A rapid blood gas mixing method and its dedicated device

Abstract

The present invention discloses a rapid blood-gas mixing method. Blood and gas are respectively introduced into a mixing channel. The mixing channel includes an inner pipe and an outer pipe sleeved outside the inner pipe. The pipe wall of the inner pipe has micropores permeable to gas molecules. A blood sample is inhaled from the inner pipe. At the same time, pressurized gas is introduced between the inner pipe and the outer pipe. The flow direction of the blood is the same as that of the gas. The pressure of the gas is regulated by a pressure sensor and a pressure regulating valve at the tail of the mixing channel, so that the gas can pass through the pipe wall of the inner pipe and slowly penetrate from the outside of the inner pipe into the pipe to be mixed with the blood in the pipe to form a blood-gas mixture. By using this method and its proprietary equipment, the mixing efficiency of the sample is high, and the gas can be quickly saturated in the blood sample. Applied to clinical detection, it can effectively shorten the sample preparation time and provide more valuable time for patient treatment.

Description

Technical Field

[0001] This application relates to the technical field of blood mixing, and more particularly, to a rapid blood gas mixing method and a dedicated device therefor. Background Art

[0002] Blood gas mixing and blood gas separation have been widely applied in the fields of biology, pharmacy, and medical in vitro diagnosis, such as the preparation of various concentration standard solutions, blood detection, gas purification, etc. A typical application is blood gas mixing.

[0003] The main purpose of blood gas mixing is to introduce gases such as oxygen and carbon dioxide at different concentrations into the blood to be tested. Through a blood gas mixing device, the blood to be tested finally contains these concentrations of oxygen, carbon dioxide, etc. The test blood containing different concentrations of oxygen and carbon dioxide represents test targets in different states (for example, blood with a low oxygen concentration represents poor oxygen-carrying capacity of the test target, and blood with a high carbon dioxide concentration represents that the test target may have carbon dioxide poisoning, etc.). The instrument detects the blood with different gas concentrations and compares it with a benchmark to confirm whether the instrument parameters are accurate. The main forms of blood gas mixing are: filling the gas to be mixed (mainly oxygen and carbon dioxide) into the container containing the test blood until the blood reaches gas equilibrium (that is, the gas in the blood has reached saturation). There are mainly the following three inflation methods: directly inserting a trachea into the blood for inflation, inflating the trachea on the surface of the blood, and centrifugal blood gas mixing.

[0004] With the rapid development of in vitro diagnostic technology, in blood gas detection, in order to accurately simulate various human conditions, there are high requirements for the inflation method of the test blood, whether the gas content in the blood is balanced, and the time required to reach equilibrium. Defects of the method of directly inserting a trachea into the blood for inflation: During the inflation process, a lot of bubbles will be generated in the viscous blood, which will cause the rupture of red blood cells in the blood and affect the measurement of potassium ions in the blood; Defects of the method of inflating the trachea on the surface of the blood: The gas only contacts the surface of the test blood, so it takes a long time or is difficult to achieve the overall gas equilibrium of the test blood, which will cause a decrease in the blood sugar value and an increase in the lactic acid value in the test blood, seriously affecting the measurement results; Defects of centrifugal blood gas mixing: The blood sample consumption is large, the preparation time is still relatively long, the device structure is complex, the gas consumption is large, the device manufacturing cost is high, and when changing different samples, the mixing container needs to be cleaned, the operation is complex, and there is a risk of cross-contamination, which cannot meet the requirements of the in vitro diagnostic industry for rapidity, accuracy, and low cost.

[0005] Therefore, none of the three commonly used blood gas mixing methods on the market is suitable for accurate blood gas detection. Summary of the Invention

[0006] In view of the deficiencies in the prior art, the present application provides an extremely fast method for mixing blood gas, which has a short mixing time, a small sample volume, uniform mixing of gas and blood, a simple device structure and a low manufacturing cost, and can effectively meet the requirements of rapidity, accuracy and portability in the field of in vitro diagnosis.

