PASCA - Platform for Advanced Single Cell Manipulation and Analysis

The European research project PASCA (Platform for Advanced Single Cell Manipulation and Analysis) was the preceding project for SICTEC.

The central theme of the project was the printing of single biological cells confined in micro-droplets of only one tenth of a millimetre in diameter. The mid-term objective of the seven research institutions and companies working together was to establish a platform for the manipulation, culture, and analysis of individual biological cells without loss of viability. 

Living biological cells and cell cultures are the essential ingredients of a wide arrea of life sciences research, from the genetic basis and mechanism of disease to drug development and drug-cell interactions. So far, cells cannot be easily isolated and systematically analyzed individually. They are commonly manipulated only as an unordered, unsorted, heterogeneous cell assembly often after lengthy periods of cell culture, labelling and isolation. This limits the depth of perspective that can be gained using modern single cell analysis methods, on single cell interactions and on the behaviour of a single cell type in a mixed cell or tissue system. The Single Cell Manipulation (SCM) technology, which will be investigated within the project, promises to open up new opportunities for enhanced life science research, especially in areas such as cell biology, stem cell research, cancer research, drug development, and in the fabrication of artificial organs.

Microsystems technology, as a cross-cutting and interdisciplinary technology provides essential technologies and processes to separate and isolate cells eg. by using sensor controlled methods in microchannels, and uses technologies similar to ink-jet printing to print cells on substrates confined in micro-droplets. Before the vision of a "single-cell printer" can become reality, there are three years of intensive research ahead for the project team. The basic feasibility of the method has been demonstrated experimentally, however reliable and manageable prototypes will be developed, which can be used to explore new and scientifically relevant methods for single cell experiments. In this regard, IMTEK was intensively supported by the project partners Sophion Bioscience A/S (Denmark), University of Dublin, Trinity College (Ireland), Primadiag SAS (France), BioFluidix GmbH (Germany), Zurich Instruments AG (Switzerland) and INNOPROT (Spain). 

A central element of the European Union funded PASCA project, with a budget of about three million Euros was the international collaboration of a team of multidisciplinary scientists. They made the new method for single cell manipulation available to other researchers and to explore new applications together.

 

Project partners:

The pasca project was conducted by a strong project team consisting of the following companies:

University of Freiburg, IMTEK (Germany)

The Department of Microsystems Engineering (IMTEK), University of Freiburg, was the principal technology partner and project coordinator. It has grown to become one of the world’s largest academic institutions in the field of microsystems engineering. With 20 professors and over 300 research and technical staff, its scientific scope encompasses nearly all technical fields relevant to the highly interdisciplinary world of microsystems technology. It has years of experience striking new paths with researchers and developers from other fields. The Laboratory for MEMS Applications is an expert on micro- and nanofluidics, especially on nanoliter and picoliter liquid handling: With its contact-free dispensing technologies fluids in very small doses with high precision can be dispensed. They are even able to cope with delicate media such as dissolved particles or living cells and guarantee high throughput.

Contact: Peter Koltay (peter.koltay@remove-this.imtek.uni-freiburg.de), Melanie Baumann (melanie.baumann@remove-this.imtek.uni-freiburg.de)
Website: http://www.imtek.de/anwendungen/index_en.php

Sophion Bioscience A/S (Denmark)

Sophion Bioscience, headquartered near Copenhagen, Denmark, has the sole focus of providing state of the art products and integrated solutions for automated patch clamping. Sophion develops and sells high throughput patch clamp solutions for functional characterization of living cells. Based on advanced microtechnology, Sophion’s QPatch systems potentially increase patch clamp throughput from 100 up to 1,000 times by a high degree of parallelism and automation. Thus the QPatch combines the accuracy of traditional patch clamp with the high throughput of indirect methods. The QPatch system is currently used in pharmaceutical and biotech companies around the world.

