CN107134208B - In-vitro interventional embolism treatment simulation system - Google Patents
In-vitro interventional embolism treatment simulation system Download PDFInfo
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Abstract
The invention discloses an in-vitro interventional embolism therapy simulation system, which comprises a microvascular simulation area, a blood flow simulation area and a pressure monitoring area, wherein the microvascular simulation area is arranged in a constant temperature device and is communicated with the blood flow simulation area through a pipeline; the microvascular simulation region includes a microfluidic chip. According to the in-vitro interventional embolism treatment simulation system, the difference of the peripheral embolism performance can be quantified by observing the classification of the pipelines in the chip blocked by different embolic agents, so that the peripheral embolism performance of different embolic agents can be more intuitively evaluated, and a simpler and more convenient data accumulation scheme is provided for research and development personnel; meanwhile, the invention can evaluate the peripheral embolism performance of different embolic agents, so that the peripheral embolism performance of the embolic agents can be better known, and the clinical risk is reduced; the pressure detection area can accurately analyze the anti-blood flow scouring effect of different embolic agents under different conditions, so that the embolic strength of the embolic agents can be evaluated in vitro, and the vascular recanalization time can be monitored.
Description
Technical Field
The invention relates to the technical field of vascular embolism material evaluation systems for medical instrument intervention and medical operation training, in particular to an in-vitro intervention embolism treatment simulation system.
Background
The interventional therapy is a medical technology which integrates image diagnosis and clinical treatment, particularly, under the guidance of image medical equipment such as a digital subtraction angiography machine, magnetic resonance, ultrasound, CT and the like, a catheter or other interventional devices are introduced into a lesion part through a tiny wound and are used for implementing treatment, and the technology has the advantages of being minimally invasive, quick in effect taking, high in accuracy, small in toxic and side effects and the like, so that the interventional therapy is playing an increasingly important role in clinical application. One branch of the intervention treatment is the intervention treatment of liver cancer, the malignant degree of the liver cancer is extremely high, the invasion and the growth are rapid, the recurrence is easy to occur after the treatment, and the survival rate of 5 years is less than 5 percent.
For early liver cancer, surgical excision is the first choice for treating liver cancer and is the most effective method, but early diagnosis of liver cancer is always a difficult problem in the medical field, many patients have missed the best opportunity for surgical treatment in diagnosis, and in addition, patients in Asian countries often have liver cirrhosis caused by hepatitis, which also causes great inconvenience to surgical excision.
In 1978, the teachings of mountain land, department of medicine, university of osaka, japan, proposed transcatheter hepatic arterial chemoembolization (TACE) as a treatment option for unresectable liver cancer. As the name suggests, the chemoembolization of hepatic artery via catheter is to inject the embolization agent into the blood vessel of tumor via microcatheter in hepatic artery to block the blood supply of tumor, and to apply local starvation therapy to tumor. Since the liver has unique 'double blood supply', in normal liver, the hepatic artery is responsible for 25% of blood supply of the liver, and 75% of the liver is transported by the portal vein for draining intestinal blood, and in liver cancer patients, the blood supply of tumors is almost completely responsible for the hepatic artery, and the blood supply of the portal vein to the liver can reach more than 90%. Because of the double blood supply of the liver, TACE can effectively block tumor blood vessels on the premise of not affecting the normal work of the liver.
Compared with the traditional surgery, the liver tumor excision wound is larger, TACE belongs to the minimally invasive surgery, femoral artery puncture is only needed to be carried out at the inguinal position of a patient, the microcatheter is guided to the hepatic artery along the perforation under the real-time X-ray perspective, and when the microcatheter reaches the target position, the embolic agent and the chemotherapeutic agent are injected, the microcatheter is extracted, and the wound is sutured. Minimally invasive makes TACE safer to handle, reducing the risk of patient surgical infection.
In interventional embolization treatment of liver cancer, the performance of the embolization agent directly affects the curative effect and the implementation of the operation, and the ideal embolization agent has the following characteristics: 1. the embolism can be effectively implemented on each grade of blood vessels of the tumor; 2. the fluidity is good, and the guide pipe is not blocked; 3. x-ray is not transmitted, so that the visualization of the embolism process is realized; 4. can load the chemotherapeutic drugs and realize the slow and controlled release of the chemotherapeutic drugs.
