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Dr Katherine Holt

Research Overview

Further information can be found on the UCL Electrochemistry group pages.

My research interests are in the area of electrochemistry and are very broad and multidisciplinary, spanning fields as diverse as materials chemistry and the life sciences. I am always keen to collaborate with people from other disciplines so please contact me by email if you are interested in any of the techniques I use.

Scanning Electrochemical Microscopy (SECM)

SECM is a scanning probe electrochemical technique, which uses an ultramicroelectrode (UME) of diameter < 25 µm to image the electrochemical activity of a substrate of interest (link:http://www.msstate.edu/dept/Chemistry/dow1/secm/secm.html). The substrate may be another electrode, a membrane allowing transport of specific species or even a living cell.

Boron-doped Diamond Ultramicroelectrodes

In recent years novel diamond electrodes have been developed, which exhibit electrochemical properties that are in many ways superior to more conventional electrode materials. Boron-doped diamond (BDD) is deposited on metal substrates using chemical vapour deposition (CVD) methodology, forming highly conductive films. When used as electrodes they show many attractive properties, such as a wide potential window, low background current and high resistance to fouling. In a very successful collaboration with Prof. John S. Foord at the University of Oxford (http://physche m.ox.ac.uk/~jsf/) we have development the methodology to reliably fabricate very sharp BDD UME tips of dimensions 1 - 50 microns. Although small diamond electrodes have previously been fabricated by other groups, our electrodes are the first of UME dimension that are suitable for use as SECM tips. The work has resulted in several publications and has recently been highlighted in the RSC 'Chemical Technology' magazine. http://www.rsc.org/Publishing/Chem Tech/ Volume/2007/10/ diamonds_ele ctron_microscopy.asp Work is now continuing on different insulation methods, modification of diamond surface for greater selectivity of analytes and application of the electrodes in biological media. This work was supported by the EPSRC (EP/D504805/1).

References:

Fabrication of Boron-doped Diamond Ultramicroelectrodes for Use in Scanning Electrochemical Microscopy. Holt, Katherine B., Hu, Jingping, Foord, John S., Analytical Chemistry (2007) 79 (6): 2556-2561. http://pubs.acs.org/cgi-bin/abstract.c gi/ancham/2007/79/i06/abs/ac061995s.html

Hot filament chemical vapour deposition of diamond ultramicroelectrodes. Hu, Jingping, Foord, John S., Holt, Katherine B., Physical Chemistry Chemical Physics (2007) 9 , 5469-5475. *Hot Article*
http://www.rsc.org/Publishing/Journals/ CP/article.asp?doi=b710241k

SEM image of boron-doped diamond coating on a sharpened tungsten wire

SEM image of boron-doped diamond coating on a sharpened tungsten wire

Diamond Nanoparticles

5 nm diamond nanoparticles, produced during detonation of carbon based explosives, have been commercially available for some time and used in for polishing or formation of super-hard composite materials. Recently there has been a significant increase in suggested applications for this material, for example in drug delivery or use as a biomarker in cellular imaging. In many cases it has been assumed that the desirable properties of diamond: it is inert, biocompatible and non-cytotoxic, can also be attributed to diamond in its nano-form.

However, we have recently found that undoped 5 nm diamond nanoparticles appear to be redox active, undergoing reduction and oxidation in solution and mediating other redox processes, including oxygen reduction. This is unexpected, since diamond is the text-book example of an insulating material, with a band gap of 5.47 eV. We believe that unsaturated surface bonding may be responsible for the observed effects, after all around 15 % of all of the atoms for a 5 nm particle are present at the surface, so at these dimensions it appears that surface chemistry dominates that of the bulk. Studies are currently underway in this laboratory to determine the origin of the observed electrochemistry and to understand the implications for posited applications and its potential for use in electroanalytical applications. This research is carried out in collaboration with Dr Daren J. Caruana (UCL).

