FIGURES
Figure 1 : The µSI process analyzer system for MAM sample preparation. (a) The fluidic diagram, (b) Left : The µSI process analyzer system connected to a LC-MS system on the manufacturing floor.Right : Close up view of the upper compartment inside the functionalized µSI process analyzer system.
Figure 2 : The µSI process analyzer system for glycosylation profile assay sample preparation. (a) The fluidic diagram, (b)Left : The µSI process analyzer system connected to a Waters Acquity UPLC system in development lab. Right : Close up to the upper compartment inside the functionalized µSI process analyzer system.
Figure 3 : The A2P2 system. (a) The fluidic diagram, (b) A configured A2P2 system utilizes a commercially available LC system. All components are integrated vertically for efficient use of laboratory footage. (c) The sample preparation unit operation beneath the autosampler in the A2P2 system. (RxN Coil: reaction coil)
Figure 4 : Engineering design of the FTP and its holder. (a)Left : FTV isometric view, cross-section of vial with arrows indicating liquid flow. Middle : FTV holder. Right : Full assembly of vial holder and FTV. (b) The FTV is a key part for the breadth of functionalities in the A2P2 system. The extended gutter and added lip to help prevent surface tension. Extrusion at the end of the gutter is conveniently placed directly over the waste port.
Figure 5 : The logical process developed by utilizing the LC chromatography data system software to enable autonomous operation in the A2P2 system. The uses of SST and IRC workflows enable autonomous and self-directed sample preparation and/or assay execution. (LLOQ: lower limit of quantitation, ULOQ: upper limit of quantitation, SEC: size exclusion, SST: system suitability testing, IRC: intelligent run control)
Figure 6 : (a) The TIC readout from the LC-MS connected µSI process analyzer system demonstrated good robustness over the course of 6 days continuous reference standard processing. (b) The real-time product quality output from a production bioreactor. The trending curves for deamidation and clips generated from the real-time MAM results can be used for process decisions, in-process control, and product release.
Figure 7 : (a) Glycan chromatogram generated from a reference standard processed by the integrated HILIC UPLC µSI process analyzer, full and zoomed view. (b) The performance of the system was verified by daily processing of the reference standard for 32 days. (c) Continuous glycan monitoring of a production bioreactor by the system over the duration of entire upstream bioproduction process.
Figure 8 : Capabilities of the A2P2 system. (a) Aggregation assessment for biological products, (b) Charge variant profile for biological products, (c) Glycosylation profile for biological products, (d) Multi-attribute method for biological products. Out-of-scope flow paths were masked for simplicity.