A combined micro fluidic single cell SRIR microscopy stage for use at Diamond

Lead Research Organisation: University of Manchester
Department Name: Chem Eng and Analytical Science


For many forms of cancer a formal diagnosis can only be made by removing a small sample of tissue, a biopsy, and having this sample analysed under a microscopy by trained pathologists. This is expensive in terms of operating theatre time surgeon time and pathologist time. It is also an invasive procedure that can result in significant discomfort to the patient. There can also be delays in getting results and there is always a finite chance that (i) the sample is inconclusive or (ii) the pathologists disagree about the result since it is a subjective analysis, thus resulting in taking a second biopsy or in rare cases, misdiagnosis. Delays in receiving test results are a major cause of stress to patients and one to the key aims of the government's Cancer Action Plan is to reduce these waiting times with the introduction of new technology and more rapid methods of diagnosis. It has been demonstrated that some cancers can be diagnosed from analysis of just a few cells. A technique known as infrared spectroscopy can measure a biochemical signature from individual types of cells and these biochemical signatures can be used like a cellular fingerprint. For example cancerous prostate cells have a slightly different signature from healthy prostate cells. It is possible therefore to make a diagnosis based on the infrared spectrum of cells without the need for a biopsy and furthermore the analysis is done in a completely non-subjective way. This should lead to a significant improvement in diagnostic accuracy. However the infrared method is not a high throughput technique so methods have to be developed that increase the number of cells analysed in a given time. Using state of the art microfluidics technology we propose to build a high throughput system that will automatically deliver cells, suspended in liquid, to the focal point of an infrared microscope. Importantly the microscope will be connected to the New Diamond Light Source that can deliver infrared light 1000 times as bright as a conventional source. Using this ultra powerful infrared microscope we can develop the novel high throughput cancer diagnostic system.
Description This grant enabled us to show that infrared spectra of cells can be obtained in an aqueous environment. This paved the way for live cell imaging studies. This means that we can use this method to study drug-cell interaction, stem cell differentiation and other cell based metabolic processes.
Exploitation Route We built a prototype micro-fluidic device. Other people in the field are now doing similar work using similar devices. We have since shown that it is possible to obtain spectra through thicker layers of water.
Sectors Healthcare

Description STFC Daresbury Laboratory 
Organisation Daresbury Laboratory
Country United Kingdom 
Sector Private 
PI Contribution We are heavy users of the IR beamline and have had two jointly funded studentships. I have also been chair of the IR user group and have sat on the Diamond Light Source Scientific Advisory Board 2012-2016 and have conducedted a number of beamline reviews. I have several joint publications.
Collaborator Contribution Diamond have jointly funded two PhD studentships and we have several joint publications.
Impact We have had several joint publications in which Gianfelice Cinque is a coauthor. G. Clemens, F. J. Ball, A. Henderson, S. Mohr, P. R Fielden, N. J Goddard, A. Whiting, S. A. Przyborski, G. Cinque, P. Gardner, A Microfluidic Device for the Infrared Study of Single Cells in Aqueous Media: An Evaluation Using Differentiating Stem Cells, Analyst submitted J. Doherty, G. Cinque and P. Gardner, Single Cell Analysis Using Fourier Transform Infrared Microspectroscopy, Applied Spectroscopy Reviews, 2016, 1252014 A. L. M. Batista de Carvalho, M. Pilling, P. Gardner, J. Doherty, G. Cinque, K. Wehbe, C. Kelley, L. A. E. Batista de Carvalho and M. P. M. Marquesa, Chemotherapeutic Response to Cisplatin-like Drugs in Human Breast Cancer Cells Probed by Vibrational Microspectroscopy. Faraday Discussion, 2016, 187, 273-298 DOI: 10.1039/c5fd00148j G. Clemens, K. R. Flower, A. P. Henderson, A. Whiting, S. A. Przyborski, M. Jimenez-Hernandez, F. Ball, P. Bassan, G. Cinque, P. Gardner. The action of all-trans-retinoic acid (ATRA) and synthetic retinoid analogues (EC19 and EC23) on human pluripotent stem cells differentiation investigated using single cell infrared microspectroscopy. Molecular BioSystems, 2013, 9 (4), 677 - 692
Start Year 2006