Project: Multi-parameter, end to end cell monitoring platform for continuous monitoring of adherent and suspension cell cultures

Project goal and background:_x000D_The manipulation of cells COtained ex vivo requires a strict control of culture conditions that may affect cell behavior. A reliable, cost effective system to monitor cell culture environments requiring minimal human handling would represent a real breakthrough in the biotechnology field. The ideal system should enable noninvasive continuous monitoring of multiple parameters relevant to cell growth (e.g. temperature, CO2, O2, pH, glucose concentration and other nutrients) to achieve quality cell growth in a safe, reliable and economical way. Also, it should instantly detect any change in cell environment and inform the operator in order to COtain the optimal conditions._x000D__x000D_In parallel, the increasing adoption of single use technology in biopharmaceutical, vaccine, and cell therapy production is one indication that such technology has moved far beyond its novelty stage. Undoubtedly, this is nowadays the preferred technology of newly developed processes such as biosimilars that are demanding greater speed and economy in process development [1]. Single use products and the systems employing them have become a standard in bioprocess development [2]._x000D__x000D_For this reason, gymetrics has positioned its offer on single use cell culture vessels where the target market has an acute lack of tools for process management and research. Also, gymetrics is investing in the development of a versatile end to end multi-parameter monitoring platform of adherent and suspension cell culture bioprocesses in incubators relying both on Radio Frequency IDentification (RFID), and optical biosensing technologies. _x000D__x000D_RFID is today the corner stone technology for pet identification, asset tracking, access control or theft prevention applications. It is well known, widely spread and consequently affordable, especially for applications where "disposability" is required. gymetrics is developing an optical biosensor based on the combination of a color sensor and a thin film containing a pH-sensitive indicator dye. In contact with the cell culture medium, the film exhibits a gradual colorimetric response to pH. The pH biosensor comprises light emitting diode sources (LED) and a digital color sensor measuring the optical absorption of the pH-induced color change of the thin film at 1 or 2 discrete wavelengths. The 2 CO advantages of this approach are limited technological developments for electronics (i.e. color sensor and LEDs are consumer market products) and in the end an all-digital pre-calibrated solution that can be sterilized by standard methods._x000D__x000D_The envisioned platform will be suitable for all cell culture types, i.e. adherent and suspension cell cultures, including multiple orbitally shaken culture flasks, single- and multi-well Petri dishes, disposable and non-disposable bioreactors, and also for downstream applications in the future._x000D__x000D_The project consortium will focus on the development of i) a miniature single use multi-parameter RFID biosensor, ii) dissolved oxygen- and carbon dioxide-sensitive dies, and iii) a multi-antenna RFID base transmitter optimized to interrogate RFID biosensors located in its neighborhood in various configurations (shaken flasks, stirred bioreactors, single- and multi-well Petri vessels) and to send the data collected out from the incubator to a remote workstation._x000D__x000D_Technical and market applications:_x000D_Cell culture capacity has grown from less than 300’000-L pre-2000 to around 3 million-L today, impelled by the requirements for Monoclonal Antibodies [3]. Cost and flexibility considerations have driven the Biotech industry increasingly to disposable bioreactors and the sales of these are expected to grow from around $200 m in 2012 to over $1 bn in 2017. A technology gap reCOs however in the monitoring of the disposable bioreactors. Probes are offered for certain bioreactors by companies such as Presens and Sartorius Stedim but require frequent calibration and are subject to drift and breakage [4]. Each probe provides a discrete measurement and no multi-parameter measurement in a single sterile disposable miniature biosensor is available. This is a drawback in smaller containers where sometimes only one parameter can be measured per container._x000D__x000D_General description of the consortium: _x000D_The project consortium comprises 2 Ps, gymetrics (CH) and Maatel (F)._x000D__x000D_gymetrics is a spin-off of the EPFL’s Stem Cell Dynamics Laboratory. Incorporated in 2011 it is a user focused technology company. Its technical expertise ranges from biology, chemistry, electronics to wireless communication._x000D__x000D_Maatel was incorporated in 1976 and its expertise lies in the field of design and manufacturing of custom-made electronic products.

Acronym	cytOsens (Reference Number: 7811)
Duration	01/06/2013 - 31/08/2015
Project Topic	The project aims to develop a versatile platform for continuous multi-parameter monitoring of adherent and suspension cell culture bioprocesses in incubators. The innovative topics are miniaturization, optimized RFID, robust optical biosensing to enable wireless disposables in R&D and manufacturing.
Project Results (after finalisation)	Maatel has contributed to develop the electronic parts concerning two products used in biologic experimentation. Based on the same design, the first has been developped for industrial biologic reactor and the second product has been developped for experimentation in PETRI boxes and Tflask boxes._x000D_Using the RFID technology those products are perfectly adapted to provide continously measurements of temperature, conductivity and in some time O2 during experimentation in biologic incubator._x000D_Those products insure an experimentation without trouble due to the actions of opening and closing the door._x000D_Maatel was responsible for the design and development of the hardware and software part of the acquisition part, the RFID transfert between Tflask or PETRI boxes and the treatment of the informations sended on USB or other electronical networks. The tasks include casing and electronic conception, documentation and manufacturing up to prototype validation for the hardware and sotfware part.
Network	Eurostars
Call	Eurostars Cut-Off 9

Project partner

Number	Name	Role	Country
2	gymetrics SA	Coordinator	Switzerland
2	Maatel SAS	Partner	France