Towards disease diagnosis through spectrochemical imaging of tissue architecture.

Lead Research Organisation: Lancaster University
Department Name: Physics

Abstract

This proposal brings together a critical mass of scientists from the Universities of Cardiff, Lancaster, Liverpool and Manchester and clinicians from the Christie, Lancaster and Liverpool NHS Hospital Trusts with the complementary experience and expertise to advance the understanding, diagnosis and treatment of cervical, oesophageal and prostate cancers. Cervical and prostate cancer are very common and the incidence of oesophageal is rising rapidly. There are cytology, biopsy and endoscopy techniques for extracting tissue from individuals who are at risk of developing these diseases. However the analysis of tissue by the standard techniques is problematic and subjective. There is clearly a national and international need to develop more accurate diagnostics for these diseases and that is a primary aim of this proposal.
Experiments will be conducted on specimens from all three diseases using four different infrared based techniques which have complementary strengths and weaknesses: hyperspectral imaging, Raman spectroscopy, a new instrument to be developed by combining atomic force microscopy with infrared spectroscopy and a scanning near field microscope recently installed on the free electron laser on the ALICE accelerator at Daresbury. The latter instrument has recently been shown to have considerable potential for the study of oesophageal cancer yielding images which show the chemical composition with unprecedented spatial resolution (0.1 microns) while hyperspectral imaging and Raman spectroscopy have been shown by members of the team to provide high resolution spectra that provide insight into the nature of cervical and prostate cancers. The new instrument will be installed on the free electron laser at Daresbury and will yield images on the nanoscale. This combination of techniques will allow the team to probe the physical and chemical structure of these three cancers with unprecedented accuracy and this should reveal important information about their character and the chemical processes that underlie their malignant behavior. The results of the research will be of interest to the study of cancer generally particularly if it reveals feature common to all three cancers.
The infrared techniques have considerable medical potential and to differing extents are on the verge of finding practical applications. Newer terahertz techniques also have significant potential in this field and may be cheaper to implement. Unfortunately the development of cheap portable terahertz diagnositic instruments is being impeded by the weakness of existing sources of terahertz radiation. By exploiting the terahertz radiation from the ALICE accelerator, which is seven orders of magnitude more intense that conventional sources, the team will advance the design of two different terahertz instruments and assess their performance against the more developed infrared techniques in cancer diagnosis. However before any of these techniques can be used by medical professionals it is essential that their strengths and limitations of are fully understood. This is one of the objectives of the proposal and it will be realised by comparing the results of each technique in studies of specimens from the three cancers that are the primary focus of the research. This will be accompanied by developing data basis and algorithms for the automated analysis of spectral and imaging data thus removing subjectivity from the diagnostic procedure.
Finally the team will explore a new approach to monitoring the interactions between pathogens, pharmaceuticals and relevant cells or tissues at the cellular and subcellular level using the instruments deployed on the free electron laser at Daresbury together with Raman microscopy. If this is successful, it will be important in the longer term in developing new treatments for cancer and other diseases.

Publications

10 25 50
 
Description It may become possible to detect early stages of Alzheimer decease using nanoscale probing of the small samples from the person body, using scanning probe microscopy methods combined with the spectroscopic identification of the toxic amyloid peptides. Also, it was found that even at advanced stages of the assembly of these peptides creating fibres and plaques in teh brain, significant proportion of small and presumed most toxic monomers still present, leading a way for designing new drugs against Alzheimer decease.
New medicines based on the retro-inverso peptides loaded in the liposomes are been developed. Using combination of QCL and SPM shown the significant benefit for identification of biomaterials.
Exploitation Route This creates a new platform for fighting Alzheimer decease and can be exploited by other groups worldwide. A new EPSRC project FLUENCE using FELIX FEL have been established for bioapplications of new method.
Further an approach used by this now is the core of the new awarded UKRI project EP/V00767X/1 High performance Wide spectral range Nanoprobe (HiWiN) for mapping spectrocopical properties on mid IR and THz radiation region to create at multi-user EPSRC facility for chemical, physical and biomedical studies using FELIX FEL in Nijmegen Netherland.
Sectors Chemicals,Communities and Social Services/Policy,Digital/Communication/Information Technologies (including Software),Electronics,Energy,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL https://academicminute.org/2014/08/kolosov/
 
Description Some of the medicines for Alzheimer decease developed over the grant methodology are being tested medically for the efficacy. Industrial application of new methods have been implemented by Anasys Instruments. The company Anasys Instruments was bought by Bruker - one of the largest international players in scientific and medical instrumentation.
First Year Of Impact 2018
Sector Communities and Social Services/Policy,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description FP7 QUANTIHEAT
Amount € 586,000 (EUR)
Funding ID 604668 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 12/2013 
End 11/2017
 
Description High performance Wide spectral range Nanoprobe (HiWiN)
Amount £745,943 (GBP)
Funding ID EP/V00767X/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 08/2020 
End 01/2023
 
Description Paul Instrument Fund
Amount £100,000 (GBP)
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2017 
End 11/2019
 
Description UCONN-ULANC collaboration 
Organisation University of Connecticut
Department Institute of Materials Science
Country United States 
Sector Academic/University 
PI Contribution Multiple new research direction were explored with 3 publications in the main Physics and materials science journals resulting from it and two more in the preparation.
Collaborator Contribution Provided financial support for travel to the UCONN, access to equipment on the order of $400,000, with technical support on-site.
Impact Publications:Nanothermal characterization of amorphous and crystalline phases in chalcogenide thin films with scanning thermal microscopy Bosse, J., Timofeeva, M., Tovee, P., Robinson, B., Huey, B. & Kolosov, O. 7/10/2014 In : Journal of Applied Physics. 116, 13, 8 p., 134904 Research output: Contribution to journal > Journal article Nanomechanical morphology of amorphous, transition, and crystalline domains in phase change memory thin films Bosse, J., Grishin, I., Huey, B. & Kolosov, O. 30/09/2014 In : Applied Surface Science. 314, p. 151-157 7 p. Research output: Contribution to journal > Journal article Nanoscale mapping of in situ actuating microelectromechanical systems with AFM Rivas, M., Vyas, V., Carter, A., Veronick, J., Khan, Y., Kolosov, O. V., Polcawich, R. G. & Huey, B. D. 14/02/2015 In : Journal of Materials Research. 30, 3, p. 429-441 13 p. Research output: Contribution to journal > Journal article
Start Year 2014
 
Title METHOD AND APPARATUS FOR ION BEAM POLISHING US patent 9082587B2 
Description A method for forming a polished facet between an edge and a face of a sample, involves removing a first portion of the sample by directing an ion beam onto the edge adjacent the first portion along an ion beam axis to leave the polished facet. The ion beam axis lies on an ion beam plane oriented at a glancing incident angle, preferably from 1° to 30°, to a sample plane defined by and parallel to the first face. The ion beam is directed to flow from the edge towards the first face. Also disclosed is a sample preparation apparatus comprising a chamber adapted for evacuation with a sample holder adapted to hold a sample comprising a first face bounded by an edge, and an ion gun arranged to direct an ion beam along an ion beam axis towards the sample. The sample holder is configurable to position the sample relative to the ion beam such that a first portion of the sample is removable by the ion beam to leave a polished facet between the edge and the first face of said sample. The sample holder is configured to hold the sample whereby the ion beam axis lies on an ion beam plane oriented at an incident angle from 1° to 30° to a sample plane defined by and parallel to the first face of the sample. 
IP Reference WO2011101613 
Protection Patent granted
Year Protection Granted 2015
Licensed Commercial In Confidence
Impact A method for forming a polished facet between an edge and a face of a sample, involves removing a first portion of the sample by directing an ion beam onto the edge adjacent the first portion along an ion beam axis to leave the polished facet. The ion beam axis lies on an ion beam plane oriented at a glancing incident angle, preferably from 1° to 30°, to a sample plane defined by and parallel to the first face. The ion beam is directed to flow from the edge towards the first face. Also disclosed is a sample preparation apparatus comprising a chamber adapted for evacuation with a sample holder adapted to hold a sample comprising a first face bounded by an edge, and an ion gun arranged to direct an ion beam along an ion beam axis towards the sample. The sample holder is configurable to position the sample relative to the ion beam such that a first portion of the sample is removable by the ion beam to leave a polished facet between the edge and the first face of said sample. The sample holder is configured to hold the sample whereby the ion beam axis lies on an ion beam plane oriented at an incident angle from 1° to 30° to a sample plane defined by and parallel to the first face of the sample.
 
Title Method for ion beam polishing and polishing sample European Patent EP 2537017B1 
Description The present invention relates to a method for the preparation of samples having polished surfaces or facets suitable for the application of high resolution microscopy techniques such as electron microscopy, scanning probe microscopy and the like. In particular it relates to a method for forming highly flat and smooth cross-sections through device structures immediately adjoining a sample surface, to allow high resolution analysis of such device structures. For instance the invention relates to formation of facets on samples having epitaxial layers, multilayer structures, semiconductor thin films and the like where the structures and layers have sub-micrometre scale dimensions. When studying such device structures, it is desirable to achieve polished surfaces or facets with a roughness of the order of 1nm (root mean square peak-to-trough height) or better. 
IP Reference WO2011101613 
Protection Patent granted
Year Protection Granted 2016
Licensed Commercial In Confidence
Impact The invention allowed to establish a new business for theLancaster University spin-off Lancaster Materials Analysis and research collaboration with several industrial partners in UK, EU and USA.
 
Company Name Lancaster Materials Analysis 
Description Services to the industry and implementation of IP based on Lancaster patent US9082587 
Year Established 2014 
Impact Demonstrated potential for replacing TEM and SEM methods by less expensive in the characterization of semiconductor and optoelectronic structures
Website http://www.lancaster.ac.uk/news/articles/2014/novel-materials-analysis-technique-promises-to-reduce-...