QSense QCM-D is increasingly used to shed light on how biopharmaceuticals interact with real surfaces – from container glass and polymers to pump metals and coatings. In this post, we outline why interfaces matter, how QSense QCM-D measures protein adsorption on relevant materials, and how recent studies have used this perspective alongside conventional stability tools.
Interfaces as a source of risk in biopharmaceutical development
As development pipelines move toward monoclonal antibodies and other complex proteins, the role of interfaces has become increasingly important. Proteins do not only experience their formulation buffer – they also encounter vial and syringe glass, polymers, pump heads, silicone oil and air–liquid interfaces during handling and filling. At these interfaces, proteins can adsorb and form interfacial layers that are associated with subvisible particles (SVPs),aggregation and compatibility issues that may only become apparent later in development.
Traditional developability and formulation assays are essential for understanding bulk behavior and stress responses. However, they often provide limited insight into how specific molecule–material combinations behave at real surfaces, or which interfaces are most closely associated with observed instabilities.
What QSense QCM-D is – and what it measures
QSense QCM-D is a surface-sensitive real-time technology that measures how proteins, surfactants, and other molecules interact with materials. In brief, QCM-D tracks changes in resonance frequency, which reflect how much material that adsorbs to the sensor surface, and changes in dissipation, which indicate whether the adsorbed layer is rigid or soft and hydrated. Because the data is time‑resolved, QCM‑D can capture both how fast molecule adsorption occurs and how the interfacial layer evolves during e.g. exposure protein formulation and solvent rinses.
By coating the sensors with materials that mirror real biopharma surfaces – for example borosilicate glass, stainless steel, PDMS and other relevant materials - QSense QCM‑D can be used to assess adsorption behavior on container closure and process materials, quantify adsorbed mass and film softness, and compare how proteins and surfactants interact with different surfaces. This information complements bulk stability and stress tests by providing mechanistic insight into protein–surface interactions, supporting more informed discussion around molecules, excipients and materials in biopharmaceutical development.
Examples from recent biopharma-focused studies
Several recent publications illustrate how QSense QCM-D can be applied to biopharma-relevant questions under formulation-like conditions:
1. Which mAbs carry higher interface‑related SVP risk?
In one study1 on monoclonal antibodies, adsorption of 15 different mAbs to borosilicate glass and HDPE was measured in a histidine–sucrose formulation using QSense Analyzer. The authors extracted parameters such as equilibrium mass, film softness and adsorption rate, and compared these with SVP levels generated by stirring and agitation, and found that adsorption kinetics (rate constant λ) correlated strongly with stirring‑induced SVPs, while equilibrium mass and film softness varied less between mAbs.
2. Which surfactant protects which surface in antibody formulations?
Other work has focused on surfactants and container/closure materials.2 Using QSense instruments with borosilicate glass and PDMS sensors, the researchers monitored how different surfactants adsorb, how stable those layers are after rinsing, and how they influence subsequent IgG adsorption, and related these interfacial observations to aggregation, subvisible particles and silicone oil droplet formation in stress tests.
3. How do pump metals and ceramic coatings impact fusion protein particles?
QSense QCM‑D has also been used to characterize adsorption of a therapeutic fusion protein on process‑relevant pump materials, comparing stainless steel with an Al₂O₃‑coated (ceramic mimic) surface.3 The irreversibly bound protein mass on stainless steel was then related to subvisible particle levels observed after filling, highlighting how pump head material can influence process‑induced particles.
4. What happens to antibody layers over longer contact times?
Long‑term interfacial behavior has been investigated by monitoring antibody layers over many hours on surfaces such as SiO₂, TiO₂ and stainless steel, and combining QCM‑D data with neutron reflection and spectroscopic measurements to describe how adsorbed layers compact or remain stable over time,4 The study showed, for example, that one engineered mAb forms stable, rigid layers while another forms thick, hydrated layers on oxides that later compact and dehydrate, but remains compact and stable on stainless steel.
Across these and related examples, QSense QCM-D has been used to quantify adsorption kinetics, adsorbed mass and layer properties on materials that are directly relevant for manufacturing, storage and administration, and to relate this nanoscale information to macroscopic outcomes such as SVP formation, aggregation, and interfacial changes reported by other methods.
Learn more in the upcoming webinar
In the webinar Understand and Mitigate Interface-Induced Risks in Biopharmaceutical Development with QSense QCM-D, Fredrik Pettersson, Senior Application Scientist at Biolin Scientific, will introduce QSense QCM-D technology and demonstrate how nanoscale adsorption measurements can be applied in biopharmaceutical development to assess interface-induced risks, drawing on the studies discussed in this post.
Join the webinar by registering below.
