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Ambulatory microdialysis sampling system

Lead Research Organisation: University of Bristol
Department Name: Henry Wellcome LINE

Abstract

Prof Stafford Lightman (Univ Bristol) has developed a medical device for the minimally invasive automated collection of regular samples from a subject 24 hours a day, including during undisturbed sleep. For the first time, this will enable the detailed study of clinical and biological analytes known to vary over the day. The device has potential applications in basic research, for prognosis and diagnosis of disease in animals and man, in clinical trials and drug development and for therapeutic monitoring. This project will deliver commercial proof of principle by developing a pre-production prototype of the device which is more user-friendly, flexible enough to be used in a range of research scenarios, and robust enough to be used on large animals as well as in man. This will be fully tested and validated, and ready for trials in man and CE marking. Achievement of a CE mark will pave the way for the device to be sold as a research tool, either through a licensee or a spinout company.

Publications

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Bhake R (2020) Continuous Free Cortisol Profiles in Healthy Men. in The Journal of clinical endocrinology and metabolism

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Bhake RC (2019) Continuous Free Cortisol Profiles-Circadian Rhythms in Healthy Men. in The Journal of clinical endocrinology and metabolism

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Klaas S (2025) Awakening not associated with an increased rate of cortisol secretion in Proceedings of the Royal Society B: Biological Sciences

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Lightman SL (2024) Clinical Endocrinology-Time for a Reset? in Journal of the Endocrine Society

 
Description We have now been able to move forward from our prototype device to a commercially sound device which has allowed us to spin out a new company, Dynamic therapeutics
Exploitation Route We already have applications from many other research groups to access or buy our device for their own research programmes
Sectors Electronics

Healthcare

Pharmaceuticals and Medical Biotechnology

 
Description Novel diagnostic methodologies
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Improved diagnostic pathways
 
Description Use of chronotherapy in glucocorticoid replacement treatment
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Early days!
 
Description EPSRC Centre for Predictive Modelling in Healthcare
Amount £2,008,954 (GBP)
Funding ID EP/N014391/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 01/2016 
End 10/2020
 
Description EU Horizon 2020 grant - Ultradian
Amount € 5,999,381 (EUR)
Funding ID Programme/Call: H2020 - H2020-PHC-2014, Proposal: 633515 - ULTRADIAN 
Organisation European Union 
Sector Public
Country European Union (EU)
Start 08/2015 
End 08/2020
 
Title Novel automated sampling system 
Description Miniaturized ambulatory microdialysis sampling system 
Type Of Material Biological samples 
Year Produced 2017 
Provided To Others? Yes  
Impact Currently under international assessment 
 
Title Interstitial cortisol measurements aligned by wake time, healthy volunteers 
Description Background: Cortisol is released upon activation of the hypothalamic-pituitary-adrenal axis, varies across the day, and possesses an underlying diurnal rhythm reactive and responsive to stressors. While the endogenous peak of cortisol occurs in the morning, the observed cortisol rise post-awakening has been named the cortisol awakening response (CAR) based on the belief that the act of waking up stimulates cortisol secretion. However, objective evidence that awakening universally induces cortisol secretion is limited. Methods: We used a mixed effects model with a linear spline fitted to the data to examine tissue free cortisol measurements obtained from 201 healthy volunteers by automated ambulatory microdialysis before and after awakening in their home environments. We also examined rate of change of cortisol depending on sleep duration and relative timing. Results: We found no evidence for a change in the rate of cortisol increase in the hour after waking when compared with the hour prior to waking. We instead observed substantial interindividual variability in absolute concentration and rate of change, and differences in dynamics that may be attributable to duration and relative timing of sleep. Conclusion: Based on these results, we strongly suggest caution is needed when interpreting cortisol measurements solely obtained in the hour after waking. 
Type Of Material Database/Collection of data 
Year Produced 2024 
Provided To Others? Yes  
URL https://datadryad.org/stash/dataset/doi:10.5061/dryad.2280gb62w
 
Description Miniaturised ambulatory microdialysis infusion collection device 
Organisation Designworks
Country United Kingdom 
Sector Private 
PI Contribution Industrial partner
Collaborator Contribution Development of device to a stage ready for commercial development
Impact EU Horizon 2020 - Dynamic hormone diagnostics (ULTRADIAN) - 5,999,381 EUR - 1.9.15 - 30.8.19
Start Year 2014
 
Title The device is protected by a UK patent, titled Fluid Sampling Apparatus and Method, P115838GB, which was filed in September 2012 
Description Automated sampling system 
IP Reference P115838GB UK jurisdiction 
Protection Patent application published
Year Protection Granted 2012
Licensed No
Impact 24 hour sampling in the home is now possible
 
Title Infusion pump 
Description This is an automated pulsatile infusion pump especially made for subcutaneous infusion of hydrocortisone. 
Type Therapeutic Intervention - Medical Devices
Current Stage Of Development Small-scale adoption
Year Development Stage Completed 2018
Development Status Actively seeking support
Clinical Trial? Yes
Impact Better understanding of the importance of chronotherapy 
URL https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001104-37
 
Company Name Dynamic Therapeutics 
Description Dynamic Therapeutics develops wearable e-health technology aimed at monitoring stress hormones. 
Year Established 2023 
Impact The device has already had a marked impact on the endocrinology and chronobiology research communities as it allows 24 hour monitoring of hormones, metabolites and drugs in subjects in their own home/work environments. This will immediately improve patient involvement ( patient support groups from UK, Europe and the US are already in direct communication with us), and will improve both diagnostic procedures and therapeutic strategies . initially in endocrine disease-but in future in hypertension and Diabetes mellitus.
Website http://dynamictherapeutics.net
 
Description Bristol Neuroscience Festival - Lecture on "The importance of rhythm for stress and the brain" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Part of the University of Bristol's outreach programme.
Year(s) Of Engagement Activity 2016
 
Description Public Lecture held at The Physiological Society in London and streamed world-wide on Facebook Live - The Physiology of Stress - Science of Stress. Lecture on "Mechanisms of stress" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact This is the first time that The Physiological Society has streamed a public lecture for a world-wide audience.
Year(s) Of Engagement Activity 2017
 
Description Royal Institution, London - Science of Sleep 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact This remains available on the Royal Institution website for all interested parties.
Year(s) Of Engagement Activity 2016
 
Description Talk to Bristol Pituitary Support Group at Southmead Hospital 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact An active discussion on recent advances in treating patients with disrupted hormone secretion
Year(s) Of Engagement Activity 2017
 
Description The importance of hormone dynamics in therapies 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Presentation followed by discussion about the importance of patterns of hormone replacement for best patient wellbeing.
Year(s) Of Engagement Activity 2017
 
Description University of Utrecht - Stress and Disorders of the Brain. Lecture on "Corticosteroid rhythms and replacement strategies" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Part of EU outreach programme
Year(s) Of Engagement Activity 2016