NIHRDataInsights/HRCSData huggingface dataset:
Title: Cross-disciplinary Interfaces Programme (C-DIP) Fellowship Fund
Funder: Engineering and Physical Sciences Research Council

Abstract: Raman spectroscopy uses laser light to provide an analysis or chemical fingerprint of materials such as human tissue. It has been shown by many research groups that Raman spectroscopy is able to distinguish between cancerous and healthy tissue in the laboratory. Previously, a Raman probe small enough to fit inside a medical endoscope that opens the way for the instant detection of cancers within the oesophagus was developed at Bristol. In the current project, we are investigating the feasibility of adapting the above core technology to make an intelligent hypodermic needle suitable for investigating cancer and cancer like conditions below the skin. The goal is to construct a probe suitable for the study of breast and prostate cancers but shorter probes will also be made for looking at lymph nodes and for tissue identification.The current Raman needle sensor relies on detecting far-field Raman scattering, which is extremely weak. However, to improve Raman scattering process the technology widely known as surface enhanced Raman spectroscopy (SERS) could be used in the new design. SERS exploits the locally enhanced electric field on rough metal surfaces to drastically improve the Raman scattering process. Another, novel, possibility to locally enhance electric fields is to use nano-antenna array as the SERS substrate. Nano-antennas (or optical antennas), currently being investigated by dr Klemm, are an emerging concept in nanophotonics. Similar to radiowave and microwave antennas, their purpose is to convert the energy of free propagating radiation to localized energy, and vice versa. Optical antennas exploit the unique property of metal nanostructures at optical wavelengths - plasmon resonance. Nanoantennas exhibiting plasmonic resonances can enhance the field leading to SERS signal enhancement that is approximately proportional to the fourth power of the field enhancement factor. This interdisciplinary project brings together research fields of electromagnetics, physics, photonics and nanotechnology. It is very timely and currently unrelated research efforts of dr Klemm and dr Day could be combined into a novel research project. Fabricating and testing first proof-of-principle prototypes we want to prove that nano-antennas can indeed improve SERS. This could results in future joint project proposal application.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: E-finger: a tactile diagnostic device with microscale resolution
Funder: Engineering and Physical Sciences Research Council

Abstract: An approach is proposed to the in vivo assessment of soft tissue quality using multi-scale mechanical measurements. The approach is applied to prostate gland compliance (as measured by dynamic modulus, E) using a micro-engineered probe for the detailed assessment of prostate cancer (PCa) building on our earlier work applied to benign prostatic hyperplasia (BPH). We have previously shown for the first time that a relationship exists between the mechanical and histological characteristics of the prostate in vitro. We wish to apply our findings to the in vivo setting, with the development of a remote palpation instrument for in vivo measurement of prostatic compliance in malignant disease. Such a device is likely to lead to major advances in the diagnosis, assessment and surveillance of men with PCa and emphasis is therefore placed on minimum levels of invasiveness. It is also expected that the study will result in a novel medical instrument and associated design paradigm of generic value for other applications where a remote or minimally-invasive measure of tissue quality is desired. The work will emphasise the importance of probe size and will investigate the interface between meso- and micro-scale measurements (tissue-level) and micro- to nano-scale measurements (cell-level) and a simple method for producing a range of probe sizes and levels of resolution is outlined.The projected is expected to deliver:- the first in vivo mechanical measurement of dynamic modulus- the first micro-scale in vivo mechanical measurement- the first approach applied to prostate compliance which integrates trans-urethral, trans- rectal and laparoscopic measurements- the first study of mechanically-assessed prostate tissue quality which uses a large number of patients A major feature of the work is the co-operation of clinicians and medical and engineering academics focused onto a problem with potential huge implications for the ageing population. The impact plan aims top exploit the immediate application to urology through two key industrial partners and a strong engagement with the UK and European urological community. A separate group will be established to examine the transfer of the findings to other medical specialisms, including hepato-biliary surgery and gastro-enterology.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: SMART-Endomicroscopy (Sensing and Mechatronically Assisted Real-Time Endomicroscopy)
Funder: Engineering and Physical Sciences Research Council