Embolic agents currently in clinical use can be divided into two general categories: the solid embolic agent mainly comprises polyvinyl alcohol particles/microspheres, gelatin sponge particles and the like, can realize high-strength blocking of tumor blood vessels, is not easy to pass through under long-term blood flow flushing, but is in a solid form, and is often agglomerated when injected through a microcatheter, so that the microcatheter is blocked, the solid embolic agent does not have X-ray shielding capability, and needs to be blended with medical contrast agent when in use, so that inconvenience is brought to clinical operation; among the liquid embolic agents, most commonly used is iodized oil injection, abbreviated as iodized oil, which itself can shield X-rays,
the iodized oil can not be used for long-term embolism in vivo, and can be recycled along with blood flow flushing, so that the iodized oil can be used together with solid embolic agents in clinic.
A series of problems are often encountered in evaluating the performance of an embolic agent, such as evaluating the strength of the embolic agent, i.e., how the embolic agent resists blood flow washout, whether the embolic agent will be washed away from the embolic site by blood flow after surgery, thereby entering the entire blood circulation system and forming thrombi in other parts of the body; how to evaluate the degree of embolism, whether the embolism can be effectively filled to the tail end of a capillary vessel, thereby further inhibiting the establishment of tumor collateral circulation and further effectively inhibiting the growth of tumors. If a set of in-vitro simulation equipment has the functions, great convenience is brought to the research and development of the embolic agent and the preclinical research. The quantitative evaluation of different embolic agents is carried out in vitro, so that not only can the development cost be saved and the development efficiency be improved, but also the understanding of the embolic agent performance by a clinician can be improved to a certain extent, and the operation risk is reduced.
Chinese patent No. 202720819U discloses an intracranial aneurysm embolism simulator which is designed according to the internal layout of a human body, can be used as an effective training tool for improving doctor technology in hospitals, can improve the proficiency and skill grasp of beginners, further reduces the operation error rate and improves the treatment effect, but can not evaluate the performance of an embolism agent when being used as a training tool.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides an in-vitro interventional embolic treatment simulation system, which realizes the evaluation of embolic agent performance in an in-vitro environment, and can quantitatively evaluate important properties such as embolic intensity, embolic degree, anti-scouring capability and the like of the embolic agent, so that embolic agent research and development personnel can evaluate embolic products more comprehensively, clinicians can know the properties of the embolic agent more, and surgical risks are reduced.
In order to achieve the above object, the present invention provides the following solutions: the invention provides an in-vitro interventional embolism therapy simulation system, which comprises a microvascular simulation region, a blood flow simulation region and a pressure monitoring region, wherein the microvascular simulation region is arranged in a constant temperature device and is communicated with the blood flow simulation region through a pipeline, and the pressure monitoring region is used for monitoring the pressure value in the pipeline; the microvascular simulation region comprises a microfluidic chip.
Alternatively, the microvascular simulation area is a microvascular simulation area formed by bonding upper and lower layers of polydimethylsiloxane, or is a microvascular simulation area formed by bonding upper layers of polydimethylsiloxane and lower layers of glass.
Alternatively, the capillary of the microvascular simulation region is graded from coarse to fine into nine stages, with the width of the capillary being 1000 μm, 800 μm, 630 μm, 500 μm, 400 μm, 300 μm, 200 μm, 100 μm, 50 μm, respectively.
Optionally, the height of the pipeline of the microvascular simulation region is 20-200 μm.
Optionally, the height of the pipeline of the microvascular simulation region is 50-100 μm.
Optionally, the preparation method of the microfluidic chip comprises the following steps,
1) Mixing polydimethylsiloxane and a curing agent according to a mass ratio of 10:1, placing the mixture into a beaker, stirring and mixing the mixture uniformly by using a glass rod, pouring the mixture onto a die preset with a chip, and curing the mixture for 2 hours at 60 ℃;
2) Cutting the solidified substrate by a blade, and perforating at a perforating position by a perforating machine;
3) Bonding the upper and lower substrates after curing, and storing in a 50 ℃ oven for 30 minutes to finish bonding.
Optionally, the number of the microfluidic chips is at least two.
