CN205517819U - Whole blood filtration and ration are moved and are got micro -fluidic chip - Google Patents
Whole blood filtration and ration are moved and are got micro -fluidic chip Download PDFInfo
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- CN205517819U CN205517819U CN201620267457.3U CN201620267457U CN205517819U CN 205517819 U CN205517819 U CN 205517819U CN 201620267457 U CN201620267457 U CN 201620267457U CN 205517819 U CN205517819 U CN 205517819U
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Abstract
The utility model relates to a micro -fluidic chip especially relates to a whole blood filtration and ration are moved and are got micro -fluidic chip, include the chip main part and set up the whole blood separating mechanism in the chip main part, little valve of preventing flowing backwards, liquid ration mechanism, propulsion liquid mechanism, the little valve of choked flow and play liquid mechanism, wherein: whole blood separating mechanism is including the inlet, whole blood filter membrane and the collector unit that set gradually for obtain plasma and at capillary action down through preventing that the little valve of refluence conveys to the quantitative mechanism of liquid with hemodiafiltration separation, prevent that the little valve of refluence is arranged in preventing plasma adverse current to the whole blood separating mechanism of liquid ration mechanism, the little valve of choked flow is used for stoping plasma to flow out under the no ambient pressure circumstances, impel liquid mechanism to be used for declining the valve propelling movement to going out liquid mechanism with quantitative plasma through the choked flow with propulsions liquid under the pressure effect, the utility model discloses a whole blood filtration and ration are moved and are got micro -fluidic chip effectively separates blood cell and plasma and ration and moves and get plasma, be fit for the use with other types chip composite.
Description
Technical field
This utility model relates to a kind of micro-fluidic chip, particularly relates to a kind of Whole Blood Filtration and quantitatively pipettes miniflow
Control chip.
Background technology
Clinical unit carries out the main method of whole blood separation at present is by blood taking tube centrifugation: one is for dividing
From glue coagulant blood taking tube, use 3000rpm low-speed centrifugal, make erythrocyte and serum because density difference is layered
Both sides to separation gel;Blood taking tube there are coagulant composition and separation gel, coagulant composition can promote coagulation process,
Make erythrocyte and blood coagulating protein gather together, be more easy to be centrifuged.Its two be EDTA/ sodium citrate/heparin resist
Solidifying blood taking tube, is also clinical common blood taking tube, with the addition of EDTA/ sodium citrate/heparin sodium anticoagulant the most respectively
Composition, can hinder coagulation process, and under conditions of 3000rpm low-speed centrifugal, erythrocyte can divide with blood plasma
Layer.In addition, Chinese patent publication No. is the utility model patent of CN204544220U, also discloses one
Planting rotating centrifugal whole blood separating chips and preparation method thereof, erythrocyte is separated with blood plasma by it by centrifugal force,
And form a siphonage after centrifugal end by supernatant separation.But use this patented technology to applied sample amount
And erythrocyte proportion has the requirement that comparison is high, applied sample amount can cause realizing siphon very little, blood red
Cell proportion during too conference causes siphonic process erythrocyte be inhaled into collecting bin, using effect is unstable;
And the method need to use centrifugation apparatus, relatively costly.
Micro-fluidic chip, also known as chip lab (Lab-on-a-Chip), is a kind of micro-full analytical system (μ
-TAS), it is a kind of to manipulate the system that micro volume fluid flows in minim channel or component, relates to thing
Reason, multiple basic subject fields such as chemical, biological.Micro-fluidic chip, based on microflow control technique, comprises
The little nanoscale devices such as the other passage of micron to nano grade, chamber, valve, pump, utilize its Characteristics Control fluid to move
And physicochemical change.
Chinese patent publication No. is the utility model patent of CN103041879A, i.e. discloses a kind of based on miniflow
Micro-/nanoliter quantitative sample injection micro-fluidic chip of control technology and preparation method thereof, the method uses electric osmose as driving
Power quantitative sample injection;But this Patent design is hydraulically full in needing to make runner, is only applicable to electrophoresis class micro-fluidic
Chip, is not suitable for using with other types chip portfolio.
Because above-mentioned defect, the design people, the most in addition research and innovation, to based on microflow control technique
Found one have Whole Blood Filtration concurrently and quantitatively pipette micro-fluidic chip so that it is have more the value in industry.
Utility model content
For solving above-mentioned technical problem, the purpose of this utility model is to provide one and efficiently separates hemocyte and blood
Slurry also quantitatively pipettes blood plasma, can use with other types chip portfolio or be integrated into detection chip further
Whole blood separates and quantitatively pipettes the Whole Blood Filtration of module and quantitatively pipette micro-fluidic chip.
This utility model provides a kind of Whole Blood Filtration and quantitatively pipettes micro-fluidic chip, including chip body, with
And be arranged in chip body whole blood separating mechanism, the micro-valve of anti-backflow, liquid quantitative mechanism, PF machine
Structure, the micro-valve of choked flow and liquid outlet mechanism;Wherein:
Described whole blood separating mechanism includes inlet, whole blood filter membrane and the collector unit set gradually, described entirely
Blood filter membrane is for the blood filtration isolated blood plasma that will enter from inlet, and described collector unit is used for collecting
Blood plasma is also sent to liquid quantitative mechanism through the micro-valve of anti-backflow by the blood plasma of isolated under capillary action;
The micro-valve of described anti-backflow is for stoping the blood plasma adverse current in liquid quantitative mechanism to whole blood separating mechanism;
Described liquid quantitative mechanism includes the liquid storage cylinder for housing quantitative blood plasma;
The micro-valve of described choked flow is arranged on the outfan of liquid quantitative mechanism and for stoping the blood plasma in liquid storage cylinder
Flow out in the case of without ambient pressure;
Described PF mechanism includes the propelling sap cavity for housing PF and propulsion unit, described propelling list
Unit is for pushing to liquid storage cylinder under pressure and by determining in liquid storage cylinder by the PF of PF intracavity
Amount blood plasma pushes to liquid outlet mechanism through the micro-valve of choked flow;
Described liquid outlet mechanism includes liquid outlet, described liquid outlet blood plasma after discharging Quantitative Separation.
