Identifiction of IBD using an electronic ‘e’ nose

1. Identifiction of IBD using an electronic ‘e’ nose Arasaradnam RP1,2, Ouaret N3, Nwokolo C1, Bardhan KD4, Covington JA3 1University Hospital Coventry & Warwickshire & 2Clinical Sciences Research Institute, Medical School, University of Warwick 3School of Engineering, University of Warwick, 4Rotherham NHS Trust 10th BROAD Meeting – February 2012 1

2. The Senses 5 Senses by Aristotle • Sight • Hearing • Smell • Taste • Touch But also… • Nociception (pain) • Equilibrioception (balance) • Proprioception & kinesthesia (joint motion and acceleration) • Sense of time • Thermoception (temperature differences) • Magnetoception (direction)

3. ‘Smell’ @ Warwick • First research group dedicated to the sense of smell • First company making artificial olfaction instruments • First commercial products manufactured here… • Long history of smell research… Life in ‘Smell’ Persaud & Dodd Nature 1982

4. Sniffing diseases..…

5. Electronic Nose

6. Human olfactory system Axel & Buck Nobel Prize 2004

7. How does it work? Array of sensors with different broad sensitivity e.g. Alcohols Operate by measuring change in resistance/capacitance/frequency e- e- e- e- e- e- e- e- e- e- e- e- e- e- e- e- e- e- If a different compound had caused the air to change, the output pattern will be different: Each sensor changes its resistance by a different amount, making a pattern of the change Measurement of baseline resistance

8. Electronic noses Food and cosmetics Gas emissions and Manufacturing processes Applications of Electronic nose Environmental pollutants Medical applications Homeland security

9. Sampling • Disease alters gut flora -altered fermentation patterns which alters the composition of gases emitted from urine • Urine headspace measured using an electronic nose and FAIMS (field asymmetric ion mobility spectrometry) • Novel method – non invasive • Possible faster and earlier detection of IBD

10. Methods • 48 patients and 14 volunteers; n = 62 • UC (n=20; active n=4), CD (n=20; active n=4) and 14 controls • Urine analysis with ‘e’ nose and FAIMS • Analysis was by Principal Component Analysis (PCA) – not pre-classified and LDA (Linear Discriminant Analysis) (pre-classified) E - nose

11. Warwick Electronic Nose Filtered air is passed over sample (1 L/min), capturing gas/vapours emanating from the sample Sample air is passed over sensors (300 secs) followed by clean air (300 secs) 10 ml of sample, placed in a sterilin bottle & heated to 40 oC

12. Separation of IBD with ‘E’ nose Arasaradnam et al JMET 2011

13. Can we detect IBD by measuring Volatile organic compounds/ gasses? Arasaradnam et al 2010

14. FAIMS – Field Asymetric Ion Mobility Spectrometry • Simple fast analysis of vapours and gases • Detects chemicals in complex mixtures • Identifies by mobility (ion movement through an electric field) • Mobility determined by molecule size and mass • Chemicals identified and separated • Can train to identify anomalies • Creates a chemical fingerprint

15. FAIMS Covington et al 2011

16. IBD flare v remission

18. What are we detecting? Summary of chemical peaks in volunteers and Crohns and UC patients HA=hydrogen azide (HN3); AA=acetic acid (CH3COOH); PG=propylene glycol (C3H6(OH)2); A=aldehydes; K=ketones; OA=organic acids.

19. Summary • Potential alternate diagnosis method • Able to distinguish between control and IBD patient groups • Can also identify specific disease groups ulcerative colitis and Crohn’s • Greatest difference is shown between diseased and non-diseased • FAIMS can also be used to identify diseased groups and supports e nose data

20. Acknowledgements: BROAD Foundation Thank you - Questions the future.......?