CN219836528U - Centrifugal micro-whole blood plasma separation micro-fluidic chip - Google Patents
Centrifugal micro-whole blood plasma separation micro-fluidic chip Download PDFInfo
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- CN219836528U CN219836528U CN202321203746.3U CN202321203746U CN219836528U CN 219836528 U CN219836528 U CN 219836528U CN 202321203746 U CN202321203746 U CN 202321203746U CN 219836528 U CN219836528 U CN 219836528U
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- 210000002381 plasma Anatomy 0.000 title claims abstract description 110
- 238000000926 separation method Methods 0.000 title claims abstract description 61
- 210000003743 erythrocyte Anatomy 0.000 claims abstract description 70
- 210000004369 blood Anatomy 0.000 claims abstract description 52
- 239000008280 blood Substances 0.000 claims abstract description 52
- 238000004062 sedimentation Methods 0.000 claims abstract description 45
- 238000000605 extraction Methods 0.000 claims abstract description 44
- 238000005534 hematocrit Methods 0.000 claims abstract description 6
- 210000002966 serum Anatomy 0.000 claims description 26
- 238000002347 injection Methods 0.000 claims description 12
- 239000007924 injection Substances 0.000 claims description 12
- 238000000034 method Methods 0.000 description 9
- 210000000601 blood cell Anatomy 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 238000005119 centrifugation Methods 0.000 description 5
- 230000009471 action Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
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- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 238000005374 membrane filtration Methods 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
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- 239000000203 mixture Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
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- 238000004445 quantitative analysis Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000002313 adhesive film Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
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- 102000004169 proteins and genes Human genes 0.000 description 1
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- 238000013139 quantization Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000009974 thixotropic effect Effects 0.000 description 1
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- Investigating Or Analysing Biological Materials (AREA)
Abstract
The utility model discloses a centrifugal micro whole blood plasma separation micro-fluidic chip, which comprises a chip body, wherein the chip body comprises a rotation center shaft and more than one micro whole blood separation groove; the at least one micro whole blood separation groove is arranged along the circumferential direction of the rotation center shaft; the trace whole blood separating tank comprises a plasma extracting groove and a red blood cell sedimentation groove communicated with the plasma extracting groove; the erythrocyte sedimentation groove is positioned at one side of the plasma extraction groove away from the rotation center shaft and extends along the radial direction of the chip body. According to the utility model, the micro whole blood is directly separated by centrifugal force, and the separated red blood cells are stably deposited in the red blood cell sedimentation groove due to the capillary force, so that the chip disclosed by the utility model has the function of measuring the hematocrit.
Description
Technical Field
The utility model relates to the technical field of medical equipment, in particular to a centrifugal micro whole blood plasma separation micro-fluidic chip.
Background
Whole blood consists of red blood cells, white blood cells, platelets and other blood cells and plasma, wherein the blood cells account for 40% -45% of the whole blood, and the plasma accounts for 55% -60%. The plasma components are complex and mainly comprise proteins, lipids, inorganic salts, saccharides and the like, and many components are directly related to various vital activities of human bodies, so that the detection and analysis of the plasma components are of great significance to basic biomedical research and clinical detection. Since blood cells and their contents often interfere with plasma component analysis, blood cells need to be removed in advance in the relevant assays.
Centrifugation and membrane filtration are the most commonly used plasma separation methods at present. In the conventional centrifugation method, a whole blood sample is collected in a blood collection tube equipped with a substance having an intermediate specific gravity between that of serum and the like and that of blood cell components, and the substance is separated by a centrifugation operation so as to be located at an intermediate position between the serum and the like and the blood cell components. However, the method is applied to the separation of milliliter-level blood samples, and cannot meet the requirements of a miniature total analysis system.
The biggest disadvantage of membrane filtration is that membrane pores are easily blocked by blood cells, resulting in reduced separation efficiency, sample loss, contamination, etc. The efficiency of plasma separation is greatly affected by the filter media.
Huangdong, zhang He, xu Tao, etc. microfluidic chips based on the principle of inertial microfluidic are used for plasma separation [ J ]. Science fiction 2011,56 (21): 1711-1719 provide a separation method using the principle of inertial microfluidic, which implements focused flow of particles of a certain size in a microchannel for separating and diluting plasma from a blood sample. However, the method is only suitable for diluting blood samples, and can not directly separate the blood plasma of trace whole blood, thereby increasing the difficulty for quantitative analysis of subsequent blood plasma detection. In addition, this method does not completely separate erythrocytes, and the plasma contains residual erythrocytes.
The centrifugal microfluidic chip technology has the characteristics of sample micro-quantization, detection item integration and the like, can meet the requirements of a miniature full-analysis system, and is widely applied to the field of blood detection at present. However, the centrifugal microfluidic chip which can be directly used for separating trace whole blood and plasma and has no medium pollution and adsorption is still blank.
Disclosure of Invention
The utility model aims to: aiming at the defects of the prior art, the utility model provides the centrifugal micro whole blood plasma separation micro-fluidic chip, which can realize the direct separation of micro whole blood under the drive of centrifugal force, has no medium pollution and adsorption, and has high plasma separation efficiency.
In order to solve the technical problems, the utility model discloses a centrifugal micro whole blood plasma separation micro-fluidic chip, which comprises a chip body, wherein the chip body comprises a rotation center shaft and more than one micro whole blood separation groove; the at least one micro whole blood separation groove is arranged along the circumferential direction of the rotation center shaft; the trace whole blood separating tank comprises a plasma extracting groove and a red blood cell sedimentation groove communicated with the plasma extracting groove; the erythrocyte sedimentation groove is positioned at one side of the plasma extraction groove away from the rotation center shaft and extends along the radial direction of the chip body.
Furthermore, serum separation gel is arranged in the erythrocyte sedimentation groove.
Specifically, the red blood cell settling groove is an elongated groove, and the transverse width of the red blood cell settling groove is smaller than the transverse width of the plasma extraction groove.
Preferably, the surface of the erythrocyte sedimentation groove is provided with scale marks for judging the hematocrit.
Preferably, the bottom surface of one side of the plasma extraction groove, which is close to the erythrocyte sedimentation groove, is connected with the bottom surface of the erythrocyte sedimentation groove; the bottom surface of the plasma extraction groove is a diversion surface which is gradually and downwards inclined from the joint of the plasma extraction groove and the bottom surface of the erythrocyte sedimentation groove to the rotation center shaft.
Preferably, the one or more micro whole blood separation grooves are arranged along the same circumference.
Preferably, the volume of the erythrocyte sedimentation tank is 10 to 50ul; the volume of the plasma extraction groove is 20-100 ul.
Preferably, the volume ratio of the plasma extraction groove to the erythrocyte sedimentation groove is 2-2.5.
Preferably, the chip further comprises a chip upper layer, injection holes for adding trace whole blood are formed in the tops of the plasma extraction grooves, and the injection holes are formed in the chip upper layer. The upper layer of the chip and the erythrocyte sedimentation groove are enclosed to form a capillary channel.
Preferably, the injection hole is positioned at the top of one side of the corresponding plasma extraction groove, which is close to the rotation center shaft.
The beneficial effects are that:
(1) The centrifugal micro whole blood and plasma separation microfluidic chip provided by the utility model drives micro whole blood to be directly separated through centrifugal force, and has small applied whole blood sample size, thereby being beneficial to the crowds such as infants and the like; in the utility model, the trace whole blood does not need to be diluted by a diluent, which is helpful for simplifying the quantitative analysis process of the subsequent plasma detection; because the dilution liquid is not needed for dilution, compared with the plasma obtained by separating the diluted whole blood sample, the plasma obtained by separating the utility model is not influenced by elements contained in the dilution liquid, and can be used for more blood detection projects later.
(2) The utility model provides a micro whole blood separating groove array arranged on the centrifugal micro whole blood plasma separating micro-fluidic chip. Each trace whole blood separating tank comprises a plasma extracting groove and a red blood cell sedimentation groove, and red blood cells are separated from the trace whole blood sample and sedimented at one end of the red blood cell sedimentation groove far away from the rotation central shaft under the drive of centrifugal force. A first portion of plasma separated from a sample of whole blood is received in the plasma extraction well and a second portion of plasma is received in an end of the erythrocyte sedimentation well adjacent the plasma extraction well. When the chip body is kept still, in the capillary microtube, the separated red blood cells and plasma are not easy to flow, and the interface between the two is relatively stable. The micro whole blood separation structure is simple, compared with the membrane filtration method, the medium pollution and adsorption are avoided, and the separation efficiency is improved.
(3) One embodiment of the utility model is to centrifuge the mixture of serum separation gel and blood, in use, by placing the serum separation gel in a red blood cell settling tank. Under the action of centrifugal force, intermolecular hydrogen bonds of the serum separation gel are broken and converted into low-viscosity fluid, and the serum separation gel is gradually accumulated between blood serum and blood plasma in the process of centrifugation due to the fact that the specific gravity of the serum separation gel is between the blood plasma and the blood serum. When the external centrifugal force disappears, the intermolecular hydrogen bonds are re-associated to form a net structure, the serum separation gel is re-formed into a colloid with high viscosity, and a compact isolation layer is formed to separate serum from blood plasma, so that the blood plasma and red blood cells in long-time standing are ensured not to be mixed.
(4) According to the utility model, the bottom surface of one side of the plasma extraction groove, which is close to the red blood cell sedimentation groove, is connected with the bottom surface of the red blood cell sedimentation groove, so that red blood cells in a trace whole blood sample are sedimented in a direction away from the rotation central shaft under the centrifugal action. The bottom surface through setting up the plasma and draw the recess is from its bottom surface phase department towards rotation center axle and the drainage face that sets up of decurrent gradually that meets with erythrocyte sedimentation tank, and its effect is when the chip body is stood still, and the direction of separated plasma along the drainage face gathers in the bottom surface lowest department of plasma extraction recess to the sample is absorbed to trace plasma.
(5) According to the utility model, the scale marks for judging and reading the hematocrit are arranged on the surface of the erythrocyte sedimentation groove, so that the chip can separate a trace amount of whole blood sample and has the hematocrit measuring function.
Drawings
The foregoing and/or other advantages of the utility model will become more apparent from the following detailed description of the utility model when taken in conjunction with the accompanying drawings and detailed description.
Fig. 1 is a top view of a chip body of a centrifugal micro whole blood plasma separation microfluidic chip according to an embodiment of the present utility model;
FIG. 2 is a top view of the upper layer of a microfluidic chip for separating whole blood from plasma in a centrifugal manner according to an embodiment of the present utility model;
fig. 3 is an a-direction cross-sectional view of the chip body shown in fig. 1.
Detailed Description
The reference numerals of the present utility model are as follows:
chip body 100, rotation center shaft 110, micro whole blood separation tank 120, plasma extraction groove 121, erythrocyte sedimentation groove 122, drainage surface 123, on-chip layer 200, and injection hole 210.
The technical scheme of the present utility model is described in detail below with reference to the accompanying drawings.
The utility model provides a centrifugal micro-whole blood plasma separation micro-fluidic chip. As shown in fig. 1 and 2, the chip includes a chip body 100 and an on-chip layer 200. The on-chip layer 200 may be a transparent adhesive film, which covers the top surface of the chip body 100.
As shown in fig. 1, the chip body 100 includes a rotation center shaft 110 and one or more micro whole blood separation grooves 120. The one or more micro whole blood separation grooves 120 are provided along the circumferential direction of the rotation center shaft 110. The micro whole blood separation tank 120 includes a plasma extraction groove 121 and a red blood cell settling groove 122 communicating with the plasma extraction groove 121. The erythrocyte sedimentation groove 122 is located at a side of the plasma extraction groove 121 remote from the rotation center axis 110 and extends in the radial direction of the chip body 100. The on-chip layer 200 encloses with the erythrocyte sedimentation groove 122 to form a capillary microtube.
The chip of the present utility model is horizontally mounted in a centrifuge at the time of use, and a trace amount of whole blood sample can be injected into the plasma extraction groove 121. After the chip body 100 rotates around the rotation center shaft 110 and runs at 3000 rpm-5000 rpm for 3-5 min, the red blood cells separated from the trace whole blood sample settle at one end of the red blood cell settling groove 122 far away from the rotation center shaft 110, a first part of the plasma separated from the trace whole blood sample is accommodated in the plasma extraction groove 121, and a second part of the plasma is accommodated at one end of the red blood cell settling groove 122 near the plasma extraction groove 121. When the chip body 100 is left standing, the separated red blood cells and plasma are not easy to flow in the capillary tube, and the interface between the two is relatively stable.
Further, to ensure that no re-mixing of plasma and red blood cells occurs over a prolonged period of time, each red blood cell settling tank 122 is also pre-filled with a serum separation gel. The amount of serum separation gel may be 3 to 5ul. The serum separation gel can be selected from commercial products provided by Shanghai Yuan Yes Biotechnology Co.
Working principle of serum separation gel: the specific gravity range of the serum separating gel is 1.045-1.065, and the serum separating gel has good thixotropic property and isolation property. The mixture of serum separation gel and blood is centrifuged, under the action of centrifugal force, the intermolecular hydrogen bond of serum separation gel is broken and converted into low-viscosity fluid, and the serum separation gel is gradually accumulated between serum and blood plasma in the course of centrifugation due to its specific gravity between blood plasma and blood serum. When the external centrifugal force disappears, the intermolecular hydrogen bonds are re-associated to form a net structure, the serum separation gel is re-formed into a colloid with high viscosity, and a compact isolation layer is formed to separate serum from blood plasma, so that the blood plasma and red blood cells in long-time standing are ensured not to be mixed.
Specifically, as shown in fig. 1, the erythrocyte sedimentation groove 122 is an elongated groove, and the lateral width of the erythrocyte sedimentation groove 122 is smaller than the lateral width of the plasma extraction groove 121.
Preferably, the surface of the erythrocyte sedimentation groove 122 is provided with scale marks for interpreting the hematocrit, so as to facilitate manual interpretation. Scale markings are not shown in the figure.
Preferably, as shown in fig. 3, the bottom surface of the plasma extraction groove 121 on the side close to the erythrocyte sedimentation groove 122 is connected to the bottom surface of the erythrocyte sedimentation groove 122. The bottom surface of the plasma extraction groove 121 is a drainage surface 123 which is gradually inclined downward toward the rotation center axis 110 from the junction with the bottom surface of the erythrocyte sedimentation groove 122.
According to the utility model, the bottom surface of one side of the plasma extraction groove 121, which is close to the red blood cell sedimentation groove 122, is connected with the bottom surface of the red blood cell sedimentation groove 122, so that red blood cells in a trace amount of whole blood sample are sedimented in a direction away from the rotation central shaft 110 under the centrifugal action. By setting the bottom surface of the plasma extraction groove 121 as a drainage surface which is gradually inclined downward from the junction with the bottom surface of the erythrocyte sedimentation groove 122 toward the rotation center shaft 110, the effect is that when the chip body 100 is stationary, the separated plasma is collected at the lowest bottom surface of the plasma extraction groove 121 along the guiding of the drainage surface, so that the sample is sucked against a trace amount of plasma.
Preferably, as shown in fig. 1, more than one micro whole blood separation tank 120 is arranged along the same circumference so that all the micro whole blood separation tanks 120 have the same separation effect under the same centrifugal condition.
Preferably, the volume of the erythrocyte sedimentation tank 122 is 10 to 50ul. The volume of the plasma extraction groove 121 is 20 to 100ul. In one particular embodiment, the structural dimensions of the red blood cell settling groove 122 are 1.0mm by 10mm to 1.0mm by 50mm, and the structural dimensions of the plasma extraction groove 121 are 1.0mm by 20mm to 1.0mm by 100mm.
As shown in fig. 2, the top of each plasma extraction groove 121 is provided with an injection hole 210 for adding a minute amount of whole blood, and each injection hole 210 is opened at the on-chip layer 200.
Preferably, as shown in fig. 2, the injection hole 210 is located at the top of one side of the corresponding plasma extraction groove 121 near the rotation center axis 110.
When the bottom surface of the plasma extraction groove 121 is a drainage surface that is gradually inclined downward toward the rotation center axis 110 from the contact point with the bottom surface of the erythrocyte sedimentation groove 122, the injection hole 210 is disposed at the top of one side of the corresponding plasma extraction groove 121 near the rotation center axis 110, so that the position of the injection hole 210 is opposite to the lowest position of the bottom surface of the plasma extraction groove 121, and the sample is conveniently sucked for a trace amount of plasma.
Preferably, the volume ratio of the plasma extraction well 121 to the erythrocyte sedimentation well 122 is 2 to 2.5 to ensure that the separated erythrocytes are all deposited in the erythrocyte sedimentation well 122.
The utility model provides a concept and a method of a centrifugal micro whole blood plasma separation micro-fluidic chip, and the method and the way for realizing the technical scheme are a plurality of methods, the above is only a preferred embodiment of the utility model, and it should be pointed out that a plurality of improvements and modifications can be made by those skilled in the art without departing from the principle of the utility model, and the improvements and modifications are also considered as the protection scope of the utility model. The components not explicitly described in this embodiment can be implemented by using the prior art.
Claims (10)
1. The centrifugal micro whole blood plasma separation micro-fluidic chip is characterized by comprising a chip body (100), wherein the chip body (100) comprises a rotation center shaft (110) and more than one micro whole blood separation groove (120); the one or more micro whole blood separation grooves (120) are provided along the circumferential direction of the rotation center shaft (110); the micro whole blood separating tank (120) comprises a plasma extracting groove (121) and a red blood cell settling groove (122) communicated with the plasma extracting groove (121); the erythrocyte sedimentation groove (122) is located at a side of the plasma extraction groove (121) away from the rotation center axis (110) and extends in a radial direction of the chip body (100).
2. The centrifugal micro-whole blood plasma separation microfluidic chip according to claim 1, wherein a serum separation gel is arranged in the erythrocyte sedimentation groove (122).
3. A centrifugal micro-whole blood plasma separation micro-fluidic chip according to claim 2, wherein the red blood cell settling groove (122) is an elongated groove, and the transverse width of the red blood cell settling groove (122) is smaller than the transverse width of the plasma extraction groove (121).
4. A centrifugal micro-whole blood plasma separation micro-fluidic chip according to claim 3, wherein the surface of the erythrocyte sedimentation groove (122) is provided with scale marks for interpreting the hematocrit.
5. A centrifugal micro-whole blood plasma separation micro-fluidic chip according to any one of claims 1 to 4, wherein the bottom surface of the plasma extraction groove (121) near one side of the red blood cell sedimentation groove (122) is connected with the bottom surface of the red blood cell sedimentation groove (122); the bottom surface of the plasma extraction groove (121) is a diversion surface which is gradually inclined downwards from the joint of the bottom surface of the plasma extraction groove and the bottom surface of the red blood cell sedimentation groove (122) towards the rotation center shaft (110).
6. The centrifugal trace whole blood plasma separation microfluidic chip according to claim 5, wherein the one or more trace whole blood separation grooves (120) are arranged along the same circumference.
7. The centrifugal micro-whole blood plasma separation micro-fluidic chip according to claim 5, wherein the volume of the erythrocyte sedimentation groove (122) is 10-50 ul; the volume of the plasma extraction groove (121) is 20-100 ul.
8. The centrifugal micro-whole blood plasma separation micro-fluidic chip according to claim 5, wherein the volume ratio of the plasma extraction groove (121) to the erythrocyte sedimentation groove (122) is 2-2.5.
9. The centrifugal micro-whole blood plasma separation micro-fluidic chip according to claim 5, further comprising an upper chip layer (200), wherein the upper chip layer (200) and the erythrocyte sedimentation groove (122) are enclosed to form a capillary channel; the top of each plasma extraction groove (121) is provided with an injection hole (210) for adding trace whole blood, and each injection hole (210) is arranged on the upper chip layer (200).
10. The centrifugal micro-whole blood plasma separation microfluidic chip according to claim 9, wherein the injection hole (210) is located at the top of one side of the corresponding plasma extraction groove (121) close to the rotation center axis (110).
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202321203746.3U CN219836528U (en) | 2023-05-18 | 2023-05-18 | Centrifugal micro-whole blood plasma separation micro-fluidic chip |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202321203746.3U CN219836528U (en) | 2023-05-18 | 2023-05-18 | Centrifugal micro-whole blood plasma separation micro-fluidic chip |
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| CN202321203746.3U Active CN219836528U (en) | 2023-05-18 | 2023-05-18 | Centrifugal micro-whole blood plasma separation micro-fluidic chip |
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- 2023-05-18 CN CN202321203746.3U patent/CN219836528U/en active Active
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