US20110186784A9 - Emulsions of Ionic Liquids - Google Patents

Emulsions of Ionic Liquids Download PDF

Info

Publication number
US20110186784A9
US20110186784A9 US12/547,379 US54737909A US2011186784A9 US 20110186784 A9 US20110186784 A9 US 20110186784A9 US 54737909 A US54737909 A US 54737909A US 2011186784 A9 US2011186784 A9 US 2011186784A9
Authority
US
United States
Prior art keywords
emulsion
composition
buffer
various embodiments
droplets
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.)
Abandoned
Application number
US12/547,379
Other versions
US20090309071A1 (en
Inventor
Zbigniew T. Bryning
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Life Technologies Corp
Original Assignee
Life Technologies Corp
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from US10/444,848 external-priority patent/US7572409B2/en
Application filed by Life Technologies Corp filed Critical Life Technologies Corp
Priority to US12/547,379 priority Critical patent/US20110186784A9/en
Publication of US20090309071A1 publication Critical patent/US20090309071A1/en
Publication of US20110186784A9 publication Critical patent/US20110186784A9/en
Priority to US13/269,476 priority patent/US20120055793A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/40Mixing liquids with liquids; Emulsifying
    • B01F23/41Emulsifying
    • B01F23/411Emulsifying using electrical or magnetic fields, heat or vibrations
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30Micromixers
    • B01F33/3031Micromixers using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids

Definitions

  • the present teachings relate to methods for creating an emulsion of ionic liquids and methods for separating mixtures of chemical and/or biological components in the emulsions.
  • the present teachings can also relate to methods for creating an emulsion in a capillary.
  • Electrophoresis as known in the art of handling a biological sample can include a process of handling, such as concentrating and/or separating charged species in the biological sample.
  • biological sample as used herein can refer to components in biological fluids (e.g. blood, lymph, urine, sweat, etc.), reactants, and/or reaction products, any of which can include peptides, nucleotides, or other charged species.
  • electrophoresis is capillary electrophoresis.
  • Capillary electrophoresis devices can, for example, be used to separate various charged species present in a liquid sample, such as a biological sample. The charged species present in the biological sample migrate through the capillary under an applied voltage created by a voltage source, such as an electrode wherein the ions are pulled through the capillary.
  • Emulsions can include at least one surfactant and at least two buffers, such as water and a non-aqueous solvent.
  • a surfactant such as water and a non-aqueous solvent.
  • o/w oil-in-water
  • w/o water-in-oil
  • w/o water-in-oil
  • Emulsions and solid phases are commonly used in separation techniques from classical chromatography to micro-emulsion electrokinetic capillary chromatography (MEEKC).
  • MEEKC micro-emulsion electrokinetic capillary chromatography
  • the emulsions or beads are created outside separation columns or capillaries and then inserted into the columns or capillaries.
  • the packaging of the emulsion or beads into small capillaries or, alternatively, in integrated microdevices can be very difficult. It can be desirable to form an emulsion inside a small capillary or integrated microdevice.
  • the present teachings can provide a method for providing an emulsion in a capillary including introducing into the capillary a composition including a buffer and an ionic liquid; and applying a voltage across the composition to form an emulsion.
  • a method for creating an emulsion can include contacting a sample including a solute with a composition including a buffer and an ionic liquid; and applying a voltage across the composition to form an emulsion.
  • the present teachings can provide a method for creating beads inside a capillary including inserting in the capillary a composition including a buffer and an ionic liquid; applying a voltage across the composition to form an emulsion; and solidifying the emulsion droplets to form beads.
  • a method for separating a solute from a sample can include applying a voltage across a composition including the sample, an ionic liquid, and a buffer to form an emulsion; and separating the solute from the sample.
  • a method for separating a solute from a sample can include applying a voltage across a composition including the sample, a buffer, and an ionic liquid to form an emulsion; packing the emulsion droplets against a barrier; and stripping the solute from the emulsion.
  • FIG. 1 illustrates a cross-section of various embodiments of a capillary with a buffer segment between two ionic liquid segments.
  • FIGS. 2A-B illustrate fluorescent images of an embodiment of the present teachings showing formation of emulsion droplets in a buffer.
  • FIGS. 3A-B illustrate a fluorescent and actual image of an embodiment of the present teachings showing formation of emulsion droplets in a buffer.
  • FIG. 4 illustrates a fluorescent image of an embodiment of the present teachings wherein the oligonucleotides are separated from the emulsion droplets.
  • FIGS. 5A-B illustrate fluorescent images of an embodiment of the present teachings showing the coalescing of emulsion droplets after a period of time.
  • FIGS. 6A-B illustrate a fluorescent and an actual image of an embodiment of the present teachings wherein small and uniform emulsion droplets are packed and seen under fluorescence light ( FIG. 6A ) and transmission light ( FIG. 6B ).
  • FIG. 1 illustrates reservoirs 10 containing ionic liquid 12 , electrode 14 , capillary 16 , and buffer 18 .
  • Capillary 16 can be shaped such that its ends are submerged below the surface of the ionic liquid 12 in the reservoir 10 .
  • Electrode 14 can be a platinum wire or any other appropriate material to apply a current across the ionic liquid segments and buffer segment.
  • the material and dimensions of the capillary device are illustrative and can be altered by one skilled in the art of microfluidics to any material and dimensions.
  • the capillary can be used in an integrated microdevice, such as a microfluidics device.
  • FIG. 1 is illustrative and any configuration can be used.
  • channels including microchannels can be used instead of capillaries.
  • Microchannels can be desirable channels because they provide several advantages over capillaries. Microchannels can facilitate manufacturing and manipulation of liquids by filling access holes to prevent evaporation. The ionic liquid segment and buffer segment can be introduced by applying vacuum, centripetal forces, active or passive capillary forces, and/or pressure.
  • a composition, for example, which can be used in the disclosed embodiments can include an ionic liquid and a buffer.
  • ionic liquid refers to salts that are liquid over a wide temperature range, including room temperature. Ionic liquids have been described at http://bama.ua.edu/ ⁇ rdrogers/webdocs/RTIL. Variations in cations and anions can produce millions of ionic liquids, including chiral, fluorinated, and antibacterial ionic liquids. The large number of possibilities can provide ionic liquid properties tailored to specific applications. Ionic liquids can be desirable because they are environmentally-friendly alternatives to organic solvents for liquid/liquid extractions, catalysis, separations, and electrochemistry.
  • Ionic liquids can reduce the cost, disposal requirements, and hazards associated with volatile organic compounds.
  • Exemplary properties of ionic liquids include at least one of high ionic conductivity, non-volatility, non-flammability, high thermal stability, wide temperature for liquid phase, highly solvability, and non-coordinating.
  • cations and anions determine the physical properties (e.g. melting point, viscosity, density, water solubility, etc.) of the ionic liquid.
  • cations can be big, bulky, and asymmetric, possibly resulting in an ionic liquid with a low melting point.
  • anions can contribute more to the overall characteristics of the ionic liquid, such as air and water stability.
  • the melting point for ionic liquids can be changed by structural variation of at least one of the ions or combining different ions.
  • Examples of ionic liquid cations can include N-butylpyridinium and 1-alkyl-3-methylimidazolium (1,3-dialkylimidazolium; alkyl mim).
  • Examples of anions can include PF 6 that is immiscible in water, and BF 4 ⁇ that is miscible in water depending on the ratio of ionic liquid to water, system temperature, and alkyl chain length of cation.
  • anions can include triflate (TfO; CF 3 SO 2 ⁇ ), nonaflate (NfO; CF 3 (CF 2 ) 3 SO 2 ⁇ ), bis(triflyl)amide (Tf 2 N; (CF 3 SO 2 ) 2 N ⁇ ), trifluoroacetate (TA; CF 3 CO 2 ⁇ ), and nonafluorobutanoate (HB; CF 3 (CF 2 ) 3 CO 2 ⁇ ).
  • ionic liquids can include haloaluminates such as chloroaluminate. Chloro- and bromo- ionic liquids can have large electrochemical windows because molten salts prevent salvation and solvolysis of the metal ion species.
  • ionic liquids can include 1-alkyl-3-methylimidazolium PF 6 such as 1-decyl-3-methylimidazolium PF 6 , 1-butyl-3-methylimidazolium PF 6 , and 1-ethyl-3-methylimidazolium with NO 3 , NO 2 , MeCO 2 , SO 4 , PF 6 , TfO, NfO, BF 4 , Tf 2 N, and TA, N-alkylpyridinium chloride or N-alkylpyridium nickel chloride with C 12 to C 18 alkyl chains, and any variations of these as are known to one skilled in the art of ionic fluids.
  • 1-alkyl-3-methylimidazolium PF 6 such as 1-decyl-3-methylimidazolium PF 6 , 1-butyl-3-methylimidazolium PF 6 , and 1-ethyl-3-methylimidazolium with NO 3 , NO 2 , MeCO 2
  • Examples include 1-ethyl-3-methylimidazolium bis(1,2-benzenediolato-O,O′)borate, 1-ethyl-3-methylimidazolium bis(salicylato)borate, 1-ethyl-3-methylimidazolium bis(oxalate)borate, and other compounds described in U.S. Pub. No. 2002/0015883 to Hilarius, et al., and N-alkyl-N′-alkoxyalkylimidazolium ionic liquids such as those described in Japanese Publication 2002/003478.
  • Sources of ionic liquids include Aldrich (Milwaukee, Wis.), Elementis Corp. (Durham, UK), Sachem (Austin, Tex.), TCl (Tokyo, Kasei), and Quill (N. Ireland).
  • buffer herein refers to liquids that do not mix with ionic liquids.
  • the buffer facilitates movement of the charged species through the capillary by providing a transportation medium through which the charged species travels.
  • Buffers can be aqueous (containing water), or they can be non-polar organic solvents such as DMF, DMSO, xylene, octane, perfluorodecalin, and other hydrocarbons that can be at least partially soluble with the biological material.
  • Buffers can be aqueous or organic because ionic liquids can be hydrophilic or hydrophobic.
  • EMI BF 4 1-ethyl-3-methylimidazolium tetrafluoroborate
  • EMI TFMS 1-ethyl-3-methylimidazolium trifluoromethanesulfonate
