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![Page 1: Nmed presentation](https://reader033.fdocuments.us/reader033/viewer/2022060120/5592fe7f1a28abae1e8b4607/html5/thumbnails/1.jpg)
Development of Hand-held Instrument for STI Diagnostics
Professor.((W.(Balachandran((Bala)(Director((of(the(Centre(For(Electronic(Systems(Research(
School(of(Engineering(&(Design(Brunel(University(
March 2013 1"
Enabling(and(TranslaGng(Advances(in(DiagnosGc(and(CommunicaGon(Technologies(to(Reduce(the(Burden(of(Sexually(
TransmiJed(InfecGons(
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Self Testing Instrument for Sexually Transmitted Infections
Taking laboratory diagnosis into the field
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Integrated System for POCT
3"
((((((Wireless(((((((Interface(
DNA(ExtracGon((&(PurificaGon((
Sample(collecGon( MicroFluidic(Network((
DNA((DetecGon(
Electronic(Control(System(
DNA((AmplificaGon(
Sample(concentraGon((&(cell(lysis(
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The Team
Professor"Wamadeva"Balachandran"(Bala)"Principal(InvesGgator
Dr"Jeremy"Ahern"MicrofabricaGon Dr"Nada"Manivannan"
MulGphysics(Modelling Professor"Chris"Hudson"Electronic(Engineering(
Professor"Rob"Evans"
Biosciences(
Dr"Predraig"Slijpevic"""
Biosciences
Pascal"Craw"PhD(Student(
Biomedical(Engineering(
Branavan"Nehru"PhD(Student(
Paper(microfluidics(
Dr"Yanmeng"Xu"Printed(Electronics(
Sara"Chaychian"PhD(Student(
Electrical(Engineering(
Tosan"Ereku"PhD(Student(
Engineering(Design(
Dr"Krishna"Burugapalli""""""Biomedical(Engineering
Shavini"Wijesuriya"PhD(Student(
Engineering(Design(
Sana"Hussain"VisiGng(Scholar(Biosciences(
Sivanesan"Tulasidas""PhD(Student"Wireless(
CommunicaGon"""
Dr"Ruth"Mackay"BioMEMS/NEMS
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Modular Research Platform
Electromagnets
Lysis
AmplificaGon
DetecGon
Sample(&(Reagents
Waste
Disposable(Cartridge
GPSRFID
Bluetooth( 3G(Mobile
USBWiFi
Microcontroller(
Power(Management(
Display(and(User(Interface
MagneGc
Electrochemical
OpGcal(
SPR
MEMS
Nanowire
Nucleic(Acid(Detector(
Pumps
Valve(actuators
Thermal(control
StandardisaGon
ConcentraGon(/(PurificaGon
Sample(preWtreatmentElectronic(System
Control(System(
CommunicaGon(
Interface
Valves
Sensors
Electromagnets
Microfluidic(Network(
Pathways
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Sample Collection
• Swab and urine • 4mL of urine • 100uL swab elute • Simple design ‘Fool-
proof’ • Direct integration to
extraction device • Integrated lysis
Urine collection devices
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FE Analysis to Inform Design
Streamline depiction of flow from inlets to device discharge orifice
CessaNonal" flow" of" urine" from" six"inlets"into"the"airQfilled"cavity"
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DNA Extraction using Superparamagnetic Beads
8"
Ports
Coil recessCentral stub to Assist
the Coil Location
1 mm PMMA
Side Via to Port
500um PDMS
9 mm
Port Position
9 mm Coil Recess Diameter
Position of Chamber in PDMS Layer
12mm Pitch Circle for Ports
Chamber Cut-outPort Vias
8 mm
(a)
(b)
(c)
Microfluidic Chamber
Stainless Steel Port-ways
Polystyrene Collars
250mm Bore PVC Tubing
A photograph of microfabricated chamber with PVC tubing
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Microfluidic Dispenser
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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 f low over device: no
centrifugation/active mixing
Two(DNA(extracGon(devices(with(embedded(biopolymer(membrane(
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DNA Extraction Performance
0"
10"
20"
30"
40"
50"
60"
70"
80"
90"
100"
0" 0.1" 100"
Percen
tage(Recovery(((%
)(
Sample(ConcentraGon((ng/uL)((Salmon(sperm(DNA)(
Spin"Column"(Qiagen)"
Bioplymer"membrane"
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Lab-in-a-Tube
Biopolymer and Lysis buffer will be integrated into the device to extract DNA
Cell Lysis and DNA Extraction"
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0"
1"
2"
3"
4"
5"
6"
7"
8"
9"
10"
Standard"25µL""tube"rea
OnQchip"25µL"reacNon"
Final"D
NA"concen
traN
on"(u
g/mL)"
On-chip helicase dependent amplification
Isothermal Amplification • Helicase dependent
amplification • Single temperature (65�C) • 109 amplification power • < 20minutes reaction time • Can be used with real-time
fluorescence chemistries RealWGme(plot(of(HDA(reacGon(
Fluo
rescen
ce"
Time"(minutes)"0""""""""""""""""""""5"""""""""""""""""""""10""""""""""""""""""15"""""""""""""""""""20"""""""""""""""""""25"""""""""""""""""""30"""""""""""""""""""35""""""""""""""""""40"
NegaNve"control"
PosiNve"Control"
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On-chip Amplification and Detection
Fluorescence"detecNon"on"microfluidic"chip"
0"
490nm"LED"
Amplified"Photodiode"
Emission"bandQpass"Filter""(530nm)"
OpNcal"Fibre"3mm"PMMA"
ReacNon"Chamber"
PMMA"Fluidic"Chip"
Finite"element"analysis"of"microfluidic"chip"to"characterise"thermal"properNes"
25µL"microfluidic"chip"
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Planar Spiral Inductor for Inductance-based biosensor
Magnetic Bead-based DNA Detection
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Silver"NPs;"a)1,"b)5"and"c)10µl"Hydrazine"in"0.1M"AOT/IPM"microemulsions"
Gold"NPs;"e)"1,"f)5"and"g)10µl"Hydrazine"in"0.1M"AOT/IPM"microemulsions"
a" b" c"
e" f" g"
Nano-particle/bead fabrication
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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((
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18"
Effect of dout on δL Effect of Beads Permeability µrB on δL
tc =2µm
tc =2µm
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19"
Effect of Conductor Thickness tC on δL Effect of Thickness of Underlying Permalloy tp on δL
The Effect of Frequency on Sensor Output
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Brass/Al"mould"for"a"detecNon"microfluidic"device"
DetecNon"device"with"automated"fluid"flow"and"electrodes"
Al"mould"for"a"fully"integrated"microfluidic"system"
Integrated"microfluidic"PDMS""device"
10mm"
10mm"
10mm"
Integrated Microfluidic Cartridges
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Communication Design Strategy
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Paper based microfluidics (µPADs)
Fabrication of µPADs
Wax"penetraNon:"comparison"of"printed"barriers"before"and"aher"curing"at"120oC"for"15"minutes"
Printed"barriers"of"500"µm"produced"fully"funcNonal"barriers."A"minimum"channel"width"of"~"300"
µm"is"achievable."
Printed"barriers"(Wax)"
Cured"barriers"(Wax)"
Xerox"ColorQubeTM"8570N"solid"ink"
Printer"
MulNplexing:"A"single"sample"effecNvely"
delivered"into"5"test"zones"
DNA"mobility"on"a"µPAD"
Inkjet"printed"silver"electrodes"(25"µm)"
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DNA Detection on µPADs
0(s( 30(s( 90(s( W(1( W(2( 0s"–"A"blank"test"device"as"a"control"before"introducNon"of""""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."
Water"as"control""
Blank"paper"as"control""
Serially"diluted"0.1pM"DNA""
Serially"diluted"1pM"DNA""
Serially"diluted"0.01nM"DNA""
Stock"DNA"soluNon"0.1nM"
All"above"pictures"are"obtained"through"the"BIOQRAD"Gel"DOCTM"XR+"system"and"the"associated"image"analysis"sohware"Image"LabTM."""
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Handheld Device Development
The current handheld system development
Future GUI