High Throughput Bioprocess Development Facility

The high throughput bioprocess development (HTBD) facility is the original experimental facility as designed and plan during the AutoBio project and extended in the LEANPROT project.

The facility consists of a Tecan Freedom EVO 200 which hosts a 2mag 48Bioreactor. This unit can operate up to 48 cultivations in a 10 mL scale. The reactors are actively gassed and stirred, the temperature is controlled by a water bath and DOT and pH are measured online. The slim steel needle of the Tecan can enter the mini bioreactors reactors by the off-gas hole. In this way process control and sampling is achieved.

In the back of the Tecan cultivation unit is a Hamilton Microlab Star pipetting robot. The Hamilton is equipped with an eight-position incubator (MWP), 8 and 96 pipetting channel, washing stations for both, vacuum station, active nest (to operate safely with sealed mwp) and a magnetic beet station for his-tag protein purification. In addition, a multi mode plate reader (BioTec Synergy MX II) and a MACS Quant flow cytometer is connected with the Microlab Star.

Both liquid handling station are connected by a linear transfer unit to exchange labware and multi well plates. In this way, samples, taken by the Tecan, are moved to the Hamilton and are directly analysed. We have several protocols on the Hamilton, the most common at-line measurements are, OD, glucose and acetic acid measurements. Both units are also connected on software level and can be control each other by SiLA 2 drivers.

The third pipetting robot in this facility is a second Tecan Freedom Evo 200. This unit host a Hettich centrifuge, and, next to the 8 pipetting arm, a 384 pipetting head. The two Tecan pipetting robots are coupled by a linear transfer unit, too.

© TU Berlin/BVT/Sebastian Hans

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Bringing together the various devices and manufacturers was certainly a major achievement in our work. However, the power of our facility is the central database in the background. For each experiment, all relevant information is stored here. This includes measurement data as well as all setpoins and process parameters required to control the bioprocess. This enables us to retrieve all information at any time, process it and import new, improved process strategies on the fly. This is a fundamental requirement for pursuing our research focus, such as model predictive control.

The hole facility is described in detail in the publication: B. Haby et al., “Integrated Robotic Mini Bioreactor Platform for Automated, Parallel Microbial Cultivation With Online Data Handling and Process Control,” SLAS TECHNOLOGY: Translating Life Sciences Innovation, vol. 24, no. 6, pp. 569–582, Dec. 2019, doi: 10.1177/2472630319860775.

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