By using 96-well plates, CellSine strikes a balance between academic and industrial goals. A superior signal-to-noise ratio is obtained thanks to the precisely configured electrode in each well.
Drug discovery is a costly and time consuming process. The fast detection potential of CellSine makes it possible to exclude dead-end candidates in an earlier stage, saving both time and money.
Due to CellSine's label-free nature, it avoids false positives, facilitates assay development, and allows for the monitoring of biological processes in a non-invasive & continuous manner.
CellSine can be used to study cell toxicity in a fast and non-invasive manner. A proprietary algorithm coupled with multi-frequent responses resulting from the innovative hardware allows CellSine to distinguish between the different types of cell death (e.g. apoptosis, necrosis, autophagy, and mitotic catastrophe).
Of particular interest to the drug development pipeline is Cellsine's possible capability to differentiate between different types of GPCR G-couplings while also discerning these from RTK signaling in a fast and efficient way. The sensitive nature of the system would allow for analysis of endogenous expressed receptors and primary cell lines.
CellSine is currently being evaluated to screen for compounds with activity against biofilms of both a bacterial and fungal nature. In fungal biofilms, CellSine will be applied to select compounds that can inhibit critical virulence factors. A mode-of-action library will be constructed that allows to screen for compounds with a novel mode-of-action.
CellSine's technology will be expanded to determine the mechanism and kinetics by which virusses enter their host cells. Additional insight in this field can help in addressing many questions concerning important viral infections (e.g. HIV, influenza). Responses from different forms of viral entry, such as receptor-mediated virus entry (endocytosis), membrane fusion, and viral penetration, will be studied.
CellSine will be used to explore response profiles from ligand-gated ion-channels. Increased understanding of these channels' function and pharmacology can help to discover efficient treatments for important channelopathies such as mucoviscidosis.
By adapting CellSine's technology for use with 3D cell cultures, cellular processes such as receptor pharmacology will be able to be studied in a more disease-relevant in vitro environment than 2D cultures can provide.
In the 80's, Giaever & Keese discovered the approach of applying electrical impedance to the detection of cellular processes. They demonstrated that the technique can be utilised to monitor for changes in cell morphology in a very precise and non-invasive manner.
Every cellular process that somehow results in changes in cell morphology is detectable with this system since it will disturb the impedance response in some way.
A weak alternating potential is applied between electrodes in the bottom of a microtiter plate and evokes a weak alternating current through the system. The culture medium functions as the electrolyte. The current (I) over the electrodes is measured using electronic hardware and is based on the AC version of Ohm’s law. The impedance (Z) is measured as Z=V/I. A thin cell layer on the bottom of the plates is monitored over time while additives can be added.
CellSine combines efficient hardware, a wide range of frequencies, and an efficient proprietary data transformation process to produce high content multifrequency (1Hz – 60KHz) EIS data, perfectly suitable for parallel detection of multiple cellular processes.
The system fits in an incubator, thereby making it possible to monitor cellular responses at physiologically relevant temperature, CO2 content and humidity.
Cellular responses can be measured over hours and days in a continuous fashion for slow developing processes. Using a small time interval between subsequent measurements (up to 2s), CellSine can also resolve quick occuring processes.