WO1994007139A1 - Improved method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations - Google Patents
Improved method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations Download PDFInfo
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- WO1994007139A1 WO1994007139A1 PCT/NO1993/000136 NO9300136W WO9407139A1 WO 1994007139 A1 WO1994007139 A1 WO 1994007139A1 NO 9300136 W NO9300136 W NO 9300136W WO 9407139 A1 WO9407139 A1 WO 9407139A1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
- G01N33/54326—Magnetic particles
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56966—Animal cells
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57415—Specifically defined cancers of breast
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/961—Chemistry: molecular biology and microbiology including a step of forming, releasing, or exposing the antigen or forming the hapten-immunogenic carrier complex or the antigen per se
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/824—Immunological separation techniques
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/828—Protein A
Definitions
- the present invention relates to an immunomagnetic method for detection of specific target cells in cell populations and solutions of cell populations.
- the invention also relates to a kit for performing the method in different cell populations.
- the cell content may be examined using a range of sofisticated methods. It is also of importance to be able to isolate the cells in viable forms.
- Affinity binding is a sofisticated way of linking chemical/bio-chemical entities together.
- a pair of binding partners which for example are attached to the substances to be linked, bind to each other when brought in contact.
- One of the binding partners in such a linkage may be represented by a molecule on the cell surface.
- binding partner systems such as antigen- antibody, enzyme- receptor, ligand- receptor interactions on cells and biotin- avidin binding, of which antigen-antibody binding is most frequently used.
- a hapten/anti-hapten binding pair method has also
- PCT/EP90/02327 The latter is directed to use a combination of positive and negative selection for the purpose of isolating and possibly growing specific cells, i.e. haematopoietic progenitor cells, in the bone marrow, and is dependent upon removal of the particles.
- PCT/EP90/01171 relates to a method of connecting target cells to an insoluble support by using the abilities of hapten, anti-hapten antibodies and anti-cell antibodies to bind to each other, thus constructing a linkage between the insoluble support, i.e. particle, and the target cell, consisting at least of hapten and anti-hapten antibody or combinations of hapten and anti-hapten antibodies and anti-anti-hapten
- the later cleavage of the complex is performed by again exposing it to hapten or hapten analogue.
- the constructed link always consists of hapten in addition to 1 or more elements.
- the method is directed to unspecified target cells and is directed to isolation of target cells and release of the insoluble support.
- the object of the present invention is to detect for diagnostic purposes specific target cells when used in a blood and bone marrow, without the problem with unspecific binding to normal cells. It represents a sensitive detection method for a variety of cell types, such that a high number of cells can be readily screened in the microscope and the procedure is rapid and simple. Furthermore, the present method can be used for isolation of cells for biochemical, biological and
- a further object of the invention is to provide a kit for performing the method as characterized in the claims.
- the method for immunomagnetic detection of target cells in a mixed cell population and physiological solutions containing cell populations is suitable for detection, but may also be used in positive isolation of specific types of both normal cells and patogenic cells.
- the method creates a linkage between a specific target cell and an insoluble support, such as paramagnetic particles , which consists of one or two elements.
- the particle is either coated with an anti-cell antibody of murine or human origin, directed to the specific antigen determinants in the membranes of the wanted target-cells, or the particles are coated with a polyclonal anti-mouse or anti-human antibody capable of binding to the Fc-portions of the specific anti-cell antibody directed to the antigen
- a monoclonal rat anti-mouse/anti-human antibody may be used instead of using the polyclonal anti-mouse/anti-human antibody for coating the particles. This last antibody, due partly to its monoclonal origin, may provide a more specific binding to the anti-cell antibody and reduce the risk for possible cross-reactions with other cells in solutions, such as blood. Furthermore,
- cancer cells as the target-cells for detection and possible isolation.
- the method is, however, not limited to cancer cells and the disclosure shall not limit the method to this particular field of use, since the method is suitable within a range of cytological research areas.
- metastatic spread has occurred to other tissues, is of utmost importance for the choice of therapeutic alternative for the individual patient.
- Malignant cells spread by direct invasion into the surrounding tissue, through the lymphatics or by the distribution of tumor cells in the blood to distant organs, including the bone marrow and the central nervous system and the cerebrospinal fluid. Detection of metastatic tumor cells has, until recently, relied on morphological methods using light and electron microscopy on biopsied tumor specimens, on smears of bone marrow and
- the invention allows for a very sensitive detection of, for example, metastatic tumor cells, since a high number of cells can readily be screened in the microscope and the attached magnetic beads are easily recognisable.
- antibodies used bind with sufficient specificity to, for example, tumor cells and not to other cells than the target-cells present in mixed cell suspensions, like blood, bone marrow, and in other tumor manifestations, such that all cells with attached beads represent the target-cells.
- the procedure is rapid and simple, and can be performed by any investigator with access to a conventional microscope.
- the novel method involves the binding of monoclonal antibodies e.g. of murine or human origin, that specifically recognize antigens present on tumor cells, and not on the normal cells in question, or for other purposes to specified subpopulations of normal cells, to paramagnetic particles, either directly or to beads first covered with antibodies specifically recognizing the respective antibodies, or the Fc-portion of IgG antibodies that bind to the tumor cells.
- the cell binding antibodies may be of the IgG or IgM type or being a fragment of ab IgG or IgM.
- Examples of used anti-target-cell antibodies may be those directed against groups of antigen determinants, for example CD56/NCAM antigen (MOC-1), Cluster 2 epithelial antigen (MOC-31), Cluster 2 (MW ⁇ 40kD) antigen (NrLu10) (Myklebust et al. Br. J. Cancer Suppl. 63, 49-53, 1991), HMW-melanoma-associated antigen (9.2, 27) (Morgan et al., Hybridoma, 1 , 27-36, 1981), 80kD, Sarcoma-associated antigen (TP1 & TP3) (Cancer Res. 48, 5302-5309, 1988), mucin antigens (Diel et al., Breast Cancer Res.
- MOC-1 CD56/NCAM antigen
- MOC-31 Cluster 2 epithelial antigen
- Cluster 2 (MW ⁇ 40kD) antigen NrLu10)
- HMW-melanoma-associated antigen (9.2, 27) (Morgan e
- EGF-receptor antigen 425.3 (Merck), in addition to the anti-pan-human antibody (Bruland et al., unpublished), which is suitable for detecting human cells among animal cells.
