Chemistry: analytical and immunological testing – Involving an insoluble carrier for immobilizing immunochemicals – Carrier is inorganic
Reexamination Certificate
2000-11-01
2003-09-23
Chin, Christopher L. (Department: 1641)
Chemistry: analytical and immunological testing
Involving an insoluble carrier for immobilizing immunochemicals
Carrier is inorganic
C436S501000, C436S518000, C436S514000, C422S050000, C422S051000, C422S068100, C422S082050, C422S082080, C422S186000, C422S186100, C435S287200, C435S287300, C435S287100, C210S695000, C210S095000, C210S222000, C210S450000, C209S214000, C209S223100
Reexamination Certificate
active
06623984
ABSTRACT:
FIELD OF THE INVENTION
The invention relates generally to particle identification systems, and more particularly, to micro electromechanical systems (MEMS) and methods for identifying and quantifying magnetically susceptible particles through magnetic sorting and bioferrography.
BACKGROUND OF THE INVENTION
Cell and pathogen analysis is an increasingly important technique in the diagnosis and treatment of various cancers and diseases. Of primary importance to this analysis is the ability to separate, identify and quantify cells and pathogens. In such an analysis, the identification of differentiating cell properties allows such properties to be used as “handles” which, in turn, can be used to separate cells or particles from other cells or particles. Among the most commonly used “handles” for sorting cells and other microbes are immunological labels that include, for example, immunofluorescent and immunomagnetic labels. Immunofluorescent labels typically include, for example, a fluorescent molecule joined to an antibody. Immunomagnetic labels typically include, for example, a paramagnetic compound or molecule joined to either a primary or secondary antibody. Cell labeling is performed by attaching the antibody to a marker of interest on the surface of the cell (i.e., cell surface marker).
In the case of immunomagnetically label cells, a magnetic field can be used to separate such cells based on their magnetic susceptibility. For example, U.S. Pat. No. 5,968,820 to Zborowski et al., which is hereby fully incorporated by reference, describes methods and apparatuses for magnetically separating cells into fractionated flow streams. More specifically, through a combination of flow compartments and one or more magnetic fields, a flow stream of heterogeneous cells is separated into fractionated flow streams based on cell magnetic susceptibility. The fractionated flow streams are then collected and the particles recovered therefrom.
By superposition, a sample of unknown cells can be identified by using the above apparatus and an antibody cocktail. The unknown cell population can be mixed with various antibodies (antibody cocktail) to screen for the presence of suspected cell populations. If in a sample one suspects pathogens A, B, C or D to be present, one mixes magnetically tagged antibodies of anti-A, anti-B, anti-C and anti-D. When the fluid stream of tagged cells is placed in a magnetic field, the force imparted on the magnetically tagged cells causes the cells to jump flow lines and move laterally into the carrier fluid. The total force imparted on the cell, which is a function of cell geometry and the cells dipole moment, determines the lateral distance that the tagged cell moves into the carrier fluid. Thus, different types of cells all immunomagnetically tagged will move different distances. If laminar flow and precise geometry can be maintained, cell types can be identified by their lateral distribution
MEMS technology creates high-precision microscopic structures on silicon. Through MEMS technology, relatively low-cost, high-volume, electromechanical systems that integrate sensors, actuators, electronics, and other components can be realized on a miniature scale. Hence, it would highly desirable to provide a MEMS-based system for identifying and quantifying magnetically susceptible particles.
SUMMARY OF THE INVENTION
According to one embodiment of the present invention, a MEMS-based integrated particle identification system employing an antibody cocktail is provided. Particles suitable for separation by the present invention include organic and non-organic particles. Organic particles preferably include, for example, cells, viruses, organelles, and DNA. Non-organic particles preferably include magnetic and paramagnetic particles such as, for example, metallic and non-metallic particles and molecules.
The system includes a substrate, a magnetic structure, and a bioferrograph is provided. The substrate includes a topside portion, backside portion and a flow system. The flow system includes a flow channel for accepting the flow of a stream of particles to identified. The magnetic structure is in physical communication with the topside and backside portions of the substrate and has at least two pole pieces. The pole pieces may be conventional flat pole pieces, may have contoured ends (e.g., hyperbolic) or each pole piece can have a plurality of discrete pole pieces generating a magnetic field that acts on magnetically susceptible particles in the flow stream. The bioferrograph has at least one sensor for identifying the presence and quantity of magnetically susceptible particles.
It is therefore an advantage of the present invention to provide a MEMS-based integrated particle identification system.
It is a further advantage of this invention to provide an integrated MEMS-based particle identification system that includes a bioferrograph.
It is a further advantage of the present invention to provide a MEMS-based magnetic structure for an integrated particle identification system.
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Chalmers Jeff
Fleischman Aaron J.
Roy Shuvo
Zborowski Maciej
Chin Christopher L.
Do Pensee T.
Tarolli, Sundheim Covell & Tummino L.L.P.
The Cleveland Clinic Foundation
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