Concentration Enrichment, Separation, and Cation Exchange in Nanoliter-Scale Water-in-Oil Droplets

Abstract

Droplet-based techniques have had a profound impact in chemistry, owing to their ability to perform rapid and massively parallel reactions in minute fluid volumes. In many applications, concentration enrichment is required to increase the speed of reactions or the sensitivity of assays; but in-droplet concentration enrichment remains challenging. Here, we interface electrokinetic concentration polarization with droplet microfluidics to accomplish in-droplet demixing. This result is significant because the concentration of any charged species in the droplet can be enriched and the approach can be readily integrated into existing droplet workflows. Further, we show that such electrokinetic enrichment is rapid, on the order of seconds, and is robust, occurring over a wide parametric space. We further demonstrate electrokinetic separation of two anionic fluorophores within the droplet. Such a capability potentiates the droplet-templated synthesis of particles with gradient composition and the development of mobility-shift assays, which rely on discrimination of multiple species tagged with a single color fluorophore. Finally, by using a calcium-binding dye as an indicator, we demonstrate in-droplet cation exchange. This demonstration of cation exchange in droplets is significant because of its broad applicability to strategies for synthesis and bioassays. These results lay the foundation for new advanced droplet techniques with transformative applications.

Lab-on-a-Chip Technologies for the Single Cell Level: Separation, Analysis, and Diagnostics

“…Individual droplets can be handled, for example, using acoustophoresis/SAW [134,167], hydrodynamic or microfluidic changes by geometries [168][169][170][171], elective emulsion separation [172], in-line passive filters [173], or even DLD [99]. It is also possible to manipulate the contents inside these droplets using DEP [174,175], magnetic fields [176,177], or beads and microfluidic ratchets [178].…”

Cation‐Specific Electrokinetic Separations Using Prussian Blue Intercalation Reactions

“…[14,15] ICP is an electrokinetic phenomenon originating from selective separation of ions, and it is most commonly implemented using nanoporous channels [10,11] or charge-selective membranes like Nafion. [7][8][9] When a voltage is applied across appropriate channels or membranes, selective ion transport leads to both an IDZ and an ion enrichment zone (IEZ). Because the IDZ is a region of low relative solution conductivity, a disproportionate amount of the applied voltage is dropped within it.…”

“…For example, the lowered electrolyte concentration within an IDZ leads to faster electroosmotic flow (EOF), which could improve desalination efficiency during electrodialysis. [20] Additionally, utilizing ICP has gained significant interest for labon-a-chip applications, including: separation of charged analytes, [21][22][23] high-voltage fluidic diodes, [24] manipulation of charged analytes in microdroplets, [9] and microfluidic mixing. [25][26][27] The electric field gradient associated with ICP has also been used for dielectrophoresis of cells, [14,28,29] salt water desalination, [17,[30][31][32] and analyte enrichment.…”

“…In the field of separation science, ion depletion zones (IDZs) are important because they can be used to enrich and separate charged analytes. As discussed later, IDZs can be formed in the presence or absence of membranes. Here, we report an alternative electrochemical method for forming IDZs at specified locations within microfluidic devices.…”

“…IDZs are formed during a process known as ion concentration polarization (ICP) . ICP is an electrokinetic phenomenon originating from selective separation of ions, and it is most commonly implemented using nanoporous channels or charge‐selective membranes like Nafion . When a voltage is applied across appropriate channels or membranes, selective ion transport leads to both an IDZ and an ion enrichment zone (IEZ).…”