Utility model content
The utility model embodiment provides a kind of blood separation and culture chip and blood separating mechanism, can be to minute quantity
Blood sample carry out quick separating, improve the detection efficiency of blood sample.
On the one hand the utility model embodiment provides a kind of blood separation and culture chip, including being flowed to successively along blood
At least one micro-pillar array of arrangement, the intercolumniation of each micro-pillar array differ, at least one micro-pillar array
Intercolumniation be sequentially reduced according to the putting in order at least one micro-pillar array, at least one micro-pillar array is at least wrapped
Include red blood cell retention micro-pillar array;
The red blood cell retention micro-pillar array retains 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, successively by least one micro-pillar array
Retention and filtering obtain the red blood cell containing less than predetermined amount and hematoblastic blood plasma from the blood separation and culture chip
Outlet outflow.
In one embodiment, at least one micro-pillar array includes cutting along the tumour cell that blood flow direction is arranged in order
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 retains the tumour cell in the blood, to filter the blood
In tumour cell;The monocyte retention micro-pillar array retains the monocyte in the blood, to filter
State the monocyte in blood;The leucocyte retention micro-pillar array retains the leucocyte in the blood, with filtering
Leucocyte in the blood;
The blood is flowed into from the entrance of the blood separation and culture chip, is retained successively by the tumour cell micro-
Column array, monocyte retention micro-pillar array, leucocyte retention micro-pillar array and red blood cell retention microtrabeculae battle array
Row, after tumour cell, monocyte, leucocyte and the red blood cell in the blood are retained and filtered, obtain containing low
It is flowed out in the red blood cell of predetermined amount and hematoblastic blood plasma from the outlet of blood separation and culture chip.
In one embodiment, the micro-pillar array includes the multiple rows of microtrabeculae being arranged in order along blood flow direction, arbitrary neighborhood
The two rows equal Heterogeneous Permutations 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 being more than in the blood and hematoblastic diameter.
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 utility model embodiment also provides a kind of blood separating mechanism, pre- including above-mentioned blood separation
Processing chip further includes micro-fluidic chip, is provided on the micro-fluidic chip and goes out with the blood separation and culture chip
The fluid channel of mouth connection;
The fluid channel includes multiple micro-channel units of periodic arrangement, and the multiple micro-channel unit connects from beginning to end successively
It connects;
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 carry out inertia focusing to the blood after the pretreatment, obtain the blood plasma of high-purity.
In one embodiment, the difference of the outer 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 outer 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 outer diameter of the first semi-circular fluid channel are less than the interior of the second semi-circular fluid channel
Footpath.
The utility model embodiment along blood flow direction by setting gradually including being used to retain and filtering the red thin of red blood cell
Born of the same parents retain at least one micro-pillar array of micro-pillar array, and the intercolumniation of each micro-pillar array is made to differ, and make at least one
The intercolumniation of micro-pillar array is sequentially reduced according to putting in order at least one micro-pillar array, makes blood pre- from blood separation
The entrance of processing chip flows into, and successively by the retention and filtering of at least one micro-pillar array, obtains containing less than default
The red blood cell of amount and hematoblastic blood plasma are flowed out from the outlet of blood separation and culture chip, can be realized to minimal amount of blood
The quick separating of sample improves the detection efficiency of blood sample.
Specific embodiment
It is real below in conjunction with the utility model in order to which those skilled in the art is made to more fully understand the utility model
The attached drawing in example is applied, the technical scheme in the embodiment of the utility model is explicitly described, it is clear that described embodiment
It is the embodiment of the utility model part, instead of all the embodiments.Based on the embodiment in the utility model, this field
Those of ordinary skill's all other embodiments obtained without making creative work, should all belong to this practicality
Novel protected scope.
Term " comprising " and their any changes in the specification and claims of the utility model and above-mentioned attached drawing
Shape, it is intended that cover non-exclusive include.Such as process, method or system comprising series of steps or unit, product or
The step of equipment is not limited to list or unit, but optionally further include the step of not listing or unit or optional
Ground is further included for the intrinsic other steps of these processes, method, product or equipment or unit.In addition, term " first ", " the
Two " and " the 3rd " etc. are for distinguishing different objects, not for description particular order.
As shown in Figure 1, one embodiment of the utility model provides a kind of blood separation and culture chip 10, including edge
Four micro-pillar arrays being arranged in order of blood flow direction, four micro-pillar arrays are respectively that tumour cell retention micro-pillar array 1, monokaryon are thin
Born of the same parents retain 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
Differ, 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 is cut
Stay the intercolumniation of the intercolumniation > leucocytes retention micro-pillar array 3 of the intercolumniation > monocytes retention micro-pillar array 2 of micro-pillar array 1
Intercolumniation away from > red blood cells retention 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
The width in the gap between two microtrabeculaes for anticipating adjacent, the intercolumniation in the present embodiment specifically refer 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 gap between column 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 appointing 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 retains the tumour cell in blood, thin with the tumour in filtering blood
Born of the same parents;Monocyte retention micro-pillar array retains the monocyte in blood, with the monocyte in filtering blood;It is white thin
Born of the same parents retain micro-pillar array and the leucocyte in blood are retained, with the leucocyte in filtering blood;Red blood cell retains microtrabeculae battle array
Row retain 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, successively by 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 tumour cell, the list in blood
After nucleus, leucocyte and red blood cell are retained and filtered, the red blood cell containing less than predetermined amount and hematoblastic blood are obtained
Slurry is 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
The red blood cell for including at least to retain and filter red blood cell in array retains micro-pillar array, and blood is from blood separation in advance
The entrance for managing chip flows into, and successively by the retention and filtering of at least one micro-pillar array, obtains containing red less than predetermined amount
Cell and hematoblastic blood plasma are flowed out from the outlet of blood separation and culture chip.
Since red blood cell is smallest size of cell in blood, setting blood separation and culture chip includes at least
Red blood cell retains micro-pillar array, can all cells in blood 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 be by the number of micro-pillar array
It measures with intercolumniation to determine, intercolumniation is smaller, and predetermined amount is smaller.
In a particular application, the quantity of the micro-pillar array included by blood separation and culture chip and species can be according to realities
Border needs to be configured.Such as, it is only necessary to retention and filtering tumour cell then only can retain microtrabeculae battle array by setting tumour cell
Row;It only needs to retain and filters monocyte, then it can setting monocyte retention micro-pillar array.Same type of microtrabeculae
Array can also set simultaneously it is multiple, with strengthen retain filter effect.
The utility model along blood flow direction by setting gradually including being used to retain and filtering the red blood cell retention of red blood cell
At least one micro-pillar array of micro-pillar array, and the intercolumniation of each micro-pillar array is made to differ, make at least one microtrabeculae battle array
The intercolumniation of row is sequentially reduced according to putting in order at least one micro-pillar array, makes blood from the blood separation and culture core
The entrance of piece flows into, and successively by the retention and filtering of at least one micro-pillar array, obtains containing red less than predetermined amount
Cell and hematoblastic blood plasma are flowed out from the outlet of blood separation and culture chip, can be realized to minimal amount of blood sample
Quick separating improves the detection efficiency of blood sample.
As shown in Fig. 2, the present embodiment illustratively shows the size knot of each microtrabeculae in blood separation and culture chip 10
Structure.In the present embodiment, four micro-pillar arrays include the multiple rows of microtrabeculae being arranged in order along blood flow direction, the two rows of arbitrary neighborhood
The equal Heterogeneous Permutation of microtrabeculae.
In the present embodiment, it is not to face setting that Heterogeneous Permutation, which specifically refers to adjacent two rows of microtrabeculaes, but mutually
The certain distance that staggers is set, and entire micro-pillar array is made to form an oblique array, the inclined degree of oblique array can be according to reality
Border needs to set.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 face setting.It is if simply every in micro-pillar array
It arranges microtrabeculae all faces to set, forms a rectangular array, 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 monocyte, leucocyte, red blood cell and the hematoblastic diameter in blood.
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.It is 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 of each microtrabeculae in tumour cell retention micro-pillar array and height can be according to realities
Border needs to set, 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 leucocyte, red blood cell and the hematoblastic diameter in blood.
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.It is 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 of each microtrabeculae in monocyte retention micro-pillar array and height can be according to realities
Border needs to set, 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 column.
In a particular application, the sectional dimension of each microtrabeculae in leucocyte retention micro-pillar array and height can be according to reality
It needs to set, 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 should be less than or equal to or slightly larger than 6 μm, to realize the retention to most red blood cells.For example, red blood cell retention is micro-
The intercolumniation of column 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 column.
In a particular application, the sectional dimension of each microtrabeculae in red blood cell retention micro-pillar array and height can be according to reality
It needs to set, 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 column is square column, microtrabeculae width refers to the square length of side of square column.
As shown in figure 3, one embodiment of the utility model also provides a kind of blood separating mechanism, including above-mentioned blood
Liquid separation and culture chip 10 further includes micro-fluidic chip 20, is provided on micro-fluidic chip 20 and blood separation and culture core
The fluid channel 21 of the outlet connection of piece 10 and the plasma outlet port for exporting connection and the haemocyte outlet with fluid channel.
Solid arrow 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
A micro-channel unit), head and the tail connect 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 outer 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 outer 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 outer 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 by the entrance of micro-fluidic chip
Road, fluid channel carry out inertia focusing to the blood after pretreatment, obtain the blood plasma and haemocyte of high-purity, high-purity
Blood plasma goes out through blood plasma outlet stream, the outflow of haemocyte menses cell outlet.
In a particular application, inertia focusing specifically refers to:By inertia focusing come small ruler remaining in filtered plasma
Very little cell or particle, cell is when particles flow in fluid channel, except being subject to mainstream driving force flow forward, also in Vertical Square
To wall surface lift (the Wall Effect that the conduit wall of the shearing force as caused by the velocity gradient difference of fluid and closure is subject to bring
Lift Force) influence, shearing force and wall surface lift synthesize inertia force.Under inertia force effect, cell will be in miniflow
Fixed position migration in road, therefore the blood platelet in separated plasma and a small amount of red blood cell are can be used to so as to obtain the blood of high-purity
Slurry.
As shown in figure 4, the specific dimensional structure of fluid channel 21 is illustratively shown 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 difference of the outer diameter R1 and internal diameter R2 of the first semi-circular fluid channel are equal to the first semi-circular fluid channel
Ring cutting the diameter L1, i.e. R1-R2=L1 at upper any place;The difference of the outer diameter R3 and internal diameter R4 of second semi-circular fluid channel are less than second
The maximum ring cutting diameter L2 of semi-circular fluid channel, i.e. R3-R4 < L2;The outer 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 above is only the preferred embodiment of the utility model only, is not intended to limit the utility model, all at this
All any modification, equivalent and improvement made within the spirit and principle of utility model etc., should be included in the utility model
Protection domain within.