Scale-out of massively parallel patient-specific cell cultures with a modified transportable conditioned cell culture chamber

Barrier Isolators, which separate the cell culture processing atmosphere from the bioburden of personnel, are the best means to reduce contamination risks. These isolators are currently being used for cGMP-compliant clinical trials1, 2. Scaling cell production processes presents non-obvious restrictions to most people. Compared to open processing, modular Cytocentric isolators can be replicated to scale proportionately with each stage in cell processing until all steps are accommodated maximally. This allows a process to efficiently and quickly scale with operations from pre-clinical through clinical studies3. However, for processing of massively parallel patient-specific cell cultures, incubation capacity in a barrier isolator, unlike in the open room, can be a bottleneck. Inexpensive and infinitely elastic incubation capacity can be provided by existing external incubators if cultures can be safely transported to and from the isolator for processing. We tested a modified transportable conditioned cell culture chamber (TC4) designed to enclose cell cultures inside the exterior incubator and fit through the airlocks of the barrier isolator to safely deliver cells to the interior for processing. We have previously published on good cell growth using this processing system to expand K562 cells, a hematopoietic stem cell-like cell line that has been used as a surrogate for CAR-T cell processing. In this study, we addressed sterility concerns by running mock production runs with a highly permissive color-changing bacterial broth. We ran three production runs, moving mock cultures between the barrier isolator and the external incubator with the TC4 transport chamber. We took samples of the final mock cell product, sealed them into sterile vials, and incubated them long-term, monitoring for bacterial growth. We also performed environmental monitoring of the barrier isolator processing chamber with an air sampler and contact plates. Positive control samples were all yellow and turbid. Negative samples and all test materials were negative for microbial growth. We concluded that this transport chamber could help safely alleviate the bottleneck in cell production presented by the unique needs of massively-parallel patient specific cell incubation. References: Mei, S.H., et al., Isolation and large-scale expansion of bone marrow-derived mesenchymal stem cells with serum-free media under GMP-compliance. mortality, 2014. 40: p. 1. Marathe, C.S., et al., Islet cell transplantation in Australia: screening, remote transplantation, and incretin hormone secretion in insulin independent patients. Horm Metab Res, 2015. 47(1): p. 16-23. Yufit, T., P. Carson, and V. Falanga, Topical Delivery of Cultured Stem Cells to Human Non-Healing Wounds: GMP Facility Development in an Academic Setting and FDA Requirements for an IND and Human Testing. Current drug delivery, 2014. 11(5): p. 572-581

The Time-resolved Atomic, Molecular and Optical Science Instrument at the Linac Coherent Light Source

The newly constructed Time-resolved atomic, Molecular and Optical science instrument (TMO), is configured to take full advantage of both linear accelerators at SLAC National Accelerator Laboratory, the copper accelerator operating at a repetition rate of 120 Hz providing high per pulse energy, as well as the superconducting accelerator operating at a repetition rate of about 1 MHz providing high average intensity. Both accelerators build a soft X-ray free electron laser with the new variable gab undulator section. With this flexible light sources, TMO supports many experimental techniques not previously available at LCLS and will have two X-ray beam focus spots in line. Thereby, TMO supports Atomic, Molecular and Optical (AMO), strong-field and nonlinear science and will host a designated new dynamic reaction microscope with a sub-micron X-ray focus spot. The flexible instrument design is optimized for studying ultrafast electronic and molecular phenomena and can take full advantage of the sub-femtosecond soft X-ray pulse generation program

2016 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1003/thumbnail.jp