CN109174220A - A kind of biochip and chip controls method - Google Patents
A kind of biochip and chip controls method Download PDFInfo
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- CN109174220A CN109174220A CN201811202869.9A CN201811202869A CN109174220A CN 109174220 A CN109174220 A CN 109174220A CN 201811202869 A CN201811202869 A CN 201811202869A CN 109174220 A CN109174220 A CN 109174220A
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- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
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Abstract
The invention discloses a kind of biochip and chip controls methods.The biochip includes chip basal body, and quantitative sampling device, multiple reagent chambers and reactor in chip basal body is arranged in；Each reagent chamber is equipped with the pipeline being connected to the reactor, and normally closed micro-valve is equipped in every root canal road；The quantitative sampling device has sample exit port, and the sample exit port is connected to the reactor.Biochip of the invention combines all advantages of integrated large automatic analysis instrument and biochip, not only strictly realizes the analysis precision of conventional automated analysis instrument, or even has been more than conventional automated analysis instrument in terms of some functions.
Description
Technical field
The present invention relates to a kind of biochip and chip controls methods, belong to biochip field.
Background technique
The prior art is divided into two kinds currently on the market: traditional large automatic analysis instrument detection technique and serial biological core
Chip technology.
As illustrated in fig. 1 and 2, traditional large automatic analysis instrument is using parallel type technology, and this technological merit is energy
Accomplish high-precision quantitative analysis detection.And the characteristics of parallel type technology is that every kind of reagent individually stores, and reacts needs according to detection,
Reagent passes sequentially through independent fluid path and enters the same reactor, realizes the analysis detection to sample.
The advantages of traditional large automatic analysis instrument detection technique, is:
1, sample and reagent can be added to reactor using sample needle accurate quantification.
2, independent pipeline avoids the cross contamination between reagent.
3, various reagents independently store, convenient for handling the reagent for having particular/special requirement.
4, thoroughly, cleaning residue can control in very little CV for reaction cleaning.
It 5, can be in order to doing various detection processings to reactor because be separate reactors.
6, based on above advantage, it can be deduced that the analysis result of an accurate quantification.
For traditional detection analysis instrument while realizing accurate quantification analysis result, there is also some disadvantages:
1, structure is complicated, and maintenance is inconvenient.
2, there are more fluid path and discharging of waste liquid.
3, need to carry out sample needle to clean etc. operation, consumption amount of reagent is big.
4, it can not accomplish portable and point of care diagnostic.
Since there are drawbacks described above, the development of micro-processing technology and material technology is so that biochip becomes a kind of possibility.
And biochip is the process the domain analysis sample such as biology, chemistry, medicine, including the bases such as preparation, reaction, separation, detection
This unit is integrated on one piece several square centimeters or even smaller chip, the overall process of analysis is automatically performed, wherein than more typical
Technology be serial microfluidic chip technology.
As shown in Figures 3 and 4, the serial microfluidic chip technology M2 type analysis core more micro- than more typical such as Shenzhen Hua Maixing
Piece.Wherein string type technology is after being added sample, when a kind of reagent of the every process of sample stores pipeline or storage chamber, this
Pipeline or storage chamber are reacted as reactor.After reaction, under driving force effect, the mixed liquor after reaction is again
The biological respinse that a kind of lower reagent continues next step is flowed to, until final result detects.This serial microfluidic chip technology
There are the advantages of be: chip technology of preparing is simple, and design and manufacture cost is low, and operation is simple, and point of care diagnostic etc. may be implemented.
But because this serial microfluidic chip technology is based on above-mentioned inherent characteristic, it is unable to reach large automatic analysis
The precision of instrument, has the disadvantage in that
1, this method not can avoid cross contamination.
2, this method is unable to reach the accurate sample-adding of amount of reagent.
3, blending process is irreversible, and there are the inconsistent risks of degree of mixedness.
4, cleaning process is irreversible, there is the halfway risk of cleaning.
Based on the above disadvantage, string type biochip is unable to complete the high-precision quantitative analysis of sample.
Biochip technology was developed rapidly at nearly 20 years, especially microflow control technique, new material technology and people
The fast development of work intellectual technology, so that biochip technology gradually moves towards industrialization.But it is micro in present biochip
Quantitative sampling is the problem of a generality.
Microfluidic chip technology is bases such as biology, chemistry, the sample preparation of medical analysis process, reaction, separation, detections
This operating unit is integrated on the chip of one piece of micro-meter scale, is automatically performed analysis overall process.Since it is in biology, chemistry, doctor
The great potential in etc. fields has been developed as the friendship of the subjects such as biology, chemistry, medicine, fluid, electronics, material, a machinery
The brand-new research field of fork.
Existing micro quantitative determination 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, then by quantity tube displacement (mobile or rotation
Turn) to designated position, it recycles air that liquid is released quantity tube, achievees the purpose that sampling.
In existing this micro quantitative determination sampling structure, quantitatively and two independent links is sampled as, is taken again after quantitative
Sample needs to shift, thus is difficult or can not be integrated in small biochip.It is this simultaneously using air to be released liquid
Air can inevitably be mixed and be released in a liquid, so that air be brought into the reactor of biochip, influence biological core by mode
Testing result of the piece to sample.
In addition, micro-fluidic chip agents useful for same is mostly that external injection is added at present, under the effect of outer power drive, make reagent by
Look after flowing.Now micro-fluidic chip detection reagent is added in chip reagent chamber in advance, outside is no longer needed in use process
Inject reagent；And the circulation for being previously implanted reagent is controlled by the variation of micro-fluidic chip micro-valve.
Micro quantitative determination sampling in present biochip is the problem of a generality.Existing micro quantitative determination sampling structure
Including quantity tube, in use, first excluding the air in quantity tube, principle of negative pressure is recycled quantitatively to draw from certain container
Then quantity tube displacement (mobile or rotation) is recycled air by liquid by micro liquid to quantity tube to designated position
Quantity tube is released, achievees the purpose that sampling.
In existing this micro quantitative determination sampling structure, quantitatively and two independent links is sampled as, is taken again after quantitative
Sample needs to shift, thus is difficult or can not be integrated in small biochip.It is this simultaneously using air to be released liquid
Air can inevitably be mixed and be released in a liquid, so that air be brought into the reactor of biochip, influence biological core by mode
Testing result of the piece to sample.
The shortcomings that prior art, mainly detection reagent must be an externally injected into when in use, and the spent time is more and nothing
Method realizes automation, it is therefore desirable to which a kind of structure that micro-valve is isolated with liquid may not flow into meeting liquid during storage micro-
Valve, and micro-valve will not be impacted on storage liquid in change procedure and liquid flowing patency influences.
Chinese invention patent publication number CN1512095C disclose it is a kind of for opening and closing the ice valve of micro-/ nano fluid channel,
Comprising: one be placed on flowing have fluid fluid channel lower end semiconductor cooler and one be located at the semiconductor cooler system
The radiator of cold end or heating end is equipped with the thermally conductive of low thermal resistance high strength insulating varniss composition between semiconductor cooler and radiator
Insulating layer；One is located at the microheater to heat fluid in fluid channel of fluid channel upper surface；The microheater
It to be passed through the steamdrum of steam, be the Mini electric device of charged, or is the miniature laser heater with laser heating source；Half
Conductor refrigerator is made of multiple semiconductor refrigerating wired in parallel；It is a kind of ideal easy convenient for controlling without any moving component
In integrated micro-valve structure.However the patent due to using ice as spool, therefore, it is impossible to for have reagent storage, just
It is not no spool under normal state；Further, ice be easy reacts with reagent, and ice as spool is oversized (can not
Accomplish micron order), it cannot achieve precision control, in addition, if the patent is used for micro-fluidic chip, then also needing in chip
Implantation circuit is wanted, the manufacture difficulty of chip will be further increased in this, reduces its reliability.
Summary of the invention
The present invention is intended to provide a kind of biochip and chip controls method, the biochip creatively combine integrated
All advantages of large automatic analysis instrument and biochip not only strictly realize point of conventional automated analysis instrument
Precision is analysed, or even has been more than conventional automated analysis instrument in terms of some functions.
To achieve the goals above, the technical scheme adopted by the invention is that:
A kind of biochip comprising chip basal body, be arranged in quantitative sampling device in chip basal body, multiple reagent chambers, with
And reactor；Each reagent chamber is equipped with the pipeline being connected to the reactor, and normally closed micro-valve is equipped in every root canal road；Institute
Quantitative sampling device is stated with sample exit port, the sample exit port is connected to the reactor.
According to an embodiment of the invention, can also make further optimization to the present invention, the following are the skills formed after optimization
Art scheme:
Preferred embodiment in accordance with the present invention, the outlet end of the pipeline are respectively positioned on the top of the reactor；The sample goes out
Mouth is located at the top of the reactor.It uses so more convenient, and facilitates processing and manufacturing.
Preferably, the quantitative sampling device and reagent chamber are arranged at the top of chip basal body, the reactor setting
In the lower part of chip basal body.In this way, can enter in reactor by gravity after liquid outflow to be added.
Preferred embodiment in accordance with the present invention, the quantitative sampling device include quantity tube, and the sample exit port setting exists
The lower part of quantity tube；It is preferred that the bottom of the quantity tube be it is coniform, sample exit port is set to quantitative bottom of the tube minimum point.Such shape
Air is discharged convenient for sample automatically into quantitative tube cavity and from bottom sample exit port in formula, is more advantageous to form not aeriferous sample
This fluid column.Meanwhile quantitative bottom of the tube advantageously forms not aeriferous sample fluid column to be coniform, playing a main purpose is to reduce to cut
Face area reduces outlet caliber, reduces remaining, raising precision.
