CSEM’s know-how in the conception of micro electro-mechanical systems suitable for biological applications (BioMEMS) has led to the development of a portfolio of novel platforms for cell growth. These platforms have been especially developed to host model biological barriers such as the lungs, intestine, skin, cardiovascular system and the blood-brain barrier and feature vastly improved transport properties for the study of drug, nanocarrier and nanparticle uptake. In addition to their improved transport properties the platforms are suitable for remote, continuous non-invasive electrical monitoring of the accommodated biological model.
Technology platform
SIMPLI-Well, (silicon microporous permeable insert-well), insert-like devices – Two chamber devices that are compatible with standard wellplates for cell culture and standard chopsticks electrodes for trans epithelial electrical resistance (TEER) measurements.
ILT standalone bioreactors – Two chamber devices for use with fluidic systems.
In both systems, the two chambers are defined by an ultrathin (less than 1μm) porous support on which a polarized cell layer is grown to confluence. At confluence a tight layer of cells separates the two compartments. The reduced thickness and the finely tunable mechanical properties of the silicon nitride permeable substrate are key features that improve the transport properties of the biological model.
Electronic and microfluidic equipment – The devices can be additionally equipped with electrodes suitable for in situ and continuous measurement of transepithelial electrical resistance (TEER). This non-invasive method can be used to ascertain the quality of the barrier model.
Applications
Co-culture systems and organ models – The reduced thickness of the porous cell culture support makes these devices particularly suitable for model biological barriers based on co-culture systems: epithelial and endothelial cell lines may be grown on the opposite sides of the porous support so that cell contact and cell-cell signaling are maximized while the cell lines are kept separate.
Connected model organ culture – Standalone bioreactors hosting in vitro models of different organs can be connected in series (e.g. liver and intestine, or alveolar / bronchial barriers with the vascular endothelium, etc.).
High quality in-vitro models are urgently required for biological and toxicological studies, drug development, risk assessment of nanoparticles etc. They give insight into the mechanisms of uptake and absorption. They provide an important step towards the reduction and replacement of in-vivo studies.
These tools facilitate the use of in vitro models, for the investigation of:
- The uptake of pharmaceutically active molecules and drug nanocarriers and their subsequent absorption in the human body. Key points for the prediction of their efficacy
- The uptake of engineered nanomaterials through biological barriers as a consequence of volun-tary or involuntary exposure and a better understanding of their fate within the human body with as-sociated toxic effects
Left image: a CSEM SIMPLI-Well in the corner well of a commercial well-plate. It combines enhanced transport properties with standard laboratory protocols: it can be used in the same way as a commercial insert for cell culture (accommodated in the next well in the picture).
Middle image: a disassembled SIMPLI-Well: the silicon nitride porous support is shown. The assembling and disassembling mechanism allows the cell culture support to be flipped, an advantage for some co-culture systems.
Right image: a standalone two-comportment bioreactor accommodating the same kind of porous support combined with a fluidic system and electrical contacts for on-line TEER measurement.