Unlock the full potential of 3D cell culture with positive displacement dispensing

3D cell culture has become an essential tool for advancing research in biology, medicine, and drug discovery. Unlike traditional two-dimensional cell culture, in which cells are grown on a flat surface, 3D cell culture allows cells to interact in a more natural, biologically-relevant three-dimensional environment. 3D models better replicate the in vivo conditions that are critical for studying biological processes and disease progression, whilst providing an alternative to animal-based studies. 

The benefits of 3D cell culture are well documented: 

• Improved physiological accuracy: 3D models provide a more realistic representation of cell-cell and cell-matrix interactions, improving studies on cell morphology, differentiation, and drug responses. 

• Increased success in drug discovery: By offering more predictive data, 3D models enhance the efficiency of preclinical studies by better identifying candidates with optimal efficacy and toxicity profiles, cutting down on costly failures further down the pipeline. 

• Versatility across applications: 3D cell culture is used effectively to screen for small molecule drugs across a wide range of therapeutic areas, as well as stem cell research and a number of biomedical applications. Additionally, the ability to use patient-derived cells in 3D models has opened the door to personalized medicine approaches.
  

Challenges in adopting 3D cell culture 

Despite these advantages, working with 3D cell cultures brings practical challenges that hinder adoption in the lab. Traditionally, 3D models require a scaffold or matrix to support cell growth, most commonly a hydrogel. The combination of cell suspensions and viscous hydrogels requires sophisticated liquid handling technology to achieve the required levels of precision at speed. 

• Material complexity: Hydrogels, like Matrigel^® and GrowDex^®, have variable viscosity that makes them a challenge to handle accurately, often requiring tiresome optimization of pipetting conditions. 

• Cell viability: When handling cells, considerations need to be taken during dispensing to ensure good cell viability. 

• Workflow demands: Preparing and maintaining 3D cultures is labor-intensive, requiring precise pipetting and multiple liquid handling steps, which quickly becomes a strain on time and resource. 

• Scalability: The time and effort required can limit throughput, posing a barrier to larger-scale studies or high-throughput screening.
  

Automation can of course facilitate speed and throughput, by removing the burden of manual pipetting. However, traditional liquid handling systems that rely on air displacement technology often struggle to meet the demands of 3D cell culture. Their performance often degrades when dealing with viscous materials, requiring lengthy optimization that adds time and complexity to already demanding workflows.

Positive displacement: Meeting the challenge 

Positive displacement liquid handling technology, as used in our dragonfly^® discovery and firefly^® liquid handling platforms, provides a fast and reliable solution to handling cells and hydrogels. Unlike air displacement pipettes, positive displacement systems use a direct plunger-to-liquid approach, ensuring precise dispensing regardless of viscosity or temperature. 

Key advantages include:

1. Accurate and reliable dispensing 
   Positive displacement technology eliminates the need for tedious liquid class optimization, allowing hydrogels and cell suspensions to be dispensed with ease and accuracy every time. This can be extended to hydrogels like GrowDex, where gel stiffness can be fine-tuned to mimic different tissue types – the variability in viscosity doesn’t bring about any workflow delays.
2. Enhanced throughput and reproducibility 
   Automation powered by positive displacement technology significantly speeds up workflows while maintaining consistency. A single dragonfly syringe can rapidly fill an entire 96-well plate in less than one minute. This scalability is vital for high-throughput studies, enabling labs to generate more data and accelerate pipelines. 
3. Miniaturization for efficiency 
   With the ability to dispense volumes as low as 200 nL without compromising precision, positive displacement systems enable reaction miniaturization with ease. This extends the reach of costly reagents and makes it feasible to work with limited starting materials, such as patient-derived cells or rare biological samples.
   

Case study: Automation-enabled human intestinal organoid research 

By using organ-specific cell types, organoids better replicate the complex structure and function of organs. We collaborated with Corning Life Sciences, combining the power of dragonfly discovery dispensing with Corning Matrigel matrix for organoid culture, to automate a forskolin-induced swelling assay of human intestinal organoids in 96-well plates. 

Both the low-volume dispensing capabilities and low dead volumes facilitate better resource management and lower the cost barrier to essential research.

Read the full application note. 

Conclusion 

3D cell culture represents a leap forward in our ability to model human biology and accelerate breakthroughs in biomedical research. However, realizing its full potential requires tools that can handle the inherent complexity of these systems. 

Our positive displacement liquid handling technology offers a practical and efficient solution, simplifying workflows, improving reproducibility, and enabling high-throughput applications. By bridging the gap between technical challenges and scientific opportunity, we are proud to support researchers in driving the next generation of discoveries.