Preparation method of hydrophilic polystyrene standard microspheres

Abstract

The invention relates to the field of intelligent medical treatment, in particular to a preparation method of hydrophilic polystyrene standard microspheres. Comprising the following steps: obtaining concentrated sulfuric acid, concentrated nitric acid, polystyrene standard microsphere particles and ultrapure water; adding the concentrated sulfuric acid and the concentrated nitric acid into the polystyrene standard microsphere particles, and mixing to obtain a mixed solution; adding the ultrapure water into the mixed solution, cleaning, and centrifuging to obtain the hydrophilic polystyrene standard microsphere particles, the hydrophilic standard particles can be obtained by the method, and the method has good application value.

Description

Technical Field

[0001] The present application relates to the field of intelligent medicine, and specifically relates to a method for preparing hydrophilic polystyrene standard microspheres, an apparatus, a program product, and a computer-readable storage medium. Background Art

[0002] Most of the existing animal inhalation exposure radioactive aerosols use two types of generators, namely a liquid aerosol generator and an electric spark + condensation device, for quasi-monodisperse (polydisperse) aerosol generation. For example, Semmler-Behnke et al. used an electric spark + condensation device to study the particulate deposition rate in mice of different ages after oral and nasal exposure to inhaled 20 nm and 80 nm radioactive polydisperse aerosols ( 129 Ir). Due to the relatively wide range of polydisperse particle sizes, the repeatability of experimental results is poor, and more samples and data are required to verify the results. Moreover, the deposition distribution and kinetic behavior of polydisperse aerosols are more complex, making it difficult to establish an accurate mathematical model. At the same time, most of them are hydrophobic particulate matters. However, most of the existing drugs are hydrophilic particles, which cannot meet the true quantification of single-sized hydrophilic aerosol particulate matters in the respiratory tract. In addition, the preparation of existing hydrophilic particles requires precise control of reaction conditions to ensure ideal particle size and distribution. The target compound precipitate is generated through a chemical reaction in a solution, and then the final product is obtained through separation, washing, drying, and other steps. Although this method is simple and easy to implement, it is difficult to precisely control the particle size. Therefore, constructing a method for preparing monodisperse hydrophilic particles is of great significance for studying the deposition distribution, deposition mechanism, and targeted drug delivery of particulate matters in the respiratory tract. Summary of the Invention

[0003] In view of the above problems, the present invention provides a method for preparing hydrophilic polystyrene standard microspheres, including: Obtaining concentrated sulfuric acid, concentrated nitric acid, polystyrene standard microsphere particles, and ultrapure water; Mixing the concentrated sulfuric acid, concentrated nitric acid, and polystyrene standard microsphere particles to obtain a mixed solution; Adding the ultrapure water to the mixed solution for washing and then centrifuging to obtain hydrophilic polystyrene standard microsphere particles.

[0004] The concentrated sulfuric acid and concentrated nitric acid are mixed with the polystyrene standard microsphere particles in a volume ratio of 1:3 to obtain a mixed solution; Optionally, the polystyrene standard microsphere particles are polystyrene standard microsphere particles of different particle sizes, and the particle size range is 0.2 μm - 10 μm; Optionally, the method further includes the preparation of a hydrophilic aerosol generating liquid, and mixing the hydrophilic polystyrene standard microsphere particles with ultrapure water to obtain a hydrophilic aerosol generating liquid. The object of the present invention is to provide a computer program product, which includes a computer program or instructions, including: The computer program or instructions are executed by a processor to implement the above-mentioned preparation method of hydrophilic polystyrene standard microspheres.

[0005] The object of the present invention is to provide a computer device, which includes a memory, a processor, and a computer program or instructions stored on the memory. The computer program or instructions are executed by the processor to implement the above-mentioned preparation method of hydrophilic polystyrene standard microspheres. The object of the present invention is to provide a computer-readable storage medium, on which a computer program or instructions are stored. The computer program or instructions are executed by a processor to implement the above-mentioned preparation method of hydrophilic polystyrene standard microspheres. The object of the present invention is to provide a method for preparing radioactive hydrophilic polystyrene standard microspheres, including: obtaining hydrophilic polystyrene standard microsphere particles according to the above-mentioned preparation method of hydrophilic polystyrene standard microspheres; obtaining a radioactive isotope and a PBS solution; Adding the hydrophilic polystyrene standard microsphere particles and the radioactive isotope to the PBS solution and mixing to obtain a radioactive mixed solution, Adding a PBS solution to the radioactive mixed solution for washing and then centrifuging to obtain radioactive hydrophilic polystyrene standard microsphere particles; Optionally, the method further includes the preparation of a radioactive hydrophilic aerosol generating liquid. Obtaining ultrapure water and mixing the ultrapure water with the radioactive hydrophilic polystyrene standard microsphere particles to obtain a radioactive hydrophilic particle aerosol generating liquid. The object of the present invention is to provide a computer program product, which includes a computer program or instructions, including: The computer program or instructions are executed by a processor to implement the above-mentioned preparation method of radioactive hydrophilic polystyrene standard microspheres.

[0006] The object of the present invention is to provide a computer device, which includes a memory, a processor, and a computer program or instructions stored on the memory. The computer program or instructions are executed by the processor to implement the above-mentioned preparation method of radioactive hydrophilic polystyrene standard microspheres. The object of the present invention is to provide a computer-readable storage medium, on which a computer program or instructions are stored. The computer program or instructions are executed by a processor to implement the above-mentioned preparation method of radioactive hydrophilic polystyrene standard microspheres. The object of the present invention is to provide a method for generating monodisperse aerosol for animals, including: The hydrophilic polystyrene standard microspheres and hydrophilic aerosol generating liquid are obtained by the above-mentioned method for preparing hydrophilic polystyrene standard microspheres; The hydrophilic aerosol generating liquid is added to an aerosol generator to obtain monodisperse aerosol. The aerosol generator includes a polydisperse aerosol generator and an aerosol diffusion drying tube. The hydrophilic standard particle aerosol generating liquid generates polydisperse aerosol in the polydisperse aerosol generator, and the polydisperse aerosol passes through the aerosol diffusion drying tube to obtain monodisperse aerosol; Optionally, the particle size range of the monodisperse aerosol is 0.2 μm - 10 μm; Optionally, the polydisperse aerosol generator includes one or more of the following: Collision three-hole polydisperse aerosol generator, German 7811 polydisperse aerosol generator, TDA-4B polydisperse aerosol generator, TDA-6C polydisperse aerosol generator, MODEL 3990-01 polydisperse aerosol generator. The particle size range of the monodisperse aerosol also includes one or more of the following: 0.2 μm - 0.7 μm, 0.7 μm - 3 μm, 3 μm - 10 μm. The hydrophilic polystyrene standard microspheres are replaced with radioactive hydrophilic polystyrene standard microspheres, and the radioactive hydrophilic polystyrene standard microspheres are obtained by the above-mentioned method for preparing radioactive hydrophilic polystyrene standard microspheres; Optionally, the hydrophilic aerosol generating liquid is replaced with a radioactive hydrophilic aerosol generating liquid, and the radioactive hydrophilic aerosol generating liquid is obtained by the above-mentioned method for preparing radioactive hydrophilic polystyrene standard microspheres; Optionally, the hydrophilic polystyrene standard microspheres are replaced with radioactive hydrophilic polystyrene standard microspheres, and the hydrophilic aerosol generating liquid is replaced with a radioactive hydrophilic aerosol generating liquid. The radioactive hydrophilic polystyrene standard microspheres and the radioactive hydrophilic aerosol generating liquid are obtained by the above-mentioned method for preparing radioactive hydrophilic polystyrene standard microspheres.

[0007] The purpose of the present invention is to provide a computer program product, which includes a computer program or instruction, including: The computer program or instruction is executed by a processor to implement the above-mentioned method for generating monodisperse aerosol for animals.

[0008] The purpose of the present invention is to provide a computer device, which includes a memory, a processor, and a computer program or instruction stored on the memory. The computer program or instruction is executed by the processor to implement the above-mentioned method for generating monodisperse aerosol for animals. An object of the present invention is to provide a computer-readable storage medium having a computer program or instruction stored thereon, and the computer program or instruction is executed by a processor to implement the above-mentioned monodisperse aerosol generation method for animals. An object of the present invention is to provide a method for quantitatively analyzing the deposition distribution of monodisperse aerosol in the respiratory tract, including: Obtaining monodisperse aerosol according to the above-mentioned monodisperse aerosol generation method for animals; After the animal inhales the monodisperse aerosol, tomographically scanning the respiratory tract of the animal to obtain image data; Based on the image data, obtaining a deposition distribution map of the monodisperse aerosol in the respiratory tract of the animal.

[0009] Optionally, the monodisperse aerosol is a radioactive monodisperse aerosol.

[0010] An object of the present invention is to provide a computer program product, which includes a computer program or instruction, including: The computer program or instruction is executed by a processor to implement the above-mentioned method for quantitatively analyzing the deposition distribution of monodisperse aerosol in the respiratory tract.

[0011] An object of the present invention is to provide a computer device, which includes a memory, a processor, and a computer program or instruction stored on the memory, and the computer program or instruction is executed by the processor to implement the above-mentioned method for quantitatively analyzing the deposition distribution of monodisperse aerosol in the respiratory tract. An object of the present invention is to provide a computer-readable storage medium having a computer program or instruction stored thereon, and the computer program or instruction is executed by a processor to implement the above-mentioned method for quantitatively analyzing the deposition distribution of monodisperse aerosol in the respiratory tract. An object of the present invention is to provide a method for constructing a prediction model of monodisperse aerosol deposition distribution, including: Obtaining an atlas and labels of deposition distribution maps of monodisperse aerosols with different particle sizes deposited in the respiratory tract of animals; Inputting the deposition distribution map atlas and labels into a neural network model for training to obtain a deposition distribution prediction model; Wherein, the deposition distribution map is obtained by the above-mentioned method for quantitatively analyzing the deposition distribution of monodisperse aerosol in the respiratory tract.

[0012] Optionally, the method further includes deposition distribution prediction: Obtaining a particle size distribution map and data of monodisperse aerosol; Inputting the particle size distribution map and data of the monodisperse aerosol into the deposition distribution prediction model to obtain the deposition distribution of particulate matter in the respiratory tract.

[0013] The object of the present invention is to provide a computer program product, which includes a computer program or instructions, comprising: The computer program or instructions are executed by a processor to implement the above-mentioned method for constructing a monodisperse aerosol deposition distribution prediction model.

[0014] The object of the present invention is to provide a computer device, which includes a memory, a processor, and a computer program or instructions stored on the memory. The computer program or instructions are executed by the processor to implement the above-mentioned method for constructing a monodisperse aerosol deposition distribution prediction model. The object of the present invention is to provide a computer-readable storage medium, on which a computer program or instructions are stored. The computer program or instructions are executed by a processor to implement the above-mentioned method for constructing a monodisperse aerosol deposition distribution prediction model. The advantages of the present invention are as follows: 1. A preparation method for hydrophilic particles is proposed, which can conduct research on hydrophilic particles, providing basic conditions for hydrophilic aerosols. Moreover, based on hydrophilic particles, the present invention prepares radioactive hydrophilic standard particles, which further helps to prepare radioactive hydrophilic aerosols, laying a basic condition for the deposition research of aerosols in the respiratory tract and facilitating the study of the deposition law of hydrophilic aerosols in the respiratory tract.

[0015] 2. A method for generating monodisperse aerosols for animals is proposed. This method can provide a single particle size with highly consistent particle sizes, making the experimental results more reliable and reproducible. Moreover, monodisperse aerosols can be deposited at specific sites, and by adjusting the particle size, the aerosols can be deposited at specific respiratory sites (such as the upper respiratory tract, lower respiratory tract, or alveolar region), which is suitable for studying the biological effects of specific sites. 3. Radioactive particles are used for aerosol generation and quantitative research on the high-resolution deposition distribution of the entire respiratory tract of animals. Compared with regional quantitative research, the deposition distribution law of a single particle size in the entire respiratory tract can be directly obtained through radioactive isotopes, laying a foundation for the construction of a numerical model of particle deposition distribution, and further facilitating subsequent research on targeted drug therapy. Description of the Drawings

[0016] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the following drawings are only some embodiments of the present invention. For those skilled in the art, without creative efforts, other drawings can be obtained based on these drawings. Figure 1 Schematic flow chart of a method for preparing hydrophilic polystyrene standard microspheres provided by an embodiment of the present invention; Figure 2Schematic diagram of a preparation system for hydrophilic polystyrene standard microspheres provided by an embodiment of the present invention; Figure 3 Schematic diagram of a preparation device for hydrophilic polystyrene standard microspheres provided by an embodiment of the present invention; Figure 4 Preparation of hydrophilic standard particles with different particle sizes and preparation of aerosol generating liquid provided by an embodiment of the present invention; Figure 5 Monodisperse radioactive standard particle aerosol generating system provided by an embodiment of the present invention; Figure 6 Particle size spectra of 0.7μm and 3μm monodisperse hydrophilic radioactive aerosols provided by an embodiment of the present invention, with a GSD of 1.16 for 0.7μm and a GSD of 1.1 for 3μm; Figure 7 Deposition distribution of radioactive aerosols with different particle sizes inhaled through the whole respiratory tract provided by an embodiment of the present invention. Detailed implementation manners

[0017] In order to enable those skilled in the art to better understand the solution of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention.

[0018] In some processes described in the specification, claims and above-mentioned drawings of the present invention, a plurality of operations appear in a specific order. However, it should be clearly understood that these operations may not be executed in the order in which they appear herein or may be executed in parallel. The serial numbers of the operations, such as S101, S102, etc., are only used to distinguish different operations, and the serial numbers themselves do not represent any execution order. In addition, these processes may include more or fewer operations, and these operations may be executed in sequence or in parallel. It should be noted that the descriptions such as "first" and "second" in this article are used to distinguish different messages, devices, modules, etc., do not represent a sequence, nor do they limit that "first" and "second" are of different types.

[0019] Figure 1 Schematic diagram of a method for preparing hydrophilic polystyrene standard microspheres provided by an embodiment of the present invention, specifically including: S101: Obtain concentrated sulfuric acid, concentrated nitric acid, polystyrene standard microsphere particles, and ultrapure water; In one embodiment, the concentrated sulfuric acid and concentrated nitric acid are mixed with polystyrene standard microsphere particles in a volume ratio of 1:3 to obtain a mixed solution.

[0020] In one embodiment, the polystyrene standard microsphere particles are polystyrene standard microsphere particles with different particle sizes, and the particle size range is 0.2μm - 10μm.

[0021] S102: Mix the concentrated sulfuric acid, concentrated nitric acid and polystyrene standard microsphere particles to obtain a mixed solution; In one embodiment, mixed solutions with different particle sizes are prepared by using polystyrene standard microsphere particles with different particle sizes.

[0022] S103: Add the ultrapure water to the mixed solution and perform centrifugal cleaning to obtain hydrophilic polystyrene standard microsphere particles.

[0023] In one embodiment, the method further includes the preparation of a hydrophilic aerosol generating liquid. Mix the hydrophilic polystyrene standard microsphere particles and ultrapure water to obtain a hydrophilic aerosol generating liquid.

[0024] In one embodiment, the preparation process of the hydrophilic polystyrene standard microsphere particles is as Figure 4 shown. Mix concentrated sulfuric acid and concentrated nitric acid in a ratio of 1:3 with hydrophobic particles to obtain a mixed solution, and add ultrapure water to the mixed solution for multiple centrifugal cleanings to obtain hydrophilic standard particles. In addition, mix the hydrophilic particles and ultrapure water to obtain a hydrophilic standard particle aerosol generating liquid.

[0025] In one embodiment, add the hydrophilic standard particle aerosol generating liquid to an aerosol generator to obtain a polydisperse aerosol. The polydisperse aerosol is dried through an aerosol diffusion drying tube to obtain a monodisperse aerosol, as Figure 5 shown.

