GB2453534A - Method for adding solutions to droplets in a microfluidic environment using electric potentials or ultrasound - Google Patents
Method for adding solutions to droplets in a microfluidic environment using electric potentials or ultrasound Download PDFInfo
- Publication number
- GB2453534A GB2453534A GB0719502A GB0719502A GB2453534A GB 2453534 A GB2453534 A GB 2453534A GB 0719502 A GB0719502 A GB 0719502A GB 0719502 A GB0719502 A GB 0719502A GB 2453534 A GB2453534 A GB 2453534A
- Authority
- GB
- United Kingdom
- Prior art keywords
- liquid
- moieties
- droplets
- conduit
- previous
- 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.)
- Withdrawn
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Classifications
-
- 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
- B01L3/50273—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 characterised by the means or forces applied to move the fluids
-
- B01F13/0059—
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
- B01F31/80—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations
- B01F31/84—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations for material continuously moving through a tube, e.g. by deforming the tube
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
- B01F33/302—Micromixers the materials to be mixed flowing in the form of droplets
- B01F33/3021—Micromixers the materials to be mixed flowing in the form of droplets the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
- B01F33/3031—Micromixers using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
-
- 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
- B01L3/02—Burettes; Pipettes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
Abstract
The invention provides a method and apparatus for coalescing liquid moieties in the presence of an immiscible carrier liquid. Typically the liquid moieties would include droplets that can be moved by moving the immiscible liquid before or after coalescence. The liquid moieties are brought into proximity and then coalesced. Coalescence can be brought about by applying an electric potential to an electrode or electrodes that are in contact with at least one of the liquid moieties. Alternatively, coalescence can be brought about by applying an electric potential to a conductor that is capacitively coupled to at least one of the liquid moieties. A third alternative is to apply high frequency sound to at least one of the liquid moieties to bring about coalescence.
Description
Method for adding solutions to droplets in a microfluidic environment using electric potentials or ultrasound
TECHNICAL FIELD
This invention relates to microfluidic systems and in particular microfluidic systems that LISC carrier liqLlids to move droplets in conduiLs. The invention facilitates the addition of solutions to droplets.
BACKGROUND OF THE INVENTION
In 1957 Leonard Skeggs invented a special flow technique named "Continuous flow analysis (CFAI" that was commercialized by Technicon Corporation. This method is disclosed by Skeggs in US patent number 2797149. issued in 1959. Originally CFA used air to segment the flow of reagents and samples.
hut the air was later sometimes replaced by an immiscible carrier liquid as disclosed by Smythe and Morris in e.g. US3479 141, issued 1969. As long as the droplets and carrier fluid are moving, a turn of carrier fluid can he maintained on the walls of the conduits. Thus the carrier liquid can prevent the sample and reagent droplets from touching the walls of the conduit system through which they pass.
preventing contamination of the walls and the subsequent samples. US3479141 also teaches the injection of solution into droplets at a T-junction. which is a useful technique for modern microfluidic applications.
Figure 3 of IJS3479l4l indicates the injection of copper neocuproine solution into droplets to assay glucose in the droplets. Here droplets are treated as a continuous stream and the droplets are not manipulated and controlled individually. Also, samples are distributed into several droplets.
An improved approach was disclosed by the inventor of the present patent in GB patent 2097692B in 1982. Here samples etc. are dispensed into oil in a conduit system as individual droplets. Liquids can he added to samples, which can be divided, heated. incubated etc. Each droplet is equivalent to a test-tube and it can he manipulated and controlled individually. Also, GB2097692B teaches miniaturization to a microscopic" scale and the construction of conduits by forming depressions in the surface of one or more sheets and bringing these sheets into face-to-face contact.
More recently microfluidic approaches have become commercially popular. Some of these approaches are similar to GB2097692B because they move droplets in immiscible liquids through conduits. For example, Ismagilov disclosed in W02004038363 (2(X)6) the simultaneous introduction of a plurality of liquids through a orifice into an immiscible fluid in a conduit. Also. UK patent application GB0704786.3 by Shaw Stewart and Sommer discloses injection of solutions into droplets.
Such droplet-based microfluidic devices have applications where it is essential to reduce contamination between droplets as much as possible. For example, potential applications include molecular diagnostics.
where the polyrnerase chain reaction is used to "amplify" DNA. If a single DNA molecule were to be transferred from a droplet to a subsequent droplet, a false positive result could result.
One method to reduce contamination of conduits. probes etc. is to add surface active agents e.g. detergents to the carrier liquid and/or to the droplets. Such surface active agents can prevent protein or other potential contaminants from reaching the surthce of the droplets, for example by establishing a "PEG brush" at the surface.
However, adding surface active agents has some disadvantages: they may reduce surface tension, which increases the tendency ftr droplets to break up when they move Iist. Also they may make it difficult to coalesce liquid moieties with other liquid moieties. The time taken for liquid moieties to coalesce is difficult to predict. For example. when coalescing droplets with other droplets, a few droplets will remain -\--uncoalesced long after the majority of droplets have coalesced. (The number of uncoalesced droplets decreases roughly exponentially.) The objective of the present invention is to provide a method that ensures the coalescence of liquids in the presence of an immiscible carrier liquid at a precise time.
Typically the liquids to he coalesced will he aqueous and the carrier liquids will be hydrocarbon. silicone or fluorinated oils.
On a macroscopic scale, it is known that electric potentials can cause liquids to coalesce. For example.
NATCO makes electrostatic dehydi-ators including the TriGridmax system that can separate water from crude oil using an electrostatic process.
BRIEF SUMMARY OF THE INVENTION
()ne aspect of the invention is a method of coalescing liquid moieties by transmitting or applying an electric potential ditThrence to the liquid moieties to be coalesced. An alternative aspect is a method of coalescing liquid moieties by the application of high frequency sound.
Another aspect is a method of adding liquid from a reservoir to one or more droplets.
A tuiih aspect is a method of coalescing droplets where at least one droplet remains in fluid communication with a reservoir.
A fifth aspect is coalescing droplets that are isolated from all reservoirs.
The method comprises the application of an electric potential or potential difference, or high frequency sound to at least one of the liquids to be coalesced.
BRIEF DESCRIPTION OF THE DRAWINGS
Figures Ia to Ic show an example of a typical sequence for adding a solution from a reservoir to a droplet.
Figures 2a to 2c show a sequence for coalescing liquids in the form of droplets. when at least one droplet remains connected to a reservoir.
Figures 3a to 3c show a sequence for coalescing two droplets while they remain connected to two reservoirs (12. 14).
Figures 4a and 4h show a sequence for coalescing droplets that are completely isolated from all reservoirs etc. inacarrier liquid.
Figures 5a and 5b show a similar embodiment with only one conducting plate.
Figures 6a and 6h show a related method of coalescing droplets that uses high frequency sound.
DETAILED DESCRIPTION OF THE INVENTION
The invention will now be described in detail, with reference to the accompanying drawings.
In the accompanying drawings, like features are denoted by like numerals.
All figures show plan views of various devices.
Droplets in conduits are sometimes referred to as plugs or sILigs when the volume of a droplet is sufficiently great Lhat the droplet fills the cross-section of the conduit and the droplet becomes elongated.
In this patent all droplets. large or small, spherical or elongated, are referred to as droplets". The term droplet is thus used in this patent to include spherical droplets, plugs, and slugs.
Figures Ia to Ic show an example of a typical sequence for adding a solution from a reservoir to a droplet.
The method is applied to systems where liquids are dispensed in the form of droplets into a conduit (2) that contains a carrier liquid (4) that is immiscible with the droplets. By moving the carrier liquid the droplets can be moved.
