Design and performance of microfluidic devices for viscoelastic-controlled encapsulation

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Abstract
Microfluidic encapsulation enables the isolation of particles or cells within picolitre-sized droplets, forming the foundation for a wide range of applications in biology, medicine, and materials science. From droplet-based single-cell ribonucleic acid (RNA) sequencing to long-term three-dimensional cell culture in microgels, the ability to efficiently encapsulate one or more objects per droplet is essential for throughput and downstream analysis. However, random encapsulation governed by Poisson statistics results in high fractions of empty droplets and undesired multiple occupancy, limiting the efficiency of current workflows between 20% and 36%, depending on the initial loading. Viscoelastic encapsulation provides a passive and scalable alternative to active sorting or inertial ordering approaches. By exploiting elastic and shear-thinning effects, objects self-organize into equally spaced trains along the channel centerline, enabling frequency-matched droplet formation. Despite its promise, only two studies have explored this phenomenon, with limitations including large droplet sizes, filament formation, and confinement constraints that restrict applicability to small biological objects. In this work, we introduce improved microfluidic platforms for viscoelastic-controlled encapsulation and co-encapsulation, demonstrating single-encapsulation efficiency up to 74% and co-encapsulation efficiency up to 46%. We design new device geometries, develop optimized hyaluronic acid formulations, and demonstrate high-efficiency encapsulation of both rigid particles and live Tetraselmis suecica algae. Our platform achieves encapsulation efficiencies well above Poisson statistics, reduced multi-occupancy, and droplet generation frequencies up to 2 kHz. These results establish viscoelastic encapsulation as a practical solution for high-throughput single-cell workflows, offering a robust path forward for droplet-based diagnostics and analytical platforms.
Funding Information
  • Biotechnology and Biological Sciences Research Council (BB/Y513337/1)
  • HORIZON EUROPE Marie Sklodowska-Curie Actions (101034245)
  • Engineering and Physical Sciences Research Council (EP/X525637/1)

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