- the 425.3 antibody is directed towards antigens in both normal and malignant cells.
- Antibodies can furthermore be directed against growth factor receptors, for example EGF-receptor, PDGF (A and B) receptor, insuline
- malignant cells these may be breast, ovarian and lung carcinoma cells, melanoma, sarcoma, glioblastoma, cancer cells of the gastrointestinal tract and the reticuloendothelial system, or the target-cells may be associated with non-neoplastic diseases, such as
- cardiovascular neurological, pulmonary, autoimmune,
- the malignant cell population may be located in bone marrow, peripheral blood, come from pleural and peritoneal effusions and other body fluid compartments, such as urine, cerebrospinal fluid, semen, lymph or from solid tumors in normal tissues and organs, for example liver, lymph nodes, spleen, lung, pancreas, bone tissue, the central nervous system, prostatic gland, skin and mucous membranes.
- body fluid compartments such as urine, cerebrospinal fluid, semen, lymph or from solid tumors in normal tissues and organs, for example liver, lymph nodes, spleen, lung, pancreas, bone tissue, the central nervous system, prostatic gland, skin and mucous membranes.
- the method comprises attachment of the antibodies directly to the paramagnetic particles, or the attachment can take place by attachment to surface-bound antibodies, such as polyclonal anti-mouse antibodies, monoclonal rat anti-mouse antibodies or monoclonal anti-human antibodies, specifically recognizing the Fc-portion of the said individual antibodies.
- surface-bound antibodies such as polyclonal anti-mouse antibodies, monoclonal rat anti-mouse antibodies or monoclonal anti-human antibodies, specifically recognizing the Fc-portion of the said individual antibodies.
- the antibody-coated paramagnetic beads are then mixed with the suspension of cells to be examined and incubated for 5-10 min to 2 h,
- the present method may also be performed in a changed order of steps, in that the free target-cell antibodies are added to the cell suspension, incubated for 5-10 min to 2h, preferably 30 min, at 0-20°C, preferably 4°C, under gentle rotation.
- the paramagnetic particles, precoated with anti-mouse or anti-human antibodies are then added to the incubated cell suspension, as described above, and the resulting suspension subjected to a further incubation of 5-10 min to 2h, preferably 30 min, at 0-25°C, preferably 4°C under gentle agitation.
- Samples of the cell suspension are then transferred to a cell counting device, and the fraction of cells with attached beads relative to the total number of cells is determined under light microscopy.
- the number of antibody-coated beads added to the cell suspension should be between 0.5-10 times the number of target cells. When this number is unknown, the amount of coated beads added should be 1-10 % of the total number of cells.
- the target cells can be positively separated from non-target cells in a magnetic field.
- the isolated target cells can then be enumerated microscopically and the fraction of target cells relative to the total number of cells in the initial cell suspension can be calculated.
- the target-cells may be characterized for the presence of specific biochemical and biological features. Of particular importance will be the use of such cells for studies in molecular biology.
- the present method allows studies and growth of the target-cells without performing a cleavage of the paramagnetic particle-target cell linkage.
- signals obtained on Southern, Northern and Western blots represent the normal cells as well as the tumor cells in the biopsy. If a single cell suspension is first prepared from the tumor material, and the tumor cells are then positively immunomagnetically detected and separated, any gene studies performed on this material would represent the target-cells only.
- This also relates to for example malignant cells present in mammalian tissues, for example in bone marrow, peripheral blood, pleural and peritoneal effusions, and other body fluids, for example urine, cerebrospinal fluid, semen and lymph.
- PCR polymerase chain reaction
- Tissue from solid or needle tumor biopsies is prepared mechanically or with mild enzymatic treatment into a single cell suspension, to which the primary, specific antibodies or antibody fragments are added directly or after washing the cell suspension with phosphate buffered saline or culture medium with or without serum, such as fetal calf serum, bovine, horse, pig, goat or human serum.
- serum such as fetal calf serum, bovine, horse, pig, goat or human serum.
- the specific antibodies or antibody fragments are either added to the samples directly, or after centrifugation with or without washings before or after the cells in the samples are spun down and brought back into suspension. c) If the material consists of blood or bone marrow aspirate, the mononuclear cell fraction is isolated by gradient
- the procedure conditions for a) and b) are established, as exemplified by results obtained in successful experiments as those described below.
- the results have been found to be influenced by a high number of factors which have been examined in detail. Among these are antibody concentration, the ratio of the number of paramagnetic particles versus number of cells, incubation times and volumes, type of incubation medium, and the pH level.
- the particle to mononuclear cell ratio in all experiments should be in the range of 0.5/1 - 2/1, depending on the binding affinity of the primary specific antibodies or fragments.
- mononuclear blood or bone marrow cells was reduced from an average of 10 to about 1 and in parallell the fraction of normal cells with particles decreased from 1-2% to 0.5-1% or less.
- hydrophobicity is thus claimed.
- One such method is preincubation of the antibody-coated particles and the cell suspension with mild detergents in suitable concentrations, for example Tween 20 in concentrations of less than 0.1% for
- the cell suspension should contain a low
- the cell suspension After incubation of the cell suspension with the primary antibodies or antibody fragments and the antibody-coated paramagnetic particles as described in previously, the cell suspension is incubated with a second set of antibodies or antibody fragments directed against other extracellular or against intracellular determinants of the target cells, with our without pretreatment with cell fixatives such as
- metallocolloids radioisotopes
- biotin-complexes or enzymes like peroxidase and alkaline phosphatase, allowing
- the target cells will both be visualized with the latter method and have bound particles to their surface, and can thus be enumerated.
- kits will contain for example precoated paramagnetic particles prepared for each monoclonal antibody.
- the kits contain paramagnetic particles pre-coated with IgG isotype specific anti-mouse or anti-human antibody as one part of it, and different target cell-associated, for example tumor cell, antibodies as another part.
- the kit contains paramagnetic particles precoated with specific anti-Fc antibodies, such as polyclonal anti-mouse, or monoclonal rat anti-mouse, or anti-mouse, or anti-human antibodies, capable of binding to the Fc-portion the target-cell associating antibodies, bound to specific anti-target-cell antibodies.
- specific anti-Fc antibodies such as polyclonal anti-mouse, or monoclonal rat anti-mouse, or anti-mouse, or anti-human antibodies, capable of binding to the Fc-portion the target-cell associating antibodies, bound to specific anti-target-cell antibodies.
