Praxair Technology, Inc.

Sp Industries, Inc.

Promega Corporation

Pure Biosolutions, LLC

Nigel Grinter

Balazs Hunek

Robert Rex Sever

Theodore Hall Gasteyer

Ying Zhou

Melinda Lee Verdone

Amitabh Gupta

Alan T Y Cheng

Alan T Cheng

Daniel Robert Gentry

Richard W Carter

Yeu-Chuan Simon Ho

Peter W Latham

Martin Rosenburg

Theodore Hall Iii Gasteyer

Alan Ty Cheng

System and method for lyophilization or freeze-drying is provided. During the freezing step, the material or solution to be frozen is initially brought to a temperature near or below its freezing temperature after which the pressure in the freeze-dryer chamber is reduced to induce nucleation of the material.

Lyophilization system and method

Methods of inducing nucleation of a material is provided. The disclosed methods comprise the steps of bringing the material to a temperature near or below a phase transition temperature and altering the pressure to induce nucleation of the material. The disclosed methods are useful in freeze-drying processes, particularly pharmaceutical freeze-drying processes.

Method of inducing nucleation of a material

A bioreactor with an upward flowing impeller system for controlling a mammalian cell culture process is provided. The disclosed system enables control of the cell culture process by controlling the level of dissolved carbon dioxide in the cell culture media and prevent increases in the osmolality level is achieved by enhanced stripping of carbon dioxide via surface gas exchange with little or no damage to the mammalian cells. The use of an upward flow impeller combined with vertical baffles converts the swirling motions of the cell culture media into a largely vertical flow and promotes the removal of dissolved carbon dioxide via surface gas exchange with a sweep gas flowing over the top surface of the cell culture media within the bioreactor vessel.

Bioreactor with upward flowing impeller system for use in a mammalian cell culture process

Methods and systems for virus inactivation in the production or processing of biological or other sensitive substances are provided. The disclosed methods and systems for virus inactivation involve the key steps of dissolving carbon dioxide into biological or other sensitive substances; and treating the substance with the dissolved carbon dioxide at conditions which are less than critical pressure and temperature for a prescribed treatment time to inactivate at least 80% of the target virus or viruses contained within the biological or other sensitive substances. The disclosed carbon dioxide treatments for virus inactivation may optionally include concurrently or sequentially subjecting the substances with an acid treatment to lower the pH of the substance and inactivate viruses contained within the biological or other sensitive substance. Operating conditions for the disclosed carbon dioxide treatments preferably involve sparging carbon dioxide gas into the substance until the composition is saturated with carbon dioxide and is conducted at pressures below about 5 MPa; at temperatures of less than or equal to 30&#xb0; C.; and for a treatment time of between about one minute and about 2000 minutes.

System and method for virus inactivation

A method and system for controlled rate freezing and nucleation of materials is provided. The presently disclosed system and method provides the ability to rapidly cool the materials contained in vials or other containers within a cooling unit via forced convective cooling using a laminar and uniform flow of cryogen in proximity to the plurality of vials disposed within the cooling unit. The rapid cooling of the biological materials is achieved by precisely controlling and adjusting the temperature of the cryogen being introduced to the system as a function of time. The presently disclosed methods to systems also provide nucleation control via temperature quench and depressurized nucleation control.

Method and system for nucleation control in a controlled rate freezer (CRF)

A system and method for controlling a mammalian cell culture process are provided. Such control of the cell culture process involves control of the level of dissolved carbon dioxide in the cell culture media and the resulting ability to prevent increases in the osmolality level is achieved by enhanced stripping of carbon dioxide with little or no damage to the mammalian cells. The disclosed methods and systems of dissolved carbon dioxide stripping include enhanced surface gas exchange mechanisms within the bioreactor vessel through the use of an upward flow impeller combined with vertical baffles to convert swirling motions of the liquid into a largely vertical flow.

System and method for controlling a mammalian cell culture process

Methods for controlling the level of dissolved carbon dioxide and limiting osmolality in a mammalian cell culture process to enhance cell growth, viability and density, and increase biologic product concentration and yield are provided. Such control of the level of dissolved carbon dioxide and pH as well as the resulting ability to limit osmolality in a mammalian cell culture process is achieved by adopting alternative pH control strategies and COstripping techniques during a mammalian cell culture process. Such pH control techniques and carbon dioxide stripping occur without foam and with little or no damage to the mammalian cells.

Method for controlling pH, osmolality and dissolved carbon dioxide levels in a mammalian cell culture process to enhance cell viability and biologic product yield

Methods for specific RNA capture, detection and quantification are presented utilizing a protein that selectively binds RNA:DNA hybrids, preferably an RNase H that is modified to reduce degradation of the nucleic acid molecules and enhance specific detection of mixed RNA:DNA nucleic acid hybrids. Labeling of the RNA and/or amplification is not required to perform these methods. Modified RNase H enzymes useful in such methods are disclosed.

Growing community of inventors

Buffalo Grove, IL, United States of America

Nigel Grinter