[0026] In one embodiment, the standard particles are radioactive standard particles, and the radioactive standard particles are obtained by an oxidation-reduction reaction between the standard particles and a radioactive isotope.

[0027] The disclosed embodiments of the present invention also provide a computer program product or system, including a computer program, which when executed by a processor implements the steps of the above-mentioned method for preparing hydrophilic polystyrene standard microspheres.

[0028] Figure 2 The schematic diagram of a system for preparing hydrophilic polystyrene standard microspheres provided by the embodiments of the present invention specifically includes: An acquisition unit: acquire concentrated sulfuric acid, concentrated nitric acid, polystyrene standard microsphere particles, and ultrapure water; A mixing unit: mix the concentrated sulfuric acid, concentrated nitric acid and polystyrene standard microsphere particles to obtain a mixed solution; A preparation unit: add the ultrapure water to the mixed solution and perform centrifugal cleaning to obtain hydrophilic polystyrene standard microsphere particles.

[0029] Figure 3Schematic diagram of a preparation device for hydrophilic polystyrene standard microspheres provided by an embodiment of the present invention, specifically including: A memory and a processor; the memory is used to store program instructions; the processor is used to call the program instructions, and when the program instructions are executed, any of the above-mentioned hydrophilic polystyrene standard microsphere preparation methods.

[0030] An embodiment of the present invention also provides a computer-readable storage medium, the computer-readable storage medium stores a computer program, and when the computer program is executed by a processor, any of the above-mentioned hydrophilic polystyrene standard microsphere preparation methods.

[0031] An embodiment of the present invention provides a method for preparing radioactive hydrophilic polystyrene standard microspheres, including: Obtaining hydrophilic polystyrene standard microsphere particles according to the above-mentioned hydrophilic polystyrene standard microsphere preparation method; obtaining radioactive isotopes and PBS solution; Adding the hydrophilic polystyrene standard microsphere particles and radioactive isotopes to the PBS solution to obtain a radioactive mixed solution, Adding PBS solution to the radioactive mixed solution and centrifuging and washing to obtain radioactive hydrophilic polystyrene standard microsphere particles.

[0032] In one embodiment, the method further includes the preparation of a radioactive hydrophilic aerosol generating liquid, obtaining ultrapure water, and mixing the ultrapure water with radioactive hydrophilic polystyrene standard microsphere particles to obtain a radioactive hydrophilic particle aerosol generating liquid.

[0033] In one embodiment, the radioactive standard particles are obtained through an oxidation-reduction reaction of standard particles and radioactive isotopes.

[0034] In one embodiment, the radioactive isotopes include one or more of the following: 125 I-NaI.

[0035] In one embodiment, the preparation process of the radioactive standard particles is as follows: Obtaining hydrophilic polystyrene standard particles, 125 I-NaI; Adding hydrophilic polystyrene standard particles, 125 I-NaI to the PBS solution and obtaining a radioactive hydrophilic standard particle solution through an oxidation-reduction reaction; Rinsing and filtering the radioactive hydrophilic standard particle solution with deionized water until no separable γ activity remains, to obtain radioactive hydrophilic polystyrene standard particles.

[0036] In one embodiment, chloramine-T is further included in the PBS solution, and a redox reaction occurs among the chloramine-T, standard particles, and radioactive isotope in the PBS solution to obtain a reaction solution.

[0037] In a specific embodiment, the process of preparing radioactive standard particles and generator solution: Experimental materials: The raw materials mainly include polystyrene particles (Thermo Scientific, USA), PBS solution (Thermo Scientific, USA), porous cellulose filter membrane (Sigma-Aldrich, USA), 125 I-NaI (McMaster University, Canada), PBS (Sigma-Aldrich, USA), chloramine-T (Sigma-Aldrich, USA), ultrafiltration tube with porous cellulose membrane (MWCO: 100 KD) (Sigma-Aldrich, USA).

[0038] 5 mg of standard particles are added to 5 mL of PBS, and 2000 μCi 125 I-NaI and 200 μL of chloramine-T with a concentration of 4 mg / mL are added, and the reaction occurs at 25 °C in PBS for 30 min. The particles are centrifugally separated using an ultrafiltration tube with a porous cellulose membrane (MWCO: 100 KD) to remove the excess 125 I, and then washed with deionized water at least 5 times until there is no separable γ activity in the filtrate solution. Then, ultrapure water is mixed to prepare the aerosol generator solution. The generator solution is left to stand for 5 hours for measurement, and the stability of the radioactive calibration of the polystyrene particles is determined using MiniScan PRO Radio-iTLC.

[0039] According to the ratio of the radioactivity on the particle surface after five hours of labeling to that at the initial moment of labeling, it can be obtained that the radioactive labeling of the particles has good stability. The ratio of the radioactivity on the particle surface after five hours of labeling to that at the initial moment of labeling is shown in the following table.

[0040]

[0041] An embodiment of the present invention provides a monodisperse aerosol generation method for animals, including: Obtaining hydrophilic polystyrene standard microsphere particles and hydrophilic aerosol generator solution through the above-mentioned preparation method of hydrophilic polystyrene standard microspheres; Add the hydrophilic polystyrene standard microsphere particle aerosol generating liquid to an aerosol generator to obtain a monodisperse aerosol, where the aerosol generator includes a polydisperse aerosol generator and an aerosol diffusion drying tube. A polydisperse aerosol is generated in the polydisperse aerosol generator, and the polydisperse aerosol passes through the aerosol diffusion drying tube to obtain a monodisperse aerosol.

[0042] In one embodiment, the particle size range of the monodisperse aerosol is 0.2 μm - 10 μm; In one embodiment, the polydisperse aerosol generator includes one or more of the following: Collision three-hole polydisperse aerosol generator, German 7811 polydisperse aerosol generator, TDA-4B polydisperse aerosol generator, TDA-6C polydisperse aerosol generator, MODEL 3990-01 polydisperse aerosol generator.

[0043] In one embodiment, the monodisperse aerosol has a single particle size.

[0044] In one embodiment, the particle size range of the monodisperse aerosol is 0.2 μm - 10 μm.

[0045] In one embodiment, the aerosol generator further includes an air compressor, a cascade filter, a valve, and a flow meter. Non-clean gas is obtained through the air compressor, the non-clean gas is filtered through the cascade filter to obtain clean gas, the clean gas is controlled to enter the polydisperse aerosol generator through the valve, the flow rate of the gas is measured through the flow meter, and the hydrophilic polystyrene standard particle aerosol generating liquid is added to the polydisperse aerosol generator. When the gas flow rate reaches the generation condition, the valve is opened to generate a polydisperse aerosol, and the polydisperse aerosol passes through the aerosol diffusion drying tube to obtain a monodisperse aerosol.

[0046] In one embodiment, the hydrophilic polystyrene standard microspheres are replaced with radioactive hydrophilic polystyrene standard microspheres, and the radioactive hydrophilic polystyrene standard microspheres are obtained by the above-mentioned preparation method of radioactive hydrophilic polystyrene standard microspheres.

[0047] In one embodiment, the hydrophilic aerosol generating liquid is replaced with a radioactive hydrophilic aerosol generating liquid, and the radioactive hydrophilic aerosol generating liquid is obtained by the above-mentioned preparation method of radioactive hydrophilic polystyrene standard microspheres.

[0048] In one embodiment, the hydrophilic polystyrene standard microsphere particles are replaced with radioactive hydrophilic polystyrene standard microsphere particles, and the hydrophilic aerosol generating liquid is replaced with radioactive hydrophilic aerosol generating liquid. The radioactive hydrophilic polystyrene standard microsphere particles and the radioactive hydrophilic aerosol generating liquid are obtained by the above-mentioned preparation method of radioactive hydrophilic polystyrene standard microspheres.

[0049] In a specific embodiment, the process of generating radioactive aerosol is as follows Figure 5 shown: Experimental materials: polystyrene particles (Thermo Scientific, USA), polystyrene-divinylbenzene cross-linked microspheres (Thermo Scientific, USA), ultrapure water, aerosol diffusion dryer (HRH-DRY2, Huironghe Technology Co., Ltd.), Collision three-hole polydisperse aerosol generator (HRH-WAG3, Huironghe Technology Co., Ltd.), air compressor (Huironghe Technology Co., Ltd.), cascade filter (Huironghe Technology Co., Ltd.), valve (Huironghe Technology Co., Ltd.), flowmeter (Huironghe Technology Co., Ltd.).

[0050] Add the radioactive polystyrene particles and the radioactive polystyrene-divinylbenzene particle aerosol generating liquid into the Collision three-hole polydisperse aerosol generator, combine with the Huironghe HRH-DRY2 aerosol diffusion drying tube for generation and drying, and use the TSI3321 aerodynamic particle size spectrometer to measure the aerosol particle size spectrum. The aerosol particle size spectrum shows that the aerosol particle size spectra of 0.7 μm and 3 μm have good concentration, GSD < 1.2, meeting the monodisperse condition. The monodisperse radioactive hydrophilic aerosol particle size spectrum is as Figure 6 shown.

[0051] In a specific embodiment, the present invention first constructs radioactive monodisperse standard particles by using the technology of labeling polystyrene-based standard particles with radioactive isotope 125 I-NaI based on the principle of redox reaction. Subsequently, use the Collision three-hole polydisperse aerosol generator combined with the aerosol drying tube to generate monodisperse radioactive aerosol. Then, use the existing small animal inhalation exposure system combined with the tail gas recovery system to expose guinea pigs to radioactive aerosol by inhalation. Finally, perform SPECT / CT high-resolution detection on the exposed guinea pigs to quantitatively determine the deposition distribution.

[0052] Compared with the existing radioactive aerosol generation technology using electric spark + condensation method, this technology uses standard particles, performs radioactive labeling on the basis of the standard particles, and then uses a polydisperse liquid aerosol generator combined with a drying tube device to obtain monodisperse aerosol, which can better control the monodispersity of the aerosol. At the same time, this technology can generate both hydrophobic particle monodisperse aerosol and hydrophilic particle monodisperse aerosol.

[0053] In a specific embodiment, the small animal inhalation exposure system and the tail gas recovery process are as follows: Experimental equipment: nose and mouth exposure tower (Huironghe Technology Co., Ltd.), TSI3321 aerodynamic particle size spectrometer, TSI scanning mobility particle size spectrometer (TSI3756, TSI3081A, TSI3082, TSI3088), cascade filter (Huironghe Technology Co., Ltd.), flowmeter (Huironghe Technology Co., Ltd.), valve (Huironghe Technology Co., Ltd.), air extraction pump (Huironghe Technology Co., Ltd.), small animal SPECT / CT (Burker, USA).

