CN113926010A - Whole blood simulation liquid for in-vitro test of hollow fiber blood purification device - Google Patents

Whole blood simulation liquid for in-vitro test of hollow fiber blood purification device Download PDF

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CN113926010A
CN113926010A CN202111180493.8A CN202111180493A CN113926010A CN 113926010 A CN113926010 A CN 113926010A CN 202111180493 A CN202111180493 A CN 202111180493A CN 113926010 A CN113926010 A CN 113926010A
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whole blood
simulated liquid
simulant
myoglobin
albumin
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CN113926010B (en
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牟倡骏
曲佳伟
于亚楠
李井龙
李祥鹏
丛慧
王晶
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Shandong Weigao Blood Purification Products Co Ltd
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Shandong Weigao Blood Purification Products Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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Abstract

The invention provides a whole blood simulation solution for in-vitro testing of a hollow fiber blood purification device, which comprises the following components: the volume ratio of the particulate matter to the simulated liquid is 1: 1-1: 9; the particulate matter is selected from silica particles or polystyrene microspheres; the simulation solution consists of soluble macromolecules and water; the soluble macromolecules are selected from at least two of glucan, hydroxyethyl starch, albumin, lysozyme and myoglobin; the water content in the simulated liquid is not more than 95 wt%. The uniformity of a test system can be ensured by adopting the in-vitro whole blood simulation liquid to simulate blood, and the instability of test results caused by the difference among different batches of bovine blood is avoided.

Description

Whole blood simulation liquid for in-vitro test of hollow fiber blood purification device
Technical Field
The invention belongs to the technical field of blood purification, and particularly relates to whole blood simulation liquid for in-vitro testing of a hollow fiber blood purification device.
Background
Repeated tests on the performance of the product are required during the development of the extracorporeal blood purification system in order to adjust the process of the product at any time. In vitro performance testing, whole blood is an important reagent, and most of animal blood is used after anticoagulation because human blood cannot be used for testing. However, the storage period after blood separation is short, and the difference between different individuals is relatively large, so that the repeatability of data is low, in order to ensure the accuracy of the result, a large number of tests are often required, and the accuracy of the test result is ensured through large data, so that the research and development cost is inevitably increased. Therefore, there is a need for a system which is stable and relatively uniform in composition and can simulate blood, and can be used for evaluating the in vitro performance of products.
Disclosure of Invention
In view of the above, the present invention provides a whole blood simulant for extracorporeal test of a hollow fiber blood purification apparatus, which is a stable and uniform simulant capable of most truly simulating the flowing state of blood in the hollow fiber blood purification apparatus.
The invention provides a whole blood simulation solution for in-vitro testing of a hollow fiber blood purification device, which comprises the following components:
the volume ratio of the particulate matter to the simulated liquid is 1: 1-1: 9;
the particulate matter is selected from silica particles or polystyrene microspheres;
the simulation solution consists of soluble macromolecules and water; the soluble macromolecules are selected from at least two of glucan, hydroxyethyl starch, albumin, lysozyme and myoglobin; the water content in the simulated liquid is not more than 95 wt%.
In the invention, the specification of the particulate matter is 5-10 μm. The particle size of the granular material is similar to the size of red blood cells, so that the flow state of the simulated liquid system in vitro is similar to the flow state of blood.
In the invention, the simulation liquid is selected from a mixed solution of water, dextran, hydroxyethyl starch, albumin and lysozyme, or a mixed solution of water, dextran, hydroxyethyl starch, albumin and myoglobin, or a mixed solution of water, polyvinylpyrrolidone and lysozyme, or a mixed solution of water, polyvinylpyrrolidone and myoglobin.
In the invention, the protein substances in the whole blood simulant can simulate the interaction of blood in the hollow fiber membrane to the maximum extent, so that the simulant is more suitable for the real use condition.
In the invention, the glucan accounts for 1-10% of the mass of the simulated liquid;
the hydroxyethyl starch accounts for 1-10% of the weight of the simulated liquid;
the lysozyme accounts for 0.5-5% of the mass of the simulation liquid;
the polyvinyl pyrrolidone accounts for 1-20% of the mass of the simulation liquid;
the myoglobin accounts for 0.5-5% of the mass of the simulated liquid.
In the invention, the molecular weight of the glucan is 70-800 kDa;
the molecular weight of the hydroxyethyl starch is 40-400 kDa;
the albumin is selected from bovine serum albumin and/or pig serum albumin.
In the present invention, the polyvinylpyrrolidone has a brand selected from one or more of K60, K85, K90, K110 and K120.
In the invention, the whole blood simulated fluid comprises polystyrene microspheres with the diameter of 6 mu m and a simulated fluid with the volume ratio of 28:100, wherein the simulated fluid comprises 30 wt% of bovine serum albumin, 3 wt% of myoglobin and 1 wt% of lysozyme;
or comprises polystyrene microspheres with the diameter of 6 mu m and a simulated liquid with the volume ratio of 28:100, wherein the simulated liquid comprises 10 wt% of glucan with the molecular weight of 70kDa, 15 wt% of albumin and 1 wt% of lysozyme;
or comprises polystyrene microspheres with the diameter of 6 mu m and a simulated liquid with the volume ratio of 28:100, wherein the simulated liquid comprises 5 wt% of glucan with the molecular weight of 400kDa, 10 wt% of albumin and 2 wt% of myoglobin;
or comprises polystyrene microspheres with the diameter of 6 mu m and a simulated liquid with the volume ratio of 28:100, wherein the simulated liquid comprises 1 wt% of dextran with the molecular weight of 800kDa, 15 wt% of albumin and 2 wt% of myoglobin;
or comprises silicon dioxide with the diameter of 6 mu m and a simulated liquid with the volume ratio of 30:100, wherein the simulated liquid comprises 30 wt% of bovine serum albumin, 3 wt% of myoglobin and 1 wt% of lysozyme;
or comprises 9 mu m polystyrene microspheres with the volume ratio of 30:100 and a simulated liquid, wherein the simulated liquid comprises 1 wt% of polyvinylpyrrolidone with the molecular weight of 1100kDa and 5 wt% of myoglobin;
or comprises polystyrene microspheres with the diameter of 6 mu m and a simulated liquid with the volume ratio of 32:100, wherein the simulated liquid comprises 6 wt% of hydroxyethyl starch with the molecular weight of 200kDa, 1 wt% of albumin and 2 wt% of myoglobin.
The whole blood simulation solution provided by the invention is low in price, and the test cost is greatly reduced. The price of 1L of bovine blood is about 1000 yuan, while the whole blood simulation fluid of the invention is 1/10 which is low in price.
The invention adopts a continuous transmembrane pressure monitoring test device diagram shown in FIG. 1 to test the simulation liquid:
after the dialyzer had been primed, the whole blood simulant was introduced into the dialyzer and the test was performed according to the following conditions: the blood flow rate is 200mL/min, the dehydration amount is 10mL/min, the inlet and outlet pressures of the dialyzer and the inlet and outlet pressures of the dialysate are read every 10min, and the transmembrane pressure is calculated as follows:
trans-membrane pressure ═ PBI+PBO)－(PDI+PDO))/2
Wherein, PBIIs the dialyzer inlet pressure, PBOIs the dialyzer outlet pressure, PDIFor dialysate inlet pressure, PDODialysate outlet pressure;
and establishing a time and transmembrane pressure curve chart by taking the time as an abscissa and the transmembrane pressure as an ordinate.
Comparing the difference between the whole blood of the cattle and the whole blood simulant, the curve has the same trend as the whole blood, and the smaller the difference is, the better the curve is (the difference between the starting point of the whole blood of the cattle and the starting point of the whole blood of the cattle is preferably within 5 mmHg).
The invention provides a whole blood simulation solution for in-vitro testing of a hollow fiber blood purification device, which comprises the following components: the volume ratio of the particulate matter to the simulated liquid is 1: 1-1: 9; the particulate matter is selected from silica particles or polystyrene microspheres; the simulation solution consists of soluble macromolecules and water; the soluble macromolecules are selected from at least two of glucan, hydroxyethyl starch, albumin, lysozyme and myoglobin; the water content in the simulated liquid is not more than 95 wt%. The uniformity of a test system can be ensured by adopting the in-vitro whole blood simulation liquid to simulate blood, and the instability of test results caused by the difference among different batches of bovine blood is avoided.
Drawings
FIG. 1 is a diagram of a continuous transmembrane pressure monitoring test device employed in the present invention;
FIG. 2 is a graph showing the change of the simulated liquid transmembrane pressure with time in example 1 of the present invention;
FIG. 3 is a graph showing the change of the simulated liquid transmembrane pressure with time in example 2 of the present invention;
FIG. 4 is a graph showing the change of the simulated liquid transmembrane pressure with time in example 3 of the present invention;
FIG. 5 is a graph showing the time-dependent change in the simulated transmembrane pressure in example 4 of the present invention;
FIG. 6 is a graph showing the time-dependent change in the simulated transmembrane pressure in example 5 of the present invention;
FIG. 7 is a graph showing the time-dependent change in the simulated transmembrane pressure in example 6 of the present invention;
FIG. 8 is a graph showing the time-dependent change in the simulated hydraulic transmembrane pressure in example 7 of the present invention.
Detailed Description
In order to further illustrate the present invention, the whole blood simulant for the in vitro test of the hollow fiber blood purification device provided by the present invention is described in detail below with reference to the examples, but they should not be construed as limiting the scope of the present invention.
Example 1
The composition of the whole blood simulant (whole blood substitute) used was as follows:
polystyrene microspheres with the diameter of 6 mu m and a simulation liquid with the volume ratio of 28:100, wherein the simulation liquid comprises 30 wt% of bovine serum albumin, 3 wt% of myoglobin, 1 wt% of lysozyme and the balance of water.
Bovine whole blood was used as a control group.
The invention adopts the monitoring device shown in FIG. 1 to simulate the change of the transmembrane pressure of whole blood and bovine whole blood along with time, and the test data are shown in Table 1;
TABLE 1 transmembrane pressure of whole blood simulant of example 1 as a function of time
Time/min Transmembrane pressure (mmHg) of bovine whole blood Transmembrane pressure (mmHg) of example 1
0 44.6 48.0
10 45.7 48.7
20 46.3 48.8
30 46.5 49.8
40 47.4 50.4
50 47.9 51.0
60 48.3 51.2
70 48.6 52.0
80 49.4 51.9
90 49.7 52.6
100 50.1 53.1
110 50.5 53.8
120 51.5 54.4
130 52.0 54.9
140 52.7 55.3
150 53.1 56.0
160 53.6 56.2
170 54.0 56.6
180 54.5 56.7
190 54.8 57.3
200 55.5 57.9
210 55.3 58.2
220 55.7 59.0
230 56.2 60.0
240 56.4 60.4
By plotting the data of table 1 in the form of a coordinate graph, see fig. 2, it can be seen from fig. 2 that: under the same test condition, the change trend of the whole bovine blood and the whole blood simulant is the same in the same time, and the difference between the initial transmembrane pressures of the whole bovine blood and the whole blood simulant is within 5mmHg, thereby meeting the requirement.
Example 2
The composition of the whole blood simulant (whole blood substitute) used was as follows:
silicon dioxide with the diameter of 6 mu m and a simulated liquid with the volume ratio of 30:100, wherein the simulated liquid comprises 30 wt% of bovine serum albumin, 3 wt% of myoglobin, 1 wt% of lysozyme and the balance of water;
bovine whole blood was used as a control group.
The invention adopts the monitoring device shown in FIG. 1 to simulate the change of the transmembrane pressure of whole blood and bovine whole blood along with time, and the test data are shown in Table 1;
TABLE 2 transmembrane pressure as a function of time for the whole blood simulant of example 2
Time/min Transmembrane pressure (mmHg) of bovine whole blood Transmembrane pressure (mmHg) of example 2
0 44.6 48.6
10 45.7 49.0
20 46.3 49.2
30 46.5 49.1
40 47.4 49.7
50 47.9 50.0
60 48.3 50.5
70 48.6 50.8
80 49.4 51.0
90 49.7 51.9
100 50.1 52.4
110 50.5 53.0
120 51.5 53.6
130 52.0 54.8
140 52.7 55.0
150 53.1 55.9
160 53.6 56.0
170 54.0 56.8
180 54.5 57.0
190 54.8 57.7
200 55.5 58.2
210 55.3 59.7
220 55.7 60.0
230 56.2 60.6
240 56.4 61.0
By plotting the data of table 2 in the form of a coordinate graph, see fig. 3, it can be seen from fig. 3 that: under the same test condition, the change trend of the whole bovine blood and the whole blood simulant is the same in the same time, and the difference between the initial transmembrane pressures of the whole bovine blood and the whole blood simulant is within 5mmHg, thereby meeting the requirement.
Example 3
The composition of the whole blood simulant (whole blood substitute) used was as follows:
polystyrene microspheres with the diameter of 6 mu m and a simulated liquid with the volume ratio of 28:100, wherein the simulated liquid comprises 10 wt% of glucan with the molecular weight of 70kDa, 15 wt% of albumin, 1 wt% of lysozyme and the balance of water;
bovine whole blood was used as a control group.
The invention adopts the monitoring device shown in FIG. 1 to simulate the change of the transmembrane pressure of whole blood and bovine whole blood along with time, and the test data are shown in Table 3;
TABLE 3 transmembrane pressure as a function of time for the whole blood simulant of example 3
Time/min Transmembrane pressure (mmHg) of bovine whole blood Transmembrane pressure (mmHg) of example 3
0 44.6 44.0
10 45.7 44.5
20 46.3 45.0
30 46.5 45.7
40 47.4 46.0
50 47.9 46.2
60 48.3 47.0
70 48.6 47.4
80 49.4 48.0
90 49.7 48.5
100 50.1 49.0
110 50.5 49.2
120 51.5 49.5
130 52.0 50.0
140 52.7 51.0
150 53.1 51.6
160 53.6 52.1
170 54.0 53.0
180 54.5 53.6
190 54.8 54.0
200 55.5 55.0
210 55.3 55.7
220 55.7 56.0
230 56.2 57.0
240 56.4 57.2
By plotting the data of table 3 in the form of a coordinate graph, see fig. 4, it can be seen from fig. 4 that: under the same test condition, the change trend of the whole bovine blood and the whole blood simulant is the same in the same time, and the difference between the initial transmembrane pressures of the whole bovine blood and the whole blood simulant is within 5mmHg, thereby meeting the requirement.
Example 4
The composition of the whole blood simulant (whole blood substitute) used was as follows:
polystyrene microspheres with the diameter of 6 mu m and a simulation liquid with the volume ratio of 28:100, wherein the simulation liquid comprises 5 wt% of glucan with the molecular weight of 400kDa, 10 wt% of albumin, 2 wt% of myoglobin and the balance of water;
bovine whole blood was used as a control group.
The invention adopts the monitoring device shown in FIG. 1 to simulate the change of the transmembrane pressure of whole blood and bovine whole blood along with the time, and the test data are shown in Table 4;
TABLE 4 transmembrane pressure as a function of time for the whole blood simulant of example 4
Time/min Transmembrane pressure (mmHg) of bovine whole blood Transmembrane pressure (mmHg) of example 4
0 44.6 43.7
10 45.7 44.1
20 46.3 44.9
30 46.5 45.2
40 47.4 45.0
50 47.9 45.6
60 48.3 46.0
70 48.6 47.0
80 49.4 47.7
90 49.7 48.0
100 50.1 49.0
110 50.5 49.6
120 51.5 50.0
130 52.0 50.8
140 52.7 51.2
150 53.1 52.0
160 53.6 52.6
170 54.0 53.0
180 54.5 53.4
190 54.8 54.0
200 55.5 54.5
210 55.3 55.0
220 55.7 55.7
230 56.2 56.0
240 56.4 56.8
By plotting the data of table 4 in the form of a coordinate graph, see fig. 5, it can be seen from fig. 5 that: under the same test condition, the change trend of the whole bovine blood and the whole blood simulant is the same in the same time, and the difference between the initial transmembrane pressures of the whole bovine blood and the whole blood simulant is within 5mmHg, thereby meeting the requirement.
Example 5
The composition of the whole blood simulant (whole blood substitute) used was as follows:
polystyrene microspheres with the diameter of 6 mu m and a simulation liquid with the volume ratio of 28:100, wherein the simulation liquid comprises 1 wt% of dextran with the molecular weight of 800kDa, 15 wt% of albumin, 2 wt% of myoglobin and the balance of water;
bovine whole blood was used as a control group.
The invention adopts the monitoring device shown in FIG. 1 to simulate the change of the transmembrane pressure of whole blood and bovine whole blood along with the time, and the test data are shown in Table 5;
TABLE 5 transmembrane pressure of whole blood simulant of example 5 as a function of time
Time/min Transmembrane pressure (mmHg) of bovine whole blood Transmembrane pressure (mmHg) of example 5
0 44.6 44.2
10 45.7 45.0
20 46.3 45.6
30 46.5 46.0
40 47.4 46.5
50 47.9 47.0
60 48.3 47.3
70 48.6 48.0
80 49.4 48.3
90 49.7 48.5
100 50.1 49.0
110 50.5 49.7
120 51.5 50.0
130 52.0 51.0
140 52.7 51.6
150 53.1 52.0
160 53.6 52.6
170 54.0 53.7
180 54.5 54.0
190 54.8 54.6
200 55.5 55.0
210 55.3 55.2
220 55.7 56.0
230 56.2 56.8
240 56.4 57.0
By plotting the data of table 5 in the form of a coordinate graph, see fig. 6, it can be seen from fig. 6 that: under the same test condition, the change trend of the whole bovine blood and the whole blood simulant is the same in the same time, and the difference between the initial transmembrane pressures of the whole bovine blood and the whole blood simulant is within 5mmHg, thereby meeting the requirement.
Example 6
The composition of the whole blood simulant (whole blood substitute) used was as follows:
polystyrene microspheres with the diameter of 6 mu m and a simulation liquid with the volume ratio of 32:100, wherein the simulation liquid comprises 6 wt% of hydroxyethyl starch with the molecular weight of 200kDa, 1 wt% of albumin, 2 wt% of myoglobin and the balance of water;
bovine whole blood was used as a control group.
The invention adopts the monitoring device shown in FIG. 1 to simulate the change of the transmembrane pressure of whole blood and bovine whole blood along with the time, and the test data are shown in Table 6;
TABLE 6 transmembrane pressure of whole blood simulant of example 6 as a function of time
Time/min Transmembrane pressure (mmHg) of bovine whole blood Transmembrane pressure (mmHg) of example 6
0 44.6 45.0
10 45.7 45.6
20 46.3 46.0
30 46.5 46.7
40 47.4 47.0
50 47.9 47.3
60 48.3 47.8
70 48.6 48.0
80 49.4 49.0
90 49.7 50.0
100 50.1 50.3
110 50.5 51.0
120 51.5 52.0
130 52.0 52.5
140 52.7 52.8
150 53.1 52.6
160 53.6 53.8
170 54.0 54.8
180 54.5 56.5
190 54.8 56.8
200 55.5 57.0
210 55.3 57.8
220 55.7 58.0
230 56.2 58.8
240 56.4 59.3
By plotting the data of table 6 in the form of a coordinate graph, see fig. 7, it can be seen from fig. 7 that: under the same test condition, the change trend of the whole bovine blood and the whole blood simulant is the same in the same time, and the difference between the initial transmembrane pressures of the whole bovine blood and the whole blood simulant is within 5mmHg, thereby meeting the requirement.
Example 7
The composition of the whole blood simulant (whole blood substitute) used was as follows:
polystyrene microspheres with the diameter of 9 mu m and a simulated liquid with the volume ratio of 30:100, wherein the simulated liquid comprises 1 wt% of polyvinylpyrrolidone with the molecular weight of 1100kDa, 5 wt% of myoglobin and the balance of water;
bovine whole blood was used as a control group.
The invention adopts the monitoring device shown in FIG. 1 to simulate the change of the transmembrane pressure of whole blood and bovine whole blood along with the time, and the test data are shown in Table 7;
TABLE 7 transmembrane pressure as a function of time for the whole blood simulant of example 7
Figure BDA0003297050880000091
Figure BDA0003297050880000101
By plotting the data of table 7 in the form of a coordinate graph, see fig. 8, it can be seen from fig. 8 that: under the same test condition, the change trend of the whole bovine blood and the whole blood simulant is the same in the same time, and the difference between the initial transmembrane pressures of the whole bovine blood and the whole blood simulant is within 5mmHg, thereby meeting the requirement.
From the above embodiments, the present invention provides a whole blood simulant for in vitro testing of a hollow fiber blood purification device, comprising: the volume ratio of the particulate matter to the simulated liquid is 1: 1-1: 9; the particulate matter is selected from silica particles or polystyrene microspheres; the simulation solution consists of soluble macromolecules and water; the soluble macromolecules are selected from at least two of glucan, hydroxyethyl starch, albumin, lysozyme and myoglobin; the water content in the simulated liquid is not more than 95 wt%. The uniformity of a test system can be ensured by adopting the in-vitro whole blood simulation liquid to simulate blood, and the instability of test results caused by the difference among different batches of bovine blood is avoided.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims (7)

1. A whole blood simulant for extracorporeal testing of a hollow fiber blood purification apparatus, comprising:
the volume ratio of the particulate matter to the simulated liquid is 1: 1-1: 9;
the particulate matter is selected from silica particles or polystyrene microspheres;
the simulation solution consists of soluble macromolecules and water; the soluble macromolecules are selected from at least two of glucan, hydroxyethyl starch, albumin, lysozyme and myoglobin; the water content in the simulated liquid is not more than 95 wt%.
2. The whole blood simulant of claim 1, wherein the particulate matter has a size of 5 to 10 μm.
3. The whole blood simulant of claim 1, wherein the simulant is selected from the group consisting of water, dextran, hydroxyethyl starch, a mixed solution of albumin and lysozyme, a mixed solution of water, dextran, hydroxyethyl starch, albumin and myoglobin, a mixed solution of water, polyvinylpyrrolidone and lysozyme, and a mixed solution of water, polyvinylpyrrolidone and myoglobin.
4. The whole blood simulant of claim 1, wherein the dextran comprises 1% to 10% of the simulant mass;
the hydroxyethyl starch accounts for 1-10% of the weight of the simulated liquid;
the lysozyme accounts for 0.5-5% of the mass of the simulation liquid;
the polyvinyl pyrrolidone accounts for 1-20% of the mass of the simulation liquid;
the myoglobin accounts for 0.5-5% of the mass of the simulated liquid.
5. The whole blood simulant of claim 1, wherein the dextran has a molecular weight of 70kDa to 800 kDa;
the molecular weight of the hydroxyethyl starch is 40-400 kDa;
the albumin is selected from bovine serum albumin and/or pig serum albumin.
6. The whole blood simulant of claim 1, wherein the polyvinylpyrrolidone has a designation selected from one or more of K60, K85, K90, K110 and K120.
7. The whole blood simulant of claim 1, wherein the whole blood simulant comprises polystyrene microspheres with a diameter of 6 μm and a simulant in a volume ratio of 28:100, wherein the simulant comprises 30 wt% of bovine serum albumin, 3 wt% of myoglobin and 1 wt% of lysozyme;
or comprises polystyrene microspheres with the diameter of 6 mu m and a simulated liquid with the volume ratio of 28:100, wherein the simulated liquid comprises 10 wt% of glucan with the molecular weight of 70kDa, 15 wt% of albumin and 1 wt% of lysozyme;
or comprises polystyrene microspheres with the diameter of 6 mu m and a simulated liquid with the volume ratio of 28:100, wherein the simulated liquid comprises 5 wt% of glucan with the molecular weight of 400kDa, 10 wt% of albumin and 2 wt% of myoglobin;
or comprises polystyrene microspheres with the diameter of 6 mu m and a simulated liquid with the volume ratio of 28:100, wherein the simulated liquid comprises 1 wt% of dextran with the molecular weight of 800kDa, 15 wt% of albumin and 2 wt% of myoglobin;
or comprises silicon dioxide with the diameter of 6 mu m and a simulated liquid with the volume ratio of 30:100, wherein the simulated liquid comprises 30 wt% of bovine serum albumin, 3 wt% of myoglobin and 1 wt% of lysozyme;
or comprises 9 mu m polystyrene microspheres with the volume ratio of 30:100 and a simulated liquid, wherein the simulated liquid comprises 1 wt% of polyvinylpyrrolidone with the molecular weight of 1100kDa and 5 wt% of myoglobin;
or comprises polystyrene microspheres with the diameter of 6 mu m and a simulated liquid with the volume ratio of 32:100, wherein the simulated liquid comprises 6 wt% of hydroxyethyl starch with the molecular weight of 200kDa, 1 wt% of albumin and 2 wt% of myoglobin.
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