S3: Towards a Third Generation Platform
TOWARDS A THIRD GENERATION PLATFORM FOR HIGH THROUGHPUT ON-LINE TOXICITY TESTING OF PHARMA, CHEMICALS AND NANOMATERIALS.
University of Leeds
A high throughput toxicity screening system is being developed within the framework of the H2020 project HISENTS. The initial system being built is an extension of the very successful FP7 ENNSATOX technology. The device is composed of a flow cell with an individual biomembrane-like sensor element interfaced to miniature resevoirs by microfluidic flow networks. The endpoint is registered as damage to the continually replaceable sensor element and recorded electronically. Throughout the duration of the project the single modular system will be further miniaturised and extended to multimodular. Additional sensor elements will be incorporated representing a variety of critical physiological functions.
This talk will initially describe the structure, workings and performance of the platform recorded against standard intercalibrant water soluble toxicants, where limits of detection (LoD) and response “fingerprints” will be shown for each toxin. The response will be compared to very standard toxicity predictors for individual compounds such as log P and, to toxicity to fish. The mechanistic details of the precise molecular event which the sensor element actually measures will be discussed for each compound-membrane interaction. The second part of the talk will describe the application of the screening platform to gold (Au) and silver (Ag) nanomaterials (NM). The synthesis and characterisation of the NM is detailed and the screening results will be reported. In particular the relation between the extent of the electronic response and the size and shape of the NM particles will be shown and related to the mechanism of interaction of the particle with the biomembrane-like sensor element. It is interesting that while it is intuitive that smaller particles have a stronger interaction than larger particles with the membrane surface, the interaction is also dependent on particle shape. Results will also define how the surface of the particle which is determined by its synthetic route relates to its biomembrane-interaction.
In the final few slides, future plans will be shown for miniaturising the platform and extending it from single modular to multimodular including more specific sensing modules.