Further, described chip body is PMMA material, glass material, PS material chip main body,
Wherein PMMA material is otherwise known as polymethyl methacrylate or acrylic material, and PS material is otherwise known as
Polystyrene material.
Further, described collector unit include collecting chamber, multiple support columns of being arranged in collecting chamber, with
And supporting layer, described supporting layer is arranged on the support columns, and described whole blood filter membrane is arranged on described supporting layer,
Described inlet is arranged on the top of described whole blood filter membrane.It should be noted that, the effect of supporting layer be by
Whole blood filter membrane is supported on the top of support column, on the one hand plays a supporting role, and on the other hand plays preventing whole blood
Filter membrane mutually attaches with support column end face, increases the filter area of whole blood filter membrane, improves the effect of filter effect;
The material of supporting layer can select multiple, such as the fibrous material of the short texture such as polyester film, glass fibre,
Blood plasma under from whole blood membrane filtration, can enter in collecting chamber through the space in fibrous material.
It should be noted that, hemocyte not can be separated completely effectively by whole blood filter membrane with blood plasma, in order to
Prevent hemocyte enter liquid quantitative mechanism, the bottom of described collecting chamber be provided be arranged as stair-stepping multiple
Base frame, described support column is arranged on described base frame, and the end face of support column is mutually flush, described collecting chamber
Liquid outlet is positioned close to that side with the base frame of extreme higher position.Stair-stepping base frame, plays precipitation blood
Cell also limits the hemocyte effect towards the displacement of liquid outlet direction, between the support column of spaced arrangement
Gap, plays again filtration and limits the hemocyte effect towards the displacement of liquid outlet direction.It should be noted that,
The quantity of base frame is 3 to 5, and the height of each ladder is about 150-250 μm, base frame negligible amounts for
The restriction effect of hemocyte is more general, and quantity is more, is confined to the most again the thickness of chip body, instead
And reduce the filter effect of hemocyte.
Further, the micro-valve of described anti-backflow is that tongue piece declines valve or the micro-valve of wall-attachment;Wherein:
The described tongue piece valve that declines includes tongue piece, described tongue piece on front side of liquid flow direction with the pressure differential of rear side
For on the occasion of being respectively opening and closure state, in other words, when collector unit is received in the case of negative value
Collection is when obtaining blood plasma, owing to the micro-valve of anti-backflow is vacant near the side of liquid storage cylinder, front and back both sides exist on the occasion of
Pressure differential, blood plasma can pass through tongue piece and decline valve, when plasmaflux reaches certain value, or PF
When entering liquid storage cylinder under the effect of propulsion unit, before and after the micro-valve of anti-backflow, there is balance or negative in the pressure of both sides
The pressure differential of value, tongue piece deforms upon or displacement under pressure differential effect, is closed by the liquid outlet of collector unit;
The micro-valve of described wall-attachment includes main channel and the multiple bypass channels being connected in parallel on main channel, described
Bypass channel two ends all with identical with liquid flow direction in main channel towards being connected on main channel;Attached wall
The valve that declines utilizes resistance difference to realize the one-way flow of liquid.
Further, the described tongue piece valve that declines includes valve channel, tongue piece chamber and tongue piece, described tongue piece
Chamber is arranged on described valve channel, and one end of described tongue piece rotates or is fixedly installed on described tongue piece intracavity.
Concrete, described tongue piece is silica gel tongue piece.
Further, described liquid storage cylinder is capillary tube or capillary channel.It should be noted that, liquid storage cylinder
Liquid storage amount and capillary tube or the internal diameter of capillary channel and length are relevant, in the case of internal diameter is certain, and Ke Yi
Capillary tube or the capillary channel of S type is used, to increase liquid storage amount in the chip body of finite size.
Further, the micro-valve of described choked flow includes stream control chamber, and the inlet aperture in described stream control chamber is more than described
The aperture of liquid quantitative mechanism outfan, the interior direction of inlet without leave in described stream control chamber to liquid outlet direction by
The least.The micro-valve of choked flow utilizes liquid surface infiltration masterpiece to be valve resistance, and when quantitative blood plasma, to flow to choked flow micro-
During valve, liquid surface area increases suddenly, thus needs a large amount of liquid volume, thus to liquid hair forward
Thread is dynamic creates large drag forces, thus plays the effect of choked flow;At applying pressure, liquid is pushed choked flow micro-
Behind the stream control chamber of valve, its structural table area is saturated rapidly, makes the micro-valve of choked flow not produce subsequent liquid flowing
Hinder.
Concrete, described stream control chamber includes front cavity and the rear chamber set gradually by liquid flow direction, institute
Stating front cavity is cubic type, and the floor height of described front cavity is less than described liquid quantitative mechanism outfan
Floor height, the internal diameter of described rear chamber is gradually reduced by liquid flow direction.
Further, described PF mechanism is dismountable PF mechanism or modular PF mechanism, its
In, described dismountable PF mechanism is removably connected in described chip body, and at described core
It is provided with joint in sheet main body;Described modular PF mechanism integrated setting is in described chip body.
