Biomembrane module screening platform. Image: HISENTS Project
Why do we need to check chemicals and pharmaceuticals including nanomaterials for toxicity? Mainly to protect people from poisoning. This is increasingly important since regulations on the safety of all compounds and materials are becoming more and more stringent – partly as a result of major accidents in the past when the free use of specific materials, especially newly synthesised ones, have led to health or environmental disasters.
Some examples include asbestos which was widely used as a building material and is now associated with mesothelioma and the pesticide, DDT, which at one time was a magic bullet but later was found to poison seabirds and other fauna in the arctic. So, there is a strong societal need for screening platforms to test compounds and materials for their safety.
The easiest way to check for safety is to use an animal or human as a proxy for another human. A bit like in the past when we took a canary down a mine to see if the air was toxic or even longer ago when the Roman emperors forced their slaves to eat their food to check for poison.
Nowadays we are still using animals under controlled conditions to screen substances for toxicity. A topic of great debate and controversy with many people who feel that it is not right that animals should suffer or even die for the sake of our own survival. It is also very expensive.
So, there has been a huge effort to develop other ways of testing for toxicity. Usually people have used living cells in culture (in vitro). However, because tests must be done faster and faster, these in vitro screens have become more and more comprehensive and sophisticated. The aim has always been to lessen the impact on live animals from toxicity screens using proxy techniques.
High level Integrated Sensor for Nanotoxicity Screening (HISENTS)
The vision of HISENTS was to use the design of the human organism as a basis for an experimental screening platform. In this platform, all the respective targets representing individual organs would be in flow cell modules and these modules would be linked up into a microfluidic network, to be used for the biologically relevant toxicity screening of nanomaterials. The platform would have added value for screening toxicants and pharmaceuticals in drug design programmes with the high-level aim to replace the use of animal testing in toxicity screens and drug design programmes with effective substitutes.
The platform mimics a living organism and is the nearest thing possible to a “human-on-a-chip”. Below is an image of the HISENTS schematic platform from which the whole programme was designed to achieve this objective.
Schematic representation of a modular automated configuration of a HISENTS testing platform. Image: HISENTS Project
Despite the ambitious nature of HISENTS which aimed to revolutionise toxicity screening, it has been remarkably successful. In fact, three platforms were developed at three separate sites.
All platforms consisting of a biomembrane, cell-line and placenta screening platform, were validated against each other using standard toxicant chemicals.
The photo above and below show examples of these platforms illustrating their modular automated configuration.
The biomembrane screen had to be robust enough to be roughly treated and remain functional – a criterion necessary for a technology intended to be used in an industrial lab.
Example of a modular automated configuration of a HISENTS platform. Image: HISENTS Project
One of the many discoveries of HISENTS was the importance of the rapid screening of nanomaterials and indeed all substances. The main reason is that nanomaterial dispersions change immediately after being manufactured. HISENTS screens enabled us to follow the changes without delay following the output of nanomaterials from the production-line. This gave birth to the concept of “Screening at the Point of Production” and a new project SABYDOMA was developed to make use of the HISENTS screen.
Safety by Design of Nanomaterials (SABYDOMA)
SABYDOMA is a technological solution to the issue of safety by design of chemicals, including nanomaterials. In essence, safety by design means modifying industrial processes based on scientific evidence to ensure they are safer and do not endanger the public.
The SABYDOMA approach is to screen nanomaterials and chemicals at the point of production using the HISENTS screen and to feed back the screening signal to the production line to moderate the toxicity of the material being produced. The whole process is done automatically as shown by the image below.
The first ideas for the project were developed originally to solve issues of environmental pollution and climate change and ensue from an evidence-based philosophy. In terms of environmental pollution, environmental screening results feed back to the original pollutant discharge and automatically control the amount of pollutant being discharged. In terms of climate change, the monitoring results of greenhouse gases feed back to the factories emitting the gases and control their content in the emission.
HISENTS biomembrane module screen coupled with nanoproduction line for safe nano manufacture. Image: HISENTS Project
We have three years to realise the SABYDOMA platform and by all accounts, judging from our success in HISENTS, we have great expectation and trust that it will succeed. The current most successful outcome for the HISENTS project is the overall use of the developed platform to configure safety by design technology in SABYDOMA. Both the HISENTS and SABYDOMA are highly ambitious and disruptive technologies and it will be a long time before they are accepted in commercial use. I see the short-term uptake of these platforms by regulators such as the the OECD and the EU Commission.
EU funded research on nanomaterials and nanotechnology
A key instrument in increasing our understanding of the potential safety concerns related to nanomaterials and nanotechnologies while exploring their capacity to usher in a new era of innovations is the European Union's research programme.
The current Horizon 2020 programme is by far the largest EU research and innovation programme with nearly €80 billion of funding allocated to different projects in a variety of different fields. Approximately €2 billion of this is allocated for projects on nanomaterials and nanotechnology.
Horizon Europe, an ambitious €100 billion research and innovation programme succeeds Horizon 2020.
HISENTS and SABYDOMA are both EU funded programmes.
Professor Andrew Nelson
I am a professor of nanotoxicology, an electrochemist and a pioneer on the use of supported phospholipid layers on metal electrodes as toxicity sensors.
My research group has developed novel toxicity sensors based on biological membrane models which have been very successfully applied to the screening of chemicals and nanoparticles for biomembrane activity.
For the last nineteen years I have worked in the School of Chemistry at the University of Leeds where I have recently focused on transferring my sensing technology to the commercial sector.
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