In figure Ia, a sample of liquid in the form of a droplet (10) is brought close to the outlet (11 of a reservoir (12) that is equipped with an electrode (13). At this point, the sample may or may not coalesce with the liquid in reservoir 11. Coalescence cannot be guaranteed, and may be improbable. With some liquid moieties, coalescence may he immediate. With other liquid moieties coalescence may occur after an extended period.
In figure lb. liquid (15) is dispensed from reservoir I 2 as indicated by the arrow. hut a hIm of oil (16) may continue to prevent the dispensed liquid (15) from coalescing with the sample (10).
In figure Ic. an electric pulse is applied to the electrode (13), causing the dispensed liquid (IS) to coalesce with the sample (10). More liquid can be added to the droplet after coalescence as indicated by the arrow.
In figure Id, the carrier liquid (4) is moved as indicated by the arrow in order to move the coalesced liquid, which takes the form of a larger droplet (16). away from the opening of the reservoir (II).
A second reservoir (14) is shown in figures Ia to Id to illustrate that the device may have many reservoirs. The original sample (10) could have been dispensed from e.g. reservoir 14 or another reservoir that is not shown or it could have been picked up by a probe from a receptacle.
Figures 2a to 2c show a sequence for coalescing liquid moieties in the form of droplets, when at least one droplet remains connected to a reservoir. This sequence might he appropriate when the droplets or the carrier liquid contain surface active agents.
Figure 2a shows the same situation as figure lb. Liquid is dispensed from the reservoir (IS). but a film of oil (16) keeps it separate from the droplet (10) as in figure lb. In figure 2h. more liquid is dispensed. which causes the original sample droplet to break into two smaller droplets (20). The volume of liquid dispensed forms a droplet (22) that remains attached to the liquid in the reservoir.
In figure 2c. an electric pulse is applied to the electrode (13). causing the dispensed liquid (22) to coalesce In figure 2d. the carrier liquid (4) is once again moved as indicated by the arrow in order to move the coalesced liquid, which takes the form of a larger droplet (16). away from the opening of the reservoir (1]).
Figures 3a to 3c show a sequence for coalescing two droplets while they remain connected to two reservoirs (12. 14). Each reservoir is equipped with an electrode (13). Liquid is dispensed from both reservoirs as shown in figure 3a. In figure 3b a current flows between the electrodes (marked + and -) causing the Iwo droplets to coalesce. In figure 3c. the carrier liquid is moved as indicted by the arrow in order to disconnect the coalesced droplet from both reservoirs.
Figures 4a and 4h show a sequence lbr coalescing droplets thai are completely isolated from all reservoirs etc. in a carrier liquid.
In figure 4a. two droplets (30) are placed in a conduit close to each other, and adjacent to two conducting plates or electrodes (32. 33 that are embedded in the wall (2) of the conduit.
In figure 4b, an electric potential difference is applied between the two conducting plates (32. 33). This causes a potential diffi.rence to arise between the droplets, which coalesce forming a larger droplet (34).
Note that the droplets may not he in direct electrical contact with the plates. because the plates (32, 33) may he embedded in the walls (2). Moreover, the droplets may advantageously he separated from the walls by films of oil as shown. However the droplets (30) are capacitively coupled to the plates (32, 33).
This gives rise to charges on surfaces of the droplets.
Figures 5a and 5h show a similar embodiment with only one conducting plate. A large (positive or negative) potential is applied to the plate. The potential on the surface ol the droplet closest to the plate changes, while the opposite charge appears on the surface of the other droplet. The resulting potential difTerence causes the droplets to coalesce. Figure 5a shows the situation before the application of the potential. Figure 5h shows that when the potential is applied the droplets coalesce to form a larger droplet (34).
In figures Ia to 5b. the conductors (including electrodes and plates) are shown as rods or flat plates.
Clearly other configurations are possible. For example a conductor could take the form of a conducting tube that encircles a conduit.
