Acoustic Sensing with Dissipation: Real-TimeAnalysis of Surface/Chemical Interactions

Mark Poggi, Ph.D.Territory Manager

Q-Sense Inc.

Mark Poggi, Ph.D.University of Kentucky

August 22nd, 2007

Outline

• Brief Q-Sense History• Introduction to Quartz Crystal Microbalance

(QCM)• The QCM with the Dissipation monitoring

principle.• Applications• Applications

• Polymers• Biochemical• Electrochemical

• Concluding Remarks• Discussions

Brief History• 1976: Start of QCM-D research at Chalmers

• 1995: QCM-D patented

• 1996: Q-Sense AB founded

• 1999: Product development, prototype sales

• 2000: Commercial focus, 1:st generation product launched

• 2001: US Subsidiary, Newport Beach, CA

• 2005: 2nd Generation product launch, Q-Sense E4

• 2006: US Office moved to the east coast, systems in 25 countries

Q-Sense is a subsidiary of Biolin AB, a public company listed on theStockholm Stock Exchange. Biolin AB is an R&D and development basedcompany that invests capital, as well as competence, in order to create valuegrowth in high tech companies within life sciences and related areas.

• 2006: Biolin AB acquires CoAT AB

• 2006: Biolin AB acquires KSV

• 2007: Over 270+ scientific publications

Laboratories Utilizing QCM-D

• Harvard University, Prof. Whitesides

• Stanford University, Prof Curtis Frank

• Rutgers University, Prof J. Kohn

• Yale University, Prof P. Van Tassel

Academic

• Procter and Gamble (2)

• Medtronic, Inc.

• Nippon Paper Industries, JP

• 3M (Dental)

Industrial

• Boston University, Dr. Brown

• Georgia Tech, Prof. Henderson

• Chalmers University of Technology, SE, Prof. B. Kasemo

• Cambridge University, Cavendish lab, UK, Prof. A. Donald

• Max-Planck Institute, DE, Prof. W. Knoll

• Amgen

• Johnson & Johnson

QuartzQuartz is the only material known that possesses the following

combination of properties:

• Piezoelectric ("pressure-electric"; piezein = to press, in Greek)

• Zero temperature coefficient cuts exist

• Stress compensated cut exists

• Low loss (i.e., high Q)

• Easy to process; low solubility in everything, under "normal" conditions,except the fluoride etchants; hard but not brittle

• Abundant in nature; easy to grow in large quantities, at low cost, andwith relatively high purity and perfection. Of the man-grown singlecrystals, quartz, at ~3,000 tons per year, is second only to silicon inquantity grown (3 to 4 times as much Si is grown annually, as of 1997).

Jiri Janata, Principles Of Chemical Sensors. 1989.

QCM Timeline

Undeformed lattice

X++

++++

+++

++++++

+ +++++

____ __ ______ __

______

Y

_

Strained lattice

+++

+++

+++

++++++

++

++++

____ __ __

_____ __

___

___

-+

Y

_ fn

Cm 1

1880 1921 1959 1980 1996

++++ ___ _

Starts as research tool

Sauerbrey

• The ”Mandatory” reference for QCMapplications

1Linear relationship between frequency and mass:

fn

Cm 1

overtonen

sngcmC

127,17

Sauerbrey, G Z. Phys. 155 (1959) 206.

Military & AerospaceCommunicationsNavigationIFFRadarSensorsGuidance systemsFuzesElectronic warfare

IndustrialCommunicationsTelecommunicationsMobile/cellular/portableradio, telephone & pagerAviationMarineNavigationInstrumentation

ConsumerWatches & clocksCellular & cordlessphones, pagers

Radio & hi-fi equipmentColor TVCable TV systemsHome computersVCR & video camera

Acoustic Sensor Applications

Electronic warfareSonobouys

Research & MetrologyAtomic clocksInstrumentsAstronomy & geodesySpace trackingCelestial navigation

InstrumentationComputersDigital systemsCRT displaysDisk drivesModemsTagging/identificationUtilitiesSensors

VCR & video cameraCB & amateur radioToys & gamesPacemakersOther medical devices

AutomotiveEngine control, stereo,

clockTrip computer, GPS

John R. Vig, U.S. Army Communications-Electronics Command

The QCM-D sensor

Mass Sensitivity D-factorMass Sensitivity D-factor

in air (1 bar) ~0.2 ng/cm2

in water (25 C) ~0.9 ng/cm2

~410-8

~110-7

• Detection range in viscoelastic films: nm - m

• Temperature Range 15-45° C; long term stability +/- 0.02° C

QCM layout

Metallicelectrodes

Active electrode(reactionsubstrate)

Crystal, sensor, QCMCounter electrode

Contact electrodes

Vibration Modes

Induced withan AC Voltage

QCM-D ping principle: Teachingan Old Dog New Tricks

Δf is related to the massof the attached film(Sauerbrey relation)

ΔD is related to the

viscoelasticity

Instrument operation: Frequencyand Dissipation

5Mhz 15Mhz 25Mhz 35Mhz 5Mhz time

Features•Sequential multi frequency measurement•Freely oscillating crystal=true crystal frequency•Enables multiple frequencies & viscoelastic modeling

driving freq ~10 ms decay recording ~2 ms data communication ~13ms

Crystal non-oscillating 50% of the time

Note: QCM-D can sample viscoelastic changes over 100 times/sec.Compared to approximately one data point per 30 seconds whenusing impedance analysis.

The Quartz Crystal Microbalance withDissipation monitoring (QCM-D) technique

A(t)=A0exp(-t/)sin(2ft+)

D=1/ f

Mathematical representation

of the decay curve

Frequency change (Df):

Time ( s)

A f

mD stiffness

Frequency change (Df): adsorbed amount: Dm=-C·Df

(Sauerbrey equation)

Voinova et al., Physica Scripta 59 (1999) 391

Energy Dissipation (DD): rigidity

Multiple frequency modeling: shear viscosity and elasticity

ΔD Provides Insight Into:

• Verify validity of Sauerbrey relation

• Monitoring swelling/hydration

• Viscoelastic modeling

• Insight into structural changes• Insight into structural changes

Surfaces, Surfaces, Surfaces

Metals & OxidesSome Examples

SiO2, Al2O3, TiO2

W, Ir, Ta, Pt, Fe

Au, Ag, Cu, Cr

Spin-CoatedPolymers

PS

PC

PMMA

Protocols Immobilization

Streptavidin on SLB

Streptavidin on biotin-BSA

NTA on SLB

SiC, FeC3, TaN

Many More!

Custom made onrequest

Quartz

Metal-/ oxide

PMMA

Custom made onrequest

Quartz

Gold

Polymer

Surface Chemistry

SAM (Thiols & Silanes)

UVO Treatment

The Q-Sense E4 System

www.q-sense.com

•4 Sensors

•Peltier Thermal Control

•Baseline stability of 0.2 Hz in liquid!

•Electrochemistry Module

•Flow / stagnant mode

•Wide range of chip coatings

Removable flow module

Quartz crystal

Flow channelsfor temperaturestabilization

Inlet

Outlet

Cross section of flow module

So, What Can QCM-D Measure???

oxidized goldvesicle adsorption

SiO2

two steps to bilayer

26 Hz

-40

-20

0

freq

uen

cy(H

z)

gold with alkane thiolmonolayer adsorption

13 Hz

Lipid VesicleAdsorption

Ø 25 nm

Pfeiffer and Hook. Analytical Chemistry. 2006, 78, 7493-7498

400 500 600 700 800time (s)

90 Hz

300 400 500 600 700time (s)

-1

0

1

2

3

4

400 500 600 700 800

Dis

sipat

ion

(10-6

)

time (s)

-80

-60

freq

uen

cy(H

z)

C.A. Keller and B. Kasemo, Biophysical J. 75 (1998) 1397.

