments, sensor assembly 814 may also include an accelerometer, gyroscope, magnetometer, pressure sensor, or temperature sensor.
[0134] Communication component 816 is configured to facilitate wired or wireless communication between electronic device 800 and other devices. Electronic device 800 can access wireless networks based on communication standards, such as WiFi, 2G, or 3G, or combinations thereof. In one exemplary embodiment, communication component 816 receives broadcast signals or broadcast-related information from an external broadcast management system via a broadcast channel. In one exemplary embodiment, communication component 816 also includes a near-field communication (NFC) module to facilitate short-range communication. For example, the NFC module may be implemented based on radio frequency identification (RFID) technology, Infrared Data Association (IrDA) technology, ultra-wideband (UWB) technology, Bluetooth (BT) technology, and other technologies.
[0135] In an exemplary embodiment, the electronic device 800 may be implemented by one or more application-specific integrated circuits (ASICs), digital signal processors (DSPs), digital signal processing devices (DSPDs), programmable logic devices (PLDs), field-programmable gate arrays (FPGAs), controllers, microcontrollers, microprocessors, or other electronic components to perform the methods described above.
[0136] In an exemplary embodiment, a non-volatile computer-readable storage medium is also provided, such as a memory 804 including computer program instructions that can be executed by a processor 820 of an electronic device 800 to perform the above-described method.
[0137] Figure 9 This is a block diagram illustrating an electronic device 1900 according to an exemplary embodiment. For example, the electronic device 1900 may be provided as a server. (Refer to...) Figure 9 The electronic device 1900 includes a processing component 1922, which further includes one or more processors, and memory resources represented by memory 1932 for storing instructions, such as application programs, that can be executed by the processing component 1922. The application programs stored in memory 1932 may include one or more modules, each corresponding to a set of instructions. Furthermore, the processing component 1922 is configured to execute instructions to perform the methods described above.
[0138] Electronic device 1900 may also include a power supply component 1926 configured to perform power management of electronic device 1900, a wired or wireless network interface 1950 configured to connect electronic device 1900 to a network, and an input / output (I / O) interface 1958. Electronic device 1900 can operate on an operating system stored in memory 1932, such as Windows Server™, Mac OS X™, Unix™, Linux™, FreeBSD™, or similar.
[0139] In an exemplary embodiment, a non-volatile computer-readable storage medium is also provided, such as a memory 1932 including computer program instructions that can be executed by a processing component 1922 of an electronic device 1900 to perform the above-described method.
[0140] This disclosure can be a system, method, and / or computer program product. A computer program product may include a computer-readable storage medium having computer-readable program instructions loaded thereon for causing a processor to implement various aspects of this disclosure. Computer-readable storage media can be tangible devices capable of holding and storing instructions for use by an instruction execution device. Computer-readable storage media can be, for example, but not limited to, electrical storage devices, magnetic storage devices, optical storage devices, electromagnetic storage devices, semiconductor storage devices, or any suitable combination thereof. More specific examples (a non-exhaustive list) of computer-readable storage media include: portable computer disks, hard disks, random access memory (RAM), read-only memory (ROM), erasable programmable read-only memory (EPROM or flash memory), static random access memory (SRAM), portable compact disc read-only memory (CD-ROM), digital multifunction disc (DVD), memory sticks, floppy disks, mechanical encoding devices, such as punch cards or recessed protrusions storing instructions thereon, and any suitable combination thereof. The computer-readable storage media used herein are not to be construed as transient signals themselves, such as radio waves or other freely propagating electromagnetic waves, electromagnetic waves propagating through waveguides or other transmission media (e.g., light pulses through fiber optic cables), or electrical signals transmitted through wires.
[0141] The computer-readable program instructions described herein can be downloaded from computer-readable storage media to various computing / processing devices, or downloaded via a network, such as the Internet, local area network, wide area network, and / or wireless network, to an external computer or external storage device. The network may include copper transmission cables, fiber optic transmission, wireless transmission, routers, firewalls, switches, gateway computers, and / or edge servers. A network adapter card or network interface in each computing / processing device receives the computer-readable program instructions from the network and forwards them to the computer-readable storage media in the respective computing / processing device.
[0142] Various aspects of this disclosure are described herein with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of this disclosure. It should be understood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented by computer-readable program instructions.
[0143] These computer-readable program instructions can be provided to a processor of a general-purpose computer, a special-purpose computer, or other programmable data processing apparatus to produce a machine such that, when executed by the processor of the computer or other programmable data processing apparatus, they create means for implementing the functions / actions specified in one or more blocks of the flowchart and / or block diagram. These computer-readable program instructions can also be stored in a computer-readable storage medium that causes a computer, programmable data processing apparatus, and / or other device to operate in a particular manner; thus, the computer-readable medium storing the instructions comprises an article of manufacture that includes instructions for implementing aspects of the functions / actions specified in one or more blocks of the flowchart and / or block diagram.
[0144] Computer-readable program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other device to cause a series of operational steps to be performed on the computer, other programmable data processing apparatus, or other device to produce a computer-implemented process, thereby causing the instructions executed on the computer, other programmable data processing apparatus, or other device to perform the functions / actions specified in one or more boxes of a flowchart and / or block diagram.
[0145] The flowcharts and block diagrams in the accompanying drawings illustrate the architecture, functionality, and operation of possible implementations of systems, methods, and computer program products according to various embodiments of the present disclosure. In this regard, each block in a flowchart or block diagram may represent a module, segment, or portion of an instruction containing one or more executable instructions for implementing a specified logical function. In some alternative implementations, the functions marked in the blocks may occur in a different order than those shown in the drawings. For example, two consecutive blocks may actually be executed substantially in parallel, and they may sometimes be executed in reverse order, depending on the functions involved. It should also be noted that each block in the block diagrams and / or flowcharts, and combinations of blocks in the block diagrams and / or flowcharts, may be implemented using a dedicated hardware-based system that performs the specified function or action, or using a combination of dedicated hardware and computer instructions.
[0146] The various embodiments of this disclosure have been described above. These descriptions are exemplary and not exhaustive, nor are they limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen to best explain the principles, practical application, or technical improvements to the embodiments in the market, or to enable others skilled in the art to understand the embodiments disclosed herein.
Claims
1. A method for establishing a gel observation chamber, characterized in that, include: A quasi-two-dimensional sealed observation chamber is constructed by stacking a first glass slide, an elastic gasket, and a second glass slide; wherein, the elastic gasket is provided with a target gel placement area; The first slide, the elastic pad, and the second slide corresponding to the target gel placement area are provided with a stimulation module that provides at least one or more of the following stimulations to the target gel placement area: temperature stimulation, pH stimulation, ionic strength stimulation, light stimulation, electric field stimulation, and magnetic field stimulation. After injecting a medium containing tracer particles into the quasi-two-dimensional sealed observation chamber until it is full, and allowing it to stand for a set time, an observable and stable flow field two-dimensional gel observation chamber is obtained.
2. The method for establishing a gel observation chamber according to claim 1, characterized in that, The first and second glass slides are configured as quartz sheets of a predetermined size; and / or, the elastic pad is configured as one or more of silicone, polydimethylsiloxane, and polytetrafluoroethylene sheets of a predetermined thickness; and / or, the target gel placement area is configured as a hollowed-out circular window, rectangular window, or square window; and / or, the tracer particles are configured as one or more of styrene, polymethyl methacrylate, and silica microspheres within a predetermined particle size range.
3. A method for determining gel deformation rate, characterized in that, include: Two-dimensional time-series gel micrographs, k-standard curves, and the proportional relationship between gel deformation rate and particle flow velocity are obtained for an observable stable flow field two-dimensional gel observation chamber established using the gel observation chamber establishment method described in claim 1 or 2 under a set quasi-step temperature stimulus. Extract the particle flow velocity corresponding to the two-dimensional time-series gel micrographs; Based on the particle flow velocity, the scaling factor corresponding to the k-standard curve, and the scaling relationship, the gel deformation rate corresponding to the two-dimensional time-series gel micrograph is determined.
4. The method for determining the gel deformation rate according to claim 3, characterized in that, Constructing the set quasi-step temperature stimulus includes: obtaining a first set temperature corresponding to the set temperature range of the set quasi-step temperature and a second set temperature greater than the first set temperature; maintaining the first set temperature and the second set temperature within the set temperature stability range in each cycle of the set temperature control cycle of the set quasi-step temperature; and switching the first set temperature to the second set temperature or the second set temperature to the first set temperature within a set heating / cooling rate and a set gradient switching time to construct the set quasi-step temperature stimulus.
5. The method for determining the gel deformation rate according to any one of claims 3 or 4, characterized in that, Determining the k-standard curve includes: under the same experimental conditions as in the gel deformation rate determination process, repeatedly and independently measuring the gel deformation rate and particle flow velocity of the standard sample corresponding to the target gel with a known formulation or degree of crosslinking; determining the k-standard curve by utilizing the proportional relationship between the gel deformation rate and particle flow velocity of the standard sample corresponding to the target gel with a known formulation or degree of crosslinking, obtained from multiple independent and repeated measurements; and / or, Determining the proportional relationship between the gel deformation rate and the particle flow velocity includes: under the same experimental conditions as in the process of determining the gel deformation rate, performing linear regression fitting on the gel deformation rate and particle flow velocity corresponding to the standard sample to determine the proportional relationship between the gel deformation rate and the particle flow velocity.
6. The method for determining the gel deformation rate according to claim 5, characterized in that, Before performing linear regression fitting on the gel deformation rate and particle flow velocity corresponding to the standard sample, the gel deformation rate corresponding to the standard sample is determined, including: segmenting the gel region of the two-dimensional time-series gel micrograph corresponding to the standard sample to obtain the corresponding two-dimensional time-series gel image; and performing edge detection on the two-dimensional time-series gel image to obtain the two-dimensional time-series gel boundary image. Projecting the gel microscopic image within the two-dimensional time-series gel boundary image yields a two-dimensional time-series gel microscopic area projection image; calculating the gel microscopic projection area of the two-dimensional time-series gel microscopic area projection image; calculating the first first derivative of the gel microscopic projection area of the two-dimensional time-series gel microscopic area projection image with time to determine the corresponding gel deformation rate; or, calculating the second first derivative of selected matching gel boundary feature points in the two-dimensional time-series gel boundary image with time to determine the corresponding gel deformation rate; and / or, The gel deformation rate corresponding to the two-dimensional time-series gel microscopy image is determined based on the first gel deformation rate corresponding to the gel microscopic projection area of the two-dimensional time-series gel microscopy image and the second gel deformation rate corresponding to the gel boundary feature points of the two-dimensional time-series gel microscopy image.
