Orbital Biosciences, LLC

W. R. Grace Co.

Agilent Technologies, Inc.

Millipore Corporation

W. R. Grace Co.-conn.

Biosystem Development, LLC

William F Bowers

Scott P Fulton

Basil Yankopoulos

Robert J Sakowski

Timothy Towle

Stephen G Hunt

Douglas B Tiffany

Peter N Rigopulos

David M Donofrio

Judith A Thompson

Kert F Ivie

The present invention relates to an improved system for efficiently and accurately performing immunoassays, such as ELISAs. The invention provides an immunoassay assembly which includes a flow-through unit and an aspiration pump. The immunoassay flow-through unit includes an outer seal; at least one bed support; an inner seal; and a packed non-porous bed. The unit is releasably attached to an aspiration pump which enables the controlled flow rate of liquid passing through the packed bed of the flow-through unit. The invention also provides a method of using the immunoassay assembly to identify analytical targets of interest.

Immunoassay assembly and methods of use

Methods and devices are provided for preparing and separating biological analytes. In one embodiment, one or more filtration devices or filter plate wells can be formed by clamping a filter sheet between first and second plates having at least one connecting cavity. First and second moveable core pins positioned on opposed sides of the sheet can be moved to remove portions of the sheet. A molten plastic can be injected to fill the volume between the cores and cavities and to form a liquid-impermeable sleeve wall or walls, each being separately sealed at the bottom to the perimeter of the sheet portion, each having liquid permeable regions of said removed and sealed sheet portion, and each remaining open at the top. Various exemplary configurations for filtration devices or filter plate wells are also disclosed.

Small volume unitary molded filters and supports for adsorbent beds

An ultrafiltration device has a ported reservoir body, and a filter membrane sealed to the body along a closed contour surrounding the port(s) to provide a large area filtered outflow path. A frusto-conical end provides hydrostatic deadstopping with little or no wicking, greatly enhancing recovery time and efficiency. Methods of using the device rapidly isolate a predetermined amount of a desired retentate in the distal portion of the tube, and are also useful for quantitative transfer of smaller molecules and for multi-step processing of sample arrays Linear array strips of such chambers may be formed by bonding together mating halves with filter areas over the chamber ports. The vessel may include a rib to guide and orient filter during assembly, and/or a ledge or recess to engage and align the filter, assuring that the filter is precisely positioned and does not wander during manufacture and bonding. The vessels have a high filter area to volume ratio, maintain open filter surfaces and high rates of filtration throughout the spin, and are fully compatible with robotic loading, multistage operation and in situ multiwell plate filtrate and/or retentate assay or transfer. Attachment of the filter may be effected by heat welding. Preferably the vessel and filter are positioned between a press member and a heat sink and a superheated tool contacts the press member to selectively deliver a defined bolus of heat to the weld areas.

Ultrafiltration device and method of forming same

An ultrafiltration device has a filter membrane sealed inside a reservoir body that has one or more ports and a closed portion distal to the port(s), and the filter membrane is sealed to the body along a closed contour widely surrounding the port(s) to provide a large area filtered outflow path. The method is effective to rapidly isolate a predetermined amount of a desired retentate in the distal portion and is also useful for quantitative transfer of smaller molecules and for multi-step processing of sample arrays. A frusto-conical peripheral filter provides high ratio of effective filter area, and may be configured for hydrostatic deadstopping and little or no wicking, greatly enhancing recovery time and efficiency. Novel constructions and methods of manufacture enhance filtration or separation vessels of various sizes.

A reusable microconcentrator device may be disassembled, cleaned and reassembled before use. The microconcentrator device of the invention is typically useful in filtering and separating small samples of solutions and suspensions. The microconcentrator device of the invention includes an elongate sample sleeve, a base element which can be removable and replaceably coupled to a centrifugal portion of the sleeve, a compliant membrane compressing feature, and a disposable membrane. Preferably, the base element includes an O-ring which compresses the membrane to seal it to the centrifugal surface of an annular ledge portion of the sleeve, which also forms a deadstop. Among the advantages of the microconcentrator device of the invention is that a reliable retentate volume remains following filtration. The elements of the microcentrator device can also be permanently assembled to one another.

Microconcentrator device

A sanitary slider valve shown specifically as a rotary carousel diaphragm valve which has a thermoplastic elastomeric diaphragm integrally molded to form the multiple sealing ports of the rotor/stator interface is described. Ports or grooves molded into the face of the elastomeric diaphragm are positioned to sealably engage grooves or ports in the stator face, and to form sanitary elastomeric tubular ducts leading through the body of the rotor or of the stator, terminating as elastomeric flanges. These flanges permit direct connection to sanitary flared piping flanges within the carousel which lead to and from multiple columns or other solid phase bed segments, or to sanitary flared piping flanges connecting the stator to piping interconnecting the multiple carousel columns to each other and to external supply and collection lines. Sanitary operation is made operable by energized flexible diaphragm wiping lip seals which maintain fluid-tight sealing engagement with the opposing face even when the rotor is lifted off the stator far enough to permit cross flushing of the port sealing faces with sanitizing fluid. The valve permits sanitary operation of advanced chromatographic separations of biopharmaceuticals, including simulated moving bed chromatography.

Sanitizable slider diaphragm valve

An integrated system and method are disclosed for filtering a fluid and for dispensing a desired volume of the fluid. The integrated system includes a feed pump sub-assembly for receiving fluid and for directing the fluid through a filter. A filtration sub-assembly is joined with the feed pump sub-assembly for receiving fluid from the feed pump sub-assembly and for housing the filter. A dispense pump sub-assembly is integrally joined with the filtration sub-assembly and defines a dispense chamber for receiving filtered fluid from the filtration sub-assembly. The dispense pump sub-assembly includes a dispensing means which is moveable from a fill position to a purge position for purging at least a portion of any gas bubbles from the dispense chamber. The gas bubbles are purged through a purge outlet disposed above a fluid inlet and a fluid outlet of the dispense chamber. The dispensing means is also moveable from the purge position to a dispense position for dispensing a desired volume of the fluid from the integrated system.

Integrated system for filtering and dispensing fluid having fill,

The present invention relates to a multiwell apparatus for biological and biochemical analysis which provides for separate collection of filtrate from each well, without cross-contamination therebetween. The present invention provides a manifold plate having an array of filtering wells, each of the wells being closed at its bottom by a planar bottom member providing a filter support surface. A discharge nozzle of passageway depends from each well bottom (planar bottom member) in a direction normal thereto, with one such discharge nozzle or port being provided in fluid communication with each filtering well. Each of these filtrate nozzles or drain ports extends from the lower surface of the planar bottom member to such an extent that it will enter into the well of a conventional multiwell, e.g., microtiter, plate in alignment therewith and mate with the sidewall of the aligned well of the multiwell plate. In this manner, the filtrate can be delivered to the collection well of the multiwell plate as a steady stream, in the manner one would use a pipette, rather than dropwise. The ability to quantitatively collect filtrate into a receiving multiwell plate provides options for improved immunoassays, nucleic acid probe assays and other test procedures.

Microfiltration apparatus with radially spaced nozzles

A filtration apparatus and method is disclosed, the apparatus including a container tube for holding a sample to be filtered and a filtering vessel inserted therein. The filtering vessel carries a filter over its lower end and includes a chamber portion for receiving the filtrate. The method includes forcibly immersing the filtration vessel into the container tube, limiting the relative axial position therebetween, and subjecting the apparatus to centrifugation. The apparatus and method is useful for filtering dilute, concentrated and particle-laden samples.

Centrifugal force-enhanced filtration of fluids

Disclosed is an apparatus and method for using the apparatus to centrifugally recover a maximal amount of concentrated macromolecular retentate.

Apparatus and method for centrifugal recovery of retentate

Disclosed is a centrifugal microconcentrator and methods for using the microconcentrator to concentrate macromolecules from a solution without filtering to dryness and to centrifugally recover a maximal amount of concentrated macromolecular retentate.

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Topsfield, MA, United States of America

William F Bowers