[0007] The rapid blood gas mixing method provided by the present invention is to introduce blood and gas into a mixing channel respectively. The mixing channel includes an inner pipe and an outer pipe sleeved outside the inner pipe. The pipe wall of the inner pipe has micropores that can permeate gas molecules. The blood sample is inhaled from the inner pipe. At the same time, pressurized gas is introduced between the inner pipe and the outer pipe. The flow direction of the blood is the same as that of the gas. The pressure of the gas is adjusted by a pressure sensor and a pressure regulating valve at the tail of the mixing channel, so that the gas can pass through the pipe wall of the inner pipe and slowly penetrate from the outside of the inner pipe into the pipe to mix with the blood in the pipe to form a blood-gas mixture.

[0008] Specifically, the present invention controls the blood flow rate to be 1-65 ml / min. Controlling within this range is because this flow rate can save the blood sample volume and at the same time ensure the mixing efficiency. The present invention controls the gas flow rate to be 1-50 ml / min. When the gas flow rate < 50 ml / min, adjusting the gas flow rate can prepare blood samples with different gas concentrations. When the gas flow rate exceeds 50 ml / min, the blood sample will quickly reach saturation, and increasing the gas flow rate will not change the gas concentration in the blood sample;

[0009] Specifically, the present invention can control the gas pressure to be 10-40 Psi. If the pressure is too low, gas molecules cannot penetrate the inner pipe wall, and gas and blood cannot be mixed; if the pressure is too high, a large amount of gas will quickly penetrate the inner pipe wall, causing the blood sample in the inner pipe to also have too high a pressure, which will lead to supersaturation of the blood sample. Therefore, the gas pressure controlled by the present invention is preferably 30-40 PSI.

[0010] Specifically, the material of the inner pipe of the present invention can be selected from materials that can permeate gases but not liquids, such as ePTFE microporous materials, hollow silica fibers, GORE-TEX(R) expanded polytetrafluoroethylene, and so on. For the present invention, Teflon AF 2400 capillary tubes are preferably used. The Teflon AF2400 tube wall has a microporous structure with a size of about 0.3nm. The sizes of oxygen and carbon dioxide molecules are 0.346nm and 0.33nm respectively. The sizes of red blood cells, white blood cells, and platelets in blood are 1 - 20um, and the size of smaller water molecules is 0.4nm. The micropore size is smaller than that of water molecules. Oxygen and carbon dioxide under a certain pressure are more likely to permeate through the tube wall, while the water molecules in the blood sample have no pressure inside and are not likely to permeate through the tube wall. Therefore, TeflonAF2400 is more suitable for the preparation of oxygen and carbon dioxide samples; secondly, Teflon AF2400 can be processed into a shape through methods such as melt compression molding, extrusion molding, and injection molding, and is more easily processed into capillary tubes; thirdly, it has characteristics such as high permanent gas permeability, hydrophobicity, and chemical inertness. When a blood sample flows through the pipeline, it is not easy to adhere and does not cause pollution, which is conducive to the rapid penetration of gases.

[0011] The present invention also provides a special device for implementing the above mixing method. The device includes a blood inlet channel, a gas inlet channel, a mixer, a mixing channel, a pressure regulating device, and a pressure detecting device; the mixing channel includes an inner pipe and an outer pipe sleeved outside the inner pipe. The mixer has 2 inlets and 1 outlet. The 2 inlets are respectively connected to the 2 inlet channels, and the outlet is connected to the mixing channel. A pressure sensor and a pressure regulating valve are provided at the tail of the mixing channel.

[0012] Specifically, the blood inlet channel and the gas inlet channel both include one-way valves, soft and hard straight-through joints, and connecting pipes.

[0013] Specifically, the mixing channel is composed of a number of straight pipes parallel to each other, and the number of straight pipes is connected in series through U-shaped pipes. The straight pipes are vertically arranged. Blood flows up and down in it, and laminar flow will be formed inside the liquid, which is more conducive to the rapid mixing of blood gas.

[0014] Specifically, the pressure sensor and the pressure regulating valve can be installed on a four-way joint and connected to the mixing channel.

[0015] In the present invention, a three-way joint can be used as the mixer. The inner pipe is made of Teflon AF2400 capillary tube. The inner pipe passes through the three-way joint and is connected to the blood inlet channel. The outer pipe is made of Teflon tube and is sleeved outside the inner pipe and connected to the lower end of the three-way joint, and is fixed using a compression ring and a compression plug joint.

[0016] More specifically, a typical solution of the present invention is as follows: After being sucked in by a peristaltic pump, the blood sample flows into the inner tube from the upper end of the three-way valve through the blood inlet channel and flows forward; Oxygen or carbon dioxide under a certain pressure flows into the gap between the inner tube and the outer tube from the left end of the three-way valve through the gas inlet channel and flows in the gap, and the gas pressure in the gap is controlled by a pressure regulating valve and a pressure sensor; Due to the microporous structure on the inner tube wall, this microporous structure allows gas molecules under a certain pressure to penetrate through the inner tube wall and enter the blood sample; The pressure of the blood sample provided by the peristaltic pump is very low, and molecules such as red blood cells, white blood cells, and platelets in the blood are relatively large in size and will not penetrate through the inner tube wall in the reverse direction. The blood sample continuously flows forward in the inner tube and continuously dissolves the gas penetrating through the tube wall during the flow; At the same time, because the inner tube diameter is very thin, only φ0.45mm, the amount of blood flowing through the cross-section of the inner tube per unit time is very small, so the blood sample can reach saturation in a very short time; Since the sample preparation of this device is a continuous process, the blood sample is sucked in by the peristaltic pump and can reach saturation after flowing through the mixing channel. From the peristaltic pump inlet to the pipeline outlet, the entire mixing channel pipeline is about 1.2 meters long, the sample preparation time is about 1 minute, and the minimum blood sample volume is about 2 milliliters.

[0017] Beneficial effects: Blood gas detection is a means of understanding the respiratory function and acid-base balance state of the human body by measuring the H+ concentration in human blood and the gases dissolved in the blood (mainly referring to CO2 and O2), and it can directly reflect the pulmonary ventilation function and its acid-base balance state.

[0018] By using the method described in the present invention, precise blood gas mixing can be achieved. When using the device of the present invention and adjusting different flow rates, for the blood sample after blood gas mixing, there is a good linear relationship between the blood gas concentrations until the gas in the blood sample reaches saturation.

[0019] The main purpose of blood gas mixing is to introduce gases such as oxygen and carbon dioxide with different concentrations into the blood to be tested to prepare blood gas mixed samples with different concentrations. Through the blood gas mixing device, the blood to be tested finally contains gases such as oxygen and carbon dioxide at this concentration. The test blood containing different concentrations of oxygen and carbon dioxide represents test targets in different states (for example, blood with a low oxygen concentration represents poor oxygen-carrying capacity of the test target, and blood with a high carbon dioxide concentration represents that the test target may have carbon dioxide poisoning, etc.). The instrument confirms whether the instrument parameters are accurate by detecting blood gas mixed samples with different concentrations and comparing them with the benchmarks.

[0020] In addition, another advantage of the present invention is its speed. Using this method, the mixing efficiency of the sample is high, and the gas can quickly reach saturation in the blood sample. Applied to clinical detection, it can effectively shorten the sample preparation time and provide more valuable time for patient treatment.

[0021] The special device provided by the present invention has simple and easily obtainable accessories, a simple assembly process, is easy for mass standardized production, has a relatively low production and manufacturing cost, and a short manufacturing cycle; the pipeline part can be used as a disposable consumable, which can effectively avoid cross-contamination. Brief Description of the Drawings

[0022] Figure 1 is the overall structure diagram of the device described in the present application;

[0023] Figure 2 is the connection schematic diagram of the device described in the present application;

[0024] Figure 3 is the internal connection schematic diagram of the mixer;

[0025] Figure 4 is the connection schematic diagram of the tail of the mixing channel;

[0026] Figure 5 is the schematic diagram of the relationship between oxygen flow rate and oxygen concentration of blood sample.

[0027] Wherein:

[0028] 1 - blood inlet channel; 2 - gas inlet channel; 3 - mixer; 4 - mixing channel; 5 - four-way joint; 6 - pressure sensor; 7 - pressure regulating valve;

[0029] 31 - plug joint; 32 - compression ring; 8 - inner tube; 9 - outer tube;

[0030] 41 - plug joint; 42 - compression ring; 43 - pressure regulating valve connection channel; 44 - pressure sensor connection channel; 45 - blood outlet channel Detailed Embodiments

[0031] In order to enable those skilled in the art to better understand the solution of the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments.

[0032] The specific structure is as Figures 1 to 3 shown;

[0033] Blood sample pipeline:

[0034] Connect the one-way valve 1 through two silicone hoses. The outlet end of the one-way valve 1 is connected to the hard-soft docking straight-through joint 1, and the inlet end is connected to the peristaltic pump. The other end of the hard-soft docking straight-through joint 1 is connected to the thin Teflon tube 1; Insert the Teflon AF 2400 capillary into the inner part of the outer tube, leaving about 50 mm and 100 mm outside the outer tube at both ends respectively; Pass the 50-mm end of the Teflon AF 2400 capillary through the T-shaped three-way joint, and apply an appropriate amount of silicone on the outer wall of the Teflon AF 2400 capillary (note that the orifice cannot be blocked), then insert it into the thin Teflon tube 1. After waiting for the silicone to dry completely, fix it on the T-shaped three-way joint using a compression ring and a compression plug joint; Pass the 100-mm end of the Teflon AF 2400 capillary through the four-way joint, and fix the outer tube and the four-way joint using a compression plug joint and a compression ring; Pass the part of the Teflon AF 2400 capillary protruding from the four-way joint through the thin Teflon tube 2, leaving about 20 mm of the Teflon AF 2400 capillary outside the thin Teflon tube 2, and connect the outer wall of the Teflon AF 2400 capillary and the inner wall of the thin Teflon tube 2 with silicone (note to keep the Teflon AF 2400 capillary unobstructed). After waiting for the silicone to dry, fix the thin Teflon tube 2 on the four-way joint using a compression plug joint and a compression ring;

[0035] Gas pipeline:

[0036] Connect the one-way valve 2 through two sections of silicone hoses. One end is connected to the hard-soft docking straight-through joint 2, and the other end is connected to the gas cylinder. The hard-soft docking straight-through joint 2 is connected to the left end of the T-shaped three-way joint 1 through the thick Teflon tube 1; Connect the pressure regulating valve to the left end of the four-way joint through the thick Teflon tube 2, and connect the pressure sensor to the right end of the four-way joint through the thick Teflon tube 3; After the gas enters the T-shaped three-way joint 1 from the hard-soft docking straight-through joint 2, it flows in the gap between the inner wall of the outer tube and the outer wall of the Teflon AF 2400 capillary, and then passes through the four-way joint and the thick Teflon tube 2 and is discharged from the pressure regulating valve; Control the gas pressure in the pipeline by adjusting the pressure regulating valve knob and the pressure sensor;

[0037] The specific working process of the device of the present invention:

[0038] Open external gas cylinders (mainly oxygen and carbon dioxide cylinders with different concentrations), mix the above two gases together through a three-way joint to form a mixed gas with a specified concentration, enter the inlet of the one-way valve 2, control the gas pressure in the pipeline by adjusting the pressure regulating valve knob and the pressure sensor, and keep the gas path unobstructed; pump the blood sample into the inlet end of the one-way valve 1 through a peristaltic pump. After the blood sample passes through the thin Teflon tube 1, it flows in the Teflon AF 2400 capillary and continuously mixes with the gas permeating through the tube wall and finally reaches saturation; if it is necessary to prepare test samples with different concentrations, it can be achieved by adjusting the gas pressure and the flow rate of the blood sample.

