With Adjustment Or Alteration Of Electro-osmotic Bulk Flow Patents (Class 204/454)
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Patent number: 6471841Abstract: The present invention generally provides methods for enhancing transport and direction of materials in fluidic systems, which systems utilize electroosmotic (E/O) flow systems, to affect that transport and direction. The methods generally comprise providing an effective concentration of at least one zwitterionic compound in the fluid containing the material that is to be transported or directed.Type: GrantFiled: July 11, 2000Date of Patent: October 29, 2002Assignee: Caliper Technologies Corp.Inventors: Theo T. Nikiforov, Sang Jeong
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Patent number: 6458259Abstract: Methods and apparatus for reducing adsorption in microscale devices are provided. In the methods and apparatus, an electrical current such as an alternating current is applied to materials under pressure-induced flow. Integrated systems for simultaneous control of current and pressure in a channel are also provided.Type: GrantFiled: May 11, 1999Date of Patent: October 1, 2002Assignee: Caliper Technologies Corp.Inventors: J. Wallace Parce, Andrea W. Chow
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Publication number: 20020130045Abstract: An apparatus and method for capillary zone electrophoresis includes a polyelectrolyte multilayer positioned in a capillary tube for analytical separations of macromolecules. The capillary comprises a passage defined by passage walls comprising fused silica. The polyelectrolyte multilayer is positioned within the passage adjacent the walls, and comprises an organic polyelectrolyte. The passage may further comprise nonporous silica particles coated with a multilayer including a plurality of polyelectrolyte layers. An apparatus includes a power supply having a positive electrode and a negative electrode for generating an electric field therebetween. The apparatus includes a capillary having a passage formed by passage walls and comprising therein a polyelectrolyte multilayer positioned substantially within the passage.Type: ApplicationFiled: May 14, 2002Publication date: September 19, 2002Inventors: Joseph B. Schlenoff, Timothy W. Graul
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Patent number: 6451264Abstract: A capillary pathway is dimensioned so that the driving force for the movement of liquid through the capillary pathway arises from capillary pressure. A plurality of groups of microstructures are fixed in the capillary pathway within discrete segments of the pathway for facilitating the transport of a liquid around curved portions of pathway. Capillary channels can be coupled between two adjacent groups of microstructures to either the inner and outer wall of the capillary pathway. The width of each capillary channel is generally smaller than the capillary pathway to which it is connected, and can be varied to achieve differences in fill initiation. The grouped microstructures are spaced from each other within each group on a nearest neighbor basis by less than that necessary to achieve capillary flow of liquid with each group. Each group of microstructures are spaced from any adjacent group by an inter-group space greater than the width of any adjacent capillary channels connected to the capillary pathway.Type: GrantFiled: January 28, 2000Date of Patent: September 17, 2002Assignee: Roche Diagnostics CorporationInventors: Raghbir Singh Bhullar, Jeffrey N. Shelton, Wolfgang O. L. Reiser
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Publication number: 20020125135Abstract: A microfluidic device comprising a set of one or more, preferably more than 5, covered microchannel structures manufactured in the surface of a planar substrate. The device is characterized in that a part surface of at least one of the microchannel structures has a coat exposing a non-ionic hydrophilic polymer. The non-ionic hydrophilic polymer is preferably attached covalently directly to the part surface or to a polymer skeleton that is attached to the surface.Type: ApplicationFiled: February 26, 2002Publication date: September 12, 2002Inventors: Helene Derand, Anders Larsson, James Van Alstine
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Patent number: 6440284Abstract: The present invention provides methods of electrophoretically separating macromolecular species, as well as compositions and systems useful in carrying out such methods. Specifically, the methods of the present invention comprise providing a substrate that has at least a first capillary channel disposed therein. The surface of the channel has a first surface charge associated therewith, and is filled with a water soluble surface adsorbing polymer solution that bears a net charge that is the same as the charge on the capillary surface.Type: GrantFiled: December 17, 1999Date of Patent: August 27, 2002Assignee: Caliper Technologies Corp.Inventor: Robert S. Dubrow
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Patent number: 6406605Abstract: In one embodiment, a fluidic module, such as a microfluidic module, has a fluid-flow channel, an electroosmotic flow membrane positioned in the channel, and a cathode located on one side and an anode located on the other side of the membrane so that an electrolyte in the channel is transported through the membrane in the presence of a voltage. In another embodiment, the channel has a port, a flexible and fluid-impermeable diaphragm is added, the electrolyte is contained in a reservoir, and the membrane moves the bladder which acts as a valve for fluid leaving the channel through the port. In a further embodiment, electrolyte in a first reservoir is transported through the membrane to move the bladder to force fluid out of a second reservoir.Type: GrantFiled: May 8, 2000Date of Patent: June 18, 2002Assignee: YSI IncorporatedInventor: Donald R. Moles
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Publication number: 20020070116Abstract: A device and method for pumping an electrolyte solution includes a conduit having a first end, a second end and a lumen for containing the electrolyte solution. An opening at each end of the conduit allows electrolyte solution to enter and exit the lumen of the conduit. The device further includes a ferroelectric member that is positioned along a portion of the conduit. The ferroelectric member is formed with a contact surface for interaction with the electrolyte solution. An electrode is positioned adjacent to the ferroelectric member to polarize the ferroelectric member and charge the contact surface. Driving electrodes are positioned to establish a potential difference in the electrolyte solution across the portion of the conduit containing the ferroelectric member.Type: ApplicationFiled: December 13, 2000Publication date: June 13, 2002Inventor: Tihiro Ohkawa
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Publication number: 20020056639Abstract: Capillary electrophoresis is performed under conventional conditions in microchannels having a norbornene based polymer surface. The norbornene based polymers can be used as a solid substrate for forming the necessary features for a microfluidic device, where the entire device may be made of norbornene based polymer. Conveniently, a norbornene based polymer layer having a lower glass transition temperature may be used to adhere a cover or enclosing layer to the substrate to enclose the microchannels and provide a bottom for the reservoirs.Type: ApplicationFiled: July 20, 2001Publication date: May 16, 2002Inventors: Hilary Lackritz, Ingrid Cruzado, Hongdong Tan
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Publication number: 20020053399Abstract: Methods are provided for the fabrication of polymeric microchannel structures having enclosed microchannels of capillary dimension. The microchannel structures are constructed of a base plate and a cover, sealed together. Microchannel structures having walls of a plastic material are formed in a generally planar surface of at least the base plate. The cover has at least one generally planar surface, and the microchannel structures are enclosed by bonding the planar surfaces of the cover and the base plate together. In some embodiments the surfaces of the cover and base plate are both of plastic material, and are directly thermally bonded. In some embodiments a bonding material is applied to one of the surface prior to bringing the surfaces together. Suitable bonding materials are disclosed.Type: ApplicationFiled: December 7, 2001Publication date: May 9, 2002Applicant: Aclara Biosciences, IncInventors: David S. Soane, Herbert H. Hooper, M. Goretty Alonso-Amigo
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Publication number: 20020053514Abstract: A microchannel device is provided with a plastic substrate having a microchannel formed therein. Polyelectrolyte multilayers are disposed along selected surfaces of the microchannel. The polyelectrolyte layers comprise alternating net positively charged layers and net negatively charged layers. A microchannel lid has a surface facing the microchannel. In making the microchannel device, selected surfaces of the microchannel are alternatively exposed to solutions comprising positively charged polyelectrolytes and negatively charged polyelectrolytes to form the desired number of polyelectrolyte layers.Type: ApplicationFiled: June 15, 2001Publication date: May 9, 2002Inventors: Laurie E. Locascio, Susan L. R. Barker, David Ross, Michael J. Tarlov
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Patent number: 6375818Abstract: An article of manufacture is provided that is useful in differentiating between solutes, such as during electrophoretic separations. An embodiment of the article is a capillary tube, that carries a polymer along the inner wall of the capillary tube. The polymer is effective to reduce undesired interactions and preferably includes a polylactam that is absorbed to the surface before the surface is exposed to the solutes. A preferred polylactam is poly(vinylpyrrolidone) with a molecular weight greater than about 1,000,000 daltons (weight-average).Type: GrantFiled: June 8, 1999Date of Patent: April 23, 2002Assignee: Beckman Coulter, Inc.Inventors: Tung-Liang Huang, M. Parameswara Reddy
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Publication number: 20020043463Abstract: An apparatus for inducing movement of an electrolytic droplet includes: a housing having an internal volume filled with a liquid immiscible with an electrolytic droplet; a distribution plate positioned within the chamber having an aperture and dividing the housing into upper and lower chambers; a lower electrode positioned below the lower chamber and the aperture in the distribution plate and being separated from the lower chamber by an overlying hydrophobic insulative layer; an upper electrode located above the upper chamber and the aperture of the distribution plate and being separated from the upper chamber by an underlying hydrophobic insulative layer; and first, second and third voltage generators that are electrically connected to, respectively, the lower and upper electrodes and the distribution plate.Type: ApplicationFiled: August 30, 2001Publication date: April 18, 2002Inventor: Alexander Shenderov
