Rebekah Byford

Nanowells and Nanocages for High Throughput Protein Recognition

Rebekah Byford - 3rd year PhD


Biological sensors are an important part of medical diagnostics and they are a growth industry reportedly worth around $10 bn worldwide. We here propose the development of a new technology for high throughput electronic recognition of proteins using nanometer sized wells (nano-wells). The dimensions of the wells are on the same order of magnitude as the protein nanocage that we are using to mediate recognition, making a natural confinement mechanism. Importantly, this allows for the efficient detection and screening of individual protein molecules as electronics can easily be integrated in the vicinity of the wells to act as independent detectors. While antibody based recognition forms a sensitive and specific readout, this is usually coupled to a quantitative optical readout through ELISA assays, or a qualitative colour readout. Although this method is perhaps considered to be a standard in diagnostics labs, there is significant room for improvement especially in the context of the classification and detection of rare events, speed, and sensitivity. Here we propose to couple biological recognition to a direct electrical output via a nano-well, enabling miniaturization that will lead to faster processing times, scalability for multiplexing and sensitivity for accurate and quantitative analysis. Furthermore, what we propose is a true single molecule technique, which will allow for statistics to be obtained on rare events. This project will deliver an unprecedented advance in single-molecule, label-free sensing that will contribute substantially to the UK’s global leadership in this area. The major outputs will result in a step-change in the development of new analytical and biophysical tools for protein screening. Specifically we will focus on using the nanowell and nanocage system for profiling cytokines at high throughput and high sensitivity.