Abstract: As surgical techniques become more minimally invasive, there is an inevitable increase in complexity of the operating platforms Clinically, it is of vital importance to integrate real-time microscopic visualisation into the surgical workflow in a seamless way and in combination with the existing imaging modalities such as MRI, CT and ultrasound. The aim of this proposal is to develop a new SMART-endomicroscopic probe that integrates in situ sensing and mechatronic control to allow for flexible and consistent tissue characterisation for Minimally Invasive Surgery (MIS). It addresses specific research and engineering challenges related to biophotonics, mechanical/optical miniaturisation and integration, super-resolution image reconstruction, as well as tracking, localisation and large area coverage for in vivo, in situ tissue characterisation. Through multi-scale minimally invasive imaging integration, the proposed SMART-Endomicroscope will potentially allow cancer staging and intervention to be performed as a single procedure, permitting histological and vascular examination to be performed at all stages of the operation, such that management decisions can be altered intra-operatively to ensure best treatment for the individual patient. This will help to transform surgical treatment options and patient cancer outcomes as personalised healthcare becomes a reality. The project echoes the current paradigm shift in MIS towards miniaturised smart instruments with integrated imaging and sensing, enhanced by robotic control. It is supported by a multidisciplinary team with complementary skills in physics, engineering, medical image computing and surgery.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.4 SURGERY
Health categories: CANCER AND NEOPLASMS
Title: Hybrid UWB Radar/Inverse Scattering for Breast Cancer Imaging
Funder: Engineering and Physical Sciences Research Council

Abstract: Breast cancer is the commonest cause of death in women between the ages of 35 and 55 in Europe. Worldwide, a woman will die from the disease every 13 minutes. Breast cancer is very much a survivable disease however it is vital that the tumour is caught at an early stage. This requires a national screening programme for all women (in addition to regular self-examination by women of their breasts). Unfortunately the existing screening techniques are not very ideal. X-ray for example, is only suitable for older women and is also quite uncomfortable. Even in these older (post-menopausal) women, it has quite high false-positive rates (resulting in women having unnecessary biopsies) and false-negative rates (in other words, it misses some tumours). There is no suitable routine screening technique available for younger women. The aim of this proposal is to continue research into a new imaging method based on UWB radar. This sends out a short burst of radio-waves into the breast and "listens" for reflections - these radio-waves are completely harmless and the imaging procedure is quick and comfortable. At the moment this new imaging technique is in its infancy and much work remains to be done if we are to reach the ultimate goal of a cheap, quick and comfortable breast imaging method for all women. Because the imaging method is harmless, it could be repeated as often as necessary and because it will be very cheap, it could be based in a GP surgery or even a van, rather than requiring a visit to hospital.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Towards disease diagnosis through spectrochemical imaging of tissue architecture.
Funder: Engineering and Physical Sciences Research Council

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


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Synthesis of glycosyl-novobiocins: probes of Hsp90 C-terminal affinity binding and novel anti-cancer drugs
Funder: Engineering and Physical Sciences Research Council

Abstract: Cancer is a leading cause of death worldwide, accounting for 7.6 million deaths (around 13% of all deaths) in 2008 (WHO cancer, 2012). There are an estimated 12.7 million cancer cases around the world every year, and this number expected to increase to 26 million by 2030.Chemotherapy has proven to be very useful in addition to surgery in treating cancer. However, its effectiveness is often limited with the number of useful drugs and their toxicities. Designing effective drugs are always required to treat cancer for public health. Here we report a new approach to target Heat Shock Protein 90 kDa (Hsp90) using glycosylation technology. Hsp90 mediates protein folding which is important to cancer cell survival. Inhibition to Hsp90 maysimultaneously inhibit multiple therapeutic targets and pathways crucial to tumour survival. Novobiocin was originally approved for clinical use in the 1960s under the trade name Albamycin (Pharmacia and Upjohn) as an antibiotic drug. Recently, Novobiocin has also been shown to have low anticancer activity via binding to Hsp90. Previously, the poor affinity to Hsp90 and higher affinity for type-II topoisomerases prevented novobiocin being evaluated as a clinical useful Hsp90 inhibitor. Recently, we demonstrated that a glycosylation approach can separate the anti-cancer activity from the antibacterial activity (as a proxy of topoisomerase) to 27,000 fold providing a useful alternative strategy for anti-cancer drug discovery. However, the mechanism on how the drug interacts with Hsp90 C-terminal is not fully clear. The important biological roles of glycosylated novobiocins suggest that carbohydrate modifications are central to the biological function of these molecules. We propose that these glycosyl-based modification strategies are a potential route to the rational design, modification of lead compounds and repurposing of existing drug molecules.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Laser-printable point-of-care sensors for low-cost medical diagnosis and disease monitoring
Funder: Engineering and Physical Sciences Research Council

