Abstract: This disclosure generally relates to systems and methods for manipulating chambers and other substrates for chemical, biological, or biochemical samples, such as cell culture and other chambers, within units such as incubators. In certain embodiments, the invention provides a technique for maintaining a plurality of substrates or chambers in a housing within which a predetermined environment is maintained, and moving substrates or chambers in and out of the housing, in some cases without creating a large opening in the housing (e.g., by opening a door significantly larger than the substrates). A technique is provided, in certain embodiments, in which a plurality of substrates are mounted in fixed, secured relation to each other within a housing providing a predetermined, controlled environment, and are moved within the housing so that they can be evenly exposed to any differences in environment within the housing.

Abstract: Chemical and biological reactors, including microreactors, are provided. Exemplary reactors include a plurality of reactors operable in parallel, where each reactor has a small volume and, together, the reactors produce a large volume of product. Reaction systems can include mixing chambers, heating/dispersion units, reaction chambers, and separation units. Components of the reactors can be readily formed from a variety of materials. For example, they can be etched from silicon. Components are connectable to and separable from each other to form a variety of types of reactors, and the reactors can be attachable to and separable from each other to add significant flexibility in parallel and/or series reactor operation.

Abstract: Chemical and biological reactors, including microreactors, are provided. Exemplary reactors include a plurality of reactors operable in parallel, where each reactor has a small volume and, together, the reactors produce a large volume of product. Reaction systems can include mixing chambers, heating/dispersion units, reaction chambers, and separation units. Components of the reactors can be readily formed from a variety of materials. For example, they can be etched from silicon. Components are connectable to and separable from each other to form a variety of types of reactors, and the reactors can be attachable to and separable from each other to add significant flexibility in parallel and/or series reactor operation.

Abstract: Disclosed are systems and methods for manipulating chemical, biological, and/or biochemical samples, optionally supported on substrates and/or within chambers, for example biological samples contained on chips, within biological chambers, etc. In certain embodiments, an apparatus configured to be able to position a chamber or other substrate in one or more modules surrounding the apparatus is disclosed. The apparatus may be configured to be able to move the chamber or substrate in any set of directions, such as radially, vertically, and/or rotationally, with respect to the apparatus. The apparatus may be manually operated and/or automatically controlled. Examples of modules include, but are not limited to, stacking or holding modules, barcode readers, filling modules, sampling modules, incubation modules, sensor modules (e.g., for determining cell density, cell viability, pH, oxygen concentration, nutrient concentration, fluorescence measurements, etc.), assay modules (e.g.

Abstract: Methods for forming chemical and/or biological products in reactors, and/or analyzing chemical and/or biological interactions in reactors are provided. The methods relate, more specifically, to forming such products and/or carrying out such analyses in small volume reactors with control over overall fluid volume in the reactors. The methods can be used to mimic processes in large scale reactors and/or to obtain reaction or interaction information relevant to large scale reactors (e.g., to adjust/optimize large-scale reactor processes). Advantageously, the methods can allow parameters of small scale reactors to be correlated with those of large scale reactors, where desired.

Abstract: Various aspects of the present invention relate to light-interacting components suitable for use in chips and other reactor systems. These components may include waveguides, optical fibers, light sources, photodetectors, optical elements, and the like. If waveguides are used, they may be fashioned out of any material able to transmit light to or from the reaction site. The chip may contain a reaction site having a volume of less than about 1 ml. In some embodiments, the chip may be constructed in such a way as to be able to support a living cell. The chip may be used for imaging or analysis, or the chip may be used to facilitate a chemical or biological reaction, which may be light-sensitive or light-activated in certain cases. Other facilitated reactions may include the production or consumption of a chemical or biological species. In some embodiments, the chip may include more than one component or component type, or more than one reaction site.

Abstract: Computer-facilitated design of large-scale, multi-factorial cell culture experiments and the like, and control of reaction sites and/or arrays of reaction sites to perform such experiments using automated devices. In certain cases, the invention is directed to controlling a plurality of cell culture experiments, e.g., using an automated cell culture device. In one set of embodiments, a data structure or a “descriptor” for use with cell culture experiments is provided. The descriptor may be used, for instance, to control one or more cell culture experiments, to identify one or more cell culture experiments, and/or to identify or “tag” data arising from one or more cell culture experiments, e.g., for further analysis or recall.

Abstract: The present invention generally relates to chemical, biological, and/or biochemical reactor microreactors and other reaction systems such as microreactor systems, as well as systems and methods for constructing and using such devices. In one aspect, a reactor on a chip has a container in fluid communication with a channel, and the channel is in fluid communication with a port for connecting the container to a source of fluid to be introduced into the container. The container can be very small, for example, with a volume of less than about 2 milliliters, and the fluid channel can have a channel volume of less than 1.5 percent of the container volume. According to another aspect, the combined volume of the port volume and the channel volume can be less than about 10 percent of the container volume. Such a configuration may increase the percentage of added fluid that reaches the container.

Abstract: The present invention is directed to materials and reactor systems having humidity and/or gas control. The material may have high oxygen permeability and/or low water vapor permeability. In some cases, the material may have sufficient permeance and/or permeability to allow cell culture to occur in a chip or other reactor system using the material. In certain embodiments, the material may be positioned adjacent to or abut a reaction site within a chip or reactor; in other embodiments, the material may be positioned such that it is in fluidic communication with the reaction site. The material may also be porous and/or transparent in some cases. In one set of embodiments, the material include a polymer that is branched, and/or contains bulky side groups that allow the polymer to have a more open structure. In some cases, the material may include two or more layers.

Abstract: The present invention is directed to materials and reactor systems having humidity and/or gas control. The material may have high oxygen permeability and/or low water vapor permeability. In some cases, the material may have sufficient permeance and/or permeability to allow cell culture to occur in a chip or other reactor system using the material. In certain embodiments, the material may be positioned adjacent to or abut a reaction site within a chip or reactor; in other embodiments, the material may be positioned such that it is in fluidic communication with the reaction site. The material may also be porous and/or transparent in some cases. In one set of embodiments, the material include a polymer that is branched, and/or contains bulky side groups that allow the polymer to have a more open structure. In some cases, the material may include two or more layers.

Abstract: Fluid transfer devices described herein can include a body portion and a tip portion. A fluid pathway extends through the body and tip portions through which fluid may be transferred, for example, from a fluid-dispensing apparatus to a fluidic chamber of a microreactor. In some embodiments, the fluid transfer device is connected to the fluid-dispensing apparatus with an engaging element. The engaging element may be part of the body, and can enable the dispensing apparatus to repeatedly engage the body at one predetermined position. The body is capable of storing the fluid received from the dispensing apparatus. The tip portion may be formed of a rigid material (e.g., a metal), and/or may be configured to repeatedly pierce a septum without damaging either the tip or the body. Advantageously, in certain embodiments, the fluid transfer device can controllably transfer small volumes of fluid (e.g., 1 ?L) with a high degree of accuracy.

Abstract: A microfermentor device that can be used for a wide variety of purposes is described. The microfermentor device includes one or more cell growth chambers having a volume of less than 1 ml. The microfermentor device can be used to grow cells used for the production of useful compounds, e.g., therapeutic proteins, antibodies or small molecule drugs. The microfermentor device can also be used in various high-throughput screening assays. For example, the microfermentor device can be used to screen compounds to assess their effect on cell growth and/or a normal or abnormal biological function of a cell and/or their effect on the expression of a protein expressed by the cell. The device can also be used to investigate the effect of various environmental factors on cell growth, biological function or production of a cell product. The device, including various controlling components and sensing components can be microfabricated on a support material.

Abstract: Immiscible substances, such as gases, solids or liquids may be included within a reaction site container as a mixer of a liquid sample. Movement of the mixer within the container may help suspend or re-suspend cells or other species. Movement of the mixer also may generate shear forces that can affect cellular activity. In some embodiments, movement of the container brings about movement of the mixer. Containers may be mounted to a rotating apparatus in various orientations to achieve different travel paths of the mixer. Varying the rotation rate and/or the relative densities of the mixer and the liquid sample also may affect the mixer travel path.

Abstract: An apparatus for performing a biological or biochemical reaction that, in certain embodiments, has the ability to apply shear stress to a component of a liquid sample and includes a biological or biochemical reactor comprising a container having a volume of less than about 2 mL and containing a liquid sample, and a shear-generating element, the shear-generating element being contained within the apparatus and constructed and arranged so that the entire shear-generating element moves along a selected path of motion intersecting a first location within the apparatus and a second location within the apparatus, with or without rotational movement is described. A method of applying shear stress to a component of a liquid sample that includes moving a liquid or gaseous shear-generating element within an apparatus along a selected path of motion to create a reproducible and controllable level of shear stress at a selected location within the liquid sample is also disclosed.

Abstract: Chemical, biological, and/or biochemical reaction systems, including chips or reactors, may be configured so as to restrain immiscible materials such as gas bubbles from interfering with the determination of environmental factors associated with the chip according to one aspect of the invention. In another aspect, a chip or other reaction system may be configured to maintain a gas headspace in the chip or other reaction system. In certain embodiments, impediments such as physical barriers may be used to contain gas bubbles within a gas containing region, or otherwise away from a detection region. In other embodiments, surface tension properties may be used to control the location of gas bubbles. The chip or other reaction systems may include reaction site containers that can be very small, for example, having a volume of less than about 2 ml.

Abstract: The present invention provides chemical compounds (compositions of matter) and methods useful for determining pH and/or pH change in an environment. Specific compounds of the invention include at least five fused molecular rings.

Abstract: In a liquid handling system including a liquid handling substrate having a plurality of channels for conducting a liquid sample in said substrate, where the channels terminate in a plurality of exit ports in an outer surface of the substrate for transfer of a quantity of the liquid sample. The handling system also includes a liquid storage and dispensing substrate having a plurality of separable cartridges corresponding to the channels, with each cartridge terminating at a microelectro mechanical system (MEMS) comprising a laminate of glass, silicon and a piezoelectric substance. The handling system further includes a liquid detecting system comprising a light emitting diode and a photo-detector, where each channel includes a reservoir in communication with a corresponding cartridge creating an interface therebetween.

Abstract: In a liquid handling system including a liquid handling substrate having a plurality of channels for conducting a liquid sample in said substrate, where the channels terminate in a plurality of exit ports in an outer surface of the substrate for transfer of a quantity of the liquid sample. The handling system also includes a liquid storage and dispensing substrate having a plurality of separable cartridges corresponding to the channels, with each cartridge terminating at a microelectro mechanical system (MEMS) comprising a laminate of glass, silicon and a piezoelectric substance. The handling system further includes a liquid detecting system comprising a light emitting diode and a photo-detector, where each channel includes a reservoir in communication with a corresponding cartridge creating an interface therebetween.

Abstract: The present invention generally relates to chemical, biological, and/or biochemical reactor chips and other reaction systems such as microreactor systems, as well as systems and methods for constructing and using such devices. In one aspect, a chip or other reaction system may be constructed so as to promote cell growth within it. In certain embodiments, the chips or other reaction systems of the invention include one or more reaction sites. The reaction sites can be very small, for example, with a volume of less than about 1 ml. In one aspect of the invention, a chip is able to detect, measure and/or control an environmental factor such as the temperature, pressure, CO2 concentration, O2 concentration, relative humidity, pH, etc. associated with one or more reaction sites, by using one or more sensors, actuators, processors, and/or control systems. In another aspect, the present invention is directed to materials and systems having humidity and/or gas control, for example, for use with a chip.