Laser light scattering device based on in-vitro blood viscous flow condition simulation

Abstract

The utility model discloses a laser light scattering device based on extracorporeal blood viscous flow condition simulation, which is characterized in that a liquid inlet of a first pulse pump is connected with a liquid outlet of a human body blood circulation model, a liquid outlet of the first pulse pump is connected with a liquid inlet pipe of a sample pipe, and a liquid outlet of the liquid inlet pipe of the sample pipe extends to one side of the bottom of an inner cavity of the sample pipe; a liquid outlet of the second pulse pump is connected with a liquid inlet of the human body blood circulation model, a liquid inlet of the second pulse pump is connected with a liquid outlet pipe of the sample pipe, and a liquid inlet of the liquid outlet pipe of the sample pipe extends to the other side of the bottom of the inner cavity of the sample pipe; the inner wall of the sample tube is coated with a layer of biological membrane for simulating vascular endothelial cells, and the sample tube can be horizontally fixed on a sample position of the laser light scatterometer; the pulse pump flow speed adjusting display screen is connected with the first pulse pump and the second pulse pump. By simulating the dynamic and static flowing conditions of human blood, the dynamic and static laser light scattering test of a flowing sample is realized, so that more accurate experimental data is obtained.

Description

TECHNICAL FIELD

[0001] The utility model relates to a dynamic and static laser light scattering instrument, in particular to a laser light scattering device based on in-vitro blood viscous flow condition simulation, which is used for simulating and researching the behavior of in-vitro nanoparticles in the blood flow state in human body. BACKGROUND

[0002] Dynamic and static light scattering instrument is a kind of precision instrument, it is widely used to determine the physical and chemical properties of nanomaterials, emulsions, macromolecular solutions, pharmaceutical preparations and biological macromolecular solutions etc. It is mainly used to analyze the morphological structure, molecular weight, hydrodynamic particle size of sample, and study the structure, size and morphology of material. The composition of copolymer and mixture, drug release process, and thermodynamic parameters of intermolecular interaction in sample solution can also be deeply analyzed by dynamic and static light scattering instrument. During the application process of pharmaceutical preparations and biological macromolecular drugs, after being injected into the body, the environment they face is completely different from that of in-vitro static liquid solution. The dynamic flowability and complexity of in-vivo blood lead to the behavior of nanoparticles in the body being significantly different from that under static conditions. The distribution, deposition, release and metabolism of nanoparticles will change in in-vivo environment. Therefore, simulating the environment under the condition of in-vivo blood flow state has important significance for studying the in-vivo behavior of nanoparticles.

[0003] Human blood flow model is a model used to simulate the flow characteristics of in-vivo blood in arteries, veins and capillaries. Human blood circulation system is composed of heart, arteries, veins and capillaries. With each beat of the heart, blood is pushed to flow at a high speed in arteries, enters capillaries at a slow flow rate, and then returns to the heart through veins. Key tissues and organs passed through during blood flow include lungs, liver, kidneys, etc., which play an important role in blood filtration, metabolism and oxygenation. Blood flow is accompanied by complex factors such as high viscosity, charged protein molecules and cell capture.

[0004] In the arteries, the blood flow rate is high, for example, the flow rate of the aorta can reach 18-22 cm / s, while in the veins, the blood flow rate is relatively slow, for example, the flow rate of the vena cava and capillaries is 0.3-0.7 mm / s. This flow rate difference is caused by the change of blood vessel diameter and blood pressure. Specifically, for a 50 kg individual, the total amount of blood flowing rapidly in the body is about 4000 ml, the linear velocity of venous blood flow is 7-8 cm / s, and the flow rate of the aorta is 18-22 cm / s, while the flow rate of the vena cava and capillaries is 0.3-0.7 mm / s.

[0005] However, the existing dynamic and static laser light scattering instrument is usually in a static state during testing, which cannot truly reflect the behavior of the sample under dynamic flow conditions. Since the speed and pressure of human blood flowing in arteries, veins and capillaries are different, the existing device cannot effectively simulate these conditions, resulting in a large difference between experimental data and actual conditions. Therefore, in order to obtain more accurate experimental data and research results, it is necessary to develop a dynamic and static light scattering instrument that can simulate the blood flow environment in the body. This can better study the behavior of nanoparticles and drugs in the complex environment of the body, and improve the development and application effect of drug preparations and biological macromolecular drugs. Content of the utility model

[0006] The utility model aims at providing a laser light scattering device based on in-vitro blood viscous flow condition simulation, which realizes dynamic and static laser light scattering test of flowing samples by simulating the dynamic and static flow conditions of human blood, so as to obtain more accurate experimental data.

[0007] The technical scheme of the utility model is: a laser light scattering device based on in-vitro blood viscous flow condition simulation, comprising a human blood circulation model, a sample tube, a laser light scattering instrument, a first pulse pump, a second pulse pump and a pulse pump flow rate adjusting display screen.

[0008] The human blood circulation model is provided with a simulation heart simulation structure, a simulation artery simulation structure, a simulation vein simulation structure and a simulation capillary structure which are interconnected, liquid flows into the human blood circulation model from a liquid inlet, and then flows out from a liquid outlet of the human blood circulation model after passing through the simulation heart simulation structure, the simulation artery simulation structure, the simulation vein simulation structure and the simulation capillary structure;

[0009] The liquid inlet of the first pulse pump is connected with the liquid outlet of the human blood circulation model, the liquid outlet of the liquid inlet of the sample tube extends to one side of the bottom of the sample tube lumen, and the liquid outlet of the first pulse pump is connected with the liquid inlet of the sample tube.

[0010] The liquid inlet of the first pulse pump is connected with the liquid outlet of the human blood circulation model, the liquid outlet of the liquid inlet of the sample tube extends to one side of the bottom of the sample tube lumen, and the liquid outlet of the first pulse pump is connected with the liquid inlet of the sample tube.

[0011] The inner wall of the sample tube is coated with a layer of biological membrane simulating vascular endothelial cells, and the sample tube can be horizontally fixed on the sample site of the laser light scattering instrument.

[0012] The pulse pump flow rate adjusting display screen is connected with the first pulse pump and the second pulse pump, and is used for adjusting the flow rate of the first pulse pump and the second pulse pump.

[0013] Further, the biomembrane material of the inner wall of the sample tube is polyurethane, to ensure compatibility with blood.

[0014] Further, the inner diameter of the sample tube is 1-2 cm, and the height is 10-50 cm.

[0015] Further, the thickness of the biomembrane of the inner wall of the sample tube is 1-10 microns, to simulate the actual thickness of the endothelial cells of blood vessels.

[0016] Further, the diameter of the blood vessels in the simulated arterial simulation structure is 2-3 cm.

[0017] Further, the diameter of the blood vessels in the simulated venous simulation structure is 1-2 cm.

[0018] Further, the diameter of the blood vessels in the simulated capillary simulation structure is 0.1-0.5 mm.

[0019] Further, the scattering angle range of the laser light scattering instrument is 5°-175°. The full angle can be adjusted to obtain full range scattering data of the sample.

[0020] Further, the material of the sample tube is high-transmittance quartz or glass.

[0021] The beneficial effects of the utility model are: a laser light scattering device based on in-vitro blood viscosity flow condition simulation is provided, which simulates the dynamic and static flow conditions of human blood, realizes dynamic and static laser light scattering test of flowing samples, and thus obtains more accurate experimental data. The laser light scattering instrument can accurately detect the size distribution, morphology and intermolecular interaction of nanoparticles in the flowing sample through dynamic and static light scattering measurement technology. Experimental results show that there is a significant difference in the distribution and deposition characteristics of nanoparticles under dynamic and static conditions. Specific data shows that the average particle size of nanoparticles is about 50 nm under dynamic conditions, while the average particle size increases to 65 nm under static conditions, indicating that the flow state has an important influence on the aggregation and dispersion behavior of nanoparticles. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 It is a structural schematic view of the laser light scattering device based on in-vitro blood viscosity flow condition simulation.

[0023] In the figure: 1 is a human blood circulation model, 2 is a sample tube, 3 is a laser light scattering instrument, 4 is a first pulse pump, 5 is a second pulse pump, and 6 is a pulse pump flow rate adjustment display screen. DETAILED DESCRIPTION

[0024] The utility model will be further described below in combination with the drawings.

[0025] AsFigure 1 As shown, the laser light scattering device based on in-vitro blood viscosity flow condition simulation includes a human blood circulation model 1, a sample tube 2, a laser light scattering instrument 3, a first pulse pump 4, a second pulse pump 5, and a pulse pump flow rate adjustment display screen 6.

[0026] The human blood circulation model 1 is provided with a simulated heart simulation structure, a simulated artery simulation structure (the diameter of the artery simulation system should be set according to the simulation target, and the typical diameter of the aorta is 2-3 centimeters, and the diameter of the artery simulation pipeline can be adjusted in the range of 1-2 centimeters), a simulated vein simulation structure (the diameter of the vein simulation system should simulate the diameter of the human vein, which is usually in the range of 1-2 centimeters), and a simulated capillary structure (the diameter of the capillary simulation system should be in the range of 0.1-0.5 millimeters to simulate the size of the actual capillary), which can reproduce the flow characteristics and pulsatile characteristics of blood in these structures, thereby providing a more realistic fluid dynamics environment. After the liquid flows into the liquid inlet of the human blood circulation model 1, it flows through the simulated heart simulation structure, the simulated artery simulation structure, the simulated vein simulation structure, and the simulated capillary structure, and then flows out from the liquid outlet of the human blood circulation model 1.

[0027] The liquid inlet of the first pulse pump 4 is connected to the liquid outlet of the human blood circulation model 1, and the liquid outlet of the first pulse pump 4 is connected to the liquid inlet tube of the sample tube 2, and the liquid outlet of the liquid inlet tube of the sample tube 2 extends to one side of the bottom of the inner cavity of the sample tube 2.

[0028] The liquid outlet of the second pulse pump 5 is connected to the liquid inlet of the human blood circulation model 1, and the liquid inlet of the second pulse pump 5 is connected to the liquid outlet tube of the sample tube 2, and the liquid inlet of the liquid outlet tube of the sample tube 2 extends to the other side of the bottom of the inner cavity of the sample tube 2.

[0029] The inner wall of the sample tube 2 is coated with a layer of biological membrane simulating vascular endothelial cells to improve the authenticity of the simulated blood flow. The thickness of the biological membrane should be 1-10 microns to simulate the actual thickness of the vascular endothelial cells. The membrane material should be selected from high biocompatibility materials such as polyurethane or other biological membrane materials to ensure compatibility with blood. The sample tube 2 is made of high-transparency quartz or glass to ensure stable optical performance. The inner diameter is 1-2 centimeters, and the height is 10-50 centimeters. Different volumes of sample tubes can be selected to meet different experimental requirements.

[0030] The sample tube 2 can be horizontally fixed on the sample position of the laser light scattering instrument 3. The laser light scattering instrument has a laser source wavelength of 632.8 nm (He-Ne laser) or selectable wavelengths such as 405 nm, 488 nm, 532 nm, and 785 nm. The power is adjustable from 10 mW to 100 mW to adapt to the scattering requirements of different samples. The spot diameter is 0.1-1 mm, adjustable according to the sample tube design and experimental requirements. The scattering angle range is 5°-175°, fully adjustable to obtain omnidirectional scattering data of the sample. The detector type is a high-sensitivity photomultiplier tube (PMT) or a high-resolution CCD detector, selected according to experimental requirements. The dynamic range is ≥10^7, ensuring accuracy in testing high and low concentration samples. The sampling frequency is up to 10 kHz, quickly capturing scattering signals to adapt to dynamic measurement requirements. It is equipped with professional multi-time correlator analysis software, supporting real-time data analysis and offline data processing. It supports multiple modes including dynamic and static light scattering analysis, size distribution analysis, morphological analysis, and fluid dynamics analysis. It also supports multiple output formats (CSV, PDF, image files) for convenient data storage and sharing.

[0031] The pulse pump flow rate adjustment display screen 6 is connected to the first pulse pump 4 and the second pulse pump 5, and is used to adjust the flow rates of the first pulse pump 4 and the second pulse pump 5.

[0032] Example

[0033] 1. Equipment Preparation Phase

[0034] First, the dynamic and static laser light scattering instrument testing device based on the human blood flow model is set up according to... Figure 1 Connect as shown. The sample tube is horizontally fixed in the sample position of the laser light scattering instrument, and simultaneously connected to the liquid inlet and outlet of the human blood circulation model via the first and second pulse pumps. Turn on the power to the device, preheat the system, and perform a self-test to ensure all components are functioning correctly.

[0035] 2. Parameter setting stage

[0036] Using the pulse pump flow rate adjustment display, set the parameters required for the simulation experiment: set the corresponding flow rate parameters according to the type of blood vessel to be simulated. For example, set the flow rate to 20 cm / s when simulating an artery; 7.5 cm / s when simulating a vein; and 0.5 mm / s when simulating a capillary.

[0037] 3. Sample preparation and injection

[0038] Prepare the sample of nanoparticles to be tested. In this example, polyethylene glycol-modified gold nanoparticles (PEG-AuNPs) with a diameter of 50 nm are used at a concentration of 0.5 mg / mL. Use a pipette to inject the sample into the sample tube's inlet, ensuring uniform distribution within the tube.

[0039] 4. Test Procedure

[0040] (1) Static Measurement: First, measure the sample under static conditions, recording baseline particle size, distribution, and scattering intensity data. Set the laser light scattering instrument to dynamic-static combined measurement mode, with a scattering angle of 90° and a data acquisition time of 60 seconds.

[0041] (2) Dynamic Measurement: Start the first and second pulse pumps to initiate simulated blood flow. The system generates a pulsatile flow according to pre-set parameters, simulating blood flow characteristics in blood vessels. At this time, the laser light scattering instrument automatically performs real-time measurements, continuously recording scattering signal changes at a 90° scattering angle.

