Liquid purification or separation – With alarm – indicator – register – recorder – signal or... – Transparent
Patent
1997-09-15
1999-03-02
Savage, Matthew O.
Liquid purification or separation
With alarm, indicator, register, recorder, signal or...
Transparent
210222, B01D 3506
Patent
active
058765930
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to the immobilization and manipulation of microscopic biological entities. More particularly, the present invention relates to magnetic labelling and immobilization of microscopic biological entities within an apparatus having an observation path for allowing observation and manipulation of such entities suspended within a fluid medium.
BACKGROUND
Many biological techniques such as are employed in biotechnology, microbiology, clinical diagnostics and treatment, in vitro fertilization, hematology and pathology, require such processes as identification, separation, culturing, or manipulation of a target entity such as a type of cell or microbe within a fluid medium such as blood, other bodily fluids, culture fluids or samples from the environment. It is often desirable to retain viability of the target entity or to culture the target entity.
Identification techniques typically involve labelling the target entity with a reagent which can be detected according to a characteristic property. Entities which can be viewed optically such as cells or certain microbes, may be identified using fluorescent MAb's or staining reagents specific to certain classes of cells or microbes. When such identification is done manually or mechanically, as by microscopy, multiple operations involving incubations and washing steps to remove excess labelling reagent are often performed. For example, in the usual method used to identify a subset of T-lymphocytes, such as T-Helper Cells or CD4-positive cells, a mixture of peripheral blood lymphocytes is incubated with a fluorescent MAb directed to CD4-positive cells. The MAb is then given sufficient incubation time to react with the CD4-positive cells. The CD4-positive cells are then washed using multiple centrifugations and can then readily be identified by fluorescent microscopy.
In the practice of manual fluorescent labelling methods employing a fluorescent microscope, direct labeling with MAb's is often impractical due to the expense of obtaining a cell-specific fluorescent Mab and because of reduced signal availability. Thus the technique of indirect analysis is common. During indirect analysis, the target entities are first labeled with a specific non-fluorescent MAb. Excess Mab is washed away. Then, a fluorescent-labeled second reagent such as fluorescent-labeled goat anti-mouse antibody is added to the medium. The medium is allowed to incubate to allow the labelled second reagent to bind with the non-fluorescent MAb and then excess reagent is removed. The target entities may then be identified due to the attachment of the fluorescent secondary reagent to the non-fluorescent biospecific MAb. Such methods are time-consuming, costly, and require considerable quantities of reagents. Moreover, as the number of operations employed in such identification processes increases, a greater number of target entities are lost or killed. Accurate microbial analyses employing such methodologies are difficult to achieve because of the small numbers of target entities involved as well as the difficulty of washing away unbound labeling agents. Other methodologies such as flow cytometry (fluorescent activated cell sorting) or field flow fractionation can be used for such analysis and in some instances require fewer manipulations. These other methods, however, require expensive equipment, highly trained personnel and typically can only analyze or separate one sample at a time.
Manipulation of target entities required by other biological techniques may also involve such processes as insertion of genetic material, organelles, subcellular components, viruses, or other foreign materials or bodies into the target entities. Inserted materials can be labeled prior to insertion so that effects and movements of these materials can be studied during incubation of the medium. In techniques such as transfection, or in vitro fertilization mechanical probes or arms are often used to hold the target entities. Such mechanical holding methods tend to obscure or damag
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Liberti Paul A.
Wang Yuzhou
Immunivest Corporation
Savage Matthew O.
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