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Publication number: 20020041831Abstract: A microfluidic device having a coating on a surface which surface properties can be altered by applying an external stimulus. Such a surface change may be used to guide or direct fluid on these surfaces, thus controlling flow in the microfluidic system.Type: ApplicationFiled: September 17, 2001Publication date: April 11, 2002Inventors: C. Frederick Battrell, Mingchao Shen
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Patent number: 6358385Abstract: The invention provides uncharged water-soluble silica-adsorbing polymers for suppressing electroendoosmotic flow and to reduce analyte-wall interactions in capillary electrophoresis. In one aspect of the invention, one or more of such polymers are employed as components of a separation medium for the separation of biomolecules, such as polynucleotides, polysaccharides, proteins, and the like, by capillary electrophoresis. Generally, such polymers are characterized by (i) water solubility over the temperature range between about 20° C. to about 50° C., (ii) concentration in a separation medium in the range between about 0.001% to about 10% (weight/volume), (iii) molecular weight in the range of about 5×103 to about 1×106 daltons, and (iv) absence of charged groups in an aqueous medium having pH in the range of about 6 to about 9.Type: GrantFiled: January 11, 1999Date of Patent: March 19, 2002Assignee: The Perkin-Elmer CorporationInventors: Ramakrishna S. Madabhushi, Steven M. Menchen, J. William Efcavitch, Paul D. Grossman
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Publication number: 20020029968Abstract: Compositions and methods are provided for performing capillary electrophoresis using a composition comprising in combination in an aqueous buffered medium a coating polymer and a sieving polymer, where the sieving polymer is more hydrophilic than the coating polymer and is present in greater amount. Of particular interest are uncrosslinked acrylamide polymer mixtures for coating plastic channels and providing sieving for performing DNA separations in microfluidic devices. Polyacrylamide or N,N-dimethyl acrylamide is used with a N,N-dialkyl acrylamide copolymer, either separately or together for sieving and coating, serving as the medium in capillary electrophoresis DNA separations.Type: ApplicationFiled: May 1, 2001Publication date: March 14, 2002Applicant: Aclara BioSciences, Inc.Inventors: Hongdong Roy Tan, Alexander Sassi, Ingrid Cruzado
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Publication number: 20020023840Abstract: A method for modifying and controlling fluid flow in channels formed in substrates. The method involves exposing a portion of a fluid flow channel to light at a fluence which modifies the surface charge of the substrate at the exposure site. The method can be used to immobilize chemical compounds or biological species in the fluid flow channels at the modified surfaces.Type: ApplicationFiled: July 13, 2001Publication date: February 28, 2002Inventors: Timothy J. Johnson, Emanuel A. Waddell, Jr., David J. Ross, Laurie E. Locascio
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Publication number: 20020017464Abstract: The present invention provides for techniques for transporting materials using electrokinetic forces through the channels of a microfluidic system. The subject materials are transported in regions of high ionic concentration, next to spacer material regions of high ionic concentration, which are separated by spacer material regions of low ionic concentration. Such arrangements allow the materials to remain localized for the transport transit time to avoid mixing of the materials. Using these techniques, an electropipettor which is compatible with the microfluidic system is created so that materials can be easily introduced into the microfluidic system. The present invention also compensates for electrophoretic bias as materials are transported through the channels of the microfluidic system by splitting a channel into portions with positive and negative surface charges and a third electrode between the two portions, or by diffusion of the electrophoresing materials after transport along a channel.Type: ApplicationFiled: May 3, 2001Publication date: February 14, 2002Inventors: J. Wallace Parce, Michael R. Knapp
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Patent number: 6344120Abstract: A method of controlling liquid movement in a chemical device comprising a porous structure involved applying an electrical potential to generate an electroosmotic force in the porous structure so as to propel a liquid through the porous structure. Also the porous structure is used to resist or prevent flow of a liquid through the porous structure in response to hydrostatic force.Type: GrantFiled: June 21, 2000Date of Patent: February 5, 2002Assignee: The University of HullInventors: Stephen John Haswell, Gillian Mary Greenway, Thomas McCreedy, Natalie Gayle Wilson, Victoria Skelton
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Patent number: 6322682Abstract: A method of capillary electrophoresis utilizing a capillary tube made up of hydrophobic plastics, charactarized in that the inner surface of said capillary is coated with a hydrophilic polymer comprising a polyhydroxy polymer exhibiting groups —B—R, where R is a hydrocarbyl group and B is a bridge binding to the polyhydroxy polymer, preferably by substituting a hydrogen in a hydroxy group of the polyhydroxy polymer.Type: GrantFiled: September 23, 1999Date of Patent: November 27, 2001Assignee: Gyros ABInventors: Lars-Erik Arvidsson, Björn Ekström
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Patent number: 6306273Abstract: A method is disclosed for controlling the direction and transport of a material on a microfluidic device formed from an acrylic polymer, by electrokinetic flow of a fluid containing the material. The method comprises providing an electrokinesis buffer containing a charged hydrophilic polymer, wherein charges on the polymer are randomly distributed. The method has applications for improved transport of proteins and transport of materials comprising differentially charged chemical species. A preferred embodiment of the present invention comprises use of the disclosed method for electrokinetic separations of a mixture of polypeptides having both positive and negative charges. Another preferred embodiment concerns use of the disclosed method for performing an assay involving mixing of two or more reagents, wherein a first reagent comprises an enzyme and a second reagent comprises species having an opposite charge to the enzyme.Type: GrantFiled: April 13, 1999Date of Patent: October 23, 2001Assignee: Aclara BioSciences, Inc.Inventors: Ann K. Wainright, Irene Visser, Sharat Singh
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Patent number: 6267858Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.Type: GrantFiled: June 24, 1997Date of Patent: July 31, 2001Assignee: Caliper Technologies Corp.Inventors: J. Wallace Parce, Anne R. Kopf-Sill, Luc J. Bousse
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Publication number: 20010008212Abstract: A polymer material useful as the porous dielectric medium for microfluidic devices generally and electrokinetic pumps in particular. The polymer material is produced from an inverse (water-in-oil) emulsion that creates a 3-dimensional network characterized by small pores and high internal volume, characteristics that are particularly desirable for the dielectric medium for electrokinetic pumps. Further, the material can be cast-to-shape inside a microchannel. The use of bifunctional monomers provides for charge density within the polymer structure sufficient to support electroosmotic flow. The 3-dimensional polymeric material can also be covalently bound to the channel walls thereby making it suitable for high-pressure applications.Type: ApplicationFiled: February 28, 2001Publication date: July 19, 2001Inventors: Timothy J. Shepodd, Leroy Whinnery, William R. Even
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Patent number: 6221226Abstract: The present invention generally provides methods and systems for monitoring and controlling electroosmotic flow rates in microfluidic systems. Generally, such methods and systems monitor flow rates in electroosmotically driven microfluidic systems by flowing signaling elements within these channels and measuring the flow rate of these signals. The methods of monitoring flow rates are also applied to methods and systems for continuously monitoring and controlling these flow rates in electroosmotically driven microfluidic systems.Type: GrantFiled: October 7, 1999Date of Patent: April 24, 2001Assignee: Caliper Technologies Corp.Inventor: Anne R. Kopf-Sill
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Publication number: 20010000103Abstract: An apparatus and method is provided for obtaining a preparative-scale, free-fluid electrophoretic separator with high resolution as well as an analytical capability commensurate with capillary zone electrophoresis. The electrophoretic focusing apparatus and method of the present invention combines features of electrophoresis and isoelectric focusing to accomplish large scale purifications and fractionations that have not previously been possible, and features a separation chamber bounded by glass-coated porous metal screens, a plurality of purge chambers, a plurality of electrode chambers, and a plurality of pump means. The separation device of the invention is capable of high speed of separation and short residency of sample through the use of high voltage gradients which are produced by relatively low voltages applied across the narrow chamber dimensions.Type: ApplicationFiled: December 7, 2000Publication date: April 5, 2001Inventors: Percy H. Rhodes, Robert S. Snyder
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Patent number: 6129826Abstract: The present invention generally provides an apparatus for enhancing transport and direction of materials in fluidic systems, which systems utilize electroosmotic (E/O) flow systems, to affect that transport and direction. The apparatus generally comprises providing an effective concentration of at least one zwitterionic compound in the fluid containing the material that is to be transported or directed.Type: GrantFiled: May 11, 1999Date of Patent: October 10, 2000Assignee: Caliper Technologies Corp.Inventors: Theo T. Nikiforov, Sang Jeong
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Patent number: 6120665Abstract: The invention provides a method of changing the electrode-based pumping parameters of a liquid, the method comprising (a) selecting a pumping additive based on the pumping pressure, pumping flow rate and electrical efficiency exhibited by the additive, and (b) mixing the pumping additive with the liquid to obtain a mixture having either (i) improved pumping pressure, pumping flow rate or electrical efficiency, or (ii) having a preference for pumping in a direction opposite that of the liquid, in the absence of pumping additive. In a particular embodiment, the invention provides a method of modifying a substantially non-pumping liquid to a liquid that can be pumped with an electrode-based pump.Type: GrantFiled: February 18, 1998Date of Patent: September 19, 2000Inventors: William Yat Chung Chiang, Sterling Eduard McBride
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Patent number: 6074541Abstract: A method of coating a solid support (e.g. a capillary or chromatography packing) to alter the properties of the support surface for separating components in a fluid stream. The method comprises (a) covalently binding a coupling agent (including functional groups capable of forming free radical sites under hydrogen abstraction conditions) to the support surface in a uniform layer, and (b) thereafter, contacting the bound coupling agent with a solution of preformed polymer comprising totally saturated carbon chain backbones including leaving groups, under hydrogen abstraction conditions of elevated temperature in the presence of a free radical catalyst to remove leaving groups from the carbon chains to form free radical carbon binding sites which covalently bond to the coupling agent layer and to crosslink at least some of the preformed polymer through the free radical carbon binding sites to form a dimensional polymer network coating on said solid support surface.Type: GrantFiled: August 12, 1997Date of Patent: June 13, 2000Assignee: Dionex CorporationInventors: Kannan Srinivasan, Nebojsa Avdalovic, Christopher A. Pohl
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Patent number: 6074542Abstract: The present invention describes a method and apparatus utilizing a capillary coating of linear and crosslinked polymers and copolymers of acrylamidomonomers or methacrylamides bearing two hydroxyethyl residues. The method and apparatus employ this coating to maintain coating integrity and suppress electroosmotic flow under basic conditions in capillary electrophoresis.Type: GrantFiled: June 3, 1999Date of Patent: June 13, 2000Inventors: Vladislav Dolnik, Marcella Chiari
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Patent number: 6056860Abstract: Electrophoretic chambers having at least a region of surface modification, and methods for their fabrication, are provided. In some embodiments the subject chambers include in the region of surface modification an anchoring polymeric layer interpenetrating the surface of the chamber and an electrophoretic polymeric layer copolymerized with the anchoring polymeric layer. The subject chambers are prepared by sequentially contacting the chamber surface with a first monomer capable of interpenetrating the surface and a second monomer capable of copolymerization with the first monomer, followed by copolymerization of the first and second monomers. In other embodiments an electrophoretic polymeric layer is noncovalently bound on the surface of a rigid polymereic base material without the aid of a separate anchoring polymeric layer. The subject devices find use in any of a variety of electrophoretic applications in which entities are moved through a medium under the influence of an applied electric field.Type: GrantFiled: September 18, 1997Date of Patent: May 2, 2000Assignee: ACLARA Biosciences, Inc.Inventors: M. Goretty Alonso Amigo, Randy M. McCormick
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Patent number: 6042710Abstract: The present invention provides methods of electrophoretically separating macromolecular species, as well as compositions and systems useful in carrying out such methods. Specifically, the methods of the present invention comprise providing a substrate that has at least a first capillary channel disposed therein. The surface of the channel has a first surface charge associated therewith, and is filled with a water soluble surface adsorbing polymer solution that bears a net charge that is the same as the charge on the capillary surface.Type: GrantFiled: May 11, 1999Date of Patent: March 28, 2000Assignee: Caliper Technologies Corp.Inventor: Robert S. Dubrow
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Patent number: 6033544Abstract: The present invention provides a liquid distribution system, which is useful in a number of contexts, including in accomplishing various synthetic, diagnostic and drug screening reactions. The distribution system can comprise an alpha reservoir and a beta reservoir, a first set of parallel and adjacent first and second feeder channels and a second set of parallel and adjacent third and fourth feeder channels which are offset from the first and second feeder channels, wherein (a) the first and third feeder channels are connected to the alpha reservoir via a first connector channel that is situated above or below the second and fourth feeder channels and are independent of the beta reservoir and (b) the second and fourth feeder channels are connected to the beta reservoir via a second connector channel that is situated above or below the first and third feeder channels and are independent of the alpha reservoir. The distribution system is preferably a microscale distribution system.Type: GrantFiled: November 7, 1996Date of Patent: March 7, 2000Assignee: Sarnoff CorporationInventors: Robert Demers, Sterling Eduard McBride, Christina Marie Knoedler, Robert Amantea, Richard Moroney, Satyam Choudary Cherukuri, Pamela Kay York, Paul L. Brown
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Patent number: 6004443Abstract: A novel free-fluid electrophoresis system applicable to both "analytical" and "preparative" separations combines the advantages of electrophoresis with those of automated liquid chromatography. The system attains plug flow of sample molecules within a separation column that has a sufficiently small diameter to avoid uncorrected convective dispersions and a sufficiently large diameter to ensure adequate preparative throughput. Sample molecules are introduced by liquid chromatographic-type injection mechanisms and moved to the separation column by means of a highly accurate, low-pressure pumping system. A novel pressure detector monitors pressure across the column during the electrophoretic separation. When the pressure across the column is zero, electroosmotic flow within the column exactly balances pump-induced flow so that there is no lateral dispersion of the separating sample molecules (i.e., plug flow is achieved).Type: GrantFiled: August 13, 1997Date of Patent: December 21, 1999Inventors: Percy H. Rhodes, Robert S. Snyder
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Patent number: 6001231Abstract: The present invention generally provides methods and systems for monitoring and controlling electroosmotic flow rates in microfluidic systems. Generally, such methods and systems monitor flow rates in electroosmotically driven microfluidic systems by flowing signaling elements within these channels and measuring the flow rate of these signals. The methods of monitoring flow rates are also applied to methods and systems for continuously monitoring and controlling these flow rates in electroosmotically driven microfluidic systems.Type: GrantFiled: July 15, 1997Date of Patent: December 14, 1999Assignee: Caliper Technologies Corp.Inventor: Anne R. Kopf-Sill
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Patent number: 5993626Abstract: A capillary electrophoresis method for resolving transferrin glycoforms in a sample is described. The capillary comprises a lumen, an inlet and an outlet. The lumenal surface of the capillary is charge-neutral and the capillary contains a buffer containing a polymeric matrix. The transferrin sample is contacted with the inlet of the capillary. A voltage is applied to the capillary such that the inlet is a cathode and the outlet is an anode and such that the voltage is effective for resolving transferrin glycoforms. A method for diagnosing chronic alcoholism or carbohydrate-deficient glycoprotein syndrome using CE to resolve abnormal populations of transferrin glycoforms is also described.Type: GrantFiled: January 24, 1997Date of Patent: November 30, 1999Inventors: James P. Landers, Rajani Prasad, Robert P. Oda, Robert L. Stout
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Patent number: 5964995Abstract: The present invention generally provides methods for enhancing transport and direction of materials in fluidic systems, which systems utilize electroosmotic (E/O) flow systems, to affect that transport and direction. The methods generally comprise providing an effective concentration of at least one zwitterionic compound in the fluid containing the material that is to be transported or directed.Type: GrantFiled: April 4, 1997Date of Patent: October 12, 1999Assignee: Caliper Technologies Corp.Inventors: Theo T. Nikiforov, Sang Jeong
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Patent number: 5964997Abstract: Provided is a method of operating an electrode-based pump to pump a liquid, the method comprising periodically reversing the voltage polarity applied to the electrodes of the pump while maintaining a net flow of liquid in a desired direction. Further provided is an apparatus for pumping liquid with an electrode-based pump comprising: a channel of capillary dimensions; a pump comprising at least two electrodes inserted into the channel; a controller for controlling the voltages applied to the electrodes such that the pumps operate under a sequentially repeated pattern of polarity cycles, and such that over the period of the repeated pattern either (a) a first ratio of a voltage-integrated area A.sub.1 associated with a first polarity to a voltage-integrated area A.sub.2 associated with the other polarity or (b) a second ratio of a charge q.sub.1 carried by the current associated with a first polarity to a charge q.sub.Type: GrantFiled: March 21, 1997Date of Patent: October 12, 1999Assignee: Sarnoff CorporationInventor: Sterling E. McBride
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Patent number: 5948227Abstract: The present invention provides methods of electrophoretically separating macromolecular species, as well as compositions and systems useful in carrying out such methods. Specifically, the methods of the present invention comprise providing a substrate that has at least a first capillary channel disposed therein. The surface of the channel has a first surface charge associated therewith, and is filled with a water soluble surface adsorbing polymer solution that bears a net charge that is the same as the charge on the capillary surface.Type: GrantFiled: December 17, 1997Date of Patent: September 7, 1999Assignee: Caliper Technologies Corp.Inventor: Robert S. Dubrow
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Patent number: 5935401Abstract: Electrophoretic chambers comprising at least a region of surface modification, and methods for their fabrication, are provided. The subject chambers comprise in the region of surface modification, an anchoring polymeric layer interpenetrating the surface of the chamber and an electrophoretic polymeric layer copolymerized with the anchoring polymeric layer. The subject chambers are prepared by sequentially contacting the chamber surface with a first monomer capable of interpenetrating the surface and a second monomer capable of copolymerization with the first monomer, followed by copolymerization of the first and second monomers. The subject devices find use a variety of electrophoretic applications in which entities are moved through a medium under the influence of an applied electric field.Type: GrantFiled: September 18, 1996Date of Patent: August 10, 1999Assignee: Aclara BiosciencesInventor: M. Goretty Alonso Amigo
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Patent number: 5916426Abstract: The invention provides uncharged water-soluble silica-adsorbing polymers for suppressing electroendoosmotic flow and to reduce analyte-wall interactions in capillary electrophoresis. In one aspect of the invention, one or more of such polymers are employed as components of a separation medium for the separation of biomolecules, such as polynucleotides, polysaccharides, proteins, and the like, by capillary electrophoresis. Generally, such polymers are characterized by (i) water solubility over the temperature range between about 20.degree. C. to about 50.degree. C., (ii) concentration in a separation medium in the range between about 0.001% to about 10% (weight/volume), (iii) molecular weight in the range of about 5.times.10.sup.3 to about 1.times.10.sup.6 daltons, and (iv) absence of charged groups in an aqueous medium having pH in the range of about 6 to about 9.Type: GrantFiled: August 19, 1997Date of Patent: June 29, 1999Assignee: The Perkin-Elmer CorporationInventors: Ramakrishna S. Madabhushi, Steven M. Menchen, J. William Efcavitch, Paul D. Grossman
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Patent number: 5900130Abstract: A method and device are provided for transporting a liquid sample into a third microchannel from an intersection of at least a first, a second, and a fourth microchannel, by stages. In a first stage, liquid sample is moved in and from the fourth microchannel through the intersection and into the second microchannel and concurrently carrier liquid is moved in and from the first and third microchannels through the intersection and into the second microchannel. Thereafter in a second stage, at least part of the contents of the intersection is moved into the third channel and concurrently a part of the contents of the second and fourth microchannels is moved through the intersection and into the third microchannel. Thereafter in a third stage, carrier liquid is moved from the first microchannel simultaneously through the intersection and into the second, third, and fourth microchannels.Type: GrantFiled: June 18, 1997Date of Patent: May 4, 1999Assignee: Alcara BioSciences, Inc.Inventors: Dominic Benvegnu, Randy M. McCormick
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Patent number: 5888366Abstract: A capillary made of plastics material that is suited for use in capillary electrophoresis. The capillary has its inner surface chemically modified for the generation of properties different from those of the original plastic capillary material. In the process of producing such capillaries, a premanufactured capillary is treated with a chemical reagent which generates functional groups directly on the capillary surface or generates attachment sites, on the capillary surface to which functional groups are later bonded.Type: GrantFiled: August 19, 1997Date of Patent: March 30, 1999Assignee: Hewlett-Packard CompanyInventors: Heinz Engelhardt, Thomas Schmitt, Konstantin Shoiket
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Patent number: 5858188Abstract: Microchannels having at least an acrylic inner surface and methods of their use in electrophoretic applications are provided. The subject microchannels may be in the form of a variety of configurations suitable for holding an electrophoretic medium. The subject microchannels give rise to substantially reduced EOF and/or adsorption as compared to fused silica under conditions of electrophoresis and find use in a variety of electrophoretic applications in which charged entities are moved through a medium under the influence of the an applied electric field.Type: GrantFiled: April 4, 1996Date of Patent: January 12, 1999Assignee: ACLARA BioSciences, Inc.Inventors: David S. Soane, Zoya M. Soane
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Patent number: 5800690Abstract: In a microfluidic system using electrokinetic forces, the present invention uses electrical current or electrical parameters, other than voltage, to control the movement of fluids through the channels of the system. Time-multiplexed power supplies also provide further control over fluid movement by varying the voltage on an electrode connected to a fluid reservoir of the microfluidic system, by varying the duty cycle during which the voltage is applied to the electrode, or by a combination of both. A time-multiplexed power supply can also be connected to more than one electrode for a savings in cost.Type: GrantFiled: July 3, 1996Date of Patent: September 1, 1998Assignee: Caliper Technologies CorporationInventors: Calvin Y. H. Chow, J. Wallace Parce
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Patent number: 5792331Abstract: A method of coating a solid support (e.g. a capillary or chromatography packing) to alter the properties of the support surface for separating components in a fluid stream. The method comprises (a) covalently binding a coupling agent (including functional groups capable of forming free radical sites under hydrogen abstraction conditions) to the support surface in a uniform layer, and (b) thereafter, contacting the bound coupling agent with a solution of preformed polymer comprising totally saturated carbon chain backbones including leaving groups, under hydrogen abstraction conditions of elevated temperature in the presence of a free radical catalyst to remove leaving groups from the carbon chains to form free radical carbon binding sites which covalently bond to the coupling agent layer and to crosslink at least some of the preformed polymer through the free radical carbon binding sites to form a dimensional polymer network coating on said solid support surface.Type: GrantFiled: December 19, 1996Date of Patent: August 11, 1998Assignee: Dionex CorporationInventors: Kannan Srinivasan, Neboisa Avdalovic, Christopher A. Pohl
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Patent number: 5779868Abstract: The present invention provides for techniques for transporting materials using electrokinetic forces through the channels of a microfluidic system. The materials are transported in slug regions of high ionic concentration, next to buffer material regions of high ionic concentration, which are separated by buffer material regions of low ionic concentration. Such arrangements allow the materials to remain localized for the transport transit time to avoid mixing of the materials. Using these techniques, an electropipettor which is compatible with the microfluidic system is created so that materials can be easily introduced into the microfluidic system. The present invention also compensates for electrophoretic bias as materials are transported through the channels of the microfluidic system by splitting a channel into portions with positive and negative surface charges and a third electrode between the two portions, or by diffusion of the electrophoresing materials after transport along a channel.Type: GrantFiled: June 28, 1996Date of Patent: July 14, 1998Assignee: Caliper Technologies CorporationInventors: J. Wallace Parce, Michael R. Knapp
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Patent number: 5755942Abstract: A system for processing a plurality of tests or syntheses in parallel comprising a sample channel for moving samples into a microlaboratory array of a plurality of wells connected by one or more channels for the testing or synthesis of samples, a station for housing the array and an optical system comprising at least one light source and at least one light detector for measuring the samples in the array, and a means of electrically connecting said array to an apparatus capable of monitoring and controlling the flow of fluids into the array.Samples are loaded from a common loading channel into the array, processed in the wells and measurements taken by the optical system. The array can process many samples, or synthesize many compounds in parallel, reducing the time required for such processes.Type: GrantFiled: August 29, 1996Date of Patent: May 26, 1998Assignee: David Sarnoff Research Center, Inc.Inventors: Peter John Zanzucchi, Satyam Choudary Cherukuri, Sterling Edward McBride
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Patent number: 5750015Abstract: Devices and methods are disclosed for moving charged molecules through a medium by the application of a plurality of electrical fields of sufficient strength and applied for sufficient amounts of time so as to move the charged molecules through the medium. The devices although preferably small in size, preferably generate large numbers (100 or more) of electrical fields to a movement area which preferably contains a liquid buffered or gel medium. Mixtures of charged molecules are pulled through the gel by the force of the electrical fields. The fields are preferably activated simultaneously or sequentially one after another at various speeds to create complex force field distributions or moving field waves along the separation medium. Charged molecules capable of moving quickly through the gel will be moved along by the faster moving field waves and be separated from slower moving molecules.Type: GrantFiled: March 13, 1996Date of Patent: May 12, 1998Assignee: Soane BiosciencesInventors: David S. Soane, Zoya M. Soane
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Patent number: 5728282Abstract: A capillary electrophoresis separation matrix for single-stranded nucleic acids, along with methods for using and preparing the matrix, are disclosed. The separation matrix provides denaturing conditions and contains hydroxyethyl cellulose (HEC) in combination with urea, and preferably also includes formamide. The separation matrix may be used for DNA sizing and sequencing applications and provides a single-base resolution to approximately 500 base pairs. The separation matrix is inexpensive, easy to prepare, requires no polymerization steps, and is of low enough viscosity to be pumped easily into and out of capillary tubes for electrophoresis. The low viscosity allows for high throughput of samples and reuse of the capillary tubes for numerous separations.Type: GrantFiled: April 12, 1996Date of Patent: March 17, 1998Assignee: Molecular DynamicsInventors: John S. Bashkin, David L. Barker, Richard F. Johnston
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Patent number: 5624539Abstract: An electrophoretic separation apparatus includes a capillary tube having a length, a cross section, an inlet and an outlet. A first reservoir containing a solvent and, upon injection, a solute is in fluid-flow communication with the inlet and a second reservoir containing at least a solvent is also in fluid flow communication with the outlet, the capillary thereby being filled at least with the solvent. A first power supply applies a direct voltage separation potential between the first and second reservoirs and along the length of the capillary to thereby establish an electrophoretic flow of the solute therethrough. A second power supply applies an alternating voltage upon the direct voltage, and the DC impedance and AC impedance values are determined and subtracted to provide a direct measurement of the electroosmotic flow.Type: GrantFiled: June 19, 1995Date of Patent: April 29, 1997Assignee: The Penn State Research FoundationInventors: Andrew G. Ewing, Mark A. Hayes