General Electric Company

Applied Biophysics, Inc.

Rensselaer Polytechnic Institute

General Electric Corporation Gmbh

National Foundation for Cancer Research

Ivar Giaever

Charles R Keese

Harvey E Cline

Thomas R Anthony

William J Ward, Iii

Charles P Bean

Richard C Keese

Dale Harrigan

Method and apparatus for processing a cell culture are provided. The method includes establishing a cell culture within a holding device having one or more wells, each well holding a cell culture, and including a well substrate with at least one electrode in contact with the cell culture; periodically applying at least one electrical pulse to the at least one electrode to prevent cells from attaching to and achieving confluence over the at least one electrode while allowing cells to attach to and achieve confluence over other portions of the well substrate; and discontinuing the periodically applying of the at least one electrical pulse to the at least one electrode after cells have achieved confluence over the other portions of the well substrate, and thereafter, monitoring the cell culture to monitor migration of cells over the electrode(s) from the other portions of the well substrate.

Apparatus for facilitating evaluating migration of cells in vitro

Method and apparatus for facilitating evaluating migration of cells in vitro

The present invention provides methods for the assessment of the metastatic potential of cells by measuring the effect of the cells on the impedance of an electrode. Accordingly, the present invention similarly provides methods for establishing indicators of metastatic potential based on a cell's effect on impedance. Such methods may be employed in vitro or in vivo. In some embodiments, the electrode is coated with endothelial or epithelial cells.

Real-time impedance assay to follow the invasive activities of metastatic cells in culture

A method and system for electrically wounding and/or monitoring cell activity in vitro. The invention comprises methods and systems for wounding and/or monitoring cells that place a cell culture on a well that has an exposed electrode. The cell culture can then be wounded and/or monitored using the electrode.

Electrical wounding assay for cells in vitro

An apparatus and method for monitoring cell-substrate impedance comprises upper and lower substrates each containing strips of metal foil which cross to form well areas. Holes in the upper substrate expose an insulation layer between the upper and lower substrates. Smaller holes in the insulation layer expose the conductive material of the lower substrate. Cylindrical well walls are positioned around each of the holes in the upper substrate and define a cell medium containing well which is exposed to an annular area of conductive foil on the upper substrate, and a small area of conducive foil on the lower substrate. The areas of foil form large and small electrodes which are positioned in an array of wells which can be used to monitor the impedance of various cell cultures under various conditions. A switching device applies currents to the well electrodes and a monitoring device measures the impedance between the electrodes in each well. In this way, cell spreading and motility can be measured.

Cell substrate electrical impedance sensor with multiple electrode array

Test method and apparatus for determining the presence of, the concentration of, or the absence of, immunologically-active substances in liquid media by measuring any change of electrical impedance of an electrode due to the presence of, or the absence of, the reaction of a product of enzyme linked immunologically-active substance and a proper enzyme substrate.

Electrical detection of the immune reaction

An antigen-covered substrate is irradiated with ultraviolet light through a mask after which the exposed areas are rendered no longer antigenic. The unexposed areas retain their antigenic behavior and are available for the occurrence and detection of an immunological reaction.

Immunological detection device and method for its preparation

An emulsion (in which an aqueous medium contains small liquid droplets coated with a protein that will interact specifically with a select protein) is mixed with a liquid sample, time is allowed for interaction to occur and the mixture is then exposed to a tagged antibody specific to the select protein. After an appropriate hold time the emulsion is broken and the protein that previously covered the disperse droplets becomes concentrated at the surface. The surface is checked for the presence of the tagged antibodies to establish the presence of absence of the select protein.

Diagnostic method of determining the presence or absence of select

Small liquid droplets, coated with protein, the protein coating containing molecules of protein that will interact specifically with a select protein, are contacted with a liquid sample to determine the presence or absence of the select protein therein depending upon whether the droplets agglutinate.

Agglutinating immunoassay using protein-coated liquid droplets

Droplets having an electrical charge on the surface thereof are prepared from a first liquid and dispersed in a second liquid, a sterile aqueous tissue culture medium containing serum proteins. The first liquid is non-toxic to living cells and is relatively immiscible with water. The electrical charge on the surfaces of the droplets has a charge density in the range of from about 10 to about 100 charges per square nanometer. Serum protein films adhere to the charged droplets strongly enough to prevent rupture by human fibroblast cells grown thereon.

Cell growth on liquid-liquid interfaces

Temperature gradient zone melting is utilized to make a solid state neuron which mimics the conducting nerve pulses by a biological nerve cell and its nerve fiber.

Method for making a solid state neuron

A diagnostic device is described employing a solid, rigid diagnostic substrate (having as a part thereof an exposed layer of first immunologically reactive biological particles) in combination with means spaced therefrom for containing a solution of second immunologically reactive biological particles specific to the first particles. Preferably these elements are arranged with the layer of first immunologically reactive biological particles on a glass slide having a metallized surface and facing the containing means with spacing therebetween. This spacing defines a wedge-shaped volume for containing test fluid. With a test fluid in place, after allowing diffusion to occur for a predetermined period of time, the extent of formation of a layer of the second particles (i.e., a second layer) on the first layer is determined. If such a second layer develops, this determination can be related to the concentration of first particles in the test fluid. Presence of the second layer is visible with good contrast to the unaided eye.

Method and apparatus for measuring antibody levels

In carrying out a purification and/or concentration step of antigens or antibodies, a substrate is immersed in a first aqueous medium containing a specifically reacting antigen to coat said substrate with a monomolecular layer of said specifically reacting antigen. The resulting coated substrate is then immersed in a second aqueous medium containing immunologically reactive antibody specific to the antigen in the first aqueous medium to complex said immunologically reactive antibody with said specifically reacting antigen. The resulting substrate is then immersed in a reagent capable of cleaving the immunological bond between said immunologically reactive antibody and said specifically reactive antigen and forming a solution of said immunologically reactive antibody in the immunological bond-cleaving solution and leaving said specifically reacting antigen coated on said substrate. The method can be reversed for preparing a purified concentration of an immunologically reactive antigen whereby a specifically reacting antibody is substituted for the antigen and the corresponding immunologically reactive antigen is substituted for the antibody.

Method for concentration and purification of antigens and antibodies

A semiconductor neuron comprises a tunnel diode having a region of recrystallized semiconductor material formed in situ in a columnar structure body of semiconductor material by thermal gradient zone melting. Individual electrical leads are affixed to the body and to both opposing faces of the recrystallized region. A voltage pulse applied between one pair of electrical leads on one surface across the P-N junction will propagate at a predetermined rate through the semiconductor body. After a predetermined delay, the applied pulse will appear across the P-N junction thereby mimicking the conducting nerve pulses by a biological nerve cell and its nerve fiber.

Solid state neuron

A mixture of two different kinds of particles having distinctive, different properties is employed for determining the presence of a select protein in, or the absence of a select protein from, a solution. The first kind of particle provides a property facilitating separation, while the second kind of particle provides a property facilitating detection. The particles are coated with the same protein, a protein able to interact specifically with the select protein.

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Schenectady, NY, United States of America

Ivar Giaever