Abstract: Methods, including culture media conditions, which provide for in vitro human stem cell division and/or the optimization of human hematopoietic progenitor cell cultures and/or increasing the metabolism or GM-CSF secretion or IL-6 secretion of human stromal cells and/or a method for assaying the effect of a substance or condition on a human hematopoietic cell population, and/or depleting the malignant cell or T-cell and B-cell content of a human hematopoietic cell population are disclosed. The methods rely on culturing human stem cells and/or human hematopoietic progenitor cells and/or human stromal cells in a liquid culture medium which is replaced, preferably perfused, either continuously or periodically, at a rate of 1 ml of medium per ml of culture per about 24 to about 48 hour period, and removing metabolic products and replenishing depleted nutrients while maintaining the culture under physiologically acceptable conditions. Optionally, growth factors are added to the culture medium.

Abstract: The invention provides a method for selecting a population of non-cellular physical entities. The method involves applying energy to one or more non-cellular physical entities having selected parameter signatures, each physical entity located at specific coordinates in a domain and contained within a population of physical entities, thereby altering a property of the one or more physical entities, wherein the alteration renders the one or more physical entities separable from other members of the population of physical entities. The invention also provides a methods for preparing a population of uniquely tagged non-cellular physical entities, and methods for preparing a population of uniquely tagged probes. The invention further provides a method for simultaneously detecting a plurality of analytes using the uniquely tagged probes.

Abstract: Methods, including culture media conditions, which provide for in vitro human stem cell division and/or the optimization of human hematopoietic progenitor cell cultures and/or increasing the metabolism or GM-CSF secretion or IL-6 secretion of human stromal cells and/or a method for assaying the effect of a substance or condition on a human hematopoietic cell population, and/or depleting the malignant cell or T-cell and B-cell content of a human hematopoietic cell population are disclosed. The methods rely on culturing human stem cells and/or human hematopoietic progenitor cells and/or human stromal cells in a liquid culture medium which is replaced, preferably perfused, either continuously or periodically, at a rate of 1 ml of medium per ml of culture per about 24 to about 48 hour period, and removing metabolic products and replenishing depleted nutrients while maintaining the culture under physiologically acceptable conditions. Optionally, growth factors are added to the culture medium.

Abstract: The invention provides an in silico model for determining a S. cerevisiae physiological function. The model includes a data structure relating a plurality of S. cerevisiae reactants to a plurality of S. cerevisiae reactions, a constraint set for the plurality of S. cerevisiae reactions, and commands for determining a distribution of flux through the reactions that is predictive of a S. cerevisiae physiological function. A model of the invention can further include a gene database containing information characterizing the associated gene or genes. The invention further provides methods for making an in silico S. cerevisiae model and methods for determining a S. cerevisiae physiological function using a model of the invention.

Abstract: The invention provides an in silico model for determining a Bacillus subtilis physiological function. The model includes a data structure relating a plurality of B. subtilis reactants to a plurality of B. subtilis reactions, a constraint set for the plurality of B. subtilis reactions, and commands for determining a distribution of flux through the reactions that is predictive of a B. subtilis physiological function. A model of the invention can further include a gene database containing information characterizing the associated gene or genes. A regulated B. subtilis reaction can be represented in a model of the invention by including a variable constraint for the regulated reaction. The invention further provides methods for making an in silico B. subtilis model and methods for determining a B. subtilis physiological function using a model of the invention.

Abstract: This invention provides a method and apparatus for selectively identifying, and targeting with an energy beam, specific cells within a cell population, for the purpose of inducing a response in the targeted cells. Using the present invention, every detectable cell in a population can be identified and affected, without substantially affecting non-targeted cells within the mixture.

Abstract: A method and apparatus is disclosed for selectively identifying, and targeting with an energy beam, specific cells within a mixed cell population, for the purpose of inducing a response in the targeted cells. Two or more fluorescent labels can be attached to the targeted cells, and distinguished from one another by a color camera. By use of this system, one can monitor and affect cells having a desired phenotype. For example, targeted cells can not only be inactivated by an energy beam, but can also be monitored through fluorescent labeling for changes in cell morphology, ion transport or other cellular functions.

Abstract: This invention provides a method and apparatus for selectively identifying, and targeting with an energy beam, specific cells within a mixed cell population, for the purpose of inducing a response in the targeted cells. Using the present invention, every detectable cell in a population can be identified and affected, without substantially affecting non-targeted cells within the mixture.

Abstract: The invention provides a method of identifying therapeutic compounds in a genetically defined setting. The method consists of contacting a cell indicative of a pathological condition from a diseased individual and a cell from a genetically related normal individual with a plurality of candidate therapeutic compounds under suitable assay conditions, and identifying a compound that preferentially alters a predetermined property of the cell from the diseased individual.

