Miniaturised Diagnostics for Health

Zulfiqur Ali, (z.ali@tees.ac.uk)

School of Science and Technology
University of Teesside

Microdiagnostics, EKTN, NetPark, 1st June 2009 1

 Miniaturised diagnostics for health

• Increasing costs of healthcare

– Demographics
– Chronic diseases (heart disease, stroke,
cancer, diabetes, lung cancer) are leading
causes of mortality and increasing in
prevalence
• Prevention and early detection of disease
• Care at the point of need
• More efficient approach for development
of drug therapies
• Need for complex chemical and biological
operations at low cost in automated
manner to allow operation by non-
specialist staff

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 Microfluidics
• Storage, dosing, moving and mixing small
volumes (mL – pL) of liquids in channels
typically 10-100m wide
• Design and construction
• Fabrication protocol
• Fluidic control (pressure, electrokinetic,
centrifugal, acoustic)
• Detection (optical, electrochemical,
acoustic…)
• Packaging, macro world interface (fluidic,
mechanical, optical, electrical)
• Materials - glass, silicon, polymer, hybrid

3
 DVT-IMP: aid diagnosis of deep vein
thrombosis
• DVT is the leading cause of unexpected death in
most developed nations
• results from the formation of blood clots in deep
veins, usually in the leg.
• Diagnosis is problematic.
– Requires blood test and clinical assessment
followed by medical imaging if required.
– Current blood tests can only eliminate DVT.
– Specificity of current tests results in false negative
results, putting patients at risk.

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http://www.diagnosingdvt.com
 DVT-IMP
• Measure D-dimer concentration
in whole blood
– Immunoassay using high
affinity antigen-antibody
binding
– Impedance based detection
– Microfluidics for sample 1200
1100
Ab - 0.4 mg/ml
Ag - 100 pg/ml
processing 1000 Ag - 500 pg/ml
Ag - 4,5 ng/ml
900
• Quantitative, accurate and
- Im (Z) ( cm )
Ag - 500 ng/ml

2
800 Ag - 4,5 µg/ml
reproducible 700
600

• Simple and easy to use 500

400
• Potential use in primary care 300

and clinics 200

100
00 500 1000 1500 2000 2500

2
Re (Z) ( cm )

Nyquist Plots for varying model [Ag]

Dynamic range: 100pg/ml – 100ng/ml, Opt. temp. 25 0C
Transducer layer
 Receptor Immobilisation
COOH

O O COOH
O O N

O N O N
+ O O ANTA N
N N
H
N Potentiometry N N PBS H H
H H H n m
n m
Py P yNHP Q=11mC/cm2
HOOC
N

HOOC NH2

HOOC

M2+
COOH COOH
M2+ M2+
COOH COOH
N N
COOH COOH

N N Sc ANTIBODY N N
H H H H
n m PBS n m

COOH
ANTIGENE M2+ a) 140
120
COOH 100
80

Z (nm)
N
60
COOH 40
20
0
720nm 0 0.5 1

N N X (m )

2.0µm
H b)
n H m 5
4

Z (nm)
3
2
1

2 3 4 200nm 200nm
0
0 100
X (nm )
200

(a )
1

(b )
7
 Diagnostic Cartridge

Electrode layer

Adhesive foil

Microfluidic body
 Roll-to-roll process
Photolithography Development Cu etch

Lamination
of photoresist

Laser dicing Cr etch Stripping of

photoresist

Technologyprototype
Technology prototype
realisedinincopper
realised copper