Not all spheroids are equal: how to choose the right 3D culture technique
3D cell culture has become an indispensable part of modern research. Spheroids and organoids mimic how cells truly behave in the body. This makes them essential for drug screening, oncology, and stem cell research. There is one important detail, however: the method used to grow these 3D structures largely determines how reliable your results are. There are several techniques available, but not all of them are equally suitable for every experiment. Below we compare the four most prominent ones.
Classic ULA plates
ULA stands for Ultra-Low Attachment. The surface of the well is coated to prevent cell adhesion, which forces cells to aggregate and spontaneously form a spheroid. This may sound ideal, and for an initial introduction to 3D culture, it actually is. The workflow is straightforward, the threshold is low, and the plates are compatible with standard laboratory equipment.
But what if you want to scale up? This is where the limitations begin to show. With flat-bottom plates, multiple spheroids often form per well, and they vary in size. This heterogeneity makes it more difficult to replicate or compare experiments.
Hanging drop
With the hanging drop method, a small droplet of fluid containing cells is placed on a surface and then inverted. The droplet hangs downwards, and gravity pulls the cells together to the lowest point, where they aggregate into good quality, highly uniform spheroids. This could be a useful technique for specialised applications.
This method is labour-intensive, however, as changing the culture medium is a delicate task. Furthermore, the droplets are sensitive to vibrations and evaporation, harvesting is more difficult, and automation presents a major challenge. When it comes to routine work in a busy laboratory, especially if you want to scale up, the hanging drop method is rarely the most practical choice.
Uniform single spheroids
Fortunately, alternatives are available that largely overcome the limitations of both methods. Spheroid Microplates feature a patented round microwell geometry: a small, rounded cavity per well that forces cells to aggregate in exactly the right location. The result is consistently one uniform spheroid per well, which yields highly reproducible data.
The plates are compatible with imaging platforms and downstream assays without requiring additional handling such as centrifugation or transfer. Available in formats up to 1536 wells, they are ideal for medium-throughput screening of cytotoxicity, drug penetration, or co-culture models.
Scalable 3D culture
If you require large numbers of spheroids or organoids for toxicology or personalised medicine, Elplasia is a strong option. Each well of an Elplasia plate contains hundreds of microcavities, and a uniform micro-spheroid forms in each one. This means hundreds of reproducible aggregates per well, with high consistency.
Elplasia is particularly well suited to laboratories that prioritise automation and standardisation. While seeding density does require some optimisation, this platform offers clear added value for those working at scale.
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