Abstract: The research we are proposing here is to develop laser-printed paper-based sensors that will satisfy the criteria of being robust, inexpensive, user-friendly, disposable, and easy to deliver to those patients and members of the public who need to access point-of-care diagnosis. Such sensors would find a ready market within the healthcare and personalised medicine areas, and would prove invaluable when rapid deployment and testing is required in the case of epidemics or worse still, pandemics. The proposal here is a first feasibility trial to confirm that we can indeed print viable biological material, for application in detection of selected breast-cancer biomarkers. The markers have been identified and validated by our IfLS/FOM team and are used to study the response of patients receiving chemotherapy. This would represent an original diagnostic product developed at the UoS. The work not only involves laser-based printing, and evaluating post-printing the viability of the printed biomaterial, but also investigating techniques for machining and processing of the paper substrate to be used for the sensor. There are many advantage of this laser-printing approach that are uniquely appropriate for non-contact delivery of biomedical materials, namely: Flexible processing (patterning and deposition) by simple changes to laser parameters. Non-contact processing (patterning and printing) which is vital when dealing with biological agents. No need for a specialist environment thereby eliminating unwarranted processing costs. The inherent speed of laser printing: a direct analogy can be drawn from current laser printers which can print many sheets per second. low production costs because of the possibility to mass-produce devices on a roll-to-roll scale. High feature resolution allowing the creation of compact devices. (Our final goal in a future follow-up proposal will be to print biomaterials in the form of bar-codes for intelligent/active diagnostics readout via smart phone applications). This laser-printing requires much smaller reagent/analyte volumes compared to current liquid based delivery (printing) methods.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Bioactive Natural Product Assembly Using Precious Metal Catalysis: Total Synthesis of Phyllostictine A
Funder: Engineering and Physical Sciences Research Council

Abstract: This project is focused on realizing the first total synthesis of phyllostictine A, the most potent member of a structurally unique class of natural product isolated from the fungus Phyllosticta cirsii. Phyllostictine A constitutes a formidable synthetic challenge, and its assembly will require us to develop a variety of new chemical reactions and processes. Emphasis will be placed on sustainable, catalytic transformations and on adhering to the principles of the 'ideal' synthesis (e.g. atom, step and redox economy). For example, the 4-, 5- and 11-membered rings will be made using palladium, gold, and ruthenium catalysis respectively. This natural product displays potent herbicidal activity against a variety of weeds, and most recently, anti-cancer activity. In parallel with the total synthesis, a selection of analogues and intermediates will be tested for bioactivity. This will help advance our understanding of the mode of action of phyllostictine A, and will pave the way for the development of simplified analogues of the natural product for use in medicine and agriculture.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Quantification of drug in live cells using label-free multi-bounce attenuated total reflection Fourier Transform Infrared (MB-ATR FTIR) spectroscopy
Funder: Engineering and Physical Sciences Research Council

Abstract: In the process of developing a new medicine, it is important to know how much of the medicine is absorbed by a human cell. This is usually achieved by adding a dye to label the medicine in order to visualise the amount of the medicine absorbed into the cell using visible or ultra-valet light. However, the added labelling dye may have an unknown effect to the overall results, therefore there is a need to develop and apply a new method that does not require any labelling of the medicine. This project will investigate on how to use a method called Fourier Transform Infrared (FTIR) spectroscopy, which is a label-free while chemically specific (this method can distinguish a large range of chemicals without labelling) analytical technique, to study the amount of medicine in living cell without any added labelling dye. FTIR spectroscopy is a well-established method for the analysis of medicine. However, it has not been used for measuring the amount of medicine in living human cell because, first, it is normally not sensitive enough to detect the small amount of medicine in a living cell. Second, it is not suitable to measure samples that are surrounded by a large amount of water such as live cells. These obstacles, fortunately, can be overcome by using a special measurement mode called the multi-bounce attenuated total reflection (MB-ATR) which can increase the sensitivity by at least 10 times as well as allowing the measurement of live cells bathing in aqueous medium. The project will use a medicine for treatment of cancer (doxorubicin) to demonstrate, for the first time, the possibility of using the FTIR technique to measure the amount of the medicine in living cells at concentration levels that is relevant to the treatment of the disease (~10 micro molar). This can be achieved by optimising the MB-ATR measurements through using the optimal number of bounces, ATR materials and measurement parameters so that the signal is maximised while the noise is minimised. The result of this development will then be compared to the results from the traditional methods to demonstrate that the FTIR technique is a reliable tool for studying medicine in living cell.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: De Novo Carbon-11 Chemistry: New and Explorative Radiolabelling Strategies for PET
Funder: Engineering and Physical Sciences Research Council

Abstract: Medical imaging technology is currently revolutionising our understanding of the human body, the human mind and the diseases that affect us. Imaging techniques are now routinely used for the diagnosis of illnesses and to assist in the discovery of new treatments and cures. Many of us are now familiar with the power of modern scanning technology, such as ultra-sound, MRI or CT, available within our hospitals for the diagnosing conditions ranging from broken bones to stroke. Positron Emission Tomography, or PET imaging for short, is certainly less familiar to the general public. Recent technological advances in computers, material sciences and radiochemistry have now enabled the routine use of PET imaging in many of the UK's major hospitals. PET is characteristically different from the other imaging techniques as it is primarily used to give a so-called 'functional' picture, as opposed to a purely anatomical image, of biological processes. The type of functional information gained from PET is extremely useful for better understanding biological processes involved in diseases such as cancer and neurodegenerative illnesses such as Alzheimer's. PET imaging requires the injection of a radioactive tracer into the body prior to scanning. The synthesis of these tracer molecules is particularly challenging because they need radioactive isotopes that have very short half-lives. PET tracers are typically prepared in the hours or even minutes prior to a scan. Chemistry therefore plays a hugely important role in the PET imaging process, both for the synthesis of existing tracers and the development of new ones. Currently, however, there is a limited range of chemical reactions that can be used to prepare tracers for PET. To develop new tracer molecules, which will ultimately lead to a greater understanding of disease processes and help to find treatments, new types of chemistry and technology need to be conceived. The aim of this research proposal is to develop completely new radiochemistry for the synthesis of new radiolabelled molecules that are currently inaccessible, and to use these new tracer molecules to probe the hall-marks of cancer. The new radiochemistry to be developed will be based on using a small reactive molecule, called carbon disulfide, that will be labelled with a radioactive carbon-11 atom. This so-called 'C-11 carbon disufide' will then be reacted to produce labelled molecules that will find applications in PET imaging.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Nanoparticles and microbubbles
Funder: Engineering and Physical Sciences Research Council

Abstract: Chemotherapy for the treatment of cancer continues to make great advances. However the current methods of drug delivery rely on injection into a blood vessel and remain very poorly optimised if at all. This results in having to administer high levels of t


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: A new nano particulate vehicle for ultrasound enhanced delivery of Cisplatin
Funder: Engineering and Physical Sciences Research Council

Abstract: Chemotherapy for the treatment of cancer continues to make great advances. However the current methods of drug delivery rely on injection into a blood vessel and remain very poorly optimised if at all. This results in having to administer high levels of the drug to the whole body, to give local concentrations in the tumour that are effective in reducing or eliminating the tumour. What this means for the patient is significant side effects such as general debilitation, but also the compounds used can be toxic to the kidneys, liver and nerve tissues. One such compound used is called Cisplatin and is the drug of choice for the treatment of head and neck cancers, which have an unacceptably high mortality rate of over 50%. This high mortality rate is due to a number of factors but one of the main factors is that these particular tumour types are quite aggressive and difficult to treat. Thus to develop a delivery system that gives much higher drug concentrations where it is needed would have significant benefits for both the patient and the healthcare provider. One method to deliver drugs to tumours is to utilise nanoparticles. The reason this potentially can be effective is that blood vessels in tumours are "leaky" and will allow nanoparticles to cross from the blood vessel into the tumour. However even though the nanoparticles cross the blood vessel, the particles can show quite poor uptake by the cancer cells. Thus our system aims to combine a nanoparticle within a microbubble. The idea behind the delivery system is that the nanoparticle trapped within the microbubble are injected and an ultrasound probe is applied to the site of the tumour. As the particles passes beneath the ultrasound probe, the ultrasound bursts the bubble and this produces a small shock wave and this has the effect of forcing the nanoparticle across the blood vessel wall and forcing the particle into the cells of the surrounding tumour. This ultimately will give much more localised delivery of the compound meaning enhanced efficacy and reduced side effects for the patient.


Research activity codes: 5.1 PHARMACEUTICALS;5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS