CN107262171A - A kind of blood separation and culture chip and blood separating mechanism - Google Patents
A kind of blood separation and culture chip and blood separating mechanism Download PDFInfo
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- CN107262171A CN107262171A CN201710565396.8A CN201710565396A CN107262171A CN 107262171 A CN107262171 A CN 107262171A CN 201710565396 A CN201710565396 A CN 201710565396A CN 107262171 A CN107262171 A CN 107262171A
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502753—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
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- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
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- B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
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Abstract
The present invention provides a kind of blood separation and culture chip and blood separating mechanism, including flowing at least one micro-pillar array being arranged in order along blood, the intercolumniation of each micro-pillar array is differed, the intercolumniation of at least one micro-pillar array is sequentially reduced according to putting in order at least one micro-pillar array, and at least one described micro-pillar array at least includes red blood cell and retains micro-pillar array；The red blood cell retention micro-pillar array is retained to the red blood cell in the blood, to filter the red blood cell in the blood；Blood is flowed into from the entrance of the blood separation and culture chip, sequentially passes through the retention and filtering of at least one micro-pillar array, is obtained red blood cell and hematoblastic blood plasma containing less than predetermined amount and is flowed out from the outlet of the blood separation and culture chip.The present invention can realize the quick separating to minimal amount of blood sample, improve the detection efficiency of blood sample.
Description
Technical field
The embodiment of the present invention belongs to field of biomedicine technology, more particularly to a kind of blood separation and culture chip and blood
Separator.
Background technology
In the therapeutic process of cancer patient, the quality of therapeutic effect can pass through the various marker molecules in blood
The reaction result of (such as albumen, miRNA (MicroRNA, non-coding single strand RNA molecule)) is weighed.Generally, it is to utilize blood inspection
Survey instrument to detect the blood sample of cancer patient, it is possible to achieve to the lossless decomposition of cancer patient, patient is monitored in real time
The state of an illness, adjust rational therapeutic scheme in time for doctor and important evidence be provided, for accurately medical treatment detection solid base is provided
Plinth.
However, except the biomolecule such as albumen, miRNA are also containing a large amount of various sizes of cells in blood.In order to improve
The detection sensitivity and reliability of biomolecule are, it is necessary to which serum is separated from blood.Traditional serum separation method is
Blood sample it is first cold put a period of time, then blood sample is separated with centrifuge.This serum separation method needs
Expend a large amount of blood and time-consuming longer, seriously reduce the detection efficiency of blood sample.
The content of the invention
The embodiment of the present invention provides a kind of blood separation and culture chip and blood separating mechanism, can be to minimal amount of blood
Liquid sample carries out quick separating, improves the detection efficiency of blood sample.
On the one hand the embodiment of the present invention provides a kind of blood separation and culture chip, and it includes being arranged in order along blood flow direction
At least one micro-pillar array, the intercolumniation of each micro-pillar array differs, the post of at least one micro-pillar array
Spacing is sequentially reduced according to putting in order at least one micro-pillar array, and at least one described micro-pillar array at least includes red
Cell retention micro-pillar array；
The red blood cell retention micro-pillar array is retained to the red blood cell in the blood, to filter in the blood
Red blood cell；
Blood is flowed into from the entrance of the blood separation and culture chip, sequentially passes through at least one micro-pillar array
Retention and filtering, obtain red blood cell and hematoblastic blood plasma containing less than predetermined amount from the blood separation and culture chip
Outlet outflow.
In one embodiment, at least one described micro-pillar array includes flowing to the tumour cell section being arranged in order along blood
Stay micro-pillar array, monocyte retention micro-pillar array, leucocyte retention micro-pillar array and red blood cell retention micro-pillar array；
The tumour cell retention micro-pillar array is retained to the tumour cell in the blood, to filter the blood
In tumour cell；The monocyte retention micro-pillar array is retained to the monocyte in the blood, to filter
State the monocyte in blood；The leucocyte retention micro-pillar array is retained to the leucocyte in the blood, to filter
Leucocyte in the blood；
The blood is flowed into from the entrance of the blood separation and culture chip, sequentially passes through the tumour cell retention micro-
Post array, monocyte retention micro-pillar array, leucocyte retention micro-pillar array and red blood cell retention microtrabeculae battle array
Row, after the tumour cell in the blood, monocyte, leucocyte and red blood cell are retained and filtered, are obtained containing low
Flowed out in the red blood cell and hematoblastic blood plasma of predetermined amount from the outlet of blood separation and culture chip.
In one embodiment, the micro-pillar array includes flowing to the multiple rows of microtrabeculae being arranged in order, arbitrary neighborhood along blood
Two rows described in the equal Heterogeneous Permutation of microtrabeculae.
In one embodiment, the intercolumniation of the tumour cell retention micro-pillar array is less than or equal to the tumour cell
Diameter and more than monocyte, leucocyte, red blood cell and the hematoblastic diameter in the blood.
In one embodiment, the intercolumniation of the monocyte retention micro-pillar array is less than or equal to the monocyte
Diameter and more than leucocyte, red blood cell and the hematoblastic diameter in the blood.
In one embodiment, the intercolumniation of the leucocyte retention micro-pillar array is less than or equal to the straight of the leucocyte
Footpath and the red blood cell and hematoblastic diameter being more than in the blood.
In one embodiment, the intercolumniation of the red blood cell retention micro-pillar array is less than or equal to the straight of the red blood cell
Footpath and the hematoblastic diameter being more than in the blood.
In one embodiment, the micro-pillar array is in cylindrical-array, cylindroid array or polygon pillar array
It is any.
On the other hand the embodiment of the present invention also provides a kind of blood separating mechanism, and it includes above-mentioned blood separation and culture
The outlet with the blood separation and culture chip is provided with chip, in addition to micro-fluidic chip, the micro-fluidic chip to connect
The fluid channel connect；
The fluid channel includes multiple micro-channel units of periodic arrangement, and the multiple micro-channel unit connects from beginning to end successively
Connect；
The micro-channel unit includes the first semi-circular fluid channel and the second semi-circular fluid channel, and first semi-circular is micro-
The entrance slitless connection of runner exit and the second semi-circular fluid channel；
Blood is flowed through after the blood separation and culture chip is pretreated, and is flowed into described on the micro-fluidic chip
Fluid channel, the fluid channel carries out inertia focusing to the blood after the pretreatment, obtains the blood plasma of high-purity.
In one embodiment, the difference of the external diameter of the first semi-circular fluid channel and internal diameter is equal to first semi-circular
The ring cutting diameter at any place in fluid channel, the external diameter of the second semi-circular fluid channel and the difference of internal diameter are less than second semi-ring
The maximum ring cutting diameter of shape fluid channel, the external diameter of the first semi-circular fluid channel is less than the interior of the second semi-circular fluid channel
Footpath.
The embodiment of the present invention is cut by flowing to set gradually along blood including the red blood cell for retaining and filtering red blood cell
At least one micro-pillar array of micro-pillar array is stayed, and the intercolumniation of each micro-pillar array is differed, makes at least one microtrabeculae
The intercolumniation of array is sequentially reduced according to putting in order at least one micro-pillar array, makes blood from the blood separation and culture
The entrance of chip is flowed into, and is sequentially passed through the retention and filtering of at least one micro-pillar array, is obtained containing less than predetermined amount
Red blood cell and hematoblastic blood plasma flow out from the outlet of blood separation and culture chip, it is possible to achieve to minimal amount of blood sample
Quick separating, improve blood sample detection efficiency.
Brief description of the drawings
Technical scheme in order to illustrate the embodiments of the present invention more clearly, makes required in being described below to embodiment
Accompanying drawing is briefly described, it should be apparent that, drawings in the following description are some embodiments of the present invention, for ability
For the those of ordinary skill of domain, on the premise of not paying creative work, it can also be obtained according to these accompanying drawings other attached
Figure.
Fig. 1 is the dimensional structure diagram for the blood separation and culture chip that one embodiment of the present of invention is provided；
Fig. 2 is the top view for the blood separation and culture chip that one embodiment of the present of invention is provided；
Fig. 3 is the structural representation for the blood separating mechanism that one embodiment of the present of invention is provided；
Fig. 4 is the front view for the microchannel chip that one embodiment of the present of invention is provided.