[0042] 5. Data Acquisition and Analysis

[0043] During the test, the data acquisition system continuously collects scattering signals at a frequency of 10 kHz, performing real-time correlation analysis using multiple time correlators. Simultaneously, the system records the real-time flow rate of the pulse pump flow rate adjustment display.

[0044] In this example, test results show that PEG-AuNPs have an average particle size of 52.3 ± 1.5 nm under static conditions, while under arterial flow conditions (20 cm / s), the average apparent particle size decreases to 48.7 ± 1.8 nm, indicating that the flow state affects the hydration layer structure of nanoparticles.

[0045] 6. System Cleaning and Maintenance

[0046] After the test is completed, use cleaning solution (0.1% SDS solution) to flush the system, especially the internal tubing of the sample tube. Then use deionized water for a second rinse, and finally use anhydrous ethanol for rinsing and air drying to ensure the accuracy of the next test.

[0047] As shown in the above example, the laser light scattering instrument in this example can accurately detect the size distribution, morphology, and intermolecular interactions of nanoparticles in flowing samples through dynamic and static light scattering measurement techniques. Experimental results show that there are significant differences in the distribution and deposition characteristics of nanoparticles under dynamic and static conditions. The specific data shows that the average particle size of nanoparticles is about 50 nm under dynamic conditions, while under static conditions, the average particle size increases to 65 nm, indicating that the flow state has an important influence on the aggregation and dispersion behavior of nanoparticles.

[0048] The above merely is preferred implementation manner of the present application, it should be pointed out, for ordinary skilled person in the technical field, on the premise of not departing from the principle of the present application, can also make several improvements and refinements, these improvements and refinements also should be regarded as the protection scope of the present application.

Claims

1. A laser light scattering device based on in vitro blood viscoelastic condition simulation, characterized by: The human blood circulation model (1), the sample tube (2), the laser light scattering instrument (3), the first pulse pump (4), the second pulse pump (5) and the pulse pump flow rate adjusting display screen (6) are included. The simulation heart simulation structure, the simulation artery simulation structure, the simulation vein simulation structure and the simulation capillary structure are arranged in the human blood circulation model (1) and are communicated with each other. The liquid inlet of the first pulse pump (4) is connected with the liquid outlet of the human blood circulation model (1), the liquid outlet of the first pulse pump (4) is connected with the liquid inlet pipe of the sample tube (2), and the liquid outlet of the liquid inlet pipe of the sample tube (2) extends to one side of the bottom of the inner cavity of the sample tube (2). The liquid outlet of the second pulse pump (5) is connected with the liquid inlet of the human blood circulation model (1), the liquid inlet of the second pulse pump (5) is connected with the liquid outlet pipe of the sample tube (2), and the liquid inlet of the liquid outlet pipe of the sample tube (2) extends to the other side of the bottom of the inner cavity of the sample tube (2). The inner wall of the sample tube (2) is coated with a layer of biological membrane simulating endothelial cells of blood vessels, and the sample tube (2) can be horizontally fixed on the sample site of the laser light scattering instrument (3). The pulse pump flow rate adjusting display screen (6) is connected with the first pulse pump (4) and the second pulse pump (5) and is used for adjusting the flow rates of the first pulse pump (4) and the second pulse pump (5).

2. The laser light scattering device based on in-vitro blood slurry condition simulation of claim 1, wherein: The biological membrane material of the inner wall of the sample tube (2) is polyurethane.

3. The laser light scattering device based on in-vitro blood slurry condition simulation of claim 1, wherein: The inner diameter of the sample tube (2) is 1-2 cm, and the height is 10-50 cm.

4. The laser light scattering device based on in-vitro blood slurry condition simulation of claim 1, wherein: The thickness of the biological membrane of the inner wall of the sample tube (2) is 1-10 microns.

5. The laser light scattering device based on in-vitro blood slurry condition simulation of claim 1, wherein: The diameter of the blood vessels in the simulation artery simulation structure is 2-3 cm.

6. The laser light scattering device based on in-vitro blood slurry condition simulation of claim 1, wherein: The diameter of the blood vessels in the simulation vein simulation structure is 1-2 cm.

7. The laser light scattering device based on in-vitro blood slurry condition simulation of claim 1, wherein: The diameter of the blood vessels in the simulation capillary structure is 0.1-0.5 mm.

8. The laser light scattering device based on in-vitro blood slurry condition simulation of claim 1, wherein: The scattering angle range of the laser light scattering instrument (3) is 5°-175°.

9. The laser light scattering device based on in-vitro blood slurry condition simulation of claim 1, wherein: The material of the sample tube (2) is high-transmittance quartz or glass.

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