Printed sensor technology: progress towards commercialisation by Tony Killard

1. UWE Bristol
Printed sensor technology:
progress towards
commercialisation
Prof. Tony Killard
Professor of Biomedical Sciences
Centre for Research in Biosciences (CRIB)
Department of Biological, Biomedical and
Analytical Sciences, UWE
Adjunct Professor
Biomedical Diagnostics Institute, Dublin
ACES: The European Dimension
NCSR, DCU
21 May 2015

2. UWE Bristol

3. ESEAC MMXVI
16TH INTERNATIONAL CONFERENCE ON ELECTROANALYSIS
12TH -16TH JUNE 2016
THE ASSEMBLY ROOMS, BATH, UK

4. Advanced diagnostic device
technologies
• Combining…
– Advanced functional materials
– Print production technology
– Polymer MEMS microfabrication
– Bioassay systems integration
• To produce…
– POC diagnostic devices
– High performance
– Design for manufacture
tony.killard@uwe.ac.uk
LOPE-C, Munich
10-13th
June 2013
Winner of prototype
demonstrator competition

5. Polyaniline
The technicolour dream

6. Ink jet printed PANI NP ammonia sensors
Wavelength (nm)
400 600 800 1000
Absorbance(a.u.)
InkjetPrintedFilm
0.10
0.15
0.20
0.25
0.30
0.35
Absorbance(a.u.)
AqueousDispersion
0.0
0.5
1.0
1.5
2.0
2.5
3.0
Inkjet Printed nanoPANI
Aqueous dispersion nanoPANI
Potential (V)
0.2 0.4 0.6 0.8 1.0
Current(mA)
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
500 mV s
-1
300 mV s
-1
200 mV s
-1
50 mV s
-1
25 mV s
-1
Scan Rate (mV s-1)
0 100 200 300 400 500
PeakCurrent(mA)
-2.0
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
2.0
A
B
A'
B'
C
C'
Peak A
Peak A'
No. of Prints
1 5 10 20 30 40
Thickness(nm)
0
500
1000
1500
2000
2500
3000
3500
4000
Electrochim. Acta. 2008, 53, 5092-
5099
Prints/film thickness/current
UV-Vis spectroscopy
Scan rate
Silver Electrode
Polyaniline Layer
13.94 mm
13.94mm
Interdigitated
Electrode
51 mm
4.44mm
Silver Electrode
Polyaniline Layer
13.94 mm
13.94mm
Interdigitated
Electrode
51 mm
4.44mm
PRECISE CONTROL OF
FILM THICKNESS
HIGHLY REPRODUCIBLE
FABRICATION PROCESS
NANOPARTICLES FORM
CONTINUOUS FILMS WITH
BULK POLYMER
ELECTROCHEMICAL
PROPERTIES

7. Ammonia breath monitoring
SIGNIFICANT OPPORTUNITY
FOR POINT OF CARE BREATH
MONITORING TECHNOLOGY
•Liver/kidney dysfunction
•Screening, monitoring,
treatment support
•Urea cycle defects (HE)
•Ulcer detection (H. pylori)
CHALLENGES
•Low cost sensor system
•Quantitative
•Limit of detection (50 ppb)
•Specific for ammonia
•No interference from
temperature and humidity

8. Breath gas
concentrations
•Typically at parts per billion
concentrations
•In the presence of high concentrations
of O2, N2, CO2
•In the presence of high concentrations
of water vapour
– 91-96% RH@ 37o
C
•In the presence of other ‘interferent’
gases from body/mouth/atmosphere
MEASUREMENT OF TRACE GASES
IN BREATH REMAINS A
SIGNIFICANT ANALYTICAL
CHALLENGE
Crit. Rev. Anal. Chem., 2011, 41: 21-35.

9. -1
1
3
5
7
9
11
13
15
17
19
21
0 50 100 150 200 250 300 350 400 450 500 550 600
Time (s)
Z/Zo
2,175 ppb
1,919 ppb
1,576 ppb
1,368 ppb
984 ppb
755 ppb
392 ppb
245 ppb
121 ppb
40 ppb
Breath by breath analysis in
artificial breath with ammonia
4 s ‘breaths’, 15 s delay
Direct, real time breath by breath responses; Cumulative response to ammonia statistical averaging;
Atmospheric subtraction
0
2
4
6
8
10
12
14
16
18
20
0 200 400 600 800 1,000 1,200 1,400 1,600 1,800 2,000 2,200
[NH3] / ppb
Z/Zo
Final Reading
Breath 16
Breath 15
Breath 14
Breath 13
Breath 12
Breath 11
Breath 10
Breath 9
Breath 8
Breath 7
Breath 6
Breath 5
Breath 4
Breath 3
Breath 2
Breath 1
Background air
sampled
Baseline
established (Z0)
{

10. Prevent bacterial
contamination in
device (no effect on
ammonia conc.)
128 ml (1/4-1/5
average tidal
volume)
Atmospheric
inflow
Breath
overflow –
late tidal
110 l/min
Switch between
sampling and
measurement
Impedance instrumentation
now integrated
Single use, disposable
printed sensor
AmBeR®

11. Calibration of AmBeR®
with spectroscopy
• Calibration with simulated breath samples (n=33; individual electrodes)
• Humidity and temperature interferences eradicated
• Breath by breath measurement (8 breaths~ 5 min test time)
• LOD <40 ppb; range 0 - >3,000 ppb (full diagnostic range)
• R2
= 0.99, Slope = 0.00076 ppbv-1
and Intercept = -0.0354

12. 0
500
1,000
1,500
2,000
2,500
0 5 10 15 20 25 30 35 40
Blood Urea Nitrogen (mmol/L)
BreathAmmonia(ppbv)
Correlations with BUN, RR, Kt/V
r=0.61, p <0.01, n=96
• Haemodialysis patients
• Moderate correlations
• Patient-specific variables
• Not improved by looking at
change or clearance rates
0
20
40
60
80
100
120
40 50 60 70 80 90
Blood Urea Nitrogen RR (%)
BreathAmmoniaRR(%)
r=0.60, p<0.01, n=45
0
20
40
60
80
100
120
0.00 0.50 1.00 1.50 2.00
Kt/V (A.U.)
BreathAmmoniaRR(%)
r=0.50, p<0.01, n=44
Kidney Int. 1997, 52, 223; r=0.63, p<0.01, n=26, SIFT-MS
Nephrol. Dial. Trans., 2000, 15, 50; r=0.51, n=10, p<0.01, n=10, HPLC

13. Intra-individual
• Good correlation between
breath ammonia and blood
urea nitrogen
• Patient-specific responses
• r=0.86 to 0.96
– p=<0.0001 to 0.07
• Potential for patient-specific
calibration?
• How stable is this over time?
• Stronger correlations with
hepatic patients?
• Other applications?
Anal. Chem. (2013) 85: 12158-12165

14. Giving AmBeR the Green Light
• Revised prototype for clinical evaluation
– Fully automated
– Improve sensor insertion/removal
– Design for manufacture
– User interface
• Mass production of sensors
– Controlled scale-up of PANI NP production
– Scale up of screen and inkjet printing
processes

15. Fan
Sensor receiver
Valve
actuator
Air inlet
Sample inlet
Electromechanical control
Impedance analyser
Firmware
AmBeR v2

18. Screen printing
Inkjet printing
Dicing

20. Clinical evaluations
St. Vincent’s Hospital
Helicobacter pylori
Stomach ulcer diagnosis
Royal Free Hospital
Chronic liver disease
Management
St. Vincent’s Hospital
Chronic kidney disease
Management

21. Acknowledgements
• Prof. Malcolm Smyth
• Prof. Gordon Wallace
• Dr. Aoife Morrin
• Dr. Orawan Ngamna
• Dr. Troy Hibbard
• Dr. Karl Crowley
• Brendan Heery
• Ms Denise Carthy
• Dr. Karen Dawson
• Dr. Fadi Hatoum
• Dr. Nigel Kent
• Mr. Kieran Flynn