QCM-D Measurement

Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) is a real-time, surface sensitive technique for analyzing surface-interaction phenomena, thin film formation and layer properties.

Areas covered in this article

What is QCM-D?

Quartz Crystal Microbalance, QCM, and extended versions, such as Quartz Crystal Microbalance with Dissipation monitoring, QCM-D, are surface sensitive, real-time technologies that detect mass changes at the sensor surface with nanoscale resolution. Essentially, these instruments are balances for very small masses and the molecule-surface interactions are detected as changes in mass, i.e. mass uptake or mass loss, as molecules adsorb or desorb.

In addition to the changes in mass, QCM-D also captures changes in energy loss. This additional information provides insight into the viscoelastic properties of the system under study and can reveal structure as well as structural changes, such as swelling, crosslinking and collapse, of the molecular layer at the sensor surface.

QSense Mass

Overview  Working principles of QCM and QCM-D technology  Download


QCM history in brief

In the early days, QCM-technology was used to monitor thin-film deposition in gas phase and vacuum environments. A couple of decades later, it was introduced to usage also in liquid phase. This opened for surface interaction analysis of, for example, biomolecules and polymers, which typically form soft, and/or thick layers at the sensor surface. In this type of measurements, extended QCM:s, that measure the energy loss, have proven to be particularly useful since information about the energy loss helps the analysis and quantification of viscoelastic layers.

Measuring the mass

In order to go from the detected frequency change, Δf, to a quantified number in mass units, a conversion is needed. The relation between frequency and mass was first identified by Günther Sauerbrey in 1959 and resulted in the so-called Sauerbrey relation. The discovery resulted in the birth of the QCM-technology.

Quantification of soft layers

For viscoelastic modelling to be possible, or even to know whether it is in fact needed, we need information about the energy losses in the system, the so-called dissipation. The energy loss is captured with extended QCM:s such as QCM-D. I.e., in contrast to standard QCM, that captures one parameter, Δf, as a function of time, QCM-D technology captures two parameters, Δf and ΔD, as a function of time.

How does QCM-D work?

The QCM is an acoustic technology, i.e. it measures changes of sound. The sound is typically in the MHz regime, however, and not detectable by the human ear.

The core of the technology is the oscillating unit - a thin quartz crystal disk, which has electrodes deposited on each side. Via an applied voltage, the crystal can be excited to resonance, and the resonance frequency is related to the thickness (mass) of the disk. If the thickness changes, so will the resonance frequency, f. By monitoring changes of the resonance frequency, Δf, it is possible to detect small changes of the crystal thickness (mass). The measurement makes it possible to detect nanoscale mass changes such as adsorption or binding of molecules to the surface, which will be detected as mass increase, whereas mass decrease will indicate mass removal, for example via molecular desorption or etching of the surface.

In addition to measuring Δf, which is measured by all QCM.:s, QCM-D measures an additional parameter, the dissipation, ΔD. The dissipation gives information about the energy losses in the system and are particularly useful in the study of soft layers, where this information is used for quantification of the layer properties.

QCM-D single harmonic

Piezoelectricity - a key phenomenon for QCM-technology

As mentioned above, the core of QCM technology is the sensor which reveals mass changes via changes of its resonance frequency. A key quality of the sensor for this excitation to be possible is that it is made of a piezoelectric material. Piezoelectricity is a phenomenon that couples the electrical and the mechanical state of a material. This means that when the material is mechanically deformed, its faces will be charged, and vice versa - i.e. when the material is exerted to an electric field, the material will be deformed. Typically, QCM sensors are made of quartz, but other piezoelectric materials could be used as well.

Piezoelectric principle

Overview  What is Piezoelectricity and how does it work?  Download

The Sauerbrey equation - converting frequency change to mass change

The relation between frequency and mass, which enables the detection of molecule-surface interactions, was first identified by Günther Sauerbrey in 1959 and resulted in the so-called Sauerbrey relation.

The equation states that there is a linear relation between frequency change and mass change according to

The Sauerbrey equation-1

where C, the so-called mass sensitivity constant, is a constant related to the properties of quartz and n=1, 3, 5… is the number of the harmonic used.

For the Sauerbrey equation to be valid, the layer on the sensor must be thin, rigid and firmly attached to the crystal surface. When hydrated systems are studied, for example polymers or biomolecules in liquid, the conditions are often not fulfilled and Sauerbrey relation will underestimate the mass. In this situation, there are other ways to quantify the layer properties, for example via so-called viscoelastic modelling.

Overview  The Sauerbrey relation  Download

The Dissipation - enabling analysis of viscoelastic layers

QCM-D measures changes of both frequency, f, and dissipation, D. The D-value gives information about the energy loss in the system, and reveals how soft, or viscoelastic the layer at the surface is. This means that the D-value will reveal whether the layer is rigid, and if the Sauerbrey equation can be used for the quantification or not. In situations where the Sauerbrey equation cannot be used, the D-value contributes with valuable information to be used as input in the quantification model and to extract mass, thickness and viscoelastic properties.

