LC2 droplet biosensors: Lipid-coated Liquid Crystal Droplets as Highly Sensitive, Selective Sensors of Bacterial Toxins and other Bio-active Molecule

Lead Research Organisation: University of Leeds
Department Name: Physics and Astronomy

Abstract

Point-of-care testing has been identified as a key element in the international strategy for combating antimicrobial resistance but really it is a key element in all areas of medical practice. At present many of the diagnostic methods which we use do not give the desired instantaneous feedback and are relatively expensive to use. This is particularly an issue in the third world. Our ultimate vision is to produce a paper or plastic strip, a bit like a liquid crystal thermometer, that will provide a specific color-change when it detects a particular bacterial toxin or other disease 'marker'. Test strips that can be used at the point of care, which are cheap and disposable and which do not require a source of power. These will be based on phospholipid (biomembrane-like) coated liquid crystal droplets. The intrinsic amplification properties and the remarkable sensitivity of liquid crystal droplets to bacterial toxins have already been demonstrated but there are a number significant problems that need to be overcome before this promise can be translated into a practicable system. Making use of the unique combination of skills and experience that exists at Leeds, this is what we aim to do. In particular we will develop systems for controlled production of uniform suspensions of droplets of the desired size, to achieve control over the alignment of the liquid crystal at the phopholipid interface, to develop methods for addressing bulk samples rather than (as has been the case so far) individual droplets, to find ways of 'packaging' the droplets either in gels or on surfaces, and to undertake a series of demonstrations of the response and selectivity of these droplets to series of increasingly difficult and demanding test systems mostly based around significant bacterial toxins. This exciting multidisciplinary approach that uses liquid crystals in a new way will both enhance our fundamental scientific understanding of liquid crystals, biomembranes and biomolecule interactions, and potentially provide a new way of diagnosing significant healthcare problems.

Planned Impact

Impact on the medical community: We believe that our project is of direct relevance to the EPSRC Theme 'Healthcare Technologies' as there is potential to transform healthcare (facilitating timely interventions) in addition to relevance with regard to developing future therapies. Our ultimate aim is to develop a quick, cheap point-of-care diagnostic test for a wide range of different infections. The vision is a disposable test 'strip' that changes color when a specific biomarker is present. This would be based on a liquid crystal droplet technology similar to that exploited in liquid crystal thermometers. The sensitivity of liquid crystal droplets to low levels of biomarkers arises in part from the particular constraints imposed on the director field within this architecture. The amplification arises because switching at the surface or interaction with disclination sites switches many molecules within the bulk and, in the systems we envisage, the selectivity would be provided though a biomembrane-like coating. Point-of-care test development has been identified as a key element in the international strategy for combating antimicrobial resistance and so diagnosis of antibiotic resistant infections is one of our targets. However, this is mainly a problem of the the developed world. Development of a diagnostic system, such as this, which is robust, cheap to make and and which does not require a power source, is most likely to have its greatest impact in a third world environment. We thus believe that our proposal is highly relevant to the Global Challenge Agenda.
Impact on the veterinary science community: As in the case of the medical community our ambition is develop a system that is globally significant.
Impact on the MoD: The ability to detect exposure to biological warfare agents is a critical problem and our approach could be applicable in the field, a key need for defence.
Impact on the liquid crystal industry: Would be both in terms of device and liquid crystal manufacture and in terms of diversification, growing novel non-display applications led by UK innovation.
 
Title Lipid coated liquid crystal droplets for the on-chip detection of Antimicrobial peptides - dataset 
Description We describe a novel biosensor based on phospholipid-coated nematic liquid crystal (LC) droplets and demonstrate the detection of Smp43, a model antimicrobial peptide (AMP) from the venom of North African scorpion Scorpio maurus palmatus. Mono-disperse lipid-coated LC droplets of diameter 16.7 ± 0.2 µm were generated using PDMS microfluidic devices with a flow-focusing configuration and were the target for AMPs. The droplets were trapped in a bespoke microfluidic trap structure and were simultaneously treated with Smp43 at gradient concentrations in six different chambers. The disruption of the lipid monolayer by the Smp43 was detected (< 6 µM) at concentrations well within its biologically active range, indicated by a dramatic change in the appearance of the droplets associated with the transition from a typical radial configuration to a bipolar configuration, which is readily observed by polarizing microscopy. This suggests the system has feasibility as a drug-discovery screening tool. Further, compared to previously reported LC droplet biosensors, this LC droplet biosensor with a lipid coating is more biologically relevant and its ease of use in detecting membrane-related biological processes and interactions has the potential for development as a reliable, low-cost and disposable point of care diagnostic tool. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes