printed sensor technology: progress towards commercialisation
TRANSCRIPT
UWE Bristol
Printed sensor technology: progress towards commercialisationProf. Tony Killard
Professor of Biomedical SciencesCentre for Research in Biosciences (CRIB)Department of Biological, Biomedical and Analytical Sciences, UWE
Adjunct ProfessorBiomedical Diagnostics Institute, Dublin
ACES: The European DimensionNCSR, DCU21 May 2015
UWE Bristol
ESEAC MMXVI16TH INTERNATIONAL CONFERENCE ON ELECTROANALYSIS12TH -16TH JUNE 2016THE ASSEMBLY ROOMS, BATH, UK
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
LOPE-C, Munich10-13th June 2013
Winner of prototype demonstrator competition
Polyaniline
The technicolour dream
Ink jet printed PANI NP ammonia sensors
Wavelength (nm)
400 600 800 1000
Abs
orba
nce
(a.u
.)In
kjet
Prin
ted
Film
0.10
0.15
0.20
0.25
0.30
0.35
Abs
orba
nce
(a.u
.)A
queo
us D
ispe
rsio
n
0.0
0.5
1.0
1.5
2.0
2.5
3.0
Inkjet Printed nanoPANIAqueous dispersion nanoPANI
Potential (V)
0.2 0.4 0.6 0.8 1.0
Cur
rent
(m
A)
-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
Pea
k C
urre
nt (
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
Th
ickn
ess
(n
m)
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 ElectrodePolyaniline Layer
13.94 mm
13.9
4 m
m
InterdigitatedElectrode
51 mm
4.44
mm
Silver ElectrodePolyaniline Layer
13.94 mm
13.9
4 m
m
InterdigitatedElectrode
51 mm
4.44
mm
PRECISE CONTROL OF FILM THICKNESS
HIGHLY REPRODUCIBLE FABRICATION PROCESS
NANOPARTICLES FORM CONTINUOUS FILMS WITH BULK POLYMER ELECTROCHEMICAL PROPERTIES
Ammonia breath monitoringSIGNIFICANT 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
Breath gasconcentrations
•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@ 37oC
•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.
-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/Z
o
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 sampledBaseline established (Z0){
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®
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
0
500
1,000
1,500
2,000
2,500
0 5 10 15 20 25 30 35 40
Blood Urea Nitrogen (mmol/L)
Bre
ath
Am
mon
ia (
ppbv
)
Correlations with BUN, RR, Kt/Vr=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 90Blood Urea Nitrogen RR (%)
Bre
ath
Am
mon
ia R
R (
%)
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.)
Bre
ath
Am
mo
nia
RR
(%
)
r=0.50, p<0.01, n=44
Kidney Int. 1997, 52, 223; r=0.63, p<0.01, n=26, SIFT-MSNephrol. Dial. Trans., 2000, 15, 50; r=0.51, n=10, p<0.01, n=10, HPLC
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
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
Fan
Sensor receiver
Valve actuator
Air inlet
Sample inlet
Electromechanical controlImpedance analyserFirmware
AmBeR v2
Screen printingInkjet printingDicing
Clinical evaluations
St. Vincent’s HospitalHelicobacter pyloriStomach ulcer diagnosis
Royal Free HospitalChronic liver diseaseManagement
St. Vincent’s HospitalChronic kidney diseaseManagement
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