The study, published today in Nature Nanotechnology, describes the exploitation of a sensor for measuring the concentration of effective antibiotics in blood, giving an indication of their efficiency against disease causing pathogens, for instance multidrug resistant hospital "superbugs".
This development could potentially give a far greater understanding of the effectiveness of drug dosages required for different individuals, reducing potential toxic effects, allowing personalised treatment for patients and leading to new insights into optimal clinical regimes, such as combination therapies.
When effective, antibiotic molecules impose cellular stress on a pathogen's cell wall target, such as a bacterium, which contributes to its breakdown. However, competing molecules in solution, for example serum proteins, can affect the binding of the antibiotic to the bacterium, reducing the efficacy of the drug. Serum proteins bind to drugs in blood and, in doing so, reduce the amount of a drug present and its penetration into cell tissues.
As the amount of antibiotics that bind to serum proteins will vary between individuals, it is extremely valuable to be able to determine the precise amount of the drug that is bound to serum proteins, and how much is free in the blood, in order to be able to accurately calculate the optimum dosage.
Existing biosensors on the market do not measure cellular stress, however, the nanomechanical sensor exploited by a group of researchers from the London Centre for Nanotechnology (LCN) at UCL, the University of Cambridge, the University of Queensland and Jomo Kenyatta University of Agriculture and Technology, can accurately measure this important information even when antibiotic drug molecules are only present at very low concentrations.
The researchers coated the surface of a nanomechanical cantilever array with a model bacterial membrane and used this as a surface stress sensor. The sensor is extremely sensitive to tiny bending signals caused by its interactions with the antibiotics, in this case, the FDA-approved vancomycin and the yet to be approved oritavancin, which appears to deal with certain vancomycin-resistant bacteria, in the blood serum.
This investigation has yielded the first experimental evidence that drug-serum complexes (the antibiotics bound to the competing serum proteins) do not induce stress on the bacteria and so could provide realistic in-vitro susceptibility tests for drugs and to define effective doses which are effective enough but less toxic to patients.
In the future, the researchers believe that with a suitably engineered surface probe, this sensor could be paired with customised drug delivery for anaesthetics, anti-cancer, anti-HIV and antibacterial therapies.
The lead author of the study, Dr. Joseph W. Ndieyira of the LCN, said "This discovery represents a major advance in our fundamental understanding of the pathways between chemical and mechanical signals in a complex media, such as blood serum, and how this information can be used to tune the efficacy of drugs and to minimise the potential toxic side effects."
Dr. Ndieyira added, "Monitoring the levels of active free drugs in serum can be crucial in honing therapeutic solutions for patients to enhance drug administration. This will be particularly helpful in addressing problems of drugs which have to be used in very precise quantities and where there are large differences in how drugs affect individuals and groups. For example, overuse of antibiotics can fuel resistance to drugs or underuse of anaesthetics may lead to a patient regaining consciousness during an operation."
Notes to editors
1. For more information or to speak to one of the researchers, please contact Dominique Fourniol in the UCL Media Relations Office on tel: +44 (0)20 3108 3843, out of hours +44 (0)7917 271 364, e-mail: firstname.lastname@example.org
2. Surface-stress sensors for rapid and ultrasensitive detection of active free drugs in human serum is published online in Nature Nanotechnology on 2 March 2014.
3. Journalists can obtain copies of the paper by contacting the UCL Media Relations Office.
About UCL (University College London)
Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender and the first to provide systematic teaching of law, architecture and medicine.
We are among the world's top universities, as reflected by our performance in a range of international rankings and tables. According to the Thomson Scientific Citation Index, UCL is the second most highly cited European university and the 15th most highly cited in the world.
UCL has nearly 27,000 students from 150 countries and more than 9,000 employees, of whom one third are from outside the UK. The university is based in Bloomsbury in the heart of London, but also has two international campuses – UCL Australia and UCL Qatar. Our annual income is more than £800 million.
Dominique Fourniol | EurekAlert!
Chances to treat childhood dementia
24.07.2017 | Julius-Maximilians-Universität Würzburg
World first: Massive thrombosis removed during early pregnancy
20.07.2017 | Universitätsspital Bern
3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects
A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...
Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.
For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...
What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.
To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...
The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....
A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...
21.07.2017 | Event News
19.07.2017 | Event News
12.07.2017 | Event News
24.07.2017 | Power and Electrical Engineering
24.07.2017 | Materials Sciences
24.07.2017 | Materials Sciences