Further, described PF mechanism includes pedestal, and described pedestal is provided with piston hole, piston hole
Can be arranged on the end face of pedestal, it is possible to be arranged on the side of pedestal, described pedestal is internally provided with PF
Chamber, described propulsion unit is piston block, and described piston block slides in described piston hole relatively, described piston
The locating part for limiting described piston block monodisplacement it is provided with on the inwall in hole.It should be noted that, this
The PF mechanism of kind of structure, could be arranged to dismountable PF mechanism, it is possible to be set to modular and advance
Liquid mechanism.
It is capable of piston block locating part of monodisplacement in piston hole it should be noted that, every, all should
Falling into protection domain of the present utility model, relatively simple, described locating part is for being disposed side by side in piston hole
A plurality of helical teeth on wall, the outer wall of described piston block is provided with the tooth engaged being meshed with helical teeth, by stinging
Close the tooth interlocking to helical teeth, prevent the reverse displacement of piston block;The effect of piston block monodisplacement is to make
Quantitative blood plasma in liquid storage cylinder is discharged, without by the blood plasma sucking-off in collector unit.
By such scheme, this utility model at least has the advantage that 1) this utility model utilizes capillary to make
Jointly act on with external source propulsive force, it is achieved that whole blood separates and quantitatively pipettes function.This utility model without
Use centrifugal force, can preferably coordinate real-time test (POCT, point-of-care testing) method
Use, can combine in the micro-fluidic chip design using or being applied to POCT by reagent micro-fluidic with POCT;
2) this utility model realizes whole blood and separates and quantitatively pipette function and complete on the same chip, can make work people
The operation of member is easier, and the testing result obtained is more stable.
Described above is only the general introduction of technical solutions of the utility model, in order to it is new to better understand this practicality
The technological means of type, and can be practiced according to the content of description, below with preferable reality of the present utility model
After executing example and coordinating accompanying drawing to describe in detail such as.
Accompanying drawing explanation
Fig. 1 is structural representation of the present utility model;
Fig. 2 is the structural representation of this utility model chips upper slice;
Fig. 3 is the structural representation of this utility model chips bottom sheet;
Fig. 4 is the partial enlarged drawing in A portion in Fig. 3;
Fig. 5 is that in this utility model, tongue piece declines the structural representation of valve;
Fig. 6 is the partial enlarged drawing in B portion in Fig. 3;
Fig. 7 is the structural representation of S type capillary channel liquid storage cylinder in this utility model;
Fig. 8 is the partial enlarged drawing in C portion in Fig. 3;
Fig. 9 is the structural representation of PF mechanism in this utility model;
Figure 10 is the structural representation of the first liquid outlet mechanism in this utility model;
Figure 11 is the structural representation of the second liquid outlet mechanism in this utility model.
Detailed description of the invention
Below in conjunction with the accompanying drawings and embodiment, detailed description of the invention of the present utility model is described in further detail.
Following example are used for illustrating this utility model, but are not limited to scope of the present utility model.
Embodiment one
See Fig. 1 to Fig. 3, a kind of Whole Blood Filtration of this utility model one preferred embodiment and quantitatively pipette miniflow
Control chip, micro-including chip body 1 and the whole blood separating mechanism 2, the anti-backflow that are arranged in chip body
Valve 3, liquid quantitative mechanism 4, PF mechanism 5, the micro-valve of choked flow 6 and liquid outlet mechanism 7.
It should be noted that, whole blood separating mechanism 2, the micro-valve of anti-backflow 3, liquid quantitative mechanism 4, PF
Mechanism 5, the micro-valve of choked flow 6 and liquid outlet mechanism 7 can be by various ways such as Laser Processing, model injection moldings
In the internal molding of chip body, it is possible to by being set to chip upper slice 11 and the chip bottom sheet 12 of separate type,
Process given shape on chip upper slice 11 or chip bottom sheet 12, then mutually encapsulate together;Due to
Former processing mode is relatively complicated, and this is repeated no more by this utility model, in subsequent embodiment, and this reality
With novel with chip body separate design for chip upper slice 11 or the mode of chip bottom sheet 12 then mutually encapsulation,
It is described further.
Whole blood separating mechanism 2 includes inlet 201, whole blood filter membrane (not shown) and the receipts set gradually
Collection unit 202, wherein inlet 201 and whole blood filter membrane may be provided on chip upper slice 11, and collector unit sets
Put under the die on sheet 12;Whole blood filter membrane is for the blood filtration isolated blood that will enter from inlet 201
Slurry, collector unit 202 is for collecting the blood plasma of isolated and by blood plasma under capillary action through anti-backflow
Micro-valve 3 is sent to liquid quantitative mechanism 4;
The micro-valve of anti-backflow 3 is for stoping the blood plasma adverse current in liquid quantitative mechanism to whole blood separating mechanism 2;
Liquid quantitative mechanism 4 includes the liquid storage cylinder for housing quantitative blood plasma;
The micro-valve of choked flow 6 is arranged on the outfan of liquid quantitative mechanism 5 and for stoping the blood plasma in liquid storage cylinder
Flow out in the case of without ambient pressure;
PF mechanism 5 includes the propelling sap cavity for housing PF and propulsion unit, and propulsion unit is used for
The PF of PF intracavity is pushed under pressure liquid storage cylinder and by the quantitative blood plasma in liquid storage cylinder
Liquid outlet mechanism is pushed to through the micro-valve of choked flow;
Liquid outlet mechanism 7 includes liquid outlet 701, the liquid outlet 701 blood plasma after discharging Quantitative Separation.
Collector unit 202, the micro-valve of anti-backflow 3, liquid quantitative mechanism 4, PF mechanism 5, the micro-valve of choked flow 6
With liquid outlet mechanism 7, can be arranged in chip bottom sheet, and chip upper slice is encapsulated in chip bottom sheet, encapsulate shape
Formula can use the one that mucilage binding, card fill, clamp etc. in various ways, it is possible to is used in conjunction with each other;Wherein,
Mucilage binding can use the modes such as double faced adhesive tape, heat-curable glue, optic-solidified adhesive, and card dress can use at chip upper slice and core
It is respectively provided with the fastener cooperated and draw-in groove in sheet bottom sheet fixing with card dress, clamps to use and be separately configured
Fixture, clamps fixing by chip upper slice and chip bottom sheet;It addition, relate to the micro-valve of anti-backflow 3, liquid quantitative machine
Structure 4, PF mechanism 5, the micro-valve of choked flow 6 and the region of liquid outlet mechanism 7, in order to prevent blood plasma from flowing out, also
Can arrange and seal structure accordingly, such as sealing gasket or the sealing ridge cooperated and groove etc., it is possible to
Coordinate mucilage binding, to reach the effect sealed.
It should be noted that, each structure shown in accompanying drawing 1 to 3, be only used for illustrating whole blood separating mechanism 2,
The micro-valve of anti-backflow 3, liquid quantitative mechanism 4, PF mechanism 5, the micro-valve of choked flow 6 and liquid outlet mechanism 7 are risen
The function arrived, every micro-fluidic structure being capable of above-mentioned technique effect, all should fall into of the present utility model
Protection domain, and it is not limited to the structure shown in accompanying drawing.
Embodiment two
Seeing Fig. 2 to Fig. 4, this utility model provides a kind of and realizes the whole blood of function described in embodiment one and divide
Disembarking structure 2, chip body 1 includes chip upper slice 11 and chip bottom sheet 12, and inlet 201 is arranged at chip
Upper slice, and the size bottom inlet 201 is more than the size at top, or the bottom of inlet 201 sets
Being equipped with the draw-in groove 203 caved inward, collector unit 202 includes collecting chamber 204, is arranged in collecting chamber 204
Multiple support columns 205 and supporting layer (not shown), supporting layer is arranged on support column 205,
And realize fixing by the mutually encapsulation between chip upper slice and chip bottom sheet, such as can be by the surrounding of supporting layer
Edge is installed in draw-in groove 203;Whole blood filter membrane is arranged on supporting layer, and the edge of whole blood filter membrane can press from both sides
It is contained in draw-in groove 203 between supporting layer and chip upper slice 11;Inlet 201 is arranged on whole blood filter membrane
Top.It should be noted that, the effect of supporting layer is to be supported on whole blood filter membrane the top of support column, one
Aspect is played a supporting role, and on the other hand plays preventing whole blood filter membrane from mutually attaching with support column end face, increases
The filter area of whole blood filter membrane, improves the effect of filter effect;The material of supporting layer can select multiple, example
Such as the fibrous material of the short texture such as polyester film, glass fibre, from whole blood membrane filtration under blood plasma, can
With through the space in fibrous material, enter in collecting chamber 204.
It should be noted that, hemocyte not can be separated completely effectively by whole blood filter membrane with blood plasma, in order to
Prevent hemocyte enter liquid quantitative mechanism 4, the bottom of collecting chamber 204 be provided be arranged as stair-stepping multiple
Base frame 206, support column 205 is arranged on base frame 206, and the end face of support column 205 is mutually flush, collecting chamber
The liquid outlet 207 of 204 is positioned close to that side with the base frame of extreme higher position.Stair-stepping base frame 206,
Play precipitation hemocyte and limit the hemocyte effect towards the displacement of liquid outlet direction, propping up of spaced arrangement
Gap between dagger, plays again filtration and limits the hemocyte effect towards the displacement of liquid outlet direction.Should
Illustrating, the quantity of base frame 206 is 3 to 5, and the height of each ladder is about 150-250 μm, the end
Platform negligible amounts is more general for the restriction effect of hemocyte, and quantity is more, is confined to the most again chip
The thickness of main body so that the height of base frame reduces, and reduces the filter effect of hemocyte on the contrary.
Embodiment three
Seeing Fig. 5 and Fig. 6, this utility model provides multiple and realizes the anti-backflow of function described in embodiment one
Micro-valve 3, identical with embodiment two, chip body 1 includes chip upper slice 11 and chip bottom sheet 12, anti-
Micro-valve 3 that flows backwards is arranged in chip bottom sheet 12, and chip upper slice 11 plays the effect of sealing.The micro-valve of anti-backflow
Having multiple implementation, valve as micro-in variable cross-section, tongue piece decline valve, the micro-valve of wall-attachment etc., it should explanation
It is, every micro-valve of anti-backflow being capable of aforementioned function, protection domain of the present utility model all should be fallen into.
Owing to chip body is lamellar, consider the problem such as practicality and production cost, in this utility model preferably
Tongue piece declines valve and the micro-valve of wall-attachment to be described further.
As it is shown in figure 5, tongue piece declines, valve includes tongue piece 301, tongue piece 301 on front side of liquid flow direction with after
The pressure differential of side is on the occasion of being respectively opening and closure state in the case of negative value;In other words, receipts are worked as
When in collection unit 202, collection obtains blood plasma, owing to the micro-valve of anti-backflow 3 is vacant near the side of liquid storage cylinder, front
Rear both sides exist on the occasion of pressure differential, blood plasma can pass through tongue piece and decline valve, when plasmaflux reaches one
Definite value, or when PF enters liquid storage cylinder under the effect of propulsion unit, both sides before and after the micro-valve of anti-backflow
There is balance or the pressure differential of negative value in pressure, and tongue piece 301 deforms upon or displacement under pressure differential effect, will
The liquid outlet of collector unit 202 is closed.
Specifically, the tongue piece valve that declines includes valve channel 302, tongue piece chamber 303 and tongue piece 301, tongue
Sheet chamber 303 is arranged on valve channel 302, and one end of tongue piece 301 rotates or is fixedly installed on tongue piece intracavity.
In the case of being rotatably connected, tongue piece intracavity is provided with rotating shaft 304, and one end of tongue piece 301 is provided with shaft hole
305, tongue piece 301 is sleeved in rotating shaft 304 by shaft hole 305 and is relatively rotated;Fixing situation about connecting
Under, one end of tongue piece 301 is fixed on the side near collector unit, the tongue piece chamber, and PF mechanism outfan is even
Being connected on the position of the other end near tongue piece 301, now tongue piece 301 seals the outfan of PF mechanism,
When PF is pushed to liquid quantitative mechanism 4 by PF mechanism 5, there is shape in tongue piece 301 under stress
Become, thus push up means of press seals on valve channel, it is achieved the one-way flow of liquid.It should be noted that, work as tongue
When sheet is for being rotatably connected, it is possible to PF mechanism outfan is connected close to the position of the other end of tongue piece 301
Put, tongue piece is set to have elasticity simultaneously and can deform upon, so under dual function, control unidirectional
The effect of flowing is more preferable.Material for tongue piece 301 selects, and can use the tongue piece of soft silica gel material.
As shown in Figure 6, the micro-valve of wall-attachment includes main channel 311 and the multiple bypasses being connected in parallel on main channel
Passage 312, bypass channel 312 two ends are all with identical with liquid flow direction in main channel main towards being connected to
On passage, in other words, liquid flow direction and the angle of liquid flow direction in main channel on front side of bypass channel
More than 90 degree, and bypass channel rear side liquid flow direction is less than with the angle of liquid flow direction in main channel
90 degree;Bypass channel 312 includes the first bypass channel set gradually on liquid flow direction along main channel
313, the second bypass channel 314 and the 3rd bypass channel 315, the first bypass channel, the second bypass channel and
3rd bypass channel is valve shape, and size tapers into, the first bypass channel, the second bypass channel and
3rd bypass channel there is also situation about being overlapped mutually, and it is other that the liquid feeding end of the i.e. second bypass channel is arranged on first
Between liquid feeding end and the liquid outlet of paths, the liquid feeding end of the 3rd bypass channel is arranged on the second bypass channel
Between liquid feeding end and liquid outlet.The quantity of bypass channel is relevant with anti-backflow effect, and bypass channel quantity is the most,
Anti-backflow effect is the best.It should be noted that, main channel may be configured as linear type, it is possible to be set to S type,
To increase reverse resistance flowing effect.
This kind of micro-valve of wall-attachment is referred to as again valve and declines valve, and in liquid is by Fig. 6, flow to the left in right side
Time, in main channel, some liquid enters bypass channel, and converges with main channel in the outlet of bypass channel,
There is certain energy in this, the liquid in main channel is pressed to tube wall, due to flow direction during converging
Identical, thus also make the liquid flowing in main channel more stable;When liquid countercurrent, i.e. liquid is by Fig. 6
Time flowing to the right in middle left side, in main channel, some liquid enters bypass channel, and this partially liq exists
The flow direction in bypass channel exit flows to contrary with the liquid in main channel, therefore adds local resistance,
Thus stop the adverse current of liquid.
Decline valve and the micro-valve of wall-attachment of tongue piece all can be effectively realized the anti-backflow function of liquid, comparatively speaking,
The decline anti-backflow effect of valve of tongue piece is more preferable, but production cost is higher, and the micro-valve of wall-attachment is Comparatively speaking,
Production and processing is the simplest, and production cost is relatively low.
Embodiment four
Seeing Fig. 3 and Fig. 7, this utility model provides a kind of and realizes the liquid of function described in embodiment one calmly
Measuring mechanism 4, identical with previous embodiment, chip body 1 includes chip upper slice 11 and chip bottom sheet 12,
Liquid quantitative mechanism 4 is arranged in chip bottom sheet 12, and chip upper slice 11 plays the effect of sealing.Liquid is fixed
Liquid storage cylinder in measuring mechanism 4, could be arranged to various structures, or is simply set to capillary tube or hair
Stria road.It should be noted that, the liquid storage amount of liquid storage cylinder and capillary tube or the internal diameter of capillary channel and length have
Close, in the case of internal diameter is certain, S type, circle etc. can be used in the chip body of finite size many
Plant capillary tube or the capillary channel of shape, to change the liquid storage amount of liquid storage cylinder.
Embodiment five
Seeing Fig. 8, this utility model provides a kind of and realizes the micro-valve of the choked flow of function described in embodiment one 6,
Identical with previous embodiment, chip body 1 includes chip upper slice 11 and chip bottom sheet 12, the micro-valve of choked flow
6 are arranged in chip bottom sheet 12, and chip upper slice 11 plays the effect of sealing.The micro-valve of choked flow 6 includes stream control chamber
601, the inlet aperture in stream control chamber 601 is more than the aperture of liquid quantitative mechanism 4 outfan, stream control chamber 601
The interior direction of inlet without leave be gradually reduced to liquid outlet direction.The micro-valve of choked flow 6 utilizes liquid surface to infiltrate power
As valve resistance, when quantitative blood plasma flows to the micro-valve 6 of choked flow, liquid surface area increases suddenly, thus needs
Want a large amount of liquid volumes, thus liquid capillary flow forward is created large drag forces, thus play resistance
The effect of stream;After liquid is pushed the stream control chamber 601 of the micro-valve of choked flow by applying pressure, its structural table area is fast
Speed is saturated, and makes choked flow micro-valve that subsequent liquid flowing is not produced obstruction.
