What is avidity?
Binding events between a T cell and its target tumor cell determine the initiation of immunological synapse formation and T-cell activation. Cell–cell interactions are, therefore, crucial parameters to consider when trying to comprehend T cell response processes.
Cell avidity defines the total intercellular force between multiple parallel interactions, including co-receptor binding, TCR clustering, cell adhesion proteins, and even orientations and valencies.
Compared with affinity, cell avidity provides a more complete and physiologically relevant picture that reflects the bona fide interaction between effector cells and tumor cells. These interactions serve to better predict cellular responses and outcomes during immunotherapy.
Why cell avidity? Filling the scientific gap
The field of immuno-oncology lacks a proper understanding of what defines a good therapy. The approaches commonly used today to select the best immunotherapeutic effector cells include surface plasmon resonance (SPR) affinity studies, tetramer staining, and functional assays.
Results from affinity and tetramer assays are inconsistent and do not correlate linearly with immune cell response. Functional assays, such as IFN-γ secretion and cell killing, are more predictive of effector response in vivo but are time-consuming and inconsistent between experiments or assays (Sibener et al., (2018) Cell; Zhang et al., (2016) Science Translational Medicine).
Through avidity measurements, the z-Movi® can help researchers investigating cell interaction properties that correspond to immune cell response in a predictive, reproducible, and fast manner. All this at a high-throughput and single-cell level, without compromising cell viability.
How does it work in practice?
It all starts with the acoustics
At the heart of the z-Movi® technology, inside the microfluidic chip, you will find the piezo element that generates resonant acoustic waves. These ultrasound waves are the foundation of cell avidity analyses, as they can pull cells vertically toward the first acoustic node where the force is zero. You can easily control the force magnitude of the waves by regulating the voltage.
Effector cells will detach from the monolayer in a force-dependent manner and accumulate at the acoustic node. You can follow the detaching of the fluorescently labeled effector cells from the top view of the flow channel.
Figures a-f show the force-induced detachment of fluorescent effector cells establishing low avidity and high avidity interactions. Low avidity effector cells will rapidly release from the target cell monolayer (a-c, green trendline and column in the graphs below) and gather at the acoustic nodes (c), while high avidity effector cells require larger forces to rupture the binding strength (d-f, orange trendline and bar in the graphs below).
Extensive data analysis options for meaningful and predictive results
Meanwhile, the z-Movi records the corresponding rupture forces of each effector cell. The avidity score describes the relative differences between different populations.
Violin dot plots
Rapid experiments with the optimized workflow
We have optimized the workflow of the z-Movi to facilitate the user experience and provide you with reliable, reproducible, and fast results. The z-Movi Chip is specialized to simplify cell culturing and maintain your samples in physiological conditions while you perform the experiments. Once you have performed one run of analyses, you can simply flush in a new batch of effector cells – up to 5 times!
Cell Avidity Analyzer
The z-Movi® is a unique instrument that measures the avidity between immune cells and their targets, enabling you to identify the most potent immunotherapeutic effector cells. This new technology provides you with predictive, reproducible, and fast high-throughput results at a single-cell resolution without compromising cell viability. All within a compact little box that easily fits inside the flow hood for sterile and safe sample handling