7. The method for determining the gel deformation rate according to claim 6, characterized in that, The step of segmenting the gel region of the two-dimensional time-series gel micrograph corresponding to the standard sample to obtain the corresponding two-dimensional time-series gel image includes: acquiring an initial reference region corresponding to the first frame gel micrograph in the two-dimensional time-series gel micrograph; performing binary segmentation on the initial reference region corresponding to the first frame gel micrograph to obtain a first frame gel segmentation micrograph; determining a global exclusion mask based on the first frame gel micrograph in the two-dimensional time-series gel micrograph; processing the first frame gel segmentation micrograph based on the global exclusion mask to obtain a first frame gel target segmentation micrograph corresponding to the two-dimensional time-series gel image; when performing gel region segmentation on gel regions other than the first frame gel micrograph, using the segmentation binary mask corresponding to the previous frame gel target segmentation micrograph as the initial reference region image of the current frame gel micrograph to perform binary segmentation on the current frame gel micrograph grayscale image to obtain the current frame gel segmentation micrograph; and processing the current frame gel segmentation micrograph based on the global exclusion mask to obtain the current frame gel target segmentation micrograph corresponding to the two-dimensional time-series gel image.
8. A gel observation chamber establishment system, characterized in that, include: A stacking unit is used to stack a first slide, an elastic pad, and a second slide to construct a quasi-two-dimensional sealed observation chamber; wherein the elastic pad is provided with a target gel placement area; a stimulation module unit is used to arrange stimulation modules corresponding to at least one or more of the following stimuli: temperature stimulation, pH stimulation, ionic strength stimulation, light stimulation, electric field stimulation, and magnetic field stimulation, on any one side of the first slide, the elastic pad, and the second slide corresponding to the target gel placement area; an injection and settling unit is used to inject a medium containing tracer particles into the quasi-two-dimensional sealed observation chamber until it is full, and then set it for a set time to obtain an observable stable flow field two-dimensional gel observation chamber; or, A processor; a memory for storing processor-executable instructions; wherein the processor is configured to invoke the instructions stored in the memory to execute the gel observation chamber establishment method according to any one of claims 1 to 2; or, Includes: a computer-readable storage medium having stored thereon computer program instructions, which, when executed by a processor, implement the gel observation chamber establishment method according to any one of claims 1 to 2; or, Includes: a computer program product, wherein the computer program product sets up a computer program / instruction, which, when executed by a processor, implements the gel observation chamber establishment method according to any one of claims 1 to 2.
9. A gel observation chamber, characterized in that, include: First glass slide, elastic gasket and second glass slide; The first glass slide and the second glass slide are respectively disposed on both sides of the elastic pad to construct a quasi-two-dimensional sealed observation chamber; wherein, the elastic pad is provided with a target gel placement area; any one of the first glass slide, the elastic pad and the second glass slide corresponding to the target gel placement area is provided with a stimulation module corresponding to at least one or more of the following stimuli: temperature stimulation, pH stimulation, ionic strength stimulation, light stimulation, electric field stimulation or magnetic field stimulation. The quasi-two-dimensional sealed observation chamber is filled with a medium containing tracer particles after being left to stand for a set time, thus constructing an observable and stable two-dimensional gel observation chamber for the flow field.
10. A system for determining gel deformation rate, characterized in that, include: The acquisition unit is used to acquire an observable stable flow field two-dimensional gel observation chamber established under a set quasi-step temperature stimulus using the gel observation chamber establishment method of claim 1 or 2, or an observable stable flow field two-dimensional gel observation chamber established using the gel observation chamber establishment system of claim 8, or a two-dimensional time-series gel micrograph, k-standard curve, and proportional relationship between gel deformation rate and particle flow velocity corresponding to the gel observation chamber of claim 9; the extraction unit is used to extract the particle flow velocity corresponding to the two-dimensional time-series gel micrograph. The determining unit is used to determine the gel deformation rate corresponding to the two-dimensional time-series gel micrograph based on the particle flow velocity, the scaling factor corresponding to the k-standard curve, and the scaling relationship. or, processor; A memory for storing processor-executable instructions; wherein the processor is configured to invoke the instructions stored in the memory to execute the gel deformation rate determination method according to any one of claims 3 to 7; or, Includes: a computer-readable storage medium having stored thereon computer program instructions, which, when executed by a processor, implement the gel deformation rate determination method according to any one of claims 3 to 7; or, Includes: a computer program product, wherein the computer program product is configured with a computer program / instruction, which, when executed by a processor, implements the gel deformation rate determination method according to any one of claims 3 to 7.
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