OH-ALIVE: A Commercialization-driven Platform that Advances the Understanding of Cell Culture Processes with Deep Analytics
What Challenges Do You Have?
If you have any of the following challenges, OH-Alive is right for you.
- You want to change from experiments in cell culture that are linear, one-factor-at-a-time to a method that improves knowledge of multiple inputs and reduces time and supply costs.
- You have a desire to reduce hands-on time and operator variability.
- You want the ability to predict how additives will create desirable cell fates in culture.
- Heterogeneous populations of cells are affecting your purity and potency.
- You desire a deeper understanding of your cells so a more precise potency assay for clinical release can be developed.
Overview of Core Facility
OH-Alive merges developmental biology and cell therapeutics with cutting edge hardware, and computerized experimental design and analysis to perform process-specific parameter optimization for customers seeking to develop cell therapies. Implementing Quality by Design (QbD) principles, cell culture optimization is done by utilizing Design of Experiment (DoE) theory combined with Multivariate Data Analysis (MVDA). This allows OH-Alive to generate mathematical models of the biological system, understand the effector-response relationship in cell culture, and provide a systems biology analysis of the differentiation space. DoE-based experimental design and robotic execution greatly reduce the number of experiments and time needed for optimizing a large number of variables simultaneously.
Its methods are more efficient and economical compared to traditional methods and reflect the desires of the FDA for cell manufacturing.
OH-Alive's goals are:
- To transform medical therapy through the use of cells rather than drugs to heal tissues and organs.
- To create world-class commercial and academic infrastructure in Ohio that is self-sufficient, vibrant, and attractive to the biotechnology and cell therapy support industry.
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Innovation in Cell Culture
The scientific community currently performs single-factor optimization work which fails to identify combinatorial effector requirements in cell culture. Classical empirical testing is tedious and expensive, and not optimized for maximal information gathering. OH-Alive uses computerized DoE, executed through robotic media preparation to test the entirety of a multidimensional factor space. MVDA is used to mathematically model the differentiation space tested and identify effector contributions, effector interaction terms, and definitions of optimal conditions for reaching specific cell fates.
OH-Alive has commonly found multi-level interactions terms (detected within 90% confidence intervals) for different signaling pathways it has tested. Identification of even two-factor interactions is challenging with standard experimentation, and when observed, such are rarely provided using a statistical basis and confidence assessment. Identification of three- and four-level factor interactions is unprecedented, and has been achieved thus proving the power and innovation of OH-Alive.
Example of Usage
There is a desire to generate nigrostriatal dopaminergic neurons from pluripotent stem cells for use in Parkinson's Disease. OH-Alive generated an Ectoderm differentiation recipe that achieved 99% conversion to SOX1, PAX6, SOX2 cells in 3 days. Further differentiation of these cells towards neurons in the substantia nigra has begun. Below are images based on this study.