Lab on a Particle

This project will produce new types of nanoparticles in combination with distinctive analytical techniques. The output will be the generation of highly significant and original research at the forefront of comparable work globally. The development of this new nanoparticle diagnostic is based upon fundamental particle synthesis and surface chemistry. The group have a track record in developing biocompatible materials (medical stents, surfaces for cell growth), materials synthesis (metallic and magnetic nanomaterials) and sensors (graphene, electrochemical and nanopores). The nanomaterials are to be used with a sensor, known as Tunable Resistive Pulse sensing, TRPS, which is a new, cheap, portable platform for diagnostic assays. To date such particle based assays have utilised spherical nanoparticles, due to ease of use and availability.

This approach will advance the technique beyond existing methods by combining several experimental aspects into one process: it will capture the analyte; perform sample preparation and extraction using magnetic particles; and provide a fast and sensitive tagless detection mechanism that can in the future be scaled down and integrated into a Point of Care microfluidic technology.

Background
If a nanoparticle surface is modified with a capture probe capable of binding to an analyte (ie antibody, DNA or protein), the particle can quickly and selectively bind to the analyte in solution. The quantification of the analyte on the particle's surface can then be achieved using the TRPS technology. In recent years, nanopore systems based upon the Coulter technology have seen resurgence, allowing the characterization of nanoparticle and proteins. Known collectively as resistive pulse sensing (RPS), they offer an attractive technology format because the measurements provide information on individual analytes within their natural environment. The nanoparticles pass through a hole in a membrane creating a blockade event. By monitoring changes in the particles velocity -and frequency (events/min) it is possible to elucidate the concentration of the analyte in situ.

In order for this assay to be multiplexed, a range of different sized particles are required. Each unique size is then modified to capture a specific analyte, i.e. if two analytes are to be detected at the same time, particles with two different and uniform diameters are needed. The limitation with spherical particles is only their diameter can be varied. With cylindrical particles the diameter and length can be controlled The TRPS technology can detect changes in cylindrical particle diameter and length, demonstrated by Platt et. al Small 2012, this technique has however never been applied to a multiplexed diagnostic assay.

The fundamental research into the reproducible and scalable synthesis of such materials as well as the protocols for data extraction and analysis of complex multimodal particle populations is proposed. Two research strands supported by the current research group and company are planned to deliver this.

Strand 1 will produce libraries of multicomponent particles functionalized with receptors capable of identifying proteins. The particle library drive will focus on synthesizing well-defined nanoparticles via electrodeposition producing multicomponent rods resembling barcodes. Scaling up their synthesis and studying their behaviour in solution, relating charge and size to translocation across a nanopore not only enhances the knowledge for the assay, but it provides a template for future nanotoxicology studies investigating the interaction between nanomaterials and biological pores.

Strand 2 Will development the methods to place aptamers (that are produced separately inhouse) onto the particle surface. As the aptamers on the surface of the particles interact with their target the Nanopore technology can follow this in real time, and quantify the analyte present.