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PhD

Exploiting the Properties of Diamond for Biosensing Applications: Electrochemical and Computational Approaches to Biomolecule Detection


Supervised by Prof. Julie Macpherson, Dr. Rebecca Notman, and Prof. Mark Newton


Key Advisors: Prof. Pat Unwin, Prof. Henry White



Background


In order to advance biosensing technologies into viable commerical devices, there is a need for new advanced materials and methods for sensing biomolecules to a high degree of accuracy, whilst ensuring cost-effectiveness, manufacturability and simplicity of use. Diamond is considered an ideal material for advancing the field of biosensors. Through the development of synthetic diamond growth processes, diamond has become more widely available and cost effective in recent years, making it a viable industrial material. This enables the use of diamond in biosensing devices to now be realised to its full potential.

My PhD project aims to explore the use of diamond in electrochemical and pore-based biosensing devices. Electrochemical biosensors involve the detection of biomolecules by measuring redox reactions at the electrode surface. When doped with boron, diamond has exceptional properties for electrochemical sensing including a wide solvent window, low background currents, chemical inertness, and the ability to to be manipulated between stable H- (hydrophobic) and O- (hydrophilic) surface terminations for chemical selectivity. Solid state pore-based devices involve the detection of molecules/particles by measuring conductance blockade events as the molecule is driven through a hole fabricated in an insulating material.1 These devices can also be manipulated to a biological pore device,2 where lipids incorporating ion channels are interfaced with micro and nanostructures.3 Diamond offers ideal electrical, optical and mechanical properties that are ideally suited to the technology including robustness, amenability to microfabrication, biocompatilibilty, high resistivity and low dielectric constant (high signal to noise).

This project is inherently interdiscipilinary lying at the interface between computational modelling, physical chemistry and life sciences. Both computational and experimental techniques are utilised to fully explore the properties of diamond for biosensing. The project is split into 4 stages, as outlined below:

(1) Atomistic molecular dynamics simulations are employed to examine how biomolecules, in particular water, ions and neurotransmitters, interact with diamond surfaces of different crystal orientation i.e. (100), (110) and (111) single crystal faces, and surface termination i.e. hydrogen- and oxygen- terminations. These studies will help to gain a fundamental understanding of biomolecule-diamond interactions at the molecular level that can assist in optimising diamond electrode and pore devices. See 1. Diamond-Solution Interface.

(2) Coarse-grained molecular dynamics simulations are employed to examine how phospholipids interact with diamond-like surfaces. This study will assist in optimising the diamond-lipid interaction as required in biological diamond pore devices or lipid-functionalised diamond sensors. Coarse-grained models of polystyrene nanoparticles are also built that are of use for a range of studies including to model nanopore-particle systems. See 2. Coarse-grained models.

(3) Electrochemical measurements of a range of species on H- (hydrogen plasma) and O- (alumina polished) terminated conducting (highly boron-doped) and semi-conducting (lowly boron-doped) diamond are explored. This study reveals the surface termination that enhances electron transfer processes for each species, enabling the diamond surface to be optimsied for chemical selectivity. It also explores how the surface conductivity introduced by H-terminated influences the electrochemical response of a mediator on semi-conducting boron-doped diamond. This has important applications to localised micropatterning of diamond electrodes. See 3. Diamond Electrochemistry.

(4) Diamond pores are fabricated for application in sensing. The fabrication of the device requires appropriate choice of diamond material, pore fabrication technique and setup. Experimental investigation focuses on (i) developing a simple fabrication protocol to produce micro and nanopores in diamond with reproducible characteristics, (ii) developing a setup to facilitate electrochemical measurements through the pore, and (iii) experiments to detect blockade events. The work outlined in this study, along with the simulations of lipid-diamond surface interactions, will assist in further studies into the feasibility of the device for use in single molecule detection and rapid, label-free DNA sequencing.4 See 4. Pore systems.

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References


[1] Dekker, C. (2007) Solid-state nanopores. Nature Nanotechnol. 209-215

[2] Bayley H. & Cremer, P.S. (2001) Stochastic sensors inspired by biology. Nature 413: 226-230.

[3] Kawano, R., et al. (2009) Controlling the Translocation of Single-Stranded DNA through α-Hemolysin Ion Channels Using Viscosity. Langmuir 25(2): 1233-1237.

[4] Branton, D., et al. (2008) The potential and challenges of nanopore sequencing. Nature Biotechnol. 26(10): 1146-1153