Abstract: Various embodiments of the present invention provide both apparatus and method for the patterning of cells onto non-adhesive substrates and the controlled regulation of cells through the use of photoactivated cellular morphogenic factors.

Abstract: A process of forming an array of powder samples arranged in predefined locations where all samples have a flat surface in a common plane has been developed. A main support having at least N perforations from a first surface of the main support through a second surface of the main support in predefined locations, where N is the number of samples in the array is provided. The main support is equipped with a flat support temporarily attached to its first surface. All N samples are loaded simultaneously with sample X in perforation X of the main support where X is an integer from 1 to N. A flat surface of each sample where the flat surfaces are a common plane is formed by forcing the samples within the perforations against the flat support. The samples are retained in position within the perforations against the flat support, and are made ready for analysis by exposing the flat surfaces of the samples by removing the flat support.

Abstract: A culture package system comprising a package preferably in the form of a container containing one or more conventional culture media dishes containing solidified culture media. Each dish includes a bottom wall and a peripheral side wall and a removable cover having a bottom wall and a peripheral side side wall which is loosely telescoped over the dish. A plurality of the dishes are preferably provided in inverted stacked relation in the container. A cover is hermetically sealed to close the container. The interior of the package has a gaseous atmosphere having less than 1% oxygen. An oxygen absorber is placed in the package to facilitate maintaining the atmosphere at less than 1% oxygen. Preferably a moisture absorber is also placed in the package. The package is made of plastic material which is impermeable to oxygen and moisture and preferably is in the form of a container which has a base wall and a peripheral wall and a cover sealed thereto.

Abstract: System and process for isolating purified biological materials with a collecting unit which has collecting vessels that are accessible from above with a matrix unit in which matrix vessels are arranged in a holder as well as a closure unit which can be placed on the collecting unit to close the collecting vessel. In addition the invention also concerns a system having a collecting unit, a matrix unit, and a closure unit as well as a lysis unit and a waste unit. Moreover a new closure arrangement is disclosed which is suitable for closing vessels in which there is excess pressure.

Abstract: A thermal cycling device for biological samples. The thermal cycling device may include a sample block, an annular plate, and a plurality of spring devices interposed between the sample block and the annular plate. The sample block has a plurality of openings for receiving sample wells of a sample well tray. The annular plate may be positioned adjacent the outer periphery of the sample block and may be configured to abut a bottom surface of the sample well tray when the sample well tray is positioned thereon. The plurality of spring device may be interposed between the sample block and the annular plate to urge the annular plate and sample well tray away from the sample block.

Abstract: A fermentation apparatus is constructed to produce a known and repeatable amount of unpoisoned fermentation product using multiple fermentation vessels. To facilitate further processing compatible with other product processing steps, the fermentation apparatus has an array of sample vessels arranged in a container frame. The container frame is configured to hold the sample vessels during fermentation and to transport the vessel array to or from another processing station. Corresponding to the number of sample vessels in the sample vessel array, a cannula array is configured such that each cannula may be placed inside a sample vessel. The cannula array is attached to a gas distributor that delivers oxygen and/or one or more other gases from a gas source through the cannula into the sample vessel.

Abstract: A perfusion incubator having a fluid conditioning unit (12), a well assembly (7) and a well assembly heating unit (14), a peristaltic pump (4) and a fluid collection unit (11). The well assembly has a number of wells (20, 21) each having a transparent lid (30) and a fluid inlet (26) and a fluid outlet (27). An illumination device (13) is under the well so that the cell being cultured in the well assembly can be observed by means of a microscope (15). Each fluid inlet (26) is positioned so as to allow a tangential entry of fluid to the well at a mid point in the well, and each fluid outlet (27) is above the fluid inlet with the cell to be cultured in a lower portion of the well so that flow of fluid in the well is formed into a vortex which tends to draw fluid from around the cell without direct flow over the embryo.

Abstract: Techniques for high throughput parallel separation, filtration and plate-to-plate transfer are described. Cells, proteins, chemical compounds and the like are being developed in multi-well, small volume well plates, such as 1536-well plates having wells of a volume on the order of 1 &mgr;l. A mechanism for clamping such plates together so that the wells will be aligned allows rapid separation or transfer by simply centrifuging the assembly. A membrane may be clamped between the plates. Alternatively, a membrane may replace one of the plates. Centrifuge dependent and independent designs are described.

Abstract: A product exhibiting an improved cell growth surface and cell attachment. According to the present invention, a stream of plasma is comprised of activated gaseous species generated by a microwave source. This stream is directed at the surface of a polymer substrate in a controlled fashion such that the surface is imparted with attributes for cell adhesion far superior to that of untreated polymer or polymer treated by other methods.

Abstract: A chamber has a lid that permits opening and closing of the chamber for inserting or removing a cell culture from the chamber while the chamber is in a stack of chambers without removing any of the chambers from the stack. The lid of the chamber may have one or more ports which enable substances to be introduced into or removed from the chamber when the chamber is sealed by the lid. In one embodiment, the lid is a side wall of a rectangular chamber in a stack of rectangular chambers. Spacers may be provided between the chambers of the stack to provide space between the chambers and restrict horizontal movement of the chambers relative to each other. A flexible container containing an atmosphere may be connected to a port of the chamber, and the atmosphere may be transferred to the chamber by compressing the flexible container. After a cell culture is introduced into the chamber, the stack of chambers may be placed into an incubator.

Abstract: The invention relates to a device for producing a three-dimensional circular muscle body from a carrier substance and from cell cultures incorporated therein comprising a cell culture dish (1) and at least one element (2) placed inside said cell culture dish (1). The invention also relates to a multi-well plate constructed of a number of devices, which are arranged side by side and/or one behind the other, for producing a three-dimensional circular muscle body. The invention additionally relates to a solution for cultivating mammal cardiomyocytes, to a method for cultivating a cell culture, to a device for measuring isometric force parameters of cell cultures, and to a method for following, in a measurable manner, contractions of a cell tissue incorporated in a carrier substance. Finally, the invention relates to an artificially produced three-dimensional muscle tissue, in particular, a heart muscle tissue.

Abstract: A three-dimensional (3D) array of solid-phase supports is adapted to provide parallel synthesis of a library of molecules with 3D diversity. Individual locations in the 3D array may be assigned to selected molecules in the library such that molecules may be synthesized at and retrieved from such locations. Also, the supports include aperture walls in stacked plates; the supports may be suspended within stacked plate apertures; the 3D array include discrete supports arranged in columns in one or more wells; the supports include tube inner walls or be suspended in tubes, the tubes being secured in stacked, two-dimensional (2D) frameworks; or the supports include beads contained in porous enclosures having non-porous side walls and being secured in stacked, 2D frameworks. A support transfer device enables transfer of solid-phase supports used in a 3D array.

Abstract: A microorganism culture plate and methods for its fabrication and use. The culture plate comprises a splash-guard that attaches to a upper rim of the plate. The splash-guard forms a removable, hermetic seal with the rim to prevent liquid media or other fluids from spilling or leaking out of the plate.

Abstract: Device and method for processing samples are provided. A first multiwell plate is stacked atop a second multiwell plate. The first multiwell plate has x wells arranged in an array, each well is capable of receiving a sample and has an outlet. The second multiwell plate has y wells arranged in an array, each well being capable of receiving a separate sample. y>x. The outlets of the first multiwell plate register with inlets of a subset of wells of the second multiwell plate when the first plate is stacked atop the second plate. Also provided are a mechanism for aligning the plates and transfer indicia for tracking transfer of sample from the first to the second plate. A mechanism for sealing the first plate to the second plate is provided so that samples can be directly transferred between the plates without cross-contamination occurring in open wells of the second plate.

Abstract: The invention relates to novel analysis slides or substrates of the open configuration. The slides may be used for any application which normally utilizes a conventional microscope slide and can be used in conjunction with any type of equipment typically used to manipulate or evaluate a standard microscope slide. In particular, the invention provides open slides for covalent immobilization of polypeptides and nucleic acids. Further provided are methods for carrying out biological assays using arrays of biomolecules immobilized on the slides of the invention.

Abstract: A multi-well plate is disclosed for holding chemical compounds for heating in a microwave oven. The plate is a substantially planar member having wells arranged in an array of rows and columns in its upper surface. The plate has heat reservoirs in the form of fluid filled channels or elongated solid bodies positioned lengthwise along the side portions of the plate to reduce temperature gradients among the wells across the length and width of the plate. The heat reservoirs prevent or mitigate heat loss from the wells near the side portions of the plate and ensure that the compounds in all of the wells have a uniform temperature.

Abstract: An on-spot selectively activated hydrophobic slide/microarray. The preparation method relates to a hydrophobic copolymer prepared by blending, grafting or co-polymerization of a hydrophobic material and a compound bearing a functional group protected by a protecting group, wherein the functional group is imide or cyclic amide, and the protecting group is a photo acid group such as a tosyloxy group. The hydrophobic copolymer coated on a substrate is then subjected to selective photolithographical activation so that the slide will have functional active copolymer spots separated by inactive copolymers. The resulting slide is suitable for the preparation of high-density and high-efficiency bio-chip/microarray.

Abstract: A system and method for applying one or more chemicals to a tissue sample is provided. The system preferably includes a cassette for housing a slide device, a film, and an injection system. The slide device preferably includes a specimen slide for containing the tissue sample and a cover plate connected to the specimen slide. The film is preferably moveable through the cassette along guide rollers and preferably contains a plurality of containers containing one or more chemicals. The injection system may include a piston for displacing the chemicals from the containers through an injection port to the tissue sample. The cassette may be placed on a cassette driver that contains a motor-driven shaft for driving the piston and moving the film.

Abstract: Provided is a cell culture apparatus for culturing cells, and optionally, for performing magnetic separation of cells desired to be cultured. The cell culture apparatus preferably comprises a frame; two membranes, preferably each being gas permeable, which are securedly sealed in a leak-proof selaing to a frame in forming a culture chamber there-between; and at least one resealable aperture to allow substances to be introduced into, or withdrawn from, the culture chamber.

Abstract: A loading station assembly for at least partially supporting the underside of a flexible cell membrane positioned in the bottom of a cell culture well. The assembly includes a planar member having a plurality of apertures. Each aperture receives a post having a flange which supports the membrane. A central opening defined in the planar member allows a vacuum to be drawn therethrough and to pull a portion of the membrane downwardly and cause a central portion of the membrane to stretch across the flange. Cells cultured on the membrane are subjected to a corresponding strain.

Abstract: The invention relates to a device for accommodating a cell culture comprising a vessel (1) having a base (3) and walls (4), and comprising a lid (2) which can be inserted into the vessel (1). The lid is provided with an evacuation opening (6) for evacuating displaced air and excess liquid. The evacuation opening can be closed after the lid (2) has been inserted. Inside the vessel (1), devices (31) which are provided on the lid (2) make it possible to form interspaced chambers (30) and to form troughs on said lid (2).

Abstract: Device and method for processing biological, biochemical or chemical samples are provided wherein a first multiwell plate is stacked atop a second multiwell plate. The first multiwell plate has x wells arranged in a regular array, each capable of receiving a separate sample. Each well of the x wells has an outlet at a lower surface of the first plate. The second multiwell plate has y wells arranged in a regular array, each well of the y wells being capable of receiving a separate sample, and wherein y>x. The outlets at the lower surface of the first multiwell plate are arrayed to register with corresponding inlets of a subset of the y wells of the second multiwell plate when the first plate is stacked atop the second plate. A mechanism for aligning the first plate to the second plate is provided, as well as transfer indicia for tracking transfer of sample from the first plate to the second plate.

Abstract: A method of testing multiple fluid samples with multiple biopolymer arrays. A cover is assembled to a contiguous substrate carrying on a first side, multiple arrays each with multiple regions of biopolymers linked to the substrate, such that the cover and the substrate together form a plurality of chambers each containing a biopolymer array and each being accessible through its own port;. Multiple fluid samples are introduced into respective chambers through a port of each such that the fluid samples contact respective arrays. A binding pattern of the arrays is observed. An apparatus and kit useful in such methods, are also provided.

Abstract: The present invention includes a microplate for performing crystallography studies and methods for making and using such microplates. In particular, the microplate has a frame which includes a plurality of wells formed therein. Each well includes a first well and a second well. The first well includes a relatively small reservoir having a substantially concaved form capable of receiving a protein solution and a reagent solution. The second well includes a relatively large reservoir capable of receiving a reagent solution that has a higher concentration than the reagent solution within the first well, wherein the protein solution and the reagent solution within the first well interact with the reagent solution within the second well via a vapor diffusion process which enables the formation of protein crystals within the first well. The microplate may be sized so that it can be handled by a robotic handling system and/or a liquid handling system.

Abstract: An adhesive backed covering for use on a microtiter plate is disclosed. The covering comprises labels printed or embossed thereon which will align on top of individual wells when the cover is placed onto the microtiter plate. Preferably each label will be unique to uniquely identify each well of the microtiter plate. The use of these covers aids in the manual identification of individual wells of microtiter plates thereby minimizing human error. Preferably the covers can easily be penetrated by a pipet tip or other extraction device, such as a wooden applicator or toothpick, to allow easy access to individual wells while protecting other wells which remain sealed.

Abstract: Provided is a cell culture apparatus for culturing cells, and optionally, for performing magnetic separation of cells desired to be cultured. The cell culture apparatus preferably comprises a frame; two membranes, preferably each being gas permeable, which are securedly sealed in a leak-proof selaing to a frame in forming a culture chamber therebetween; and at least one resealable aperture to allow substances to be introduced into, or withdrawn from, the culture chamber.

Abstract: The present invention relates to a novel container and process, and more specifically, to a rectilinear plastic container whose interior is divided into two or more channels (a multi-channel plate) which is filled with a microbial growth medium and is utilized in a process for enumeration of microorganisms found in clinical or industrial samples. Different microbial growth media may be placed in adjacent channels of the rectilinear plastic container for the process of the present invention. The process of the present invention demonstrates a more efficient and rapid means to identify and enumerate microorganisms in a sample.

Abstract: Provided for heating cultured cells is a controlled heater device comprising a cell culture apparatus, a transparent heater in thermal contact with the cell culture apparatus, and may further comprise one or more of a transparent filter provided to prevent a predetermined spectral range of light from passing through the transparent filter, and a power source for controlling the amount of heat generated by the transparent heater of the controlled heater device.

Abstract: A method of testing multiple fluid samples with multiple biopolymer arrays. A cover is assembled to a contiguous substrate carrying on a first side, multiple arrays each with multiple regions of biopolymers linked to the substrate, such that the cover and the substrate together form a plurality of chambers each containing a biopolymer array and each being accessible through its own port. Multiple fluid samples are introduced into respective chambers through a port of each such that the fluid samples contact respective arrays. A binding pattern of the arrays is observed. An apparatus and kit useful in such methods, are also provided.

Abstract: There is provided a carrier for co-culturing a fertilized ovum of an animal by which behavior of the fertilized ovum of an animal can be easily observed in a culture system and by which adhesion and three-dimensional growth of the fertilized ovum become possible at first, as well as there is provided a method of culturing the fertilized ovum of an animal using the co-culturing carrier. There is provided a carrier for co-culturing a fertilized ovum of an animal composed of a cell incorporated type three-dimensionally reconstructed tissue for co-culturing the fertilized ovum of an animal to induce adhesion and three-dimensional growth, of the fertilized ovum as well as there is provided a method of culturing the fertilized ovum of an animal characterized in that the co-culturing carrier is introduced into a culture vessel to culture the fertilized ovum of an animal.

Abstract: The synthesis of arrays of DNA probes sequences, polypeptides, and the like is carried out using a patterning process on an active surface of a substrate. An image is projected onto the active surface of the substrate utilizing an image former that includes a light source that provides light to a micromirror device comprising an array of electronically addressable micromirrors, each of which can be selectively tilted between one of at least two positions. Projection optics receives the light reflected from the micromirrors along an optical axis and precisely images the micromirrors onto the active surface of the substrate, which may be used to activate the surface of the substrate. The first level of bases may then be applied to the substrate, followed by development steps, and subsequent exposure of the substrate utilizing a different pattern of micromirrors, with further repeats until the elements of a two dimensional array on the substrate surface have an appropriate base bound thereto.

Abstract: Methods, apparatus, and applications for use of a stacked, reconfigurable system for electrophoretic transport are provided. In one embodiment, a system having a first chamber including at least a bottom support and an intermediate support, and a second chamber, said second chamber including a bottom support and a top member, the first and second chambers being coupled through a via. Electrophoretic, and optional electro-osmotic and thermal, transport is effected. In another aspect of this invention, three or more chambers are coupled by an electrophoretic buss. The electrophoretic buss includes driving electrodes and is adapted to receive fluid containing materials for transport. The chambers are coupled to the electrophoretic buss and serve as a tap from the buss for delivery of charged materials. In one embodiment, certain functions are performed in different chambers.

Abstract: The invention features a method for preparing a high-density functional slide by coating a sol-gel containing amine-group bearing silanes and a solution containing polyaldehyde groups onto an organic or inorganic substrate, respectively. The resulting slide is useful in the preparation of highly homogeneous functional-group slides and the high-density and high-efficiency bio-chip/microarray.

Abstract: The present invention relates to an in vitro cell culture device which includes a vessel comprising an inner surface, a layer of cartilage disposed on at least a portion of said inner surface, the layer of cartilage including a plurality of chondrocytes in an extracellular matrix, and a growth medium in the vessel, the layer of cartilage being bathed in the growth medium. Also disclosed is a composite cell culture prepared from the in vitro cell culture device, the composite cell culture includes a first layer including chondrocytes in an extracellular matrix, a second layer disposed on the first layer and including type I collagen, and a third layer disposed on the second layer and including cells at least partially covering the second layer.

Abstract: The invention relates to a culture dish consisting of a plastic material and intended for growing cell and tissue cultures (6). The growth surface (5) has a micro-structure and raised areas (9) whose height (A) is less than 110 micrometres and preferably less than approximately 100 micrometres. The micro-structure (8) of the growth surface increases the cell yield, with adherent cells being both optically easily accessible and readily harvested.

Abstract: A method for partitioning an aqueous biological liquid sample into discrete microvolumes for detection and enumeration of microorganisms is described. The method involves distributing microvolumes of a sample to a plurality of hydrophilic liquid-retaining zones of a culture device, where each liquid-retaining zone is surrounded by a portion of a hydrophobic “land” area. Also disclosed are devices for carrying out these methods.

Abstract: An apparatus (1) for measuring physiological parameters has a test chamber (2) having boundaries defined by a first semiconductor chip (3) and a second semiconductor chip (4), between which chips a seal (7) bordering the test chamber (2) is arranged as a distance spacer. The first semiconductor chip (3) has an active side, which faces the test chamber (2) and has planar sensors, on which biological cells (6) located in a nutrient medium can be adherently deposited in order to measure physiological parameters directly on the cells (6). The second semiconductor chip (4) has on an active side, facing the test chamber (2), at least one additional sensor to measure global physiological parameters. The semiconductor chips (3, 4) are held in the sealing position using a mounting (8) that grasps over them on the outer side. Outside of the test chamber (2) the semiconductor chips (3, 4) each have electric connection contacts, which contact with opposing contacts of the mounting.

Abstract: An adjustable-volume, sealed chemical-solution-confinement vessel for enclosing the inner bottom surface of the chemical-solution-confinement vessel within a sealed chamber. The chemical-solution-confinement vessel comprises a well-shaped base into which a complementarily-shaped lid is inserted. The lid can be inserted to a first position, in order to create a small volume sealed chamber above the inner bottom surface of the chemical-solution-confinement vessel, and can be retracted to a second position in order to create a larger volume sealed chamber above the inner bottom surface of the chemical-solution-confinement vessel. The lid may contain a port or aperture for introducing a fluid or material into the sealed chamber.

Abstract: A bacterium can be detected and examined with identification thereof by simply and specifically labeling the bacterium itself without resort to a change in color tone due to the metabolism of a fermentable substrate or the like, whereby there is provided an excellent method of detecting a bacterium with a simple operation, a shortened determination time, an improvement in efficiency and an improvement in detection accuracy.

Abstract: A container for examination and storage of a placenta includes a bottom wall, at least one substantially upright side wall joined to the bottom wall to define an interior and an open top. The side walls and/or the bottom wall have indicia thereon adapted to measure the size of the placenta in three dimensions. Indicia are also provided to measure the umbilical cord. The container is stackable for storage, and labeling areas are provided. A basic method of examining a placenta is disclosed, along with further steps and variations.

Abstract: Device and method for processing biological, biochemical or chemical samples are provided wherein a first multiwell plate is stacked atop a second multiwell plate. The first multiwell plate has x wells arranged in a regular array, each capable of receiving a separate sample. Each well of the x wells has an outlet at a lower surface of the first plate. The second multiwell plate has y wells arranged in a regular array, each well of the y wells being capable of receiving a separate sample, and wherein y>x. The outlets at the lower surface of the first multiwell plate are arrayed to register with corresponding inlets of a subset of the y wells of the second multiwell plate when the first plate is stacked atop the second plate. A mechanism for aligning the first plate to the second plate is provided, as well as transfer indicia for tracking transfer of sample from the first plate to the second plate.

Abstract: Disclosed are methods for producing co-cultures of cells in which at least two cell types are present in a micropattern configuration.

Abstract: A loading station assembly for at least partially supporting the underside of a flexible cell membrane positioned in the bottom of a cell culture well. The assembly includes a planar member having a plurality of apertures. Each aperture receives a post having a flange which supports the membrane. A central opening defined in the planar member allows a vacuum to be drawn therethrough and to pull a portion of the membrane downwardly and cause a central portion of the membrane to stretch across the flange. Cells cultured on the membrane are subjected to a corresponding strain.

Abstract: A patient replica is created from layered culture medium where solid culture medium is formed so that a discontinuity exists, for example, between layers of culture medium or between culture medium and the container holding the medium. An injection port is provided in registration with the discontinuity so that a sample of patient blood can be infused into the discontinuity to form a thin layer of blood in contact with a surface of culture medium. The thin layer of blood obviates the requirement for any anticoagulant allowing blood-borne pathogens to be readily cultured without using broth. Further antibiotics or other drug samples may be placed on an exposed surface of the culture medium above the blood layer so that the antibiotic can diffuse through the culture medium and reveal the sensitivities of the cultured pathogens.

Abstract: A dispensing apparatus is which, even when a small amount of a medium is to be dispensed, can satisfactorily dispense the medium.