- kit contains other specific antibodies or antibody
- fragments are conjugated to peroxidase, alkaline phosphatase, or other enzymes, together with relevant substrates to such enzymes, or where said antibody or antibody fragment is bound to non-paramagnetic particles with specific colours or with bound enzymes such as peroxidase and alkaline phosphatase.
- model experiments were performed where specific antibodies and SAM-coated paramagnetic particles were added either to such mononuclear cells or to a cell suspension where a different number of cancer cells from in vitro cultivated cell lines were added to said mononuclear cells.
- the mononuclear cells, or the malignant cells were prestained with a fluorescent dye, to be able to distinguish beteween the two types of cells.
- non-binding primary antibodies, and/or sheep-anti mouse antibody-coated beads were used separately as controls.
- Example 1 Similar procedures for malignant melanoma, sarcoma, neuroblastoma and several other cancers have been established or are under development.
- tissue biopsies are obtained by surgical procedures or by e.g. needle biopsies
- a much more simple and rapid diagnosis can be made with the new method, used on prepared cell suspensions, compared to conventional morphological or immunohisto- or cytochemical procedures.
- the present method can be used to identify prognostic indicators, for example as described in application Example 2.
- rheumatoid diseases such as rheumatoid arthritis
- allergic, autoimmune and rheumatoid arthritis
- cell membrane molecules mentioned in sections 1-6 may also be used as targets for immunotherapy with several types of activiated killer cells or e.g. with immunotoxins.
- the identification with the new method of expression of such molecules is, therefore, also of value for determining in which cases such types of therapy should be used.
- MOC-31, NrLu10, BM2 , BM7, 12H12, and MLuCl anti-carcinoma antibodies to determine whether or not micrometastatic disease from breast, lung, colorectal, and prostate cancer might be sensitively identified in such body fluids.
- the successful results with these antibodies have significant clinical implications.
- serveral cell membrane molecules have been shown to correlate with progression of the malignant disease in several types of cancer.
- the detection of binding of such antibodies to respective antibodies can therefore be used to obtain information of high prognostic value.
- antigens are a high number of adhesion molecules, carbohydrate antigens, glycolipids, growth factor receptors and carcinoma markers listed below. We have, with the new procedure
- the cells were suspended in a volume of 2 ml of RPMI with a 10% fetal calf serum, incubated with 9.2.27 anti-melanoma antibody (10 ⁇ g/ml) at 4°C for 30 min, washed and again incubated with Dynabeads SAM M450/IgG2A at 4°C for
- paramagnetic cells attached to their surface.
- the diagnosis of malignant melanoma was confirmed, as about 10% of the cells had a significant number of particles rosettes.
- Biopsied tissue was obtained from a subcutaneous tumor in a case with clinical indications of either small cell lung cancer or a malignant melanoma.
- a single cell suspension was prepared from the biopsy, divided in 2 fractions, one incubated with the 9.2.27 anti-melanoma antibody, and the other with MOC-31 anti-carcinoma antibody (both at 10 ⁇ g/ml). The incubation was similar to that used in the example above. None of the cells incubated with the melanoma antibody bound any beads, whereas all tumor cells incubated with MOC-31 were positive.
- Example 5 Biopsied tissue from a patient suspected to have malignant melanoma was examined by preparing single cell suspension, incubating with 9.2.27 anti-melanoma antibody, and then following the procedure as above. Most of the cells were positive with a high number of particle-rosettes attached to their membranes.
- a pleural effusion from a breast cancer patient was studied to examine whether tumor cells could be detected in the fluid.
- On litre of the fluid was centrifuged, the cells resuspended, and in separate vials incubate with each of 3 different anti-carcinoma antibodies (MOC-31, 2E11, 12H12). After completing the procedure as in the previous example, it was found that most of the cells bound to antibody-coated particles in all 3 cases.
- a bone marrow suspension obtained from a breast cancer patient was studied to examine whether micrometastic tumor cells could be present. After the preparation of mononuclear cells, these were incubated with the same 3 anti-carcinoma antibodies used in the example above, but in this case the antibodies were first attached to Dynabeads SAM IgG paramagneteic particles. After 1 incubation with these directly coated particles, the cell suspension was examined in the microscope, and a high number of cells were found positive with a number of particle-rosettes attached to their membrane.
- T47D human breast carcinoma cells were incubated for varying lenghts of time with Hoechst fluoresence dye, and the viability of the labeled cells was checked. Varying numbers of labeled breast carcinoma cells were then added to 1 ⁇ 10 6 bone marrow cells obtained from healthy volunteers. In different
- Pleural and ascites fluid from patients with breast cancer and ovarian carcinoma were sentrifuged, the same coated
- paramagnetic particles used in Example 1 were added, incubated and concentrated in a magnetic field before the suspension was examined under light microscopy. Typically, cells that had the clear morphological features of tumor cells had beads attached, whereas none of the few normal cells bound the antibody-coated beads. In two cases with pleural effusion, an independent morphological examination did not reveal the presence of any tumor cells, whereas a significant number malignant cells were detected by the use of anibody-coated beads. In some cases, tumor cells were separated in a magnetic field and transferred to tissue culture flasks containing growth medium specially prepared for growing breast cancer cells, in attempts to establish permanent cell lines from these cultures. In
- bone marrow and peripheral blood obtained from patients with breast cancer were examined with the present procedure by adding antibody-coated paramagnetic beads, incubating for 30 min at 4°C and concentrating in a magnetic field and by examining the suspension under light microscopy.
- binding of the paramagnetic beads to tumor cells, representing 0,1-1 % of the nucleated cells in the bone marrow and blood was detected, cells that could not be identified by any other method.
- Beads coated with anti-transferrin receptor antibodies, used in the novel method according to the present invention were shown to represent a rapid, simple and sensitive method for identification of cells expressing the transferrinreceptor.
- capillary or small vessels in normal or tumorous tissue could be positively selected from cell suspensions prepared from the relevant tissues.
- the procedure involved the use of beads coated with antibody directed against structures expressed on the endothelial cells, but not on the other normal cells in the cell mixture.
- Human cells injected into immunodeficient rodents was shown to be present in cell suspensions prepared from tumor xenografts and from various host organs/tissues by employing magnetic particles coated with an anti-pan human antibody.
- Fibronectin receptor ( ⁇ 5 ⁇ 1 integrin) Pierce 36114, BTC 21/22
- V ⁇ tronectin receptor ( ⁇ v ⁇ 3 integrin) TP36.1, BTC 41/42
- CD44-variants 11.24, 11.31, 11.10
- High molecular weight antigen (HMW 250.000) 9.2.27, NrML5, 225.28,
- MOC-31 epitope cluster 2 epithelial antigen
- MUC-1 antigens such as DF3-epitope (gp290kD)
- Ovarian carcinoma OC125 epitope (m w 750 kD) OC125
- G9-epitope (colon cardnoma)
- gpl60 lung cancer antigen (Cancer Res. 43, 2768, 1988) anti gp160
- Hepemal epitope (gp43) Hepatocellular care, ag Hepema-1
- Neuroblastoma-associated such as UJ13A epitope UJ13A
Abstract
Description
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Priority Applications (15)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PL93308109A PL177136B1 (en) | 1992-09-14 | 1993-09-10 | Improved method of detecting specific target cells among specialised or mixed populations of cells or in suspensions containing mixed populations of cells |
HU9500723A HU221234B1 (en) | 1992-09-14 | 1993-09-10 | Method for defecting specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
JP50799194A JP3417563B2 (en) | 1992-09-14 | 1993-09-10 | Special cell population or mixed cell population and method for detecting specific target cells in a solution containing mixed cell population |
AU48363/93A AU686569B2 (en) | 1992-09-14 | 1993-09-10 | Improved method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
SK329-95A SK281566B6 (en) | 1992-09-14 | 1993-09-10 | Method for detection of specific target cells and means for realisation |
US08/403,844 US6893881B1 (en) | 1992-09-14 | 1993-09-10 | Method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
CA2144328A CA2144328C (en) | 1992-09-14 | 1993-09-10 | Improved method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
DE69326956T DE69326956T2 (en) | 1992-09-14 | 1993-09-10 | IMPROVED METHOD FOR DETECTING SPECIFIC TARGET CELLS IN SPECIALIZED OR MIXED CELL POPULATION AND CONTAINING MIXED CELL POPULATIONS |
EP93921134A EP0660930B1 (en) | 1992-09-14 | 1993-09-10 | Improved method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
PT93921134T PT660930E (en) | 1992-09-14 | 1993-09-10 | IMPROVED METHOD OF DETERMINING SPECIFIC TARGET CELLS IN A POPULATION OF SPECIALIZED OR MIXED CELLS AND SOLUTIONS CONTAINING MIXED CELLULITE POPULATIONS |
DK93921134T DK0660930T3 (en) | 1992-09-14 | 1993-09-10 | Improved method for detecting specific target cells in specialized or mixed cell population and solution |
NO950918A NO950918L (en) | 1992-09-14 | 1995-03-10 | Method for Detecting Specific Target Cells in Specialized or Mixed Cell Populations and Solutions Containing Mixed Cell Population |
FI951161A FI951161A (en) | 1992-09-14 | 1995-03-13 | Improved method for detecting specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
GR20000400243T GR3032547T3 (en) | 1992-09-14 | 2000-02-02 | Improved method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations. |
US10/359,677 USRE43979E1 (en) | 1992-09-14 | 2003-02-05 | Method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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NOPCT/NO92/00151 | 1992-09-14 | ||
PCT/NO1992/000151 WO1994007138A1 (en) | 1992-09-14 | 1992-09-14 | Detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
Related Child Applications (2)
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US08403844 A-371-Of-International | 1993-09-10 | ||
US08/881,393 Division US6184043B1 (en) | 1992-09-14 | 1997-06-24 | Method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
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WO1994007139A1 true WO1994007139A1 (en) | 1994-03-31 |
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PCT/NO1992/000151 WO1994007138A1 (en) | 1992-09-14 | 1992-09-14 | Detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
PCT/NO1993/000136 WO1994007139A1 (en) | 1992-09-14 | 1993-09-10 | Improved method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
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PCT/NO1992/000151 WO1994007138A1 (en) | 1992-09-14 | 1992-09-14 | Detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
Country Status (17)
Country | Link |
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US (3) | US6893881B1 (en) |
EP (1) | EP0660930B1 (en) |
JP (1) | JP3417563B2 (en) |
AT (1) | ATE186402T1 (en) |
AU (2) | AU2593192A (en) |
CA (1) | CA2144328C (en) |
CZ (1) | CZ65995A3 (en) |
DE (1) | DE69326956T2 (en) |
DK (1) | DK0660930T3 (en) |
ES (1) | ES2141170T3 (en) |
FI (1) | FI951161A (en) |
GR (1) | GR3032547T3 (en) |
HU (1) | HU221234B1 (en) |
PL (1) | PL177136B1 (en) |
PT (1) | PT660930E (en) |
SK (1) | SK281566B6 (en) |
WO (2) | WO1994007138A1 (en) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995024648A1 (en) * | 1994-03-10 | 1995-09-14 | Fodstad Oeystein | Method and device for detection of specific target cells in specialized or mixed cell populations and solutions containing mixed cell populations |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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US20030119185A1 (en) * | 2000-02-24 | 2003-06-26 | Xcyte Therapies, Inc. | Activation and expansion of cells |
US20030235908A1 (en) * | 2000-02-24 | 2003-12-25 | Xcyte Therapies, Inc. | Activation and expansion of cells |
AR028039A1 (en) * | 2000-05-03 | 2003-04-23 | Oncolytics Biotech Inc | REMOVAL OF REOVIRUS FROM NEOPLASTIC CELLS INTERMEDIATE BY RAS FROM MIXED CELL COMPOSITIONS |
