Abstract: An apparatus for collecting or culturing cells or cell colonies includes: a common substrate formed from a flexible resilient polymeric material and having a plurality of wells formed therein; and a plurality of rigid cell carriers releasably connected to said common substrate, with said carriers arranged in the form of an array, and with each of the carriers resiliently received in one of the wells. A method of collecting or culturing cells or cell colonies with such an apparatus is carried out by depositing a liquid media carrying cells on the apparatus so that said cells settle on or adhere to said the carriers; and then (c) releasing at least one selected carrier having said cells thereon by gradual application of release energy to each carrier from the cavity in which it is received (e.g., by pushing with a probe).

Abstract: A method of making such is carried out by (a) providing a reverse template for said article, said template comprising an elastomeric polymer such as PDMS; (b) providing a solution comprising a polymer dissolved in a first solvent; wherein said polymer is selected from the group consisting of polystyrene, poly(methyl methacrylate), epoxy, and aliphatic polyesters; and wherein said solvent comprises a lactone; (c) depositing said solution on said template; (e) removing said solvent from said template to form said article from said polymer on said template; and then (f) separating said template from said article.

Abstract: Systems and methods are provided for patterning biological and non-biological material at specific sites on a plate, as well as growing three dimensional structures. Preferred embodiments comprise a plate with regions that will trap gas, usually in the form of bubbles, when the plate is submerged in liquid. Other embodiment of the present invention include a method for placing materials on the plate at pre-determined locations through the use of trapped gas to prevent materials from collecting at unwanted regions. The plate has great utility for plating cells and tissues at specific sites, such as on an array. The disclosed method can also be used to coat the surface of a plate with coatings at specific locations for patterned coating applications and to build up materials to produce three dimensional structures, including micro-mechanical structures—where the structures may be formed from living or non-living material, tissue or non-tissue, organic or inorganic, and the like.

Abstract: An apparatus for collecting or culturing cells or cell colonies has a common substrate and a plurality of cell carriers releasably connected to the common substrate. The carriers are arranged in the form of an array. The invention employs microcups as the cell carriers. The substrate is preferably free of barriers between the microcups, and in some embodiments the microcups have porous walls. Methods of using the apparatus are also described.

Abstract: Selecting and propagating a cell colony of interest from among a plurality of cell colonies carried on a common substrate in culture is carried out by: (a) selecting a cell colony of interest from among the plurality of cell colonies; (b) isolating a cell subset from the cell colony of interest; (c) analyzing (for example, by a destructive analysis) the cell subset isolated from the cell colony of interest to confirm the presence or absence of a desired feature therein; and then (d) propagating the cell colony of interest when the desired feature is present in the cell subset. A micropallet apparatus may include: (a) a substrate; (b) a plurality of discrete arrays formed on the substrate, each of the arrays comprising a plurality of releasable pallets, and (c) a plurality of gap forming regions, wherein the gap forming regions surround the pallets and separate the pallets from one another.

Abstract: Systems and methods are providing for performing high-throughput, programmable, multiplexed assays of biological, chemical or biochemical systems. Preferably, a micro-pallet includes a small flat surface designed for single adherent cells to plate, a cell plating region designed to protect the cells, and shaping designed to enable or improve flow-through operation. The micro-pallet is preferably patterned in a readily identifiable manner and sized to accommodate a single cell to which it is comparable in size. Each cell thus has its own mobile surface. The cell can be transported from place to place and be directed into a system similar to a flow cytometer. Since, since the surface itself may be tagged (e.g., a bar code), multiple cells of different origin and history may be placed into the same experiment allowing multiplexed experiments to be performed.

Abstract: A micro-patterned plate composed of an array of releasable elements surrounded by a gel or solid wall and methods of manufacture of the micropatterned plate. The surface properties of walls can be tailored if needed to be repellent or attracting to proteins. The walls can also inhibit cell attachment. The walls enable cells or other materials to be localized to the tops of the releasable elements. The individual element in the array of releasable elements can be released from the array by a mechanical force.

Abstract: A plate manufactured to enable samples of cells, micro-organisms, proteins, DNA, biomolecules and other biological media to be positioned at specific locations or sites on the plate for the purpose of performing addressable analyses on the samples. Preferably, some or all of the sites are built from a removable material or as pallets so that a subset of the samples of interest can be readily isolated from the plate for further processing or analysis. The plate can contain structures or chemical treatments that enhance or promote the attachment and/or function of the samples, and that promote or assist in their analyses. Use of the plate advantageously enables the selection and sorting of cells based on dynamic phenomena and the rapid establishment of stable tranfectants.

Abstract: A plate manufactured to enable samples of cells, micro-organisms, proteins, DNA, biomolecules and other biological media to be positioned at specific locations or sites on the plate for the purpose of performing addressable analyses on the samples. Preferably, some or all of the sites are built from a removable material or as pallets so that a subset of the samples of interest can be readily isolated from the plate for further processing or analysis. The plate can contain structures or chemical treatments that enhance or promote the attachment and/or function of the samples, and that promote or assist in their analyses.

Abstract: A plate manufactured to enable samples of cells, micro-organisms, proteins, DNA, biomolecules and other biological media to be positioned at specific locations or sites on the plate for the purpose of performing addressable analyses on the samples. Preferably, some or all of the sites are built from a removable material or as pallets so that a subset of the samples of interest can be readily isolated from the plate for further processing or analysis. The plate can contain structures or chemical treatments that enhance or promote the attachment and/or function of the samples, and that promote or assist in their analyses.

