A new form of impedance spectroscopy could eliminate the need for animal testing in determining the potential toxicity of experimental compounds, UK researchers claim.
Work carried out by the University of the West of England in conjunction with instrumentation company Kaiku has shown that, by measuring changes in the electrical characteristics of cells, the toxic effects of pharmaceuticals can be assessed more rapidly and cheaply than with traditional animal testing protocols, Kaiku says.
A cell’s electrical characteristics stem from its composition and the charge distribution across various membranes within the cell and cell organelles, the company notes. While electrical impedance measurements are by no means a new concept in medical research or diagnosis, not to mention other, non-medical applications, Kaiku says it has advanced the technology through the use of tuned or “resonant” electrical circuits.
The initial application for this Resonance Impedance Spectroscopy was in the beverages industry, in the form of an intelligent pipe with embedded Kaiku technology – the i-Pipe range – that detects contamination or changes in fluids through continuous non-contact monitoring and analysis.
The Kaiku Medical Limited subsidiary is also exploring the technology’s potential with researchers from Southampton University, as a clinical research tool for the detection and separation of individual biological cells, and with UWE as a means of replacing animal toxicity testing.
The UWE researchers have used the Kaiku Medical Well Plate Analyser System to measure toxicity in endothelial cells exposed to varying concentrations of dimethyl sulphoxide (DMSO), which induces apoptosis (programmed cell death) through membrane depolarisation. A Resonance Impedance Analyser with eight electrodes recorded the impedance spectra.
In the experiment, increasing concentrations of DSMO (0.75%, 1.25%, 2.5% and 5%) were added to the endothelial cells. The impedance spectra were recorded three hours post-dose and changes in the resonance frequency registered. Flow cytometry was used to evaluate cell death and cell morphology in terms of changes in granularity and size compared with untreated cells.
A whole cell 'biosensor'
The researchers found there was a dose-dependent change in resonance frequency in response to DSMO concentration, which was also reflected in dose-dependent changes in the percentages of cell death, cell granularity and cell size. This demonstrated that impedance spectroscopy could be used in a whole-cell biosensor for monitoring cell toxicity, they concluded.
According to Kaiku, which is looking for strategic partners for its technology in the process instrumentation and medical device sectors, the emergence of a new approach to measuring cell toxicity is particularly important at a time when European legislation – the REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) regulation – calls for more than 30,000 industrial chemicals to have their toxicity evaluated and defined by 2018, with the first tests scheduled to begin next year.
“There is a real moral dimension here,” commented Kaiku’s technical director Dr Hassan Amrani. “European legislators are driving organisations both academic and commercial towards a huge programme of testing, with animals in the front line. However, with this technology the testing can be carried out in a way that removes any social conflict.”