Abstract: Systems, methods and kits are described for culturing one or more biological cells in a microfluidic device, including provision of nutrients and gaseous components configured to enhance cell growth, viability, portability, or any combination thereof. In some embodiments, culturing a single cell may produce a clonal population in the microfluidic device.

Abstract: Biological activity in holding pens in a micro-fluidic device can be assayed by placing in the holding pens capture objects that bind a particular material of interest produced by the biological activity. The biological material of interest that binds to each capture object can then be assessed, either in the micro-fluidic device or after exporting the capture object from the micro-fluidic device. The assessment can be utilized to characterize the biological activity in each holding pen. The biological activity can be production of the biological material of interest. Thus, the biological activity can correspond to or arise from one or more biological cells. Biological cells within a holding pen can be clonal cell colonies. The biological activity of each clonal cell colony can be assayed while maintaining the clonal status of each colony.

Abstract: Individual biological cells can be selected in a micro-fluidic device and moved into isolation pens in the device. The cells can then be lysed in the pens, releasing nucleic acid material, which can be captured by one or more capture objects in the pens. The capture objects with the captured nucleic acid material can then be removed from the pens. The capture objects can include unique identifiers, allowing each capture object to be correlated to the individual cell from which the nucleic acid material captured by the object originated.

Abstract: In some cases, the described systems and methods include obtaining a cell sample containing multiple antibody-producing cells. In such cases, the cells can be tagged with a cross-linking reagent having a first portion configured to bind to a marker on the antibody-producing cells and a second portion configured to bind to an antigen of interest. In some instances, the tagged antibody-producing cells are exposed to the antigen of interest such that the antigen becomes bound to the cells. In some such instances, the antibody-producing cells are also allowed to produce an antibody, such that a portion of the antibody-producing cells produce an antigen-specific antibody that binds to the antigen of interest. To identify cells that produce the antigen-specific antibody, the tagged cells can be exposed to a labeled secondary antibody that is configured to bind to the antigen-specific antibody. Other implementations are also described.

Abstract: In some cases, the described systems and methods include obtaining a cell sample containing multiple antibody-producing cells. In such cases, the cells can be tagged with a cross-linking reagent having a first portion configured to bind to a marker on the antibody-producing cells and a second portion configured to bind to an antigen of interest. In some instances, the tagged antibody-producing cells are exposed to the antigen of interest such that the antigen becomes bound to the cells. In some such instances, the antibody-producing cells are also allowed to produce an antibody, such that a portion of the antibody-producing cells produce an antigen-specific antibody that binds to the antigen of interest. To identify cells that produce the antigen-specific antibody, the tagged cells can be exposed to a labeled secondary antibody that is configured to bind to the antigen-specific antibody. Other implementations are also described.

Abstract: In some cases, the described systems and methods include obtaining a cell sample containing multiple antibody-producing cells. In such cases, the cells can be tagged with a cross-linking reagent having a first portion configured to bind to a marker on the antibody-producing cells and a second portion configured to bind to an antigen of interest. In some instances, the tagged antibody-producing cells are exposed to the antigen of interest such that the antigen becomes bound to the cells. In some such instances, the antibody-producing cells are also allowed to produce an antibody, such that a portion of the antibody-producing cells produce an antigen-specific antibody that binds to the antigen of interest. To identify cells that produce the antigen-specific antibody, the tagged cells can be exposed to a labeled secondary antibody that is configured to bind to the antigen-specific antibody. Other implementations are also described.

Abstract: Individual biological micro-objects can be deterministically selected and moved into holding pens in a micro-fluidic device. A flow of a first liquid medium can be provided to the pens. Physical pens can be structured to impede a direct flow of the first medium into a second medium in the pens while allowing diffusive mixing of the first medium and the second medium. Virtual pens can allow a common flow of medium to multiple ones of the pens.

Abstract: Two or more biological micro-objects can be grouped in a liquid medium in a chamber. Grouping can comprise bringing into and holding in proximity or contact the micro-objects in a group, breaching the membrane of one or more of the micro-objects in a group, subjecting one or more of the micro-objects in a group to electroporation, and/or tethering to each other the micro-objects in a group. The micro-objects in the group can then be combined into a single biological object.

Abstract: The present invention relates to substituted benzimidazoles, compositions containing such compounds and methods of treatment The compounds are glucagon receptor antagonists and thus are useful for treating, preventing or delaying the onset of type 2 diabetes mellitus.

Abstract: The present invention addresses substituted cyanothiophene derivatives of the formula I: as well as compositions containing such compounds and methods of treatment. The compounds in the present invention are glucagon antagonists. The compounds block the action of glucagon at its receptor and thereby decrease the levels of plasma glucose providing a treatment of diabetes.

Abstract: Pyrrolidine compounds of Formula (I), (wherein R1, R2, R3, R4, R5, R6a, R6b, R7 and R8 are defined herein) are described. The compounds are modulators of CCR5 chemokine receptor activity. The compounds are useful, for example, in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

Abstract: The present invention relates to vancomycin analogs in which the vancosamine residue is substituted with a lipid-like substituent that includes a first aryl moiety and a second aryl moiety joined together by a flexible linker moiety, that is not a single bond directly joining the first aryl moiety and the second aryl moiety, and a glucose C-6 substituent modified to be other than the naturally occurring hydroxyl group, or pharmaceutically acceptable salts thereof.

Abstract: The present invention addresses substituted cyanothiophene derivatives of the formula I: 1

Abstract: The present invention addresses substituted cyanothiophene derivatives of the formula I: 1

Abstract: Pyrrolidine compounds of Formula (I), (wherein R1, R2, R3, R4, R5, R6a, R6b, R7 and R8 are defined herein) are described. The compounds are modulators of CCR5 chemokine receptor activity. The compounds are useful, for example, in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Abstract: The present invention relates to vancomycin analogs in which the vancosamine residue is substituted with a lipid-like substituent that includes a first aryl moiety and a second aryl moiety joined together by a flexible linker moiety, that is not a single bond directly joining the first aryl moiety and the second aryl moiety, and a glucose C-6 substituent modified to be other than the naturally occurring hydroxyl group, or pharmaceutically acceptable salts thereof.

Abstract: &ggr;-Hydroxy-2-(fluoroalkylaminocarbonyl)-1-piperazinepentanamide compounds are inhibitors of HIV protease and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described. These compounds are effective against HIV viral mutants which are resistant to HIV protease inhibitors currently used for treating AIDS and HIV infection.

Abstract: The present invention is directed to compounds of the formula I: (wherein R1, R3, R4, R5, R6, R7, R8, X, n, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.

Abstract: Pyrrolidine compounds of Formula I: (wherein R1, R2, R3, R4, R5, R6, R7, R8a, R8b, j, k, 1, m, and n are defined herein) are described. The compounds are modulators of CCR5 chemokine receptor activity. The compounds are useful, for example, in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Abstract: Compounds of Formula I: (wherein R1, R2, R3, R4, Q, and X are defined herein) are described. The compounds are modulators of CCR5 chemokine receptor activity. The compounds are useful, for example, in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.