Chemistry: electrical and wave energy – Processes and products – Electrophoresis or electro-osmosis processes and electrolyte...
Reexamination Certificate
1999-05-11
2002-10-01
Warden, Jill (Department: 1743)
Chemistry: electrical and wave energy
Processes and products
Electrophoresis or electro-osmosis processes and electrolyte...
C204S450000, C204S451000, C204S600000, C204S601000
Reexamination Certificate
active
06458259
ABSTRACT:
BACKGROUND OF THE INVENTION
Surface adsorption of biological materials, such as proteins, to the walls of microscale fluid conduits can cause a variety of problems. For example, in assays relying on flow of material in the conduits, adsorption of test or reagent materials to the walls of the conduits (or to reaction chambers or other microfluidic elements) can cause generally undesirable biasing of assay results.
For example, charged biopolymer compounds can be adsorbed onto the walls of the conduits, creating artifacts such as peak tailing, loss of separation efficiency, poor analyte recovery, poor retention time reproducibility and a variety of other assay biasing phenomena. The adsorption is due, in part, e.g., to electrostatic interactions between, e.g., positively charged residues on the biopolymer and negatively charged groups resident on the surface of the separation device.
Reduction of surface adsorption in microscale applications is typically achieved by coating the surfaces of the relevant microscale element with a material which inhibits adsorption of assay components. For example, glass and other silica-based capillaries utilized in capillary electrophoresis have been modified with a range of coatings intended to prevent the adsorption of charged analytes to the walls of the capillaries. See, for example Huang et al., J. Microcol. Sep. 4, 135-143 (1992), Bruin et al., Journal of Chromatogr., 471, 429-436 (1989); Towns et al., Journal of Chromatogr., 599, 227-237 (1992); Erim, et al., Journal of Chromatogr., 708, 356-361 (1995); Hjerten, J. Chromatogr., 347, 191 (1985); Jorgenson, Trends Anal. Chem. 3, 51 (1984); and McCormick, Anal. Chem., 60, 2322 (1998). These references describe the use of a variety of coatings, including surface derivatization with poly(ethyleneglycol) and poly(ethyleneimine), functionalization of poly(ethyleneglycol)-like epoxy polymers as surface coatings, functionalization with poly(ethyleneimine) and coating with polyacrylamide, polysiloxanes, glyceroglycidoxypropyl coatings and others. Surface coatings have also been used for, e.g., modification of electroosmotic potential of the relevant microscale surface e.g., as taught in U.S. Pat. No. 5,885,470, CONTROLLED FLUID TRANSPORT IN MICROFABRICATED POLYMERIC SUBSTRATES by Parce et al.
Other than the use of surface coatings, few approaches exist for controlling surface adsorption of biopolymers in microscale systems. In general, other design parameters used to control adsorption include the material used in the device, modulation of flow rates and the like. Generally, surface adsorption of biological materials in capillary fluidics applications is a significant issue for at least some applications, and additional mechanisms for inhibiting surface adsorption in microfluidic applications are desirable. The present invention provides new strategies for inhibiting surface adsorption of polymers, molecules and biological materials, e.g., in pressure-based microscale flow applications. Additional features will become apparent upon complete review of the following disclosure.
SUMMARY OF THE INVENTION
The present invention derives from the surprising discovery that electroosmotic flow can be,used in a pressure-driven microfluidic system to modulate surface adsorption. In particular, application of an electric field in a fluidic conduit during pressure-based flow prevents or reduces adsorption of materials such as proteins from adhering to the walls of a microchannel or other microscale element. Thus, application of an electric field during pressure-based flow can be used to reduce adsorption of proteins and other molecules or materials to the walls of the microscale element. Thus, application of electrokinetic force during pressure based flow can be regular and reversible, e.g., as applied by an alternating current. In this embodiment, movement of components in a microscale conduit due to electrokinetic forces can be minimized, a desirable feature, e.g., for applications in which separation of materials by charge is not desired.
Accordingly, the invention provides methods of regulating surface adsorption in a channel. In the method, a fluid is flowed through a channel by applying pressure to the fluid in the channel. An electric field (which is alternating or constant) is continuously or periodically applied to, the fluid in the channel. The electric current field can be used as an additional motive force directing movement of a material in the fluid (or directing the fluid itself, as occurs, e.g., during electroosmosis) adding or subtracting from the pressure-based velocity of the material in the channel (electrokinetic and pressure-based flow effects can have the same or an opposite force vector). Alternatively, the electric field can be applied in such a way that the effects of the electric field on the overall velocity of the material are negligible or non-existent (e.g., other than at the walls of the conduit, where the electric field modulates adsorption). For example, the overall contribution to the velocity of a fluid or material in a fluid, exclusive of adsorption effects, can be anywhere from 0.1× of the total velocity or less, to less than 50% of the total velocity (0.5×) to 90% of the total velocity (0.9×) or more. For example when using alternating current, there may be essentially no contribution to velocity of fluids or materials in the fluids.
A variety of fields and current types can be used in the methods of the invention. For example, an alternating square wave or sine wave field can be applied. Similarly, adsorption of a variety of materials can be regulated by the application of electric fields, including proteins, cells, carbohydrates, nucleic acids, lipids and a combination thereof Application of the electric field can be simultaneous with application of a pressure gradient, or pressure and electrokinetic forces can be alternated. Pressure gradients can be applied by any of a variety of methods, including use of a vacuum source, a hydraulic pressure source, a pneumatic pressure source, an electroosmotic pressure pump, or contact with an absorbent material or a set of fluidly coupled capillary channels.
The use of electrokinetic movement of materials during pressure-induced flow can also be used in conjunction with other methods of eliminating surface adsorption. For example, a coating can be applied to a microscale element to additionally reduce adsorption, or, e.g., to provide for electroosmosis.
In addition to the use of electrical current to prevent adsorption of materials to walls of conduits, adsorption prevention agents can also be used to reduce unwanted adsorption, including, e.g., detergents and blocking agents (e.g., a combination of NDSB and BSA). These adsorption prevention agents can be used in place of or in concert with application of electric fields for reduction of surface adsorption.
Devices and systems for practicing the methods of the invention are also provided. The devices and systems include a body having a one or a plurality of fluidly coupled microchannels disposed therein. A source of fluidic material is fluidly coupled to at least one of the plurality of microchannels. A fluid pressure controller is fluidly coupled to the at least one microchannel and at least-two electrodes are in fluidic or ionic contact with the at least one microchannel. An electrical controller is typically in electrical contact with the at least two electrodes. In a preferred embodiment, the electrical controller applies an alternating electrical field between the at least two electrodes. Typically, the device is configured to apply an electric field of sufficient duration and intensity to dislodge a protein from a surface of the at least one microchannel, or to prevent protein binding to a surface of the at least one microchannel.
In general, the device or system can be configured for electrokinetic or pressure-based flow, or both. For example, flow can be primarily driven by pressure with a small or negligible contribution by electrokinetic forces, or, optio
Chow Andrea W.
Parce J. Wallace
Caliper Technologies Corp.
Filler Andrew L.
Quine Intellectual Property Law Group
Starsiak Jr. John S.
Warden Jill
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