Specifically, stream control chamber 601 includes front cavity 602 and the back cavity set gradually by liquid flow direction
Body 603, front cavity 602 is cubic type, and the floor height of front cavity 602 exports less than liquid quantitative mechanism
The floor height of end, the internal diameter of rear chamber 603 is gradually reduced by liquid flow direction.
Embodiment six
Seeing Fig. 1 and Fig. 9, this utility model provides multiple and realizes the PF of function described in embodiment one
Mechanism 5, unlike previous embodiment, although chip body 1 includes chip upper slice 11 and chip bottom sheet
12, but for mounting means, PF mechanism 5 may be configured as dismountable PF mechanism or modular pushes away
Feed liquor mechanism, wherein, as it is shown in figure 1, dismountable PF mechanism is removably connected to chip master
On body 1, and in chip body, it is provided with joint 13;Also can be as it is shown in figure 9, with modular PF machine
The mode integrated setting of structure is in chip body.
For structure, PF mechanism may be configured as multiple, such as existing syringe, liquid-transfering gun etc., all
It is that by pushing to the PF of PF intracavity under pressure the PF mechanism of liquid storage cylinder,
Protection domain of the present utility model all should be fallen into;For syringe and liquid-transfering gun, it is both needed in chip body
Joint is set to connect, simultaneously because need an independent hand propelled or press pressure handle during operation, thus needs
Two handss operate the use that can complete chip simultaneously, have inconvenience more.To this, PF mechanism 5 can be set
It is set to the flat shaped body matched with chip thickness, including pedestal 501, pedestal 501 is provided with piston hole
502, piston hole 502 can be arranged on the end face of pedestal 501, it is possible to is arranged on the side of pedestal 501, seat
Body 501 is internally provided with propelling sap cavity 503, and propulsion unit is piston block 504, and piston block 504 is at piston hole
Relatively slide in 502, the inwall of piston hole 502 is provided with the locating part for limiting piston block monodisplacement.
It should be noted that, the PF mechanism of this structure, could be arranged to dismountable PF mechanism, it is possible to
It is set to modular PF mechanism.If modular PF mechanism, can be as it is shown in figure 9, under the die
On sheet 12, fluting is for advancing sap cavity 503, and on chip upper slice, perforate is piston hole 502, then by chip
Sheet 11 seals with chip bottom sheet 12 phase, then arranges a piston block closed with piston hole 502 matching size.
It addition, it should be noted that, advance sap cavity 503 liquid outlet bottom gradually rise, until be opened in chip
Flush bottom capillary channel in bottom sheet, go out liquid with meet PF.
It is capable of piston block 504 locating part of monodisplacement in piston hole it should be noted that, every,
All should fall into protection domain of the present utility model, relatively simple, locating part is for being disposed side by side in piston hole
A plurality of helical teeth on wall, the outer wall of piston block is provided with the tooth engaged being meshed with helical teeth, passes through tooth engaged
Interlocking to helical teeth, prevents the reverse displacement of piston block;The effect of piston block 504 monodisplacement is to make
Quantitative blood plasma in liquid storage cylinder is discharged, without by the blood plasma sucking-off in collector unit.
Embodiment seven
See Figure 10 and 11, this utility model provide multiple realize function described in embodiment one go out liquid machine
Structure 7, identical with previous embodiment two to five, chip body 1 includes chip upper slice 11 and chip bottom sheet
12, liquid outlet mechanism 7 is arranged in chip bottom sheet 12, and chip upper slice 11 plays the effect of sealing.Go out liquid machine
Structure 7 includes that liquid outlet 701, the inner side of liquid outlet 701 are provided with attachment structure 702, attachment structure be draw-in groove,
Female thread or projection, be mutually matched with the connector on other chip to facilitate, it is achieved position is fixed.Or
Person, liquid outlet mechanism also includes jointing 703, the size of jointing 703 and EP pipe etc. collect container,
Or the connector on other chip is mutually matched, to realize the collection of blood plasma.
Embodiment eight
This utility model also provides for a kind of Whole Blood Filtration and the processing method quantitatively pipetting micro-fluidic chip, including
Following steps:
S1 pretreatment: one piece of PMMA plate cutting is become 100mm*60mm, cut out two pieces standby;
Use 3M 3701-3702 pure transparent double face glue, be attached to smooth for double faced adhesive tape on one of PMMA sheet material,
The sheet material sticking double faced adhesive tape is put on roller bearing press and repeatedly suppress twice, remove double faced adhesive tape and PMMA plate
Bubble in material.
S2 chip manufacture: use CO2 laser machine that pretreated PMMA sheet material is processed.