Optionally, the blood flow simulation area comprises a constant flow pump and a simulated blood flow medium which are sequentially connected with the pipeline, and the pressure monitoring area is connected with the constant flow pump.
Optionally, the flow rate of the constant flow pump is 0.05-1.00ml/min.
Alternatively, the simulated blood flow medium is phosphate buffer with ph=7.4 or 0.9% physiological saline.
Compared with the prior art, the invention has the following technical effects:
1. the invention provides an in vitro interventional embolism treatment simulation system, which is provided with a microvascular simulation area, and is formed by connecting 2 or more high-light-transmittance microfluidic chips in parallel, wherein the microfluidic chips are provided with high-precision pipelines, and can be subjected to multistage classification aiming at the pipelines, so that the classification of a microvascular network is simulated, the minimum pipeline width is only 50 microns, the minimum pipeline width can be observed under a microscope, the maximum pipeline width is 1000 microns, the pipeline height is adjustable from 20-200 microns, the preparation degree of freedom is higher, the preparation can be prepared according to actual conditions, the pipeline height is 50-100 microns, the pipeline classification is 1000 microns, 800 microns, 630 microns, 500 microns, 400 microns, 300 microns, 200 microns, 100 microns and 9 grades altogether, and the multistage classification can be used for better evaluating the embolism degree of different embolism agents under the same conditions, so that the peripheral embolism performance is quantized, and for tumor embolism agents, if insufficient to blood vessels, the peripheral embolism generation can be induced, thereby forming side circulation, restoring the great influence on the peripheral embolism can be greatly influenced, and the peripheral embolism can be effectively inhibited. The invention can quantify the difference of the peripheral embolism performance by observing the classification of the pipelines in the chip blocked by different embolic agents, thereby more intuitively evaluating the peripheral embolism performance of different embolic agents and providing a simpler and more convenient data accumulation scheme for research and development personnel. For clinicians, the invention can give the property evaluation of different embolic agents to the peripheral embolism, so that the property of the embolic agents can be better known, and the clinical risk is reduced.
2. The in-vitro interventional embolism treatment simulation system provided by the invention can detect the pressure change of the post-system before and during the embolism process in real time, so that the embolism intensity of different embolic agents is reflected, and the embolism intensity is further evaluated. If the embolism agent completely plugs the microvascular simulation chip, the system pressure is in an ascending trend and becomes stable after reaching the peak value; if the embolic agent is flushed away by the simulated blood flow medium after the embolism, the system pressure can be reduced to some extent or even the value before the embolism is restored; if the embolic agent fails to effectively plug the chip during the embolization process, the system pressure will not change significantly. According to the monitoring of the system pressure in the embolism process of the system, the effect of different embolic agents on resisting blood flow scouring under different conditions can be accurately analyzed, so that the embolism strength of the embolic agents can be evaluated in vitro, and if recanalization occurs, the vascular recanalization time can be monitored.
3. According to the in-vitro interventional embolism treatment simulation system provided by the invention, 2 or more than 2 microvascular simulation microfluidic chips are connected in parallel, so that the function of pressure protection is realized. When the pressure is too high, more simulated blood flow media pass through other chips except the embolic chip, but the embolic chip is blocked, which is equivalent to partial pressure rise caused by partial blockage in the total passage of the system, so that the embolic firmness is judged; if such a parallel connection is not adopted, the pressure can be continuously increased in the process of embolism until the inside of the chip or the joint of the pipeline leaks, thereby damaging the equipment.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions of the prior art, the drawings that are needed in the embodiments will be briefly described below, it being obvious that the drawings in the following description are only some embodiments of the present invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic diagram of the overall structure of an in vitro interventional embolic simulation system of the present invention;
FIG. 2 is a schematic diagram of a microfluidic chip I;
FIG. 3 is a schematic diagram of a microfluidic chip II;
FIG. 4 is a graph of pressure change for various embolic agents at a simulated blood flow medium flow rate of 0.3 ml/min;
FIG. 5 is a graph of the permeability of a microfluidic chip after embolization with a high viscosity temperature sensitive microgel;
FIG. 6 is a graph of the permeability of a microfluidic chip after embolization with a low viscosity temperature sensitive microgel;
FIG. 7 is a photomicrograph of a microfluidic chip after embolization (in sequence from left to right);
wherein, 1 microvascular simulation zone; 2 a constant temperature device; 3, a micro-fluidic chip; 4, a blood flow simulation area; 5 simulating blood flow medium; 6, a pressure monitoring area; 7, a constant flow pump; 8, simulating a pressure change curve of a blood flow medium when the embolic agent is high-viscosity temperature sensitive microgel; 9 simulating a pressure change curve of a blood flow medium when the embolic agent is low-viscosity temperature sensitive microgel; the 10 embolic agent is a pressure change curve of simulated blood flow medium when the iodized oil injection is adopted; the 10 embolic agent was blank to simulate the pressure profile of the blood flow medium.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
In order to solve the problems in the prior art, the invention provides an in-vitro interventional embolic treatment simulation system, which realizes the evaluation of embolic agent performance in an in-vitro environment, and can quantitatively evaluate important properties such as embolic intensity, embolic degree, anti-scouring capability and the like of the embolic agent, so that embolic agent research and development personnel can evaluate embolic products more comprehensively, clinicians can know the properties of the embolic agent more, and surgical risks are reduced.
