In biotechnologischen Laboratorien ist die Qualitat der typischerweise pharmazeutischen Produkte ein wortwortlich lebenswichtiges Ziel. Die Qualitat der Zellkultivierungen wurde historisch nur durch off-line Messungen von physikalischen Prozessparametern wie pH und pO2 sichergestellt. Biologische Parameter wie die Zelldichte und -viabilitat wurden nur off-line gemessen, weil das dazu notwendige Probenmanagement hochkomplizierte Manipulationen und Analysen beinhaltet und deshalb nicht automatisiert werden konnte. Es gibt zwar mehrere automatisierte Gerate, um einem Labortechniker zu assistieren, aber kein System, welches das gesamte Probenmanagement automatisiert. In dieser Arbeit wird ein neuer Typ von Serviceroboter prasentiert, der aus einem auf einer mobilen Plattform montierten Roboterarm besteht und diese Lucke schliest.
Dieser Roboter muss eine ganze Reihe von Problemen bewaltigen: Er muss seine Position im Labor bestimmen konnen (Lokalisation), er muss eine kollisionsfreie Bahn zu den beteiligten Geraten finden konnen (Bahnplanung mit Hindernisvermeidung), er darf bei seinen Bewegungen keine Menschen gefahrden oder Laborausrustung beschadigen (Kollisionsvermeidung), er muss die zu bedienenden Gerate erkennen und ihre Position prazise messen konnen (Bildverarbeitung), er muss sie bedienen konnen (Armsteuerung), er muss Objekte greifen konnen (Greifer und Finger) und er muss sie gefugig handhaben konnen, um sie nicht zu beschadigen (Kraftregelung). Er muss autonom sein, um nur die allernotwendigste Menge an Benutzereingriffen zu benotigen, und doch durch ein Laborsteuerprogramm kontrollierbar sein, um Eingriffe zu erlauben. Schlieslich muss er einfach durch ungeschultes Personal zu warten sein. All diese Aspekte werden von dem in dieser Arbeit prasentierten neuen Robotersystem abgedeckt.

A mobile service robot for automisation of sample taking and sample management in a biotechnological pilot laboratory

A newly developed Protein-Processing Platform (3P) for cell cultivation and sample handling is presented. The 3P-concept is based on a 6-well microtiter plate for cell cultivation, an autoclavable top plate as a sampling system using a new kind of microvalve and an x-y-z-plotter to manage the sample handling procedures. Furthermore, the sample can be stored in a water-cooled deep well plate and transported to a detector e.g. by addressing a dedicated protein chip based on a Black-Silicon structure. The function of microvalves is based on the swelling behavior of hydrogel depending on its temperature. The regulation system of this temperature is integrated into the 6-well microtiter top plate. In this paper, the realization of this concept is exemplarily carried out using the cultivation of hybridoma and their production of monoclonal antibodies. The cultivation conditions were not optimized. However, using different mixing methods, their influence on the antibody production was investigated. The best cell growth was observed in the dormant 6-well microtiter plate. As under these conditions, a gradient of antibody concentrations occurs, the depth of immersion of the sampling probes has to be investigated. A reproducible sampling was possible by withdrawing the sample from the middle of the cell suspension level. Procedures for sampling and washing under sterile conditions were developed using the tools of the x-y-z-plotter. The optical detection of the samples can be performed using the new protein chip based on the Black-Silicon technology in any kind of commercial reader. It is possible to integrate the single modular components of the platform into every protein expression process. Additionally, the adaptation of the sampling system to commercial microtiter plates guarantees a wide range of applications.

Protein-Processing Platform (3P) – a New Concept for the Characterization of Cell Cultures in the mL-Scale Using Microfluidic Components

In mammalian cell culture technology the last key issue for a completely automated process is the taking, analysing and storing of a sample from the bioreactor. It was necessary to develop a new device which fulfils the need to be steam sterilizable for an application in industrial production environment. The status of the culture is derived from the results of the analysed parameters of these samples. The normal procedure includes determination of the total and viable cell densities in relation to the media parameters (glucose, lactic acid, ammonia). The cell densities are retrieved by counting a stained cell sample. A cell free aliquot is stored in a freezer for further analyses (e.g. amino acids and product). Information for optimisation of feed and harvest strategies can be retrieved from the analysed parameters additionally.

Robot Automation of Sampling and Sample Management during Cultivation of Mammalian Cells in Pilot Scale

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Robot Automation of Sampling and Sample Management during Cultivation of Mammalian Cells in Pilot Scale