TEM image of 5 nm diamond nanoparticles

TEM image of 5 nm diamond nanoparticles

References:

Redox properties of undoped 5 nm diamond nanoparticles. Holt, Katherine B., Ziegler, Christoph, Caruana, Daren J., Zang, Jianbing, Millán-Barrios, Enrique J.2 June, 2010 October 2007) http://www.rsc.org/Publishing/Journals/CP/art icle.asp?doi=b711049a

Diamond at the nanoscale: applications of diamond nanoparticles from cellular biomarkers to quantum computing. Holt, Katherine B., Philosophical Transactions of the Royal Society of Chemistry A, Triennial Issue: Chemistry and Engineering (2007) 365, 2841 - 2861. http://www.journals.royalsoc.ac.uk/content/nh65658g61521223/fulltext.html

Redox Properties of Living Cells and Cell Components

The initial objectives of this study are to probe the function of the respiratory chain of E. coli bacteria using SECM. The redox properties of the respiratory chain are studied under conditions of normal function, using redox mediators of different standard potentials.

SECM apparatus used to probe the function of the respiratory chain of E. coli bacteria.

The bacteria are then treated with known respiratory inhibitors and the SECM experiments repeated to determine any resulting changes in the redox properties of the cells. The intention is to elucidate the processes by which the respiratory chain enzymes become damaged and to determine the resulting effect on the respiratory behaviour of the cell.

This work is being extended to the study of respiratory chain dysfunction in mitochondria, which has implications for understanding processes involved in cell death and aging in humans. This project has previously been funded by a Royal Society Research Grant and now by an EPSRC Advanced Research Fellowship 2006 - 2011 (EP/D070538/1): Probing Respiratory Chain Function of Isolated Mitochondria Using Scanning Electrochemical Microscopy (EPSRC Life Sciences Interface).

Understanding the properties of biological components such as bilayer membranes is very important, in order to study transport or electron transfer processes in living cells. However, the isolation and handling of such components is difficult so model systems such as electrode-supported lipid bilayers are often used as biomimics. I use such membranes to study the electron transfer properties of the membrane-associated protein cytochrome c, which is an important component of the respiratory chain of mitochondria.

References

Using Scanning Electrochemical Microscopy (SECM) to Measure the Electron-transfer Kinetics of Cytochrome c Immobilised on a COOH-Terminated Alkanethiol Monolayer on a Gold Electrode. Holt, Katherine B., Langmuir (2006) 22 (9) 4298 - 4304. http://pubs.acs.org/cgi-bin/abstract.cgi/l angd5/2006/22/i09/abs/la0529916.html

The Interaction of Silver (I) Ions with the Respiratory Chain of Escherichia coli: An Electrochemical and Scanning Electrochemical Microscopy Study of the Antimicrobial Mechanism of Micromolar Ag +. Holt, Katherine B.; Bard, Allen J., Biochemistry (2005) 44 (39) 13214-13223. http://pubs.acs.org/cgi-bin/abstract.cgi/bichaw/2005/44/i39/abs/bi0508 542.html

Hydrogenase biomimetics for electrochemical hydrogen production

An important component of future energy systems is postulated to be the use of hydrogen as a clean fuel, however a problem in this technology is the difficulty in transportation and storage of hydrogen gas. A potential solution is to generate hydrogen in situ by the electrocatalytic reduction of protons, a reaction traditionally catalysed by platinum. Nature has a evolved more efficient mechanisms for this process in the form of hydrogenase enzymes that contain Fe-Fe centres that reduce two protons to hydrogen gas at close to the thermodynamic ideal. Unfortunately the isolated enzyme is fragile and sensitive to oxygen, so cannot function for prolonged periods without damage. Dr Graeme Hogarth (UCL) and his group have devised synthetic methods to produce Fe-Fe complexes that mimic the structure of the active centre of the hydrogenase enzyme and we are working with him to investigate the electrochemical properties of these molecules and also their catalytic efficiency towards hydrogen production. The results of our electrochemical investigations will then feed back into the design and synthesis of further biomimetic complexes in order to obtain the most efficient catalysts.

Electrochemistry at electrode-supported bilayers

Understanding the properties of biological components such as bilayer membranes is very important, in order to study transport or electron transfer processes in living cells. However, the isolation and handling of such components is difficult so model systems such as electrode-supported lipid bilayers are often used as biomimics. I am using such membranes to study the electron transfer properties of the membrane-associated protein cytochrome c, which is an important component of the respiratory chain of mitochondria.

Redox properties of living E. coli cells

The objectives of this study are to probe the function of the respiratory chain of E. coli bacteria using SECM . The redox properties of the respiratory chain are studied under conditions of normal function, using redox mediators of different standard potentials. The bacteria under study will then be treated with known respiratory inhibitors and the SECM experiments repeated to determine any resulting changes in the redox properties of the cells. The intention is to elucidate the processes by which the respiratory chain enzymes become damaged and to determine the resulting effect on the respiratory behaviour of the cell. This work can then be extended to the study of mitochondria, which has implications for understanding processes involved in cell death and aging in humans. This project is funded by a Royal Society Research Grant.

Diamond based electrode materials

In recent years novel diamond-based electrodes have been developed, which exhibit electrochemical properties that are in many ways superior to more conventional electrode materials. Boron-doped diamond (BDD) and nanocrystalline diamond (NCD) are deposited on metal substrates using chemical vapour deposition ( CVD ) methodology, forming highly conductive films. When used as electrodes they show many attractive properties, such as a wide potential window, low background current and high resistance to fouling. It is this latter property that I wish to exploit in the electrochemical detection of metabolic products of living cells and the development of enzyme-based UME biosensors. This work is carried out in collaboration with Prof John S Foord at the University of Oxford and Dr Daren Caruana (UCL).

Selected Publications

2010

  1. Undoped Diamond Nanoparticles: Origin of Surface Redox ActivityKatherine B. HoltPhys. Chem. Chem. Phys., (2010), 12, 2048 - 2058.
  2. Astroelectrochemistry: The role of redox chemistry in cosmic dust chemistryDaren J. Caruana, Katherine B. HoltPhys. Chem. Chem. Phys. (2010), 12, 3072 - 3079.

2009

  1. Electrochemistry of Undoped Diamond Nanoparticles: Accessing Surface Redox States. Katherine B. Holt, Enrique Millan-Barrios, Daren J. Caruana, J. Am. Chem. Soc., (2009) 131, 13272+
  2. Focused Ion beam Fabrication of Boron-doped Diamond Ultramicroelectrodes. Jingping Hu, Katherine B. Holt, John S. Foord, Analytical Chemistry (2009) 81, 5663-5670.
  3. Bimetallic complexes based on carboxylate and carbamate ligands: synthesis and electrochemical investigations.Lin, Y.H., Leung, N.H., Holt, K.B., Thompson, A.L., Wilton-Ely, J.D.E.T., Dalton Trans, (2009) 38, 6891 - 7901.
  4. Soap Film Electrochemistry.Dandisonba Chinwe Bamidele Braide-Azikiwe, Katherine B. Holt, David E. Williams and Daren J. Caruana. Electrochemistry Communications (2009) 11, 1226 - 1229.
  5. Scanning Electrochemical Microscopy studies of redox processes at undoped nanodiamond surfaces. Holt, Katherine B., Ziegler, C., Zang, J.B., Hu, JP, Foord, J.S., J. Phys Chem C, (2009), 113, 6761.

2008

  1. Multimetallic Assemblies using piperizine-based dithiocarbamate linkers. Wilton-Ely, James D. E. T., Solanki, Dina, Knight, Edward R., Holt, Katherine B., Thompson, Amber L., Hogarth, Graeme, Inorganic Chemistry, (2008), 47, 9642.
  2. Redox properties of undoped 5 nm diamond nanoparticles. Holt, Katherine B., Ziegler, Christoph, Caruana, Daren J., Zang, Jianbing, Millán-Barrios, Enrique J., Hu, Jingping, Foord, John S. Physical Chemistry Chemical Physics (2008) 10, 303 - 310.