OPTICAL WAVEGUIDE SENSORS FOR HIGHLY SENSITIVE DETECTION & QUANTIFICATION OF CYTOKINES IN BIOLOGICAL FLUIDS

Lead Research Organisation: University of Southampton
Department Name: Optoelectronics Research Centre

Abstract

Cytokines are the proteins in our bodies that are responsible for controlling inflammation. The inflammatory response occurs when we are infected by a bacterial, viral or chemical agent, or damage ourselves from either a burn or a cut. When we are sick we have increased levels of cytokines in our blood. As well as helping the body fight off infection, recover and repair itself, these proteins can act on the brain to cause changes in behaviour, making it more difficult for us to think clearly, make decisions and interact with others. Even very low levels of cytokines in our brain can change our behaviour. For example, a very few molecules of a cytokine can change the way in which a neurone, or a group or neurones, behaves. In order to better understand how cytokines can change our behaviour we must be able to measure them accurately in fluids and tissues of the body, such as blood and the brain. However, the techniques that are currently available to us are very insensitive, and can only detect cytokines when millions of molecules are present at once. Therefore we need to develop more sensitive biological methods for detecting these proteins. Optical waveguide sensors have been developed for the detection of low levels of environmental pollutants; for example, the presence of the female sex hormone, oestrogen, in rivers. These sensors can be reused 400 times and are currently the most sensitive biological sensors available worldwide. It is important to discover whether this technology can be used for the detection of other molecules, particularly low copy numbers of proteins in biological fluids, such as human blood and tissue. Here, we propose to develop these systems for the detection of low levels of cytokines. Creation of this technology will be very valuable for our current research in inflammation biology and neuroscience, and should be of significant value to the pharmaceutical industry and clinic, particularly in the context of clinical diagnositics.

Technical Summary

The detection of low levels of cytokines in biological matrices is currently limiting for a range of research and clinical diagnostic applications. This is particularly true for our studies on the inflammation biology of the nervous system. The limiting factors for our studies are sensitivity, sample size and interference from complex proteins or molecules. Current conventional methods for cytokine detection/quantification include Mass Spectrometry approaches, enzyme linked immunosorbant assays (ELISA) and western blot methods; a detection of cytokines of approximately 3 pg/ml is possible. Here we propose to develop an optical waveguide sensor technology for cytokine detection and quantification. This optical sensor array has been developed recently in the Optoelectronics Research Centre, in collaboration with a number of European academic and industrial groups, for the detection of low levels of environmental pollutants. The detection limit for the pollutant, oestrone, was determined to be 0.1ng/L. We now propose to adapt this array of optical sensors for the detection of cytokines, starting first with IL-6. A number of issues are to be addressed. These include fluidic handling developed for the small volumes in a wide range of biological matrices and creation of the chemistry on the sensors. Our aim is to provide a sensitive, simple assay for the detection of cytokines to provide further evidence for the role of inflammatory proteins in neurological function.

Publications

10 25 50
 
Description Novel microfluidic devices for effective mass transport of low levels of analyte to sensors were designed and fabricated. These were integrated onto an optical waveguide with each sensor having a detection limit of ~1600 molecules. These microfluidic/optical structures were specially designed for the analysis of 100_l volumes of serum.



A novel 'protein-printing press' system, inspired by techniques used for the fabrication of microelectronic devices and with a Michelson interferometer for u
Exploitation Route We have built up contacts with two companies involved in 1) Antibody production (UK) 2) nanopattern printing (France). Non-disclosure agreements are in place.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description The results have been elaborated by us for the design of novel chromatographic systems (see The design of microfluidic affinity chromatography systems for the separation of bioanalytes Friedrich, D., Please, C. P. & Melvin, T. 2012 In : Journal of Chromatography B. 910, p. 163-171), which has been identified in the industry based review 'Support of academic synthetic chemistry using separation technologies from the pharmaceutical industry Erik L. Regalado, Marisa C. Kozlowski, John M. Curto, Tobias Ritter, Michael G. Campbell, Anthony R. Mazzotti, Bruce C. Hamper, Christopher D. Spilling, Michael P. Mannino d, Li Wan, Jin-Quan Yu, Jinchu Liu and Christopher J. Welch. This continues to be a work in progress.
First Year Of Impact 2012
Sector Chemicals,Pharmaceuticals and Medical Biotechnology
Impact Types Economic