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Multiscale Modeling of Nanostructured Interfaces for Biological Sensors

Final Report Summary - MNIBS (Multiscale Modeling of Nanostructured Interfaces for Biological Sensors)

The unusual properties of liquid cyrstals have been known and very profitably exploited for more than half a century. Yet they still seem to keep useful surprises in store: the realisation that liquid crystalline materials can be applied to detect the presence of peptides, proteins and toxins is very new. The first experiments on liquid crystal-based biosensors are only a few years old. Understanding how these sensors can, under favourable conditions, detect individual molecules is still a work in progress, which requires a combined, multi-level approach.

The development of such a multi-level, hierachical modelling technique was the primary objective of the 'Multiscale modeling of nanostructured interfaces for biological sensors' (MNIBS) project. In addition to its intrinsic scientific value, a thorough understanding of the mechanisms of the extreme sensitivity of liquid crystals to certain biological molecules would make it possible to design sensors tailored to specific proteins or viruses.

The most striking, and most useful, feature of liquid crystals in the context of biosensors is their ability to 'amplify' a signal at the molecular level. The arrival of a single protein molecule at the exposed surface of a liquid crystal has been observed to trigger a re-organisation of the liquid crystal around the protein. This remarkable amplification effect that takes place in liquid crystal sensors is triggered by an event at the molecular level (a few nanometres) and spontaneously develops macroscopic size (a few millimetres). It is thus not surprising that the techniques used to model the ordering transition of liquid crystal molecules around the protein cannot be applied to the spreading of ordering to macroscopic size. Conversely, those continuum models that are the most natural framework to describe macroscopic behaviour have no molecular resolution. There is thus no single, all-encompassing technique that can tackle the amplification problem MNIBS has addressed this apparent impasse by means of a hierarchical strategy, in which different techniques, each ideally suited to a particular length and time scale, are combined in a thermodynamically consistent way.

An outstanding success of MNIBS was the fruitful collaboration of groups from the EC, USA, and Mexico. Thanks to the joint character of the call, EC and US groups received independent but coordinated financial support. A TTC project enabled the Mexican group to join the project after its first year. Given the variety of modelling techniques used in MNIBS, it was a prerequisite to include in the consortium the leading experts in the fields, which not always reside in EC member countries. The joint call scheme has proved to be a very flexible tool for enabling collaboration beyond the borders of the EC.

All participants in MNIBS have contributed highly specialised expertise in areas as diverse as atomistic molecular modelling, mesoscopic, stochastic techniques, dynamic mean field and single-molecule theory, and continuum mechanics. Overall thermodynamic consistency was given high priority. A group specialising in non-equilibrium thermodynamics was charged with the task of guaranteeing that information transfer across the different spatial and temporal scales complied with thermodynamic consistency.

In this respect, one of the most prominent successes of MINBS was the effective integration of all modelling techniques into a multiscale tool that went all the way from the molecular to the macroscopic level:

- at the microscopic (atomistic) level, the dynamic behaviour of both the liquid crystal and the biological molecule have been studied in great detail. Phase transitions, analyte dynamics, and diffusive behaviour could be fully characterised and quantitatively described.

- at the mesoscopic level, a series of coarse-grained representations were developed based on widely differing methodologies, all of which have proved to be capable of describing LC-analyte interaction based on a few parameters extracted from the microscopic level simulations.

- at the macroscopic level, three independent and parallel routes (continuum mechanical, micro-macro, and lattice Bolzmann) to the design of actual liquid crystal sensors have been pursued. All three have been developed to the point of practical utility.

The successful meshing of the three description levels into a practical simulation and design tool by means of a thermodynamically consistent formalism was a very satisfactory confirmation of the ideas advanced in the proposal phase. As a result of the convergence of all the modelling techniques developed or applied in MNIBS, a first principles simulation and design of LC-based, single-molecule sensors for proteins and toxins is now possible.

Several of the techniques developed in the project represent the current state-of-the-art in the simulation of soft condensed matter at the micro-, meso-, and macroscopic levels. These advances are reflected in over 40 publications in top level journals, including several Physical Review Letters, Soft Matter, Journal of Physical Chemistry B, etc.

MNIBS also made a significant contribution to dissemination and outreach through successful contacts with a number of industrial and academic partners. In view of the successful achievement of all objectives, and thanks to a contract extension granted by the EC, such dissemination activities were given greater priority than originally planned.

The predictive power of the modelling hierarchy developed in MNIBS has also attracted the attention of companies keen on the large scale manufacturing of liquid crystal sensors by low cost processes such as inkjet printing. These collaborations born from MNIBS have resulted in long-lasting collaborations with industrial partners (both SMEs and large multinationals), and in the diffusion of MNIBS-related methods in industrial areas where they had been unknown up to now.