Figures Ôa and 6h show a related method of coalescing droplets. In figure ôa two droplets are placed in a conduit near an ultrasonic (high frequency sound) generator (36). This ultrasonic generator produces standing sound waves in the conduit. When the drops are close to a minimum or maximum in the standing waves, they experience a force that moves them together. causing them to coalesce as shown in figure 6h. In one useful method, the generator (36) is turned on once the droplets are already in position.
In another useful method. first the generator is turned on, and then the droplets are moved towards the generator.
The methods shown above can he applied with larger numbers of droplets or liquid moieties. For example, three, tour or more droplets or liquid moieties can be coalesced simultaneously.
-Lf---
Claims (15)
- What 1 claim is: 1. A method of combining liquid moieties in the presence of an immiscible fluid where electric potentials or high frequency sound causes said moieties to coalesce.
- 2. A method as claimed in claim 1 where at least one conductor is iii electrical contact with said liquid moieties.
- 3. A method as claimed in claim 1 where at least one conductor is capacitively coupled to said liquid moieties.
- 4. A method as claimed in claim I where at least one high Frequency sound generator transmits sound that reaches at least two liquid moieties and causes them to coalesce.
- 5. A method as claimed in any previous claim where said immiscible fluid is a liquid that is partially or completely ininiiscible with said liquid moieties.
- 6. A method as claimed in any previous claim where at least one of said liquid moieties is round or elongated or has the form of a droplet. slug or plug.
- 7. A method as claimed in any previous claim where at least one liquid moiety in a carrier liquid is situated in a conduit.
- K A method as claimed in any previous claim where liquid moves from one or more liquid reservoirs into a conduit.
- 9. A method as claimed in any previous claim where an electric potential is applied to a conductor that is capacitively coupled to at least two liquid moieties, causing said liquid moieties to coalesce.
- 10. A method as claimed in aiiy previous claim where an electric potential difference is applied to two conductors, where the conductors are adjacent to at least two liquid moieties, causing said liquid moieties to coalesce.
- 11. An apparatus for carrying out the method of any previous claim where a conduit is provided for coalescing liquids.
- 12. An apparatus for carrying out the method of any previous claim where at least one reservoir for a liquid is provided.
- 13. An apparatus as claimed in claim 12 where at least one of said reservoirs is equipped with a conductor that can establish electrical contact with a liquid.
- 14. An apparatus as claimed in claims 11 or 12 where at least one conductor is provided that is adjacent to said conduit, where said conductor is close enough to said conduit to become capacitively coupled to liquid moieties in said conduit.
- 15. An apparatus as claimed in claims II or 12 where a high frequency sound generator is provided that can communicate sound to liquid moieties in said conduit.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0719502A GB2453534A (en) | 2007-10-08 | 2007-10-08 | Method for adding solutions to droplets in a microfluidic environment using electric potentials or ultrasound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0719502A GB2453534A (en) | 2007-10-08 | 2007-10-08 | Method for adding solutions to droplets in a microfluidic environment using electric potentials or ultrasound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB0719502D0 GB0719502D0 (en) | 2007-11-14 |
| GB2453534A true GB2453534A (en) | 2009-04-15 |
Family
ID=38739202
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB0719502A Withdrawn GB2453534A (en) | 2007-10-08 | 2007-10-08 | Method for adding solutions to droplets in a microfluidic environment using electric potentials or ultrasound |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2453534A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120132288A1 (en) * | 2009-06-26 | 2012-05-31 | President And Fellows Of Harvard College | Fluid injection |
| FR3000688A1 (en) * | 2013-01-08 | 2014-07-11 | Centre Nat Rech Scient | PROCESS FOR ACTIVATING A CHEMICAL REACTION, MIXTURE ACTIVABLE THEREBY AND DEVICE FOR CARRYING OUT SAID METHOD |
| US10258987B2 (en) | 2014-06-26 | 2019-04-16 | President And Fellows Of Harvard College | Fluid infection using acoustic waves |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5958203A (en) * | 1996-06-28 | 1999-09-28 | Caliper Technologies Corportion | Electropipettor and compensation means for electrophoretic bias |
| US20030000835A1 (en) * | 2001-06-28 | 2003-01-02 | Agilent Technologies, Inc. | Microfluidic system |
| US20040066703A1 (en) * | 2002-10-03 | 2004-04-08 | Protasis Corporation | Fluid-handling apparatus and methods |
| US20060034735A1 (en) * | 2004-08-10 | 2006-02-16 | Yokogawa Electric Corporation | Microreactor |
| WO2006027757A2 (en) * | 2004-09-09 | 2006-03-16 | Institut Curie | Microfluidic device using a collinear electric field |
| WO2007089541A2 (en) * | 2006-01-27 | 2007-08-09 | President And Fellows Of Harvard College | Fluidic droplet coalescence |
-
2007
- 2007-10-08 GB GB0719502A patent/GB2453534A/en not_active Withdrawn
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5958203A (en) * | 1996-06-28 | 1999-09-28 | Caliper Technologies Corportion | Electropipettor and compensation means for electrophoretic bias |
| US20030000835A1 (en) * | 2001-06-28 | 2003-01-02 | Agilent Technologies, Inc. | Microfluidic system |
| US20040066703A1 (en) * | 2002-10-03 | 2004-04-08 | Protasis Corporation | Fluid-handling apparatus and methods |
| US20060034735A1 (en) * | 2004-08-10 | 2006-02-16 | Yokogawa Electric Corporation | Microreactor |
| WO2006027757A2 (en) * | 2004-09-09 | 2006-03-16 | Institut Curie | Microfluidic device using a collinear electric field |
| WO2007089541A2 (en) * | 2006-01-27 | 2007-08-09 | President And Fellows Of Harvard College | Fluidic droplet coalescence |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9757698B2 (en) * | 2009-06-26 | 2017-09-12 | President And Fellows Of Harvard College | Fluid injection |
| AU2010266010B2 (en) * | 2009-06-26 | 2015-08-20 | President And Fellows Of Harvard College | Fluid injection |
| EP2446278A4 (en) * | 2009-06-26 | 2015-10-21 | Harvard College | Fluid injection |
| US20120132288A1 (en) * | 2009-06-26 | 2012-05-31 | President And Fellows Of Harvard College | Fluid injection |
| US20170354937A1 (en) * | 2009-06-26 | 2017-12-14 | President And Fellows Of Harvard College | Fluid injection |
| US10919008B2 (en) | 2009-06-26 | 2021-02-16 | President And Fellows Of Harvard College | Fluid injection |
| US11358105B2 (en) | 2009-06-26 | 2022-06-14 | President And Fellows Of Harvard College | Fluid injection |
| EP4019977A1 (en) * | 2009-06-26 | 2022-06-29 | President and Fellows of Harvard College | Fluid injection |
| US11724237B2 (en) | 2009-06-26 | 2023-08-15 | President And Fellows Of Harvard College | Fluid injection |
| FR3000688A1 (en) * | 2013-01-08 | 2014-07-11 | Centre Nat Rech Scient | PROCESS FOR ACTIVATING A CHEMICAL REACTION, MIXTURE ACTIVABLE THEREBY AND DEVICE FOR CARRYING OUT SAID METHOD |
| WO2014108627A1 (en) * | 2013-01-08 | 2014-07-17 | Centre National De La Recherche Scientifique - Cnrs - | Method for activating a chemical reaction, solution that can be activated by said method and device for implementing said method |
| US9545375B2 (en) | 2013-01-08 | 2017-01-17 | Centre National de la Recherche Scientifique—CNRS | Method for activating a chemical reaction, solution that can be activated by said method and device for implementing said method |
| US10258987B2 (en) | 2014-06-26 | 2019-04-16 | President And Fellows Of Harvard College | Fluid infection using acoustic waves |
Also Published As
| Publication number | Publication date |
|---|---|
| GB0719502D0 (en) | 2007-11-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |