An acoustofluidic platform for non-contact trapping of cell-laden hydrogel droplets compatible with optical microscopy

Abstract

Production of cell-laden hydrogel droplets as miniaturized niches for 3D cell culture provides a new route for cell-based assays. Such production can be enabled by droplet microfluidics and here we present a droplet trapping system based on bulk acoustic waves for handling hydrogel droplets in a continuous flow format. The droplet trapping system consists of a glass capillary equipped with a small piezoelectric transducer. By applying ultrasound (4 MHz), a localized acoustic standing wave field is generated in the capillary, trapping the droplets in a well-defined cluster above the transducer area. The results show that the droplet cluster can be retained at flow rates of up to 76 μl/min, corresponding to an average flow speed of 3.2 mm/s. The system allows for important operations such as continuous perfusion and/or addition of chemical reagents to the encapsulated cells with in situ optical access. This feature is demonstrated by performing on-chip staining of the cell nuclei. The key advantages of this trapping method are that it is label-free and gentle and thus well-suited for biological applications. Moreover, the droplets can easily be released on-demand, which facilitates downstream analysis. It is envisioned that the presented droplet trapping system will be a valuable tool for a wide range of multistep assays as well as long-term monitoring of cells encapsulated in gel-based droplets.

Optoelectronic Manipulation, Trapping, Splitting, and Merging of Water Droplets and Aqueous Biodroplets Based on the Bulk Photovoltaic Effect

“…In fact, an important issue for these technologies are the development of efficient methods to manipulate the droplets inside the inactive/passive fluid medium. Among the diverse approaches [35], optoelectronic methods, such as that proposed here, have been considered an efficient alternative.…”

Acoustic focusing of beads and cells in hydrogel droplets

“…The composition of the hydrogel material should be selected depending on the intended application. Previously, hydrogel droplets have for example been produced in hydrogels from natural-derived polymers such as alginate 11 , agarose 12 and hyaluronic acid 13 as well as hydrogels from synthetic polymers such as polyethylene glycol (PEG) 14 . In this work we have selected to generate PEG droplets as PEG is a cheap, inert, highly water-soluble and well-characterised material 15 , and the precursor solution has low viscosity compared with many other hydrogel precursor solutions 16 .…”

3D Printing Hydrogel-Based Soft and Biohybrid Actuators: A Mini-Review on Fabrication Techniques, Applications, and Challenges

“…Similar to magnetic actuation, acoustic energy can be utilized to remotely manipulate micro/nano objects in fluid with high precision ( Matouš et al, 2019 ; Guo et al, 2016 ; Ozcelik et al, 2018 ; Ren et al, 2019 ; Tao et al, 2019 ; Fornell et al, 2019 ). Hydrogel structures that are acoustically stimulated at their resonant frequency can manipulate fluids for mixing ( Orbay et al, 2018 ) or generating fluid flow ( Kaynak et al, 2020 ).…”