Classifying – separating – and assorting solids – Stratifiers – With liquid treatment
Reexamination Certificate
1999-10-12
2004-02-24
Walsh, Donald P. (Department: 3653)
Classifying, separating, and assorting solids
Stratifiers
With liquid treatment
C209S208000, C209S210000, C210S198100, C210S645000, C435S029000
Reexamination Certificate
active
06695147
ABSTRACT:
FIELD OF THE INVENTION
This invention relates generally to extraction systems and methods for separating analytes from streams containing other constituents by differential transport principles such as diffusion and applied fields, providing an improved method involving the use of absorbents or adsorbents in the extraction stream. The devices and methods of this invention can be used for diagnostic and therapeutic/treatment purposes.
BACKGROUND OF THE INVENTION
Field flow fractionation devices involve particle size separation using a single inlet stream. See, e.g., Giddings, J. C., U.S. Pat. No. 3,449,938, Jun. 17, 1969, “Method for Separating and Detecting Fluid Materials”; Giddings, J. C., U.S. Pat. No. 4,147,621, Apr. 3, 1979, “Method and Apparatus for Field-Flow Fractionation”; Giddings, J. C., U.S. Pat. No. 4,214,981, Jul. 29, 1980, “Steric Field-Flow Fractionation”; Giddings, J. C. et al., U.S. Pat. No. 4,250,026, Feb. 10, 1981, “Continuous Steric FFF Device for The Size Separation of Particles”; Giddings, J. C. et al. (1983), “Outlet Stream Splitting for Sample Concentration in Field-Flow Fractionation,” Separation Science and Technology 18:293-306; Giddings, J. C. (1985), “Optimized Field-Flow Fractionation System Based on Dual Stream Splitters,” Anal. Chem. 57:945-947; Giddings, J. C., U.S. Pat. No. 4,830,756, May 16, 1989, “High Speed Separation of Ultra-High Molecular Weight Polymers by Hyperlayer Field-Flow Fractionation”; Giddings, J. C., U.S. Pat. No. 4,141,651, Aug. 25, 1992, “Pinched Channel Inlet System for Reduced Relaxation Effects and Stopless Flow Injection in Field-Flow Fractionation”; Giddings, J. C., U.S. Pat. No. 5,156,039, Oct. 20, 1992, “Procedure for Determining the Size and Size Distribution of Particles Using Sedimentation Field-Flow Fractionation”; Giddings, J. C., U.S. Pat. No. 5,193,688, Mar. 16, 1993, “Method and Apparatus for Hydrodynamic Relaxation and Sample Concentration in Field-Flow Fraction Using Permeable Wall Elements”; Caldwell, K. D. et al., U.S. Pat. No. 5,240,618, Aug. 31, 1993, “Electrical Field-Flow Fractionation Using Redox Couple Added to Carrier Fluid”; Giddings, J. C. (1993), “Field-Flow Fractionation: Analysis of Macromolecular, Colloidal and Particulate Materials,” Science 260:1456-1465; Wada, Y. et al., U.S. Pat. No. 5,465,849, Nov. 14, 1995, “Column and Method for Separating Particles in Accordance with Their Magnetic Susceptibility”; Yve, V. et al. (1994), “Miniature Field-Flow Fractionation Systems for Analysis of Blood Cells,” Clin. Chem. 40:1810-1814; Afromowitz, M. A. and Samaras, J. E. (1989), “Pinch Field Flow Fractionation Using Flow Injection Techniques,” Separation Science and Technology 24(5 and 6):325-339.
Thin-channel split flow fractionation (SPLITT) technology also provides particle separation in a separation cell having a thin channel. A field force is exerted in a direction perpendicular to the flow direction. Particles travel from a particle-containing stream across a transport stream to a particle-free stream. The device for operating the process is generally fabricated from glass plates with teflon sheets used as spacers to form the channels. The channel depth can therefore be no smaller than the spacers, which are generally about 100 to 120 &mgr;m thick. See, e.g., Giddings, J. C., U.S. Pat. No. 4,737,268, Apr. 12, 1988, “Thin Channel Split Flow Continuous Equilibrium Process and Apparatus for Particle Fractionation”; Giddings, J. C., U.S. Pat. No. 4,894,146, Jan. 16, 1990, “Thin Channel Split Flow Process and Apparatus for Particle Fractionation”; Giddings, J. C., U.S. Pat. No. 5,093,426, Aug. 13, 1991, “Process for Continuous Particle and Polymer Separation in Split-Flow Thin Cells Using Flow-Dependent Lift Forces”; Williams, P. S. et al. (1992), “Continuous SPLITT Fractionation Based on a Diffusion Mechanism,” Ind. Eng. Chem. Res. 31:2172-2181; and Levin, S. and Tawil, G. (1993), “Analytical SPLITT Fractionation in the Diffusion Mode Operating as a Dialysis-like System Devoid of Membrane. Application to Drug-Carrying Liposomes,” Anal. Chem. 65:2254-2261.
The object of this invention is to provide an improved extraction system utilizing differential transport principles in which the analyte can be extracted, detected and quantified. A further object of this invention is to provide an improved extraction system for purification and treatment of fluids, including bodily fluids such as blood.
All publications, patents and patent applications referred to herein are incorporated in their entirety by reference.
SUMMARY OF THE INVENTION
Differential extraction devices as described above allow desired particles to move from a sample stream into an extraction stream running in parallel laminar flow with the extraction stream. A simple embodiment of such systems uses a concentration gradient across the streams so that desired particles diffuse from the sample stream into the extraction stream. Other gradients and forces can also be used, e.g., magnetic, electrical, gravitational, dielectrical, sedimentation, shear, centrifugal force, temperature, pressure, and cross-flow gradients.
An improvement in the above processes provided herein is the addition of a sequestering material to the extraction stream.
The invention provides an extraction device for extracting desired particles from a sample stream containing said desired particles, said device comprising:
a. a sample stream inlet;
b. an extraction stream inlet;
c. an extraction channel in fluid communication with said sample stream inlet and said extraction stream inlet for receiving a sample stream from said sample stream inlet in adjacent laminar flow with an extraction stream from said extraction stream inlet;
d. a sequestering material within said extraction channel for capturing desired particles in said extraction stream;
e. a by-product stream outlet in fluid communication with said extraction channel for receiving a by-product stream comprising at least a portion of said sample stream from which desired particles have been extracted;
f. a product outlet in fluid communication with said extraction channel for receiving a product comprising said sequestering material and at least a portion of said desired particles.
A sequestering material is a material which captures, e.g., by adsorbing, binding or sticking to the desired particles, or by absorbing them. Enzymes, antibodies, antigens and other ligands for desired particles are known to the art and are useful sequestering materials for this invention. Any ligand known to the art for a desired particle may be used as a sequestering material. Such ligands may be added to the extraction stream “as-is” or may be immobilized on substrates such as polymeric beads, high molecular weight polymers, or other materials known to the art. “High molecular weight polymers” refers to those polymers of sufficient molecular weight that they do not substantially diffuse into the sample stream during their transit through the device. Examples of high molecular weight polymers include but are not limited to high molecular weight dextrans, high molecular weight polypeptides, and high molecular weight nucleic acids. The sequestering material may also be an absorbent material such as activated charcoal, or porous polymers. Absorbents or adsorbents may be either specific to a particular particle type, such as an antibody, or nonspecific, such as activated charcoal.
The sequestering material is preferably substantially non-diffusing, i.e., should diffuse sufficiently slowly that it does not cross from the extraction stream into the sample stream to any significant degree, so that it does not become detectable in the by-product stream, or does not interfere with analysis of analytes in the by-product stream.
The sequestering material captures the desired particles by preventing them from exiting the device with the exiting by-product stream. The desired particles may be loosely bound to the sequestering material, so long as the sequestering material retains the particles long enough to prevent them from exiting with the by-pro
Brody James P.
Yager Paul
Joerger Kaitlin
Seed IP Law Group PLLC
University of Washington
Walsh Donald P.
LandOfFree
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