1. Development of Hand-held Instrument for STI
Diagnostics
Enabling(and(TranslaGng(Advances(in(DiagnosGc(and(
CommunicaGon(Technologies(to(Reduce(the(Burden(of(Sexually(
TransmiJed(InfecGons(
Professor.((W.(Balachandran((Bala)(
Director((of(the(Centre(For(Electronic(Systems(Research(
School(of(Engineering(&(Design(
Brunel(University(
emstwwb@brunel.ac.uk(
March 2013
1"

2. Self Testing Instrument for Sexually
Transmitted Infections
Taking laboratory diagnosis into the field

3. Integrated System for POCT
Sample(
collecGon(
MicroFluidic(Network((
Sample(
concentraGon(
(&(cell(lysis(
DNA(ExtracGon(
(&(PurificaGon((
DNA((
AmplificaGon(
Electronic(Control(System(
DNA((
DetecGon(
((((((Wireless((
(((((Interface(
3"

4. The Team
Professor"Wamadeva"Balachandran"(Bala)"
Principal(InvesGgator
Professor"Rob"Evans" Professor"Chris"Hudson" Dr"Predraig"Slijpevic"""
Biosciences
Biosciences(
Electronic(Engineering(
Sivanesan"Tulasidas""
Sara"Chaychian"
PhD(Student"
PhD(Student(
Wireless(
Electrical(Engineering(
CommunicaGon"
""
Dr"Jeremy"Ahern"
MicrofabricaGon
Tosan"Ereku"
PhD(Student(
Engineering(Design(
Dr"Yanmeng"Xu"
Dr"Nada"Manivannan"
MulGphysics(Modelling Printed(Electronics(
Branavan"Nehru"
PhD(Student(
Paper(microfluidics(
Shavini"Wijesuriya"
PhD(Student(
Engineering(Design(
Dr"Krishna"Burugapalli"""""" Dr"Ruth"Mackay"
Biomedical(Engineering
BioMEMS/NEMS
Sana"Hussain"
VisiGng(Scholar(
Biosciences(
Pascal"Craw"
PhD(Student(
Biomedical(Engineering(

5. Modular Research Platform
Sample(preWtreatment
Electronic(System
Display(and(User(
Interface
ConcentraGon(/(PurificaGon
Electromagnets
StandardisaGon
Pumps
Valve(actuators
Microcontroller(
Power(Management(
Sample(&(Reagents
Nucleic(Acid(
Detector(
MagneGc
SPR
CommunicaGon(
Disposable(Cartridge
Thermal(control
MEMS
RFID
GPS
Electrochemical
Bluetooth(
3G(Mobile
OpGcal(
WiFi
USB
Interface
Control(System(
Microfluidic(
Network(
Lysis
Sensors
Electromagnets
AmplificaGon
Nanowire
Valves
Pathways
DetecGon
Waste

6. Sample Collection
•
•
•
•
Swab and urine
4mL of urine
100uL swab elute
Simple design ‘Foolproof’
• Direct integration to
extraction device
• Integrated lysis
Urine collection devices

7. FE Analysis to Inform Design
CessaNonal" flow" of" urine" from" six"
inlets"into"the"airQfilled"cavity"
Streamline depiction of flow from
inlets to device discharge orifice

8. DNA Extraction using
Superparamagnetic Beads
(a)
Ports
9 mm
1 mm PMMA
Central stub to Assist
the Coil Location
500um PDMS
Coil recess
Microfluidic
Chamber
Side Via to Port
Stainless Steel
Port-ways
(b)
Position of Chamber
in PDMS Layer
Port Position
8 mm
12mm Pitch
Circle for Ports
9 mm Coil
Recess Diameter
250mm Bore
PVC Tubing
(c)
Port Vias
Polystyrene
Collars
Chamber
Cut-out
A photograph of microfabricated
chamber with PVC tubing
8"

9. Microfluidic Dispenser

10. DNA Extraction using Cationic
Biopolymer
• Novel membrane in development
• Cationic bioploymer membrane
• Reduces number of steps for DNA
extraction
• No toxic reagents
• Simple pH (5-9) change in aqueous
solutions
• 2 reagents required
• Simple flow over device: no
centrifugation/active mixing
Two( DNA( extracGon( devices( with( embedded(
biopolymer(membrane(

11. DNA Extraction Performance
100"
Percentage(Recovery(((%)(
90"
80"
70"
60"
50"
Spin"Column"(Qiagen)"
40"
Bioplymer"membrane"
30"
20"
10"
0"
0"
0.1"
Sample(ConcentraGon((ng/uL)(
(Salmon(sperm(DNA)(
100"

12. Lab-in-a-Tube
Biopolymer and Lysis buffer
will be integrated into the
device to extract DNA
Cell Lysis and DNA Extraction"

13. Isothermal Amplification
• Helicase dependent
amplification
• Single temperature (65 C)
• 109 amplification power
• < 20minutes reaction time
• Can be used with real-time
fluorescence chemistries
On-chip helicase
dependent amplification
10"
9"
8"
Final"DNA"concentraNon"(ug/mL)"
7"
RealWGme(plot(of(HDA(reacGon(
Fluorescence"
6"
PosiNve"
Control"
5"
4"
3"
2"
NegaNve"
control"
OnQ
chi
p"
25
µL"
rea
cN
on"
Time"(minutes)"
0"
Sta
nd
ard"
25
µL""
tub
e"
rea
0""""""""""""""""""""5"""""""""""""""""""""10""""""""""""""""""15"""""""""""""""""""20"""""""""""""""""""25"""""""""""""""""""30"""""""""""""""""""35""""""""""""""""""40"
1"

14. On-chip Amplification and Detection
0"
ReacNon"
Chamber"
490nm"
LED"
PMMA"
Fluidic"
Chip"
OpNcal"Fibre"
3mm"PMMA"
Emission"bandQpass"Filter""
(530nm)"
25µL"microfluidic"chip"
Amplified"
Photodiode"
Finite"element"analysis"of"
microfluidic"chip"to"characterise"
thermal"properNes"
Fluorescence"detecNon"on"microfluidic"chip"

15. Magnetic Bead-based DNA Detection
Planar Spiral Inductor for Inductance-based
biosensor

16. Nano-particle/bead fabrication
a"
b"
c"
Silver"NPs;"a)1,"b)5"and"c)10µl"Hydrazine"in"0.1M"AOT/IPM"microemulsions"
e"
f"
g"
Gold"NPs;"e)"1,"f)5"and"g)10µl"Hydrazine"in"0.1M"AOT/IPM"microemulsions"

17. Inductance Sensor: Simulation
(
Circular(planar(coil(
I(=(100(mA,((N(=(5((
Maximum(electric(potenGal(=(160((mV(
MagneGc(Flux(Density(=((4"Q"16(mT(
(
(
Square(planar(coil(
I(=(100(mA,((N(=(5((
Maximum(electric(potenGal(=(110((mV(
MagneGc(Flux(Density(=((4"Q"12(mT(
(

18. Effect of dout on δL
Effect of Beads Permeability µrB on δL
tc =2µm
18"

19. Effect of Conductor Thickness tC on δL
Effect of Thickness of Underlying
Permalloy tp on δL
The Effect of Frequency on Sensor Output
19"

20. Integrated Microfluidic Cartridges
10mm"
10mm"
Brass/Al"mould"for"a"detecNon"microfluidic"
device"
Al"mould"for"a"fully"integrated"microfluidic"
system"
10mm"
DetecNon"device"with"
automated"fluid"flow"and"
electrodes"
Integrated"microfluidic"PDMS""
device"

21. Communication Design Strategy

22. Paper based microfluidics (µPADs)
Fabrication of µPADs
Printed"barriers"(Wax)"
Cured"barriers"(Wax)"
Xerox"ColorQubeTM"
8570N"solid"ink"
Printer"
Wax"penetraNon:"comparison"of"
printed"barriers"before"and"aher"
curing"at"120oC"for"15"minutes"
MulNplexing:"A"single"
sample"effecNvely"
delivered"into"5"test"zones"
DNA"mobility"on"a"
µPAD"
Printed"barriers"of"500"µm"
produced"fully"funcNonal"barriers."
A"minimum"channel"width"of"~"300"
µm"is"achievable."
Inkjet"printed"silver"
electrodes"(25"µm)"

23. DNA Detection on µPADs
0(s(
30(s(
90(s(
W(1(
0s"–"A"blank"test"device"as"a"control"before"introducNon"of""""
W(2( FITC"tagged"25mer"DNA"sample"(0.01nM)."
"
30s"–"DNA"sample"moving"within"the"hydrophilic"channel."
"
90s"–"Further"movement"of"the"sample"into"the"waste"zone."
"
W1"–"DNA"sample"gelng"washed"away"by"water"into"the"
waste"zone."
"
W2"–"Further"washing"of"the"DNA"by"water"into"the"waste"
zone."
Stock"DNA"
soluNon"0.1nM"
Serially"diluted"
0.01nM"DNA""
Serially"diluted"
1pM"DNA""
Serially"diluted"
0.1pM"DNA""
Water"as"
control""
Blank"paper"
as"control""
All"above"pictures"are"obtained"through"the"BIOQRAD"Gel"DOCTM"XR+"system"and"the"associated"image"analysis"sohware"Image"LabTM."""

24. Handheld Device Development
The current handheld
system development
Future GUI