Abstract: An apparatus and methods for using biological material to discriminate an agent. In one embodiment of the present invention, the method includes the steps of providing at least one cell, exposing at least one cell to an agent, measuring the response of the cell to the agent in terms of a physical quantity related to at least one of the cellular physiological activities of the cell, and identifying the agent from the measured response. The method further includes the step of quantifying the agent from the measured response.

Abstract: A bioreactor for cultivating living cells in a liquid medium. In one embodiment of the present invention, the bioreactor includes a first substrate having a first surface, an opposite second surface and edges. The bioreactor further includes a second substrate having a first surface and an opposite second surface, defining a cavity with a bottom surface, where the bottom surface is located therebetween the first surface and the second surface. The first surface of the first substrate is received by the second surface of the second substrate to cover the cavity so as to form a channel for receiving cells and a liquid medium. In forming the bioreactor, the channel is sized to allow the growth of a layer of cells on a biocompatible coating layer and a flow of liquid in the channel. The flow of liquid is controlled so as to provide a known shear force to the layer of cells. The flow of liquid can be further controlled so as to provide an environment that simulates a vascular space in the channel.

Abstract: A bioreactor for cultivating living cells in a liquid medium. In one embodiment of the present invention, the bioreactor has a first substrate having a first surface and an opposite second surface, defining a chamber therebetween for receiving the cells and the liquid medium. The bioreactor further has a barrier dividing the chamber into a first subchamber and a second subchamber, wherein the barrier has a porosity to allow the first subchamber and the second subchamber in fluid communication and allow at least one predetermined type of cells to permeate between the first subchamber and the second subchamber.

Abstract: A bioreactor for cultivating living cells in a liquid medium. In one embodiment of the present invention, the bioreactor includes a first substrate having a first surface, an opposite second surface and edges. The bioreactor further includes a second substrate having a first surface and an opposite second surface, defining a cavity with a bottom surface, where the bottom surface is located therebetween the first surface and the second surface. The first surface of the first substrate is received by the second surface of the second substrate to cover the cavity so as to form a channel for receiving cells and a liquid medium. In forming the bioreactor, the channel is sized to allow the growth of a layer of cells on a biocompatible coating layer and a flow of liquid in the channel. The flow of liquid is controlled so as to provide a known shear force to the layer of cells. The flow of liquid can be further controlled so as to provide an environment that simulates a vascular space in the channel.

Abstract: A bioreactor for cultivating living cells in a liquid medium. In one embodiment of the present invention, the bioreactor has a first substrate having a first surface and an opposite second surface, defining a chamber therebetween for receiving the cells and the liquid medium. The bioreactor further has a barrier dividing the chamber into a first subchamber and a second subchamber, wherein the barrier has a porosity to allow the first subchamber and the second subchamber in fluid communication and allow at least one predetermined type of cells to permeate between the first subchamber and the second subchamber.

Abstract: An apparatus and methods for monitoring the status of a cell that consumes oxygen. In one embodiment of the present invention, the method includes the steps of confining the cell in a sensing volume, measuring dynamically intracellular or extracellular signaling of the cell, and determining the status of the cell from the measured intracellular or extracellular signaling of the cell.

Abstract: An apparatus and methods for monitoring the status of a cell that consumes oxygen. In one embodiment of the present invention, the method includes the steps of confining the cell in a sensing volume, measuring dynamically intracellular or extracellular signaling of the cell, and determining the status of the cell from the measured intracellular or extracellular signaling of the cell.

Abstract: A bioreactor for cultivating living cells in a liquid medium. In one embodiment of the present invention, the bioreactor includes a first substrate having a first surface, an opposite second surface and edges. The bioreactor further includes a second substrate having a first surface and an opposite second surface, defining a cavity with a bottom surface, where the bottom surface is located therebetween the first surface and the second surface. The first surface of the first substrate is received by the second surface of the second substrate to cover the cavity so as to form a channel for receiving cells and a liquid medium. In forming the bioreactor, the channel is sized to allow the growth of a layer of cells on a biocompatible coating layer and a flow of liquid in the channel. The flow of liquid is controlled so as to provide a known shear force to the layer of cells. The flow of liquid can be further controlled so as to provide an environment that simulates a vascular space in the channel.

Abstract: A system and methods for calculating at least one unknown metabolic flux of a plurality of cells. In one embodiment, the method includes the steps of constructing a metabolic network having a plurality of reaction components, the reaction components representing at least glycolysis, reduction of pyruvate to lactate, TCA cycle, and oxidative phosphorylation, measuring at least two metabolic rates of a plurality of cells corresponding to at least two of the metabolic network reactions, and calculating metabolic fluxes of a plurality of cells for the rest of the metabolic network reactions from at least two measured metabolic rates of a plurality of cells corresponding to at least two of the reactions.

Abstract: An apparatus and methods for using biological material to discriminate an agent. In one embodiment of the present invention, the method includes the steps of providing at least one cell, exposing at least one cell to an agent, measuring the response of the cell to the agent in terms of a physical quantity related to at least one of the cellular physiological activities of the cell, and identifying the agent from the measured response. The method further includes the step of quantifying the agent from the measured response.

Abstract: The present invention provides biocompatible, low molecular weight nanoparticulate formulations that are designed to retain and deliver therapeutics over an extended time course. The therapeutic may be conjugated or adsorbed to the periphery of the corona or conjugated to a core polymer. The nanoparticles comprise targeting ligands also conjugated or adsorbed to the periphery of the corona and/or a contrast agent in the core of the nanoparticle. As such, methods of selective targeting and/or methods of noninvasive imaging using bioluminescence and/or magnetic resonance imaging. Also provided are methods of delivering to and, optionally, imaging of a cell or tissue. Further provided are methods of producing the nanoparticles in batch or continuous mode via simple mixing or laminar flow.

Abstract: An apparatus and methods for measuring response of at least one cell to a medium, the response of at least one cell to a medium being characterized by a reaction time. In one embodiment of the present invention, the device includes a membrane and a side substrate defining a sample well in communication with the ambient air and for receiving the at least one cell such that the membrane is underneath the at least one cell. A sensor is positioned underneath the second surface of the membrane, and an inlet is in fluid communication with the sample well. A medium is introduced into the chamber through the inlet to form a droplet that surrounds the cell, and the sensor measures the response of the cell to the medium at a time period shorter than the reaction time.

Abstract: A system and methods for discriminating an agent. In one embodiment of the present invention, the method includes the steps of (a) constructing a decision tree having a plurality of branches, each branch corresponding to at least one defined action, wherein each branch includes a plurality of successive branches, each successive branch corresponding to at least one defined action, (b) providing a conditioned environment sensitive to the agent, (c) obtaining data from response of the agent to the conditioned environment, (d) extracting features from the obtained data, (e) selecting a branch from the decision tree corresponding to the features, (f) performing on the features at least one defined action corresponding to the branch, (g) producing a classification of the agent, and (g) iteratively repeating steps of (d)-(g) until the agent is discriminated.

Abstract: The present invention provides a series of biocompatible, nanoparticulate formulations that are designed to retain and deliver peptides such as anti-angiogenic factors over an extended time course. The nanoparticles can be targeted to a cell or tissue by targeting ligands crosslinked or conjugated to the corona of the nanoparticles. In addition to selective targeting, the nanoparticles also may perform noninvasive imaging using bioluminescence and/or magnetic resonance imaging via a contrast agent in the core of the nanoparticle. Also provided are methods of delivering to and, optionally, imaging of a cell or tissue. Furthermore, methods of producing the nanoparticles in batch or continous mode via simple mixing or micromixing.

Abstract: The present invention provides compositions comprising a water-based core solution and a water-based corona solution surrounding the core solution. The compositions comprise polyanionic polymers and salts and polycationic polymers and cations and is useful for adenoviral delivery of a gene or delivery of another drug. The compositions may be nanoparticulate, microcapsular or form a polymeric sheet. Also provided are methods of use for the compositions.

Abstract: The present invention provides a method of making particles useful in drug delivery, comprising the steps of: contacting polyanionic polymers with cations in a stirred reactor so that polyanions and the cations react to form particles.

Abstract: The present invention provides a method of making particles, e.g., nanoparticles that are stable in a physiological environment for at least a day. The nanoparticles comprise polyanionic polymers and polycations in a complex useful for drug delivery. The method comprises the step of capturing droplets comprising the polyanionic polymers in a solution comprising the polycations; or, alternatively, capturing droplets comprising the polycations in a solution comprising the polyanionic polymers. Also provided are methods of use for the particles.

Abstract: Microparticles and nanoparticles prepared from oppositely charged polymers are provided in which a drug is incorporated into the core and is conjugated to one polymer by a Schiff-base crosslink. The particles are suitable for use in injectable formulations in which the rate of release of the drug through the particle shell is slowed as compared to noncrosslinked drugs. Enzymatically degradable polymers can be incorporated in otherwise hydrolytically stable particles to provide drug release at particular sites within the body where the enzyme of interest is present.

Abstract: Microparticles and nanoparticles prepared from oppositely charged polymers are provided in which a drug is incorporated into the core and is conjugated to one polymer by a Schiff-base crosslink. The particles are suitable for use in injectable formulations in which the rate of release of the drug through the particle shell is slowed as compared to noncrosslinked drugs. Enzymatically degradable polymers can be incorporated in otherwise hydrolytically stable particles to provide drug release at particular sites within the body where the enzyme of interest is present.

Abstract: Microparticles and nanoparticles prepared from oppositely charged polymers are provided in which a drug is incorporated into the core and is conjugated to one polymer by a Schiff-base crosslink. The particles are suitable for use in injectable formulations in which the rate of release of the drug through the particle shell is slowed as compared to noncrosslinked drugs. Enzymatically degradable polymers can be incorporated in otherwise hydrolytically stable particles to provide drug release at particular sites within the body where the enzyme of interest is present.