CN108795729B - A kind of biochip and its micro liquid sampling structure - Google Patents
A kind of biochip and its micro liquid sampling structure Download PDFInfo
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- CN108795729B CN108795729B CN201811135415.4A CN201811135415A CN108795729B CN 108795729 B CN108795729 B CN 108795729B CN 201811135415 A CN201811135415 A CN 201811135415A CN 108795729 B CN108795729 B CN 108795729B
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- sample
- cavity
- quantity tube
- hemofiltration
- hematocrit
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
Abstract
The invention discloses a kind of biochip and its micro liquid sampling structures, wherein micro liquid sampling structure includes quantity tube and hemofiltration structure, quantitative plunger is equipped at the top of quantity tube, quantity tube side wall upper part opens up the sample inlet communicated with quantitative tube cavity, and the bottom of quantity tube opens up sample exit port；The plasma outlet port of hemofiltration structure is connected with sample inlet.The present invention does not need discharge air and forms negative pressure absorbing sample, is easy to be directly integrated in small biochip；Not aeriferous fluid column can be formed in quantity tube in sample introduction, avoids bringing air in the reactor of biochip into, to the testing result of sample without any adverse effect；Red blood cell is not easy to plug filter membrane when prepared by plasma sample, and hemofiltration is abundant, and the hemofiltration time is short, high-efficient, red blood cell is oppressed that risk is low, and sample is not easy to be contaminated, and is particularly suitable for the preparation of biochip blood plasma test sample, testing cost is reduced, testing efficiency is improved.
Description
Technical field
The invention belongs to biochip test field, in particular to a kind of biochip and its micro liquid sampling structure.
Background technique
Existing micro liquid sampling structure includes quantity tube, in use, first excluding the air in quantity tube, then benefit
Micro liquid is quantitatively drawn from certain container with principle of negative pressure to quantity tube, completes sample introduction process.When sampling, by quantity tube
Displacement (mobile or rotation) recycles air that liquid is released quantity tube, achievees the purpose that sampling to designated position.
Existing this micro liquid sampling structure needs to shift in sampling process, thus is difficult or can not be integrated in micro-
In small biochip.This mode is easy to draw air into quantity tube simultaneously, to can inevitably mix air in a liquid
It releases, air is brought into the reactor of biochip, influences biochip to the testing result of sample.
In addition, in the prior art, the plasma sample preparation that biochip test is used all is using vertical hemofiltration form
Hemofiltration structure, hemofiltration structure includes shell, and horizontal positioned filter membrane is equipped in shell, and cover top portion is equipped with opening up
First cavity, shell is interior to be equipped with the second cavity being located at immediately below the first cavity, passes through between the first cavity and the second cavity
Filter membrane connection.When hemofiltration, the first cavity is added in whole blood first, is then pressurizeed to the first cavity airtight, the small blood plasma of molecule will
Filter membrane below the first cavity enters the second cavity, and the big red blood cell of molecule will be detained in the first cavity, to reach
To the purpose of hemofiltration.
In above-mentioned this vertical hemofiltration structure, since red blood cell is detained in the first cavity and can be deposited on the first cavity
On the filter membrane of bottom, with the progress of hemofiltration, the concentration of red blood cell is higher and higher in the first cavity, to be easy blocking filtering
Film causes hemofiltration insufficient, and the time that the sample of filter unit amount needs is elongated, and efficiency reduces, it could even be possible to crushing red thin
Born of the same parents cause sample to fail.
