Abstract: Methods for balancing multiplexed PCR reactions are provided which exploit differences in primer and amplicon Tms. The methods may be controlled by a computer process. Also provided are articles of manufacture useful in such methods and compositions containing primers and probes useful in such methods.

Abstract: The invention relates to methods and agents for thermal conditioning of a biological cell, methods and uses of said agents for releasing and insulating ingredients outside the biological cell, and for quantitatively and qualitatively detecting the released ingredient and to a method for sampling biological cells which consists in carrying out in one step the sampling said biological cells in a culture medium and in releasing cellular ingredients during said sampling. Sampling devices are also disclosed.

Abstract: Parallel, integrated bioreactor. The bioreactor includes a plurality of growth chambers, each growth chamber associated with a peristaltic oxygenating mixer and separated therefrom by a porous membrane. Each oxygenating mixture has a gas inlet and a gas outlet with the gas inlet in fluid communication with a gas reservoir. A gas mixer switch is provided for controlling oxygen concentration in the reservoir. The apparatus and methods disclosed in the application allow precise control over dissolved oxygen concentration with a quick response time.

Abstract: The present invention relates to methods and processes for controlling fermentation. Two proportional feedback control loops are implemented in a cascade. One control loop is used to maintain the pH by adjusting the dissolved oxygen-stat setpoint. The other control loop is used to maintain the dissolved oxygen by regulating the nutrient feed rate using the newly adjusted dissolved oxygen-set point.

Abstract: An extra-capillary fluid cycling unit for maintaining and cycling fluid volumes in a cell culture chamber includes a housing and a first flexible reservoir extra-capillary fluid reservoir disposed in the housing. The extra-capillary fluid reservoir is in fluid communication with a cell culture chamber. A second flexible reservoir is also located in the housing, the second flexible reservoir being in fluid communication with a pressure source. A sensor plate is movably disposed in the housing between the extra-capillary reservoir and the second reservoir, wherein the second reservoir is pressurized to move the sensor plate in relation to the extra-capillary reservoir to cause fluid cycling and maintain fluid volumes in the cell growth chamber.

Abstract: The embodied composition is a dose of bio-identical hormones in a solvent with a vasodilator, a hormone modulator, and a carrier for balancing and maintaining Cortisol level in a human. The dose comprises progesterone ranging from about 0.005 wt % to about 41 wt %; pregnenolone ranging from about 0.005 wt % to about 41 wt %; ethoxydiglycol ranging from about 0.005 wt % to about 10 wt %; pentoxifylline ranging from about 0.005 wt % to about 10 wt %; ginseng ranging from about 0.005 wt % to about 41 wt %, and carrier q.s. Embodied herein is a method for balancing and maintaining Cortisol levels in humans by identifying the hormonal needs for a human, testing to ascertain the baseline hormone levels, inserting the values of baseline hormone level for each hormone into a hormone tree, balancing the hormones to a normal level, adjusting the levels for symptoms and sex type, and forming a resultant composition.

Abstract: A method for identifying biological samples that are collected using the wrong anticoagulant for subsequent analytical testing. The method also provides for identification of certain analytical test results that are substantially or partly adversely affected.

Abstract: The present invention relates to a device (1) comprising: a sample of reconstructed tissue (4); and a detection system (20), (30) that is at least partially in contact with the tissue sample and/or with a device serving to culture said sample, said detection system making it possible to measure the influence of a physical, biological, and/or chemical stress on at least a fraction of the sample, or vice-versa.

Abstract: A thermal cycler for automatic performance of the polymerase chain reaction is provided. The thermal cycler comprises a heater control that provides close temperature control of the reaction.

Abstract: The present invention provides a technology called Pulse-Multiline Excitation or PME. This technology provides a novel approach to fluorescence detection with application for high-throughput identification of informative SNPs, which could lead to more accurate diagnosis of inherited disease, better prognosis of risk susceptibilities, or identification of sporadic mutations. The PME technology has two main advantages that significantly increase fluorescence sensitivity: (1) optimal excitation of all fluorophores in the genomic assay and (2) “color-blind” detection, which collects considerably more light than standard wavelength resolved detection. Successful implementation of the PME technology will have broad application for routine usage in clinical diagnostics, forensics, and general sequencing methodologies and will have the capability, flexibility, and portability of targeted sequence variation assays for a large majority of the population.

Abstract: A receptacle having a plurality of interconnected chambers arranged to permit multiple process steps or processes to be performed independently or simultaneously. The receptacles are manufactured to separate liquid from dried reagents and to maintain the stability of the dried reagents. An immiscible liquid, such as an oil, is included to control loading of process materials, facilitate mixing and reconstitution of dried reagents, limit evaporation, control heating of reaction materials, concentrate solid support materials to prevent clogging of fluid connections, provide minimum volumes for fluid transfers, and to prevent process materials from sticking to chamber surfaces. The receptacles can be adapted for use in systems having a processing instrument that includes an actuator system for selectively moving fluid substances between chambers and a detector. The actuator system can be arranged to concentrate an analyte present in a sample.

Abstract: A receptacle having a plurality of interconnected chambers arranged to permit multiple process steps or processes to be performed independently or simultaneously. The receptacles are manufactured to separate liquid from dried reagents and to maintain the stability of the dried reagents. An immiscible liquid, such as an oil, is included to control loading of process materials, facilitate mixing and reconstitution of dried reagents, limit evaporation, control heating of reaction materials, concentrate solid support materials to prevent clogging of fluid connections, provide minimum volumes for fluid transfers, and to prevent process materials from sticking to chamber surfaces. The receptacles can be adapted for use in systems having a processing instrument that includes an actuator system for selectively moving fluid substances between chambers and a detector. The actuator system can be arranged to concentrate an analyte present in a sample.

Abstract: A system (1) for producing a dough starter culture is provided which comprises a plurality of reservoirs (15) pre-loaded with a small amount (“mother level”) of a previously obtained starter culture. Into the reservoirs (15) are inoculated the other ingredients required for the preparation of starter culture and the contents are left to ferment for a specified period of time to produce the required starter culture, which is then discharged as required from each reservoir (15). A “mother level” portion is retained in the reservoirs and is used to produce a next batch of starter culture.

Abstract: A bioreactor includes a sensor linked to a model free adaptive controller or optimizer. The sensor can provide a real time measurement of a quantity that correlates with final product titer or other desired product quality attribute.

Abstract: This invention fills several voids in bioreactor technology that allows efficient connection of aspects of physical science (optics, electronics, physical chemistry, sensors) to aspects of microbial and cell culture physiology in a uniquely interactive manner. This is accomplished mathematically through decision making software that utilizes detected changes in the course of fermentation. Decisions are aimed at determining the optima for cellular growth, optimizing for production or degradation of metabolites or substrates, or determining the limits of growth under various combinations of conditions. The invention determines optima or limits in a manner more quickly and at less cost than traditional methods. The basis for the computer generated decisions may be first or second derivative changes observed such as inflection points, limits on allowable rates of change, or the like. The most common measured parameter controlling the decision making process is the optically observed growth of the cells (e.g.

Abstract: This invention provides a novel methods and devices for measurement of particle concentration or changes in particle concentration over a wide linear range. The invention comprises one or more radiation sources and one or more detectors contained in a housing which is interfaced to a medium containing particulate matter. The one or more radiation sources are directed into the medium, scattered or transmitted by the particulate matter, and then some portion of the radiation is detected by the one or more detectors. Methods for confining the measurement to a specific volume within the medium are described. Algorithms are provided for combining the signals generated by multiple source-detector pairs in a manner that results in a wide linear range of response to changes in particle concentration. In one embodiment the sensor provides non-invasive measurements of biomass in a bioreactor. In another embodiment an immersible probe design is described, which may be suited for one-time use.

Abstract: The present invention is a cell-based method of identifying a set of signal transduction proteins having an intracellular localization pattern responsive to toxic compounds. The method requires identifying and screening an initial set of signal transduction proteins against a set of toxic compounds, and determining changes in intracellular localization pattern of each of the proteins. Proteins whose changes in intracellular localization pattern are redundant are discarded from the initial set, and new proteins are added to provide a new set of proteins. I repeat the method steps with new sets of proteins until the set of proteins provides me at least 5 principal components with respect to the range of compounds marketed as small organic molecules.

Abstract: A biological specimen film reel, a biological specimen film assembler, and a biological specimen scanner are provided. The biological specimen film reel comprises a reel carrying a film having a plurality of biological specimens disposed thereon. The biological specimen film assembler comprises a film manipulator and a specimen transfer device. The biological specimen scanner comprises a film manipulator for mechanically manipulating a strip of flexible film with a plurality of biological specimens affixed thereto and a scanning device. Methods for preparing and analyzing the biological specimen film are also provided.

Abstract: The invention relates to a method for the non-invasive selection of single living cells under gentle conditions from mixtures of cells or cell cultures with respect to a specific production performance. To this end, the concentration of substances produced by the individual cells which become enriched at the cell membrane, such as reporter gene products (GFP) or specifically secreted products, such as antibodies, is determined by fluorescence-microscopic detection methods.

Abstract: Systems and methods for site-specific dosing of cellular cultures are provided. Some of the systems provided comprise at least two laminar flow channels; and an ablatable membrane that is disposed between the at least two laminar flow channels. Other systems provided comprise at least two laminar flow channels; and an ablated membrane that is disposed between the at least two laminar flow channels. Some of the methods provided comprise providing at least two laminar flow channels; providing a membrane disposed between the at least two laminar flow channels, wherein the membrane is selected from the group consisting of an ablatable membrane and an ablated membrane; placing cells into at least one of the at least two laminar flow channels; providing a reagent medium; and flowing the reagent medium through at least one other of the at least two laminar flow channels.

Abstract: Hydraulic device for a blood analysis apparatus includes elements 302, 106 for injecting a flow of blood sample into a flow-through optical tank 300 and for creating a flow of sleeving liquid 303 around the sample flow, with a sleeving liquid. The device also includes elements 134, 150 for adjusting a flow rate of the sample flow with respect to the flow rate of the sleeving liquid.

Abstract: The invention relates to a novel circuit arrangement for electrotransfection or electrofusion, which enables the transportation of DNA and/or other biologically active molecules to the nucleus of higher eukaryotic cells or the fusion of cells, independent of cell division and with reduced cell mortality.

Abstract: In one embodiment, the present invention introduces integrated fluid injection and mixing devices to enable pH control in a miniature parallel integrated bioreactor array system. In another embodiment, the environmental conditions of the growth chamber is enabled through fluidic injections in a miniature parallel cell culture system. In still another embodiment, the present invention utilizes gas switches to control oxygen concentration within a miniature parallel integrated bioreactor array.

Abstract: Methods for refining the compositions of bacterial growth media to improve heterologous expression of desired recombinant target genes are provided. Also provided are compositions and culture media obtained using the above methods.

Abstract: Systems and methods for automatically controlling conditions of a process are disclosed. In one example, a controller is programmed with a sequence of steps and parameters required to carry out a bioreactor process. The controller receives information related to a condition of the process over a first communication network, determines a control signal based on the received information and the programmed process, and sends the control signal over a second communication network to a benchtop utility tower. In one example, the utility tower can include transmitters for temperature, pH, and dissolved oxygen that send information related to a condition of the process to the controller over the first communication network, and an agitation system, a gas control system, a temperature control system and a pump control system that perform a control action based on the control signal affecting the process condition.

Abstract: A process is provided for decomposing hydrogen sulfide in a biogas fermenter (10) for generating biogas from biomass, which is fed as a fermentation substrate into the biogas fermenter (10). A reaction gas with increased oxygen content compared to air is fed into a gas space (26) of the biogas fermenter (10).

Abstract: A bioreactor with an anode and a cathode, and a plurality of reaction chambers each having an inlet and an outlet and each including a porous solid ion exchange wafer having ion-exchange resins. Each of the reaction chambers is interleaved between a cation exchange membrane and an anion exchange membrane or between either a cation or an anion exchange membrane and a bipolar exchange membrane. A product chamber is separated from one of the reaction chambers by either a cation or an anion exchange membrane. Recirculation mechanism is provided for transporting material between the reaction chamber inlets and outlets. A method of producing organic acids, amino acids, or amines using the separative bioreactor is disclosed.

Abstract: The invention provides a microfabricated device for sorting cells based on a desired characteristic, for example, reporter-labeled cells can be sorted by the presence or level of reporter on the cells. The device includes a chip having a substrate into which is microfabricated at least one analysis unit. Each analysis unit includes a main channel, having a sample inlet channel, typically at one end, and a detection region along a portion of its length. Adjacent and downstream from the detection region, the main channel has a discrimination region or branch point leading to at least two branch channels. The analysis unit may further include additional inlet channels, detection points, branch points, and branch channels as desired. A stream containing cells is passed through the detection region, such that on average one cell occupies the detection region at a given time.

Abstract: The present invention provides an approach for the simultaneous determination of the activation states of a plurality of proteins in single cells. This approach permits the rapid detection of heterogeneity in a complex cell population based on activation states, and the identification of cellular subsets that exhibit correlated changes in activation within the cell population. Moreover, this approach allows the correlation of cellular activities or properties. In addition, the use of potentiators of cellular activation allows for characterization of such pathways and cell populations.

Abstract: The invention provides methods and compositions for simultaneously detecting the activation state of a plurality of proteins in single cells using flow cytometry. The invention further provides methods and compositions of screening for bioactive agents capable of coordinately modulating the activity of a plurality of proteins in single cells. The methods and compositions can be used to determine the protein activation profile of a cell for predicting or diagnosing a disease state, and for monitoring treatment of a disease state.

Abstract: The present invention relates generally to kits that provide reagent mixes and instructions for the use thereof, in performing high-throughput assay methods that determine the proliferative status of isolated target cell populations. The methods measure the luminescent output derived from the intracellular ATP content of incubated target cells, and correlate the luminescence with the proliferative status of the cells. The present invention further relates to kits that provide reagent mixes and instructions for high-throughput assays methods for screening compounds that may modulate the proliferative status of a target cell population. The kits of the present invention and methods therein described may be used for determining the proliferative status of any isolated cell line or type. The kits and methods of the present invention address the need for rapid assays that determine the proliferative status of isolated hematopoietic stem and progenitor cells and of subpopulations of differentiated cells thereof.

Abstract: The present invention relates generally to high-throughput assay methods that determine the proliferative status of hematopoietic stem and progenitor cells. The present invention further relates to high-throughput assays for screening compounds that modulate the growth of hematopoietic stem and progenitor cells and for identifying subpopulations thereof that are suitable for transplantation. The assay of the present invention is particularly useful for quality control and monitoring of the growth potential in the stem cell transplant setting and would provide improved control over the reconstitution phase of transplanted cells.

Abstract: One or more set point values are generated by a dynamic fermentation controller for one or more of temperature, pH, and enzyme dosage for a fermentation system. The one or more set point values are output to one or more controllers of the fermentation system. The generation of the one or more set point values and the outputting of the one or more set point values is repeated until a change in conditions in the fermentation system is detected.

Abstract: A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridization, antibody/antigen reaction, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micro-machining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific micro-locations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.

Abstract: The invention is based on the development of several sensitive and simple methods for detecting erythropoietin and the erythropoietin receptor and associated antibodies. The methods and reagents are useful for differential diagnosis in Epo and EpoR related clinical problems. Methods and kits for simultaneous measurement of erythropoietin and erythropoietin receptor in a biological sample are described.

Abstract: Biooxidation reactions can be controlled by a method which comprises the steps of: (1) independently adding a substrate and a co-substrate at predetermined rates to a bioxidation reaction mixture comprised of a biocatalyst; (2) measuring the oxygen consumption rate and carbon dioxide evolution rate from the reaction mixture; (3) determining the instantaneous rates of substrate and cosubstrate consumption by solving simultaneous equations relating carbon dioxide evolution rate and oxygen consumption rate to the substrate oxidation stoichiometry, the cosubstrate combustion stoichiometry, and optionally the biomass formation stoichiometry; (4) simultaneously adjusting the substrate and cosubstrate addition rates to the rates of substrate oxidation and cosubstrate consumption in order to maximize the rate of product formation while simultaneously minimizing the rate of cosubstrate usage.

Abstract: The present invention provides a feedback controlled bioculture platform for use as a precision cell biology research tool and for clinical cell growth and maintenance applications. The system provides individual closed-loop flowpath cartridges, with integrated, aseptic sampling and routing to collection vials or analysis systems. The system can operate in a standard laboratory or other incubator for provision of requisite gas and thermal environment. System cartridges are modular and can be operated independently or under a unified system controlling architecture, and provide for scale-up production of cell and cell products for research and clinical applications. Multiple replicates of the flowpath cartridges allow for individual, yet replicate cell culture growth and multiples of the experiment models that can be varied according to the experiment design, or modulated to desired cell development of cell culture end-points.

Abstract: Cell based assays are used to assess the hepatotoxicity of a stimulus. Imaging technologies are used to analyze the effects of a stimulus on hepatocytes. Image analysis may characterize the stimulus on the basis of whether it is hepatotoxic, and if so what type of pathology is exhibited; e.g., apoptosis, necrosis, cholestasis, and/or steatosis.

Abstract: The use of cortisol agonist for preparing a system for diagnosis of the metabolic syndrome and related conditions as belly fatness, insulin resistancy including increased risk of developing senile diabetes, i.e. diabetes type II, high blood fats and high blood pressure, in which system the dose of cortisol agonist is in an interval where a difference is obtained in the inhibitory effect of the autoproduction of cortisol in individuals suffering from the metabolic syndrome, compared to normal values.

Abstract: The invention concerns lactic acid bacteria strains capable of regulating the production of NO and inflammatory cytokines by enterocytes, depending on the inflammatory condition of said enterocytes. The strains can also be incorporated in food supplements such as fermented dairy products used for regulating inflammatory response and non-specific immunity.

Abstract: An apparatus and method for an aseptic fluidic interface between bioprocess systems is provided. The apparatus includes an inlet valve, adapted for automatic control, that is coupled to a biofluid source site. A sampling conduit extends from the inlet valve to an outlet valve. The outlet valve is adapted for automatic control and is coupled to a biofluid process site. A trap is at the sampling conduit. A waste valve, adapted for automatic control, is located at a waste conduit extending from the sampling conduit to a waste site. Also included is a wash fluid source that is coupled to at least one of the inlet or outlet valves. In the method, the sample is automatically directed to the biofluid process site by opening the outlet valve, and closing the waste valve Also included is isolating the biofluid sites by closing the inlet and outlet valves, and opening the waste valve to drain biofluid from the trap to the waste site.

Abstract: The present invention is directed to compositions and methods related to the use of human OGC as an uncoupling protein.

Abstract: The present invention provides for an isolated Sml1 protein or a homologue thereof. The present invention also provides for a screening assay for identifying compounds that are capable of reducing the division rate of a cell by altering an interaction between a ribonucleotide reductase and a Sml1 protein in the cell, which comprises: (a) contacting the cell with a compound, (b) comparing the division rate of the cell in step (a) with the division rate of the cell in the absence of the compound so as to determine whether the compound alters the interaction between the ribonucleotide reductase and the Sml1 protein of the cell, thereby reducing the cell division rate of the cell.

Abstract: Human and mouse TREK-1 potassium transport proteins are disclosed as well a method for using potassium transport proteins for identifying substances having anesthetic properties, such as producing a safe, reversible state of unconsciousness with concurrent amnesia and analgesia in a mammal upon inhalation, in a method comprising (a) contacting the test substance with a mammalian potassium transport protein, wherein said potassium transport protein exhibits outward-going potassium rectification; and (b) determining the potassium transport activity of the potassium transport protein, wherein an activation of potassium transport is indicative of the test substance having anesthetic properties.

Abstract: Disclosed is a method for the measurement of a cellular process, or for the measurement of the effect of a test compound on a cellular process, in one or more different populations of cells. The method comprises providing separate samples of one or more different populations of cells adhering to support particles, the support particles comprising a scintillant substance and being adapted for cell growth. In one embodiment, different samples of cells are introduced into separate reaction vessels in a fluid medium, together with a reagent labelled with a radioisotope, in the presence or the absence of the test compound, under conditions so as to cause a portion of said radiolabelled reagent to become associated with the cells. In another embodiment, multiparameter analysis may be performed to determine the effect of a test compound on a cellular process using two or more different cell populations present in the same well.

Abstract: The present invention relates to a method for monitoring the effect of in vivo administration of Cathepsin S inhibitors by measuring accumulation of an intermediate degradation product of invariant chain (Ii), in particular the p10 Ii fragment, in blood of dosed subjects.

Abstract: A method for cell-based combinatorial logic includes the steps of providing at least one genetically engineered cell, the genetically engineered cell having at least one transcriptional unit. The transcriptional unit includes a gene and a promoter, wherein application of a stimulus to the promoter results in the expression of a gene product. An energetic or chemical stimulus is applied to activate the promoter, wherein the detection of an output signal corresponds to the presence of a gene product. The cell can include a plurality of transcriptional units configured to form logic gates. The logic gates of a plurality of cells can be operably interconnected by release of output signals, such as chemical stimuli.

Abstract: A method and apparatus for running a plurality of tests concurrently to obtain data relating to the electrophysiological properties of receptors and channels in biological membranes of test subjects, such as, for example, Xenopus oocytes. The invention further provides software for controlling, acquiring, and recording data relating to electrophysiological properties of receptors and channels in biological membranes of test subjects, such as, for example, oocytes. This invention increases the throughput rate for experiments and assays employing receptors and ion channels expressed in biological membranes of test subjects, such as, for example, oocytes. In the case of an oocyte, these receptors and channels may be natively expressed (endogenous), may be placed into the oocyte (exogenous), or may be expressed from other RNA or DNA previously placed into the oocyte (exogenous).

Abstract: A system dynamically adjusts the delivery rate of a cryopreservation solution to red blood cells to permit freezing. The delivery rate is preferably determined according to an equation that maintains a linear change of red blood cell osmolarity over time so as to prevent osmolarity shock of the red blood cells. In the preferred embodiment, the system includes a controller that is preconfigured to automatically deliver the cryopreservation solution to the red blood cells in accordance with the equation. The system may also support the recovery of thawed red blood cells by diluting the red blood cells and washing them of the cryopreservative. Again, the system preferably adjusts the delivery rate of a dilution solution so as to prevent osmolarity shock of the red blood cells during the recovery phase. The recovered red blood cells may be suspended in a preservation solution to further increase their shelf-life following the recovery phase.

Abstract: A method for determining the ion channel activity of a substance comprises the steps of (i) expressing the substance as a heterologous protein in a host cell, and (ii) determining changes in permeability of the plasma membrane of the host cell induced by expression of the heterologous protein. A screening method for determining ion channel modulating activity of a test substance is also disclosed.