1. Evaluation and validation of a breath ammonia measurement technology for the improved management of patients with urea cycle defects

2. SIGNIFICANTLY REDUCED QUALITY AND QUANTITY OF LIFE
The Problem
Urea Cycle Defects (UCD)
Rare inherited disorders
Predominantly affect children
600 in UK, 250,000 globally
Toxic build up of ammonia
Cognitive impairment and neurological damage
Lifelong chronic and acute management
Constant threat of increased disability and death
CPS1 Carbamoyl phosphate synthase 1 deficiency
OTC Ornithine transcarbamylase deficiency
ASS Argininosuccinate acid synthetase deficiency
ASL Argininosuccinate acid lyase deficiency
ARG Arginase deficiency
NAGS N-acetylglutamate synthase deficiency
SIGNIFICANTLY REDUCED QUALITY AND QUANTITY OF LIFE

3. The Need Difficult to identify elevated ammonia
No easy way to measure ammonia
Poor acute management
Requires high index of suspicion
Results in regular hospitalisation
Poor chronic management
Quality of life
Stress
Cost of care
Risk
ACCURATE, CONVENIENT SELF-MANAGEMENT OF AMMONIA LEVELS

4. Engaging with patients and carers
“I cannot deal with upset. I am all over the place and I can feel my ammonia go up and cannot control it. If I had a way of measuring it, I would know when it was critical.”
“I go to school, I socialise I have a great life. If I could manage my ammonia, I would be able to avoid catastrophe whilst trying to continue as normal.”
“When we have to go to hospital it takes us an hour to get there. It then takes them one hour to assess the situation. Even though we know speed is critical and there should be no delay, we cannot prove to them that something needs to happen. Thus, the ammonia continues rising and rising.”

5. The Gap Point of care blood ammonia Qualitative breath assays
Instrumental breath methods
Ammonia breath sensors
NOT SUITABLE FOR THE QUANTITATIVE MEASUREMENT OF AMMONIA AT POC

6. The Ammonia Breath Monitor
The solution
AmBeR®
The Ammonia Breath Monitor
Printed conducting polymer nanoparticle sensor technology
10 years of research
£900,000 investment
15 high-impact peer reviewed publications
2 patents and 1 trademark
Evaluated in normal and patient populations
Comparable analytical performance to instrumental methods
Low cost, disposable sensors
Small portable instrument
40 – 3,000 ppbv, r2 >0.99, rsd <11%

7. The Questions
Can the AmBeR system be used to improve the management of patients with UCDs?
Can it be used for the effective measurement of ammonia in the breath of UCD patients?
Can it be used to estimate blood ammonia accurately and reliably across the clinical range?
Can it be used for home self testing?
Will it facilitate remote management?
Will it reduce costs?
Will it improve quality of life?

8. The Team Project Leader Dr. Suresh Vijay Dr. Lara Abulhoul
Prof. Tony Killard
Dr. Lara Abulhoul
Prof. Julian Hamilton-Shield
Dr. Jo White
Dr. Michael Champion

9. The Plan 2016 2017 2018 2019 Project start Ethics submission
Availability of AmBeR system prototypes
Prototype prep.
Regulatory prep.
Lab
Verify ability to estimate blood ammonia from breath
Clinic
Potential of AmBeR UCD for remote management
Home
Estimations of NHS costs and quality of life
Exploitation phase

10. The AmBeR clinical system
Instrument
Laptop
Sensor cartridge
Software
Sampling system

11. The AmBeR R&D clinical system

12. The sensor How does it work?
Plastic cartridge for holding, inserting and removing from instrument
Protects sensor layer from damage
Green sensor ink which detects ammonia – don’t touch!
Silver conductive connectors to connect sensor layer to the instrument

13. How does it work?
Software

14. AmBeR can measure ammonia in breath
What now?
AmBeR can measure ammonia in breath
We think this can be used as an easier way of measuring ammonia levels in the body
However, no-one has yet demonstrated this

15. What now?
Firstly, we want to find out if the levels of ammonia in blood relate to those in breath
We then want to see if the levels of ammonia we measure relate to patient health status

16. If measuring breath ammonia can be used to help manage ammonia levels…
What then?
If measuring breath ammonia can be used to help manage ammonia levels…
We want to develop an AmBeR system that patients and families can use in their own home
Simple to use and does not require a separate computer

17. AmBeR UCD (home use) system
Touch screen user interface
Insertion of sensor cartridge
Flip top operational access
Games console style design

18. Current prototype

19. Current prototype