CN114166615A - Dilution method of digital microfluidic droplets - Google Patents
Dilution method of digital microfluidic droplets Download PDFInfo
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- CN114166615A CN114166615A CN202111385222.6A CN202111385222A CN114166615A CN 114166615 A CN114166615 A CN 114166615A CN 202111385222 A CN202111385222 A CN 202111385222A CN 114166615 A CN114166615 A CN 114166615A
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- 238000003113 dilution method Methods 0.000 title description 4
- 239000007788 liquid Substances 0.000 claims abstract description 53
- 239000002904 solvent Substances 0.000 claims abstract description 32
- 238000010790 dilution Methods 0.000 claims abstract description 26
- 239000012895 dilution Substances 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 22
- 238000007865 diluting Methods 0.000 claims abstract description 17
- 238000004070 electrodeposition Methods 0.000 claims abstract description 4
- 239000002245 particle Substances 0.000 claims description 19
- 239000007787 solid Substances 0.000 claims description 10
- 239000002699 waste material Substances 0.000 claims description 6
- 238000000926 separation method Methods 0.000 claims description 2
- 239000000243 solution Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002608 ionic liquid Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/38—Diluting, dispersing or mixing samples
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- 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
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Clinical Laboratory Science (AREA)
- Hematology (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
The invention provides a method for diluting a digital microfluidic droplet, wherein the digital microfluidic droplet is positioned in a driving electrode unit array constructed by a digital microfluidic platform, and the method comprises the following steps: s1: separating a sample droplet and a solvent droplet with specific sizes from the sample pool and the blank solvent pool respectively, wherein the sample droplet and the solvent droplet are first droplets; s2: moving the sample liquid drop and the solvent liquid drop to the same electrode position for mixing and forming a mixed liquid drop; s3: uniformly mixing the mixed liquid drops; s4: splitting the mixed droplet into two droplets, both droplets being second droplets. The invention can control the small volume of the liquid drop, and can dilute rare samples or samples with little demand; the liquid drop moving speed is high, and the time consumption can be greatly reduced; and a large amount of liquid drops are controlled at the same time, so that high-flux dilution can be realized.
Description
Technical Field
The invention relates to the technical field of digital micro-fluidic, in particular to a method for diluting a digital micro-fluidic liquid drop.
Background
In the prior art, the solution dilution is carried out by the digital microfluidic technology, the concentration of chemical substances or solid particles in the existing solution is firstly measured, and then a solvent is added and mixed according to requirements for dilution, so that the dilution can be carried out manually or automatically by a machine. When the volume of the solution is actually needed to be small, the operation difficulty of solution proportioning is increased, and the error may be large; or when the solid particles need to be diluted to a fixed amount per volume of liquid to be taken, the sampling is repeated and observed each time until the required liquid drops can be taken. When a large amount of samples need to be diluted, manual operation needs a lot of time, and the operation is complicated and the efficiency is low.
Therefore, it is necessary to design a new method for diluting the digital microfluidic droplets.
Disclosure of Invention
The invention aims to provide a method for diluting a digital microfluidic droplet, which can dilute a rare sample or a sample with little demand, has high droplet moving speed and reduces time consumption.
The invention provides a method for diluting a digital microfluidic droplet, wherein the digital microfluidic droplet is positioned in a driving electrode unit array constructed by a digital microfluidic platform, and the method comprises the following steps:
s1: separating a sample droplet and a solvent droplet with specific sizes from the sample pool and the blank solvent pool respectively, wherein the sample droplet and the solvent droplet are first droplets;
s2: moving the sample liquid drop and the solvent liquid drop to the same electrode position for mixing and forming a mixed liquid drop;
s3: uniformly mixing the mixed liquid drops;
s4: splitting the mixed droplet into two droplets, both droplets being second droplets.
Further, the position where the sample cell and the blank solvent cell are uniformly mixed and the splitting position of the sample cell and the blank solvent cell are located in any unit of the driving electrode unit array.
Further, in step S3, the specific method for uniformly mixing the mixed droplets is as follows: the mixed liquid drops reciprocate among the plurality of driving electrode units so that the mixed liquid drops are uniformly mixed.
Further, the mixing and separation area of the droplets is located in the central region of the array of drive electrode units.
Further, step S4 includes step S41 of retaining one of the two droplets, moving the other droplet to a waste reservoir or both droplets being retained.
Further, step S4 includes step S42, re-separating a new droplet from the sample cell or the blank solvent cell, where the new droplet is a third droplet, and the third droplet and one of the second droplets are uniformly mixed to obtain a fourth droplet.
Further, step S4 includes step S43, splitting the second droplet into two fourth droplets after the other droplets of the digital microfluidic platform are uniformly mixed with the second droplet.
Further, according to actual requirements, step S4 is repeated.
Further, if the number of the solid particles is detected, the liquid drop is moved to a micro fluorescent microscope to be photographed after each dilution and the photograph is automatically processed to identify the number of the particles, and if the number of the particles does not meet the requirement, the dilution step is repeated until the requirement is met.
Further, the sample cell to be diluted is located in the left region of the driving electrode unit array; the sample collecting pool for collecting the diluted liquid drops is positioned in the upper right area of the driving electrode unit array; the waste liquid pool is positioned in the lower area of the right side of the driving electrode unit array; the blank solvent pool is located in the upper region of the array of drive electrode units.
The invention can control the small volume of the liquid drop, and can dilute rare samples or samples with little demand; the liquid drop moving speed is high, and the time consumption can be greatly reduced; and a large amount of liquid drops are controlled at the same time, so that high-flux dilution can be realized.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without creative efforts.
Fig. 1 is a schematic structural diagram of a digital microfluidic platform for constructing a driving electrode unit array according to an embodiment of the invention;
FIG. 2 is a schematic illustration of the mixed dilution of a plurality of different droplets of an embodiment of the present invention.
Detailed Description
Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar elements or elements having the same or similar function throughout. The embodiments described below with reference to the drawings are illustrative and intended to be illustrative of the invention and are not to be construed as limiting the invention.
In the description of the present invention, it is to be understood that the terms "length", "width", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", and the like, indicate orientations or positional relationships based on the orientations or positional relationships illustrated in the drawings, and are used merely for convenience in describing the present invention and for simplicity in description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed in a particular orientation, and be operated, and thus, are not to be construed as limiting the present invention. Further, in the description of the present invention, "a plurality" means two or more unless specifically defined otherwise.
As shown in FIG. 1, the digital microfluidic platform is constructed with an array of driving electrode units, and each driving electrode unit is powered up under the control of operating software on an upper computer. The left area of the driving electrode unit array is a sample cell 10 to be diluted (the sample cell 10 is a sample stock solution to be diluted), the right upper area of the driving electrode unit array is a sample collection cell 20 for collecting diluted liquid drops, the right lower area of the driving electrode unit array is a waste liquid cell 100, the upper area of the driving electrode unit array is a diluted blank solvent cell 30, the central area of the driving electrode unit array is a mixing and separating area 40 of the liquid drops, and the microscope is an observation area (optional) of the liquid drops.
The invention relates to a method for diluting a digital microfluidic droplet, wherein the digital microfluidic droplet is positioned in a driving electrode unit array constructed by a digital microfluidic platform, and the method comprises the following steps:
s1: separating a sample droplet 11 and a solvent droplet 31 with specific sizes from the sample pool 10 and the blank solvent pool 30 respectively, wherein the sample droplet 11 and the solvent droplet 31 are first droplets;
s2: the sample liquid droplet 11 of the sample cell 10 and the solvent liquid droplet 31 of the blank solvent cell 30 move to the same electrode position to be mixed and form a mixed liquid droplet 41;
s3: the mixed liquid drops 41 reciprocate among the plurality of driving electrode units so that the mixed liquid drops 41 are uniformly mixed;
s4: splitting the mixed droplet 41 into two droplets, both droplets being second droplets;
wherein step S4 includes: step S41, of course, only one of the two droplets 411 may be retained, the other droplet 412 may be moved to the waste reservoir 100 or both droplets may be retained, as desired, when theoretically each of the two droplets has a half diluted concentration of chemical or solid particles; step S42: depending on the desired concentration, a new droplet can be re-isolated from either the sample cell 10 or the blank solvent cell 30, the new droplet being the third droplet 413; step S43: the other droplets of the digital microfluidic platform are uniformly mixed with the second droplet and then split into two fourth droplets 414;
s5: repeating the step S4 according to actual requirements;
s6: if the solid particle count is detected, the droplet 414 is moved to the micro fluorescence microscope after each dilution and the photograph is automatically processed to identify the particle count, and if the particle count does not meet the requirement, the dilution step is repeated until the requirement is met.
With respect to step S3, the specific meaning that the mixed droplet 41 reciprocates between the plurality of driving electrode units so that the two droplets are uniformly mixed is: mixed droplet 41 reciprocates between M x N drive electrode units, and if M and N are both 3, mixed droplet 41 makes a circular loop between 3 x 3 drive electrode units until it is mixed uniformly, i.e., dashed area 50 shown in fig. 1.
For the dilution method of the present invention, the various droplets are defined as M1, M2, M3, M4, … …, M10, … …, respectively, and the mixing and dilution are referred to fig. 2.
The kind of the liquid droplet may be classified into an aqueous solution, an aqueous particle dispersion, an organic solution, an ionic liquid solution, a polymer monomer, and the like.
Example A: original solution concentration of 10(a), solvent concentration of 0(B), target concentration of 2:
first dilution: a + B/2 ═ 5 (C);
and (3) second dilution: c + B/2 ═ 2.5 (D);
and (3) third dilution: d + B/2 ═ 1.25 (E);
fourth dilution: e + D/2 ═ 1.875 (F);
fifth dilution: f + D/2 ═ 2.1875 (G);
sixth dilution: g + F/2 ═ 2.03125 (H).
H liquid drops are close to the target concentration (the error is only 1.5%), and if more accurate concentration is needed, mixing and dilution among the liquid drops can be repeatedly carried out until the condition is met within the error allowable range.
Example B: the number of original solid particles was 10(A), the number of solvent particles was 0(B), and the number of target particles was 7:
first dilution: a + B/2 ═ 5 (C);
and (3) second dilution: c + B/2 ═ 2(D) +3 (E);
and (3) third dilution: e + a/2 ═ 6(F) +7 (G);
g droplets meet the requirements.
The above examples are under ideal conditions, since the solid is not divisible. If the third dilution is actually 5+8 or other cases, the two drops can be mixed again and separated, and the required drops can be obtained by multiple cycles.
Because the liquid drop moving speed is high, the platform can control a large amount of liquid drops at the same time, even if repeated dilution is needed for many times, the liquid drops with required concentration can be quickly obtained, and required steps can be automatically generated by a computer.
The above examples are merely illustrative of the invention. In other embodiments, the position where the sample cell 10 and the blank solvent 30 cell are uniformly mixed (i.e., the position where the mixed droplet 41 is located) and the splitting position of the sample cell 10 and the blank solvent cell 30 (i.e., the position where the mixed droplet 41 is split into two droplets) are located in any cell of the driving electrode cell array. The invention relates to a method for fully automatically proportioning the concentration of a solution by using a digital microfluidic technology, which comprises the step of diluting chemical substances or solid particles and the like in the solution.
The digital microfluidic droplet dilution method of the invention is characterized in that a micro fluorescence microscope is arranged above a platform to observe substances capable of emitting fluorescence, such as cells, a fluorescence mode is used, common particles are used, and the quantity of solid particles can be observed in real time.
The invention can control the small volume of the liquid drop, and can dilute rare samples or samples with little demand; the liquid drop moving speed is high, and the time consumption can be greatly reduced; and a large amount of liquid drops are controlled at the same time, so that high-flux dilution can be realized.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (10)
1. A method for diluting a digital microfluidic droplet is characterized in that the digital microfluidic droplet is positioned in a driving electrode unit array constructed by a digital microfluidic platform, and comprises the following steps:
s1: separating a sample liquid drop (11) and a solvent liquid drop (31) with specific sizes from a sample pool (10) and a blank solvent pool (30) respectively, wherein the sample liquid drop (11) and the solvent liquid drop (31) are first liquid drops;
s2: the sample liquid drop (11) and the solvent liquid drop (31) move to the same electrode position to be mixed and form a mixed liquid drop (41);
s3: uniformly mixing the mixed liquid drops (41);
s4: splitting the mixed droplet (41) into two droplets, both droplets being second droplets.
2. The method for diluting digital microfluidic droplets according to claim 1, wherein the position where the sample cell (10) and the blank solvent cell (30) are uniformly mixed and the position where the sample cell (10) and the blank solvent cell (30) are split are located in any cell of the driving electrode cell array.
3. The method for diluting digital microfluidic droplets as claimed in claim 1, wherein in step S3, the specific method for uniformly mixing the mixed droplets (41) is as follows: the mixed liquid drops (41) reciprocate among the plurality of driving electrode units so that the mixed liquid drops (41) are uniformly mixed.
4. The method of diluting digital microfluidic droplets according to claim 1, wherein the mixing and separation region of the droplets is located in a central region of the array of driving electrode units.
5. The method for diluting digital microfluidic droplets according to claim 1, wherein step S4 includes step S41 of retaining one of the two droplets, moving the other droplet to a waste reservoir (100) or retaining both droplets.
6. The method for diluting digital microfluidic droplets according to claim 1, wherein step S4 comprises step S42, a new droplet is separated from the sample cell (10) or the blank solvent cell (30), the new droplet is a third droplet (413), and the third droplet (413) and one of the second droplets are uniformly mixed to obtain a fourth droplet.
7. The method for diluting digital microfluidic droplets according to claim 1, wherein step S4 includes step S43, in which other droplets of the digital microfluidic platform are uniformly mixed with the second droplet and then split into two fourth droplets.
8. The method for diluting digital microfluidic droplets according to any one of claims 5 to 7, wherein step S4 is repeated according to actual requirements.
9. The method for diluting digital microfluidic droplets according to claim 8, wherein if the number of solid particles is detected, the droplets are moved to a micro fluorescence microscope after each dilution and automatically processed to identify the number of particles, and if the number of particles does not meet the requirement, the dilution step is repeated until the requirement is met.
10. The method for diluting digital microfluidic droplets according to claim 1, wherein the sample cell (10) to be diluted is located in the left region of the array of driving electrode units; a sample collecting pool (20) for collecting the diluted liquid drops is positioned in the upper right area of the driving electrode unit array; the waste liquid pool (100) is positioned in the lower right area of the driving electrode unit array; a blank solvent pool (30) is located in an upper region of the array of drive electrode elements.
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| CN202111385222.6A CN114166615A (en) | 2021-11-22 | 2021-11-22 | Dilution method of digital microfluidic droplets |
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| CN202111385222.6A CN114166615A (en) | 2021-11-22 | 2021-11-22 | Dilution method of digital microfluidic droplets |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| US20160375437A1 (en) * | 2015-06-23 | 2016-12-29 | Sharp Kabushiki Kaisha | Ewod device with calibrated serial dilution function |
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| CN109164073A (en) * | 2018-08-03 | 2019-01-08 | 大连大学 | Digital microcurrent-controlled chip system and method for heavy metal in water ion measurement |
| CN109557150A (en) * | 2019-01-14 | 2019-04-02 | 大连大学 | Digital microcurrent-controlled chip and pathogen immunologic detection method based on it |
-
2021
- 2021-11-22 CN CN202111385222.6A patent/CN114166615A/en active Pending
Patent Citations (7)
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| US20130105319A1 (en) * | 2010-07-15 | 2013-05-02 | Indian Statistical Institute | Architectural layout for dilution with reduced wastage in digital microfluidic based lab-on-a-chip |
| CN107249743A (en) * | 2014-12-31 | 2017-10-13 | 雅培制药有限公司 | Digital microcurrent-controlled diluent facilities, system and correlation technique |
| US20160375437A1 (en) * | 2015-06-23 | 2016-12-29 | Sharp Kabushiki Kaisha | Ewod device with calibrated serial dilution function |
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| CN107754962A (en) * | 2017-11-22 | 2018-03-06 | 南方科技大学 | A kind of Digital Microfluidic droplet drive device and driving method |
| CN109164073A (en) * | 2018-08-03 | 2019-01-08 | 大连大学 | Digital microcurrent-controlled chip system and method for heavy metal in water ion measurement |
| CN109557150A (en) * | 2019-01-14 | 2019-04-02 | 大连大学 | Digital microcurrent-controlled chip and pathogen immunologic detection method based on it |
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| Title |
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