Objectives and results of the first project year (01 Mar 2004 – 28 Feb 2005)
According to the CellPROM workplan the first year’s objectives were grouped in three different fields: deriving and providing an operational and effective non-scientific framework for the project; developing and evaluating feasible device concepts for the different modules and starting first biological cell experiments working towards proof of concepts and evaluating first technological prototypes.
For the technological approach, work was concentrated on the evaluation of existing technology, setting up of overall specifications and deriving concepts for the module implementation. Two different overall concepts have been derived and specified: A magnetic warehouse concept manipulating magnetically value added flat carriers holding adherent cells and a fluidic lab-on-chip-like concept using ultrasound and di-electrophoretic forces for cell manipulation (see following figure). Both concepts will be pursued during the next periods and modules will be developed and evaluated.
Virtual view on a cell trapped in a high frequency electromagnetic field (left) and basic principle schematic of the magnetic warehouse device concept (right).
Images courtesy of FhG-IBMT.
As cell differentiation via immobilised molecules, in analogy to early in-vivo differentiation processes via cell-cell interactions, has not been investigated in great detail before, many issues have to be taken into account and studied. So in parallel to the specification phase biological experiments were conducted and various cell models either with differentiation potential or easy to handle for first technological implementation have been identified and evaluated. Besides cell lines for technological developments and well defined primary differentiation systems for the establishment of cell differentiation assays at the solid phase, adult stem cell systems will be established at many partners labs for the next period, representing more complex but clinically highly interesting models to be implemented into the CellPROM processes at a later stage of the project.
Silicon master prepared by e-beam writing presenting 50 nm posts to be used as mould for nano-imprinting (left). Glass slide with patterned transparent surface (1, 2, 4, 6 µm periodicity) (right.)
Images courtesy of AMO GmbH (left) and INM GmbH (right).
Materials and coatings have been designed with enhanced or suppressed cell adhesion capabilities and tested for biocompatibility. For cell differentiation at the solid phase the surfaces have to meet various new demands: enhanced signal factor binding, topological structuring and bio-patterning. Materials and surfaces (see figure above) as candidates for NanoScapes (or tissue carriers) have been checked for their stability under cell culturing conditions, biocompatibility and compatibility with sterilisation procedures. A positive influence of microstructuring on cell adhesion and cell proliferation could be detected in first experiments, but has to be matured. Further the functionality of bound signal factors could be shown by functional testing through differentiation experiments. These first proofs of principle showed promising results towards differentiation with immobilised factors but have to be matured in future as well.