Closed loop control systems for optimisation of treatment

Lead Research Organisation: University of Nottingham
Department Name: Faculty of Engineering


A treatment that is optimised and personalised to the individual patient can significantly improve outcomes across a range of medical conditions. The closed-loop control approach involves continuously monitoring key clinical parameters and, informed by mathematical models, adapting treatment. The advent of massive computer power, highly sensitive, specific and flexible sensors, and finely-titratable treatments has finally allowed closed-loop control systems to offer a revolutionary leap in medical treatment. Examples of challenges that might now be met include: the delivery of treatment to cancer patients, the moment-to-moment management of critically ill (or injured) patients, and the accelerated healing of chronic wounds. We propose the formation of a multidisciplinary team comprising academics, clinicians and industrialists, supported by stakeholders, to address these challenges.

The first year of the network involves bringing together the community in a series of Grand Challenge Workshops to establish a roadmap. Areas where there are gaps in technology or knowledge will be addressed by eight feasibility studies or secondments that will run during years 2 and 3 and will provide proof of concept data for grand challenge funding applications. These larger funding applications will be developed in parallel to the feasibility studies.

Planned Impact

This network will work directly with beneficiaries to ensure that feasibility studies funded by the network are of relevance to a range of stakeholders, and have the potential for implementation in a healthcare context. These will include;

1) The healthcare sector, in particular the NHS through improved patient care (more efficient, better outcomes).
2) The general public will benefit through personalised models of healthcare
3) A range of commercial private sector beneficiaries small and medium sized enterprises and larger companies who participate in network meetings.

Healthcare Impact
Critical care patients and their relatives would benefit from improved critical care. Over 100,000 patients are admitted to intensive care units (ICU) in the UK per year. Over the 5 years following an ICU admission there is an excess mortality for these patients there is now a substantial body of evidence to show that significant numbers of survivors of critical illness experience reduced cognitive function and longer term physical and psychological impairments (Griffiths et al, Critical Care 2013, 17:R100). Survivors of critical illness in the UK face a negative impact on employment and commonly have a care requirement after discharge from hospital.

Cancer patients would benefit from optimised treatment. About 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world (Jemal et al, CA Cancer Journal for Clinicians, 2011, 61:69019). A substantial proportion of the worldwide burden of cancer could be prevented with one of the major factors being early detection and treatment.

People with chronic wounds would benefit from improved treatment. 200,000 patients in the UK have a chronic wound with the cost to the NHS conservatively estimated at £2.3bn-3.1bn per year (at 2005-2006 costs), around 3% of the total estimated expenditure on health (£89.4bn) for the same period. With proper diagnosis and treatment, much of this burden should be avoidable (Posnett, J, Franks, PJ, Nursing Times 2008, 104:3, 44-45)

Commercial Impact
Industry partners will benefit from the partnerships with clinicians, academia, public and patients. They will also benefit from intellectual property that will be generated during the feasibility studies and future funding streams. A protocol will be established to govern aspects such as confidential information, IPR and associated benefits. Appropriate contractual arrangements will be put in place, including a collaboration agreement, to ensure compliance with all UK Research Council terms including Clause GC 21 Exploitation and Impact.


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Hernandez F (2022) U-shape functionalized optical fibre sensors for measurement of anaesthetic propofol in Sensors and Actuators B: Chemical

Description Through funding seven feasibility studies, a number of potentially-automated solutions have been developed to address prevention and personalised treatments in chronic wounds, cancer and critical care.
Examples of developments in chronic wounds include:
• The use of non-invasive methods to prevent pressure ulcers from forming in patients who have been lying on hospital beds for prolonged periods. The technology uses sensors to monitor and regulate certain physiological conditions and then tilt the hospital bed to decreasing pressure on sensitive areas of the body.
• The development of a smart footbed, able to accurately measure foot pressure distribution to stimulate foot ulcers. This enables the potential production of shoe 'insoles' for personalisation, by addressing pressure points of a particular individual's foot.
• The creation of a sensor system to detect and kill bacteria in chronic wounds to minimise infections. The technology works by using a 'smart wound dressing' material to detect presence of bacteria in the wound, and then release a drug that kills the bacteria. Sensors are used to monitor and regulate dosage of drug delivery into the wound.

Examples of developments in cancer care include:
• The development of an experimental system to mimic tumour environments and detect influencing factors of cells that respond to, or resist drugs; and factors preventing cancer cells from receiving full therapeutic dosages.
• The use of machine-learning algorithm to measure physiological parameters (circadian clock) of patients undergoing chemotherapy, and gauge the effectives of the therapy based on the parameters.

Examples of developments made in critical care include:
• The creation of synthetic chemical and novel optical sensors to measure sedative and analgesic drugs such as fentanyl and propofol. This is a critical part of a technology that monitors and detects drug over-dosage in critical care patients.
• The design of intelligent simulator to monitor patients' physiological conditions on mechanical ventilator, in order to adopt the most effect ventilation strategy.

Key overall discoveries made are:
1. Creation of closed-loop templates: re-usable models and algorithms.
2. Adaptable models for other clinical areas.
3. Potential production of a collaborative commercial product for prevention and management of chronic wounds.
Exploitation Route Most of the technologies of the closed-loop systems are in the prototype stages. Key findings have established feasibility of feedback solutions being created. The next stages in the development will require rigorous testing and the design of fully autonomous systems.
Sectors Digital/Communication/Information Technologies (including Software),Electronics,Healthcare,Manufacturing, including Industrial Biotechology

Description 3DBioNet: an integrated technological platform for 3D micro-tissues
Amount £626,046 (GBP)
Funding ID MR/R025762/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2018 
End 02/2022
Description Border detection of illicit drugs and precursors by highly accurate electrosensors
Amount € 5,504,415 (EUR)
Funding ID 833787 
Organisation University of Antwerp 
Sector Academic/University
Country Belgium
Start 08/2019 
End 09/2023
Title High-fidelity, multi-organ simulation of human cardiopulmonary pathophysiology 
Description A novel and highly-integrated, high-fidelity suite of models or human pathology and physiology. To-date, we have very detailed, validated models of the pulmonary, cardiac and vascular systems. Cardiopulmonary interaction is fully realised, and novel outputs are already arising from this. We have less detailed models of renal, cerebrovascular and haematological systems, which will be developed over coming months and years. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2015 
Provided To Others? Yes  
Impact - High impact publications have been produced. These have influenced policies and guidelines in medicine. - Large pharma companies (e.g. Bayer) have contracted our group to use our simulation to investigate new medicinal products. - Large manufacturers of mechanical ventilators (e.g. Medtronic, Draeger) have expressed an interest in collaborating to progress understanding of methods of ventilating critically ill patients' lungs. 
Description Care of Sweden 
Organisation Care of Sweden
Country Sweden 
Sector Private 
PI Contribution University of Southampton expertise in smart mattress systems developed under cyclops project.
Collaborator Contribution expertise in mattress design
Impact ongoing collaboration in development of smart active mattresses to prevent pressure ulcers
Start Year 2021