Summary of the invention
Existing micro liquid sampling structure needs to shift in sampling process, is difficult or can not be integrated in small biology
In chip.It is easy sucking air in simultaneous quantitative pipe, air can inevitably be mixed and be released in a liquid, to bring air into life
In the reactor of object chip, biochip is influenced to the testing result of sample.In addition, the blood plasma that existing biochip test is used
Sample preparation is all the hemofiltration structure using vertical hemofiltration form, since red blood cell is detained in the first cavity and can be deposited on the
On the filter membrane of the bottom of one cavity, with the progress of hemofiltration, the concentration of red blood cell is higher and higher in the first cavity, to be easy
Blocking filter membrane causes hemofiltration insufficient, and the time that the sample of filter unit amount needs is elongated, and efficiency reduces, it could even be possible to pressure
Broken red blood cell, causes sample to fail.It is an object of the present invention in view of the above shortcomings of the prior art, provide a kind of biological core
Piece and its micro liquid sampling structure do not need discharge air and form negative pressure absorbing sample, be easy to be directly integrated in small life
In object chip；Not aeriferous fluid column can be formed in quantity tube in sample introduction, avoids bringing air into the anti-of biochip into
It answers in device, to the testing result of sample without any adverse effect；Meanwhile red blood cell is not easy to plug filtering when plasma sample preparation
Film, hemofiltration is abundant, and the hemofiltration time is short, high-efficient, and it is low that red blood cell is oppressed risk.
In order to solve the above technical problems, the technical scheme adopted by the invention is that:
A kind of micro liquid sampling structure, including quantity tube and hemofiltration structure are structurally characterized in that at the top of the quantity tube
Equipped with the quantitative plunger sealed to quantity tube bore seal, the quantity tube side wall upper part opens up the sample communicated with quantitative tube cavity
The bottom of this inlet, quantity tube opens up sample exit port；The plasma outlet port of hemofiltration structure is connected with sample inlet.
By above structure, after Whole Blood Filtration is obtained plasma sample by hemofiltration structure, blood of the plasma sample from hemofiltration structure
Slurry outlet by sample inlet is injected into quantitative tube cavity, since quantity tube upper end seals, lower ending opening, sample automatically into
Quantitative tube cavity, in sample injection process, the air in quantity tube is continued to release from sample exit port by sample, and control injection is quantitative
The sample size of tube cavity finally forms one section of not aeriferous sample fluid column in quantity tube, and providing for accurate quantitative sampling can
Energy.Finally, pressing down on quantitative plunger, the sample in quantity tube can be released on demand.The present invention is empty due to not needing discharge
Gas forms negative pressure absorbing sample, thus is easy to be directly integrated in small biochip；Due to that can be formed in quantity tube
Not aeriferous fluid column, thus sample air entrainment enters in the reactor of biochip when sample-adding, to the testing result of sample
Without any adverse effect.
Micro quantitative determination of the invention refer to the sampling sample size released from quantity tube sample exit port every time be 3 ul to
100ul。
The bottom of quantity tube is coniform as a preferred method, and sample exit port is set to quantitative bottom of the tube minimum point.This
Air is discharged convenient for sample automatically into quantitative tube cavity and from bottom sample exit port in kind form, is more advantageous to be formed without air
Sample fluid column.
As a preferred method, under initial sample introduction state, quantitative plunger bottom surface is coplanar with sample inlet highest point；
Or quantitative plunger bottom surface is located between sample inlet the highest point and the lowest point.
When quantitative plunger bottom surface is located between sample inlet the highest point and the lowest point, it is more advantageous to be formed without air
Sample fluid column.
Sample inlet open height is 1mm ~ 2.5mm, the middle section of quantity tube and the pipe of upper section as a preferred method,
Diameter is 0.5mm ~ 3.5mm.The caliber of quantity tube is designed according to the viscosity of fluid (blood plasma), is discharged convenient for air when sample injection.
Further, the hemofiltration structure includes shell, and filter membrane is equipped in shell, and cover top portion is equipped with opening up
First cavity, shell is interior to be equipped with the second cavity, is connected between the first cavity and the second cavity by filter membrane, filter membrane and level
It is vertical between face；Second cavity is connected with sample inlet.
By above structure, due to vertical between filter membrane and horizontal plane, compared with the existing technology in filter membrane it is horizontal
It places, the filter membrane in the present invention is vertically arranged in the first cavity side.During hemofiltration, even if red blood cell is trapped in first
In cavity, since filter membrane is vertically arranged, since red blood cell is deposited on the first cavity bottom, thus red blood cell is not easy to plug setting
Filter membrane in the first cavity side, thus blood plasma is more unobstructed by filter membrane, hemofiltration is abundant, and the hemofiltration time is short, high-efficient,
It is low to be oppressed risk for red blood cell simultaneously.
Further, hematocrit chamber is additionally provided in shell, hematocrit chamber is connected with the first cavity bottom, hematocrit chamber it is small in size
In the volume of the first cavity, hematocrit chamber is connected by filter membrane with the second cavity, and the volume of hematocrit chamber is greater than or equal to mistake
Filter the total volume of red blood cell in whole blood.
By above structure, the first cavity bottom is connected with hematocrit chamber, and the intracorporal whole blood to be filtered of the first chamber continues past
The intracavitary conveying of hematocrit, then blood plasma passes through filter membrane and enters the second cavity, and it is intracavitary that red blood cell is trapped in hematocrit, reaches hemofiltration mesh
's.It is red thin since the volume of hematocrit chamber is greater than or equal to the total volume of red blood cell in whole blood to be filtered, thus during hemofiltration
Born of the same parents are deposited on hematocrit bottom of chamber portion, and hematocrit chamber upper space is reserved for receiving the whole blood newly injected, and filter membrane is more not easy red
Cell blocking, hemofiltration are more unobstructed.
Further, further including can be to the hemofiltration plunger of the first cavity top opening pressurizing window.
When hemofiltration, driving force is applied to hemofiltration plunger using driving mechanism, so that hemofiltration plunger adds the first cavity airtight
Pressure promotes whole blood to flow toward filter membrane direction, reaches hemofiltration purpose.
The hematocrit chamber connects the highest of the highest point side corresponding thereto of side with filter membrane as a preferred method,
Point is in same level；Alternatively, the hematocrit chamber connects with filter membrane, the highest point of side is higher than the highest of its opposite flank
Point.
Hematocrit chamber connect with filter membrane side highest point be higher than its opposite flank highest point in the case of, filter membrane is less
Easily it is blocked.
It further include described the present invention also provides a kind of biochip, including reactor based on the same inventive concept
Micro liquid sampling structure, the sample exit port are located above reactor.
Compared with prior art, the present invention does not need discharge air and forms negative pressure absorbing sample, is easy to be directly integrated in micro-
In small biochip；Not aeriferous fluid column can be formed in quantity tube in sample introduction, avoids bringing air into biological core into
In the reactor of piece, to the testing result of sample without any adverse effect；Meanwhile red blood cell is not easy to plug when plasma sample preparation
Filter membrane, hemofiltration is abundant, and the hemofiltration time is short, high-efficient, and red blood cell is oppressed that risk is low, and sample is not easy to be contaminated, especially suitable
In the preparation of biochip blood plasma test sample, testing cost is greatly reduced, improves testing efficiency.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of one embodiment of micro liquid sampling structure.
Fig. 2 is to insert filter membrane schematic diagram toward shell insert port.
Wherein, 1 is shell, and 101 be the first cavity, and 102 be the second cavity, and 103 be hematocrit chamber, and 104 be insert port, and 2 are
Filter membrane, 3 be hemofiltration plunger, and 4 be quantity tube, and 401 be sample inlet, and 402 be sample exit port, and 5 be quantitative plunger.
Specific embodiment
As shown in Figure 1, micro liquid sampling structure includes quantity tube 4 and hemofiltration structure, it is equipped at the top of the quantity tube 4 pair
The quantitative plunger 5 of 4 bore seal of quantity tube sealing, 4 side wall upper part of quantity tube open up the sample communicated with 4 inner cavity of quantity tube
Inlet 401, the bottom of quantity tube 4 open up sample exit port 402；The plasma outlet port of hemofiltration structure is connected with sample inlet 401
It is logical.Quantitative plunger 5 can select different material and thickness as needed.
After Whole Blood Filtration is obtained plasma sample by hemofiltration structure, plasma sample passes through sample from the plasma outlet port of hemofiltration structure
Inlet 401 is injected into 4 inner cavity of quantity tube, and due to the sealing of 4 upper end of quantity tube, lower ending opening, sample is automatically into quantity tube 4
Chamber, in sample injection process, the air in quantity tube 4 is continued to release from sample exit port 402 by sample, control injection quantity tube 4
The sample size of inner cavity finally forms not aeriferous sample fluid column in quantity tube 4, provides possibility for accurate quantitative sampling.Most
Afterwards, quantitative plunger 5 is pressed down on, can on demand be released the sample in quantity tube 4.The present invention is not due to needing discharge air shape
At negative pressure absorbing sample, thus it is easy to be directly integrated in small biochip；It is free of due to that can be formed in quantity tube 4
The fluid column of air, thus sample air entrainment when sample introduction is avoided to enter in the reactor of biochip, to the testing result of sample
Without any adverse effect.
The bottom of quantity tube 4 be it is coniform, sample exit port 402 be set to 4 bottom minimum point of quantity tube.Such form is convenient for sample
Air is discharged automatically into 4 inner cavity of quantity tube and from bottom sample exit port 402 in this, is more advantageous to form not aeriferous sample liquid
Column.
Under initial sample introduction state, 5 bottom surface of quantitative plunger is coplanar with 401 highest point of sample inlet；Or quantitative plunger 5
Bottom surface is located between 401 the highest point and the lowest point of sample inlet.When 5 bottom surface of quantitative plunger is located at 401 highest of sample inlet
When between point and minimum point, it is more advantageous to form not aeriferous sample fluid column.
401 open height of sample inlet is 1mm ~ 2.5mm, the caliber of the middle section of quantity tube 4 and upper section be 0.5mm ~
3.5mm.The caliber of quantity tube is designed according to the viscosity of fluid (blood plasma), is discharged convenient for air when sample injection.Except in embodiment
Outside the structure, quantity tube 5 can also use other structures, such as rectangular parallelepiped structure.
The quantity tube 4 is made by hydrophobic material.
The inner surface of the quantity tube 4 is mirror surface.
The hemofiltration structure includes shell 1, and filter membrane 2 is equipped in shell 1, is equipped with opening up first at the top of shell 1
Cavity 101, shell 1 is interior to be equipped with the second cavity 102, is connected between the first cavity 101 and the second cavity 102 by filter membrane 2, mistake
It is vertical between filter membrane 2 and horizontal plane；Second cavity 102 is connected with sample inlet 401.Hematocrit chamber is additionally provided in shell 1
103, hematocrit chamber 103 is connected with 101 bottom of the first cavity, volume of the volume less than the first cavity 101 of hematocrit chamber 103, pressure
Product chamber 103 is connected by filter membrane 2 with the second cavity 102, and the volume of hematocrit chamber 103 is greater than or equal to red in whole blood to be filtered
The total volume of cell.Preferably, vertical between filter membrane 2 and horizontal plane.
By the demand to plasma volume is obtained by filtration, the volume of whole blood to be filtered can be calculated, and then is obtained red in whole blood
The total volume of cell.Such as: if desired 20 microlitres of blood plasma, due to probably there was only 40 ~ 50% blood plasma in the whole blood of people, then
50 microlitres of whole blood is at least needed, there is 25 ~ 30 microlitres of red blood cell in 50 microlitres of whole blood, thus the volume of hematocrit chamber 103 is
25 ~ 30 microlitres or be slightly larger than this value.
Hematocrit chamber 103 can be the regular shapes such as square, cuboid, or anomalistic object.
Due to vertical between filter membrane 2 and horizontal plane, compared with the existing technology in filter membrane 2 it is horizontal positioned, the present invention
In filter membrane 2 be vertically arranged in 103 side of hematocrit chamber.First cavity, 101 bottom is connected with hematocrit chamber 103, the first cavity
Whole blood to be filtered in 101 continues the conveying in hematocrit chamber 103, and then blood plasma enters the second cavity 102 across filter membrane 2, red
Cellular retention reaches hemofiltration purpose in hematocrit chamber 103.
Since the volume of hematocrit chamber 103 is greater than or equal to the total volume of red blood cell in whole blood to be filtered, thus in hemofiltration mistake
Cheng Zhong, red blood cell are deposited on 103 bottom of hematocrit chamber, and 103 upper space of hematocrit chamber is reserved for receiving the whole blood newly injected, due to
Filter membrane 2 is vertically arranged in 103 side of hematocrit chamber, and filter membrane 2 is not easy to be blocked by red blood cell, and hemofiltration is more unobstructed, and hemofiltration is abundant, filter
The blood time is short, high-efficient, while to be oppressed risk low for red blood cell.
Hemofiltration structure further includes can be to the hemofiltration plunger of the first cavity top opening pressurizing window.
When hemofiltration, driving force is applied to hemofiltration plunger 3 using driving mechanism, so that hemofiltration plunger 3 is close to the first cavity 101
Pressurization is closed, promotes whole blood to flow toward 2 direction of filter membrane, reaches hemofiltration purpose.
In the present embodiment, the hematocrit chamber 103 connects the highest of the highest point side corresponding thereto of side with filter membrane 2
(connect with filter membrane 2 highest point of side of the hematocrit chamber 103 can be above its opposite flank to point in same level
Highest point is not shown in the accompanying drawings, but has no effect on those skilled in the art's the understanding of the present invention and realization.In hematocrit chamber
103 highest points for connecting side with filter membrane 2 are higher than in the case of the highest point of its opposite flank, and filter membrane 2 is less susceptible to be blocked
Plug).
The insert port 104 for inserting the filter membrane 2 is opened up on the shell 1.In Fig. 2, the insert port 104 is opened up
In 1 side wall of shell, insert port 104 can also be opened in 1 top of shell or bottom.
It further include the micro liquid sampling structure, institute the present invention also provides a kind of biochip, including reactor
Sample exit port 402 is stated to be located above reactor.
The embodiment of the present invention is described with above attached drawing, but the invention is not limited to above-mentioned specific
Embodiment, the above mentioned embodiment is only schematical, rather than limitation, those skilled in the art
Under the inspiration of the present invention, without breaking away from the scope protected by the purposes and claims of the present invention, it can also make very much
Form, within these are all belonged to the scope of protection of the present invention.
Claims (8)
1. a kind of micro liquid sampling structure, including quantity tube (4) and hemofiltration structure, which is characterized in that quantity tube (4) top
Portion is equipped with the quantitative plunger (5) sealed to quantity tube (4) bore seal, and quantity tube (4) side wall upper part opens up and quantity tube
(4) the sample inlet (401) that inner cavity communicates, the bottom of quantity tube (4) open up sample exit port (402)；The blood plasma of hemofiltration structure
Outlet is connected with sample inlet (401)；
The hemofiltration structure includes shell (1), is equipped with filter membrane (2) in shell (1), is equipped at the top of shell (1) opening up
First cavity (101), shell (1) is interior to be equipped with the second cavity (102), passes through between the first cavity (101) and the second cavity (102)
Filter membrane (2) connection, it is vertical between filter membrane (2) and horizontal plane；Second cavity (102) is connected with sample inlet (401).
2. micro liquid sampling structure as described in claim 1, which is characterized in that the bottom of quantity tube (4) is coniform, sample
This outlet (402) is set to quantity tube (4) bottom minimum point.
3. micro liquid sampling structure as described in claim 1, which is characterized in that under initial sample introduction state, quantitative plunger
(5) bottom surface is coplanar with sample inlet (401) highest point；Or quantitative plunger (5) bottom surface is located at sample inlet (401) highest
Between point and minimum point.
4. micro liquid sampling structure as described in claim 1, which is characterized in that sample inlet (401) open height is
1mm ~ 2.5mm, the middle section of quantity tube (4) and the caliber of upper section are 0.5mm ~ 3.5mm.
5. micro liquid sampling structure as described in claim 1, which is characterized in that be additionally provided with hematocrit chamber in shell (1)
(103), hematocrit chamber (103) is connected with the first cavity (101) bottom, and the volume of hematocrit chamber (103) is less than the first cavity (101)
Volume, hematocrit chamber (103) is connected by filter membrane (2) with the second cavity (102), the volume of hematocrit chamber (103) be greater than or
Equal to the total volume of red blood cell in whole blood to be filtered.
6. micro liquid sampling structure as described in claim 1, which is characterized in that further include that can be pushed up to the first cavity (101)
The hemofiltration plunger (3) of portion's opening pressurizing window.
7. micro liquid sampling structure as claimed in claim 5, which is characterized in that the hematocrit chamber (103) and filter membrane (2)
Connect side highest point side corresponding thereto highest point in same level；Alternatively, the hematocrit chamber (103) and filtering
Film (2) connect side highest point be higher than its opposite flank highest point.
8. a kind of biochip, including reactor, which is characterized in that further include as described in any one of claim 1 to 7 micro
Liquid sample introduction structure, the sample exit port (402) are located above reactor.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811135415.4A CN108795729B (en) | 2018-09-28 | 2018-09-28 | A kind of biochip and its micro liquid sampling structure |
| PCT/CN2019/108336 WO2020063795A1 (en) | 2018-09-28 | 2019-09-27 | Biochip, micro liquid sample loading structure thereof, and micro quantitative sampling method |
| EP19868007.6A EP3858971A4 (en) | 2018-09-28 | 2019-09-27 | Biochip, micro liquid sample loading structure thereof, and micro quantitative sampling method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811135415.4A CN108795729B (en) | 2018-09-28 | 2018-09-28 | A kind of biochip and its micro liquid sampling structure |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108795729A CN108795729A (en) | 2018-11-13 |
| CN108795729B true CN108795729B (en) | 2019-02-05 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201811135415.4A Active CN108795729B (en) | 2018-09-28 | 2018-09-28 | A kind of biochip and its micro liquid sampling structure |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3858971A4 (en) * | 2018-09-28 | 2021-11-17 | Hunan Legend Ai Chip Biotechnology Co., Ltd. | Biochip, micro liquid sample loading structure thereof, and micro quantitative sampling method |
| CN111999488A (en) * | 2019-05-11 | 2020-11-27 | 南京岚煜生物科技有限公司 | Quantitative method convenient for whole blood detection |
| CN110058007A (en) * | 2019-05-12 | 2019-07-26 | 南京岚煜生物科技有限公司 | Single channel micro-fluidic chip |
| CN111707507B (en) * | 2020-06-23 | 2023-02-28 | 合肥安为康医学检验有限公司 | Biochemical quantitative detection device of blood sample |
| CN111829826A (en) * | 2020-06-24 | 2020-10-27 | 温州医科大学 | Blood sample extraction device for gene marker detection |
| CN111939599B (en) * | 2020-07-14 | 2024-01-12 | 山东中保康医疗器具有限公司 | Method and device for preparing platelet-rich plasma |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60119133T2 (en) * | 2000-07-31 | 2007-01-25 | Matsushita Electric Industrial Co., Ltd., Kadoma | BIOSENSOR |
| EP2637788A1 (en) * | 2010-11-10 | 2013-09-18 | Boehringer Ingelheim Microparts GmbH | Device for filtering blood |
| CN203350078U (en) * | 2013-07-19 | 2013-12-18 | 杭州中肽生化有限公司 | Rapid detection device for liquid sample |
| CN205426562U (en) * | 2015-12-21 | 2016-08-03 | 天津市正江高科技有限公司 | Blood serum sampler |
| CN206868242U (en) * | 2017-04-01 | 2018-01-12 | 南京岚煜生物科技有限公司 | Micro-fluidic chip based on the flowing of active control liquid |
| CN107199061B (en) * | 2017-05-28 | 2021-07-27 | 合肥赫博医疗器械有限责任公司 | Application method of multi-task full-automatic biochemical detection chip |
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