The invention provides an in-vitro interventional embolism therapy simulation system, which comprises a microvascular simulation area, a blood flow simulation area and a pressure monitoring area, wherein the microvascular simulation area is arranged in a constant temperature device and is communicated with the blood flow simulation area through a pipeline; the microvascular simulation region includes a microfluidic chip.
The invention comprises four components of a microvascular simulation area, a blood flow simulation area, a pressure monitoring area and a constant temperature device, the constant temperature device is started after the four components are built according to the diagram shown in the figure 1, the pressure monitoring area is started for real-time pressure detection, the flow rate is set, when the system temperature is stable, an injector is used for injecting embolic agent into the microvascular simulation area, the pressure change is monitored synchronously, and when the injection is finished, the pressure change can be continuously detected to evaluate the embolic strength and the anti-blood flow scouring time of different embolic agents. And taking out the microvascular simulation chip after the embolism strength evaluation is finished, and evaluating the peripheral embolism effect by observing the embolism conditions of the embolic agents under different grades by visual inspection or under a microscope.
In order that the above-recited objects, features and advantages of the present invention will become more readily apparent, a more particular description of the invention will be rendered by reference to the appended drawings and appended detailed description.
Referring to fig. 1-3, fig. 1 is a schematic diagram of an overall structure of an in vitro interventional embolic simulation system according to the present invention; FIG. 2 is a schematic diagram of a microfluidic chip I; FIG. 3 is a schematic diagram of a microfluidic chip II; FIG. 4 is a graph of pressure change for various embolic agents at a simulated blood flow medium flow rate of 0.3 ml/min; FIG. 5 is a graph of the permeability of a microfluidic chip after embolization with a high viscosity temperature sensitive microgel; FIG. 6 is a graph of the permeability of a microfluidic chip after embolization with a low viscosity temperature sensitive microgel; fig. 7 is a micrograph of a microfluidic chip after embolization.
As shown in fig. 1-7, the invention provides an in-vitro interventional embolic therapy simulation system, which comprises a microvascular simulation zone 1, a blood flow simulation zone 4 and a pressure monitoring zone 6, wherein the microvascular simulation zone 1 is placed in a thermostat 2 and is communicated with the blood flow simulation zone 4 through a pipeline, and the pressure monitoring zone 6 is used for monitoring the pressure value in the pipeline; the microvascular simulation region 1 comprises a microfluidic chip 3.
The in-vitro interventional embolism therapy simulation system consists of a microvascular simulation area 1, a blood flow simulation area 4, a pressure monitoring area 6 and a constant temperature device 2, wherein the microvascular simulation area 1 consists of a microfluidic chip 3, and the chip is prepared from polydimethylsiloxane and glass and is used for simulating a microvascular network and has detailed pipe network classification; the blood flow simulation area 4 is a cross flow pump and a simulated blood flow medium 5, and the constant flow pump 7 is used as a power end to inject the simulated blood flow medium 5 into the microvascular simulation area 1 according to a set flow speed; the pressure monitoring area 6 can monitor the pressure change caused by blockage in the pipeline in real time, and can collect system pressure data in the whole process; the thermostat 2 is a thermostatic water bath for maintaining the system temperature constant.