Pretreated PMMA sheet material double face glue surface is upwards snapped in laser machined die groove;Needs are added
Work figure is edited in Laser Processing software, and adjusting laser power is that 8W is processed;Reprocessabilty
10 times, take off after molding to be processed;The most pretreated for another sheet PMMA sheet material is snapped in Laser Processing mould
In tool groove;Needs graphics processing being edited in Laser Processing software, adjusting laser power is that 8W enters
Row processing;Reprocessabilty 10 times, takes off after molding to be processed;
S3 chip assembles: is cut into appropriately sized by whole blood filter membrane and glass fibre, is sequentially loaded into whole blood seperator
In structure;Tearing the overlay film on double faced adhesive tape off, after the chip fluctuating plate alignment that will process, runner direction is glued inwardly
Close instrument, put into and repeatedly suppress twice on roller bearing press, remove the gas in double faced adhesive tape and PMMA sheet material
Bubble;Check and be bonded whether chip has blocking or gas leakage, PF is sucked push structure, propelling is tied
Structure liquid outlet and the correspondence position tubule of chip assembled connect, then with buckle by push structure
Fix, make total become an entirety.
Embodiment nine
This utility model also provides for using different materials and method prepare Whole Blood Filtration and quantitatively pipette micro-fluidic core
The comparing result of sheet, as follows:
Being respectively adopted PMMA material, glass material, PS material making chip, every kind of chip prepares 5 pieces,
Wherein, the mode of PMMA materials'use Laser Processing is processed into desired structure, and glass material uses photoetching
Mode forms desired structure, and the mode of PS materials'use injection forms desired structure.PMMA materials'use heat
Glue processing is bonded, and glass material uses double faced adhesive tape to be bonded, PS materials'use hot glue and pressure-sensitive cementing
Rubber alloy film is bonded.After being bonded, the chip that three different is connected syringe, the design of three kinds of chips
Quantitatively pipetting capacity is 20ul, and design sample-adding amount is 100ul..
Before bonding completes, use lithium aluminium hydride reduction diethyl ether solution join PMMA material passage is carried out blunt
Change processes.After Passivation Treatment completes, PMMA material chip is bonded.
When using chip, whole blood sample is added separately in the inlet of three chip blocks, treats that serum flows to resistance
When flowing before micro-valve, the blood plasma in three kinds of chips all stopped the capillary flow along duct orientation.Promote PF
The propulsion unit of mechanism, pushes in the liquid storage cylinder of liquid quantitative mechanism by PF, promotes serum specimen forward
Mobile.Now, the serum specimen in three chip blocks all flows in the micro-valve of choked flow, and passes therethrough, from going out liquid
Flow out in Kou.
Treat that Specimen liquid flows out completely from chip, collect in EP pipe respectively, measure three kinds of different chips and receive
The liquid volume that collection arrives.Result is as shown in table 1, according to the meansigma methods of quality difference, it is seen that three kinds of chips are equal
Have and preferably quantitatively pipette effect, be scaled Plasma volumes, meet design and quantitatively pipette capacity 20ul.
1 three kinds of chips of table quantitatively pipette Contrast on effect result
It addition, this utility model also makes a collection of PMMA micro-fluidic chip, its design quantitatively pipettes capacity and is
20ul, design sample-adding amount is 100ul.Use clinic to obtain health examination blood to test.From different specimens
Taking 100ul and join in well, result is as shown in table 2, according to the meansigma methods of quality difference, it is seen that PMMA
Micro-fluidic chip is respectively provided with and preferably quantitatively pipettes effect, and life-time service stability is higher, is scaled blood plasma body
Long-pending, meet design and quantitatively pipette capacity 20ul.
Table 2PMMA micro-fluidic chip life-time service quantitatively pipette Contrast on effect result
The above is only preferred implementation of the present utility model, is not limited to this utility model, should
When pointing out, for those skilled in the art, without departing from this utility model know-why
On the premise of, it is also possible to making some improvement and modification, these improve and modification also should be regarded as this utility model
Protection domain.
Claims (10)
1. a Whole Blood Filtration and quantitatively pipette micro-fluidic chip, it is characterised in that: include chip body, with
And be arranged in chip body whole blood separating mechanism, the micro-valve of anti-backflow, liquid quantitative mechanism, PF machine
Structure, the micro-valve of choked flow and liquid outlet mechanism;Wherein:
Described whole blood separating mechanism includes inlet, whole blood filter membrane and the collector unit set gradually, described entirely
Blood filter membrane is for the blood filtration isolated blood plasma that will enter from inlet, and described collector unit is used for collecting
Blood plasma is also sent to liquid quantitative mechanism through the micro-valve of anti-backflow by the blood plasma of isolated under capillary action;
The micro-valve of described anti-backflow is for stoping the blood plasma adverse current in liquid quantitative mechanism to whole blood separating mechanism;
Described liquid quantitative mechanism includes the liquid storage cylinder for housing quantitative blood plasma;
The micro-valve of described choked flow is arranged on the outfan of liquid quantitative mechanism and for stoping the blood plasma in liquid storage cylinder
Flow out in the case of without ambient pressure;
Described PF mechanism includes the propelling sap cavity for housing PF and propulsion unit, described propelling list
Unit is for pushing to liquid storage cylinder under pressure and by determining in liquid storage cylinder by the PF of PF intracavity
Amount blood plasma pushes to liquid outlet mechanism through the micro-valve of choked flow;
Described liquid outlet mechanism includes liquid outlet, described liquid outlet blood plasma after discharging Quantitative Separation.
Whole Blood Filtration the most according to claim 1 and quantitatively pipette micro-fluidic chip, it is characterised in that:
Described collector unit includes collecting chamber, be arranged in collecting chamber multiple support columns and supporting layer, described
Supporting layer is arranged on the support columns, and described whole blood filter membrane is arranged on described supporting layer, and described inlet is arranged
Above described whole blood filter membrane.
Whole Blood Filtration the most according to claim 2 and quantitatively pipette micro-fluidic chip, it is characterised in that:
The bottom of described collecting chamber is provided with and is arranged as stair-stepping multiple base frame, and described support column is arranged on the described end
On platform, the liquid outlet of described collecting chamber is positioned close to that side with the base frame of extreme higher position.
Whole Blood Filtration the most according to claim 1 and quantitatively pipette micro-fluidic chip, it is characterised in that:
The micro-valve of described anti-backflow is that tongue piece declines valve or the micro-valve of wall-attachment;The described tongue piece valve that declines includes tongue piece, described
Tongue piece on front side of liquid flow direction with the pressure differential of rear side on the occasion of and negative value in the case of respectively open shape
State and closure state;The micro-valve of described wall-attachment includes main channel and the multiple bypasses being connected in parallel on main channel
Passage, described bypass channel two ends are all with identical with liquid flow direction in main channel main logical towards being connected to
On road.
Whole Blood Filtration the most according to claim 4 and quantitatively pipette micro-fluidic chip, it is characterised in that:
The described tongue piece valve that declines includes that valve channel, tongue piece chamber and tongue piece, described tongue piece chamber are arranged on described valve
On body passage, one end of described tongue piece rotates or is fixedly installed on described tongue piece intracavity.
Whole Blood Filtration the most according to claim 1 and quantitatively pipette micro-fluidic chip, it is characterised in that:
Described liquid storage cylinder is capillary tube or capillary channel.
Whole Blood Filtration the most according to claim 1 and quantitatively pipette micro-fluidic chip, it is characterised in that:
The micro-valve of described choked flow includes stream control chamber, and the inlet aperture in described stream control chamber is defeated more than described liquid quantitative mechanism
Going out the aperture of end, the interior direction of inlet without leave in described stream control chamber is gradually reduced to liquid outlet direction.
Whole Blood Filtration the most according to claim 7 and quantitatively pipette micro-fluidic chip, it is characterised in that:
Described stream control chamber includes front cavity and the rear chamber set gradually by liquid flow direction, and described front cavity is vertical
Cube type, the floor height of described front cavity is less than the floor height of described liquid quantitative mechanism outfan, institute
The internal diameter stating rear chamber is gradually reduced by liquid flow direction.
Whole Blood Filtration the most according to claim 1 and quantitatively pipette micro-fluidic chip, it is characterised in that:
Described PF mechanism is dismountable PF mechanism or modular PF mechanism, wherein, described dismountable
PF mechanism is removably connected in described chip body, and is provided with in described chip body
Joint;Described modular PF mechanism integrated setting is in described chip body.
Whole Blood Filtration the most according to claim 1 and quantitatively pipette micro-fluidic chip, it is characterised in that:
Described PF mechanism includes pedestal, and described pedestal is provided with piston hole, and described pedestal is internally provided with and pushes away
Admission chamber, described propulsion unit is piston block, and described piston block slides in described piston hole relatively, described
The locating part for limiting described piston block monodisplacement it is provided with on the inwall of piston hole.
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
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CN105879936A (en) * | 2016-03-31 | 2016-08-24 | 苏州市博纳泰科生物技术有限公司 | Whole blood filtration and quantitative transfer micro-fluidic chip |
EP3457137A4 (en) * | 2017-07-03 | 2019-08-07 | Nanjing Lansion Biotechnology Co., Ltd. | Single-channel chemiluminescence microfluidic chip and detection method thereof |
WO2019205781A1 (en) * | 2018-04-27 | 2019-10-31 | 广州万孚生物技术股份有限公司 | Liquid metering device and use thereof |
CN111604095A (en) * | 2020-05-09 | 2020-09-01 | 东莞市东阳光诊断产品有限公司 | Microfluidic chip, chip control device and operation method thereof |
WO2021073381A1 (en) * | 2019-10-17 | 2021-04-22 | 京东方科技集团股份有限公司 | Microfluidic substrate and fluid driving method therefor, and microfluidic device |
EP3779439A4 (en) * | 2018-04-27 | 2021-04-28 | Guangzhou Wondfo Biotech. Co., Ltd. | Micro-fluidic chip and analysis instrument having same |
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2016
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Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
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CN105879936A (en) * | 2016-03-31 | 2016-08-24 | 苏州市博纳泰科生物技术有限公司 | Whole blood filtration and quantitative transfer micro-fluidic chip |
EP3457137A4 (en) * | 2017-07-03 | 2019-08-07 | Nanjing Lansion Biotechnology Co., Ltd. | Single-channel chemiluminescence microfluidic chip and detection method thereof |
US10648975B2 (en) | 2017-07-03 | 2020-05-12 | Lansion Biotechnology Co., Ltd. | Single channel chemiluminescent micro-fluidic chip and detection method thereof |
WO2019205781A1 (en) * | 2018-04-27 | 2019-10-31 | 广州万孚生物技术股份有限公司 | Liquid metering device and use thereof |
EP3779439A4 (en) * | 2018-04-27 | 2021-04-28 | Guangzhou Wondfo Biotech. Co., Ltd. | Micro-fluidic chip and analysis instrument having same |
WO2021073381A1 (en) * | 2019-10-17 | 2021-04-22 | 京东方科技集团股份有限公司 | Microfluidic substrate and fluid driving method therefor, and microfluidic device |
CN111604095A (en) * | 2020-05-09 | 2020-09-01 | 东莞市东阳光诊断产品有限公司 | Microfluidic chip, chip control device and operation method thereof |
CN111604095B (en) * | 2020-05-09 | 2022-02-15 | 东莞市东阳光诊断产品有限公司 | Microfluidic chip, chip control device and operation method thereof |
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Granted publication date: 20160831 Effective date of abandoning: 20171013 |
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