Electrocoalescence of Water-in-Oil Droplets with a Continuous Aqueous Phase: Implementation of Controlled Content Release

Abstract

Droplet-based microfluidics have emerged as an important tool for diverse biomedical and biological applications including, but not limited to, drug screening, cellular analysis, and bottom-up synthetic biology. Each microfluidic water-in-oil droplet contains a well-defined biocontent that, following its manipulation/maturation, has to be released into a physiological environment toward possible end-user investigations. Despite the progress made in recent years, considerable challenges still loom at achieving a precise control over the content release with sufficient speed and sensitivity. Here, we present a quantitative study in which we compare the effectiveness and biocompatibility of chemical and physical microfluidic release methods. We show the advantages of electrocoalescence of water-in-oil droplets in terms of high-throughput release applications. Moreover, we apply programmable DNA nanotechnology to achieve a segregation of the biochemical content within the droplets for the controlled filtration of the encapsulated materials. We envision that the developed bifunctional microfluidic approach, capable of content segregation and selective release, will expand the microfluidic toolbox for cell biology, synthetic biology, and biomedical applications.

Controlled microfluidic droplet acoustoinjection on one chip

“…Finally, modifications in the design of the injection nozzle could improve the accuracy of the injected volume into each droplet. Our IDT design and operation in the kHz frequency domain could be applied in other droplet manipulation strategies like droplet merging [13,14] and content release [11,12]. All in all, our acoustoinjection device is a cost-effective, reliable, and gentle option for microfluidic applications in which future biological content within water-in-oil droplets is not negatively impacted by thermal energy.…”

“…1 and S1 show a precise sketch of our designs and explain the constructions. As previously described [12], for the production of the master wafer, negative photoresist (SU8-3025, MicroChem, USA) is spin-coated (Laurell Technologies Corp., USA) onto a silicon wafer at 2650 rpm to achieve a uniform coating of 30 µm thickness. The wafer is then placed on a hot plate for a 5 min soft bake at 65 °C, then ramped slowly to 95 °C and held for 15 mins.…”

“…Surfactant-stabilized droplets and their contents can further be manipulated by external physical stimuli in a variety of ways by integrating functional microfluidic units into device construction. For example, implementing electric field generation into microfluidic units enables tasks such as: sorting and selection of specific water-in-oil droplet populations [8][9][10]; releasing droplet content [11,12]; initiating reactions by merging droplets with different cargos [13,14]; or injecting additional fluids directly into the aqueous phase of the droplets [15,16]. Apart from sorting in the microfluidic units described above, droplet manipulations including picoinjection may be achieved by electrocoalescence.…”

Label‐free monitoring and manipulation of microfluidic water‐in‐oil droplets

“…This is the last step toward a real multipurpose lab‐on‐a‐chip device that is able to contain an entire process requiring active surveillance. For example, single microfluidic droplet manipulation units for pico‐injection, [ 19 ] droplet sorting, and release of the droplet content [ 20 ] could be implemented in a synergetic application and controlled with the developed optical device. This kind of microfluidic factory utilizing our developed optical device has the potential to be a game changer in basic biological research as well as in pharmaceutical and medical research and applications.…”

Can Bottom-Up Synthetic Biology Generate Advanced Drug-Delivery Systems?

“…As an alternative, Krafft and coworkers developed a simplified system relying solely on sucrose/salt solution as the inner and outer aqueous phases [58]. To completely dewet the Droplet-based microfluidics features various functional units: a droplet production unit to encapsulate a variety of chemical and biochemical contents [26]; a pico-injector for the sequential injection of picoliter volumes into individually produced droplets [94]; a fusion module to provoke the fusion of two distinct droplets, thus enabling the mixture of various chemical and biochemical reagents with high temporal control [95]; a mixing module to improve convection and thereby facilitate molecular reactions within the droplet [96]; a sorting module to precisely separate individual droplets based on various analytical signals such as fluorescence [62] or mass spectrometry [97]; a releasing unit to liberate the entrapped mixture from the droplet into an aqueous continuous phase by applying an electrical field [98] or by using a passive trapping structure [26]; and a detection or observation module that facilitates the assessment of a large droplet population [43,99]. Adding to the various possibilities of droplet-based microfluidics, capillary microfluidicswhich in contrast to PDMS-based microfluidics uses glass capillariesis even compatible with the use of organic solvent [52].…”