The microvascular simulation area 1 is a microvascular simulation area 1 formed by bonding upper and lower layers of polydimethylsiloxane, or is a microvascular simulation area 1 formed by bonding upper layers of polydimethylsiloxane and lower layers of glass; the tube classification of the microvascular simulation region 1 is divided into nine stages from coarse to fine, and the tube widths thereof are 1000 μm, 800 μm, 630 μm, 500 μm, 400 μm, 300 μm, 200 μm, 100 μm, 50 μm, respectively; and the tube height of the microvascular simulation region 1 is 20 to 200 μm (tube height refers to the length in the Z-axis of the tube).
Wherein, the preparation method of the micro-fluidic chip 3 comprises the following steps,
1) Mixing polydimethylsiloxane and a curing agent according to a mass ratio of 10:1, placing the mixture into a beaker, stirring and mixing the mixture uniformly by using a glass rod, pouring the mixture onto a die preset with a chip, and curing the mixture for 2 hours at 60 ℃;
2) Cutting the solidified substrate by a blade, and perforating at a perforating position by a perforating machine;
3) Bonding the upper and lower substrates after curing, and storing in a 50 ℃ oven for 30 minutes to finish bonding.
The curing agent adopted in the invention is a Dow Corning Sylgard184.
The simulated blood flow medium 5 in the present invention is phosphate buffer with ph=7.4 or physiological saline with 0.9%.
The in-vitro interventional embolic treatment simulation system is realized by the following steps:
example 1
Step one: the polydimethyl siloxane and the curing agent are mixed according to the mass ratio of 10:1, stirring for 30 minutes by a glass rod, fully stirring uniformly, pouring the mixture on a mould (the pipeline in the mould is designed into 9-grade grades, and the pipeline widths are respectively 1000 mu m, 800 mu m, 630 mu m, 500 mu m, 400 mu m, 300 mu m, 200 mu m, 100 mu m and 50 mu m, and the pipeline heights are 20-50 mu m), and solidifying for 2 hours at 60 ℃;
step two: cutting the solidified substrate by a blade, and perforating at a perforating position by a perforating machine;
step three: bonding the solidified substrate with glass, and storing in a 50 ℃ oven for 30 minutes to enable the bonding to be complete, thus obtaining a microvascular simulation chip;
step four: repeating the steps to prepare 2 or more than 2 microvascular simulation chips;
step five: according to figure 1, the construction of each component is completed, a constant temperature device 2 is started, the temperature of the system is set to be 37 ℃, a constant flow pump 7 is started, the real-time pressure monitoring is carried out, the flow rates are respectively set to be 0.05ml/min,0.5ml/min and 1.0ml/min, and when the temperature of the system is stable, different embolic agents are injected into a microvascular simulation area 1 by using an injector, and the pressure change is synchronously monitored.
Example two
Step one: the polydimethyl siloxane and the curing agent are mixed according to the mass ratio of 10:1, stirring for 30 min with a glass rod, pouring the mixture on a mold (the pipeline in the mold is designed into 9-level grades, the pipeline width is respectively 1000 mu m, 800 mu m, 630 mu m, 500 mu m, 400 mu m, 300 mu m, 200 mu m, 100 mu m, 50 mu m and the pipeline height is 50-100 mu m), and solidifying for 2 hours at 60 ℃;
step two: cutting the solidified substrate by a blade, and perforating at a perforating position by a perforating machine;
step three: bonding the solidified substrate with glass, and storing in a 50 ℃ oven for 30 minutes to enable the bonding to be complete, thus obtaining a microvascular simulation chip;
step four: repeating the steps to prepare 2 or more than 2 microvascular simulation chips;
step five: according to figure 1, the construction of each component is completed, a constant temperature device 2 is started, the temperature of the system is set to be 37 ℃, a constant flow pump 7 is started, the real-time pressure monitoring is carried out, the flow rates are respectively set to be 0.05ml/min,0.5ml/min and 1.0ml/min, and when the temperature of the system is stable, different embolic agents are injected into a microvascular simulation area 1 by using an injector, and the pressure change is synchronously monitored.
Example III
Step one: the polydimethyl siloxane and the curing agent are mixed according to the mass ratio of 10:1, stirring for 30 minutes by a glass rod, fully stirring uniformly, pouring the mixture on a mould (the pipeline in the mould is designed into 9-grade grades, and the pipeline widths are respectively 1000 mu m, 800 mu m, 630 mu m, 500 mu m, 400 mu m, 300 mu m, 200 mu m, 100 mu m and 50 mu m, and the pipeline heights are 100-150 mu m), and solidifying for 2 hours at 60 ℃;
step two: cutting the solidified substrate by a blade, and perforating at a perforating position by a perforating machine;
step three: bonding the solidified substrate with glass, and storing in a 50 ℃ oven for 30 minutes to enable the bonding to be complete, thus obtaining a microvascular simulation chip;
step four: repeating the steps to prepare 2 or more than 2 microvascular simulation chips;
step five: according to figure 1, the construction of each component is completed, a constant temperature device 2 is started, the temperature of the system is set to be 37 ℃, a constant flow pump 7 is started, the real-time pressure monitoring is carried out, the flow rates are respectively set to be 0.05ml/min,0.5ml/min and 1.0ml/min, and when the temperature of the system is stable, different embolic agents are injected into a microvascular simulation area 1 by using an injector, and the pressure change is synchronously monitored.
Example IV
Step one: the polydimethyl siloxane and the curing agent are mixed according to the mass ratio of 10:1, stirring for 30 minutes by a glass rod, fully stirring uniformly, pouring the mixture on a mould (the pipeline in the mould is designed into 9-grade grades, and the pipeline width is respectively 1000 mu m, 800 mu m, 630 mu m, 500 mu m, 400 mu m, 300 mu m, 200 mu m, 100 mu m and 50 mu m, and the pipeline height is 150-200 mu m), and solidifying for 2 hours at 60 ℃;
step two: cutting the solidified substrate by a blade, and perforating at a perforating position by a perforating machine;
step three: bonding the solidified substrate with glass, and storing in a 50 ℃ oven for 30 minutes to enable the bonding to be complete, thus obtaining a microvascular simulation chip;
step four: repeating the steps to prepare 2 or more than 2 microvascular simulation chips;
step five: according to figure 1, the construction of each component is completed, a constant temperature device 2 is started, the temperature of the system is set to be 37 ℃, a constant flow pump 7 is started, the real-time pressure monitoring is carried out, the flow rates are respectively set to be 0.05ml/min,0.5ml/min and 1.0ml/min, and when the temperature of the system is stable, different embolic agents are injected into a microvascular simulation area 1 by using an injector, and the pressure change is synchronously monitored.
TABLE 1 examples 1-4 microvascular simulation chip tube height and embolic agent selected
Table 2 pressure peak monitoring results for examples 1 to 4
The data in tables 1-2 and FIGS. 4-6 above were analyzed as follows:
1. as shown in table 2 and fig. 4, the iodized oil can maintain a high system pressure during the injection process when the iodized oil injection is injected, but after the injection is stopped, the system pressure is rapidly reduced until the iodized oil injection is flush with a base line, which indicates that the iodized oil injection is poor in embolism strength, so that in clinical use, a solid embolic agent gelatin sponge is usually used for plugging after the injection of the iodized oil, and a good embolism effect can be achieved. The pressure curves of the two embolic agents, namely the low-viscosity temperature-sensitive microgel and the high-viscosity temperature-sensitive microgel, can be maintained at a higher level after the embolism, and no pressure drop trend is found in the next 60 minutes, which shows that the two embolic agents are superior to iodized oil injection in the embolic strength, and can implement effective embolism without adding other embolic agents. From the analysis of the data, it can be concluded that the embolic strength of different embolic agents can be measured by using the present invention.
2. As shown in fig. 5 to 6, after the embolism and continuous flushing for 60 minutes, the chip using the temperature-sensitive microgel still maintains the state of the embolism, but the high-viscosity temperature-sensitive microgel only completely plugs the 5 th-stage pipeline, the degree of the embolism is not high in the narrower high-stage pipeline, and the chip using the low-viscosity temperature-sensitive microgel embolism almost completely plugs the 9 th-stage pipeline. This demonstrates that the invention can evaluate not only the embolic strength of different embolic agents, but also the distal embolic performance of different embolic agents by observation, and in this example, it is evident that the low viscosity temperature sensitive microgel has more excellent distal embolic performance.
It should be noted that, the pipeline classification of the microvascular simulation area and the width of each stage of pipeline in the extracorporeal interventional embolic treatment simulation system are not limited to the above values, and can be properly adjusted according to specific test conditions, which are all within the protection scope of the invention; the value of the tube height of the microvascular simulation region is not limited to the above value either; the temperature control in the preparation process of the micro-fluidic chip can be adjusted within a certain range, and the temperature control is adjusted and used within a reasonable range and falls into the protection scope of the invention; meanwhile, the selection of the curing agent is not limited to the types of the curing agents, and other curing agents which can meet the corresponding requirements are also within the protection scope of the invention.
The principles and embodiments of the present invention have been described in detail with reference to specific examples, which are provided to facilitate understanding of the method and core ideas of the present invention; also, it is within the scope of the present invention to be modified by those of ordinary skill in the art in light of the present teachings. In view of the foregoing, this description should not be construed as limiting the invention.
Claims (8)
1. An in vitro interventional embolic therapy simulation system, characterized in that: the blood flow monitoring device comprises a micro-blood vessel simulation area, a blood flow simulation area and a pressure monitoring area, wherein the micro-blood vessel simulation area is placed in a constant temperature device and is communicated with the blood flow simulation area through a pipeline, and the pressure monitoring area is used for monitoring the pressure value in the pipeline; the micro-blood vessel simulation area comprises a micro-fluidic chip; the microfluidic chip has a conduit that is multi-stage graded to simulate grading of a microvascular network; taking out the micro-fluidic chip after the embolism strength evaluation is completed, and observing the embolism conditions of the embolic agents in different grades in the micro-fluidic chip by visual inspection or under a microscope to evaluate the peripheral embolism effect; the pipeline of the microvascular simulation region is classified into nine stages from coarse to fine, and the pipeline widths are 1000 mu m, 800 mu m, 630 mu m, 500 mu m, 400 mu m, 300 mu m, 200 mu m, 100 mu m and 50 mu m respectively;
the microvascular simulation area is formed by bonding upper and lower layers of polydimethylsiloxane, or is formed by bonding upper layers of polydimethylsiloxane and lower layers of glass.
2. The in vitro interventional embolic therapy simulation system according to claim 1, wherein: the height of the pipeline of the microvascular simulation region is 20-200 mu m.
3. The in vitro interventional embolic therapy simulation system according to claim 2, wherein: the height of the pipeline of the microvascular simulation region is 50-100 mu m.
4. The in vitro interventional embolic therapy simulation system according to claim 1, wherein: the preparation method of the microfluidic chip comprises the following steps,
1) Mixing polydimethylsiloxane and a curing agent according to a mass ratio of 10:1, placing the mixture into a beaker, stirring and mixing the mixture uniformly by using a glass rod, pouring the mixture on a die preset with a chip for curing, and curing for 2 hours at 60 ℃;
2) Cutting the solidified substrate by a blade, and perforating at a perforating position by a perforating machine;
3) Bonding the upper and lower substrates after curing, and storing in a 50 ℃ oven for 30 minutes to finish bonding.
5. The in vitro interventional embolic therapy simulation system according to claim 1, wherein: the number of the microfluidic chips is at least two.
6. The in vitro interventional embolic therapy simulation system according to claim 1, wherein: the blood flow simulation area comprises a constant flow pump and a simulated blood flow medium which are sequentially connected with the pipeline, and the pressure monitoring area is connected with the constant flow pump.
7. The in vitro interventional embolic therapy simulation system according to claim 6, wherein: the flow rate of the constant flow pump is 0.05-1.00ml/min.
8. The in vitro interventional embolic therapy simulation system according to claim 6, wherein: the simulated blood flow medium is phosphate buffer with ph=7.4 or 0.9% physiological saline.
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| WO2019094963A1 (en) | 2017-11-13 | 2019-05-16 | Shifamed Holdings, Llc | Intravascular fluid movement devices, systems, and methods of use |
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