Preferably, the plunger for sealing the quantitative tube cavity is equipped at the top of the quantity tube.
For the ease of carrying out the driving machine moved to sample, the plunger and a driving plunger along quantity tube axial direction
Structure；It is preferred that the quantity tube side is equipped with camera unit, the quantity tube is made of clear material and quantity tube is located at camera shooting list
In first field range, the camera unit is electrically connected with the controller, which is electrically connected with driving mechanism.Camera unit can
The sample image in quantity tube is shot, controller can calculate the injection of sample by the sample image of shooting and release feelings
Condition, to realize accurate control.
Preferably, the quantitative sampling device is connected to by lateral filter structure with injection port.It is highly preferred that described lateral
Filter structure includes the filter membrane being vertically arranged, and the first cavity between filter membrane and injection port is arranged in, and is arranged in filter membrane
The second cavity between quantitative sampling device.It is vertical between filter membrane and horizontal plane, compared with the existing technology in filter membrane
Horizontal positioned, 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
In first 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
The filter membrane of first cavity side is set, thus blood plasma is more unobstructed by filter membrane, hemofiltration is abundant, and the hemofiltration time is short, imitates
Rate is high, while it is low that haemolysis risk occurs under stress.
The bottom of first cavity is equipped with hematocrit chamber, and first cavity, hematocrit chamber and the second cavity are sequentially communicated；It is excellent
Select the volume of the hematocrit chamber less than the volume of the first cavity, the volume of the hematocrit chamber is greater than or equal to red in whole blood to be filtered
The total volume of cell.Since the first cavity bottom is connected with hematocrit chamber, the intracorporal whole blood to be filtered of the first chamber continues toward hematocrit
Intracavitary conveying, 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 purpose.By
It is greater than or equal to the total volume of red blood cell in whole blood to be filtered in the volume of hematocrit chamber, thus during hemofiltration, red blood cell is heavy
Product is in 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 by red blood cell
Blocking, hemofiltration are more unobstructed.
The first cavity top opening, and plunger is installed in the top open part；The injection port is arranged first
Cavity top side, and be in tilted layout.When hemofiltration, driving force is applied to plunger using driving mechanism, so that plunger is to the first chamber
The closed pressurization of body promotes whole blood to flow toward filter membrane direction, reaches hemofiltration purpose.When work, plunger pressure less than in hematocrit chamber, because
It is filtered from filter membrane to the second cavity for extra sample blood plasma, volume of whole blood reduces, so hematocrit chamber is in no pressure shape
Haemolysis risk occurs under stress for state low.
In order to guarantee to close, the first cavity is reliably effective, and when the plunger protrudes into first cavity, which is arrived
The distance of first cavity top end is greater than the outlet end lower extreme point of injection port to the distance of the first cavity top end.Plunger depresses it in this way
Afterwards, the reservoir channel is closed to realize the closing of the cavity in the bottom of plunger.
The quantitative sampling device side is equipped with the insufflation unit being located at outside chip basal body, is provided with air blowing in the chip basal body
Through-hole, one end of the air blown thru-hole is towards the inflatable mouth of the insufflation unit, and one end of the air blown thru-hole is towards the sample
Outlet.After each quantity tube quantitatively releases sample liquid, quantitative trace sample drop adherency is suspended on sample outlet.This
When, air blown thru-hole is passed sequentially through using insufflation unit and crosses gas channel and is blown to sample exit port direction, so as to be adhered to
The quantitative trace sample drop of sample outlet is blown off, neither pollution sample, in turn ensures sample quantitative accuracy.
Sample liquid of the invention is injected into quantitative tube cavity from sample inlet, due to the sealing of quantity tube upper end, lower end
Opening, sample is automatically into quantitative tube cavity, in sample injection process, since the caliber of quantity tube is according to the viscous of fluid (blood plasma)
Degree design is discharged convenient for air when sample injection, and the air in quantity tube is continued to release from sample exit port by sample, control injection
The sample size of quantitative tube cavity, finally forms one section of not aeriferous sample fluid column in quantity tube, mentions for accurate quantitative sampling
For possible.Then, it is moved downward using driving mechanism driving quantitative plunger, controls the stroke of quantitative plunger, will can determine on demand
Sample in buret is quantitatively released.The present invention forms negative pressure absorbing sample due to not needing discharge air, thus is easy directly to collect
At in small biochip；Since not aeriferous fluid column can be formed in quantity tube, thus avoid that air will be had
Sample be added in the reactor of biochip, to the testing result of sample without any adverse effect；By controlling quantitative plunger
Stroke, quantitative and sampling process can be completed in same link, it is simple to operate.
Micro quantitative determination in the present invention refers to that the sampling sample size released from quantity tube sample exit port every time is 3 ul
To 100ul.
Raffinate surplus after drain in reaction tank is toppled in order to be reduced as far as reactor, and the inner wall of the reactor applies
It is covered with hydrophobic material layer；It is preferred that hydrophobic material layer is Micron-nano composites layer or polytetrafluoroethylene ethylene layer.
Preferably, the reactor has pour spout, is equipped with water-absorbent material on the outside of the pour spout, the water-absorbent material with topple over
The contact of mouth edge；It is preferred that the water-absorbent material is blotting paper.The cup body of the reactor has for accommodating reaction liquid as a result,
Reaction tank, by cup body design hydrophobic material layer and rim of a cup design water-absorbent material, such one dredge one inhale, can be by cup
Raffinate surplus in precursor reactant pond is down to accounting generally 1% or so.
The present invention excludes waste liquid using water-absorbent material auxiliary, allows waste liquid to exclude cleaner, and liquid in the chips will not
Exist with flow regime.The present invention increases hydrophobic coating by the inner surface of container in reactor and achievees the purpose that drain is clean.
In order to realize two-way any side drain, there are two pour spout, two pour spouts to be symmetrical arranged for the reactor, and
Water-absorbent material is equipped on the outside of each pour spout.
Preferably, the reactor is made of one piece by polypropylene material, makrolon material or acrylic material.
Absolute construction design is formed in order to separate reaction cup and chip base, is equipped with and is used in the chip basal body
First installation cavity of reactor is installed, the reactor suspension is mounted in first installation cavity；It is preferred that the reactor is logical
Rotating member suspension is crossed to be mounted in first installation cavity；The side wall of the more preferable reactor is equipped with two shafts, and two
Shaft is total to axial line, the turn hole with shaft cooperation is offered on the first installation cavity wall, which passes through described
Shaft pivot joint is suspended in first installation cavity；Or set on the side wall of the reactor there are two turn hole, two turn holes are coaxial
Heart line, the first installation cavity wall are equipped with the shaft cooperated with the turn hole, which is pivotally connected outstanding by the turn hole
It hangs in first installation cavity.When toppling over, liquid inside the reaction tank outflow reactor under self gravity, simultaneously
Under the vibration of vibrating mechanism, reactor opposite chip seat vibration is arrived so that residual liquid is easier to flow out in liquid
When reaction tank mouthpiece, water-absorbent material can be rapidly clean by corresponding liquid absorption, and cup body is being poured out in liquid
It is bundled when outer by water-absorbent material, it will not be to flow liquid presence.
The cooperation of shaft turn hole can preferably drive the relatively described chip base vibration of the reactor, while entire reaction
Device forms motor pattern of playing on a swing under the driving of vibrating mechanism, so that vibrational energy needed for reactor is substantially dropped
It is low and more easily precisely controlled, to reach more preferably mixed effect.
The side of the reactor is equipped with the vibrating mechanism for driving the relatively described chip basal body vibration of the reactor；It is preferred that
The chip basal body is arranged on a pallet, and the vibrating mechanism is mounted on the pallet；It is preferred that the vibrating mechanism packet
The vibrating reed being mounted on pallet is included, and the driving device being mounted on vibrating reed；The top of the vibrating reed is arranged anti-
Answer device bottom side.Cup body side of the present invention is equipped with vibrating mechanism, is not limited to entire vibrating mechanism integral installation and exists
Cup body side, and vibrating mechanism should be included and be arranged below cup body, but the component of vibrating mechanism extends to the feelings of cup body side
Condition is substantially to realize the relatively described chip base vibration of drive response device.
Reactor vibration is driven by the vibration of vibrating mechanism as a result, can realize reaction solution in reactor before the reaction
The mixing of body, reactor of the invention can facilitate control in small space, and structure is simple, be easily installed, vibrates mixing effect
Fruit is good, can be suitble to mix different viscosities, different densities sample liquid.
The top of vibrating reed is arranged in reactor bottom side, in this way, when not needing vibration and mixing, vibrating reed with react
Device does not contact, and when needing to vibrate mixing, the vibration that the vibrating reed of reactor bottom side is arranged in can directly drive reactor
Itself is vibrated.
In order to facilitate liquid reactions situation in observation cup, the cup body is by transparent macromolecule polymer material material system
At.Meanwhile in order to realize lightweight and reduce the purpose of cup body wall thickness, the cup body is by polypropylene material (PP), polycarbonate
(PC) material or acrylic (polymethyl methacrylate, PMMA) material are made of one piece.This integrated formed structure avoids
Existing bond design bring adverse effect.
The bottom of the reactor has the sheet protrusion extended downwardly.It in this way can be real by vibrating the sheet protrusion
The purpose for now driving entire reactor vibration, does not have to direct vibration removing reactor itself.
For the present invention, toppling over drain is not only merely to pour out liquid, and most important index is in reactor
Residual volume want considerably less.And in the art, routine techniques does not go to study, the residual volume after generally toppling over drain be all with
Milliliter is unit, and in other words, conventional drain of toppling over all is not concerned with residual volume.So in view of this consideration, routine techniques does not have
There is motivation to go to study and a kind of topple over drainage structure to cope with the present invention to the use environment for requiring residual volume considerably less.
The present invention by the way of rotary dumping come removal waste fluid, by reaction tank and chip substrate be split as two it is relatively independent
Components, the two are combined together using activity assembly method.Further, the drainage structure of toppling over that the present invention uses does not need volume
Outer driving structure, the driving structure of co-used chip Micropump.
Through the invention topple over drainage structure drain after, residual volume in reactor generally by microlitre as unit of count, it is residual
Surplus accounting is generally 1% or so.
The pipeline includes the first pipeline and the second pipeline；One end of the outlet end of the reagent chamber and the first pipeline connects
Logical, the other end of first pipeline and one end of the second pipeline are separated by normally closed micro-valve, the other end of second pipeline and institute
State reactor connection；There is in first pipeline air column, the normally closed micro-valve of the end thereof contacts of the air column, the air column it is another
Liquid in end thereof contacts reagent chamber, first pipeline are connected to the second pipeline when normally closed micro-valve is opened；It is preferred that the sky
The length of air column is greater than 5mm.The present invention is due to the presence of air-isolation column, and the energy that generates passes through after air column when micro-valve changes
The form of liquid will not be had an impact.In addition, reagent chamber is to laser valve pipeline structure conducive to reagent flowing, fluid temperature and liquid
It is good that body flows patency.Normally closed micro-valve of the invention is normally closed in conventional sense, when needing to open, (preferably by heating device
Laser heating) so that spool is melted or is gasified, to guarantee the first pipeline and the second pipeline connection.
Quantitative control is refined in order to facilitate realizing, first pipeline and the second pipeline caliber are 100 μm -1000 μm,
The valve core diameter of the normally closed micro-valve is 100 μm -1000 μm；And/or the spool of the normally closed micro-valve is along the first pipeline or
The size in two length of pipe directions is 100 μm -1000 μm.
Preferably, the spool of the normally closed micro-valve is made of high molecular polymer.The high molecular polymer refers to by key weight
It is multiply-connected connect made of high molecular weight (usually up to 10~106) compound.
In order to solve the problems, such as micro-valve and integrated chip, the tube wall and second of the spool of the normally closed micro-valve, the first pipeline
The tube wall of pipeline is that material of the same race is made；It is preferred that the side of the chip basal body is equipped with laser light source.It can be reduced in this way
Technology difficulty and processing cost, and there is better sealing.
Normally closed micro-valve described in the present embodiment is the key that microfluidic system execution unit, is realized under the effect of the laser micro-
Switching of the fluid channel of valve from normally closed to normally opened.
Laser described in the present embodiment is a kind of artificial light, is able to achieve directional lighting, and light stability, and wavelength is single, energy
Amount is very big.Preferably, the light source of the laser is blue and violet laser sources.It is preferred that the wave-length coverage of the laser is 400nm-
980nm。
In order to guarantee that the liquid after spool fusing flows into run-off, the flow for influencing pipeline is avoided, to guarantee to manage
Road is unimpeded, and the downstream side that the upstream side of the normally closed micro-valve is equipped with the run-off and/or the spool that are located on the first pipeline is set
There is the run-off being located on the second pipeline.It is highly preferred that the depth of the run-off is in opposite first pipeline or the second pipeline
The recessed 0.5mm-1mm of wall surface；And/or the run-off is 0.5mm- along the size in the first pipeline or the second length of pipe direction
1mm.This design of run-off ensure that the spool after fusing does not influence the flow of pipeline.
Preferably, the fusing point of the normally closed micro-valve is 40 DEG C -170 DEG C, and the gasification temperature of the normally closed micro-valve is 80 DEG C -300
℃.When needing to open normally closed micro-valve in this way, irradiation spool, the fusing of such spool or gasification are pinpointed by laser, the first pipeline and
Second pipeline connection.The tube wall of the spool of the normally closed micro-valve, the tube wall of the first pipeline and the second pipeline is material system of the same race
At being advantageous in that processing cost is lower, and pass through the fusing of laser fixed point or gasification spool, it is ensured that in spool fusing or gas
While change, the tube wall of the tube wall of the first pipeline and the second pipeline will not be melted or gasify.
Preferably, the chip base is formed by cover board and base combination, and the pipe is formed between the cover board and pedestal
Road；It is preferred that the normally closed micro-valve, cover board and pedestal are integrated.
Based on the same inventive concept, the present invention also provides the control methods of the biochip described in one kind comprising
Following steps:
1), sample exit port of the sample through quantitative sampling device quantitatively flows into reactor；
2) the normally closed micro-valve in the pipeline being connected with the reagent chamber for storing reagent, is successively opened as needed, is stored in corresponding
Reagent in reagent chamber, which flows into reactor, to be reacted.
In step 1, whole blood is sent into quantitative sampling device and is filtered acquisition blood plasma, blood plasma quantitatively flows into reactor again
It is interior.In step 2), normally closed micro-valve melts unlatching after passing through the laser light source fixed point irradiation that chip base side is arranged in.
It is a kind of Preferable scheme is that, the present invention injects the desired amount of liquid using preceding in biochip into reagent chamber in advance
After block inlet, liquid end, which arrives between normally closed micro-valve, when injecting liquid passes through air column isolation；It needs for liquid to be delivered to
When reaction chamber, it is radiated on the spool of the normally closed micro-valve by the laser light source being arranged on the outside of normally closed micro-valve and melts spool
Change or gasification, normally closed micro-valve are opened, the first pipeline and the second pipeline connection, liquid flow into reaction chamber out of reagent chamber.
When normally closed micro-valve is opened, when liquid is flowed into reaction chamber out of reagent chamber, due to the first pipeline and the second pipeline
Caliber is smaller, be all it is micron-sized, therefore, can by external force push reagent chamber top the plunger as piston, in this way
It can guarantee that the liquid in reagent chamber flows into reaction chamber as early as possible.
Due to the presence of air column, liquid, which is stored in reagent chamber, be may not flow at normally closed micro-valve, when such micro-valve changes
The energy of generation will not generate big influence to storage liquid.
The present embodiment separates normally closed micro-valve and actuating power source as a result, simplifies the production work of normally closed micro-valve entirety
Skill makes to be easier integrated micro-valve in microfluidic system, considerably reduces the manufacturing cost of microfluidic system.
Compared with prior art, the beneficial effects of the present invention are:
By the way that Micropump, the technological break-through of micro-valve and independent microreactor, we have developed parallel type biochip.With such as
Lower feature:
1, it is designed by the exploitation of micro quantitative determination structure, realizes sample more accurately than traditional large-sized analytic instrument and quantitatively add
Sample.
2, the design of the independent pipeline in chip is realized by micro-valve technology, avoids cross contamination, and do not need pair
Pipeline is cleaned through row.
3, the drop loading techniques of independent development realize the accurate sample-adding of reagent.
4, independent reactor is designed by forming technique, so that cleaning, which mixes, is able to achieve closed-loop control, it is ensured that 100% is mixed
It is even.
5, independent reactor design, by process for treating surface, so that removal waste fluid excludes completely.
6, by the research of water-absorbent material, so that the waste liquid of discharge will not be stored in waste liquid pool with the liquid form of flowing
In, the external zero-emission of waste liquid.
7, using separate reactors, all reaction environments can accomplish high consistency, and environment is to reaction result
Interference also minimizes, and analyzes convenient for the self diagnosis of instrument exception.
8, outside the precision for realizing conventional automated analysis instrument, parallel biochip structure is simple, easy to operate, can
To realize the external zero-emission of waste liquid.
9, the reagent consumption of parallel biochip is minimum.
10, parallel biochip has many advantages, such as portable and point of care diagnostic.
11, quantitative sampling device of the invention will be quantitative and be sampled in the completion of the same link, not need discharge air shape
At negative pressure absorbing sample, micro quantitative determination sampling structure is directly integrated in small biochip；It can be quantitative in sampling
Not aeriferous fluid column is formed in pipe, avoids for the sample with air being added in the reactor of biochip, the inspection to sample
Result is surveyed without any adverse effect；Meanwhile adherency is suspended on quantitative pipe end sample exit port using the mode of non-contact drop
Quantitative trace sample drop blow off in biochip reaction device, sample will not be polluted, sample quantitative accuracy is high；Structure simultaneously
Simply, low in cost, constancy is good.
12, compared with CN1512095C, the present invention does not need refrigeration part, and spool can be accomplished 0.3mm-1mm's
Level is easy to implement precision control.In addition, micro-valve of the invention is normally closed micro-valve, it is only necessary to it is opened when specific, and
It does not need to be again switched off.Finally, spool of the invention will not react with reagent, pollution reagent is avoided.
13, the time is short, there is no the risks of cross contamination, minimum reagent with testing and analyzing for biochip of the invention
Consumption, achievable immediately accurate detection, automation easy to accomplish, the disposable purchase cost of equipment is low, operates the advantages that simple.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of conventional automated analysis instrument；
Fig. 2 is the schematic diagram of conventional automated analysis instrument；
Fig. 3 is the structural schematic diagram of existing string type biochip；
Fig. 4 is the schematic diagram of existing string type biochip；
Fig. 5 is the elevational schematic view of one embodiment of the invention；
Fig. 6 is the schematic diagram of the front portion of chip basal body of the invention；
Fig. 7 is the schematic diagram of the back portion of chip basal body of the invention；
Fig. 8 is the effect picture that liquid is added after reagent chamber；
Fig. 9 is the partial schematic diagram before normally closed micro-valve fusing；
Figure 10 is the partial schematic diagram in normally closed micro-valve fusing；
Figure 11 is the preceding sectional stereogram of Fig. 5；
Figure 12 is the rear sectional stereogram of Fig. 5；
Figure 13 is the structure principle chart that quantitative sampling device of the present invention carries out quantitative sampling；
Figure 14 is the sectional view of Figure 13；
Figure 15 is the circuit module figure of quantitative sampling device work；
Figure 16 is the work flow diagram of quantitative sampling device；
Figure 17 is the software operation timing diagram of quantitative sampling device；
Figure 18 is the working state figure of Figure 13；
Figure 19 is the outline drawing of Figure 13；
Figure 20 is the partial schematic diagram at reaction cup of the present invention；
Figure 21 is the schematic diagram that biochip of the invention is mounted on chip placement tray；
Figure 22 is the vertical section schematic diagram of Figure 21；
Figure 23 is the chip base schematic diagram of an embodiment of the present invention；
In figure
1- shell, the first cavity of 101-, the second cavity of 102-, 103- hematocrit chamber, 105- installation through-hole, 106- air blown thru-hole, 2-
Filter membrane, 3- plunger, 4- quantity tube, 401- sample inlet, 402- sample exit port, 5- plunger, 6- insufflation unit, it is logical that 7- crosses gas
Road, 8- camera unit, 9- controller, 10- reactor, 11- driving mechanism, 12- chip basal body, the first groove of 13-, 14- second
Groove, 15- injection port；16- reagent chamber；17- pipeline；The first pipeline of 171-；The normally closed micro-valve of 172- the second pipeline 18-；19- air
Column；20- quantitative sampling device；21- plunger；22- liquid；23- laser light source；24- water-absorbent material；25- hydrophobic material layer；26-
Vibrating reed；27- vibrating motor；28- sheet protrusion；29- pallet；30- spool；31- cover board；32- pedestal；33- run-off.
Specific embodiment
A kind of biochip, such as Fig. 5, shown in 11,12 comprising chip basal body 12 is arranged in chip basal body 12 and determines
Measure sampling device 20, multiple reagent chambers 16 and reactor 10；Each reagent chamber 16 is equipped with and is connected to the reactor 10
Pipeline 17, in every root canal road 17 be equipped with normally closed micro-valve 18；The quantitative sampling device has sample exit port 402, the sample
This outlet 402 is connected to the reactor 10.The liquid feeding end of the pipeline 17 is connected to the outlet end of the reagent chamber 16, described
The outlet end of pipeline 17 is respectively positioned on the top of the reactor 10；The sample exit port 402 is located at the top of the reactor 10.
Such as Fig. 5-7, shown in 11,12, normally closed micro-valve is divided into the first pipeline 171 and the second pipeline 172 in pipeline 17.It is described
Reagent chamber 16 is for storing liquid 22, and the bottom end of the reagent chamber 16 is connected to one end of the first pipeline 171, first pipeline 171
The other end separated by normally closed micro-valve 18 and one end of the second pipeline 172, the other end of second pipeline 172 and reactor 10
Connection；It is greater than the air column 19 of 5mm, the normally closed micro-valve of the end thereof contacts of the air column 19 in first pipeline 171 with length
18, the other end contact liq 22 of the air column 19, first pipeline 171 and the second pipeline 172 are opened in normally closed micro-valve 18
Shi Liantong.In the present embodiment, the mode that normally closed micro-valve 18 is opened is preferably the valve for using laser fixed point to heat normally closed micro-valve 18
Core, the spool fusing of micro-valve 18 normally closed in this way, so that the first pipeline 171 and the second pipeline 172 form access.
When the unused plunger 21 in 16 upper end of reagent chamber seals, liquid 22 is may not flow into substantially in micro-pipe road 4 when liquid 22 is added,
Liquid stream end-position can be moved down some to such as the position Fig. 6, pre- hydraulic plunger 21 by the effect of 21 pressure of plunger after pre- indentation plunger 21
It sets after determining, the reservation air column 19 between liquid stream tail end and normally closed micro-valve 18 plays being isolated for normally closed micro-valve 18 and liquid 22
Effect.The air retained between liquid stream tail end and normally closed micro-valve 18 in a sealed meter environment reaches an equilibrium state, plunger not
It pushes and in the case that pipeline is obstructed, the position of air-isolation column will not change meeting.As shown in figure 9, chip have passed through top
Rock, due to there is the presence of air column between liquid stream tail end and micro-valve, liquid stream tail end between micro-valve at a distance from remain unchanged.
The top of the reagent chamber 16 is equipped with the plunger 21 as piston.First pipeline 171 and the second pipeline 172 pipe
Diameter is 100 μm -1000 μm, preferably 300um-500um.The valve core diameter of the normally closed micro-valve 18 is 100 μm -1000 μm, most
It is well 300um-500um.The spool of the normally closed micro-valve 18 along 172 length direction of the first pipeline 171 or the second pipeline ruler
Very little is 100 μm -1000 μm, preferably 300um-500um.
The tube wall of the spool of the normally closed micro-valve 18, the tube wall of the first pipeline 171 and the second pipeline 172 is material of the same race
It is made, the side of the chip basal body 12 is equipped with laser light source 23.The upstream side of the spool, which is equipped with, to be located on the first pipeline 171
The downstream side of run-off and/or the spool is equipped with the run-off being located on the second pipeline 172.In this way, when spool melts, it can be with
In automatic stream run-off, to avoid influencing the caliber of the first pipeline 171 and the second pipeline 172, flow is influenced.
The depth of the run-off is opposite first pipeline 171 or the recessed 0.5mm-1mm of 172 inner wall of the second pipeline.Institute
It is 0.5mm-1mm that run-off, which is stated, along the size of 172 length direction of the first pipeline 171 or the second pipeline.
When liquid is added to reagent chamber, the structure that the micro-valve of the present embodiment is isolated with liquid passes through the interior air retained of pipeline
Column is isolated by liquid miniflow with micro-valve, and the generation of air-isolation column is because protecting between liquid stream tail end and micro-valve in a sealed meter environment
The air stayed reaches an equilibrium state, then plunger does not push and in the case that pipeline is obstructed, and the position of air-isolation column will not
It changes, plays the buffer action of micro-valve and liquid, thus the liquid being added will not influence the variation of micro-valve and micro-valve changes
Generated energy will not have an impact to liquid is added.
In addition, as shown in fig. 7, plunger is mounted in reagent chamber upper end, the gap very little of liquid 23 and plunger 21, generally 0-
3mm, in this way, biochip is during reverse rock, the activity space very little in liquid, the magnetic bead in liquid can be in always
Liquid is not exposed in air in impregnating.
A kind of biochip, such as Fig. 5-7, shown in 11,12, including chip basal body 12, the chip basal body 12 are interior equipped with more
Shielding system between a micro-valve and liquid, the reagent chamber 16, the first pipeline 171, the second pipeline 172 and reactor
10 are provided in chip basal body 12.Shielding system between each micro-valve and liquid shares a reaction chamber.
A method of liquid being controlled using the shielding system between the micro-valve and liquid, as shown in Figure 8 comprising
Following steps:
S1, it is injected in advance into reagent chamber 16 after the desired amount of liquid 22 through the closure inlet of plunger 21, as shown in FIG. 8 and 9,
Liquid end is completely cut off between normally closed micro-valve 18 by air column 19 when injecting liquid 22；Since reagent chamber has one to micro-valve pipeline
Determine warp architecture, and when micro-valve is not destroyed pipeline configuration be it is closed, liquid end has one section of sky to micro-valve when injecting liquid
Air column isolation, liquid may not flow at micro-valve.
S2, when needing liquid being delivered to reactor 10, as shown in Figure 10, by the way that swashing for normally closed 18 outside of micro-valve is arranged in
The fixed point of radiant 23 is radiated on the spool of the normally closed micro-valve 18 and spool is melted or gasified, and normally closed micro-valve 18 is opened, the
One pipeline 171 is connected to the second pipeline 172, and liquid 23 flows into reactor 10 out of reagent chamber 16.Changed as a result, by micro-valve
Pipeline is set to become to circulate, since the energy generated when the isolation structure of pre-implant liquid and micro-valve changes micro-valve will not be to storage
Liquid storage body has an impact.
In order to guarantee that the liquid in reagent chamber is flowed into as early as possible in reactor 10, plunger 21 can be depressed as needed, thus
Liquid 23 is pressed out to reactor 10 by the first pipeline 171 and the second pipeline 172 from reagent chamber 16.
The present embodiment injects solution in the reagent chamber of chip in advance as a result, and when reagent is injected in reagent chamber, reagent chamber is arrived
There is one section of air column isolation in micro-valve pipeline, liquid may not flow into normally closed micro-valve 18 during storage, and normally closed micro-valve 18 exists
The energy generated in change procedure will not impact storage liquid, and reagent chamber has certain warp architecture to micro-valve pipeline, no
Can have an adverse effect to liquid flowing patency.
The spool of the normally closed micro-valve of the present embodiment blocks between the first pipeline 171 and the second pipeline 172.The normally closed micro-valve
The tube wall of 18 spool, the tube wall of the first pipeline 171 and the second pipeline 172 is that material of the same race is made.The fusing point of the spool
It is 40 DEG C -170 DEG C, preferably 100 DEG C -120 DEG C.The boiling point of the spool is 80 DEG C -300 DEG C.The valve of the normally closed micro-valve 18
Core is made of high molecular polymer.The diameter of the spool is 0.5mm.The internal diameter of first pipeline 171 and the second pipeline 172
For 0.5mm.In order to improve extinction efficiency, the valve core outer surface is equipped with dark coating.Preferably black coating or preferred valve
Core is made of black material.The time of fusing or the spool that gasifies can be shortened in this way.The laser light source is blue and violet laser sources.
The wave-length coverage of the laser is 400nm-980nm.
Conventional sense bottom spool is non-fusible as a result, or gasifies, and micro-valve is normally closed, when needing to open, (preferably by heating device
For laser heating) so that spool is melted or is gasified, to guarantee that pipeline is unimpeded.
Micro-valve start-up course is as follows: first with the penetrability of laser, making laser penetration chip basal body 12, by laser focal pair
Quasi- micro-valve spool position.Due to the high-energy of laser, after absorbing laser photon energy, normally closed micro-valve 18 can be heated rapidly spool
Deformation fusing or gasification, are divided out (as shown in Figure 10) along tube wall, and the pipeline of blocking is just got through originally, realize micro-valve
It opens, laser irradiation time 0.1s-30s.
According to the embodiment of the design run-off of the present embodiment, when spool mutually becomes liquid, in gravity and surface tension
Under effect, the spool for becoming liquid flows to run-off position, to realize the unimpeded of the first pipeline 171 and the second pipeline 172.
Laser light source as actuating power is located at chip exterior, is not required to install with integrated chip, and performance is stablized, and can repeatedly weigh
It is multiple to use, be conducive to the commercial applications of micro-fluidic chip.
The micro-valve of the present embodiment possesses that structure is simple, simple processing compared to common micro-valve, is not required to integrate, low in cost,
It is easy the advantages that producing in enormous quantities.
For being not easy the spool of extinction, dark pigment can be smeared on its surface, to improve its extinction efficiency, to realize
The control function of micro-valve.
As shown in figure 13, it is equipped with reactor 10 in the chip substrate 12 of the present embodiment, is additionally provided in chip substrate 12 quantitative
Pipe 4, the bottom of quantity tube 4 open up sample exit port 402；The sample exit port 402 is located at 10 top of reactor；The quantity tube 4
Top is equipped with the quantitative plunger 5 sealed to 4 bore seal of quantity tube, and 4 side wall upper part of quantity tube opens up and 4 inner cavity of quantity tube
The driving mechanism that the sample inlet 401 communicated further includes controller 9, quantitative plunger 5 can be driven to move axially along quantity tube 4
11, controller 9 is electrically connected with driving mechanism 11, and driving mechanism 11 is connected with the driving of quantitative plunger 5.Quantitative plunger 5 can be according to need
Select different material and thickness.
Micro quantitative determination sampling structure can be an entirety with 10 connection of reactor, or two independences not interconnected
Component.
4 lateral wall of quantity tube is equipped with the first groove 13 and the second groove 14, and the first groove 13 is located on the second groove 14
Side.
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.Meanwhile quantitative bottom of the tube advantageously forms not aeriferous sample fluid column to be coniform, playing a main purpose is to reduce section face
Product reduces outlet caliber, reduces remnants, improves precision.
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 4 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 or 4 inner wall of quantity tube has hydrophobic coating.
The inner surface of the quantity tube 4 is shiny surface.
Biochip further includes camera unit 8, and quantity tube 4 is made of clear material and quantity tube 4 is located at the view of camera unit 8
In the range of field, camera unit 8 is electrically connected with controller 9.Camera unit 8 can shoot the sample image in quantity tube 4, controller
9 can calculate injection and release situation of the sample in quantity tube 4 by the sample image received, to realize accurate control
System.
Biochip further includes insufflation unit 6, and shell 1 is equipped in chip substrate 12, and shell 1 is equipped with installation through-hole 105,
4 lower section of quantity tube protrudes into the installation through-hole 105, is opened up under connection 6 gas outlet of insufflation unit and quantity tube 4 on 1 side wall of shell
The air blown thru-hole 106 of section forms between 4 lower section of quantity tube and installation through-hole 105 and is connected to air blown thru-hole 106 and sample exit port 402
Outer wall crosses gas channel 7.
In Figure 14, the gas outlet of insufflation unit 6 is set to 106 side of air blown thru-hole, in fact, insufflation unit 6 goes out
Port may be set according to actual conditions, that is, can adjust according to the actual situation between 6 gas outlet of insufflation unit and shell 1
Whether distance, the gas outlet that insufflation unit 6 may be set according to actual conditions need to protrude into inside shell 1.Meanwhile insufflation unit
The blowing direction of 6 gas outlets also can according to need setting, and blowing direction can be all directions of air blown thru-hole up and down,
It can laterally blow, can also vertically blow, air blowing can also be tilted.
After each quantity tube 4 quantitatively releases sample liquid, quantitative trace sample drop adherency is suspended on sample exit port 402
Place.It blows at this point, passing sequentially through air blown thru-hole 106 using insufflation unit 6 and crossing gas channel 7 to 402 direction of sample exit port, thus
The quantitative trace sample drop being adhered at sample exit port 402 can be blown off, neither pollution sample, in turn ensure that sample is quantitative
Precision.
After drop is blown off, has sub-fraction and remain in the end of quantity tube 4 (air cannot blow away all liquid completely
Body), but this part residual be every time it is stable, it is a part of that this is contained when quantitatively sample be discharged in quantity tube 4
Residual, to not influence quantitative accuracy.The installation through-hole 105 is up big and down small conical bore.
What above structure was formed, which crosses gas channel 7, can change the flow direction of air, air-flow effectively be collapsed, so that air
Focused airflow blows to the drop top adhered at sample exit port 402, and drop is vertically dropped down onto and is referred to below sample exit port 402
Determine in region, will not be dispelled, be further ensured that sample quantitative accuracy.4 lateral wall middle section of quantity tube fits with shell 1.One
Aspect can prevent air from flowing upwards, on the other hand can also ensure that positioning of the quantity tube 4 in shell 1.
The tracheae that the insufflation unit 6 includes air pump, is connected with air pump gas outlet, control terminal and the controller 9 of air pump
Output end electrical connection, the gas outlet of tracheae and air blown thru-hole 106 are opposite.Contactless air blowing supplementary structure further includes camera unit
8 and controller 9, sample exit port 402 be located in 8 field range of camera unit, camera unit 8 and insufflation unit 6 with controller 9
Electrical connection.After each quantity tube 4 quantitatively releases sample liquid, quantitative trace sample drop adherency is suspended on sample exit port 402
Place.It blows at this point, passing sequentially through air blown thru-hole 106 using insufflation unit 6 and crossing gas channel 7 to 402 direction of sample exit port, thus
The quantitative sample droplets being adhered at sample exit port 402 can be blown off, neither pollution sample, in turn ensure the quantitative essence of sample
Degree.
Camera unit 8 can shoot the Liquid particle image at sample exit port 402, while camera unit 8 sends out the data of acquisition
It send to controller 9, controller 9 calculates the volume of drop according to image processing method, and controller 9 is according to the fixing fabric structure of drop
The output quantity of insufflation unit 6, it is ensured that different size of sample droplets can be refined blows off vertically.Droplet size is big, then
6 air-blowing quantity of insufflation unit is big, air pressure is big, the time is long；Droplet size is small, then 6 air-blowing quantity of insufflation unit is small, air pressure is small, the time is short.
Hemofiltration structure is equipped in shell 1, hemofiltration structure includes the filter membrane 2 in shell 1, is equipped with and opens at the top of shell 1
The first cavity 101 of mouth upward, 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 is connected to, which is characterized in that vertical between filter membrane 2 and horizontal plane；Second cavity 102 is connected with sample inlet 401
It is logical.
Preferably, hematocrit chamber 103 is additionally provided in shell 1, hematocrit chamber 103 is connected with 101 bottom of the first cavity, hematocrit chamber
103 are connected by filter membrane 2 with the second cavity 102.First cavity 101, hematocrit chamber 103, filter membrane 2, the second cavity 102 according to
Secondary connection.Less than the volume of the first cavity 101, the volume of hematocrit chamber 103 is greater than or equal to be filtered full the volume of hematocrit chamber 103
The total volume of red blood cell in blood.
The elevation of highest point relative level of side of connecting on hematocrit chamber 103 with filter membrane 2 is a, on hematocrit chamber 103 with
The elevation of the highest point relative level of 2 opposite flank of filter membrane is b, in the present embodiment, a=b.
A can also be greater than b, and such situation is not shown in the accompanying drawings, but has no effect on those skilled in the art to this hair
Bright understanding and realization.In a > b, filter membrane 2 is less susceptible to be blocked.
The insert port for inserting the filter membrane 2 is opened up on the shell 1.The insert port is opened in 1 side wall of shell,
Insert port can also be opened in 1 top of shell or bottom.2 periphery of filter membrane is handled with flexible glue bound edge, when installation, filter membrane
2 are interference fitted with insert port side wall, play sealing function, prevent sample side leakage excessive.
Hemofiltration structure further includes can be to the plunger 3 of 101 top opening pressurizing window of the first cavity.Driving mechanism 11 and plunger
3 drivings are connected.
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 one section of not aeriferous sample fluid column in quantity tube 4, and providing for accurate quantitative sampling can
Energy.Then, it drives quantitative plunger 5 to move downward using driving mechanism 11, controls the stroke of quantitative plunger 5, will can determine on demand
Sample in buret 4 is quantitatively released.The present invention forms negative pressure absorbing sample due to not needing discharge air, thus is easy directly to collect
At in small biochip；Since not aeriferous fluid column can be formed in quantity tube 4, thus avoid that air will be had
Sample be added in the reactor 10 of biochip, to the testing result of sample without any adverse effect；By controlling quantitative column
The stroke of plug 5 can complete quantitative and sampling process in same link, simple to operate.
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.
Filter membrane 2 is vertically arranged, and hemofiltration effect is best, efficiency highest.
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 it is low that haemolysis risk occurs under stress.
Driving mechanism 11 is mobile motor.Driving mechanism 11 and plunger 3, quantitative plunger 5 connection relationship not attached
It is shown in figure, but has no effect on those skilled in the art's the understanding of the present invention and realization.
When hemofiltration, driving force is applied to plunger 3 using driving mechanism 7, so that plunger 3 is to the closed pressurization of the first cavity 101,
Promote whole blood to flow toward 2 direction of filter membrane, reaches hemofiltration purpose.When work, the pressure of plunger 3 is less than in hematocrit chamber 103, because extra
Sample blood plasma filter from filter membrane 2 to the second cavity 102, volume of whole blood reduces, so hematocrit chamber 103 is in no pressure shape
Haemolysis risk occurs under stress for state low.
The control method of above-mentioned biochip includes the following steps:
1), reagent is filled in each reagent chamber 16；
2), whole blood is sent into quantitative sampling device 20 and is filtered acquisition blood plasma, sample of the blood plasma through quantitative sampling device 20
Outlet 402 quantitatively flows into reactor 10；
3) the normally closed micro-valve 18 in each pipeline 17, is successively opened as needed, and reagent 17, which flows into reactor 10, to be reacted.
Specifically, step 2 is divided into following steps:
Plasma sample is injected 4 inner cavity of quantity tube from sample inlet 401 by step A.；
Step B. plasma sample reaches 4 bottom of quantity tube；
Step C. quantitative plunger 5 is moved axially downwards along quantity tube 4, and a certain amount of plasma sample is released out of quantity tube 4；
Step D. plasma sample enters reactor 10.
In the step B, when plasma sample reaches the first groove 13 on quantity tube 4, stop injecting into quantity tube 4
Plasma sample, meanwhile, quantitative plunger 5 moves axially downwards along quantity tube 4 and pushes down on plasma sample, when in quantity tube 4
Plasma sample when reaching the second groove 14 being located under the first groove 13 on quantity tube 4, as plasma sample reaches quantitative
4 bottom of pipe.
The stroke that quantitative plunger 5 when a certain amount of plasma sample is released quantity tube 4 is calculated using controller 9, is controlled simultaneously
Device 9 drives quantitative plunger 5 mobile according to the stroke of calculating by driving mechanism 11.
As shown in Figure 15 and Figure 16, specific micro quantitative determination sampling method of the invention is as follows:
First, whole blood sample is injected into the first cavity 101 by injection port 15.
Second, after biochip inspection, drive plunger 3 to move down by driving mechanism 11 by controller 9.
Third, after the filtration of filter membrane 2, plasma sample is injected whole blood sample by the second cavity 102, sample
Mouth 401 enters 4 inner cavity of quantity tube.
4th, plasma sample reaches the first groove 13 on quantity tube 4, and the intake of camera unit 8 arrives plasma sample image simultaneously
It is sent to controller 9, after controller 9 identifies, control plunger 3 stops pushing, filter ring section end.
5th, controller 9 drives quantitative plunger 5 to move down by driving mechanism 11, carries out precompressed to plasma sample.
6th, plasma sample reaches the second groove 14 on quantity tube 4, and the intake of camera unit 8 arrives plasma sample image simultaneously
It is sent to controller 9, after controller 9 identifies, control quantitative plunger 5 stops pushing, filter ring section end.
7th, controller 9 calculates the stroke for taking a certain amount of plasma sample that quantitative plunger 5 is also needed to push, and issues instruction
It drives quantitative plunger 5 to move down according to calculated stroke value by driving mechanism 11, releases the sample size of needs.In this reality
It applies in example, the stroke of driving quantitative plunger 5 is calculated according to being accumulated at sampling amount with 4 intracavity section of quantity tube.
8th, quantitative plasma sample adheres to be formed after the discharge of 4 quantification of quantity tube at the sample exit port 402 of quantity tube 4
The sample droplets of micro quantitative determination (less than 50 microlitres), drop are suspended at sample exit port 402.It is empty to control the blowout of air pump gas outlet
Gas, the air of blowout after air blown thru-hole 106, concentrate after the gathering effect for crossing gas channel 7 by the air flowed downwards
Drop top is blowed to, so that drop is fallen into vertically downward in reactor 10, drop, which will not be dispelled, sputters reactor 10
Or 10 side wall of reactor is blowed to, guarantee sample quantitative accuracy.Wherein, the output quantity of air pump is adopted by controller 9 according to camera unit 8
The calculated droplet size control of the Liquid particle image of collection.
As illustrated in figs 20-22, the reactor 10 includes for accommodating reaction liquid cup body；It is opened up in chip base 12
There is the installation cavity of an accommodating reactor, reactor suspension is mounted in the installation cavity.The inner wall of the cup body applies
It is covered with hydrophobic material layer 25, preferably Micron-nano composites layer or polytetrafluoroethylene ethylene layer.It is equipped with and inhales on the outside of the rim of a cup of cup body
Water material 24, water-absorbent material are preferably macromolecule composite absorbent paper.The water-absorbent material 24 is contacted with the rim of a cup edge of cup body.
As shown in figure 20, the cup body side is equipped with the vibration for driving the relatively described chip base 12 of the reactor to vibrate
Mechanism.The outside wall surface of the reactor is mounted on the wall surface of the installation cavity by rotating member suspension, and such cup body can phase
Chip base 12 is swung.As shown in figure 20, as one embodiment, the side wall of the cup body be equipped with two shafts, two
Shaft is total to axial line, and the turn hole with shaft cooperation is offered on the installation cavity wall, which passes through the shaft pivot
It connects and is suspended in the installation cavity.The embodiment equivalent as another is set on side wall of cup body there are two turn hole, two
Turn hole is total to axial line, and the installation cavity wall is equipped with the shaft cooperated with the turn hole, which is pivotally connected by the turn hole
It is suspended in the installation cavity.
When toppling over waste liquid, since reactor 10 is assembled on chip base 12, and be placed in chip base 12 with instead
Answer the water-absorbent material 24 of the outlet edge contact of device 10.Water-absorbent material 24 is preferably macromolecule composite absorbent paper.
The entire chip of the present embodiment is placed on a pallet of detecting instrument, whole when needing to exclude waste liquid
A chip is that center of rotation rotates counterclockwise around the center of circle of reaction bottom of pond portion.Pass through the knot for being designed to easily be dehydrated by reaction tank
Structure is inclining in this way after using hydrophobic material, such as Micron-nano composites or polytetrafluoroethylene (PTFE) design on the pond inner wall of reaction tank
When, while under the vibration of vibrating mechanism, reactor opposite chip seat vibration, so that residual liquid is easier
It flowing out, the liquid inside reaction tank flows out reaction tank under self gravity, when liquid has arrived the outlet edge of reaction tank, water suction
Material can be rapidly clean by corresponding liquid absorption, so that the liquid being poured out outside cup body be bundled by water-absorbent material
It firmly, will not be to flow liquid presence.
In order to facilitate liquid reactions situation in observation cup, the cup body is by transparent macromolecule polymer material material system
At.Meanwhile in order to realize lightweight and reduce the purpose of cup body wall thickness, the cup body is by polypropylene material, makrolon material
Or acrylic material is made of one piece.This integrated formed structure avoids existing bond design bring adverse effect.This
The cup body of embodiment uses light-weight design, and product wall ratio is relatively thin, improves cup body transparency, convenient for the examination shallower to color
Agent is identified, to expand use scope.
The reactor of the present embodiment is designed using absolute construction, and reactor quality is small, so vibration mixes the exciting needed
Power is small, and reaction solution can be carried out adequately vibration and mixed by low power vibrating motor, and will not be to other in chip
Part have an impact, while conveniently in micro- reaction reaction and actual reagent amount make corresponding detection.
In order to guarantee that reaction solution is mixed well in reaction, as shown in figs. 21 and 22, the chip base 12 is arranged one
On a chip placement tray 29, the vibrating mechanism is mounted on the chip placement tray 29.The vibrating mechanism includes peace
Vibrating reed 26 on chip placement tray, and the micro flat ribbon vibrating motor 27 being mounted in 26 side wall surface of vibrating reed.
As shown in figure 20, the bottom of the reactor has the sheet protrusion 28 extended downwardly；The top of the vibrating reed 26
Portion has U-shaped prong like, and the sheet protrusion 28 is located in the U-shaped region of U-shaped prong like, even if the piece of reactor lower part
Shape protrusion 28 is just inserted into U-shaped prong like.In this way, reactor lower bottom part is a sheet protrusion 28, vibrating reed 26
Head is U-shaped prong like, and the metal vibration plate of a commercially available micro flat ribbon vibrating motor 27 is fixed in the side of vibrating reed 26.
After flat vibration motor connects suitable DC voltage, the eccentric vibrating that motor generates produces metal vibration plate
Life is of reciprocating vibration similar to tuning fork.Vibrate the lower sheet protrusion that the amplitude generated acts on reactor by U-shaped prong like
On, realize reactor around own rotation axis of reciprocating vibration, so that reaching makes the vibration of inside reactor liquid mix effect
Fruit.
The reactor of the present embodiment is a kind of independent levitation component of cup body independently of matrix itself, material selection and
Motor pattern etc. by arrying main body do not influenced limitation movement special cup body, convenient for related reagent suspension reactor reaction tank
Middle progress chemiluminescence reaction, detection, calibration.
The reactor of the present embodiment uses independent design, can be easy design and process some have particular/special requirement, special knot
The microreactor of structure, while independent design is used, because not needing to be bonded again, eliminating bonding bring influences.Now with skill
Closed space can just be formed by needing two parts to be bonded together in art, and glue may overflow pollution examination in bonding process
Agent, surface evenness is not high is bonded with gap for bonding, and reaction reagent may flow out, and the above problem occur will have a direct impact on analysis result
Accuracy.
Under the premise of not needing external complex structure, the present invention can be realized the clean exclusion waste liquid of chip, existing chip
The residual volume of drain is 1%, and following data is the experimental data of 20 groups of samplings of random continuous during test.Experimental condition: reaction
After 400ul cleaning solution is added in device 10, then topple over, surveys residual volume.0.001g=1ul.
As shown in figure 23, laser light source 23 is equipped on the outside of chip base 12, the laser light source 23 is for institute of melting or gasify
It states the spool 30 of normally closed micro-valve 18 and opens the normally closed micro-valve 18.As shown in figure 22, valve is equipped in the micro fluid circuits 17
Micro fluid circuits 17 are separated into the first pipeline 171 and the second pipeline 172 by core 30, the spool 30, and when spool 30 is opened first
Pipeline 171 is connected to the second pipeline 172；The spool 30 is identical as the tube wall material of micro fluid circuits 17, the outer wall of described matrix 6
There is transparent material, the purpose that transparent material is arranged is easy for laser and passes through, to pinpoint fusing or gas between face and spool 30
Change the spool.In the present embodiment, the mode that normally closed micro-valve 18 is opened preferably uses laser fixed point to heat normally closed micro-valve 18
Spool, micro-valve 18 normally closed in this way spool fusing so that the first pipeline 171 and the second pipeline 172 formation access.
In order to facilitate manufacture, a kind of embodiment is that the normally closed micro-valve 18 includes spool 30 and by chip cover board 31 and chip
The valve body that pedestal 32 is formed, forms micro fluid circuits 17 between the chip cover board 31 and chip pad 32, the spool 30 blocks
In the micro fluid circuits 17.The chip cover board 31 and chip pad 32 are made of dark material, preferably black material system
At the fusing point of the spool 30 is below the fusing point of cover board 31 and pedestal 32 higher than the fusing point of room temperature and spool 30.The spool
30 fusing point is 40 DEG C -170 DEG C, preferably 100 DEG C -120 DEG C.The boiling point of the spool 30 is 80 DEG C -300 DEG C.The spool
It is made of high molecular polymer.The diameter of the spool is 0.5mm.The internal diameter of the micro fluid circuits 17 is 0.5mm.Described first
The internal diameter of pipeline 171 and the second pipeline 172 is 0.5mm.
The material not strong to laser absorption rate, it is difficult to generate fuel factor and melt or gasify, can be smeared on its surface layer deep
Color coating, preferably black coating or the spool are made of black material, using dark color to the strong absorbent of laser, improve
Its surface makes its temperature distortion to the absorption efficiency of laser photon, opens micro fluid circuits.
The laser light source 23 is blue and violet laser sources.The wave-length coverage of the laser is 400nm-980nm.
When manufacture, the first pipeline 171 and the second pipeline 172, the first pipeline 171 and the second pipeline are directly opened up on matrix
172 are coaxially arranged and are separated by the spool.The aperture end of first pipeline 171 and the second pipeline 172 is blocked by plunger
?.
As shown in figure 23, the upstream side of the spool is equipped with the run-off 33 or the spool being located on the first pipeline 171
Downstream side be equipped with the run-off 33 being located on the second pipeline 172, be all provided on best first pipeline 171 and on the second pipeline 172
There is run-off 33.In this way, when spool melts, it can be in automatic stream run-off, to avoid influencing the first pipeline 171 and second
The caliber of pipeline 172, influences flow.The depth of the run-off is under opposite 172 inner wall of first pipeline 171 or the second pipeline
Recessed 0.5mm-1mm.The run-off is 0.5mm-1mm along the size of 172 length direction of the first pipeline 171 or the second pipeline.
The present invention using laser penetrability and focus positioning, by specific wavelength, power, power level laser penetration table
Face translucent material focuses on predetermined micro-valve position, recycles the fuel factor of laser energy, so that spool 2 is absorbed laser photon and turns
Turn to thermal energy.Spool 30 is heated to keep the pipeline blocked originally unimpeded by processes such as deformation, thawing, gasifications, realizes miniflow keyholed back plate
Closed state is routed to open state.
Micro-valve is not only that spool 30 Micro-flow pipe can be jammed in, and to realize that pipeline is closed, can also directly utilize
Chip material makes micro-valve, at this point, the spool 30, chip cover board 31 and chip pad 32 are integrated.It can be direct
Micro-valve structure is placed on chip structure in chip design, the machine-shaping together with chip.Such micro-valve structure is not present
The integration problem of micro-valve and chip can be greatly lowered processing cost and technology difficulty, and have more preferable airtightness.
Micro-valve start-up course is as follows: first with the penetrability of laser, making the transparent cover plate on laser penetration upper layer, by laser coke
Away from alignment micro-valve spool position.Due to the high-energy of laser, after absorbing laser photon energy, spool 30 can be heated rapidly spool
Deformation is melted or gasification, divides out along tube wall, and the pipeline of blocking is just got through originally, realizes the unlatching of micro-valve, and laser shines
Time most fast 2s or so is penetrated, the wave-length coverage of laser is 400nm-980nm.The implementation of design run-off according to the present invention
Example, when spool mutually becomes liquid, under the action of gravity and surface tension, the spool for becoming liquid flows to run-off position, from
And realize the unimpeded of micro fluid circuits 17.
Laser light source as actuating power is located at chip exterior, is not required to install with integrated chip, and performance is stablized, and can repeatedly weigh
It is multiple to use, be conducive to the commercial applications of micro-fluidic chip.
Micro-valve of the invention possesses that structure is simple, simple processing compared to common micro-valve, is not required to integrate, low in cost, holds
The advantages that easily producing in enormous quantities.
For being not easy the spool of extinction, dark pigment can be smeared on its surface, to improve its extinction efficiency, to realize
The control function of micro-valve.
The normally closed micro-valve 18 of the present embodiment has the advantages that
1, the actuating power steady sources of micro-valve, are not take up micro-fluidic chip resource, and valve core structure is simple, and micro-valve is easy to collect with chip
At process equipment and raw material are of less demanding, and production cost is greatly lowered, and are suitable for mass production and commercially use.
2, micro-valve opening speed is fast, and 2s or so can puncture spool, realizes the unlatching of micro-valve.Laser energy is high, expands
The material range of micro-valve is not limited to low melting point phase-change material.Laser beam energy is concentrated, and laser spot and breakdown time are controlled,
It can be achieved only to hit micro-valve spool, the other parts structure and material of microfluidic system not damaged, application prospect is extensive.
3, normally closed micro-valve 18 and actuating power source separate, and simplify the manufacture craft of micro-valve entirety, make microfluidic system
It is upper to be easier integrated micro-valve, the manufacturing cost of microfluidic system is considerably reduced, the micro- of extensive industrialization is applicable to
The generation and use of flow control system.
Claims (23)
1. a kind of biochip, which is characterized in that including chip basal body (12), the quantitative sampling being arranged on chip basal body (12)
Device (20), multiple reagent chambers (16) and reactor (10)；
Each reagent chamber (16) is equipped with the pipeline (17) being connected to the reactor (10), is equipped in every root canal road (17)
Normally closed micro-valve (18)；
The quantitative sampling device has sample exit port (402), and the sample exit port (402) is connected to the reactor (10).
2. biochip according to claim 1, which is characterized in that the outlet end of the pipeline (17) is respectively positioned on described anti-
Answer the top of device (10)；The sample exit port (402) is located at the top of the reactor (10).
3. biochip according to claim 1, which is characterized in that the quantitative sampling device (20) and reagent chamber (16)
It is arranged at the top of chip basal body (12), lower part of reactor (10) setting in chip basal body (12).
4. biochip according to claim 1, which is characterized in that the quantitative sampling device (20) includes quantity tube
(4), lower part of sample exit port (402) setting in quantity tube (4)；It is preferred that the bottom of the quantity tube (4) is coniform, sample
This outlet (402) is set to quantity tube (4) bottom minimum point.
5. biochip according to claim 1, which is characterized in that it is described fixed to be equipped with sealing at the top of the quantity tube (4)
The plunger (5) of buret (4) inner cavity；It is preferred that the plunger (5) is moved with a driving plunger (5) along quantity tube (4) axial direction
Dynamic driving mechanism (11)；It is preferred that quantity tube (4) side is equipped with camera unit (8), the quantity tube (4) is by transparent material
It is made and quantity tube (4) is located in camera unit (8) field range, the camera unit (8) is electrically connected with controller (9), should
Controller (9) is electrically connected with driving mechanism (11).
6. biochip according to any one of claims 1-5, which is characterized in that the quantitative sampling device (20) is logical
Lateral filter structure is crossed to be connected to injection port (15).
7. biochip according to claim 6, which is characterized in that the lateral filter structure includes the mistake being vertically arranged
Filter membrane (2), the first cavity (101) being arranged between filter membrane (2) and injection port (15), setting is filter membrane (2) and quantitative
The second cavity (102) between sampler (20).
8. biochip according to claim 7, which is characterized in that the bottom of first cavity (101) is equipped with hematocrit
Chamber (103), first cavity (101), hematocrit chamber (103) and the second cavity (102) are sequentially communicated；It is preferred that the hematocrit chamber
(103) volume is less than the volume of the first cavity (101), and the volume of the hematocrit chamber (103) is more than or equal to whole blood to be filtered
The total volume of middle red blood cell.
9. biochip according to claim 7, which is characterized in that the first cavity (101) top opening, and at this
Top open part is equipped with plunger (3)；Injection port (15) setting is in tilted layout in the first cavity (101) top side.
10. biochip according to any one of claims 1-5, which is characterized in that the quantitative sampling device (20)
Side, which is equipped with, is located at the insufflation unit (6) of chip basal body (12) outside, is provided with air blown thru-hole (106), institute in the chip basal body (12)
One end of air blown thru-hole (106) is stated towards the inflatable mouth of the insufflation unit (6), one end of the air blown thru-hole (106) is towards institute
State sample exit port (402).
11. biochip according to any one of claims 1-5, which is characterized in that the inner wall of the reactor (10)
Coated with hydrophobic material layer (25)；It is preferred that hydrophobic material layer (25) is Micron-nano composites layer or polytetrafluoroethylene ethylene layer.
12. biochip according to any one of claims 1-5, which is characterized in that the reactor (10), which has, to be inclined
Mouth, pour spout outside are equipped with water-absorbent material (24), which contacts with pour spout edge；It is preferred that the water suction
Material (24) is blotting paper；It is preferred that there are two pour spouts for the reactor (10), two pour spouts are symmetrical arranged, and are each toppled over
Water-absorbent material (24) are equipped on the outside of mouthful.
13. biochip according to any one of claims 1-5, which is characterized in that set in the chip basal body (12)
There is the first installation cavity for installing reactor (10), reactor (10) suspension is mounted in first installation cavity；It is excellent
The reactor (10) is selected to be mounted in first installation cavity by rotating member suspension；
The side wall of the more preferable reactor (10) is equipped with two shafts, and two shafts are total to axial line, first installation cavity
The turn hole with shaft cooperation is offered on inner wall, which is suspended on first peace by shaft pivot joint
In behaveing affectedly；Or
It is set on the side wall of the reactor (10) there are two turn hole, two turn holes are total to axial line, and described first installs on cavity wall
Equipped with the shaft cooperated with the turn hole, which is suspended in first installation cavity by turn hole pivot joint.
14. biochip according to any one of claims 1-5, which is characterized in that the side of the reactor (10)
Equipped with the vibrating mechanism for driving relatively described chip basal body (12) vibration of the reactor (10)；It is preferred that the chip basal body (12)
It is arranged on a pallet (29), the vibrating mechanism is mounted on the pallet (29)；It is preferred that the vibrating mechanism includes peace
Vibrating reed (26) on pallet (29), and the driving device being mounted on vibrating reed (26)；The vibrating reed (26)
Top is arranged in reactor bottom side；It is preferred that the bottom of the reactor (10) has the sheet extended downwardly raised (27).
15. biochip according to any one of claims 1-5, which is characterized in that the pipeline (17) includes first
Pipeline (171) and the second pipeline (172)；The outlet end of the reagent chamber (16) is connected to one end of the first pipeline (171), this
The other end of one pipeline (171) and one end of the second pipeline (172) are separated by normally closed micro-valve (18), second pipeline (172)
The other end be connected to the reactor (10)；There are air column (19) in first pipeline (171), the air column (19)
The normally closed micro-valve of end thereof contacts (18), the liquid in another end in contact reagent chamber (16) of the air column (19), first pipeline
(171) it is connected to the second pipeline (172) when normally closed micro-valve (18) are opened；It is preferred that the length of the air column (19) is greater than 5mm.
16. biochip according to claim 15, which is characterized in that first pipeline (171) and the second pipeline
(172) caliber is 100 μm -1000 μm, and spool (30) diameter of the normally closed micro-valve (18) is 100 μm -1000 μm；And/or institute
It is 100 μ that the spools (30) of normally closed micro-valve (18), which is stated, along the size of the first pipeline (171) or the second pipeline (172) length direction
m-1000μm。
17. biochip according to claim 15, which is characterized in that the spool (30) of the normally closed micro-valve (18),
The tube wall of one pipeline (171) and the tube wall of the second pipeline (172) are that material of the same race is made；It is preferred that the chip basal body (12)
Side is equipped with laser light source (23).
18. biochip according to claim 15, which is characterized in that the upstream side of the normally closed micro-valve (18) is equipped with position
It is equipped with and is located on the second pipeline (172) in the downstream side of run-off (33) and/or the spool (30) on the first pipeline (171)
Run-off (33)；
It is preferred that the depth of the run-off (33) is that opposite first pipeline (171) or the second pipeline (172) inner wall is recessed
0.5mm-1mm；And/or the run-off (33) is along the size of the first pipeline (171) or the second pipeline (172) length direction
0.5mm-1mm。
19. biochip according to any one of claims 1-5, which is characterized in that the normally closed micro-valve (18) is melted
Point is 40 DEG C -170 DEG C, and the gasification temperature of the normally closed micro-valve (18) is 80 DEG C -300 DEG C.
20. biochip according to any one of claims 1-5, which is characterized in that the chip base (11) is by covering
Plate (31) and pedestal (32) are composed, and form the pipeline (17) between the cover board (31) and pedestal (32)；It is preferred that described
Normally closed micro-valve (18), cover board (31) and pedestal (32) are integrated.
21. a kind of control method of the biochip as described in any one of claim 1-20, which is characterized in that including as follows
Step:
1), sample exit port (402) of the sample through quantitative sampling device (20) quantitatively flows into reactor (10)；
2) the normally closed micro-valve in the pipeline (17) being connected with the reagent chamber (16) for storing reagent, is successively opened as needed
(18), the reagent being stored in corresponding reagent chamber (16), which flows into reactor (10), to be reacted.
22. the control method of biochip according to claim 21, which is characterized in that in step 1), whole blood is sent into
Acquisition blood plasma is filtered in quantitative sampling device (20), blood plasma quantitatively flows into reactor (10) again.
23. the control method of biochip according to claim 21, which is characterized in that in step 2), normally closed micro-valve
(18) it is melted and is opened after the laser light source fixed point irradiation of chip base (12) side by setting.
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|---|---|---|---|
| CN201811202869.9A CN109174220B (en) | 2018-10-16 | 2018-10-16 | Biochip and chip control method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811202869.9A CN109174220B (en) | 2018-10-16 | 2018-10-16 | Biochip and chip control method |
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| CN109174220B CN109174220B (en) | 2023-11-14 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109999934A (en) * | 2019-04-29 | 2019-07-12 | 上海观流智能科技有限公司 | A kind of microfluidic test device |
| CN110308296A (en) * | 2019-07-10 | 2019-10-08 | 深圳金迈隆电子技术有限公司 | A kind of on piece laboratory |
| CN110523448A (en) * | 2019-09-03 | 2019-12-03 | 广东顺德工业设计研究院(广东顺德创新设计研究院) | Droplet preparation system and preparation method |
| CN113156100A (en) * | 2021-04-29 | 2021-07-23 | 南阳理工学院 | Tumor drug resistance detection device based on artificial intelligence |
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| CN109999934A (en) * | 2019-04-29 | 2019-07-12 | 上海观流智能科技有限公司 | A kind of microfluidic test device |
| CN110308296A (en) * | 2019-07-10 | 2019-10-08 | 深圳金迈隆电子技术有限公司 | A kind of on piece laboratory |
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| CN114130434A (en) * | 2020-09-03 | 2022-03-04 | 湖南乐准智芯生物科技有限公司 | Method for adjusting droplet size of microfluidic biochip and application thereof |
| CN114130434B (en) * | 2020-09-03 | 2023-04-11 | 湖南乐准生物科技有限公司 | Method for adjusting droplet size of microfluidic biochip and application thereof |
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| CN113156100A (en) * | 2021-04-29 | 2021-07-23 | 南阳理工学院 | Tumor drug resistance detection device based on artificial intelligence |
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