Development of Point of Use Bionanosensors

Programme of research involves the development of innovative bionanosensors combined with portable Raman instrumentation that can be deployed at the point of use. The developed bionanosensors will have superior performance in terms of sensitivity, ability to quantify bioanalytes and multiplexing capabilities compared to existing technologies. Project will focus on the development of low cost, disposable point of use sensors and their integration, in terms of sampling and readout, with portable Raman instruments.

The approach investigated will be the development of 3D paper based diagnostics which will work from the direct application of a clinical sample (drop of blood, urine) applied to the device to produce a quantifiable response to measure the concentration of a clinically relevant biomarker. The concept is to make use of cheap, paper-based devices where the blood sample can be applied directly onto the surface of the device allowing movement in the XY plane followed by movement in the Z direction to a second or third layer of paper which allows separation of the red blood cells. Detection will then be carried out using biorecognition molecule functionalised gold nanoparticles which our previous work shows works well in terms flow capabilities and functionalisation. Gold nanoparticles are also optically bright and visible to the naked eye, however better sensitivity and quantitation can be achieved by using surface enhanced Raman scattering (SERS). This increased sensitivity will be required to detect the levels the low levels of biomarker which are required to be detected in clinical samples. We have an interest in the detection of biomarkers related to sepsis and clinical collaborations in the detection of biomarkers indicative of liver damage and monitoring cancer treatment and we will deploy this format in areas that are of particular interest to the student. Therefore, we propose to produce a cheap, disposable, 3D paper diagnostics device that can be used to give a highly sensitive and quantifiable SERS response for clinical biomarkers that we will integrate with portable Raman instrumentation.

Development of specific Bionanosensor
Initial paper-based assay will be developed and the focus will be on initially developing a 2D lateral flow assay before integrating it into a 3D paper based assay and integrating them with portable Raman detection with appropriate sampling accessories.

Quantitation of biomarker/bacteria and multiplexing
The assays will be optimised to be as sensitive as possible and a model to allow quantitative detection developed. One of the main benefits of using SERS as a detection technique, along with its inherent sensitivity, is its multiplexing capability, specifically the ability to detect multiple analytes within the same sample without the need for separation. Therefore, we will also develop a multiplexed POU test that will identify the presence of multiple biomarkers in one measurement. Once the multiplexed quantitative SERS signal is generated it needs to be interpreted such that the unequivocal detection of each analyte is made and/or the concentration predicted giving a response using an easily interpretable interface.

Development of Detection platform
The ultimate aim is to develop a simple, portable detection platform which has the potential to enable POU detection using the assays developed. In the initial stages of the project a portable Raman device will be used for detection. In collaboration with Wasatch we will investigate different detection optics that can be combined with simple fluidics and magnetic separation to maximise the data capture and ensure the sampling geometry is aligned with the assay format.

Field Testing
We will carry out field testing of the assay using real samples, clinical and food. This will allow us to factor in matric effects for real samples as well as the practicalities of sampling and detection within different environments.