  • the buffer segment can include a biological sample including a solute.
  • the solute can be chosen from a particle, such as a silica particle or an inert particle, and a charged species, for example a positively charged species or a negatively charged species.
  • the solute can be chosen from biomolecules and bioparticles.
  • biomolecules refers to any molecule associated with a life function. Suitable non-limiting examples of biomolecules include proteins, peptides, nucleotides, DNA, and RNA.
  • bioparticles refers to particles formed by, or useful in, any biological process. Suitable non-limiting examples of bioparticles include cells, cell organelles, cell aggregates, tissue, bacteria, protozoans, viruses, and other small organisms.
  • the solute can act as a “seed” or an initiator of the formation of the emulsion.
  • the charged species present in the solute can become associated with the emulsion droplets.
  • the term “associated” and grammatical variations thereof as used herein refers to a situation wherein the charged species and the emulsion droplets are joined or connected together in a spatial relationship.
  • the charged species can be bound to the emulsion droplets either directly or indirectly.
  • the association of the charged species with the emulsion droplet can transport charged species through the ionic liquid by the emulsion droplet.
  • DNA can act as a seed to form emulsion droplets, which can associate with the DNA. Due to the applied voltage, the associated emulsion droplets and DNA can then be transported to an electrode, such as a positive electrode of the capillary, to form a compacted emulsion.
  • the biological sample can be adapted for at least one of PCR, ligase chain reaction, antibody binding reaction, oligonucleotide ligations assay, and hybridization assay.
  • the sample can then be detected by at least one of absorbance, fluorescence spectroscopy, Raman spectroscopy, reflectance, and colorimetry.
  • a composition including a buffer and an ionic liquid is introduced into a capillary.
  • a voltage is then applied across the composition to form an emulsion.
  • the voltage can be applied for a sufficient period of time for an emulsion to form.
  • the voltage can be applied from 1 minute to 48 hours, for example from 1 minute to 24 hours, as a further example from 2 minutes to 5 minutes.
  • the voltage applied across the composition can range from 100 v to 2000 v, for example from 500 v to 1000 v.
  • the electric field strength can vary.
  • the electric field strength can range from 1 v/cm to 1000 v/cm.
  • an emulsion can include emulsion droplets.
  • the size, shape, electric charge, and polarizability of the emulsion droplets can depend on several factors, including, for example, the properties of the biomolecules or bioparticles present in the biological sample.
  • the size of the emulsion droplets can be controlled by at least one of the buffer composition, the current density, the ionic liquid, and time.
  • the emulsion droplets can range, for example, in size from 1 nm to 10 nm, such as in a microemulsion.
  • emulsion droplets can range up to the order of millimeters.
  • the initial emulsion droplets can be nanometer in size.
  • the size of the emulsion droplets can increase to millimeters in size.
  • the emulsion droplets can solidify or coalesce to form larger emulsion droplets, as shown in FIGS. 5A-B .
  • the emulsion droplets cannot be the same size throughout the capillary, but can vary in size.
  • the charge of the emulsion droplets can be controlled by the buffer composition, i.e., the emulsion droplets can be positive, negative, or have no charge.
  • the charge of the emulsion droplets and the solute present in the buffer can be the same or different.
  • separation and grammatical variations thereof as used herein refers to the process of separating charged species based on their charge/size. Separation can result from differentiating the charged species by charge/size ratio by using a separation polymer as known in the art of electrophoresis.
  • polymer as used herein refers to oligomers, homopolymers, and copolymers and mixtures thereof as known in the art of polymer chemistry.
  • the polymer can be used to at least one of stabilize the emulsion or help separate the charged species associated with the emulsion droplets.
  • the emulsion droplets can be packed against a barrier.
  • the solute such as the charged species
  • the solute can be stripped from the emulsion droplets by reversing the direction of the voltage applied across the composition, such as shown in FIG. 4 .
  • the timing of emulsion droplet formation and charged species travel can be correlated In the properties of the buffer as is known in the art of electrophoresis.
  • the emulsion droplets can be solidified to form solid phases, for example beads. Once formed, the beads can be used in standard chromatography or as, for example, a filtration grid in microfluidic devices.
  • the emulsion is formed at a first temperature, which is then decreased to a second temperature wherein the emulsion solidifies.
  • a composition including a biological sample, an ionic liquid, and a buffer can be at a first temperature ranging from 20° C. to 200° C. immediately prior to application of the voltage.
  • the emulsion droplets can be solidified by providing an ionic liquid having a combination of ions resulting in the solidification of the emulsion droplets.
  • a reaction can be performed within the buffer.
  • reaction refers to the process of reacting reactants to form reaction products within the buffer.
  • a reaction can result from providing reaction conditions such as temperature changes to the reactants within the buffer.
  • reaction conditions such as temperature changes to the reactants within the buffer.
  • the charged species can be concentrated to provide better detection of the reaction products by absorbance, spectroscopy (fluorescence or Raman), reflectance, colorimetry and any other detection known in the art of analysis of biological materials.
  • the ionic liquid and buffer can be static or they can be in a continuous segmented flow.
  • continuous flow can provide the ability to pass the segments flowing through a channel through different process conditions such as water baths or other heating/cooling devices to thermally cycle the segments as in polymerase chain reaction (PCR), for example.
  • PCR polymerase chain reaction
  • the present teachings can provide a device for sample preparation including a substrate with at least one capillary channel.
  • a capillary channel operates functionally like a capillary but is constructed by etching or cutting a volume into a portion of the substrate.
  • the capillary channel can be difficult to fill with an emulsion.
  • the present teachings permit introduction of the emulsion into the capillary channel for samples preparation.
  • a solution of ionic liquids and buffer can be introduced into the capillary channel such that an emulsion forms separating biomolecules and bioparticles.
  • At least two electrodes can provide a voltage across the capillary channel to form the emulsion.
  • the device has a network of capillary channels and a plurality of electrodes to provide multiple emulsions.
  • the emulsion includes emulsion droplets with biomolecules that can be separated from the bioparticles.
  • the emulsion droplets are solid.
  • the device includes other unit operations such as PCR or ligase reaction for analysis, and detection of biomolecule analysis.
  • FIGS. 2A-B are exemplary illustrations of various embodiments of the invention.
  • FIG. 2A illustrates an embodiment wherein a voltage was applied across a composition including a buffer, an ionic liquid, and oligonucleotides. In a period of minutes, the oligonucleotides appeared to associate with the small emulsion droplets. The oligonucleotides were dragged toward the positive electrode. As illustrated in FIG. 2B , near the ionic liquid/buffer interface, the emulsion droplets collided and fused, forming larger emulsion droplets. At higher voltages (e.g. 500 v) the oligonucleotides became disassociated with the emulsion droplets and continued to move toward the positive electrode whereas the emulsion droplets moved toward the negative electrode.
  • higher voltages e.g. 500 v
  • FIGS. 3A-B are exemplary illustrations of various embodiments of the invention.
  • FIG. 3A illustrates the formation of emulsion droplets in a buffer wherein the emulsion was detected by fluorescence imaging.
  • FIG. 3B illustrates the formation of emulsion droplets in a buffer wherein the emulsion was detected by transmitted light.
  • BMI PF 6 1-butyl-3-methylimidazolium hexafluorophosphate
  • DMBI PF 6 1,2-dimethyl-3-butylimidazolium hexafluorophosphate
  • FIG. 6A wherein the formation of small and uniformly packed emulsion droplets is seen under fluorescence light.
  • FIG. 6B shows small and uniformly packed emulsion droplets seen under transmission light.
  • the oligonucleotides and associated emulsion droplets were packed against a barrier.
  • the oligonucleotides disassociated from the emulsion droplets when the voltage was changed from positive to negative as illustrated in FIG. 4 .
  • An emulsion was formed in a capillary as described in Examples 1 and 2. After an hour the small emulsion droplets began to coalesce as shown in FIG. 5A . After 24 hours, the emulsion droplets had coalesced into larger droplets as shown in FIG. 5B .

Abstract

The present teachings provide emulsions using ionic liquids for separation of biomolecules and related methods, compositions, and devices.

Description

    CROSS REFERENCE TO RELATED APPLICATION
  • This application is a divisional of U.S. patent application Ser. No. 10/853,911 filed May 25, 2004.
  • FIELD
  • The present teachings relate to methods for creating an emulsion of ionic liquids and methods for separating mixtures of chemical and/or biological components in the emulsions. The present teachings can also relate to methods for creating an emulsion in a capillary.
  • INTRODUCTION
  • Electrophoresis as known in the art of handling a biological sample can include a process of handling, such as concentrating and/or separating charged species in the biological sample. The term “biological sample” as used herein can refer to components in biological fluids (e.g. blood, lymph, urine, sweat, etc.), reactants, and/or reaction products, any of which can include peptides, nucleotides, or other charged species. One example of electrophoresis is capillary electrophoresis. Capillary electrophoresis devices can, for example, be used to separate various charged species present in a liquid sample, such as a biological sample. The charged species present in the biological sample migrate through the capillary under an applied voltage created by a voltage source, such as an electrode wherein the ions are pulled through the capillary.
  • Emulsions can include at least one surfactant and at least two buffers, such as water and a non-aqueous solvent. One type of emulsion, commonly known as an oil-in-water (o/w) emulsion, has a continuous phase (water) and a disperse phase (droplets of non-aqueous solvent stabilized by a surfactant). Another type of emulsion, commonly known as a water-in-oil (w/o) emulsion, has a disperse aqueous phase and a continuous non-aqueous phase.
  • Emulsions and solid phases, for example solid beads, are commonly used in separation techniques from classical chromatography to micro-emulsion electrokinetic capillary chromatography (MEEKC). The emulsions or beads are created outside separation columns or capillaries and then inserted into the columns or capillaries. However, the packaging of the emulsion or beads into small capillaries or, alternatively, in integrated microdevices can be very difficult. It can be desirable to form an emulsion inside a small capillary or integrated microdevice.
  • SUMMARY
  • In various embodiments, the present teachings can provide a method for providing an emulsion in a capillary including introducing into the capillary a composition including a buffer and an ionic liquid; and applying a voltage across the composition to form an emulsion. In various embodiments, a method for creating an emulsion can include contacting a sample including a solute with a composition including a buffer and an ionic liquid; and applying a voltage across the composition to form an emulsion.
  • In various embodiments, the present teachings can provide a method for creating beads inside a capillary including inserting in the capillary a composition including a buffer and an ionic liquid; applying a voltage across the composition to form an emulsion; and solidifying the emulsion droplets to form beads.
  • In various embodiments, a method for separating a solute from a sample can include applying a voltage across a composition including the sample, an ionic liquid, and a buffer to form an emulsion; and separating the solute from the sample. In various embodiments, a method for separating a solute from a sample can include applying a voltage across a composition including the sample, a buffer, and an ionic liquid to form an emulsion; packing the emulsion droplets against a barrier; and stripping the solute from the emulsion.
  • It is to be understood that both the foregoing general description and the following description of various embodiments are exemplary and explanatory only and are not restrictive.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate various embodiments.
  • FIG. 1 illustrates a cross-section of various embodiments of a capillary with a buffer segment between two ionic liquid segments.
  • FIGS. 2A-B illustrate fluorescent images of an embodiment of the present teachings showing formation of emulsion droplets in a buffer.
  • FIGS. 3A-B illustrate a fluorescent and actual image of an embodiment of the present teachings showing formation of emulsion droplets in a buffer.
  • FIG. 4 illustrates a fluorescent image of an embodiment of the present teachings wherein the oligonucleotides are separated from the emulsion droplets.
  • FIGS. 5A-B illustrate fluorescent images of an embodiment of the present teachings showing the coalescing of emulsion droplets after a period of time.
  • FIGS. 6A-B illustrate a fluorescent and an actual image of an embodiment of the present teachings wherein small and uniform emulsion droplets are packed and seen under fluorescence light (FIG. 6A) and transmission light (FIG. 6B).
  • DESCRIPTION OF VARIOUS EMBODIMENTS
  • Reference will now be made to various exemplary embodiments, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers are used in the drawings and the description to refer to the same or like parts. in various embodiments, as illustrated in FIGS. 1-5B, the present teachings can relate to methods for creating an emulsion in a capillary. In various embodiments, FIG. 1 illustrates reservoirs 10 containing ionic liquid 12, electrode 14, capillary 16, and buffer 18. Capillary 16 can be shaped such that its ends are submerged below the surface of the ionic liquid 12 in the reservoir 10. Submerging the openings of capillary 16 provides a continuous ionic liquid segment from the reservoir 10 and into the capillary 16 on either end of a segment of buffer 18. The term “segment” refers to a section of liquid. Electrode 14 can be a platinum wire or any other appropriate material to apply a current across the ionic liquid segments and buffer segment. The material and dimensions of the capillary device are illustrative and can be altered by one skilled in the art of microfluidics to any material and dimensions. For example, the capillary can be used in an integrated microdevice, such as a microfluidics device. FIG. 1 is illustrative and any configuration can be used.
  • In various embodiments, channels, including microchannels can be used instead of capillaries. Microchannels can be desirable channels because they provide several advantages over capillaries. Microchannels can facilitate manufacturing and manipulation of liquids by filling access holes to prevent evaporation. The ionic liquid segment and buffer segment can be introduced by applying vacuum, centripetal forces, active or passive capillary forces, and/or pressure.
  • A composition, for example, which can be used in the disclosed embodiments can include an ionic liquid and a buffer. The term “ionic liquid” refers to salts that are liquid over a wide temperature range, including room temperature. Ionic liquids have been described at http://bama.ua.edu/˜rdrogers/webdocs/RTIL. Variations in cations and anions can produce millions of ionic liquids, including chiral, fluorinated, and antibacterial ionic liquids. The large number of possibilities can provide ionic liquid properties tailored to specific applications. Ionic liquids can be desirable because they are environmentally-friendly alternatives to organic solvents for liquid/liquid extractions, catalysis, separations, and electrochemistry. Ionic liquids can reduce the cost, disposal requirements, and hazards associated with volatile organic compounds. Exemplary properties of ionic liquids include at least one of high ionic conductivity, non-volatility, non-flammability, high thermal stability, wide temperature for liquid phase, highly solvability, and non-coordinating.
  • The choice of cations and anions determine the physical properties (e.g. melting point, viscosity, density, water solubility, etc.) of the ionic liquid. For example, cations can be big, bulky, and asymmetric, possibly resulting in an ionic liquid with a low melting point. As another example, anions can contribute more to the overall characteristics of the ionic liquid, such as air and water stability. The melting point for ionic liquids can be changed by structural variation of at least one of the ions or combining different ions.
  • Examples of ionic liquid cations can include N-butylpyridinium and 1-alkyl-3-methylimidazolium (1,3-dialkylimidazolium; alkyl mim). Examples of anions can include PF6 that is immiscible in water, and BF4 that is miscible in water depending on the ratio of ionic liquid to water, system temperature, and alkyl chain length of cation. Other anions can include triflate (TfO; CF3SO2 ), nonaflate (NfO; CF3(CF2)3SO2 ), bis(triflyl)amide (Tf2N; (CF3SO2)2N), trifluoroacetate (TA; CF3CO2 ), and nonafluorobutanoate (HB; CF3(CF2)3CO2 ). Other examples of ionic liquids can include haloaluminates such as chloroaluminate. Chloro- and bromo- ionic liquids can have large electrochemical windows because molten salts prevent salvation and solvolysis of the metal ion species. Further examples of ionic liquids can include 1-alkyl-3-methylimidazolium PF6 such as 1-decyl-3-methylimidazolium PF6, 1-butyl-3-methylimidazolium PF6, and 1-ethyl-3-methylimidazolium with NO3, NO2, MeCO2, SO4, PF6, TfO, NfO, BF4, Tf2N, and TA, N-alkylpyridinium chloride or N-alkylpyridium nickel chloride with C12 to C18 alkyl chains, and any variations of these as are known to one skilled in the art of ionic fluids. Other examples include 1-ethyl-3-methylimidazolium bis(1,2-benzenediolato-O,O′)borate, 1-ethyl-3-methylimidazolium bis(salicylato)borate, 1-ethyl-3-methylimidazolium bis(oxalate)borate, and other compounds described in U.S. Pub. No. 2002/0015883 to Hilarius, et al., and N-alkyl-N′-alkoxyalkylimidazolium ionic liquids such as those described in Japanese Publication 2002/003478.
  • Sources of ionic liquids include Aldrich (Milwaukee, Wis.), Elementis Corp. (Durham, UK), Sachem (Austin, Tex.), TCl (Tokyo, Kasei), and Quill (N. Ireland).
  • The term ‘buffer’ herein refers to liquids that do not mix with ionic liquids. The buffer facilitates movement of the charged species through the capillary by providing a transportation medium through which the charged species travels. Buffers can be aqueous (containing water), or they can be non-polar organic solvents such as DMF, DMSO, xylene, octane, perfluorodecalin, and other hydrocarbons that can be at least partially soluble with the biological material. Buffers can be aqueous or organic because ionic liquids can be hydrophilic or hydrophobic. In various embodiments, hydrophobic ionic liquid segments of 1-butyl-3-methylimidazolium hexafluorophosphate (BMI PF6) and 1,2-dimethyl-3-butylimidazolium hexafluorophosphate (DMBI PF6) from Sachem, Inc. (Austin, Tex.) can be used with aqueous buffer segments, and hydrophilic ionic liquid segments of 1-ethyl-3-methylimidazolium tetrafluoroborate (EMI BF4) and 1-ethyl-3-methylimidazolium trifluoromethanesulfonate (EMI TFMS) from TCl (Tokyo Kasei) can be used with non-polar organic solvent buffer segments.
  • The buffer segment can include a biological sample including a solute. The solute can be chosen from a particle, such as a silica particle or an inert particle, and a charged species, for example a positively charged species or a negatively charged species. For example, the solute can be chosen from biomolecules and bioparticles. In various embodiments, the term “biomolecules” refers to any molecule associated with a life function. Suitable non-limiting examples of biomolecules include proteins, peptides, nucleotides, DNA, and RNA.
  • In various embodiments, the term “bioparticles” refers to particles formed by, or useful in, any biological process. Suitable non-limiting examples of bioparticles include cells, cell organelles, cell aggregates, tissue, bacteria, protozoans, viruses, and other small organisms.
  • In various embodiments, the solute can act as a “seed” or an initiator of the formation of the emulsion. For example, the charged species present in the solute can become associated with the emulsion droplets. The term “associated” and grammatical variations thereof as used herein refers to a situation wherein the charged species and the emulsion droplets are joined or connected together in a spatial relationship. For example, the charged species can be bound to the emulsion droplets either directly or indirectly. The association of the charged species with the emulsion droplet can transport charged species through the ionic liquid by the emulsion droplet. For example, DNA can act as a seed to form emulsion droplets, which can associate with the DNA. Due to the applied voltage, the associated emulsion droplets and DNA can then be transported to an electrode, such as a positive electrode of the capillary, to form a compacted emulsion.
  • The biological sample can be adapted for at least one of PCR, ligase chain reaction, antibody binding reaction, oligonucleotide ligations assay, and hybridization assay. The sample can then be detected by at least one of absorbance, fluorescence spectroscopy, Raman spectroscopy, reflectance, and colorimetry.
  • In various embodiments, a composition including a buffer and an ionic liquid is introduced into a capillary. A voltage is then applied across the composition to form an emulsion.
  • The voltage can be applied for a sufficient period of time for an emulsion to form. The voltage can be applied from 1 minute to 48 hours, for example from 1 minute to 24 hours, as a further example from 2 minutes to 5 minutes.
  • The voltage applied across the composition can range from 100 v to 2000 v, for example from 500 v to 1000 v. Depending upon the length of the capillary, the electric field strength can vary. For example, the electric field strength can range from 1 v/cm to 1000 v/cm. By varying the electric field, the solute can be transported through the ionic liquid. Moreover, once an emulsion is formed, the solute can become disassociated or separated from the emulsion droplets by increasing and/or reversing the voltage from the initial voltage used to create the emulsion.
  • In various embodiments, an emulsion can include emulsion droplets. The size, shape, electric charge, and polarizability of the emulsion droplets can depend on several factors, including, for example, the properties of the biomolecules or bioparticles present in the biological sample. For example, the size of the emulsion droplets can be controlled by at least one of the buffer composition, the current density, the ionic liquid, and time. In various embodiments, the emulsion droplets can range, for example, in size from 1 nm to 10 nm, such as in a microemulsion. In various embodiments, emulsion droplets can range up to the order of millimeters. For example, at an initial time T0, the initial emulsion droplets can be nanometer in size. However, at a second time, T1, the size of the emulsion droplets can increase to millimeters in size. As the time progresses from an initial time T0 to a time T1, then it is believed that the emulsion droplets can solidify or coalesce to form larger emulsion droplets, as shown in FIGS. 5A-B. Moreover, the emulsion droplets cannot be the same size throughout the capillary, but can vary in size.
  • In various embodiments, the charge of the emulsion droplets can be controlled by the buffer composition, i.e., the emulsion droplets can be positive, negative, or have no charge. The charge of the emulsion droplets and the solute present in the buffer can be the same or different.
  • The term “separation” and grammatical variations thereof as used herein refers to the process of separating charged species based on their charge/size. Separation can result from differentiating the charged species by charge/size ratio by using a separation polymer as known in the art of electrophoresis. The term “polymer” as used herein refers to oligomers, homopolymers, and copolymers and mixtures thereof as known in the art of polymer chemistry. For example, the polymer can be used to at least one of stabilize the emulsion or help separate the charged species associated with the emulsion droplets. In various embodiments, once the emulsion is formed, the emulsion droplets can be packed against a barrier. The solute, such as the charged species, can then be disassociated or separated from the emulsion droplets by using standard techniques. For example, the solute can be stripped from the emulsion droplets by reversing the direction of the voltage applied across the composition, such as shown in FIG. 4.
  • The timing of emulsion droplet formation and charged species travel can be correlated In the properties of the buffer as is known in the art of electrophoresis.
  • The emulsion droplets can be solidified to form solid phases, for example beads. Once formed, the beads can be used in standard chromatography or as, for example, a filtration grid in microfluidic devices. In various embodiments, the emulsion is formed at a first temperature, which is then decreased to a second temperature wherein the emulsion solidifies. For example, a composition including a biological sample, an ionic liquid, and a buffer can be at a first temperature ranging from 20° C. to 200° C. immediately prior to application of the voltage. In various embodiments, the emulsion droplets can be solidified by providing an ionic liquid having a combination of ions resulting in the solidification of the emulsion droplets.
  • In various embodiments, a reaction can be performed within the buffer. The term “reaction” refers to the process of reacting reactants to form reaction products within the buffer. A reaction can result from providing reaction conditions such as temperature changes to the reactants within the buffer. Several biological reactions are described herein. In various embodiments, the charged species can be concentrated to provide better detection of the reaction products by absorbance, spectroscopy (fluorescence or Raman), reflectance, colorimetry and any other detection known in the art of analysis of biological materials.
  • In various embodiments, the ionic liquid and buffer can be static or they can be in a continuous segmented flow. In various embodiments, continuous flow can provide the ability to pass the segments flowing through a channel through different process conditions such as water baths or other heating/cooling devices to thermally cycle the segments as in polymerase chain reaction (PCR), for example.
  • In various embodiments, the present teachings can provide a device for sample preparation including a substrate with at least one capillary channel. A capillary channel operates functionally like a capillary but is constructed by etching or cutting a volume into a portion of the substrate. The capillary channel can be difficult to fill with an emulsion. The present teachings permit introduction of the emulsion into the capillary channel for samples preparation. A solution of ionic liquids and buffer can be introduced into the capillary channel such that an emulsion forms separating biomolecules and bioparticles. At least two electrodes can provide a voltage across the capillary channel to form the emulsion. In various embodiments, the device has a network of capillary channels and a plurality of electrodes to provide multiple emulsions.
  • In various embodiments, the emulsion includes emulsion droplets with biomolecules that can be separated from the bioparticles. In various embodiments, the emulsion droplets are solid.
  • In various embodiments, the device includes other unit operations such as PCR or ligase reaction for analysis, and detection of biomolecule analysis.
  • EXAMPLES
  • The following examples are illustrative and are non-limiting to the present teachings.
  • Example 1
  • FIGS. 2A-B are exemplary illustrations of various embodiments of the invention. FIG. 2A illustrates an embodiment wherein a voltage was applied across a composition including a buffer, an ionic liquid, and oligonucleotides. In a period of minutes, the oligonucleotides appeared to associate with the small emulsion droplets. The oligonucleotides were dragged toward the positive electrode. As illustrated in FIG. 2B, near the ionic liquid/buffer interface, the emulsion droplets collided and fused, forming larger emulsion droplets. At higher voltages (e.g. 500 v) the oligonucleotides became disassociated with the emulsion droplets and continued to move toward the positive electrode whereas the emulsion droplets moved toward the negative electrode.
  • FIGS. 3A-B are exemplary illustrations of various embodiments of the invention. FIG. 3A illustrates the formation of emulsion droplets in a buffer wherein the emulsion was detected by fluorescence imaging. FIG. 3B illustrates the formation of emulsion droplets in a buffer wherein the emulsion was detected by transmitted light.
  • Example 2
  • A buffer, TRIS-EDTA with 0.5% of POP-6® (Applied Biosystems, Foster City), containing a sample of oligonucleotides, a mixture of 30 and 90 base oligonucleotides labeled with Lys, and an ionic liquid, a 50:50 mixture of 1-butyl-3-methylimidazolium hexafluorophosphate (BMI PF6) and 1,2-dimethyl-3-butylimidazolium hexafluorophosphate (DMBI PF6) from Sachem, Inc. (Austin, Tex.) were introduced into a capillary tube. A voltage of 1000 v was applied for 20 minutes. The oligonucleotides acted as “seeds” for the formation of the emulsion droplets which then associated with the oligonucleotides. This is illustrated by FIG. 6A wherein the formation of small and uniformly packed emulsion droplets is seen under fluorescence light. FIG. 6B shows small and uniformly packed emulsion droplets seen under transmission light.
  • The oligonucleotides and associated emulsion droplets were packed against a barrier. The oligonucleotides disassociated from the emulsion droplets when the voltage was changed from positive to negative as illustrated in FIG. 4.
  • Example 3
  • An emulsion was formed in a capillary as described in Examples 1 and 2. After an hour the small emulsion droplets began to coalesce as shown in FIG. 5A. After 24 hours, the emulsion droplets had coalesced into larger droplets as shown in FIG. 5B.
  • For the purposes of this specification and appended claims, unless otherwise indicated, all numbers expressing quantities, percentages or proportions, and other numerical values used in the specification and claims, are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.
  • Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Moreover, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein. For example, a range of “less than 10” includes any and all subranges between (and including) the minimum value of zero and the maximum value of 10, that is, any and all subranges having a minimum value of equal to or greater than zero and a maximum value of equal to or less than 10, e.g., 1 to 5.
  • It is noted that, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the,” include plural referents unless expressly and unequivocally limited to one referent. Thus, for example, reference to “a charged species” includes two or more different charged species. As used herein, the term “include” and its grammatical variants are intended to be non-limiting, such that recitation of items in a list is not to the exclusion of other like items that can be substituted or added to the listed items.
  • It will be apparent to those skilled in the art that various modifications and variations can be made to various embodiments described herein without departing from the spirit or scope of the present teachings. Thus, it is intended that the various embodiments described herein cover other modifications and variations within the scope of the appended claims and their equivalents.

Claims (10)

1. A composition comprising:
an emulsion, the emulsion comprising.
a solute, wherein the solute comprises biomolecules;
a buffer; and
an ionic liquid,
wherein the emulsion is formed by applying a voltage across the composition.
2. The composition of claim 1, wherein the emulsion comprises droplets ranging in size from 1 nm to 10 mm.
3. The composition of claim 2, wherein the size of the emulsion droplets is controlled by at least one of the buffer composition, the current density, and the ionic liquid.
4. Solid beads formed by solidifying the emulsion of claim 1.
5. The composition of claim 1, wherein the emulsion forms into droplets having an electric charge.
6. The composition of claim 5, wherein the charge of the emulsion droplets is controlled by the buffer composition.
7. The composition of claim 1, wherein the solute is a charged species.
8. The composition of claim 7, wherein the charged species is a positively charged species.
9. The composition of claim 7, wherein the charge of the emulsion droplets and the solute is the same.
10. The method of claim 7, wherein the charge of the emulsion droplets and the solute is different.
US12/547,379 2003-05-23 2009-08-25 Emulsions of Ionic Liquids Abandoned US20110186784A9 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US12/547,379 US20110186784A9 (en) 2003-05-23 2009-08-25 Emulsions of Ionic Liquids
US13/269,476 US20120055793A1 (en) 2003-05-23 2011-10-07 Emulsions of Ionic Liquids

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US10/444,848 US7572409B2 (en) 2003-05-23 2003-05-23 Ionic liquid apparatus and method for biological samples
US10/853,911 US7578916B2 (en) 2004-05-25 2004-05-25 Emulsions of ionic liquids
US12/538,763 US20090294286A1 (en) 2003-05-23 2009-08-10 Ionic Liquid Apparatus and Method for Biological Samples
US12/547,379 US20110186784A9 (en) 2003-05-23 2009-08-25 Emulsions of Ionic Liquids

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US10/853,911 Division US7578916B2 (en) 2003-05-23 2004-05-25 Emulsions of ionic liquids

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US13/269,476 Continuation US20120055793A1 (en) 2003-05-23 2011-10-07 Emulsions of Ionic Liquids

Publications (2)

Publication Number Publication Date
US20090309071A1 US20090309071A1 (en) 2009-12-17
US20110186784A9 true US20110186784A9 (en) 2011-08-04

Family

ID=34971592

Family Applications (3)

Application Number Title Priority Date Filing Date
US10/853,911 Active 2026-10-18 US7578916B2 (en) 2003-05-23 2004-05-25 Emulsions of ionic liquids
US12/547,379 Abandoned US20110186784A9 (en) 2003-05-23 2009-08-25 Emulsions of Ionic Liquids
US13/269,476 Abandoned US20120055793A1 (en) 2003-05-23 2011-10-07 Emulsions of Ionic Liquids

Family Applications Before (1)

Application Number Title Priority Date Filing Date
US10/853,911 Active 2026-10-18 US7578916B2 (en) 2003-05-23 2004-05-25 Emulsions of ionic liquids

Family Applications After (1)

Application Number Title Priority Date Filing Date
US13/269,476 Abandoned US20120055793A1 (en) 2003-05-23 2011-10-07 Emulsions of Ionic Liquids

Country Status (3)

Country Link
US (3) US7578916B2 (en)
EP (1) EP1763671A1 (en)
WO (1) WO2006127011A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019077114A1 (en) 2017-10-20 2019-04-25 Stilla Technologies Emulsions with improved stability

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7578916B2 (en) * 2004-05-25 2009-08-25 Applied Biosystems, Llc Emulsions of ionic liquids
US7629124B2 (en) * 2006-06-30 2009-12-08 Canon U.S. Life Sciences, Inc. Real-time PCR in micro-channels
US7935242B2 (en) * 2006-08-21 2011-05-03 Micron Technology, Inc. Method of selectively removing conductive material
US8276664B2 (en) * 2007-08-13 2012-10-02 Baker Hughes Incorporated Well treatment operations using spherical cellulosic particulates
US8380457B2 (en) * 2007-08-29 2013-02-19 Canon U.S. Life Sciences, Inc. Microfluidic devices with integrated resistive heater electrodes including systems and methods for controlling and measuring the temperatures of such heater electrodes
FR2934050B1 (en) * 2008-07-15 2016-01-29 Univ Paris Curie METHOD AND DEVICE FOR READING EMULSION
US8262880B2 (en) * 2010-03-09 2012-09-11 Empire Technology Development Llc Electrokinetic pumping of nonpolar solvents using ionic fluid
WO2012042697A1 (en) * 2010-09-27 2012-04-05 Panasonic Corporation A method for quantifying a chemical substance with substitutional stripping volammetry and a sensor chip used therefor
CN102778494A (en) * 2012-06-01 2012-11-14 江南大学 Method for separating and detecting six cortical hormones in skin-care cosmetic
US10233261B1 (en) 2016-08-19 2019-03-19 The United States Of America As Represented By The Secretary Of The Air Force Natural polymer nanoparticles from ionic liquid emulsions
CN106248741B (en) * 2016-08-23 2019-04-02 重庆大学 Bridge-type capacitive coupling non-contact conductance difference detector

Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4121466A (en) * 1977-04-19 1978-10-24 Technicon Instruments Corporation Liquid dispenser with an improved probe
US5212992A (en) * 1991-06-14 1993-05-25 Medical Laboratory Automation, Inc. Capacitive probe sensor with reduced effective stray capacitance
US5407609A (en) * 1989-05-04 1995-04-18 Southern Research Institute Microencapsulation process and products therefrom
US5580434A (en) * 1996-02-29 1996-12-03 Hewlett-Packard Company Interface apparatus for capillary electrophoresis to a matrix-assisted-laser-desorption-ionization mass spectrometer
US5779868A (en) * 1996-06-28 1998-07-14 Caliper Technologies Corporation Electropipettor and compensation means for electrophoretic bias
US6143496A (en) * 1997-04-17 2000-11-07 Cytonix Corporation Method of sampling, amplifying and quantifying segment of nucleic acid, polymerase chain reaction assembly having nanoliter-sized sample chambers, and method of filling assembly
US6197229B1 (en) * 1997-12-12 2001-03-06 Massachusetts Institute Of Technology Method for high supercoiled DNA content microspheres
US6267858B1 (en) * 1996-06-28 2001-07-31 Caliper Technologies Corp. High throughput screening assay systems in microscale fluidic devices
US6524456B1 (en) * 1999-08-12 2003-02-25 Ut-Battelle, Llc Microfluidic devices for the controlled manipulation of small volumes
US20040228882A1 (en) * 2003-05-16 2004-11-18 Dongming Qiu Process for forming an emulsion using microchannel process technology
US20040234966A1 (en) * 2003-05-23 2004-11-25 Applera Corporation Ionic liquid apparatus and method for biological samples
US6890409B2 (en) * 2001-08-24 2005-05-10 Applera Corporation Bubble-free and pressure-generating electrodes for electrophoretic and electroosmotic devices
US20060147532A1 (en) * 2002-12-06 2006-07-06 Michael Ausborn Microparticles prepared using an ionic liquid
US7166724B2 (en) * 2000-05-30 2007-01-23 Merck Patent Gmbh Ionic liquids
US7578916B2 (en) * 2004-05-25 2009-08-25 Applied Biosystems, Llc Emulsions of ionic liquids

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5429734A (en) 1993-10-12 1995-07-04 Massachusetts Institute Of Technology Monolithic capillary electrophoretic device
US6939453B2 (en) 2002-08-14 2005-09-06 Large Scale Proteomics Corporation Electrophoresis process using ionic liquids

Patent Citations (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4121466A (en) * 1977-04-19 1978-10-24 Technicon Instruments Corporation Liquid dispenser with an improved probe
US5407609A (en) * 1989-05-04 1995-04-18 Southern Research Institute Microencapsulation process and products therefrom
US5212992A (en) * 1991-06-14 1993-05-25 Medical Laboratory Automation, Inc. Capacitive probe sensor with reduced effective stray capacitance
US5580434A (en) * 1996-02-29 1996-12-03 Hewlett-Packard Company Interface apparatus for capillary electrophoresis to a matrix-assisted-laser-desorption-ionization mass spectrometer
US5779868A (en) * 1996-06-28 1998-07-14 Caliper Technologies Corporation Electropipettor and compensation means for electrophoretic bias
US6267858B1 (en) * 1996-06-28 2001-07-31 Caliper Technologies Corp. High throughput screening assay systems in microscale fluidic devices
US6143496A (en) * 1997-04-17 2000-11-07 Cytonix Corporation Method of sampling, amplifying and quantifying segment of nucleic acid, polymerase chain reaction assembly having nanoliter-sized sample chambers, and method of filling assembly
US6197229B1 (en) * 1997-12-12 2001-03-06 Massachusetts Institute Of Technology Method for high supercoiled DNA content microspheres
US6524456B1 (en) * 1999-08-12 2003-02-25 Ut-Battelle, Llc Microfluidic devices for the controlled manipulation of small volumes
US7166724B2 (en) * 2000-05-30 2007-01-23 Merck Patent Gmbh Ionic liquids
US6890409B2 (en) * 2001-08-24 2005-05-10 Applera Corporation Bubble-free and pressure-generating electrodes for electrophoretic and electroosmotic devices
US20060147532A1 (en) * 2002-12-06 2006-07-06 Michael Ausborn Microparticles prepared using an ionic liquid
US20040228882A1 (en) * 2003-05-16 2004-11-18 Dongming Qiu Process for forming an emulsion using microchannel process technology
US20040234966A1 (en) * 2003-05-23 2004-11-25 Applera Corporation Ionic liquid apparatus and method for biological samples
US7572409B2 (en) * 2003-05-23 2009-08-11 Applied Biosystems, Llc Ionic liquid apparatus and method for biological samples
US20090294286A1 (en) * 2003-05-23 2009-12-03 Life Technologies Corporation Ionic Liquid Apparatus and Method for Biological Samples
US7578916B2 (en) * 2004-05-25 2009-08-25 Applied Biosystems, Llc Emulsions of ionic liquids

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019077114A1 (en) 2017-10-20 2019-04-25 Stilla Technologies Emulsions with improved stability
US11634757B2 (en) 2017-10-20 2023-04-25 Stilla Technologies Emulsions with improved stability

Also Published As

Publication number Publication date
US20050274617A1 (en) 2005-12-15
US20120055793A1 (en) 2012-03-08
US20090309071A1 (en) 2009-12-17
EP1763671A1 (en) 2007-03-21
WO2006127011A1 (en) 2006-11-30
WO2006127011A8 (en) 2007-02-22
US7578916B2 (en) 2009-08-25

Similar Documents

Publication Publication Date Title
US20090309071A1 (en) Emulsions of Ionic Liquids
US8153417B2 (en) Ionic liquid apparatus and method for biological samples
Xu et al. Review of microfluidic liquid–liquid extractors
US10569268B2 (en) Injection of multiple volumes into or out of droplets
Paik et al. Electrowetting-based droplet mixers for microfluidic systems
Kim et al. Amplified electrokinetic response by concentration polarization near nanofluidic channel
Menard et al. Electrokinetically-driven transport of DNA through focused ion beam milled nanofluidic channels
EP2962117B1 (en) Nanofluidic devices with integrated components for the controlled capture, trapping, and transport of macromolecules and related methods of analysis
Michler et al. Are antagonistic salts surfactants?
Mashaghi et al. External control of reactions in microdroplets
US7465381B2 (en) Electrokinetic molecular separation in nanoscale fluidic channels
Zhao et al. Direct current dielectrophoretic manipulation of the ionic liquid droplets in water
GB2474228A (en) Microfluidic device for removing oil from oil separated aqueous sample droplets
Krishnamurthy et al. Recent advances in microscale extraction driven by ion concentration polarization
US10710079B2 (en) Electro-kinectic device for species exchange
Fujino et al. Size-Tunable Micro-/Nanofluidic Channels Fabricated by Freezing Aqueous Sucrose
Sidelman et al. Rapid particle patterning in surface deposited micro-droplets of low ionic content via low-voltage electrochemistry and electrokinetics
NL2008662C2 (en) Electroextraction.
Ugaz et al. Electrophoresis in microfluidic systems
Fukuyama et al. Time-resolved electrochemical measurement device for microscopic liquid interfaces during droplet formation
EP3011305B1 (en) Two-phase electroextraction from moving phases
Inagawa Ice Microfluidics: Ice as Size-Tunable Separation Field and Physicochemical Nature of Freeze Concentrated Solutions
JPS63259091A (en) Electrokinetic separation method and apparatus utilizing surface of moving charged colloidal particle
EP1682881B1 (en) Method for separating chemical substances and/or particles, device and use thereof
Liu Experimental Study of Free-solution Separation under Pulsed Electrophoresis in Microchip

Legal Events

Date Code Title Description
STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION