Revolutionizing 3D cell culture with simplified digital microfluidic technology

Most cells within the human physique exist in advanced three-dimensional environments, but they’re nonetheless generally studied on flat plastic dishes. These two-dimensional cultures distort cell conduct, limiting their relevance for predicting organic responses in actual tissues. Microfluidic applied sciences have improved management over cell tradition situations, however many programs depend on steady fluid circulate, exterior pumps, and complex fabrication processes. Digital microfluidics gives exact droplet-level manipulation however has struggled to assist true 3D cell progress as a result of absence of on-chip microstructures. Based mostly on these challenges, there’s a clear want for easier, built-in platforms that mix exact management with physiologically related 3D cell tradition.

In a examine printed (DOI: 10.1038/s41378-025-01098-9) in Microsystems & Nanoengineering in 2025, researchers from the College of Macau and collaborators describe an built-in digital microfluidic platform designed particularly for 3D cell tradition. The staff used a one-step micro-nano 3D printing course of to manufacture three-dimensional microstructures immediately onto microfluidic electrodes. The ensuing chip allows managed droplet motion, environment friendly cell seize, and speedy formation of 3D cell spheroids. Experiments confirmed steady operation and excessive cell viability for as much as 72 hours, demonstrating the platform’s practicality for superior organic research.

On the coronary heart of the platform is a producing technique that merges digital microfluidics and 3D microstructures right into a single machine. As a substitute of counting on multi-step lithography and cleanroom fabrication, the researchers used projection stereolithography to print the dielectric layer, confinement fences, and micro-well arrays in a single step. This method dramatically simplifies chip manufacturing whereas permitting exact management over the 3D mobile microenvironment.

The staff optimized key parameters that govern droplet actuation, together with voltage, electrode geometry, and microstructure peak. The chip reliably supported important digital microfluidic operations resembling droplet transport, splitting, and merging throughout each flat and 3D surfaces. Importantly, cell suspensions may very well be guided into the micro-wells with excessive precision.

As soon as confined inside the 3D microstructures, cells quickly self-assembled into compact spheroids. In contrast with typical two-dimensional cultures, these spheroids confirmed enhanced cell-cell interactions and extra tissue-like group. Viability and proliferation assays confirmed that cells remained wholesome over 24, 48, and 72 hours. Imaging analyses additional revealed dense multicellular architectures that carefully resemble in vivo tissue constructions, underscoring the organic relevance of the platform.

The researchers be aware that integrating 3D microstructures immediately right into a digital microfluidic chip addresses a long-standing bottleneck in microfluidic cell tradition. They emphasize that the platform combines exact droplet management with a biologically related 3D setting, whereas avoiding advanced fabrication workflows. In line with the staff, this stability between simplicity and performance may assist convey superior 3D cell tradition instruments into broader use, notably in laboratories that lack entry to specialised microfabrication amenities.

The brand new platform has quick implications for areas the place practical cell fashions are important. In drug screening, 3D cell spheroids typically present extra correct predictions of drug efficacy and toxicity than flat cultures. The chip may additionally assist analysis in most cancers biology, tissue engineering, and organ-on-chip growth by enabling managed formation of multicellular constructions. Wanting forward, the researchers plan to additional scale back working voltages and combine sensing and multi-cell co-culture capabilities. Such advances may permit longer-term tradition and extra advanced tissue fashions, narrowing the hole between laboratory experiments and dwelling programs.