Immunivest Corporation

Immunicon Corporation

Biomagnetic Solutions LLC

Other

Nycomed Imaging As

Janssen Diagnostics, LLC

Paul A Liberti

Galla Chandra Rao

Leon W M M Terstappen

Dhanesh I Gohel

Yuzhou Wang

Leon W Terstappen

Brian P Feeley

Jonathan W Uhr

Weixin Tang

Emilian V Racila

Gerald J Dolan

Herman Rutner

Gerald V Doyle

Louis D'Angelo

John C Silvia

Charles S Owen

Joseph N Chiarappa

Dustin W Ritter

Steven Gross

Leon Wmm Terstappen

William J Cronin

Steven P Piccoli

Leon M M Terstappen

Ellen S Church

Yozhou Wang

Galla Candra Rao

Maria A Pino

Paul Pollara

Todor R Khristov

Devices and methods for immunomagnetic separation having a flexible inflatable processing chamber and magnetic array.

Large scale immunomagnetic separation device

An apparatus and methods are provided for the magnetic separation of target bioentities. The apparatus includes a fluid chamber and a magnetic element for drawing target bioentities toward a collection surface of the fluid chamber. The apparatus may include a positioning assembly operable to variable change the position and orientation f the fluid chamber relative to the magnetic element.

Apparatus and method for immunomagnetic cell separation

Method consists of placing a flexible container within a rigid frame and expanding the container by pneumatic or hydraulic pressure such that the walls of the container conform to the inside walls of the rigid frame thus forming a well-defined chamber. The system has the capability of reducing the volume of the chamber by adjusting the distance between the walls of the rigid container. The methods and systems so described are applicable to closed sterile systems that employ immunomagnetic isolation or purging of components from blood products. By providing a fixed volume and at least one surface upon which targeted entities can be magnetically deposited, target cells in the case of positive isolations can be magnetically held, flushed with wash buffers over them to remove entrapped cells and finally the recovery of product of very high purifies and at high yields.

Rigid chamber for cell separation from a flexible disposable bag

A highly sensitive assay is disclosed which combines immunomagnetic enrichment with multiparameter flow cytometric and immunocytochemical analysis to detect, enumerate and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blood and has a greater sensitivity than conventional PCR or immunohistochemistry by 1-2 orders of magnitude. In addition, the assay facilitates the biological characterization and staging of carcinoma cells.

Methods and reagents for the rapid and efficient isolation of circulating cancer cells

Separation apparatus and method for separating magnetic and/or magnetically-labeled particles from a test medium. Test medium within a reaction chamber is caused to flow past a collecting surface, and a high-gradient magnetic field is applied to the surface to capture magnetically responsive particles in the test medium. The particles are deflected toward the collection surface by baffles, a spinner, or a sprayer, or are funneled past the surface by a plunger operable to be displaced into close proximity to the surface to provide a narrow flow path for the particle-laden test medium. The particles normally suspended in the medium are separated out of suspension by adhesion to the collection surface. The particles may be resuspended by removal of the surface from the high-gradient field, or removal of the high-gradient field from the surface. The collection surface is a thin-walled non-magnetic material having a plurality of magnetic pole faces positioned therearound.

Apparatus and methods for magnetic separation

Compositions and methods are disclosed which enhance the microscopic observation and analysis of biological entities such as cells, bacteria and viruses by eliminating interfering magnetic clusters created by naturally occurring aggregators of colloidal magnetic particles. Additionally means for significantly enhancing the magnetic isolation of low antigen density target cells from biological samples are disclosed.

Increased separation efficiency via controlled aggregation of magnetic nanoparticles

Disclosed is a method that improves the efficiency of reactions between specific binding pairs. By translating one member of the pair through a suspension of the second member, or across a surface to which the second member is immobilized, collision and binding frequencies are greatly increased. The resulting increased binding frequency allows for reduced incubation times and lower incubation temperatures. The enhanced collisions are advantageous for both molecular reactions, in which mixing is not always effective, and cellular reactions, in which the cells may be damaged by mixing.

Methods for enhancing binding interactions between members of specific binding pairs

Separation apparatus and method for separating magnetic and/or magnetically-labeled particles from a test medium in a reaction chamber which incorporates baffles, a spinner, a stirrer, or a plunger operable to be displaced along a collection surface to define a narrow flow path through which the particle-laden test medium must flow. The collection surface is a thin-walled non-magnetic material having a plurality of magnetic pole faces positioned therearound. Test medium within a reaction chamber is caused to flow past a collecting surface, and a high-gradient magnetic field is applied to the surface to capture magnetically responsive particles in the test medium. The particles are deflected toward the collection surface in the flow path for the test medium. The narrow flow path assures that substantially all of the particles pass within the high-gradient magnetic field along the collection surface. The particles are normally suspended in the medium, and are separated out of suspension by adhesion to the collection surface. The particles may be resuspended by removal of the surface from the high-gradient field, or removal of the high-gradient field from the surface.

The invention relates to an improved method for the manufacture of magnetically responsive particles, also called ferrofluids. The improved method involves a heat treatment step, which may occur at various times during the preparation of the materials, including during subdivision of the magnetic starting material, during the addion of a coating material, after formation of a magnetically responsive particle, or some combination thereof. The materials formed by such a process have numerous advantages over materials formed by other processes, including enhanced salt stability, increased coating uptake, and increased binding capacity. These ferrofluids have applications in a variety of preparative and diagnostic techniques, including immunoassay, cell separations, toxicity testing, food testing, environmental analysis, and MRI.

Coated, resuspendable magnetically responsive, transition metal oxide

A method of qualitative analysis of microscopic biological specimens is disclosed in which the specimens are rendered magnetically responsive by immunosspecific binding with feuromagnetic colloid. The specimens are placed in a vessel having a feuromagnetic capture structure supported on a transparent wall. The vessel is then placed in a magnetic field for inducing a high gradient region in the vicinity of the capture structure and, in particular, adjacent to the capture structure along the direction of the applied field. The magnetically responsive specimens are collected and immobilized by the high gradient along the wall adjacent to the capture structure for unobstructed microscopic observation. Subpapulations of distinct types of cells can thus be observed and differentiated. As transport force, such as gravity or an externally applied magnetic gradient, may be applied to the vessel to move the specimens into the high gradient region.

Methods for biological substance analysis employing internal magnetic

Microbiological entities, such as cells or microbes, are immobilized in a single-file linear array for optical analysis. Colloidal magnetic particles having a binding agent, such as ligand for attachment with a corresponding receptor, are bound to the entities suspended in a fluid medium. The fluid medium is placed into a vessel having a ferromagnetic capture structure including an elongated linear collection surface with a diameter less than that of the microbiological species of interest. The vessel is placed into a magnetic field for inducing a magnetic gradient in a region along the collection surface of the ferromagnetic capture structure. The magnetically-labeled entities are attracted toward the collection surface and immobilized thereon in a linear array. Microscopic optical and fluorescence observations, and sequential chemical reactions and mechanical manipulations may be performed on the line of immobilized entities. Methods of analysis for blood and immune cells, such as leukocytes and lymphocytes, are disclosed.

Methods for magnetic immobilization and manipulation of cells

A method of quantitative analysis of microscopic biological specimens in a fluid medium is disclosed in which the specimens are rendered magnetically responsive by immunospecific binding with ferromagnetic colloid. A known quantity of magnetically-responsive marker particles are added to the fluid medium. The fluid medium is then subjected to a magnetic separation process, to collect the magnetic species from the fluid. The collected species are resuspended in a second fluid medium, and the relative quantities thereof are enumerated to determine the concentration of the desired biological specimen in the first fluid medium. The marker particles may comprise magnetic particles having a relatively large magnetic moment, a magnetic moment approximately equal to the magnetically-labelled biological speciment of interest, or both in order to compensate the determination for variations in immunospecific binding affinity and/or magnetic collection efficiency. The present method is useful for conducting hematological assays, such as red blood cell counts and related determinations. In the case of red blood cells, the specimens may be rendered magnetically responsive by reduction of the iron atoms present in hemoglobin. The enumeration step of the method may be conducted with such equipment as a flow cytometer, or by a novel optical scanning magnetic cell immobilization apparatus.

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Huntingdon Valley, PA, United States of America

Paul A Liberti