Determining appropriate input excitation for model identification of a continuous bio-process
Bibliographic record
Abstract
This manuscript addresses the problem of determining input excitation for data driven model identification appropriate for cell culture bio-processes in general, and for an industrial bioreactor used for the production of monoclonal antibodies, in particular. The design space is set up to give us the operating parameters for the key objective of demonstrating the feasibility of using far more perturbations than typically done in bio process identification, although significantly less than other applications, to yield data rich enough for the purpose of data driven modelling (and subsequently, control). A proprietary mechanistic model developed by Sartorius for their Cellca cell line is first introduced to serve as a test bed, based on AMBR 250® (Sartorius registered trademark for integrated high throughput bioreactor systems). Subsequently, this test bed is used to address the question of determining the frequency of input perturbation sufficient to identify a data driven dynamic model. To this end, the test bed is used to generate data at various frequencies and a linear time invariant model identified. The predictive capability of the identified model is used to ascertain the frequency of changes in data generation such that the changes are acceptable from a biological standpoint, and yet generate sufficiently rich data. In particular, a frequency of perturbations at once every three days is found to balance these tradeoffs for the monoclonal antibody process under consideration. The results from the manuscript are meaningful both from a specific results standpoint (as illustrated by subsequent adoption by Sartorius), but also by providing a mechanism to ascertain such information for other bio-processes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".