Basic QCM-D and Q-Sense Product range

Malin Edvardsson, PhD

Product manager, Q-Sense

P A G E 1

O U T L I N E

Background

Basic QCM-D Theory

What can QCM-D Characterize

Application examples

Q-Sense Product Offering

P A G E 2

QCM AE QCM-D AE Q-Sense

1960s: QCM for monitoring of thin films in air and vacuum

1972 QCM as biosensor

1980s QCM is operated in liquid

1990s QCM is further developed into QCM-D

1995 QCM-D technology patented

1996 Q-Sense founded

1999 1st QCM-D generation launched

2005 2nd QCM-D generation launched

2010 Q-Sense => Biolin Scientific

2013 >500 instruments in >30 countries

>1400 publications

P A G E 3

M E A S U R E M E N T

P R I N C P L E

P A G E 4

What does QCM-D offer?

Follow molecular events in real-time, in liquid or in air Measure mass (ng) and thickness of molecular layers (resolution 1Å-1 µm) Analyze structural and mechanical properties of molecular layers

Water content info, swelling/contraction etc

Flexible choice of surfaces/samples

HOW?

P A G E 5

QCM-D: a sensor-based, acoustic technique

Top View Bottom View

electrodes

Quartz Crystal covered with Au layer

Sensor Diameter 14 mm

Acoustic= based on increases/decrease in oscillation frequencies (Quartz Crystal Microbalance with Dissipation monitoring)

P A G E 6

How does the sensor oscillate?

f = Change in frequency (Hz) tq= thickness of quartz

Vq= 3420 m/s

Overtones

n = 1 n = 3

If fundamental frequency 5MHz:

q qq t vnvnf 2

Resonance condition

~ tq Ʌ tq dtq

P A G E 7

Rigid film

large Ɏ ĺLow D

Soft film

small ɎĺHigh D

QCM - D

ǻf (ĺfilm mass)

ǻD (ĺ film viscoelastic properties)

Monitoring:

Rodahl, M. et al.; Review of Scientific Instruments 1995, 66, 3924-3930 Rodahl, M. and Kasemo, B. Review of Scientific Instruments 1996, 67, 3238-3241

D-D: Dissipation

P A G E 8

U Rodahl, M. et al.; Review of Scientific Instruments 1995, 66, 3924-3930 Rodahl, M. and Kasemo, B. Review of Scientific Instruments 1996, 67, 3238-3241 Find resonance ~ ms decay recording ~ ms data communication ~ ms

Ɏ Umax

Umax/e

t QCM-D f

Q-Sense sensor excited to resonance

Drive voltage is perodically swithced on and off

P A G E 9

Schematic QCM-D measurement

ȟfn1, ȟDn1

ȟfn2, ȟDn2

ǻD time

ǻf ȟf

ǻD ǻD

t U ~1V

I(t)=I0·e-t/Ɏ sin (2Ɋft-ɐ)

Mass coupled to the surface

viscoelasticity of the coupled layer

P A G E 10

Systems that QCM-D can characterize

Surface adsorption/desorption

Biomolecules (protein, vitamin, antibody, DNA, ...)

Polymers/polyelectrolytes

Cells

Surface reaction

Conformation change (protein, DNA, polymer, cells)

Crosslinking (protein, polymer, ...)

Hydration (polymer)

Bulk characterization

Viscoelastic properties of fluids (protein solutions, ...)

P A G E 11

QCM-D Application overview

P A G E 12

APPLICATION EXAMPLES

P A G E 13

Adsorption

P A G E 14

QCM-D in protein drug formulation and storage

Protein in contact with surfaces

(concentrators, filters, containers, syringes, tubing, beakers)

Risk of protein unfolding and aggregation

Surface interactions poorly understood

P A G E 15

Surface interactions of monoclonal

antibodies

Parameters

Two different antibodies

(one stable, one known to self associate)

High/low concentrations

(1 mg/ml, 50 mg/ml)

With/without surfactant

(PS-80)

Four surfaces

(Au, PS, teflon and silica)

QCM-D Outcome

Mass/thickness

Viscosity

Shear modulus

Oom et al - J. Pharm. Sc. - 2011

P A G E 16

Effect of surface and surfactant

mAb2 generally adsorbs

stronger than mAb1

Addition of PS-80 reduces

protein aggregation for both antibodies Adsorption of protein onto different surfaces from 1 mg/ml (low conc) solutions of mAb1 and mAb2

Oom et al - J. Pharm. Sc. - 2011

P A G E 17

Swelling

P A G E 18

Cell membrane water permeability

P A G E 19

Effect of composition on water permeability of

model stratum corneum lipid membranes

Myung Han Lee et al: Soft Matter, 2012, 1539-1546

Deposition and swelling of a supported

membrane under introduced humidity

The swelling kinetics correlates to

diffusion of water molecules

P A G E 20

Permeability (P), diffusivity (D) and solubility (S) of water vapour in the membrane as a function of membrane thickness, FFA chain length, saturation level, and CER structure

Myung Han Lee et al: Soft Matter, 2012, 1539-1546

P A G E 21

Crosslinking

P A G E 22

Adsorption

Protein adsorption and re-arrangment

P A G E 23

Protein adsorption and re-arrangment

MefP-1 mussle adhesive protein- elongated structure

NaI04- crosslinker- release of water

P A G E 24

Modeling results

before after x 1.04103 1.18103 kgm-3 x (QCM-D) 22.4 7.3 nm x (QCM-D) 1.8 x10-3 6 x10-3 Nsm-2 x (QCM-D) 6.6 x104 3 x105 Nm-2 NaIO4

Release of Water

Protein adsorption and re-arrangment

before after

P A G E 25

Degradation

P A G E 26

Follow break-up of films,

mass removal, swelling,

Three commercially

available kitchen spray cleaners treating a sensor coated with a model stain (triolein ~40 nm).

1: Stain put on

sensor, and detergent added.

2: Detergent

penetrates film, and film swells

3. Film stain

degradation starts.

Q-Sense 2008

Detergent effectiveness

P A G E 27

Polyelectrolytes & Nanoparticles

P A G E 28

Nanoparticles for drug delivery

Great potential for non-

invasive drug delivery (oral, nasal, pulmonary)

P A G E 29

Structural rearrangements of polymeric Insulin-loaded Nanoparticles Interacting with Surface-Supported Model Lipid

Membranes

Frost et al. J. Biomat. and Nanobiotech., 2011, 2, 181 - 193 (Anionic)

Polyelectrolyte

complexes

P A G E 30

Formation of a supported lipid bilayer

Mimic for human

cell membranes

P A G E 31

NP-HI interaction with model membranes of different charge

Positive membrane

Negative membrane

Neutral/ slightly

negative membrane

High dissipation = soft film

Spreading of overtones = soft film

Frost et al. J. Biomat. and Nanobiotech., 2011, 2, 181 - 193

1.Lipid membrane (pre-formed)

2.Injection of Nanoparticles

3.Rinsing

P A G E 32

Schematics of possible NP adsorption

Frost et al. J. Biomat. and Nanobiotech., 2011, 2, 181 - 193quotesdbs_dbs9.pdfusesText_15

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