Antibody Detection of AlbuminAdsorbed on a TiO2 Surface

Albumin Antibody

C.W. Frank et al. Colloids and Surfaces B: Biointerfaces. 50 (2006) 76–84Höök, F., Rodahl, M., Kasemo, B. and Brzezinski, P. (1998) Proc Natl Acad Sci, 95 (21), 12271-12276.

Adsorption and Cross-linking

of a Mussel AdhesiveProtein

Release Dm (Ellipsometry / SPR):

Mefp-180

n=1

Time (min)

Rinsing

QCM-D:

-70

-60

-50

-40

-30

-20

-10

0

0 20 40 60

fn=1

Dn=1

f

(Hz)

Time (min)

Exposure to Mefp-1

0

2

4

6

8

10

12

14

100 120 140

D

(10

-6)Exposure to

NaIO4

Fant, C & Höök, F; Anal. Chem. (2001), 73, 5796-5804

NaIO4

Release

of Water

DmQCM = 1200 ngcm-2

Dm (Ellipsometry / SPR):

0

40

80

120

160

m (ELM)

0 20 40 60 80 100 120 140

m

(ng/c

m2)

Exposure to Mefp-1 Rinsing Exposure toNaIO

4

Time (min)

Polyelectrolyte Multilayer

- - - - - A – Negative charge

++ +

++ + B – Positive charge

Raw data indicate mass loss

[(POD-PSS)c] and oppositelycharged (PAH)

SiO2

- - - - - - - -

++ +

++ +- - - - -

++ +

++ +

MP

0,0

1,0

2,0

3,0

4,0

5,0

6,0

7,0

8,0

A 1st layer A 2nd layer A 3rd layer A 4th layer A 5th layer NaCl Water

thic

kness

[nm

]

Sauerbrey

Model

Modeling reveals swelling

Caruso et al. Chem. Mater. 2005, 17, 171-175

Moisture Uptake of ThermoresponsiveHydrogel Films: Impact of Cross-link Density

vs.

Tamirisa et al. Macromolecules 2006, 39, 7092-7097

The Effect of Silica Nanopartice Coatings onProtein Adsorption

vs.

Lord et al. Biomaterials 27 (2006) 4856–4862

Complexation Chemistry for Tuning Releasefrom Polymer Coatings

Co-polymer (PVM) + Cu2+

vs.

MedetomidineRelease

Fant et al. J. Phys. Chem B. (2006).

vs.

Co-polymer (PVM) + Zn2+

PVM = Poly-vinyl-methacrylate

Plotting D vs f – Dextran on SiO2 and Al2O3

Dextran behavesdifferently on a Al2O3

substrate (black) than ona SiO2 substrate (grey).

Two-phase process

indicated on Al O .Al2O3

SiO2

indicated on Al2O3.

Phase 1

Phase 2

Kwon et al, Environ Sci Technology 2006, 40, 7739-7744

Al2O3

Lipase-Mediated Lipid DegradationMechanism

Detergent with Enzyme (lipase)

Stain (lipids)

Fabric

Water Water

Fabric

Stain (lipids)

JacketGreasy stain

Stain (lipids)

Crystal

Water

Lipase activity study

In. Situ, QCM-D

Stain (lipids)

Crystal

Water

Snabe et al. Chemistry and Physics of Lipids 125(2003), 69-82

Lipase solution

~100 nm

Practical Example:

Lipase (E.C. 3.1.1.3)Molecular Weight ~30kDaConcentration 1 μg/ml

Lipoprime (lipase)

Quartz crystal

Lipid film ~100 nmConcentration 1 μg/ml

Formula: C57H104O6

Molecular Weight: 885.43 DaCAS Registry Number: 122-32-7

Triolein (triacylglycerol)

Snabe et al. Chemistry and Physics of Lipids 125(2003), 69-82

0

1

2

3

4

5

6

Vis

c(k

gm

-1s-1

)o

rE

lasti

cit

y(1

05

Pa)

0

20

40

60

80

100

120

Fil

mT

hic

kn

ess

(nm

)

A B CD

Enzymatic Degradation of Lipids

4

5

6

)o

rE

las

tic

ity

(105

80

100

120

Fil

mT

hic

kn

es

s(n

m)

A

D

BC

4

5

6

)o

rE

las

tic

ity

(105

80

100

120

Fil

mT

hic

kn

es

s(n

m)

A

D

BC

0

0 1 2Time (min)

0

Quartz Crystal

Lipid film

A

A) Adsorption of lipase

Quartz crystal

Lipid film

B

B) Cluster formation

Quartz Crystal

Lipid film

C

C) Mass ejection

Quartz Crystal

Lipid film

D

D) Lipid layer removal

0

1

2

3

0 5 10 15 20

Time (min)

Vis

c(k

gm

-1s-1

)o

rE

las

tic

ity

(10

Pa

)

0

20

40

60

Fil

mT

hic

kn

es

s(n

m)

0

1

2

3

0 5 10 15 20

Time (min)

Vis

c(k

gm

-1s-1

)o

rE

las

tic

ity

(10

Pa

)

0

20

40

60

Fil

mT

hic

kn

es

s(n

m)

viscositythickness elasticity

Snabe et al. Chemistry and Physics of Lipids 125(2003), 69-82

Biomaterial Protein Resistancy

Eye

Contac lens

Eye

Tear fluid

Contact lens polymer

Protein film (unwanted)

Crystal

Tear fluid

Protein resistance optimization

Crystal

In. Situ, QCM-D

Contact lens

Contac lens Contact lens material (HEMA)

Lord et. al. Biomaterials 2005

Protein resistant modification

E4 Electrochemistry Module

Module SpecificationsSensor crystals All Q-Sense crystals can be usedInternal volume ~ 600 mLCleaning Simple, can be disassembled

ElectrodesWorking electrode The sensor crystal itselfWorking electrode The sensor crystal itselfCounter electrode Platinum discReference electrode Custom modified Ag/AgCl

Common application areas

Surface(QCM-D)

Drug development

Surfactants

Biofouling

Biosensors(QCM-D)

Biomaterials

Drug discovery

Polymers

Concluding Remarks

• QCM-D provides not only mass uptake butalso viscoelastic properties of thin films.

• Real-time surface sensitive technique

• Overtones (different sensitivity, modeling)• Overtones (different sensitivity, modeling)

• Surface interaction/reaction

The Q-Sense QCM-D Solution

Education&Training

Turn key QCM-D systemAdvanced Modeling

Q-Sense E4Turn key QCM-D system

Advanced Modelingsoftware

Data evaluationsupport

Annual User meetings

User’s 19 Countries

Thank You!

Mark A. Poggi, Ph.D.Territory ManagerQ-Sense, Inc808 Landmark Drive, Suite 124Glen Burnie, MD 21061

Direct #: 404-863-4257Office #: 877-773-6730

DiscussionDiscussion

E-Chem moduleCounter electrode99.95% Pt

Reference electrodeReference electrodeAg/AgCl

Left or Right hand configuration1 or 2 modules can be used with one E4

QTools SoftwareTheoretical Modeling of the QCM-D Response (Viscoelastic

Modeling)

Δf=f1(n,ηf,ρf,μf,δf)

ΔD=f2(n,ηf,ρf,μf,δf) Fluid(ρ l, l)

n=1n=3

n=...

ρ: density, (kg/m3)

η: viscosity (G’’/ω), (kg/ms)

Crystal

Adlayer(ρ f, f, f)

δf

Voinova et al., Physica Scripta 59 (1999) 391

G = G' + jG''= m + j2πf

η: viscosity (G’’/ω), (kg/ms)

μ: elasticity (G’), (Pa)

δ: thickness, (m)

Viscoelastic model -Assumptions

Homogeneous Adlayer

Maxwell

viscoelastic fluid

Voight

viscoelastic solid

Newtonian Fluid

G = G' + jG''= m + jw