Contact: Jonatan Kutchinsky (jku@remove-this.sophion.dk)
Website: http://www.sophion.dk/

University of Dublin, Trinity College (Ireland)

The Department of Histopathology, Trinity College Dublin (TCD), are part of the PASCA Applications Team. The Department belongs to the School of Medicine and is part of the Institute of Molecular Medicine, St James’s Hospital, with its state of the art Molecular Pathology Laboratories based at The Coombe Women and Infants University Hospital and St. James’s Hospital Dublin. During the PASCA project, TCD will use a variety of techniques including whole genome microarray, low-density array for biomarker expression, immunocytochemistry, SOLiD [2nd generation sequencing] technology and RAMAN spectroscopy to demonstrate the utility of the single cell manipulator (SCM) to isolate single cells for downstream diagnostic and theranostic applications such as the creation of a diagnostic slide based cervical cancer array, the isolation of cancer stem cells from a mixed tumour cell model and the analysis of chemotherapy efficiency in a thyroid cancer model. The TCD team of investigators include: Prof. John O’Leary, Prof. Orla Sheils, Dr. Helen Keegan, Dr. Cara Martin, Dr. Michael Gallagher, Dr. Sharon O’Toole, Dr. Paul Smyth and Dr. Cathy Spillane.

Contact: Prof. John O’Leary (olearyjj@remove-this.tcd.ie), Dr. Helen Keegan (keeganhe@remove-this.tcd.ie)
Website: http://www.medicine.tcd.ie/histopathology/research/

Primadiag SAS (France)

PrimaDiag is a company which develops instruments for research and diagnostic laboratories. In particular, PrimaDiag has developped the PrimaRWS system, a modular platform allowing scientists to easily automate their biological processes. PrimaRWS consists of a set of simple and robust robotic bases on which, depending on the users' experimental needs, different tools can ben mounted (pipettes, spectrophotometer, camera, thermostated block, vacumm pump,...).
PrimaDiag contributes to the PASCA project by bringing its unique know-how, at the interface of robotics and biology. Our company acts both by integrating other partners’ high added value technological bricks on the PrimaRWS system, and by developping additional add-ons aimed at allowing the manipulation of living cells on the Single Cell Manipulator (SCM).

Contact: Guillaume LHERMITE (glhermite@remove-this.primadiag.com)
Website: http://www.primadiag.com/

BioFluidix GmbH (Germany)

BioFluidix GmbH is a micro technology company focused on low volume liquid handling. Our proprietary non-contact technologies are based on micro machined components providing highest quality, throughput and functionality. Our long-standing expertise in working with liquid droplets, jets and sprays in the picoliter to nanoliter range inspired our unique product portfolio which comprises hardware and consumables as well as R&D services. Our leading-edge printing, dispensing and coating solutions enable our customers in life-science research and industrial production to reduce volumes, increase throughput and cut costs. Being a young and innovative company we are dedicated to continuous research and development of our products and performance in order to exceed our customers’ expectations in every respect.

Contact: Wolfgang Streule (wolfgang.streule@remove-this.biofluidix.com)
Website: http://www.biofluidix.com/

Zurich Instruments AG (Switzerland)

Technology-leader Zurich Instruments (ZI) designs and manufactures high performance dynamic signal analysis instruments for advanced scientific research and leading industrial applications. ZI products include lock-in amplifiers, instruments for electrical impedance spectroscopy, and application specific pre-amplifiers. Headquartered in Zurich, Switzerland, ZI is a technology spin-off from the Swiss Federal Institute of Technology (ETH Zurich). ZI customers are scientists and engineers in leading research labs and organizations worldwide.

Contact: Stephan Koch (stephan.koch@remove-this.zhinst.com)
Website: http://www.zhinst.com/

INNOPROT (Spain)

Innoprot, spin-off from the University of the Basque Country, is a biotechnology company focused on the generation of recombinant cell lines and primary cells intended for use in cell-based drug screening. Our efforts are directed to increase speed and efficiency of "in vitro" assays, allowing the collection of more information about the compounds in less time than other biological systems. The types & formats of our products fit the specific needs of the market, allowing the pharmaceutical and biopharmaceutical companies to choose between cell lines for single assays, cell lines for High Content Screening and cell lines for High Throughput Screening.

Contact: Clarisa Salado (csalado@remove-this.innoprot.com), Jorge Gamiz (jgamiz@remove-this.innoprot.com)
Website: http://www.innoprot.com/

Coordinator's office

Please address general remarks and inquiries to the coordinator's office:

Mrs. Melanie Baumann
Department of Microsystems Engineering – IMTEK
University of Freiburg
Georges-Koehler-Allee 103
79110 Freiburg, Germany 

Telephone: +49 761 203 - 73211
Fax: +49 761 203 - 73299

Acknowledgements

The PASCA project team gratefully acknowledges financial funding by the EC within the 7th framework programme within the objective ICT-2009.3.9 “Microinstrumentation for microinjection and cell-manipulation”.