Abstract: A plate manufactured to enable samples of cells, micro-organisms, proteins, DNA, biomolecules and other biological media to be positioned at specific locations or sites on the plate for the purpose of performing addressable analyses on the samples. Preferably, some or all of the sites are built from a removable material or as pallets so that a subset of the samples of interest can be readily isolated from the plate for further processing or analysis. The plate can contain structures or chemical treatments that enhance or promote the attachment and/or function of the samples, and that promote or assist in their analyses. Use of the plate advantageously enables the selection and sorting of cells based on dynamic phenomena and the rapid establishment of stable tranfectants.

Abstract: The activity of multiple proteins in a single living cell, portion of a cell or in a group of cells is simultaneously measured by introducing reporter molecules into the cell(s) or a portion thereof, chemically modifying the reporter(s) by the enzyme of interest, terminating the modification reactions, removing the reporter(s) and modified reporter(s), and determining the amount of enzyme activity present by measuring or comparing the amount of reporter(s) and modified reporter(s) present. By performing a series of experiments at different time points, conditions, and varieties of cell types, a database is developed for molecular cellular mechanisms in health and disease states. By exposing cells to a variety of compounds data for drug development and screening is provided.

Abstract: Systems and methods are provided for patterning biological and non-biological material at specific sites on a plate, as well as growing three dimensional structures. Preferred embodiments comprise a plate with regions that will trap gas, usually in the form of bubbles, when the plate is submerged in liquid. Other embodiment of the present invention include a method for placing materials on the plate at pre-determined locations through the use of trapped gas to prevent materials from collecting at unwanted regions. The plate has great utility for plating cells and tissues at specific sites, such as on an array. The disclosed method can also be used to coat the surface of a plate with coatings at specific locations for patterned coating applications and to build up materials to produce three dimensional structures, including micro-mechanical structures—where the structures may be formed from living or non-living material, tissue or non-tissue, organic or inorganic, and the like.

Abstract: The activity of intracellular chemical reactions of molecules is measured by the use of fluorescently labeled substrate molecules that undergo a change in electrophoretic mobility upon chemical reaction such as that catalyzed by an enzyme. Specificity is achieved by using labeled substrate molecules that can be acted upon only by specific enzymes. Thus the activity of a specific enzyme or class of enzymes can be determined. Measurements are made with the intracellular presence of such substrate molecules, at some time of interest, typically after exposure of the cell to a stimulus that activates a particular enzymatic pathway. To ensure accuracy, measurements must be made in a timely manner so as to minimize chemical reactions occurring subsequent to the time of interest. Fast controllable laser lysis is used to obtain the contents of a single cell into which reporter substrate molecules have been introduced.

Abstract: A plate manufactured to enable samples of cells, micro-organisms, proteins, DNA, biomolecules and other biological media to be positioned at specific locations or sites on the plate for the purpose of performing addressable analyses on the samples. Preferably, some or all of the sites are built from a removable material or as pallets so that a subset of the samples of interest can be readily isolated from the plate for further processing or analysis. The plate can contain structures or chemical treatments that enhance or promote the attachment and/or function of the samples, and that promote or assist in their analyses.

Abstract: A membrane traversing peptide conjugate comprises (i) a label, (ii) a target peptide, attached to the label, and (iii) a transduction domain, attached to the target peptide. The target peptide is a reactant for a chemical reaction occurring in a cell.

Abstract: Systems and methods are providing for performing high-throughput, programmable, multiplexed assays of biological, chemical or biochemical systems. Preferably, a micro-pallet includes a small flat surface designed for single adherent cells to plate, a cell plating region designed to protect the cells, and shaping designed to enable or improve flow-through operation. The micro-pallet is preferably patterned in a readily identifiable manner and sized to accommodate a single cell to which it is comparable in size. Each cell thus has its own mobile surface. The cell can be transported from place to place and be directed into a system similar to a flow cytometer. Since, since the surface itself may be tagged (e.g., a bar code), multiple cells of different origin and history may be placed into the same experiment allowing multiplexed experiments to be performed.

Abstract: Polymer-based biomaterials are popular due to ease of fabrication and low costs. However, many polymer substrates have undesirable surface properties. The invention provides a procedure to covalently apply a graft polymer to the surface of a polymer substrate by ultraviolet graft polymerization. The graft polymer is formed from monomers such as PEG, AA, monomethoxy acrylate PEG, HEMA, or DMA. Also, mixed monomers may be used to create the graft and the surface properties of the graft may be tailored for different properties, including hydrophobicity, friction coefficient, electroosmotic mobilities and electrophoretic separations. The invention has particular utility in tailoring surface chemistries in ocular lenses and polymer microdevices. I. II.

Abstract: A method of introducing a fluorescent label into a cell, comprising: exposing a reporter to the cell, wherein the reporter comprises: a peptide substrate for an enzyme, a docking domain for the enzyme, attached to the peptide substrate, a membrane traversing moiety, and the label.

Abstract: The activity of oncogenic intracellular chemical reactions of molecules is measured by the use of fluorescently labeled substrate molecules that undergo a change in electrophoretic mobility upon a chemical reaction such as that catalyzed by an enzyme or kinase. Specificity is achieved by using labeled substrate molecules that can be acted upon only by specific oncogenic enzymes. Thus the activity of an oncogenic enzyme or class of oncogenic enzymes can be determined. Measurements are made with the intracellular presence of such substrate molecules, at some time of interest. To ensure accuracy, measurements must be made in a timely manner so as to minimize chemical reactions occurring subsequent to the time of interest. Fast controllable laser lysis is used to obtain the contents of said cell or cells into which reporter substrate molecules have been introduced.