W. R. Grace Co.-conn.

David M Donofrio

James A Braatz

William F Bowers

Aaron H Heifetz

Scott P Fulton

Richard A Wolfe

Judith A Thompson

Kert F Ivie

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

The cell culturing system of the present invention includes a tubular membrane, e.g. hollow fiber, cartridge. Provision is made for the continuous circulation of a nutrient-containing medium through the tube side of the cartridge by pumping the nutrient-containing medium in an endless loop. The cells to be cultured are placed within the cartridge on the shell side where the desired extracellular products are accumulated. Nutrients are assimilated into the cell culture through the semipermeable tubular membranes and waste products are removed by passing through the semipermeable membranes into the recirculating nutrient-containing medium. Within the endless loop are located a circulating pump, an oxygenator and a pH probe. The system additionally includes a variable delivery feed pump for continuously injecting fresh nutrient-containing solution into the loop, which feed pump is operated at a rate responsive to the measured pH. A portion of the stream exiting the cartridge is continuously split off at a rate identical to that for the introduction for fresh nutrient-containing solution in order to maintain cellular waste products at a suitably low level. The conventional nutrient-solution preparation reservoir has been eliminated from the loop in order to simplify the system and reduce the potential points of entry for contaminating microorganisms. The membrane cartridge is mounted with its longitudinal axis at approximately 60.degree. with respect to the horizontal.

Hollow fiber bioreactor culture system and method

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Rockport, MA, United States of America

David M Donofrio