Embodiment
In order that those skilled in the art more fully understand the present invention program, below in conjunction with the embodiment of the present invention
Accompanying drawing, the technical scheme in the embodiment of the present invention is explicitly described, it is clear that described embodiment is the present invention one
The embodiment divided, rather than whole embodiments.Based on the embodiment in the present invention, those of ordinary skill in the art are not doing
Go out the every other embodiment obtained under the premise of creative work, should all belong to the scope of protection of the invention.
Term " comprising " and their any deformations in description and claims of this specification and above-mentioned accompanying drawing, meaning
Figure is to cover non-exclusive include.Process, method or system, product or equipment for example comprising series of steps or unit do not have
The step of being defined in the step of having listed or unit, but alternatively also include not listing or unit, or alternatively also wrap
Include for the intrinsic other steps of these processes, method, product or equipment or unit.In addition, term " first ", " second " and
" 3rd " etc. is to be used to distinguish different objects, not for description particular order.
As shown in figure 1, one embodiment of the present of invention provides a kind of blood separation and culture chip 10, it is included along blood
Four micro-pillar arrays being arranged in order are flowed to, four micro-pillar arrays are respectively tumour cell retention micro-pillar array 1, monocyte section
Stay micro-pillar array 2, leucocyte retention micro-pillar array 3 and red blood cell retention micro-pillar array 4；The intercolumniation of each micro-pillar array is not
It is identical, and the intercolumniation of four micro-pillar arrays is sequentially reduced according to putting in order for micro-pillar array, i.e. and tumour cell retention is micro-
The intercolumniation ＞ leucocytes of the intercolumniation ＞ monocytes retention micro-pillar array 2 of post array 1 retain the intercolumniation ＞ of micro-pillar array 3
Red blood cell retains the intercolumniation of micro-pillar array 4.
In the present embodiment, intercolumniation is specifically referred in any micro-pillar array, and appointing on vertical direction is flowed to blood
Intercolumniation in the width in the space between two adjacent microtrabeculaes of meaning, the present embodiment specifically refers to horizontal intercolumniation.
In a particular application, in any micro-pillar array, two that arbitrary neighborhood on parallel direction is flowed to blood are micro-
The width (i.e. longitudinal intercolumniation) in the space between post can be set according to actual needs, and longitudinal intercolumniation can be equal to transverse post
Spacing.
In a particular application, micro-pillar array can be times in cylindrical-array, cylindroid array or polygon pillar array
It is a kind of.The merely exemplary situation for showing that micro-pillar array is cylindrical-array in Fig. 1.
The operation principle for the blood separation and culture chip that the present embodiment is provided is：
Tumour cell retention micro-pillar array is retained to the tumour cell in blood, thin with the tumour in filtering blood
Born of the same parents；Monocyte retention micro-pillar array is retained to the monocyte in blood, with the monocyte in filtering blood；It is white thin
Born of the same parents' retention micro-pillar array is retained to the leucocyte in blood, with the leucocyte in filtering blood；Red blood cell retention microtrabeculae battle array
Row are retained to the red blood cell in blood, with the red blood cell in filtering blood；
Blood is flowed into from the entrance of blood separation and culture chip, sequentially passes through tumour cell retention micro-pillar array, monokaryon
Cell retention micro-pillar array, leucocyte retention micro-pillar array and red blood cell retention micro-pillar array, to the tumour cell in blood, list
After nucleus, leucocyte and red blood cell are retained and filtered, red blood cell and hematoblastic blood containing less than predetermined amount are obtained
Starch and flowed out from the outlet of blood separation and culture chip.
In one embodiment, blood separation and culture chip includes at least one micro-pillar array and this at least one microtrabeculae
At least include the red blood cell retention micro-pillar array for being used to retaining and filtering red blood cell in array, blood is from blood separation in advance
The entrance for managing chip is flowed into, and sequentially passes through the retention and filtering of at least one micro-pillar array, is obtained containing red less than predetermined amount
Cell and hematoblastic blood plasma flow out from the outlet of blood separation and culture chip.
Because red blood cell is smallest size of cell in blood, therefore, setting blood separation and culture chip at least includes
Red blood cell retains micro-pillar array, all cells in blood can be retained and filtered, to obtain containing less than predetermined amount
Red blood cell and hematoblastic blood plasma.
In the present embodiment, why also the red blood cell containing less than predetermined amount is because red blood cell in the blood plasma after filtering
It is planar as, due to the limitation of manufacture craft, intercolumniation cannot accomplish the size less than all red blood cells, therefore have part
Red blood cell can not be by effectively catching.In the controlled range of intercolumniation, the number of predetermined amount specifically can by micro-pillar array number
Measure with intercolumniation to determine, intercolumniation is smaller, and predetermined amount is smaller.
In a particular application, the quantity and species of the micro-pillar array included by blood separation and culture chip can be according to realities
Border needs to be configured.For example, it is only necessary to retention and filtering tumour cell, then only microtrabeculae battle array can be retained by setting tumour cell
Row；Only need to retain and filter monocyte, then only can retain micro-pillar array by setting monocyte.Same type of microtrabeculae
Array can also set multiple simultaneously, to strengthen retaining filter effect.
The present invention retains microtrabeculae by flowing to set gradually along blood including the red blood cell for retaining and filtering red blood cell
At least one micro-pillar array of array, and the intercolumniation of each micro-pillar array is differed, make at least one micro-pillar array
Intercolumniation is sequentially reduced according to putting in order at least one micro-pillar array, makes blood from the blood separation and culture chip
Entrance is flowed into, and is sequentially passed through the retention and filtering of at least one micro-pillar array, is obtained the red blood cell containing less than predetermined amount
Flowed out with hematoblastic blood plasma from the outlet of blood separation and culture chip, it is possible to achieve to the quick of minimal amount of blood sample
Separation, improves the detection efficiency of blood sample.
As shown in Fig. 2 the exemplary size knot for showing each microtrabeculae in blood separation and culture chip 10 of the present embodiment
Structure.In the present embodiment, four micro-pillar arrays include flowing to the multiple rows of microtrabeculae being arranged in order, two rows of arbitrary neighborhood along blood
The equal Heterogeneous Permutation of microtrabeculae.
In the present embodiment, it is not to face setting that Heterogeneous Permutation, which specifically refers to two adjacent row's microtrabeculaes, but mutually
The certain distance that staggers is set, and whole micro-pillar array is constituted an oblique array, the inclined degree of oblique array can be according to reality
Border needs setting.By making the microtrabeculae Heterogeneous Permutation of adjacent row in each micro-pillar array, can improve retention to haemocyte and
Filter effect.
In a particular application, the often row microtrabeculae in micro-pillar array can also be just to setting.If simply every in micro-pillar array
Microtrabeculae is arranged all just to setting, a rectangular array is formed, then haemocyte is easy to along the rectilinear slot outflow do not blocked, from
And reduce the retention to haemocyte and filter effect.
In a particular application, in order to realize preferable haemocyte filter effect, it is necessary to make the intercolumniation of each micro-pillar array
The diameter of the haemocyte of retention and filtering both less than required for it.
In one embodiment, tumour cell retention micro-pillar array intercolumniation be less than or equal to tumour cell diameter and
More than the monocyte in blood, leucocyte, red blood cell and hematoblastic diameter.
In a particular application, the diameter of tumour cell is usually 17 μm~52 μm, therefore, tumour cell retention micro-pillar array
Intercolumniation should be less than or equal to 17 μm or slightly larger than 17 μm, to realize the retention to most tumour cells.For example, swollen
The intercolumniation of oncocyte retention micro-pillar array can be in 17 μm~25 μ ms.
As shown in Fig. 2 in the present embodiment, the intercolumniation of tumour cell retention micro-pillar array 1 is 20 μm, and tumour cell is cut
It is 20 μm to stay micro post diameter.
In a particular application, the sectional dimension and height of each microtrabeculae in tumour cell retention micro-pillar array can be according to realities
Border needs setting, for example, height can be more than 52 μm；When tumour cell retain microtrabeculae width range in micro-pillar array for 10~
30 μm, for example, 10 μm, 15 μm, 20 μm, 25 μm or 30 μm；When microtrabeculae is cylinder, microtrabeculae width refers to the diameter of cylinder；When
When microtrabeculae is square column, microtrabeculae width refers to the square length of side of square column.
In one embodiment, monocyte retention micro-pillar array intercolumniation be less than or equal to monocyte diameter and
More than the leucocyte in blood, red blood cell and hematoblastic diameter.
In a particular application, the diameter of monocyte is usually 15 μm~25 μm, therefore, monocyte retention micro-pillar array
Intercolumniation should be less than or equal to 15 μm or slightly larger than 15 μm, to realize the retention to most monocytes.For example, single
The intercolumniation of nucleus retention micro-pillar array can be in 15 μm~17 μ ms.
As shown in Fig. 2 in the present embodiment, the intercolumniation of monocyte retention micro-pillar array 1 is 15 μm, and monocyte is cut
Stay microtrabeculae a diameter of 18 μm.
In a particular application, the sectional dimension and height of each microtrabeculae in monocyte retention micro-pillar array can be according to realities
Border needs setting, for example, height can be more than 25 μm；When the width range that monocyte retains the microtrabeculae in micro-pillar array is 10
μm~30 μm, for example, 10 μm, 15 μm, 20 μm, 25 μm or 30 μm；When microtrabeculae is cylinder, microtrabeculae width refers to the straight of cylinder
Footpath；When microtrabeculae is square column, microtrabeculae width refers to the square length of side of square column.
In one embodiment, the intercolumniation of leucocyte retention micro-pillar array is less than or equal to the diameter of leucocyte and is more than
Red blood cell and hematoblastic diameter in blood.
In a particular application, the diameter of leucocyte is usually 7 μm~10 μm, 12 μm~20 μm or 14 μm~20 μm, therefore,
The intercolumniation of leucocyte retention micro-pillar array should be less than or equal to 7 μm or slightly larger than 7 μm, to realize to most leucocytes
Retention.For example, the intercolumniation of leucocyte retention micro-pillar array can be in 7 μm~14 μ ms.
As shown in Fig. 2 in the present embodiment, the intercolumniation of leucocyte retention micro-pillar array 1 is 10 μm, and leucocyte retention is micro-
A diameter of 12 μm of post.
In a particular application, the sectional dimension and height of each microtrabeculae in leucocyte retention micro-pillar array can be according to reality
Setting is needed, for example, height can be more than 20 μm；Microtrabeculae width range in leucocyte retention micro-pillar array is 5 μm~25 μm,
For example, 5 μm, 10 μm, 15 μm, 20 μm or 25 μm；When microtrabeculae is cylinder, microtrabeculae width refers to the diameter of cylinder；When microtrabeculae is
During square column, microtrabeculae width refers to the square length of side of square column.
In one embodiment, the intercolumniation of red blood cell retention micro-pillar array is less than or equal to the diameter of red blood cell and is more than
Hematoblastic diameter in blood.
In a particular application, the diameter of red blood cell be usually 6 μm~8 μm therefore, red blood cell retain micro-pillar array intercolumniation
Away from 6 μm or slightly larger than 6 μm should be less than or equal to, to realize the retention to most red blood cells.For example, red blood cell retention is micro-
The intercolumniation of post array can be in 4 μm~7 μ ms.
As shown in Fig. 2 in the present embodiment, the intercolumniation of red blood cell retention micro-pillar array 1 is 5 μm, and red blood cell retention is micro-
A diameter of 10 μm of post.
In a particular application, the sectional dimension and height of each microtrabeculae in red blood cell retention micro-pillar array can be according to reality
Setting is needed, for example, height can be more than 8 μm；Microtrabeculae width range in red blood cell retention micro-pillar array is 5 μm~25 μm,
For example, for example, 5 μm, 10 μm, 15 μm, 20 μm or 25 μm；When microtrabeculae is cylinder, microtrabeculae width refers to the diameter of cylinder；When micro-
When post is square column, microtrabeculae width refers to the square length of side of square column.
As shown in figure 3, one embodiment of the present of invention also provides a kind of blood separating mechanism, it includes above-mentioned blood point
From preprocessed chip 10, in addition to micro-fluidic chip 20, it is provided with micro-fluidic chip 20 and blood separation and culture chip 10
Outlet connection fluid channel 21 and the plasma outlet port and haemocyte that are connected with the outlet of fluid channel export.
Filled arrows direction represents blood main flow direction in Fig. 3.
(it is one that dotted line encloses the part come in Fig. 3 to multiple micro-channel units 211 of the fluid channel 21 including periodic arrangement
Individual micro-channel unit), head and the tail are connected multiple micro-channel units 211 successively.
Micro-channel unit 211 includes the first semi-circular fluid channel and the second semi-circular fluid channel, the first semi-circular fluid channel
Outlet and the entrance slitless connection of the second semi-circular fluid channel.
In a particular application, the size of fluid channel can be set according to actual needs.
In one embodiment, the difference of the external diameter of the first semi-circular fluid channel and internal diameter is equal in the first semi-circular fluid channel
The ring cutting diameter at any place, the external diameter of the second semi-circular fluid channel and the difference of internal diameter are less than the maximum loop of the second semi-circular fluid channel
Diameter is cut, the external diameter of the first semi-circular fluid channel is less than the internal diameter of the second semi-circular fluid channel.
The operation principle for the blood separating mechanism that the present embodiment is provided is：
After blood stream is pretreated through blood separation and culture chip, miniflow is flowed into by the entrance of micro-fluidic chip
Road, fluid channel carries out inertia focusing to the blood after pretreatment, obtains the blood plasma and haemocyte of high-purity, high-purity
Blood plasma flows out through plasma outlet port, the outflow of haemocyte menses cell outlet.
In a particular application, inertia focusing is specifically referred to：By inertia focusing come small chi remaining in filtered plasma
Very little cell or particle, when the particle such as cell flows in fluid channel, except by main flow driving force flow forward, also in Vertical Square
Wall lift (the Wall Effect that the conduit wall of shearing force and closure is brought to caused by by the velocity gradient difference by fluid
Lift Force) influence, shearing force and wall lift synthesize inertia force.Under inertia force effect, cell will be in miniflow
Fixed position migration in road, therefore can be used to the blood platelet in separated plasma and a small amount of red blood cell to obtain the blood of high-purity
Slurry.
As shown in figure 4, the specific dimensional structure for showing fluid channel 21 exemplary in the present embodiment.In order to show in Fig. 4
Meaning is convenient, the merely exemplary micro-channel unit for showing two cycles.
In the present embodiment, the external diameter R1 and internal diameter R2 of the first semi-circular fluid channel difference are equal to the first semi-circular fluid channel
Ring cutting the diameter L1, i.e. R1-R2=L1 at upper any place；The external diameter R3 and internal diameter R4 of second semi-circular fluid channel difference are less than second
The maximum ring cutting diameter L2 of semi-circular fluid channel, i.e. R3-R4 ＜ L2；The external diameter R1 of first semi-circular fluid channel is less than the second semi-ring
The internal diameter R4 of shape fluid channel, i.e. R1 ＜ R4；The ring cutting diameter L1 at any place is less than the second semi-circular in first semi-circular fluid channel
The maximum ring cutting diameter L2 of fluid channel, i.e. L1 ＜ L2.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
Any modifications, equivalent substitutions and improvements made within refreshing and principle etc., should be included in the scope of the protection.
Claims (10)
1. a kind of blood separation and culture chip, it is characterised in that including flowing at least one microtrabeculae being arranged in order along blood
Array, the intercolumniation of each micro-pillar array is differed, the intercolumniation of at least one micro-pillar array according to it is described extremely
Few putting in order for micro-pillar array is sequentially reduced, and at least one described micro-pillar array at least includes red blood cell retention microtrabeculae battle array
Row；
The red blood cell retention micro-pillar array is retained to the red blood cell in the blood, red thin in the blood to filter
Born of the same parents；
Blood is flowed into from the entrance of the blood separation and culture chip, sequentially passes through the retention of at least one micro-pillar array
And filtering, red blood cell and hematoblastic blood plasma containing less than predetermined amount are obtained from the outlet of the blood separation and culture chip
Outflow.
2. blood separation and culture chip as claimed in claim 1, it is characterised in that at least one described micro-pillar array includes
The tumour cell retention micro-pillar array being arranged in order, monocyte retention micro-pillar array, leucocyte retention microtrabeculae are flowed to along blood
Array and red blood cell retention micro-pillar array；
The tumour cell retention micro-pillar array is retained to the tumour cell in the blood, to filter in the blood
Tumour cell；The monocyte retention micro-pillar array is retained to the monocyte in the blood, to filter the blood
Monocyte in liquid；The leucocyte retention micro-pillar array is retained to the leucocyte in the blood, described to filter
Leucocyte in blood；
The blood is flowed into from the entrance of the blood separation and culture chip, sequentially passes through the tumour cell retention microtrabeculae battle array
Row, monocyte retention micro-pillar array, leucocyte retention micro-pillar array and red blood cell retention micro-pillar array are right
After tumour cell, monocyte, leucocyte and red blood cell in the blood are retained and filtered, obtain containing less than default
The red blood cell of amount and hematoblastic blood plasma flow out from the outlet of blood separation and culture chip.
3. blood separation and culture chip as claimed in claim 1, it is characterised in that the micro-pillar array is included along blood stream
To the multiple rows of microtrabeculae being arranged in order, the equal Heterogeneous Permutation of microtrabeculae described in two rows of arbitrary neighborhood.
4. the blood separation and culture chip as described in any one of claims 1 to 3, it is characterised in that the tumour cell is cut
The intercolumniation of micro-pillar array is stayed to be less than or equal to the diameter of the tumour cell and more than the monocyte in the blood, white thin
Born of the same parents, red blood cell and hematoblastic diameter.
5. the blood separation and culture chip as described in any one of claims 1 to 3, it is characterised in that the monocyte is cut
The intercolumniation of micro-pillar array is stayed to be less than or equal to the diameter of the monocyte and more than the leucocyte in the blood, red blood cell
With hematoblastic diameter.
6. the blood separation and culture chip as described in any one of claims 1 to 3, it is characterised in that the leucocyte retention
The intercolumniation of micro-pillar array is less than or equal to the diameter of the leucocyte and more than the red blood cell in the blood and hematoblastic
Diameter.
7. the blood separation and culture chip as described in any one of claims 1 to 3, it is characterised in that the red blood cell retention
The intercolumniation of micro-pillar array is less than or equal to the diameter of the red blood cell and more than the hematoblastic diameter in the blood.
8. blood separation and culture chip as claimed in claim 1, it is characterised in that the micro-pillar array be cylindrical-array,
Any of cylindroid array or polygon pillar array.
9. a kind of blood separating mechanism, it is characterised in that including the pre- place of blood separation as described in any one of claim 1~8
Manage the outlet being provided with chip, in addition to micro-fluidic chip, the micro-fluidic chip with the blood separation and culture chip
The fluid channel of connection and the outlet of the plasma outlet port being connected with the outlet of the fluid channel and haemocyte；
The fluid channel includes multiple micro-channel units of periodic arrangement, and head and the tail are connected the multiple micro-channel unit successively；
The micro-channel unit includes the first semi-circular fluid channel and the second semi-circular fluid channel, the first semi-circular fluid channel
Outlet and the entrance slitless connection of the second semi-circular fluid channel；
Blood is flowed through after the blood separation and culture chip is pretreated, and the entrance for passing through the micro-fluidic chip flows into institute
State fluid channel, the fluid channel carries out inertia focusing to the blood after the pretreatment, obtain high-purity blood plasma and
Haemocyte, the blood plasma of the high-purity flows out through the plasma outlet port, and the haemocyte is exported through the haemocyte to flow out.
10. blood separating mechanism as claimed in claim 9, it is characterised in that the external diameter of the first semi-circular fluid channel with
The difference of internal diameter is equal to the ring cutting diameter at any place in the first semi-circular fluid channel, the external diameter of the second semi-circular fluid channel
And the difference of internal diameter is less than the maximum ring cutting diameter of the second semi-circular fluid channel, the external diameter of the first semi-circular fluid channel is small
In the internal diameter of the second semi-circular fluid channel.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710565396.8A CN107262171A (en) | 2017-07-12 | 2017-07-12 | A kind of blood separation and culture chip and blood separating mechanism |
| PCT/CN2017/100741 WO2019010788A1 (en) | 2017-07-12 | 2017-09-06 | Blood separation pretreatment chip and blood separation device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710565396.8A CN107262171A (en) | 2017-07-12 | 2017-07-12 | A kind of blood separation and culture chip and blood separating mechanism |
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| CN107262171A true CN107262171A (en) | 2017-10-20 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201710565396.8A Pending CN107262171A (en) | 2017-07-12 | 2017-07-12 | A kind of blood separation and culture chip and blood separating mechanism |
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| Country | Link |
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| CN (1) | CN107262171A (en) |
| WO (1) | WO2019010788A1 (en) |
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