06.06.2014 Views

Download Professor Chris Lowe's presentation

Download Professor Chris Lowe's presentation

Download Professor Chris Lowe's presentation

SHOW MORE
SHOW LESS

You also want an ePaper? Increase the reach of your titles

YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.

DIAGNOSTICS: THE SCIENTIFIC AND<br />

TECHNOLOGY HORIZONS<br />

PROFESSOR C R LOWE FREng<br />

INSTITUTE OF BIOTECHNOLOGY<br />

DEPARTMENT OF CHEMICAL ENGINEERING AND BIOTECHNOLOGY<br />

UNIVERSITY OF CAMBRIDGE


BIOMEDICAL SENSING TECHNOLOGIES<br />

NON-INVASIVE<br />

IMAGING/SPECTROSCOPIC<br />

TECHNIQUES<br />

NON-CONTACT<br />

MINIMALLY-INVASIVE<br />

PERCUTANEOUS<br />

BIOLOGICAL FLUIDS:<br />

SWEAT<br />

TEARS<br />

SALIVA<br />

BREATH<br />

URINE<br />

CONTACT<br />

BIOSENSORS<br />

INVASIVE<br />

BLOOD<br />

CSF<br />

IN-VIVO<br />

IMPLANTED


BIOSENSOR PRINCIPLES<br />

ANALYTE<br />

HOME<br />

(BIO)RECOGNITION SYSTEM<br />

PHYSICIAN’S<br />

OFFICE<br />

TRANSDUCER<br />

CENTRAL LABORATORY<br />

REFERRAL SITE<br />

OPERATING THEATRE<br />

ITU<br />

WORKPLACE<br />

ROADSIDE<br />

FIELD/<br />

FIRST RESPONDERS<br />

INSTRUMENTATION<br />

BATTLEFIELD


(BIO)SENSOR TRANSDUCERS<br />

ELECTRICAL<br />

OPTICAL<br />

ACOUSTIC<br />

THERMAL<br />

MAGNETIC<br />

MICROENGINEERED<br />

POTENTIAL (V)<br />

CURRENT (I)<br />

CONDUCTANCE (Λ)<br />

CAPACITANCE (C)<br />

INDUCTANCE (H)<br />

IMPEDANCE (Z)<br />

FLUORESCENCE<br />

LUMINESCENCE<br />

SPR<br />

RESONANT MIRROR<br />

GRATING COUPLERS<br />

DIFFRACTION GRATINGS<br />

FIBRE OPTIC<br />

QCM<br />

SAW<br />

LOVE/LAMB WAVE


MICROAMPEROMETRIC<br />

BIOSENSORS


MODERN CHALLENGES FOR BIOSENSOR<br />

TECHNOLOGIES<br />

SIMPLE, COST-EFFECTIVE (BIO)SENSORS<br />

FOR ANALYTES IN THE mM-fM RANGE<br />

MULTI-ANALYTE (ARRAY) DEVICES<br />

RAPID, LOW (NO) POWER CONSUMPTION<br />

FULLY INTEGRATED SYSTEMS WITH<br />

SAMPLE PREPARATION, SEPARATION<br />

AND ANALYSIS ON SAME DEVICE<br />

FACILE, COST-EFFECTIVE FABRICATION<br />

E-INTERFACE


MAGNETIC ACOUSTIC RESONATOR SENSOR<br />

(MARS)<br />

LIQUID SAMPLE<br />

PIEZOELECTRIC<br />

QUARTZ DISC<br />

(AT-cut, 0.25mm<br />

thick, 12mm dia)<br />

ACOUSTIC WAVE<br />

RF COIL<br />

N<br />

NdFeB MAGNET<br />

AIR GAP<br />

S


LOCK-IN<br />

AMPLIFIER<br />

MARS EXPERIMENTAL SET-UP<br />

PC/SOFTWARE<br />

SIGNAL<br />

GENERATOR<br />

AM DETECTOR DIODE<br />

MARS DEVICE


hIMMUNOGLOBULIN G BINDING TO MARS<br />

600<br />

500<br />

400<br />

-Δf (Hz)<br />

300<br />

200<br />

100<br />

0<br />

0 25 50 75 100 125 150 175200<br />

[hIgG] (μg/ml)


ACOUSTIC SPECTRA OF PROTEIN MULTILAYERS<br />

Frequency shift (KHz)<br />

50<br />

40<br />

30<br />

20<br />

10<br />

ACOUSTIC SPECTRA<br />

1. IgG 1000 ug/ml<br />

2. Prot A 250 ug/ml<br />

3. IgG 250 ug/ml<br />

4. Prot A 250 ug/ml<br />

5. IgG 250 ug/ml<br />

0<br />

0 100 200 300 400 500 600<br />

Penetration depth (nm)<br />

ACOUSTIC EVANESCENT WAVE<br />

200<br />

150<br />

100<br />

50<br />

0<br />

10 30 50 100 200 500 1000<br />

IgG<br />

Frequency (MHz)<br />

Frequency (MHz)<br />

MASS LOADING<br />

..<br />

ƒ n = n V s / λ = n V s / 2t<br />

Δƒ ∝ mass of the layer<br />

Sauerbrey<br />

t<br />

VISCOELASTIC COUPLING (MOLECULAR<br />

CONFORMATION/ACOUSTIC FINGERPRINT)<br />

. .<br />

Δƒ ∝ (ρη) 1/2<br />

Kanazawa


MULTI-ANALYTE ANALYSIS BY FREQUENCY TAGGING OF<br />

QUARTZ CRYSTAL FRAGMENTS<br />

2<br />

Amplitude (mV)<br />

-2<br />

-6<br />

-10<br />

-14<br />

221.35 221.39 221.43 221.47 221.51<br />

Frequency (MHz)<br />

2<br />

Amplitude (mV)<br />

-2<br />

-6<br />

-10<br />

-14<br />

221.35 221.39 221.43 221.47 221.51<br />

Frequency (MHz)


REMOTE ACOUSTIC MEASUREMENTS<br />

WITH A TOROIDAL ELECTRIC FLUX<br />

GLASS BEAKER<br />

30<br />

20<br />

10<br />

0<br />

-10<br />

QUARTZ DISC<br />

-20<br />

-30<br />

20.1 20.12 20.14 20.16 20.18 20.2<br />

TOROIDAL ANTENNA<br />

(TRANSCEIVER)<br />

f (MHz)


FABRICATION OF HOLOGRAPHIC<br />

SENSORS<br />

LASER<br />

SPATIAL<br />

FILTER<br />

MIRROR<br />

ACHROMAT<br />

GLASS TANK<br />

EMULSION<br />

4°<br />

MIRROR


PRINCIPLE OF HOLOGRAPHIC SENSORS<br />

θ<br />

n<br />

“Smart” Polymer<br />

reflectance (%)<br />

35<br />

30<br />

25<br />

20<br />

15<br />

10<br />

5<br />

l pk<br />

R<br />

pk<br />

ΣR i<br />

0<br />

600 610 620 630 640 650 660<br />

wavelength (nm)<br />

d<br />

λ max<br />

= 2ndcosθ<br />

COLOUR<br />

BRIGHTNESS<br />

IMAGE/<br />

ALPHANUMERIC<br />

MESSAGE<br />

POSITION


DETERMINATION OF WATER CONTENT<br />

OF AVIATION FUEL<br />

No trace of<br />

water in Jet<br />

Fuel<br />

Water<br />

detected in<br />

Jet Fuel


HOLOGRAPHIC<br />

“BREATHALYSER”


Wavelength (nm)<br />

800<br />

750<br />

700<br />

650<br />

600<br />

550<br />

500<br />

pH SENSITIVE HOLOGRAMS<br />

MAA<br />

pH<br />

450<br />

2.5 4.5 6.5 8.5 10.5<br />

pH<br />

3 4 5 6 7 8 9<br />

λ max<br />

(nm)<br />

850<br />

800<br />

750<br />

700<br />

650<br />

600<br />

550<br />

500<br />

450<br />

400<br />

mol%<br />

5<br />

6<br />

4<br />

3<br />

2<br />

1.5<br />

3 4 5 6 7 8 9 10<br />

pH<br />

0<br />

λ max (nm)<br />

800<br />

750<br />

700<br />

650<br />

600<br />

550<br />

500<br />

0 1000 2000 3000 4000 5000 6000 7000 8000 9000 4.0 4.5 5.0 5.5 6.0<br />

time (s)<br />

pH


CATION-SENSITIVE HOLOGRAMS<br />

O<br />

O<br />

O<br />

O<br />

O<br />

50mol% 18C6/HEMA<br />

O<br />

O<br />

O<br />

18C6<br />

Δλ max<br />

(nm)<br />

290<br />

240<br />

190<br />

140<br />

90<br />

40<br />

-10<br />

K + (1.33Å)<br />

Na + (0.97Å)<br />

0 10 20 30 40<br />

[X + ] (mM)<br />

150mM Na + +20mM K +


PENICILLIN-RESPONSIVE HOLOGRAM<br />

200<br />

diffraction wavelength shift (nm)<br />

180<br />

160<br />

140<br />

120<br />

100<br />

80<br />

60<br />

40<br />

20<br />

0<br />

-20<br />

0 2 4 6 8 10 12<br />

diffraction wavelength (nm)<br />

750<br />

700<br />

650<br />

600<br />

550<br />

0<br />

0.1<br />

0.5<br />

1<br />

0 200 400 600 800 1000 1200 1400 1600 1800<br />

time (s)<br />

4<br />

3<br />

2<br />

5<br />

6<br />

7<br />

8<br />

9<br />

10<br />

rate of diffraction wavelength shift (nm / s)<br />

3.5<br />

3.0<br />

2.5<br />

2.0<br />

1.5<br />

1.0<br />

0.5<br />

0.0<br />

-0.5<br />

[penicillin] mM<br />

0 2 4 6 8 10 12<br />

[penicillin G] (mM)


BORONATE-BASED GLUCOSE HOLOGRAM<br />

1<br />

0<br />

Elapsed Time (min)<br />

200 400 600 800 900<br />

Δλmax (nm)<br />

-4<br />

-9<br />

6<br />

HO<br />

11<br />

R1<br />

O R2<br />

- O<br />

B<br />

15.5<br />

19<br />

-14<br />

R<br />

23.5<br />

27 [Glucose]


REAL-TIME HOLOGRAPHIC GLUCOSE<br />

CONTACT LENS BIOSENSOR<br />

KEY ISSUES TO ADDRESS<br />

TOXICITY<br />

TEAR [GLUCOSE] < BLOOD<br />

[GLUCOSE]<br />

pH VARIATION<br />

TIME LAG (~MIN)<br />

SELECTIVITY (LACTATE)<br />

OPTICAL<br />

PHYSICS/DETECTION


TRACKING OF BLOOD GLUCOSE IN<br />

TEAR FLUID IN VIVO<br />

160<br />

740<br />

Blood-Glucose [mg%]<br />

140<br />

120<br />

100<br />

720<br />

700<br />

Wavelength [nm]<br />

80<br />

0 12 16 19 23 26<br />

Time [minutes]<br />

680


L-LACTATE HOLOGRAM<br />

140<br />

730<br />

120<br />

15mol%<br />

710<br />

100<br />

20mol%<br />

Peak Wavelength (nm)<br />

690<br />

670<br />

650<br />

630<br />

Peak Shift (nm)<br />

80<br />

60<br />

40<br />

12mol%<br />

25mol%<br />

10mol%<br />

8mol%<br />

30mol%<br />

610<br />

20<br />

5mol%<br />

40mol%<br />

590<br />

0 5000 10000 15000<br />

20000<br />

0<br />

0 5 10 15<br />

Time (s)<br />

[Lactate] (mM)


“BIOLOGY-ON-A-CHIP” CONCEPT<br />

580nm<br />

2mm<br />

NANOWELL<br />

INPUT<br />

100μm<br />

OUTPUT<br />

HOLOGRAMS<br />

λ max<br />

DETECTORS<br />

A 580


ALCOHOLIC FERMENTATION IN SACCHAROMYCES<br />

CEREVISIAE<br />

30<br />

25<br />

20<br />

Δλ (nm)<br />

15<br />

10<br />

5<br />

0<br />

0 200 400 600 800 1000<br />

Time (min)