Abstract: A method is presented to remove contaminating tumor cells from a cell population. The method includes labeling individual tumor cells in the population and then killing them with a high energy laser beam. The laser is focused so that it specifically kills the identified tumor cell, but not the remaining cells in the population.

Abstract: Methods, including culture media conditions, which provide for in vitro human stem cell division and/or the optimization of human hematopoietic progenitor cell cultures and/or increasing the metabolism or GM-CSF secretion or IL-6 secretion of human stromal cells and/or a method for assaying the effect of a substance or condition on a human hematopoietic cell population, and/or depleting the malignant cell or T-cell and B-cell content of a human hematopoietic cell population are disclosed. The methods rely on culturing human stem cells and/or human hematopoietic progenitor cells and/or human stromal cells in a liquid culture medium which is replaced, preferably perfused, either continuously or periodically, at a rate of 1 ml of medium per ml of culture per about 24 to about 48 hour period, and removing metabolic products and replenishing depleted nutrients while maintaining the culture under physiologically acceptable conditions. Optionally, growth factors are added to the culture medium.

Abstract: The invention provides a model of a reaction network integrated with regulatory controls related to the reactions. A method is provided for determining a systemic property of a reaction network using a model of the invention. Also provided is a method for modeling changes that occur in a reaction network at various time points due to regulatory events.

Abstract: This invention provides a method and apparatus for selectively identifying, and targeting with an energy beam, specific cells within a mixed cell population, for the purpose of inducing a response in the targeted cells. Using the present invention, every detectable cell in a population can be identified and affected, without substantially affecting non-targeted cells within the mixture.

Abstract: The invention provides a method of identifying therapeutic compounds in a genetically defined setting. The method consists of contacting a cell indicative of a pathological condition from a diseased individual and a cell from a genetically related normal individual with a plurality of candidate therapeutic compounds under suitable assay conditions, and identifying a compound that preferentially alters a predetermined property of the cell from the diseased individual.

Abstract: This invention provides a method and apparatus for selectively identifying, and targeting with an energy beam, specific cells within a cell population, for the purpose of inducing a response in the targeted cells. Using the present invention, every detectable cell in a population can be identified and affected, without substantially affecting non-targeted cells within the mixture.

Abstract: The invention provides an apparatus for electromagnetically affecting a particle of interest in a specimen. The apparatus includes (a) a stage capable of supporting the specimen; (b) a detector including at least one camera, wherein the detector is capable of resolving a particle of interest within the specimen; (c) a means for locating the particle of interest in three dimensions; (d) a means for focusing electromagnetic radiation to a focal volume within the specimen; and (e) a means for adjusting the relative positions of the stage and electromagnetic radiation focusing means, thereby positioning the particle of interest within the focal volume.

Abstract: The present invention relates to methods for achieving an optimal function of a biochemical reaction network. The methods can be performed in silico using a reconstruction of a biochemical reaction network of a cell and iterative optimization procedures. The methods can further include laboratory culturing steps to confirm and possibly expand the determinations made using the in silico methods, and to produce a cultured cell, or population of cells, with optimal functions. The current invention includes computer systems and computer products including computer-readable program code for performing the in silico steps of the invention.

Abstract: Optoinjection method for transiently permeabilizing a target cell by (a) illuminating a population of cells contained in a frame; (b) detecting at least one property of light directed from the frame; (c) locating a target cell by the property of light; and (d) irradiating the target cell with a pulse of radiation.

Abstract: Methods, compositions and devices are provided for the growth of hematopoietic cells in culture. Bioreactors are provided in which diverse cell types are simultaneously cultured in the presence of appropriate levels of nutrients and growth factors substantially continuously maintained in the bioreactor while removing undesirable metabolic products. This simultaneous culture of multiple cell types is required for the successful reconstruction of hematopoietic tissue ex vivo. At least one growth factor is provided through excretion by transfected stromal cells, particularly heterologous cells. Means are provided for maintaining the stromal cells and hematopoietic cells separately, to allow for early removal of the hematopoietic cells.

Abstract: Methods, including culture media conditions, which provide for ex vivo human stem cell division and/or the optimization of human hematopoietic progenitor cell cultures and/or increasing the metabolism or GM-CSF secretion or IL-6 secretion of human stromal cells are disclosed. The methods rely on culturing human stem cells and/or human hematopoietic progenitor cells and/or human stromal cells in a liquid culture medium which is replaced, preferably perfused, either continuously or periodically, at a rate of 1 ml of medium per ml of culture per about 24 to about 48 hour period, and removing metabolic products and replenishing depleted nutrients while maintaining the culture under physiologically acceptable conditions. Optionally growth factors are added to the culture medium.