Periodic Reporting for period 2 - HISENTS (High level Integrated SEnsor for NanoToxicity Screening)
Período documentado: 2017-10-01 hasta 2019-03-31
HISENTS is important to society as:
1. It leads to a step increase in the speed of screening nanomaterials;
2. The HISENTS platform will have widespread applications in addition to nanosafety;
3. It enables screening systems to be fully computer controlled increasing their reliability and reproducibility;
4. The platform is very amenable to PBPK modelling in effect developing the animal-on-a-chip toxicity testing technology backed up by computer prediction;
5. The approach has derived quantitative structure activity relationship ((Q)SAR) properties of NMs so that very general principles of bio-nano-interaction have been derived;
6. HISENTS has created a technology with high translational potential to the pharma, water, health and safety and security industries.
HISENTS overall objectives have been:
1. Synthesised/characterised NM for use as standard test analytes;
2. Designed/tested effective screening devices, each representing a particular physiological function which have been incorporated into a multimodular platform for sensing nanotoxicity;
3. Configured robust electrochemical & optical techniques to interrogate the individual devices.
4. Developed/innovated instrumentation for interfacing to sensor chips;
5. Incorporated/integrated the screening devices into miniaturised and effective flow systems for HTS of NM along a directional pathway;
6. Developed smart automated signal processing data recognition techniques;
7. Carried out comprehensive performance evaluation of platform with respect to each individual device and the whole platform.
1.Pioneers synthesis of new types of NM. Novel NMs are used to understand more carefully structure-activity relationships and individual pathway analyses of each specific material in multimodular system;
2.Programme included miniaturisation, automation and integration of in-vitro devices into a chip based multimodular smart screening platform;
3.Developed several novel endpoints, including: (a) membrane modification (b) cell deformability change (c) impedance change in cells and (d) DNA structural damage;
4.Took DNA transforming their interrogation to high throughput multimodular devices;
5.Substituted well plates for a flow module interconnected by a microfluidic network that provided each compartment with necessary reagents/media components;
6.Modified the chip-based transducer design miniaturising it from macro to micro/nano dimensions and reconfigured the interrogation system to allow for the highest sensitivity;
7.Integrated a series of high level toxicity assays into a multimodular platform within a microfluidic system where each module contains a sensor element at a successively higher level of biological organisation;
8.Interfaced multimodule flow-through system with smart customised multichannel electronic potentiostatic instrumentation which synchronised flow system manipulation with sensor element handling and allowed several modules to be cross-examined simultaneously;
9.Developed a conceptual framework of the PBPK model approach side by side with experimental systems.
Potential impact:
The global HISENTS technology rationalised current toxicity testing allowing them to be carried out by a few instruments rather than by a whole series of “wet” tests. HISENTS technology revolutionised the way toxicity testing is carried out.
Wider socioeconomic impacts of HISENTS arise from its capacity as a generic automated toxicity screener for appropriate organisations, for instance:
-Water industry: toxins/NM in potable water;
-Environmental/marine agencies of toxins/NMs in the river, estuarine and marine environments;
-Government agencies/statutory bodies: toxicants/NMs in aqueous environments in particular to develop risk assessments for the NMs' use;
-Commercial/academic NM producers for formulation of risk assessment procedures and disposal methods for the materials; and,
-Defence/security industry throughout the EU including NATO, border control and civil defence for the toxicity of NMs where these are manufactured with terrorist ambitions.