[0054] First, the radioactive standard particulate matter is made into monodisperse aerosol and introduced into the nose and mouth exposure tower to construct a stable gas environment (monitor the aerosol particle size spectrum using the TSI3321 aerodynamic particle size spectrometer and the TSI scanning mobility particle size spectrometer); then the guinea pigs are placed in the inhalation exposure chamber for nose and mouth exposure breathing, and the breathing duration is 2 hours. After the exposure, the guinea pigs are anesthetized with 5 mL of 0.25% sodium pentobarbital, and the quantitative distribution of particle deposition in the guinea pigs is carried out using SPECT / CT. The remaining radioactive aerosol in the exposure tower is output from the outlet and recovered in sequence through the cascade filter, flowmeter + valve, and air extraction pump.

[0055] Among them, the SPECT / CT quantitative results show that the constructed system can quantitatively analyze the deposition distribution of particulate matter with different particle sizes in the respiratory tract with high resolution, and there are significant differences in the deposition distribution of 0.7-micron particulate matter and 3-micron particulate matter in the respiratory tract. As Figure 7 shown, the red color represents the deposition of the aerosol. It can be seen that the deposition regions of 0.7-micron particulate matter and 3-micron particulate matter in the respiratory tract are different, and most of the 0.7-micron particulate matter is deposited in the lungs.

[0056] The embodiment of the present invention provides a method for quantitatively analyzing the deposition distribution of monodisperse aerosol in the respiratory tract, including: Obtaining monodisperse aerosol according to the above-mentioned method for generating monodisperse aerosol for animals; After the animal inhales the monodisperse aerosol, tomographically scan the respiratory tract of the animal to obtain image data; Based on the image data, obtain the deposition distribution map of the monodisperse aerosol in the respiratory tract of the animal; In one embodiment, the monodisperse aerosol is a radioactive monodisperse aerosol.

[0057] The disclosed embodiments of the present invention also provide a computer program product or system, including a computer program, which when executed by a processor implements the steps of the above-mentioned method for quantitatively determining the deposition distribution of monodisperse aerosol in the respiratory tract.

[0058] The system for quantitatively determining the deposition distribution of monodisperse aerosol in the respiratory tract provided by the embodiments of the present invention specifically includes: Aerosol unit: obtaining monodisperse aerosol according to the above-mentioned method for generating monodisperse aerosol for animals; Imaging unit: obtaining image data by tomographically scanning the respiratory tract of an animal after the animal inhales the monodisperse aerosol; Distribution unit: obtaining a deposition distribution map of the monodisperse aerosol in the respiratory tract of the animal based on the image data.

[0059] A device for quantitatively determining the deposition distribution of monodisperse aerosol in the respiratory tract provided by the embodiments of the present invention specifically includes: A memory and a processor; the memory is used for storing program instructions; the processor is used for calling the program instructions, and when the program instructions are executed, any one of the above-mentioned methods for quantitatively determining the deposition distribution of monodisperse aerosol in the respiratory tract.

[0060] The disclosed embodiments of the present invention also provide a computer-readable storage medium, which stores a computer program, and when the computer program is executed by a processor, any one of the above-mentioned methods for determining the deposition distribution of monodisperse aerosol.

[0061] The embodiments of the present invention provide a method for constructing a prediction model of monodisperse aerosol deposition distribution, including: Obtaining an atlas and labels of deposition distribution maps of monodisperse aerosols with different particle sizes deposited in the respiratory tract of animals; Inputting the atlas and labels of the deposition distribution maps into a neural network model for training to obtain a deposition distribution prediction model; Wherein, the deposition distribution map is obtained by the above-mentioned method for quantitatively determining the deposition distribution of monodisperse aerosol in the respiratory tract.

[0062] In one embodiment, the neural network includes one or more of the following: convolutional neural network, Transformer, residual network, dilated convolutional neural network.

[0063] In one embodiment, the method further includes deposition distribution prediction: Obtaining a particle size distribution map and data of monodisperse aerosol; Input the monodisperse aerosol particle size distribution map and data into the deposition distribution prediction model to obtain the deposition distribution of particulate matter in the respiratory tract.

[0064] The disclosed embodiments of the present invention also provide a computer program product or system, including a computer program, which when executed by a processor implements the steps of the above method for constructing a monodisperse aerosol deposition distribution prediction model.

[0065] The system for constructing a monodisperse aerosol deposition distribution prediction model provided by the embodiments of the present invention specifically includes: Deposition unit: Obtain the deposition distribution atlas and labels of monodisperse aerosol deposition in the respiratory tract of animals with different particle sizes; Construction unit: Input the deposition distribution atlas and labels into the neural network model for training to obtain the deposition distribution prediction model; Wherein, the deposition distribution map is obtained by the above quantitative method for the deposition distribution of monodisperse aerosol in the respiratory tract.

[0066] The device for constructing a monodisperse aerosol deposition distribution prediction model provided by the embodiments of the present invention specifically includes: A memory and a processor; the memory is used to store program instructions; the processor is used to call the program instructions, and when the program instructions are executed, it is any one of the above methods for constructing a monodisperse aerosol deposition distribution prediction model.

[0067] The disclosed embodiments of the present invention also provide a computer-readable storage medium, which stores a computer program, and when the computer program is executed by a processor, it is any one of the above methods for constructing a monodisperse aerosol deposition distribution prediction model.

[0068] The method for predicting the deposition distribution of monodisperse aerosol in the respiratory tract of animals provided by the embodiments of the present invention includes: Obtain the monodisperse aerosol particle size distribution map; Input the monodisperse aerosol particle size distribution data into the above method for constructing a monodisperse aerosol deposition distribution prediction model to obtain the prediction model.

[0069] The disclosed embodiments of the present invention also provide a computer program product or system, including a computer program, which when executed by a processor implements the steps of the above method for predicting the deposition distribution of monodisperse aerosol in the respiratory tract of animals.

[0070] The system for predicting the deposition distribution of monodisperse aerosol in the respiratory tract of animals provided by the embodiments of the present invention specifically includes: Particle size module: Obtain the monodisperse aerosol deposition distribution map; Prediction module: Input the monodisperse aerosol deposition distribution map into the prediction model obtained by the above-mentioned method for constructing the deposition distribution prediction model to obtain the prediction result of the particle deposition distribution in the animal respiratory tract.

[0071] A device for predicting the deposition distribution of monodisperse aerosol in the animal respiratory tract provided by an embodiment of the present invention specifically includes: A memory and a processor; the memory is used to store program instructions; the processor is used to call the program instructions, and when the program instructions are executed, it is any one of the above-mentioned methods for predicting the deposition distribution of monodisperse aerosol in the animal respiratory tract.

[0072] An embodiment of the present invention also provides a computer-readable storage medium, which stores a computer program, and when the computer program is executed by a processor, it is any one of the above-mentioned methods for predicting the deposition distribution of monodisperse aerosol in the animal respiratory tract.

[0073] The verification results of this verification embodiment show that allocating fixed weights for indications can improve the performance of this method compared to the default settings. Those skilled in the art can clearly understand that for the convenience and brevity of description, the specific working processes of the systems, devices, and units described above can refer to the corresponding processes in the foregoing method embodiments and will not be elaborated herein. In several embodiments provided by this application, it should be understood that the disclosed systems, devices, and methods can be implemented in other ways. For example, the device embodiments described above are merely illustrative. For example, the division of the units is only a logical function division, and there can be other division methods in actual implementation. For example, multiple units or components can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the displayed or discussed couplings or direct couplings or communication connections to each other can be through some interfaces, and the indirect couplings or communication connections of the devices or units can be in electrical, mechanical, or other forms. The units described as separate components may or may not be physically separated, and the components displayed as units may or may not be physical units, that is, they can be located in one place or distributed to multiple network units. Some or all of the units can be selected according to actual needs to achieve the purpose of the solution of this embodiment. In addition, in each embodiment of the present invention, the functional units can be integrated into one processing unit, or each unit can exist physically alone, or two or more units can be integrated into one unit. The above-mentioned integrated units can be implemented in the form of hardware or in the form of software functional units. Those of ordinary skill in the art can understand that all or part of the steps in the various methods of the above embodiments can be completed by instructing relevant hardware through a program, and this program can be stored in a computer-readable storage medium. The storage medium can include: read-only memory (ROM, Read Only Memory), random access memory (RAM, Random Access Memory), magnetic disk, or optical disc, etc.

[0074] Those of ordinary skill in the art can understand that all or part of the steps in implementing the methods of the above embodiments can be completed by instructing relevant hardware through a program, and the program can be stored in a computer-readable storage medium. The above-mentioned medium storage can be read-only memory, magnetic disk, or optical disc, etc.

[0075] The above has introduced in detail a computer device provided by the present invention. For those of ordinary skill in the art, according to the idea of the embodiments of the present invention, there will be changes in the specific implementation manners and application scopes. In summary, the content of this specification should not be construed as a limitation to the present invention.

Claims

1. A method for preparing hydrophilic polystyrene standard microspheres, characterized in that: include: Obtain concentrated sulfuric acid, concentrated nitric acid, polystyrene standard microsphere particles, and ultrapure water; The concentrated sulfuric acid, concentrated nitric acid and polystyrene standard microsphere particles are mixed to obtain a mixed solution; The ultrapure water is added to the mixed solution for washing and then centrifuged to obtain hydrophilic polystyrene standard microsphere particles.

2. The method for preparing hydrophilic polystyrene standard microspheres according to claim 1, characterized in that: The concentrated sulfuric acid and concentrated nitric acid are mixed with polystyrene standard microsphere particles in a volume ratio of 1:3 to obtain a mixed solution; Optionally, the polystyrene standard microsphere particles are polystyrene standard microsphere particles of different particle sizes, with a particle size range of 0.2 μm-10 μm; Optionally, the method further comprises preparing a hydrophilic aerosol generating liquid, and mixing the hydrophilic polystyrene standard microsphere particles with ultrapure water to obtain the hydrophilic aerosol generating liquid.

3. A method for preparing radioactive hydrophilic polystyrene standard microspheres, characterized in that: include: Obtain hydrophilic polystyrene standard microsphere particles according to the method for preparing hydrophilic polystyrene standard microspheres according to claim 1; obtain radioactive isotopes and PBS solution; Adding the hydrophilic polystyrene standard microsphere particles and radioactive isotopes into a PBS solution and mixing to obtain a radioactive mixed solution; Adding PBS solution to the radioactive mixed solution for washing and centrifugation to obtain radioactive hydrophilic polystyrene standard microsphere particles; Optionally, the method further comprises preparing a radioactive hydrophilic aerosol generating liquid, obtaining ultrapure water, and mixing the ultrapure water with radioactive hydrophilic polystyrene standard microsphere particles to obtain a radioactive hydrophilic particle aerosol generating liquid.

4. A method for generating monodisperse aerosol for animals, characterized in that: include: Obtaining hydrophilic polystyrene standard microsphere particles and hydrophilic aerosol generating liquid by the hydrophilic polystyrene standard microsphere preparation method described in claims 1-2; Adding the hydrophilic polystyrene standard microsphere particle aerosol generating liquid into an aerosol generator to obtain a monodisperse aerosol, wherein the aerosol generator comprises a polydisperse aerosol generator and an aerosol diffusion drying tube, the standard particles and the aerosol generating liquid generate a polydisperse aerosol in the polydisperse aerosol generator, and the polydisperse aerosol passes through the aerosol diffusion drying tube to obtain a monodisperse aerosol; Optionally, the particle size of the monodisperse aerosol ranges from 0.2 μm to 10 μm; Optionally, the polydisperse aerosol generator includes one or more of the following: Collision three-hole polydisperse aerosol generator, German 7811 polydisperse aerosol generator, TDA-4B polydisperse aerosol generator, TDA-6C polydisperse aerosol generator, MODEL 3990-01 polydisperse aerosol generator.

5. The method for generating monodisperse aerosol for animals according to claim 4, characterized in that: The hydrophilic polystyrene standard microsphere particles are replaced with radioactive hydrophilic polystyrene standard microsphere particles, and the radioactive hydrophilic polystyrene standard microsphere particles are obtained by the preparation method of radioactive hydrophilic polystyrene standard microspheres according to claim 3; Optionally, the hydrophilic aerosol generating liquid is replaced with a radioactive hydrophilic aerosol generating liquid, and the radioactive hydrophilic aerosol generating liquid is obtained by the method for preparing radioactive hydrophilic polystyrene standard microspheres according to claim 3; Optionally, the hydrophilic polystyrene standard microsphere particles are replaced by radioactive hydrophilic polystyrene standard microsphere particles, and the hydrophilic aerosol generating liquid is replaced by a radioactive hydrophilic aerosol generating liquid, and the radioactive hydrophilic polystyrene standard microsphere particle aerosol generating liquid is obtained by the method for preparing radioactive hydrophilic polystyrene standard microspheres according to claim 3.

6. A quantitative method for the deposition distribution of monodisperse aerosol in the respiratory tract, characterized in that: include: Obtaining a monodisperse aerosol according to the method for generating a monodisperse aerosol for animals according to any one of claims 4 to 5; After the animal inhales the monodisperse aerosol, a tomographic scan of the animal's respiratory tract is performed to obtain imaging data; Obtaining a deposition distribution map of monodisperse aerosol in the respiratory tract of the animal based on the image data; Optionally, the monodisperse aerosol is a radioactive monodisperse aerosol.

7. A method for constructing a monodisperse aerosol deposition distribution prediction model, characterized in that: include: Obtain deposition distribution atlases and labels of monodisperse aerosols of different particle sizes deposited in the animal respiratory tract; Inputting the deposition distribution atlas and labels into a neural network model for training to obtain a deposition distribution prediction model; Wherein, the deposition distribution diagram is obtained by the quantitative method for the deposition distribution of monodisperse aerosol in the respiratory tract as claimed in claim 6; Optionally, the method further comprises a deposition distribution prediction: Obtain monodisperse aerosol particle size distribution diagram and data; The monodisperse aerosol particle size distribution diagram and data are input into a deposition distribution prediction model to obtain the deposition distribution of particles in the respiratory tract.

8. A computer program product comprising a computer program or instructions, characterized in that include: The computer program or instructions are executed by the processor to implement the method for preparing hydrophilic polystyrene standard microspheres as described in any one of claims 1-2, or to implement the method for preparing radioactive hydrophilic polystyrene standard microspheres as described in claim 3, or to implement the method for generating monodisperse aerosols for animals as described in any one of claims 4-5, or to implement the quantitative method for the deposition distribution of monodisperse aerosols in the respiratory tract as described in claim 6, or to implement the method for constructing a monodisperse aerosol deposition distribution prediction model as described in claim 7.

9. A computer device comprising a memory, a processor and a computer program or instruction stored in the memory, characterized in that: The computer program or instructions are executed by the processor to implement the method for preparing hydrophilic polystyrene standard microspheres as described in any one of claims 1-2, or to implement the method for preparing radioactive hydrophilic polystyrene standard microspheres as described in claim 3, or to implement the method for generating monodisperse aerosols for animals as described in any one of claims 4-5, or to implement the quantitative method for the deposition distribution of monodisperse aerosols in the respiratory tract as described in claim 6, or to implement the method for constructing a monodisperse aerosol deposition distribution prediction model as described in claim 7.

10. A computer-readable storage medium having a computer program or instruction stored thereon, characterized in that: The computer program or instructions are executed by the processor to implement the method for preparing hydrophilic polystyrene standard microspheres as described in any one of claims 1-2, or to implement the method for preparing radioactive hydrophilic polystyrene standard microspheres as described in claim 3, or to implement the method for generating monodisperse aerosols for animals as described in any one of claims 4-5, or to implement the quantitative method for the deposition distribution of monodisperse aerosols in the respiratory tract as described in claim 6, or to implement the method for constructing a monodisperse aerosol deposition distribution prediction model as described in claim 7.

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