Overview  What is Dissipation and why is it important?  Download

QCM sensitivity

A parameter that is often discussed in the context of QCM is the mass sensitivity, C, in the Sauerbrey equation, (eq 1). This constant, which is often referred to as the ‘sensitivity’, says how many ng of material per cm2 of the sensor that is needed to shift the resonance frequency 1 Hz, i.e. the smaller the C, the higher the mass sensitivity. The value depends purely on the fundamental resonant frequency of the crystal, and is defined as

QCM mass sensitivity

where υq is the shear wave velocity in quartz, ρq is the density of the quartz plate, and f0 is the fundamental resonant frequency. It is noted in eq. 2 that the higher the fundamental mode, the higher the theoretical mass sensitivity. As an example, the theoretical mass sensitivity of a 5MHz crystal is 17.7 ng/(cm2∙Hz) and that of a 10MHz crystal is  and 4.4 ng/(cm2∙Hz).

Guide  How to read a QCM specification  Download

The importance of the overtones

QCM is an acoustic technology, and like an acoustic instrument, the QCM crystal can be excited to resonate at several different harmonics, n. For AT-cut QCM crystals, which oscillate in the thickness shear mode, only the odd harmonics, n = 1, 3, 5,…. are possible to excite. The lowest resonance frequency, n = 1, is called the fundamental, and n = 3, 5, 7 etc are overtones to the fundamental. As an example, if the fundamental frequency is 5HMz, then available overtone resonances would be 15 MHz, 25 MHz, 35 MHz etc.

Each harmonic measured will contribute with unique information about the system under study and be useful when interpreting the QCM data. Additionally, information from multiple overtones is also key when performing viscoelastic modeling - the model contains several unknown parameters, and at least the same number of measured variables are needed to feed into the model.

When is QCM-D used?

QCM-D technology is used in academic as well as in industrial settings to get answers throughout the research process. The nature of the technology makes it useful in a vast range of areas - areas where molecule-surface interactions play an important role.

Depending on the focus of the research, and of course the phase of the project, QCM-D technology is used to answer different types of questions.


A. Explore – map out the system behavior to increase your understanding

QCM-D technology is used in basic research and other projects of similar character to help answer fundamental questions such as "What happens when/if..?" and "How does this molecule interact with the surface at these conditions?" Examples of questions that QCM-D are used to answer are:

    • What happens if I change the lipid mixture - will a bilayer form?
    • Will the protein bind to this functionalized surface at this pH?
    • At what temperature will the polymer brush go from swollen to collapsed state?

B. Characterize or verify the surface interaction processes, or system behavior

If the work is more applied, QCM-D technology can be used to verify a certain surface-interaction behavior. For example, it could be used to:

    • Verify bilayer formation
    • Double-check that the protein is binding to the functionalized surface
    • Verify polymer brush swelling/collapse transition at known T

C. Optimize - Identify optimum performance as a function of the parameter(s)

If the project is in a development phase, it could be relevant to tweak parameters, conditions and settings to identify the optimum performance or to obtain a certain surface interaction behavior. In this situation, QCM-D can help answer questions such as:

    • What is the optimal lipid-ratio for a bilayer to form?
    • At which pH will I get the fastest protein uptake?
    • Which polymer-chain configuration should I use to get a phase transition at this T?

Molecular size range and film thicknesses

QSense QCM-D measures at the nanoscale, and the detection range is ~1 Å to 1 um, depending on the layer properties.

Typical molecules and entities that are studied are biomolecules, surfactants, polymers, nanoparticles, cells and other structures in the same size range.

Length scale

Vary the conditions

Most surface interaction processes depend on the context such as surface chemistry and the ambient solvent conditions. To get an understanding of the system under study it is important to mimic these real-life conditions. 

QSense QCM-D technology allows you vary key parameters such as:

    • Surface material
    • Sample concentration
    • Temperature
    • Solvent
    • pH
    • Ionic strength

Examples of application areas

For decades, QCM technology has been used to monitor thin-film deposition in vacuum and gas phase. When it was discovered that QCM could also be used for measurements in liquid phase in the 80’s, the number of possible applications increased significantly. Today, QCM, and extended versions, such as QCM-D, are used in a broad range of areas where surface interaction processes need to be explored and controlled. Examples include the areas of biomaterials, nanotoxicology, cleaning products and detergents, oil and gas, and CMP.


Information you can extract with QCM-D

QSense QCM-D monitors molecule-surface interactions as well as properties of the layer formed at the sensor surface. The collected data enables characterization of the system under study, and questions that can be answered are for example:

    • is there is a molecule-surface interaction taking place or not?
    • how much material adsorbs/desorbs or binds? 
    • how fast is the process?

Mass, thickness and viscoelastic properties

The collected f and D at multiple harmonics allow for both qualitative information, such as revealing whether a molecule-surface interaction is taking place or not, as well as quantitative information on mass, thickness, and viscoelastic properties of the formed layer. This makes it possible to study molecular adsorption, desorption and binding as well as layer degradation and etching.

Time-resolved data

The information is time resolved, which not only allows for characterization of the formed layer, but also makes it possible to follow dynamic processes such as film formation, film degradation and structural rearrangements.

Hydrated mass, conformation and conformational changes

When molecules adsorb or bind to the surface, the surrounding solvent will couple to the molecules as an additional dynamic mass via direct hydration and/or entrapment within the adsorbed film. The mass sensed by QCM:s, includes both the mass of the mole­cules at the surface and the mass of the associated solvent. Therefore, it is often referred to as “hydrated mass”.

The amount of coupled solvent depends on how the molecules are arranged at the surface. For example, molecules in an elongated conformation, stretching out from the surface, will typically couple more solvent than if the molecules would be arranged in a tightly packed manner along the surface. If the molecular arrangement changes, there will be a mass change reflecting the amount of coupled solvent. As this mass change will be detected by the QCM, it is possible to detect and monitor conformational changes of the molecular layer, such a swelling, crosslinking and collapse.

Asset 1@4x


Asset 2@4x

Binding and interactions

Asset 4@4x


Asset 5@4x


Asset 3@4x

Degrading and etching

Overview  Information obtained with QSense QCM-D  Download

Examples of how QCM-D data can be used in different areas

Here we show examples of what information QCM-D can provide in the three different areas i) lipid-based research, research that includes ii) biomolecule-surface interactions and iii) polymer-based research.

i) QCM-D in lipid-based research

QCM-D has been used for about two decades to analyze and characterize lipid-based systems. Thanks to the time-resolved information on hydrated mass and layer softness, it is an unsurpassed technology in this area, where it enables monitoring of interaction dynamics between lipids and the solid support.

QCM-D allows you to:

    • Study lipid-surface interaction dynamics
    • Tell the difference between structures, such as
      • Monolayers
      • Bilayers
      • Vesicles
    • Study molecular/particle interaction with lipid-based systems

Analyze lipid-based systems with QCM-D

In practice, this means that QCM-D can be used to:

    • Analyze lipid - solid surface interaction dynamics, e. g. adsorption rate and adsorbed amount
    • Reveal the structure of the lipid system, e.g. intact vesicles, monolayers and bilayers
    • Detect structural rearrangements, e.g. vesicle rupture and fusion
    • Evaluate lipid membrane quality
    • Quantify the layer thickness
    • Quantify the mechanical properties of the layer
    • Analyze molecular interaction with the lipid-membrane

Overview  Characterization of model membranes with QSense QCM-D  Download

Analyze biomolecule surface interactions with QCM-D

As for the lipids-based systems, QCM-D has been used since the beginning of this millenium to analyze biomolecular-based systems.

Thanks to the time-resolved information on hydrated mass and layer softness, the technology enables monitoring of interaction dynamics between the biomolecule and the surface. For example, you can monitor and characterize events such as:

    • Adsorption/desorption
    • Binding
    • Enzymatic action/reactions
    • Conformational and structural changes
    • Fibril formation (not shown in fig)

Analyze biomolecular interactions with QCM-D

In practice, this means that QCM-D can be used to:

    • Analyze biomolecule - surface interaction dynamics, e.g.

      • adsorption/desorption/binding rates
      • adsorbed/desorbed/bound amount

    • Detect structural arrangement and rearrangement
    • Quantify the layer thickness
    • Quantify the mechanical properties of the layer

Overview  Characterization of biomolecular interactions with QSense  Download


QCM-D in polymer-based research

Thanks to the time-resolved information on hydrated mass and layer softness, QCM-D is particularly good at analyzing highly hydrated systems (structures) and systems where the  degree of hydration changes over time.

For example, you can monitor and characterize events such as:

    • Polymer grafting
    • Buildup of PEMs
    • Conformational changes, swelling, collapse and crosslinking
    • Molecular interactions with polymer layers

Particularly, it is important to note that thes processes can be analzyed as a function of molecular and ambient conditions such as:

    • Molecule structure
    • Solvent
    • Temperature
    • Charge
    • pH
    • Counter ions
    • Ionic strength

Analyze polymer-based systems with QCM-D

In practice, this means that QCM-D can be used to:

    • Analyze build-up dynamics of polymer layers and multilayers
    • Characterize structure and structural rearrangements
      • pancake, mushroom and brush
      • swelling, collapse, and crosslinking
    • Quantify the layer thickness
    • Quantify the mechanical properties of the layer
    • Analyze molecular interactions with polymer layer

Overview  Characterization of polymer-based systems with QSense  Download

Related products

   QSense Pro Looking for a companion in large-scale QCM-D analysis? The fully automated  QSense Pro is best fit for the job.
   QSense Explorer Discover the many possibilities of our most versatile and modular QCM-D  instrument.
   QSense Analyzer Both fast and flexible, QSense Analyzer enables you to compare several samples  at the same time.


Save it for later?

Download the pdf version of this page to read when you have the time.

Download the guide

Save it for later?

Download the pdf version of this page to read when you have the time.

Download the guide
Preview image