Methods for controlling a biological manufacturing system include directing a light beam to pass through a wall of a vessel containing a first fluid generated by the biological manufacturing system, measuring an angle of refraction of the light beam in the first fluid, the angle of refraction corresponding to an angle between a propagation direction of the light beam in the first fluid and a normal to an interface between the vessel wall and the first fluid, determining information about the first fluid based on the measured angle of refraction, and adjusting a parameter of the biological manufacturing system based on the information about the first fluid.

A parallel assembly (2; 11; 51) of chromatography column modules (3a,b,c; 13a,b,c; 53a,b,c, 90a, b) connected in a rigid housing (21; 61), the assembly having one common assembly inlet (15; 55) and one common assembly outlet (17; 57), each column module comprising a bed space (29) filled with chromatography medium and each column module comprises integrated fluid conduits which when the column module is connected with other column modules in the rigid housing are adapted to connect the bed space (29) of the column module with the assembly inlet (15; 55) and the assembly outlet (17; 57), wherein the total length and/or volume of the fluid conduit from the assembly inlet to one bed space together with the length and/or volume of the fluid conduit from the same bed space to the assembly outlet is substantially the same for all bed spaces and modules installed in the parallel assembly.

A parallel assembly (2; 11; 51) of chromatography column modules (3a,b,c; 13a,b,c; 53a,b,c, 90a, b) connected in a rigid housing (21; 61), the assembly having one common assembly inlet (15; 55) and one common assembly outlet (17; 57), each column module comprising a bed space (29) filled with chromatography medium and each column module comprises integrated fluid conduits which when the column module is connected with other column modules in the rigid housing are adapted to connect the bed space (29) of the column module with the assembly inlet (15; 55) and the assembly outlet (17; 57), wherein the total length and/or volume of the fluid conduit from the assembly inlet to one bed space together with the length and/or volume of the fluid conduit from the same bed space to the assembly outlet is substantially the same for all bed spaces and modules installed in the parallel assembly.

A parallel assembly of chromatography column modules, the assembly having one common assembly inlet and one common assembly outlet, each column module comprising a bed space filled with chromatography medium and each column module comprises integrated fluid conduits which when the column module is connected with other column modules are adapted to connect the bed space of the column module with the assembly inlet and the assembly outlet, wherein the total length and/or volume of the fluid conduit from the assembly inlet to one bed space together with the length and/or volume of the fluid conduit from the same bed space to the assembly outlet is substantially the same for all bed spaces and modules installed in the parallel assembly.

Provided herein are methods of reducing bioburden of (e.g., sterilizing) a chromatography resin that include exposing a container including a composition including a chromatography resin and at least one antioxidant agent and/or chelator to a dose of gamma-irradiation sufficient to reduce the bioburden of the container and the chromatography resin, where the at least one antioxidant agent and/or chelator are present in an amount sufficient to ameliorate the loss of binding capacity of the chromatography resin after/upon exposure to the dose of gamma-irradiation. Also provided are reduced bioburden chromatography columns including the reduced bioburden chromatography resin, compositions including a chromatography resin and at least one chelator and/or antioxidant agent, methods of performing reduced bioburden column chromatography using one of these reduced bioburden chromatography columns, and integrated, closed, and continuous processes for reduced bioburden manufacturing of a purified recombinant protein.

The invention relates to a process for the chromatographic purification of a starting stream containing ammonium sulfate and 2-hydroxy-2-methylpropionic acid, comprising: passage of the starting stream through a bed of stationary phase; elution of a raffinate enriched in ammonium sulfate and depleted in 2-hydroxy-2-methylpropionic acid; and elution of an extract enriched in 2-hydroxy-2-methylpropionic acid and depleted in ammonium sulfate.

Provided is a method for control and/or monitoring and/or optimization of a chromatographic process, in which the method comprises at least 2 columns which are operated, alternatingly, wherein this operation can be carried out in that the at least 2 columns are operated in interconnected and disconnected states, wherein the columns switch positions after such a sequence of interconnected and disconnected state, and wherein downstream of at least one, or of each column, a detector is located capable of detecting the desired product and/or impurities when passing the detector.

Systems for measuring a product quality attribute of an analyte of a biological sample include a first flow control device, a sample purification device, a second flow control device in fluid communication with first and second sample analyzers, where the first sample analyzer includes a first chromatography column, and a control unit configured so that during operation of the system, the control unit adjusts a configuration of the second flow control device to direct a portion of the biological sample to one of the first and second sample analyzers, and determines a product quality attribute of an analyte of the biological sample based on an analysis of the portion of the biological sample by the one of the first and second sample analyzers.

Systems and methods for efficient, effective, and safe separation and isolation of multiple isotopes (e.g., Mo, Zr, Ba, Sr, Te, and lanthanide isotopes) from fission products includes use of a plurality of chromatography columns, each containing a chromatographic resin formulated to target one or more particular isotopes. The system is operable in a series configuration to load the multiple columns by a single pass of the sample. Then, the system may be transitioned (e.g., using valves) to a parallel configuration in which multiple columns of the system may be operated simultaneously to elute targeted isotopes. Additional parallel operations of the columns, using different eluent compositions, may be used to elute different targeted isotopes. The system may be reconditioned in preparation for a subsequent sample.

A liquid chromatographic (LC) system is introduced which comprises at least one fluidic stream, the fluidic stream comprising a sample-injection valve, a trap-bypass-selection valve, a column-bypass valve, a load-elute valve and a trap-selection valve. Also, a liquid chromatographic (LC) system is introduced which comprises at least one fluidic stream. The fluidic stream comprises a first substream and a second substream. The first substream comprises a first sample-injection valve, a load-elute valve and a trap-selection valve. The second substream comprises a second sample-injection valve and a column-bypass valve. The fluidic stream further comprises a trap-LC substream transfer valve and a substream-selection valve. The LC systems provide a broad choice of chromatographic options and modes and enable to flexibly and rapidly switch between them.