[0039] Use the device of the present invention for actual measurement of samples:

[0040] Use this device to prepare blood samples with different oxygen concentrations, and use a NOVA blood gas biochemical analyzer to detect the blood samples. When no gas is introduced, the initial oxygen content of the blood sample is 196.2 mmHg. Keep the pressure in the gas channel at 40 PSI, and prepare blood samples with different oxygen concentrations by adjusting the oxygen flow rate and the rotation speed of the peristaltic pump, and detect the oxygen content in the blood samples. The results are shown in the following table:

[0041]

[0042] It can be seen from the analysis of the above table that the oxygen content in the blood sample increases with the increase of the input oxygen flow rate; at the same oxygen flow rate, the oxygen content in the blood sample is basically the same, but there is still a trend that the faster the flow rate of the blood sample, the lower the oxygen content; plot the above data as a line graph, as Figure 4 shown.

[0043] Through the Figure 4 analysis, it can be seen that when 0.4 L / Min of oxygen is introduced into the blood sample, it is already close to saturation. When 0.5 L / Min of oxygen is introduced, it quickly reaches saturation. The average preparation time of the blood sample with a saturated oxygen concentration is 48 seconds; and from the initial sample state to before saturation, the oxygen content of the blood sample and the introduced oxygen flow rate are in a linear distribution relationship and increase with the increase of the introduced oxygen flow rate; this shows that different oxygen concentration blood samples can be prepared by controlling the oxygen flow rate.

[0044] The above is only the preferred embodiment of the present application and is not used to limit the present application.

Claims

1. A special device for rapid blood gas mixing, characterized in that, It includes a blood inlet channel, a gas inlet channel, a mixer, a mixing channel, a pressure sensor and a pressure regulating valve; the mixing channel includes an inner pipe and an outer pipe sleeved outside the inner pipe, the mixer has 2 inlets and 1 outlet, the two inlets are respectively connected to the blood inlet channel and the gas inlet channel, the outlet is connected to the mixing channel, and the pressure sensor and the pressure regulating valve are arranged at the tail of the mixing channel; The mixer is a tee, the inner pipe passes through the tee and is connected to the blood inlet channel, the outer pipe is sleeved outside the inner pipe and is connected to the lower end of the tee, and is fixed by a compression ring and a compression plug joint; The blood inlet channel and the gas inlet channel both include one-way valves, soft and hard straight-through joints, and connecting pipes; The mixing channel is composed of a number of straight pipes parallel to each other, and the number of straight pipes is connected in series through U-shaped pipes; The pressure sensor and the pressure regulating valve are installed on a four-way joint and are connected to the mixing channel; The material of the inner pipe is a TeflonAF 2400 capillary.

2. A rapid blood gas mixing method for a dedicated device suitable for rapid blood gas mixing as described in claim 1, characterized in that, Blood and gas are respectively introduced into the mixing channel. The mixing channel includes an inner pipe and an outer pipe sleeved outside the inner pipe. The wall of the inner pipe has micropores that can permeate gas molecules. The blood sample is inhaled from the inner pipe. At the same time, pressurized gas is introduced between the inner pipe and the outer pipe. The flow direction of the blood is the same as that of the gas. The pressure of the gas is adjusted by the pressure sensor and the pressure regulating valve at the tail of the mixing channel, so that the gas can slowly penetrate from the outside of the inner pipe into the pipe through the wall of the inner pipe and mix with the blood in the pipe to form a blood-gas mixture; The blood flow rate is 1 - 65 ml / min; The gas flow rate is 1 - 50 ml / min; The pressure of the gas is 10 - 40 Psi.

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