WO2001089539A2 (en) * | 2000-05-25 | 2001-11-29 | Xcyte Therapies, Inc. | Methods for restoring or enhancing t-cell immune surveillance following naturally or artifically induced immunosuppression |
FR2810045B1 (en) * | 2000-06-07 | 2004-09-03 | Assist Publ Hopitaux De Paris | METHOD FOR OBTAINING CELLULAR CELLULAR POPULATIONS OF MUSCLE ORIGIN AND USES THEREOF |
US6913697B2 (en) | 2001-02-14 | 2005-07-05 | Science & Technology Corporation @ Unm | Nanostructured separation and analysis devices for biological membranes |
US7285412B2 (en) * | 2001-07-27 | 2007-10-23 | Surface Logix Inc. | Device for magnetic immobilization of cells |
US7169578B2 (en) * | 2001-07-27 | 2007-01-30 | Surface Logix, Inc. | Cell isolation and screening device and method of using same |
US7169577B2 (en) * | 2001-07-27 | 2007-01-30 | Surface Logix, Inc. | Cell isolation and screening device and method of using same |
WO2003023571A2 (en) * | 2001-09-12 | 2003-03-20 | Burstein Technologies, Inc. | Methods for differential cell counts including related apparatus and software for performing same |
US8986944B2 (en) | 2001-10-11 | 2015-03-24 | Aviva Biosciences Corporation | Methods and compositions for separating rare cells from fluid samples |
US8980568B2 (en) | 2001-10-11 | 2015-03-17 | Aviva Biosciences Corporation | Methods and compositions for detecting non-hematopoietic cells from a blood sample |
WO2003066191A1 (en) * | 2002-02-04 | 2003-08-14 | Colorado School Of Mines | Laminar flow-based separations of colloidal and cellular particles |
KR20040105717A (en) * | 2002-02-14 | 2004-12-16 | 이뮤니베스트 코포레이션 | Methods and algorithms for cell enumeration in a low-cost cytometer |
US7764821B2 (en) * | 2002-02-14 | 2010-07-27 | Veridex, Llc | Methods and algorithms for cell enumeration in a low-cost cytometer |
WO2004011128A1 (en) * | 2002-07-26 | 2004-02-05 | Aclara Biosciences, Inc. | Methods and compositions for screening cell binding molecules |
ES2375724T3 (en) | 2002-09-27 | 2012-03-05 | The General Hospital Corporation | MICROFLUDE DEVICE FOR SEPERATION OF CELLS AND ITS USES. |
EP1604184A4 (en) * | 2003-02-27 | 2010-10-27 | Stephen A Lesko | Standardized evaluation of therapeutic efficacy based on cellular biomarkers |
JP2006524991A (en) * | 2003-05-08 | 2006-11-09 | エクサイト セラピーズ インコーポレーティッド | Method for producing and isolating antigen-specific T cells |
AU2004250131A1 (en) * | 2003-06-13 | 2004-12-29 | The General Hospital Corporation | Microfluidic systems for size based removal of red blood cells and platelets from blood |
EP1494028A1 (en) * | 2003-07-03 | 2005-01-05 | Labsoft Diagnostics AG | Immunomagnetic separation of specific target cells |
US20050020899A1 (en) * | 2003-07-25 | 2005-01-27 | Rubicor Medical, Inc. | Post-biopsy cavity treatmetn implants and methods |
WO2005030251A1 (en) * | 2003-09-22 | 2005-04-07 | Xcyte Therapies, Inc. | Compositions and methods to accelerate hematologic recovery |
US20050266433A1 (en) * | 2004-03-03 | 2005-12-01 | Ravi Kapur | Magnetic device for isolation of cells and biomolecules in a microfluidic environment |
US8189899B2 (en) * | 2004-07-30 | 2012-05-29 | Veridex, Llc | Methods and algorithms for cell enumeration in a low-cost cytometer |
WO2006020936A2 (en) * | 2004-08-12 | 2006-02-23 | Immunivest Corporation | A method for assessing disease states by profile analysis of isolated circulating endothelial cells |
US20060171846A1 (en) * | 2005-01-10 | 2006-08-03 | Marr David W M | Microfluidic systems incorporating integrated optical waveguides |
US20070026414A1 (en) * | 2005-07-29 | 2007-02-01 | Martin Fuchs | Devices and methods for enrichment and alteration of circulating tumor cells and other particles |
US20070196820A1 (en) | 2005-04-05 | 2007-08-23 | Ravi Kapur | Devices and methods for enrichment and alteration of cells and other particles |
US20070026413A1 (en) * | 2005-07-29 | 2007-02-01 | Mehmet Toner | Devices and methods for enrichment and alteration of circulating tumor cells and other particles |
US20070026415A1 (en) * | 2005-07-29 | 2007-02-01 | Martin Fuchs | Devices and methods for enrichment and alteration of circulating tumor cells and other particles |
US20070026417A1 (en) * | 2005-07-29 | 2007-02-01 | Martin Fuchs | Devices and methods for enrichment and alteration of circulating tumor cells and other particles |
KR20080023292A (en) * | 2005-05-27 | 2008-03-13 | 더 보드 오브 리전츠 오브 더 유니버시티 오브 텍사스 시스템 | Optical coherence tomographic detection of cells and compositions |
US20090181421A1 (en) * | 2005-07-29 | 2009-07-16 | Ravi Kapur | Diagnosis of fetal abnormalities using nucleated red blood cells |
US8921102B2 (en) | 2005-07-29 | 2014-12-30 | Gpb Scientific, Llc | Devices and methods for enrichment and alteration of circulating tumor cells and other particles |
US20070059680A1 (en) * | 2005-09-15 | 2007-03-15 | Ravi Kapur | System for cell enrichment |
US20070026416A1 (en) * | 2005-07-29 | 2007-02-01 | Martin Fuchs | Devices and methods for enrichment and alteration of circulating tumor cells and other particles |
US7901950B2 (en) * | 2005-08-12 | 2011-03-08 | Veridex, Llc | Method for assessing disease states by profile analysis of isolated circulating endothelial cells |
US20070059774A1 (en) * | 2005-09-15 | 2007-03-15 | Michael Grisham | Kits for Prenatal Testing |
US20070059719A1 (en) * | 2005-09-15 | 2007-03-15 | Michael Grisham | Business methods for prenatal Diagnosis |
US20070059781A1 (en) * | 2005-09-15 | 2007-03-15 | Ravi Kapur | System for size based separation and analysis |
US20070059718A1 (en) * | 2005-09-15 | 2007-03-15 | Mehmet Toner | Systems and methods for enrichment of analytes |
US20070059683A1 (en) * | 2005-09-15 | 2007-03-15 | Tom Barber | Veterinary diagnostic system |
US7807459B2 (en) * | 2005-09-27 | 2010-10-05 | Reneuron, Inc. | EphA4-positive human adult pancreatic endocrine progenitor cells |
US9487812B2 (en) | 2012-02-17 | 2016-11-08 | Colorado School Of Mines | Optical alignment deformation spectroscopy |
US9885644B2 (en) | 2006-01-10 | 2018-02-06 | Colorado School Of Mines | Dynamic viscoelasticity as a rapid single-cell biomarker |
US9878326B2 (en) * | 2007-09-26 | 2018-01-30 | Colorado School Of Mines | Fiber-focused diode-bar optical trapping for microfluidic manipulation |
US8119976B2 (en) * | 2007-07-03 | 2012-02-21 | Colorado School Of Mines | Optical-based cell deformability |
US20080076727A1 (en) * | 2006-03-29 | 2008-03-27 | John Wayne Cancer Institute | Utility of high molecular weight melanoma associated antigen in diagnosis and treatment of cancer |
US20080050739A1 (en) * | 2006-06-14 | 2008-02-28 | Roland Stoughton | Diagnosis of fetal abnormalities using polymorphisms including short tandem repeats |
US8372584B2 (en) | 2006-06-14 | 2013-02-12 | The General Hospital Corporation | Rare cell analysis using sample splitting and DNA tags |
EP2029779A4 (en) | 2006-06-14 | 2010-01-20 | Living Microsystems Inc | Use of highly parallel snp genotyping for fetal diagnosis |
US8137912B2 (en) | 2006-06-14 | 2012-03-20 | The General Hospital Corporation | Methods for the diagnosis of fetal abnormalities |
US20080090239A1 (en) * | 2006-06-14 | 2008-04-17 | Daniel Shoemaker | Rare cell analysis using sample splitting and dna tags |
US20080007838A1 (en) * | 2006-07-07 | 2008-01-10 | Omnitech Partners, Inc. | Field-of-view indicator, and optical system and associated method employing the same |
CA2657621A1 (en) * | 2006-07-14 | 2008-01-17 | Aviva Biosciences Corporation | Methods and compositions for detecting rare cells from a biological sample |
US10722250B2 (en) | 2007-09-04 | 2020-07-28 | Colorado School Of Mines | Magnetic-field driven colloidal microbots, methods for forming and using the same |
US20090062828A1 (en) * | 2007-09-04 | 2009-03-05 | Colorado School Of Mines | Magnetic field-based colloidal atherectomy |
EP2584360A1 (en) | 2007-12-05 | 2013-04-24 | Zyomyx Inc. | Cell assay kit and method |
US8071395B2 (en) * | 2007-12-12 | 2011-12-06 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and apparatus for magnetic separation of cells |
KR101384142B1 (en) * | 2007-12-28 | 2014-04-14 | 삼성디스플레이 주식회사 | Display substrate, method for manufacturing the display substrate and display apparatus having the display substrate |
US7927561B2 (en) * | 2008-01-10 | 2011-04-19 | Becton, Dickinson And Company | Rapid particle detection assay |
EP2334812B1 (en) | 2008-09-20 | 2016-12-21 | The Board of Trustees of The Leland Stanford Junior University | Noninvasive diagnosis of fetal aneuploidy by sequencing |
CN110470835A (en) * | 2009-03-24 | 2019-11-19 | 生物概念股份有限公司 | The device and method of cell capture and analysis |
US20120100538A1 (en) * | 2009-03-24 | 2012-04-26 | Biocept, Inc. | Devices and methods of cell capture and analysis |
US8187979B2 (en) * | 2009-12-23 | 2012-05-29 | Varian Semiconductor Equipment Associates, Inc. | Workpiece patterning with plasma sheath modulation |
US20120020938A1 (en) * | 2010-07-26 | 2012-01-26 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | MHC- less cells |
KR20120026959A (en) | 2010-09-10 | 2012-03-20 | 인제대학교 산학협력단 | Microparticle separator based on magnetophoresis and microparticle separating method using the same |
KR101213971B1 (en) | 2010-09-14 | 2012-12-20 | 서울대학교산학협력단 | method and device for remote moving of organelle, and magnetic particle complex for the same |
MX353566B (en) * | 2012-02-21 | 2018-01-18 | Laboratory Corp America Holdings | Methods and systems for signal amplification of bioassays. |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0403960A2 (en) * | 1989-06-19 | 1990-12-27 | BEHRINGWERKE Aktiengesellschaft | Magnetic protein conjugates, method to make them and their use |
WO1991001368A1 (en) * | 1989-07-24 | 1991-02-07 | Dynal A.S. | Hapten/anti-hapten affinity linking in cell separation |
WO1991009938A1 (en) * | 1989-12-29 | 1991-07-11 | Dynal A.S. | Method of separating haemopoietic progenitor cells |
WO1992004961A1 (en) * | 1990-09-26 | 1992-04-02 | Immunicon Corporation | Apparatus and methods for magnetic separation |
Family Cites Families (52)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4219411A (en) * | 1978-09-18 | 1980-08-26 | California Institute Of Technology | Cell sorting apparatus |
US4230685A (en) * | 1979-02-28 | 1980-10-28 | Northwestern University | Method of magnetic separation of cells and the like, and microspheres for use therein |
US4510244A (en) | 1980-04-17 | 1985-04-09 | The Board Of Trustees Of The Leland Stanford Jr. University | Cell labeling with antigen-coupled microspheres |
US4497900A (en) * | 1982-04-12 | 1985-02-05 | Abbott Laboratories | Immunoassay for Neisseria gonorrhoeae antigens |
US4511662A (en) | 1982-06-18 | 1985-04-16 | Bio-Rad Laboratories, Inc. | Simultaneous assay for T and B lymphocyte populations and subpopulations |
AU563827B2 (en) | 1982-07-01 | 1987-07-23 | Millipore Corp. | Filtration apparatus |
US4659678A (en) | 1982-09-29 | 1987-04-21 | Serono Diagnostics Limited | Immunoassay of antigens |
US4925922A (en) | 1983-02-22 | 1990-05-15 | Xoma Corporation | Potentiation of cytotoxic conjugates |
US4664911A (en) | 1983-06-21 | 1987-05-12 | Board Of Regents, University Of Texas System | Immunotoxin conjugates employing toxin B chain moieties |
US4704255A (en) | 1983-07-15 | 1987-11-03 | Pandex Laboratories, Inc. | Assay cartridge |
US4920061A (en) * | 1984-03-02 | 1990-04-24 | The University Of Texas System | Biological magnetic colloids |
US4752569A (en) * | 1984-06-21 | 1988-06-21 | The Regents Of The University Of California | Sialylated Lewisx epitope, antibodies and diagnosis |
US5019497A (en) * | 1984-11-09 | 1991-05-28 | Lennart Olsson | Human squamous lung carcinoma cell specific antigens and antibodies |
US4710472A (en) * | 1985-09-25 | 1987-12-01 | The United States Of America As Represented By The Secretary Of The Navy | Magnetic separation device |
US5076950A (en) | 1985-12-20 | 1991-12-31 | Syntex (U.S.A.) Inc. | Magnetic composition for particle separation |
EP0241042A3 (en) | 1986-04-11 | 1988-05-04 | Hitachi, Ltd. | A method for cell analysis |
EP0256471A3 (en) | 1986-08-15 | 1989-10-25 | Xoma Corporation | Cytotoxic conjugates for cancer therapy |
US4895706A (en) | 1986-10-28 | 1990-01-23 | Costar Corporation | Multi-well filter strip and composite assemblies |
US4857452A (en) * | 1986-12-04 | 1989-08-15 | E. I. Du Pont De Nemours And Company | Assay for carcinoma of breast, colon and ovary |
WO1988005309A1 (en) | 1987-01-27 | 1988-07-28 | Xoma Corporation | Potentiation of cytotoxic conjugates |
US4847199A (en) | 1987-02-27 | 1989-07-11 | Eastman Kodak Company | Agglutination immunoassay and kit for determination of a multivalent immune species using a buffered salt wash solution |
JPH07104349B2 (en) | 1987-04-11 | 1995-11-13 | 株式会社日立製作所 | Cytometry |
US5194300A (en) | 1987-07-15 | 1993-03-16 | Cheung Sau W | Methods of making fluorescent microspheres |
US5322678A (en) | 1988-02-17 | 1994-06-21 | Neorx Corporation | Alteration of pharmacokinetics of proteins by charge modification |
US5256532A (en) | 1988-05-02 | 1993-10-26 | Zynaxis Technologies, Inc. | Methods, reagents and test kits for determination of subpopulations of biological entities |
US5385822A (en) | 1988-05-02 | 1995-01-31 | Zynaxis, Inc. | Methods for detection and quantification of cell subsets within subpopulations of a mixed cell population |
FR2638848B1 (en) | 1988-11-04 | 1993-01-22 | Chemunex Sa | METHOD OF DETECTION AND / OR DETERMINATION IN A LIQUID OR SEMI-LIQUID MEDIUM OF AT LEAST ONE ORGANIC, BIOLOGICAL OR MEDICINAL SUBSTANCE, BY AN AGGLUTINATION METHOD |
FR2638849B1 (en) | 1988-11-04 | 1994-03-18 | Chemunex Sa | METHOD FOR AMPLIFYING A FLUORESCENT SIGNAL FOR THE SPECIFIC SEARCH OF THE POSSIBLE PRESENCE OF PARTICLES AND APPLICATION TO THE DETECTION AND NUMBERING OF SAID PARTICLES |
ATE114507T1 (en) * | 1988-12-28 | 1994-12-15 | Stefan Miltenyi | METHODS AND MATERIALS FOR HIGH GRADUATION MAGNETIC SEPARATION OF BIOLOGICAL MATERIALS. |
GB8905001D0 (en) | 1989-03-04 | 1989-04-19 | Univ Leicester | Screening for natural products of microbial metabolism |
WO1990010692A1 (en) * | 1989-03-15 | 1990-09-20 | University Of Florida | Monoclonal antibody for use in detection and treatment of childhood leukemia |
US5081030A (en) * | 1989-04-25 | 1992-01-14 | The Johns Hopkins University | Release of cells from affinity matrices |
DE3919873A1 (en) | 1989-06-19 | 1990-12-20 | Behringwerke Ag | MAGNETIC PROTEIN CONJUGATES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE |
AU659083B2 (en) | 1989-12-14 | 1995-05-11 | Sloan-Kettering Institute For Cancer Research | Therapeutic uses of the hypervariable region of monoclonal antibody M195 and constructs thereof |
GB9007966D0 (en) | 1990-04-09 | 1990-06-06 | Dynal As | Antigen/anti-antigen cleavage |
US5340719A (en) | 1990-11-23 | 1994-08-23 | Corporation Coulter | Method and apparatus for optically screening microscopic cells |
JPH05107249A (en) | 1991-02-04 | 1993-04-27 | Toyobo Co Ltd | High-sensitivity detection method of ligand/receptor reaction |
US5491068A (en) | 1991-02-14 | 1996-02-13 | Vicam, L.P. | Assay method for detecting the presence of bacteria |
AU2115092A (en) | 1991-10-08 | 1993-04-22 | Eastman Kodak Company | Method, test device and kit for assay of specific binding ligand using controlled flow through filtration membrane |
US5290707A (en) | 1991-11-25 | 1994-03-01 | The United States Of America As Represented By The Secretary Of The Army | Method for detection of microorganisms |
US5256542A (en) | 1992-03-09 | 1993-10-26 | Tanox Biosystems, Inc. | Selecting low frequency antigen-specific single B lymphocytes with correction for background noise |
JPH07509120A (en) | 1992-03-20 | 1995-10-12 | セルシス・インターナショナル・パブリック・リミテッド・カンパニー | Biological substance analysis method and device |
US5422277A (en) | 1992-03-27 | 1995-06-06 | Ortho Diagnostic Systems Inc. | Cell fixative composition and method of staining cells without destroying the cell surface |
EP0652703A4 (en) | 1992-07-28 | 1996-05-29 | Steven Kessler | Methods for positive immunoselection of stem cells. |
JP3420765B2 (en) | 1992-09-14 | 2003-06-30 | エス・アール・アイ・インターナシヨナル | Upconvertable reporter for biological and other analysis using laser excitation technology |
WO1994007138A1 (en) | 1992-09-14 | 1994-03-31 | Fodstad Oystein | Detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
FR2700010B1 (en) | 1992-12-24 | 1995-03-17 | Rocher Yves Biolog Vegetale | Method and device for testing the reactivity of cells with regard to products. |
US5374531A (en) | 1993-03-22 | 1994-12-20 | Zynaxis, Inc. | Immunoassay for determination of cells |
US5514340A (en) | 1994-01-24 | 1996-05-07 | Magnetix Biotechnology, Inc. | Device for separating magnetically labelled cells |
NO180658C (en) | 1994-03-10 | 1997-05-21 | Oeystein Fodstad | Method and Device for Detecting Specific Target Cells in Specialized or Mixed Cell Populations and Solutions Containing Mixed Cell Populations |
US5968753A (en) | 1994-06-14 | 1999-10-19 | Nexell Therapeutics, Inc. | Positive and positive/negative cell selection mediated by peptide release |
AUPN214095A0 (en) | 1995-04-03 | 1995-04-27 | Australian Water Technologies Pty Ltd | Method for detecting microorganisms using flow cytometry |
-
1992
- 1992-09-14 WO PCT/NO1992/000151 patent/WO1994007138A1/en active Application Filing
- 1992-09-14 AU AU25931/92A patent/AU2593192A/en not_active Abandoned
-
1993
- 1993-09-10 WO PCT/NO1993/000136 patent/WO1994007139A1/en not_active Application Discontinuation
- 1993-09-10 DK DK93921134T patent/DK0660930T3/en active
- 1993-09-10 HU HU9500723A patent/HU221234B1/en not_active IP Right Cessation
- 1993-09-10 PL PL93308109A patent/PL177136B1/en unknown
- 1993-09-10 DE DE69326956T patent/DE69326956T2/en not_active Revoked
- 1993-09-10 JP JP50799194A patent/JP3417563B2/en not_active Expired - Lifetime
- 1993-09-10 US US08/403,844 patent/US6893881B1/en not_active Expired - Lifetime
- 1993-09-10 AU AU48363/93A patent/AU686569B2/en not_active Ceased
- 1993-09-10 CZ CZ95659A patent/CZ65995A3/en unknown
- 1993-09-10 EP EP93921134A patent/EP0660930B1/en not_active Revoked
- 1993-09-10 AT AT93921134T patent/ATE186402T1/en not_active IP Right Cessation
- 1993-09-10 CA CA2144328A patent/CA2144328C/en not_active Expired - Lifetime
- 1993-09-10 ES ES93921134T patent/ES2141170T3/en not_active Expired - Lifetime
- 1993-09-10 PT PT93921134T patent/PT660930E/en unknown
- 1993-09-10 SK SK329-95A patent/SK281566B6/en unknown
-
1995
- 1995-03-13 FI FI951161A patent/FI951161A/en unknown
-
1997
- 1997-06-24 US US08/881,393 patent/US6184043B1/en not_active Ceased
-
2000
- 2000-02-02 GR GR20000400243T patent/GR3032547T3/en not_active IP Right Cessation
-
2003
- 2003-02-05 US US10/359,677 patent/USRE43979E1/en not_active Expired - Lifetime
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0403960A2 (en) * | 1989-06-19 | 1990-12-27 | BEHRINGWERKE Aktiengesellschaft | Magnetic protein conjugates, method to make them and their use |
WO1991001368A1 (en) * | 1989-07-24 | 1991-02-07 | Dynal A.S. | Hapten/anti-hapten affinity linking in cell separation |
WO1991009938A1 (en) * | 1989-12-29 | 1991-07-11 | Dynal A.S. | Method of separating haemopoietic progenitor cells |
WO1992004961A1 (en) * | 1990-09-26 | 1992-04-02 | Immunicon Corporation | Apparatus and methods for magnetic separation |
Cited By (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6184043B1 (en) | 1992-09-14 | 2001-02-06 | FODSTAD øYSTEIN | Method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
USRE43979E1 (en) | 1992-09-14 | 2013-02-05 | Abbott Laboratories | Method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
US6893881B1 (en) | 1992-09-14 | 2005-05-17 | Abbott Laboratories, Inc. | Method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations |
US6265229B1 (en) * | 1994-03-10 | 2001-07-24 | Oystein Fodstad | Method and device for detection of specific target cells in specialized or mixed cell populations and solutions containing mixed cell populations |
WO1995024648A1 (en) * | 1994-03-10 | 1995-09-14 | Fodstad Oeystein | Method and device for detection of specific target cells in specialized or mixed cell populations and solutions containing mixed cell populations |
US6680301B2 (en) | 1994-09-08 | 2004-01-20 | Photocure As | Transfer of molecules into the cytosol of cells |
US7198787B2 (en) | 1996-03-13 | 2007-04-03 | Oystein Fodstad | Method of killing target cells in harvested cell populations with one or more immuno-toxins |
WO1997036004A1 (en) * | 1996-03-26 | 1997-10-02 | Fodstad Oeystein | Immuno-magnetic cell separation used in identification of genes associated with site-preferenced cancer methastasis formation |
AU703262B2 (en) * | 1996-03-26 | 1999-03-25 | Oystein Fodstad | Immuno-magnetic cell separation used in identification of genes associated with site-preferenced cancer methastasis formation |
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Also Published As
Publication number | Publication date |
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AU2593192A (en) | 1994-04-12 |
AU686569B2 (en) | 1998-02-12 |
US6893881B1 (en) | 2005-05-17 |
EP0660930A1 (en) | 1995-07-05 |
PT660930E (en) | 2000-04-28 |
USRE43979E1 (en) | 2013-02-05 |
AU4836393A (en) | 1994-04-12 |
JP3417563B2 (en) | 2003-06-16 |
PL308109A1 (en) | 1995-07-24 |
HU9500723D0 (en) | 1995-04-28 |
DE69326956D1 (en) | 1999-12-09 |
GR3032547T3 (en) | 2000-05-31 |
CZ65995A3 (en) | 1995-11-15 |
DE69326956T2 (en) | 2000-06-15 |
HU221234B1 (en) | 2002-08-28 |
JPH08501390A (en) | 1996-02-13 |
HUT73741A (en) | 1996-09-30 |
SK32995A3 (en) | 1995-10-11 |
PL177136B1 (en) | 1999-09-30 |
FI951161A (en) | 1995-05-09 |
WO1994007138A1 (en) | 1994-03-31 |
CA2144328C (en) | 2010-11-30 |
EP0660930B1 (en) | 1999-11-03 |
FI951161A0 (en) | 1995-03-13 |
SK281566B6 (en) | 2001-05-10 |
CA2144328A1 (en) | 1994-03-31 |
US6184043B1 (en) | 2001-02-06 |
DK0660930T3 (en) | 2000-05-08 |
ES2141170T3 (en) | 2000-03-16 |
ATE186402T1 (en) | 1999-11-15 |
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