SPOILAGE OF WHOLE MILK BY<br />

LACTOBACILLUS CASEI<br />

640<br />

6.5<br />

620<br />

6.3<br />

6.1<br />

600<br />

5.9<br />

λ max<br />

(nm)<br />

580<br />

560<br />

540<br />

λ max (nm)<br />

700<br />

600<br />

500<br />

5.7<br />

5.5<br />

5.3<br />

5.1<br />

pH<br />

520<br />

400<br />

4 5 6 7<br />

pH<br />

4.9<br />

500<br />

4.7<br />

0 2000 4000 6000 8000 10000 12000 14000<br />

Time (s)


30<br />

650<br />

B. SUBTILIS<br />

FERMENTATIO<br />

N<br />

[Glucose] (mM)<br />

25<br />

20<br />

15<br />

10<br />

5<br />

HEXOKINASE<br />

ACCU-CHECK<br />

640<br />

630<br />

620<br />

610<br />

600<br />

590<br />

580<br />

570<br />

Peak Wavelength (nm)<br />

0<br />

560<br />

0 1 2 3 4 5 6 7 8 9 10<br />

Time (h)<br />

10<br />

7.3<br />

7.2<br />

Peak Wavelength (nm)<br />

660<br />

650<br />

640<br />

630<br />

620<br />

610<br />

600<br />

590<br />

580<br />

570<br />

5 10 15 20 25 30<br />

OD 600 nm<br />

1<br />

0.1<br />

7.1<br />

6.9<br />

6.8<br />

6.7<br />

6.6<br />

6.5<br />

0.01<br />

6.4<br />

0 1 2 3 4 5 6 7 8 9 10<br />

7<br />

pH<br />

[Glucose] (mM)<br />

Time (h)


GERMINATION OF Bacillus SPORES:<br />

MONITORED WITH A Ca ++ -SENSITIVE<br />

HOLOGRAM<br />

1.1<br />

0<br />

1.1<br />

1.0<br />

1.0<br />

0.9<br />

Δλ max<br />

(nm)<br />

-1<br />

-2<br />

-3<br />

OD 600nm<br />

0.8<br />

0.7<br />

0.6<br />

0.5<br />

0.4<br />

-5 -4 -3 -2 -1 0<br />

Δλnm<br />

0.9<br />

0.8<br />

0.7<br />

0.6<br />

OD 600nm<br />

-4<br />

0.5<br />

-5<br />

0 5 10 15 20 25 30<br />

Time (min)<br />

0.4


HAND-HELD PATHOGEN DETECTION


APPLICATIONS OF<br />

HOLOGRAPHIC SENSORS<br />

MEDICAL DIAGNOSTICS/DEVICES<br />

INDUSTRIAL<br />

DRUG DISCOVERY<br />

HIGH THROUGHPUT BIOLOGY<br />

FOOD/BEVERAGES<br />

COSMETICS<br />

SECURITY/AUTHENTICITY<br />

BRAND PROTECTION<br />

PACKAGING<br />

TOYS/DECORATIVES<br />

SMART CLOTHES<br />

LIVING ARCHITECTURE


E-MEDICINE<br />

EMERGENCY<br />

ROOM<br />

WEARABLE<br />

PERCUTANEOUS<br />

IMPLANTED<br />

SENSORS<br />

PATIENT<br />

2-WAY VIDEO LINK<br />

FOR IMAGE DATA<br />

CENTRALISED<br />

RECORDS<br />

DATABASE<br />

NETWORK<br />

SWITCHING<br />

FIRST<br />

RESPONDERS<br />

HOME<br />

WORKPLACE<br />

PHYSICIAN’S<br />

OFFICE<br />

BLOOD<br />

CHEMISTRY<br />

PC PERIPHERALS<br />

PRIMARY CARE<br />

PROVIDER


KEY DRIVERS FOR POINT-OF-CARE<br />

DIAGNOSTICS<br />

LIFESTYLE DIAGNOSTICS<br />

WELLBEING MONITORING<br />

PERSONALISED MEDICINE<br />

COST REDUCTION<br />

MINIATURISATION<br />

E-MEDICINE

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!