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Oct 26, 2017 - www.toulouse-white-biotechnology.com. Céline Jouanin – Anthony Vollant ... Environmental parameter optimization. Process optimization.
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Version 2017-10-23

Céline Jouanin – Anthony Vollant – Amélie Briane 2017-10-26 Rencontre IngéStats

Julien Cescut

TECHNOLOGY PLATFORMS OF TWB

Strain engineering

Biotransformation & culture

Process development

Analytic Bio-informatic Environnemental Evaluation Ethic www.toulouse-white-biotechnology.com

1

BIOTRANSFORMATION FROM 50 mL TO 200L

50 mL

500 mL

200 L

20 L 2L

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2

THE NEED TO SCREEN Strain evaluation Environmental parameter optimization Medium optimization Process optimization bottleneck

Up & down process optimization Process robustness optimization

Time consuming

Industrial approved

10n combinaisons

HTS 3

THE SOLUTIONS Miniaturisation

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THE SOLUTIONS

Parallelization

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THE SOLUTIONS

Automatisation

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CUSTOM ROBOTIC PLATEFORM

X

X

ROBOTIC MOVEMENT PROGRAMMING

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MAIN WORKFLOW

I

II

Preculture

Conditionnal seeding

III

Culture process 1-50

IV

Sampling

Sample processing

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I PRECULTURE PHASE Incubation in plate reader (Xenius, Safas)  monitoring of optical density

Preculture

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II SEEDING PHASE Communication between reader and liquid handling robot  Conditionnal seeding

Conditional seeding

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III CULTURE

Overview of numerous signals  regulator adaptation to the biological kinetics Culture process

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IV SAMPLING

Sampling

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SAMPLE PROCESSING

Cytometry, CDW, biobank total sample

HPLC, GC-MS Filtration; centrifugation

- 20 °C to + 4 °C Sample processing

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RAW DATA

MULTIFACTOR OPTIMIZATION Statistics exploitation of DoE with R, JMP Glucose

Cartography

Acetic Acid

+

Optimum : • 37.4 °C • 7.1 upH

µmax DO

Validation in 20 L (not shown) 16

DATA PROCESSING Acquire data Analysis - Automatisation Reformat and clean data Preparation

Execute scripts

Filtering Algorithm

Edit analysis scripts

Quality indicators Vizualization

Explore alternatives

Debug

New project New equipment New Analysis

Make comparison New idea Meeting Reflection

Inspect outputs Distribution&Storage Report Share experiment Archive experiment in database 17

CONCLUSION • Custom design of fermentation robotic plateform • 24 instrumented mini-reactors • Automatisation steps from preculture to supernatant separation  Acceleration of best strain or optimal environmental parameters finding  In progress: implementation of automatic data/file processing and database setting up 18

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THANK YOU

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