Feasibility studies funded by Cyclops
- “SPI-CLOPS” (Surface Polymer Imprinted Closed Loop Optical Patient Sensors) for Dose Detection and Prevention of Cancer Resistance. (2017)
The treatment of melanoma has improved dramatically since the introduction of drugs that interfere with disease specific pathways. However, the development of resistance to these drugs is a major cause of concern, as it leads to treatment failure and poor patient outcomes. Early stage detection of resistance to cancer drugs could revolutionise therapeutic regimens for melanoma and other cancers. This proposal sets out the first stages in a new healthcare technology which could enable clinicians to monitor the efficacy of cancer drugs in appropriate time scales, and detect the first signs of resistance thus indicating the optimum time to administer combination therapies. Specifically, the project will develop advanced fibre-optic sensors with polymer coatings which allow simultaneous detection of drug levels in a cancer model and the onset of resistance pathways. Our vision is for sensing electronics and polymer materials science to be combined with mathematical modelling and 3D tumour mimics thus providing the critical proof-of-concept data prior to in vivo studies. We have assembled a multi-disciplinary, and international team with expertise linking physical and engineering science to advanced clinical oncology to tackle this vital unmet societal and medical need. Ultimately we envisage a fully automated system in which drug delivery and tumour properties are monitored so that the appropriate dose can be delivered at the appropriate time.
Critical (intensive) care projects
- Closed loop drug monitoring and delivery in intensive care (2017)
Survival in intensive care (IC) depends on having a comprehensive picture of a patient’s condition. Accurate continuous monitoring of vital parameters such as gas exchange, blood pressures and heart rate, temperature, ventilator mechanics, renal function, nutrition, and metabolism are available. However, continuous monitoring of drug levels is an unmet clinical need, the solving of which would provide a step change in IC practice and enable clinicians to provide optimised and individualized treatment of critically ill patients, with potential for reduced length of stay and of adverse events. Each patient day costs ~£1900
Using novel optical chemical sensors, we propose to develop real-time blood level monitoring of sedative and analgesic drugs such as fentanyl, midazolam and propofol. This would enable precise and individualized monitoring of infusion rates or other dosing schedules to maintain continuously effective drug levels while minimizing adverse effects due to overdosage and accumulation. This is particularly important in drugs which have a narrow therapeutic window, or those with significant toxic side effects, for example, aminoglycosides and ciclosporin, if not administered correctly, can induce hearing loss and kidney failure
Currently in IC many drugs are administered by continuous intravenous infusion devices which deliver a specified volume per minute or per hour. The actual drug preparation and the delivery rate itself are managed by clinical staff. Our proposal of feedback control of infusion devices using data from our sensors would allow more accurate and individualized management. Monitoring of blood levels would also provide an error trap in the event of mistakes in the preparation or delivery of these drugs.
- Investigation of closed-loop ventilation strategies for neonatal ICU patients using computational simulation (2017)
Ventilated critically ill newborn babies are prone to sudden and large changes in their respiratory state, requiring frequent and rapid interventions by ICU staff. If not acted on promptly, these can increase the risk of brain injury or eye disorders resulting in long-term disabilities and blindness. Closed-loop ventilation control modes have the potential to simultaneously improve patient care and reduce staff workload, by automatically adapting ventilator settings in response to changes in the physiological state of the patient. To date, however, such closed-loop technologies have only been applied to the care of adult ICU patients. We will extend and adapt a computational simulation platform, that has been developed by the investigators over the past 10 years, so that it can accurately represent the unique (patho)physiology of mechanically ventilated neonatal patients. Using extant and prospectively acquired date we will validate the capability of our simulator to replicate the responses of individual newborn babies to a variety of changes in mechanical ventilator settings. Once validated, the simulator will be used to investigate the feasibility of developing closed-loop control algorithms that are tailored to the specific requirements of neonatal patients. Throughout the project, we will engage with our industrial partners (Medtronic, Philips Research, etc) to expedite the transfer of our closed-loop control technologies into the next generation of mechanical ventilators. On completion of the feasibility study, we will write a large-scale EPSRC/MRC grant application that will provide the resources to fully realise the many potential clinical and industrial applications of this work.
Position paper, and special issue on 'imaging and sensing' forthcoming!
Das, M. Haque, M. Chikhani, O. Cole, W. Wang, J.G. Hardman and D.G. Bates, "Hemodynamic effects of lung recruitment maneuvers in acute respiratory distress syndrome", BMC Pulmonary Medicine, 17:34, DOI: 10.1186/s12890-017-0369-7, 2017
M. Chikhani, A. Das, M. Haque, W. Wang, D.G. Bates, and J.G. Hardman, "High PEEP in ARDS: evaluating the trade-off between improved oxygenation and decreased oxygen delivery", British Journal of Anaesthesia, 117 (5): 650–8 (2016) DOI: 10.1093/bja/aew314, 2016
Other related articles
Rohit Karnik, Closed-Loop dynamic dosing: A system consisting of an aptamer-based microfluidic biosensor and a simple feedback-control algorithm adjusts therapeutic dosing in near real time in small animals.
Sara Bagherifard et al, Dermal Patch with Integrated Flexible Heater for on Demand Drug Delivery.
A. Nolan Wilson & Anthony Guiseppi-Elie, Targeting homeostasis in drug delivery using bioresponsive hydrogel microforms.
Y. T. Liew et al. Severe descending necrotizing mediastinitis: vacuum-assisted dressing did wonder.
Luca A Dessy et al, Retention of polyurethane foam fragments during VAC therapy: a complication to be considered.
P. L. Mage et al, Closed-loop control of circulating drug levels in live animals.