CN104492508A - Ultramicro droplets manipulator based on liquid residues and method thereof - Google Patents
Ultramicro droplets manipulator based on liquid residues and method thereof Download PDFInfo
- Publication number
- CN104492508A CN104492508A CN201410640394.7A CN201410640394A CN104492508A CN 104492508 A CN104492508 A CN 104492508A CN 201410640394 A CN201410640394 A CN 201410640394A CN 104492508 A CN104492508 A CN 104492508A
- Authority
- CN
- China
- Prior art keywords
- liquid
- drop
- probe
- getting
- array chip
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Physical Or Chemical Processes And Apparatus (AREA)
Abstract
The invention discloses an ultramicro droplets manipulator based on liquid residues. which comprises a porous plate, an ultramicro droplets array chip; a liquid collecting probe comprising a support part and a liquid collecting end at bottom of the support part; wherein the surface of the liquid collecting end has endophilicity to liquid to be collected, and the external surface of the support part has no endophilicity to liquid to be collected; and a switching mechanism; so that the sampling process of the liquid collecting probe on the liquid to be collected as well as sample placing processes that the liquid to be collected is placed in the ultramicro droplets array chip can be carried out in order. The invention also discloses a method for control the ultramicro droplets based on liquid residues. According to the invention, volume precision with lower than PL grade and even low to FL grade to AL grade can be reached, consumption of samples and reagents in chemical and biology reaction and analysis can be effectively reduced, experiment cost is saved, driving parts such as an injection pump and a peristaltic pump as well as pipelines such as capillary are not required, system operation is simple, reliability is high, array form and automation can be easily realized.
Description
Technical field
The invention belongs to the Microfluidic droplet analysis field in analytical chemistry, specifically relate to a kind of ultramicron liquid drop control device and method based on liquid residue.
Background technology
The liquid manipulation method and apparatus of trace plays a part more and more important in the development of present analysis chemical field.On the one hand, the reduction of liquid manipulation volume decreases the demand to rare sample, significantly reduces experiment difficulty and cost.On the other hand, the bulk effect of microbody system avoids the excess dilution to submicrosample, thus achieves the chemical analysis task that conventional large volume system has been difficult to, as unicellular and single molecule analysis.Microfluidic chip technology is by micro electronmechanical process technology, the substrate such as glass or plastics is processed the micro scale channel of networking, and in conjunction with the drivings such as pressure, electricity, magnetic, light, sound, heat and control method, the ultramicron liquid in passage is manipulated, thus complete micro biochemical reaction and analyze.Microflow control technique has become the platform technology of micro liquid manipulation, is widely used in the fields such as chemistry and bioanalysis, chemical synthesis, drug screening, medical diagnosis, group research.
Microflow control technique based on drop is a kind of novel micro liquid manipulation fast-developing in recent years and biochemical analysis technology.Drop microflow control technique is by the manipulation to two-phase liquid immiscible in microchannel or micro-structural, realize skin to rise to and receive the quantitative generation, mixing, division, screening etc. of upgrading water-in-oil type (or oil-in-water type) drop reactor, thus the liquid manipulation operation needed for conventional chemical and biological respinse can be completed on ultramicron volume.Compared with Continuous Flow (single-phase) microflow control technique, drop microflow control technique eliminates dilution and the diffusion of reactant or product in microreactor, and significantly improves mass transfer and heat transfer rate in reactor.Meanwhile, the oil-water interfaces of bio-compatible, also for ultramicron biochemical reaction provides gentle homogeneous microenvironment, effectively improve its reaction efficiency.
At present, most liquid droplet system all adopts has formation and the manipulation that microchip that is T-shaped or cross focus type passage carries out drop.Size and two-phase flow velocity generally by regulating passage regulate size and generated frequency (Thorsen T, Roberts R W, Arnold F H, Quake S R., Phys.Rev.Lett., 2001,86:4163 ~ 4166 of drop; Anna S L, Bontoux N, Stone H A., Appl.Phys.Lett., 2003,82:364 ~ 366).In order to inject sample or reagent solution carries out biochemical reaction mensuration in drop, main employing two class methods: a kind of is adopt T-shaped passage continuous sample to be injected into (Zheng B in different drops, Ismagilov R F., Angew.Chem.Int.Ed., 2005,44:2520 ~ 2523); Another kind adopts the drop that two or more are contained different component by fluid pressure or electronic method to carry out merging (Niu X, Gulati S, Edel J B, deMello A J., LabChip, 2008,8:1837 ~ 1841; Mazutis L, Araghi A F, Miller O J, Baret J C, FrenzL, Janoshazi A, Taly V, Miller B J, Hutchison J B, Link D, Griffiths A D, Ryckelynck M., Anal.Chem., 2009,81:4813 ~ 4821).This kind of liquid drop control technology based on microchannel network has drop formation and manipulation speed is fast, and automaticity advantages of higher, is particularly suitable for the application scenario needing to carry out extensive liquid drop control.But also there are some obvious limitation in this kind of drop technique.First, these class methods are difficult to generate fast the drop of different chemical composition and concentration, limit its application in the high-flux medicaments sifting etc. taking Multi-example as principal character.Secondly, adding to realize sample the pressure or electrical means that adopt with droplet coalescence, all needing the composition to drop and oil phase, the flow velocity of drop, position accurately controls, operation easier is large, and the cost of chip needed for it is also higher.In addition, because drop is stored in closed chip channel, be difficult to from drop, directly sample the analysis carrying out next step and measure.
Recently, the seminar at applicant place has developed a kind of liquid drop control method (Fang Qun, Zhu Ying, Zhang Yunxia based on planar droplet array, there is a using method for the automation microlayer model array screening system of skin upgrading precision, application number: 201210589055; Zhu Ying, Fang Qun, Zhang Yunxia, Zhu Lina, the continuous point sample of drop and liquid feeding method under a kind of oil of semi-contact, application number: 201410161574; Zhu Y., Zhang Y.X., Cai L.F., Fang Q., Anal.Chem., 2013,85:6723 ~ 6731).Be different from the method for generation and manipulation drop in closed channel, the method carries out the manipulation of drop in the planar chip being coated with certain thickness oil phase.The method adopt based on syringe pump, peristaltic pump or other carry out the quantitative extraction of liquid based on pressure-actuated two-way liquid driven system, in the capillary channel drawing point, generate drop, and the drop in capillary is dropped in planar chip by combined high precision D translation platform.Because the drop storage chip being coated with one deck oil phase is a kind of open liquid droplet system, adding and sampling of sample can directly be realized by method capillary being inserted drop.Therefore, liquid drop control system based on two-dimentional droplet array solves that Conventional drop system is difficult to generate a large amount of different chemical composition drop, liquid feeding is complicated, cost is high, be difficult to the feature that samples, in high throughput chemical and bioanalysis and screening, single cell analysis, medical diagnosis etc., have great application potential.But, owing to adopting the liquid measuring method based on syringe pump, peristaltic pump equal pressure actuation techniques, be subject to the impact of mechanical movement precision and capillary channel interface stress, the liquid manipulation volume of its system usually rises at tens of skin and receives upgrading, is difficult to the ultramicron liquid volume that accurately manipulation rises lower than skin.Especially for the system can carrying out ultramicron liquid manipulation in the level of upgrading lower than skin of Multi-example, there is no bibliographical information at present.
Summary of the invention
The object of this invention is to provide one and can have skin liter (10
-12rise) below, be even low to moderate Ah's upgrading (10 of ascending to heaven
-15to 10
-18rising) this device of ultramicron liquid drop control device based on liquid residue of liquid manipulation precision adopts surface to be had the solid of affinity interaction get liquid probe to getting liquid, utilize it getting liquid end surfaces and remain the phenomenon of a small amount of liquid when departing from and being got liquid, in Microfluidic droplet system, realize the drop formation of ultramicron, get liquid, the complicated liquid manipulation such as mixing and transfer.
Invention also provides a kind of ultramicron liquid drop control method based on liquid residue, the method is applicable to the chemistry of ultramicron and bioanalysis, high-flux medicaments sifting, protein crystallization condition screening, single cell analysis, single molecule analysis etc. need in the occasion of ultramicron liquid manipulation.
Based on a ultramicron liquid drop control device for liquid residue, comprising:
Porous plate, this porous plate is provided with one or morely is got the hole slot of liquid for holding;
Microfluidic droplet array chip, this Microfluidic droplet array chip is provided with one or more micro-structural for carrying drop;
Get liquid probe, this sample probe has support part and be positioned at support member base end get liquid end; Described liquid end surfaces of getting is to being more than or equal to described support partial outer face by the compatibility of getting liquid to being got the compatibility of liquid;
Switching mechanism, realize successively getting liquid probe to got the sampling operation of liquid and by get and got the setting-out that liquid is placed in Microfluidic droplet array chip and operate.Described switching mechanism can adopt three-dimensional motion workbench.
Described liquid probe of getting for adopting the processing of glass, quartz, metal or macromolecule polymer material, described in get liquid probe profile be solid aciculiform or solid cylindricality.Described liquid probe of getting is divided into and gets liquid end and support part two parts.Described surface of getting liquid end is had compatibility to getting liquid, or the surface of getting liquid end is processed into the surface got liquid to compatibility, and the surface of described support part is not had compatibility to getting liquid.Or the surface of support part is processed into the surface got liquid to without compatibility.
The described shape of the cross section of liquid probe of getting is for circle, or ellipse, or triangle, or quadrangle, or other polygons.The described areal extent getting the cross section of liquid probe is 100 square nanometers to 1000 square millimeter.The described length range getting liquid probe is 1 micron to 10 centimetres; Adopt multiple liquid probe formation one dimension of getting to get liquid probe array, or two dimension get liquid probe array, can complete Multi-example manipulation.
The described area getting liquid end surfaces is 100 square nanometers to 1000 square millimeter.According to the character of got liquid, select suitable materials processing to get liquid probe, described in selecting respectively, get region suitable on liquid probe as sampling end and the support part of getting liquid probe; As described in get liquid probe the surface of getting liquid end and support part can not reach requirement to by the compatibility of getting liquid, then adopt the grinding of physics or polishing or illumination method, or adopt corrosion or adsorption or the surface grafting method of chemistry, respectively the surface of getting liquid end and support part of getting liquid probe is processed, make the surface of getting liquid end be had compatibility to getting liquid, the surface of support part is not had compatibility to getting liquid.
Described Microfluidic droplet array chip, for adopting the processing of glass, quartz, metal or macromolecule polymer material, described Microfluidic droplet array chip is processed with the micro-structural of carrying drop.The shape of the micro-structural that described Microfluidic droplet array chip is processed is spill, or convex, or plane-shaped structure, and as preferably, described micro-structural is the groove structure be arranged in Microfluidic droplet array chip, planar structure, columnar projections structure; The volume range carrying drop in described micro-structural is that 1 Ah rises to 1 milliliter.
According to the character of institute's handling liquids, utilize physics or chemical method, the surface of described micro-structural is processed, make surface have compatibility to handling liquids.As preferably, described micro-structure surface is had compatibility to getting liquid.
As preferably, described in get liquid end be planar structure or pyramidal structure.Adopting this technical scheme, liquid measure can be got as required, being adjusted by the degree of depth of getting in liquid getting the immersion of liquid end.
Described porous plate can adopt commercial 96 orifice plates, or 384 orifice plates, or 1536 orifice plates, or other types orifice plate, is got liquid for loading and storing.Based on a ultramicron liquid drop control method for liquid residue, comprising:
(1) mobilely get liquid probe or porous plate, get liquid probe described in making and insert and got in liquid in porous plate hole slot, make to get liquid probe and get the part surface of liquid end or all surfaces and be immersed into and describedly got in liquid, dip and got liquid in porous plate; The surface of getting liquid probe support part can not be immersed or part immerses and got in liquid;
(2) mobilely get liquid probe or porous plate, the liquid end of getting making to get liquid probe departs from and is got liquid in porous plate, gets liquid end upper surface and is formed and got liquid drop; In this step, got the liquid end surfaces of getting that liquid residue is getting liquid probe on a small quantity and formed drop, complete and get liquid operation; This operation also can be described as the operation dipping liquid; Immerse got in the process of liquid at described liquid probe of getting, the surface of getting liquid probe support part is residual is got liquid, or it is residual, and to be got the amount of liquid that amount of liquid gets liquid end residual relatively minimum, can be left in the basket;
(3) liquid probe or Microfluidic droplet array chip are got in movement, make to get liquid probe get liquid end surfaces by the microstructured contact got on liquid drop and Microfluidic droplet array chip, part is got liquid rotating and to be moved on on Microfluidic droplet array chip in micro-structural; Micro-structural end face on described Microfluidic droplet array chip is coated with and is got the immiscible oil phase of liquid;
(4) liquid probe or Microfluidic droplet array chip are got in movement, the liquid end of getting getting liquid probe is made to depart from Microfluidic droplet array chip, formed by the drop getting liquid in the micro-structural of Microfluidic droplet array chip, complete the operation generating drop on described Microfluidic droplet array chip.
Carrying out, step (1) is front, can according to being got the character of liquid, respectively the surface of getting liquid end and support part of getting liquid probe is selected or processed in advance, the surface of getting liquid end described in making is had compatibility to getting liquid, and the surface of described support part is not had compatibility to getting liquid.Then add in the hole slot of porous plate and multiplely got liquid, by the kind of getting liquid be in chemistry and biological respinse, analysis and screening required for sample or reagent.
For realizing the married operation of two kinds of drops, as preferably, carrying in advance in described micro-structural and being got the different drop of liquid.Adopt the operation of step (1), other getting that liquid probe inserts in porous plate container are got in liquid, make to get liquid probe to get the part surface of liquid end or all surfaces and be immersed into and describedly got in liquid, the liquid end surfaces of getting getting liquid probe described in utilization dips liquid in this container; Then according to step (3), move and get liquid probe or Microfluidic droplet array chip, make to get liquid probe get liquid end surfaces by the drop contact that the micro-structural of getting on liquid drop and Microfluidic droplet array chip carries in advance, described two drops mutually mix (fusion) and form new drop, complete drop filling operation or two droplets mixings (fusion) operation; The drop that micro-structural on described Microfluidic droplet array chip carries in advance can adopt the above-mentioned operation of the present invention to be formed, or adopt institute in the micro-structural of additive method on Microfluidic droplet array chip preformed, or adopt and get the liquid probe drop got on liquid end surfaces from another and replace the drop that the micro-structural on Microfluidic droplet array chip carries in advance to carry out filling operation or the operation of two droplets mixings.
Complete after aforesaid operations completes, move and get liquid probe or Microfluidic droplet array chip, the liquid end of getting getting liquid probe is made to depart from the new drop that the micro-structural of Microfluidic droplet array chip is formed, also remained partially liq in the new drop formed at the liquid end surfaces of getting getting liquid probe, completed and get liquid operation from this drop; Complete from drop get liquid operation also can adopt following method, move and get liquid probe or Microfluidic droplet array chip, another is got liquid end surfaces without the getting liquid probe or get liquid probe with a small amount of blank affine liquid of affine liquid, first the drop that the micro-structural of Microfluidic droplet array chip carries is inserted, and then depart from this drop, remain partially liq in this drop at the described liquid end surfaces of getting getting liquid probe, completed and get liquid operation from this drop.
Get some or all of surface that liquid probe gets liquid end described in the present invention utilizes to dip and got liquid in porous plate or in drop, carry out getting liquid operation; By reduce with by get liquid comes into contact get liquid probe get liquid end surface area, reduce get liquid measure, getting liquid volume range is that 0.1 Ah rises to 1 milliliter.
The present invention can adopt multiple liquid probe of getting to form and get liquid probe array, parallel carry out plurality of liquid get liquid, mixing and transfer operation, complete high-throughout chemistry and biological respinse, analysis and screening.As preferably, described in get in liquid probe array and get the number of liquid probe and the position of probe and commercial 96 orifice plates, or 384 orifice plates, or 1536 orifice plates, or other types orifice plate matches, and realizes the seamless connection with existing system; As preferably, before carrying out reacting, analyze and screen, the liquid of being got of various needs is loaded in advance and is stored in described porous plate, the step that simplifies the operation and shorten the operating time; As preferably, described porous plate carries and is multiplely got liquid, and multiplely got strength of fluid or composition is incomplete same.As preferably, described Microfluidic droplet array chip carries multiple drop in advance, and multiple concentration of liquid drops or composition incomplete same.As preferably, adopt and get the disposable different liquids dipped in some or all of porous plate of liquid probe array, improve the flux getting liquid operation.
The present invention carry out receiving below upgrading volume get liquid, mixing and transfer operation time, get the some or all of of liquid probe, Microfluidic droplet array chip and porous plate, immerse respectively and got in the immiscible oil phase of liquid, or be placed in closed system, or be placed in high humility system, to prevent the evaporation of micro liquid.Namely as preferably, describedly got liquid and be placed in porous plate, and got liquid surface and be coated with and got the immiscible oil phase of liquid.In addition, the use of oil phase contributes to reducing is got liquid in the absorption of sample probe support part and residual, meanwhile, is also conducive to reducing and is got liquid and getting liquid probe and get the resid vol of liquid end surfaces.
In the present invention, described liquid probe of getting is that disposable liquid of getting uses, or muptiple-use liquid of getting uses; When get liquid probe carry out muptiple-use get liquid use time, before dipping different liquids, cleaning treatment is carried out to the sampling end getting liquid probe, or get under liquid operates the insignificant situation of cross pollution produced muptiple-use, direct utilization is got liquid probe and is dipped multiple different liquids, and does not need the sampling end to getting liquid probe to carry out cleaning treatment.
Advantage of the present invention is mainly: (1) handling liquids has skin liter (10
-12rise) below, be even low to moderate Ah's upgrading (10 of ascending to heaven
-15to 10
-18rise) volume accuracy, effectively reduce chemistry and biological respinse and analysis in sample and reagent consumption, save experimental cost; (2) without the need to adopting the pipelines such as the driver part such as syringe pump, peristaltic pump and capillary, system architecture simplifies greatly, and cost significantly reduces; (3) Dynamic System is simple, reliability is high, be easy to realize array and automation.
Accompanying drawing explanation
Fig. 1 is the manipulation schematic diagram of the ultramicron liquid drop control method based on liquid residue of embodiment 1.
Fig. 2 is the another kind manipulation schematic diagram of the ultramicron liquid drop control method based on liquid residue of embodiment 1.
Fig. 3 is microphoto side view (left side) and the cross-sectional plan view (right side) that the sample probe processed by stainless steel pin used in embodiment 1 gets liquid end.
Fig. 4 is the fluorescence micrograph of the uranin mixing drop generated during embodiment 1 is tested.
Fig. 5 is the manipulation schematic diagram of the ultramicron liquid drop control method based on liquid residue of embodiment 2.
In above-mentioned accompanying drawing:
1, liquid probe is got; 2, liquid end is got; 3, part is supported; 4, liquid is got; 5, porous plate; 6, Microfluidic droplet array chip; 7, micro-structural; 8, oil phase; 9, drop; 10, drop; 11, drop; 12, probe array.
Detailed description of the invention
With specific embodiment, the present invention will be further described below, but protection scope of the present invention is not limited thereto.
Embodiment 1
Fig. 1 is the schematic diagram of the ultramicron liquid drop control method based on liquid residue of embodiment 1.
Adopt stainless steel pin (diameter 600 microns) as getting liquid probe 1, first with chemical reagent, overall hydrophobization process is carried out to the surface of getting liquid probe 1 cleaned up, then is polished in the tip of getting liquid probe 1 on sand paper, finally obtain that most advanced and sophisticated cross section (diameter 60 microns) is hydrophily, remaining surface is and hydrophobicly gets liquid probe 1, wherein having hydrophilic most advanced and sophisticated cross section as what get liquid probe 1 gets liquid end 2, and the cross-sectional area radius getting liquid end 2 is about 30 microns; There is hydrophobic surface of getting liquid probe 1 as the support part 3 (Fig. 3) of getting liquid probe 1.By 10
-3m (mol/L) Fluress is added commercially to have in the porous plate 5 in 384 holes as getting liquid 4.The Microfluidic droplet array chip 6 of processed glass matrix, Microfluidic droplet array chip 6 is processed with shallow hole and carries drop as micro-structural 7, Microfluidic droplet array chip 6 is put into the culture dish adding mineral oil oil phase 8, make oil phase 8 submergence Microfluidic droplet array chip 6.The support part 3 of getting liquid probe 1 is fixed on a support, porous plate 5 and Microfluidic droplet array chip 6 are fixed on D translation platform.
Get liquid method of operating: mobile translation stage, the liquid end 2 of getting making to get liquid probe 1 inserts and is got (in Fig. 1 shown in (2)) in liquid 4 in porous plate 5, and then the liquid end 2 of getting that mobile translation stage makes to get liquid probe 1 departs from and is got liquid 4 in porous plate 5, the liquid 4 of being got of trace residues in the surface of getting liquid end 2 of getting liquid probe 1, formed and got the drop 9 of liquid 4 (in Fig. 1 shown in (3)) (volume is about 10 skin liters), complete and dipped operation in porous plate 5 by what get liquid 4.: mobile translation stage make getting the method for operating that drop 9 that liquid probe 1 is formed transfers on Microfluidic droplet array chip 6 specific microstructure 7 on the Microfluidic droplet array chip 6 of immersion oil phase 8 and get the drop 9 that liquid probe 1 is formed and contact (in Fig. 1 shown in (4) and (5)).Move translation stage again, make Microfluidic droplet array chip 6 and get liquid probe 1 to depart from, a part of liquid in drop 9, transferred to once in the micro-structural 7 of Microfluidic droplet array chip 6 and form new drop 9, what also have partial drop 9 to remain in get liquid probe 1 gets liquid end 2 (in Fig. 1 shown in (6)).Aforesaid operations also can think the splitting operation completing drop 9.
Fig. 2 is another fluid operated schematic diagram of embodiment 1.
Another fluid operated method of employing embodiment 1 is, first in porous plate 5, added the appropriate mineral oil oil phase 8 of one deck by the top of getting liquid 4 to prevent by the evaporation of getting liquid 4, mobile translation stage, the liquid end 2 of getting making to get liquid probe 1 inserts and is got (in Fig. 2 shown in (2)) in liquid 4 in porous plate 5, and then the liquid end 2 of getting that mobile translation stage makes to get liquid probe 1 departs from and is got liquid 4 in porous plate 5, the liquid 4 of being got of trace residues in the surface of getting liquid end 2 of getting liquid probe 1, formed and got the drop 9 (in Fig. 2 shown in (3)) of liquid 4, complete and dipped operation in porous plate 5 by what get liquid 4.The drop 9 getting the uranin solution that liquid probe 1 is formed and the volume formed in micro-structural 7 on Microfluidic droplet array chip 6 are in advance that 10 drops 10 receiving the blank solution risen mix mutually by next step.Its method of operating is: mobile translation stage, make the drop 10 in the specific microstructure 7 on the Microfluidic droplet array chip 6 of immersion oil phase 8 and get the drop 9 that liquid probe 1 is formed and contact (in Fig. 2 (4) and (5) shown in), the liquid of drop 9 mixes mutually with the liquid of drop 10, and drop 9 and drop 10 merge and become one and new mix drop 11.Move translation stage again, make Microfluidic droplet array chip 6 and get liquid probe 1 to depart from, drop 11 is split into two drops, a drop is retained in the micro-structural 7 of Microfluidic droplet array chip 6, and what also have drop to remain in get liquid probe 1 gets liquid end 2 (Fig. 2 (6)).Be retained in the microscopic fluorescence photo of the drop 11 in the micro-structural 7 of Microfluidic droplet array chip 6 as shown in Figure 4.
Fig. 3 is microphoto side view (left side) and the cross-sectional plan view (right side) that the sample probe processed by stainless steel pin used in embodiment 1 gets liquid end.
Fig. 4 is the fluorescence micrograph of the uranin mixing drop generated during embodiment 1 is tested.
Embodiment 2
Fig. 5 is the schematic diagram of the ultramicron liquid drop control method based on liquid residue of embodiment 2.
Adopting the long rod (diameter 1.8 millimeters, length 40 millimeters) of ABS plastic processing column shape as getting liquid probe 1, not needing the surface to getting liquid probe 1 to carry out surface treatment, only it simply being cleaned before using.Utilize the circular cross section of getting the cylinder top end of liquid probe 1 to get liquid end 2 as what get liquid probe 1, get other parts of liquid probe 1 as the support part 3 of getting liquid probe 1.The other end or its support part 3 of six being got liquid probe 1 are fixed on the sample probe array 12 one block of supporting plate being formed an one dimension, and for mating with commercialization 384 orifice plate, the adjacent spacing of getting between liquid probe 1 is 4.5 millimeters (Fig. 5).By 10
-3m Fluress is added commercialization have in six holes of the porous plate 5 in 384 holes as getting liquid 4.The Microfluidic droplet array chip 6 of processing dimethyl silicone polymer (PDMS) matrix, Microfluidic droplet array chip 6 is processed with protruding cylindrical (diameter 2 millimeters, height 0.1 millimeter) carry drop as micro-structural 7, Microfluidic droplet array chip 6 is put into the culture dish adding mineral oil oil phase 8, make oil phase 8 submergence Microfluidic droplet array chip 6.Sample probe array 12 is fixed on a support by its supporting plate, porous plate 5 and Microfluidic droplet array chip 6 are fixed on D translation platform.
Liquid method of operating: mobile translation stage, make each get liquid probe 1 get that liquid end 2 inserts correspondence in porous plate 5 respectively got (Fig. 5 (1)) in liquid 4, and then mobile translation stage make each get liquid probe 1 get that liquid end 2 departs from correspondence in porous plate 5 respectively got liquid 4, the liquid 4 of being got of trace residues in the surface of getting liquid end 2 that each gets liquid probe 1 respectively, formed and multiplely got the drop 9 of liquid 4 (in Fig. 5 shown in (2)) (volume be about 800 receive liters), complete and by what get liquid 4, operation is dipped to interior each of porous plate 5.Next step is that the 800 drop 10 difference one_to_one corresponding receiving another solution risen mix by getting the drop 9 that liquid probe 1 is formed and the volume formed in micro-structural 7 on Microfluidic droplet array chip 6 in advance.Its method of operating is: mobile translation stage, make each drop 10 in the specific microstructure 7 on the Microfluidic droplet array chip 6 of immersion oil phase 8 and get each drop 9 one_to_one corresponding that liquid probe 1 is formed and contact (in Fig. 5 (3) shown in), the liquid of drop 9 mixes mutually with the liquid of drop 10, and drop 9 and drop 10 merge and become one and new mix drop 11 (in Fig. 5 shown in (4)).Move translation stage again, make Microfluidic droplet array chip 6 and each get liquid probe 1 to depart from, each drop 11 is split into two drops, a drop is retained in Microfluidic droplet array chip 6 and micro-structural 7, and what also have drop to remain in get liquid probe 1 gets liquid end 2 (in Fig. 5 shown in (5)).
The composition forming the solution of six drops 9 can be identical, to carry out the reaction of same sample or reagent, analyzes and screening; Their composition also can be different, to carry out the reaction of multiple different sample or reagent, analyzes and screening.Similarly, the composition forming the solution of Microfluidic droplet array chip 6 six drops 10 also can be identical, to carry out the reaction of same sample or reagent, analyzes and screening; Their composition also can be different, to carry out the reaction of multiple different sample or reagent, analyzes and screening.
Claims (10)
1., based on a ultramicron liquid drop control device for liquid residue, it is characterized in that, comprising:
Porous plate, this porous plate is provided with one or morely is got the hole slot of liquid for holding;
Microfluidic droplet array chip, this Microfluidic droplet array chip is provided with one or more micro-structural for carrying drop;
Get liquid probe, this sample probe has support part and be positioned at support member base end get liquid end; Described liquid end surfaces of getting is to being more than or equal to described support partial outer face by the compatibility of getting liquid to being got the compatibility of liquid;
Switching mechanism, realize successively getting liquid probe to got the sampling operation of liquid and by get and got the setting-out that liquid is placed in Microfluidic droplet array chip and operate.
2. the ultramicron liquid drop control device based on liquid residue according to claim 1, is characterized in that, described in get liquid end surfaces area be 100 square nanometers to 1000 square millimeter.
3. the ultramicron liquid drop control device based on liquid residue according to claim 1, is characterized in that, described micro-structural is the groove structure be arranged in Microfluidic droplet array chip, planar structure, columnar projections structure; The volume range carrying drop in described micro-structural is that 1 Ah rises to 1 milliliter.
4. the ultramicron liquid drop control device based on liquid residue according to claim 1, it is characterized in that, described micro-structure surface is had compatibility to getting liquid.
5. the ultramicron liquid drop control device based on liquid residue according to claim 1, is characterized in that, described in get liquid end be planar structure or column construction or pyramidal structure.
6. utilize the device described in the arbitrary claim of claim 1-5 to carry out a ultramicron liquid drop control method, it is characterized in that, comprising:
(1) make to get liquid probe to get the part surface of liquid end or all surfaces and be immersed into and got in liquid in porous plate, dip and got liquid in porous plate, got liquid adhesive and get liquid end in getting liquid probe;
(2) the liquid end of getting making to get liquid probe departs from and is got liquid in porous plate, gets liquid end upper surface and is formed and got liquid drop;
(3) make to get liquid probe get liquid end surfaces by the microstructured contact got on liquid drop and Microfluidic droplet array chip, or when micro-structural carrying in advance drop, with this drop contact, part is got liquid rotating and is moved on on Microfluidic droplet array chip in micro-structural, or with the droplets mixing that carries in advance in micro-structural; Micro-structural end face on described Microfluidic droplet array chip is coated with and is got the immiscible oil phase of liquid;
(4) make the liquid end of getting getting liquid probe depart from Microfluidic droplet array chip, formed by the drop getting liquid in the micro-structural of Microfluidic droplet array chip, complete the operation generating drop on described Microfluidic droplet array chip;
Optionally enter step (5) and (6):
(5) select another to get liquid probe, make to get liquid probe and get the part surface of liquid end or all surfaces and be immersed into Flow Control droplet array chip generates in drop, dip drop, partial drop adheres to be got liquid probe and gets liquid end;
(6) make the liquid end of getting getting the disengaging of liquid probe depart from Microfluidic droplet array chip, what complete partial drop gets liquid operation.
7. the ultramicron liquid drop control method based on liquid residue according to claim 6, is characterized in that, is describedly got liquid and is placed in porous plate, and is got liquid surface and be coated with and got the immiscible oil phase of liquid.
8. the ultramicron liquid drop control method based on liquid residue according to claim 6, is characterized in that, carries in advance and got the different drop of liquid in described micro-structural.
9. the ultramicron liquid drop control method based on liquid residue according to claim 6, is characterized in that, described porous plate carries multiplely got liquid, and is multiplely got strength of fluid or composition is incomplete same.
10. the ultramicron liquid drop control method based on liquid residue according to claim 8, is characterized in that, described Microfluidic droplet array chip carries multiple drop in advance, and multiple concentration of liquid drops or composition incomplete same.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410640394.7A CN104492508B (en) | 2014-11-13 | 2014-11-13 | A kind of ultramicron liquid drop control device and method based on liquid residue |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410640394.7A CN104492508B (en) | 2014-11-13 | 2014-11-13 | A kind of ultramicron liquid drop control device and method based on liquid residue |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104492508A true CN104492508A (en) | 2015-04-08 |
| CN104492508B CN104492508B (en) | 2016-08-24 |
Family
ID=52934010
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410640394.7A Active CN104492508B (en) | 2014-11-13 | 2014-11-13 | A kind of ultramicron liquid drop control device and method based on liquid residue |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104492508B (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106249663A (en) * | 2016-09-18 | 2016-12-21 | 山东省科学院能源研究所 | A kind of method realizing automatically preparing microsphere continuously |
| CN107422059A (en) * | 2017-03-27 | 2017-12-01 | 浙江大学 | A kind of device and its application method for submicrosample original position chromatography column feed materials |
| CN109865904A (en) * | 2019-02-01 | 2019-06-11 | 清华大学 | The fine hydrophilic probe operation microlayer model method and device of electrical discharge machining |
| CN110873657A (en) * | 2018-08-31 | 2020-03-10 | 北京致雨生物科技有限公司 | Sampling method of micro-sample |
| GB2543616B (en) * | 2015-10-16 | 2020-04-08 | Univ Oxford Innovation Ltd | Microfluidic arrangements |
| CN112191189A (en) * | 2020-09-26 | 2021-01-08 | 宁波大学 | Method and device for generating picoliter single liquid drop |
| CN112444530A (en) * | 2019-09-04 | 2021-03-05 | 浙江大学 | Micro sample preparation device for cryoelectron microscope and sample preparation method thereof |
| WO2021143894A1 (en) * | 2020-01-19 | 2021-07-22 | 吴明翰 | Apparatus for obtaining micro-droplets |
| CN113189358A (en) * | 2021-05-06 | 2021-07-30 | 上海迈振电子科技有限公司 | Semi-contact type sample applicator and preparation method of micro-cantilever sensor chip |
| CN114126760A (en) * | 2020-05-13 | 2022-03-01 | 京东方科技集团股份有限公司 | Microfluidic chip, liquid adding method thereof and microfluidic system |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005078441A1 (en) * | 2004-02-18 | 2005-08-25 | Ani Biotech Oy | Sampling device, the method and use thereof |
| JP2006231166A (en) * | 2005-02-23 | 2006-09-07 | Fukae Kasei Kk | Treatment instrument of liquid sample and its usage |
| CN201997343U (en) * | 2011-01-14 | 2011-10-05 | 郝玉有 | Perforated plate sampling height adjustor |
| CN103008037A (en) * | 2012-12-31 | 2013-04-03 | 浙江大学 | Automatic micro-droplet array screening system using method with pico-liter-scale precision |
| CN103954786A (en) * | 2014-04-21 | 2014-07-30 | 浙江大学 | Semi-contact under-oil continuous droplet sample applying and liquid adding method |
-
2014
- 2014-11-13 CN CN201410640394.7A patent/CN104492508B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005078441A1 (en) * | 2004-02-18 | 2005-08-25 | Ani Biotech Oy | Sampling device, the method and use thereof |
| JP2006231166A (en) * | 2005-02-23 | 2006-09-07 | Fukae Kasei Kk | Treatment instrument of liquid sample and its usage |
| CN201997343U (en) * | 2011-01-14 | 2011-10-05 | 郝玉有 | Perforated plate sampling height adjustor |
| CN103008037A (en) * | 2012-12-31 | 2013-04-03 | 浙江大学 | Automatic micro-droplet array screening system using method with pico-liter-scale precision |
| CN103954786A (en) * | 2014-04-21 | 2014-07-30 | 浙江大学 | Semi-contact under-oil continuous droplet sample applying and liquid adding method |
Non-Patent Citations (1)
| Title |
|---|
| YING ZHU ET AL.: "Sequential Operation Droplet Array: An Automated MicrofluidicPlatform for Picoliter-Scale Liquid Handling, Analysis, and Screening", 《AMERICAN CHEMICAL SOCIETY》, 13 January 2013 (2013-01-13) * |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2543616B (en) * | 2015-10-16 | 2020-04-08 | Univ Oxford Innovation Ltd | Microfluidic arrangements |
| CN106249663A (en) * | 2016-09-18 | 2016-12-21 | 山东省科学院能源研究所 | A kind of method realizing automatically preparing microsphere continuously |
| CN107422059A (en) * | 2017-03-27 | 2017-12-01 | 浙江大学 | A kind of device and its application method for submicrosample original position chromatography column feed materials |
| CN110873657A (en) * | 2018-08-31 | 2020-03-10 | 北京致雨生物科技有限公司 | Sampling method of micro-sample |
| CN110873657B (en) * | 2018-08-31 | 2022-02-08 | 北京致雨生物科技有限公司 | Sampling method of micro-sample |
| CN109865904A (en) * | 2019-02-01 | 2019-06-11 | 清华大学 | The fine hydrophilic probe operation microlayer model method and device of electrical discharge machining |
| WO2020155728A1 (en) * | 2019-02-01 | 2020-08-06 | 清华大学 | Method and device for operating microdroplets by means of electrical discharge machining fine hydrophilic probe |
| CN112444530A (en) * | 2019-09-04 | 2021-03-05 | 浙江大学 | Micro sample preparation device for cryoelectron microscope and sample preparation method thereof |
| WO2021143894A1 (en) * | 2020-01-19 | 2021-07-22 | 吴明翰 | Apparatus for obtaining micro-droplets |
| CN114126760A (en) * | 2020-05-13 | 2022-03-01 | 京东方科技集团股份有限公司 | Microfluidic chip, liquid adding method thereof and microfluidic system |
| CN112191189A (en) * | 2020-09-26 | 2021-01-08 | 宁波大学 | Method and device for generating picoliter single liquid drop |
| CN113189358A (en) * | 2021-05-06 | 2021-07-30 | 上海迈振电子科技有限公司 | Semi-contact type sample applicator and preparation method of micro-cantilever sensor chip |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104492508B (en) | 2016-08-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104492508B (en) | A kind of ultramicron liquid drop control device and method based on liquid residue | |
| US11590503B2 (en) | Microfluidic arrangements | |
| Mashaghi et al. | Droplet microfluidics: A tool for biology, chemistry and nanotechnology | |
| Oliveira et al. | Recent advances on open fluidic systems for biomedical applications: A review | |
| Kaigala et al. | Microfluidics in the “open space” for performing localized chemistry on biological interfaces | |
| Kaigala et al. | A vertical microfluidic probe | |
| US6409832B2 (en) | Protein crystallization in microfluidic structures | |
| Liu et al. | Microfluidic systems for biosensing | |
| He et al. | Concentrating solutes and nanoparticles within individual aqueous microdroplets | |
| CN103954786B (en) | Semi-contact under-oil continuous droplet sample applying and liquid adding method | |
| US20030080143A1 (en) | System and method for dispensing liquids | |
| AU2001251218A1 (en) | Protein crystallization in microfluidic structures | |
| CN103003450B (en) | Method manufacturing micro-chamber plate for analysis and micro-chamber plate with samples, micro-chamber plate for analysis and apparatus set manufacturing micro-chamber plate with samples | |
| Dong et al. | Automated, flexible and versatile manipulation of nanoliter-to-picoliter droplets based on sequential operation droplet array technique | |
| CN110787851B (en) | Multi-channel liquid drop quantitative measuring device and method based on pressure driving | |
| CN107422059B (en) | Device for ultra-micro sample in-situ chromatography sample introduction and use method thereof | |
| US20170216838A1 (en) | Microfluidic device with channel plates | |
| Zeng et al. | Miniaturizing chemistry and biology using droplets in open systems | |
| Yu et al. | Gravitational effect on the formation of surface nanodroplets | |
| GB2572699A (en) | Microfluidic arrangements | |
| CN108906144B (en) | Synchronous high-flux sample adding system for multiple samples | |
| Jin et al. | Nanoliter-scale liquid metering and droplet generation based on a capillary array for high throughput screening | |
| US20230364607A1 (en) | Open fluidic device for autonomous droplet generation and related methods of use for droplet formation and manipulation | |
| Ge et al. | Open and closed microfluidics for biosensing | |
| Akhtar | A microsystem for on-chip droplet storage and processing |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |