Instytut Podstawowych Problemów Techniki

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Two decades of research on droplet formation in microchannels have led to the widely accepted view that droplets form through the squeezing mechanism when interfacial forces dominate over viscous forces. The initially surprising finding that the volume of the droplets is insensitive to the relative importance of these two forces is nowadays well understood from the constrained deformation of the droplet interface during formation. In this work, we show a lower limit of the squeezing mechanism for droplets produced in microfluidic cross-junctions. Below this limit, in the leaking regime, which was recently discovered for droplets produced in T-junctions, the volume of the produced droplets strongly depends on the relative importance of interfacial and viscous forces, as captured by the capillary number. We reveal a fundamental difference in the mechanisms at play in the leaking regime between T- and cross-junctions. In cross-junctions, the droplet neck elongates substantially, and unlike the case of the T-junction, the magnitude of this elongation depends strongly on the value of the capillary number. This elongation significantly affects the final droplet volume in a low capillary number regime. Generalizing the classical squeezing law by lifting the original assumptions and incorporating both identified mechanisms of leaking through gutters and neck elongation, we derive a model for droplet formation and show that it agrees with our experiments.

Słowa kluczowe:

Microfluidics,Cross-junction,Flow-focusing device,Droplet formation,Two-phase flow,Scaling law,Squeezing regime

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Two oppositely charged surfaces separated by a dielectric medium attract each other. In contrast we observe a strong repulsion between two plates of a capacitor that is filled with an aqueous electrolyte upon application of an alternating potential difference between the plates. This long-range force increases with the ratio of diffusion coefficients of the ions in the medium and reaches a steady state after a few minutes, which is much larger than the millisecond timescale of diffusion across the narrow gap. The repulsive force, an order of magnitude stronger than the electrostatic attraction observed in the same setup in air, results from the increase in osmotic pressure as a consequence of the field-induced excess of cations and anions due to lateral transport from adjacent reservoirs.

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While shear emulsification is a well understood industrial process, geometrical confinement in microfluidic systems introduces fascinating complexity, so far prohibiting complete understanding of droplet formation. The size of confined droplets is controlled by the ratio between shear and capillary forces when both are of the same order, in a regime known as jetting, while being surprisingly insensitive to this ratio when shear is orders of magnitude smaller than capillary forces, in a regime known as squeezing. Here, we reveal that further reduction of—already negligibly small—shear unexpectedly re-introduces the dependence of droplet size on shear/capillary-force ratio. For the first time we formally account for the flow around forming droplets, to predict and discover experimentally an additional regime—leaking. Our model predicts droplet size and characterizes the transitions from leaking into squeezing and from squeezing into jetting, unifying the description for confined droplet generation, and offering a practical guide for applications.

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Injection of cell‐laden scaffolds in the form of mesoscopic particles directly to the site of treatment is one of the most promising approaches to tissue regeneration. Here, a novel and highly efficient method is presented for preparation of porous microbeads of tailorable dimensions (in the range ≈300–1500 mm) and with a uniform and fully interconnected internal porous texture. The method starts with generation of a monodisperse oil‐in‐water emulsion inside a flow‐focusing microfluidic device. This emulsion is later broken‐up, with the use of electric field, into mesoscopic double droplets, that in turn serve as a template for the porous microbeads. By tuning the amplitude and frequency of the electric pulses, the template droplets and the resulting porous bead scaffolds are precisely produced. Furthermore, a model of pulsed electrodripping is proposed that predicts the size of the template droplets as a function of the applied voltage. To prove the potential of the porous microbeads as cell carries, they are tested with human mesenchymal stem cells and hepatic cells, with their viability and degree of microbead colonization being monitored. Finally, the presented porous microbeads are benchmarked against conventional microparticles with nonhomogenous internal texture, revealing their superior performance.

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Conducting reactions in droplets in microfluidic chips offers several highly attractive characteristics, among others, increased yield and selectivity of chemical syntheses. The use of droplet microfluidic systems in synthetic chemistry is, however, hampered by the intrinsically small throughput of micrometric channels. Here, we verify experimentally the potential to increase throughput via an increase of the scale of the channels.We use the results of these experiments characterizing the processes of (1) generation of droplets, (2) mixing in droplets, (3) inter-phase extraction, and (4) the yield of synthesis of pyrrole, to postulate a number of guidelines for scaling up the throughput of microfluidic droplet systems. In particular, we suggest the rules for maximizing the throughput via an increase of the size of the channels and via parallelization to optimize the throughput of synthesis against the cost of fabrication of the chips and against the kinetic requirements of specific reactions.

Słowa kluczowe:

flow chemistry, microfluidics, synthesis, emulsions, droplets

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Blood is the richest source of diagnostic information. The growing interest in point-of-care analytics prompted several attempts to extract plasma from whole blood in simple diagnostic devices. The simplest method of separation is sedimentation. Here we show the first microfluidic system that uses sedimentation to extract plasma from undiluted blood and integrates execution of liquid assays on the extracted material. We present a microfluidic chip that accepts a small sample (27 μL) of whole blood, separates up to 6 μL of plasma, and uses metered volumes of plasma and of reagent (2-chloro-4-nitrophenyl-α-maltotrioside, CNP-G3) for a liquid enzymatic assay. With a custom designed channel, the system separates blood by sedimentation within few minutes of accepting the sample, mixes it with the reagent, and quantifies spectrophotometrically the product of the enzymatic reaction. As a model demonstration, we show a quantitative enzymatic α-amylase assay that is routinely used in diagnosis of pancreas diseases. The paper reports the design and characterization of the microfluidic device and the results of tests on clinically collected blood samples. The results obtained with the microfluidic system compare well to a reference bench-top analyzer.

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We report automated generation of arbitrary sequences of multiple microdroplets with online and individual control over the number of cores and volumes of all the constituents (cores and shells) of each of the multiple droplets. We show that a given sequence of volumes of the cores always folds to the same final three-dimensional architecture. The method presents the first proof-of-concept for the ability to design the three-dimensional structure of multiple droplets. We discuss the potential use of the technique in the formulation of predetermined distribution of drug release capsules and for automated generation of functional chemical microdroplet networks.

Słowa kluczowe:

multiple droplets, microfluidics

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We present microfluidic modules (traps) that allow us to lock, shift, dose and merge micro-aliquots of liquid precisely. The precision is hard-wired into the geometry of the device: small values of the capillary number guarantee reproducibility of operation over a range of rates of flow that need not be controlled precisely. The modules can be integrated into systems that perform complicated protocols on micro-droplets while not requiring precision in forcing the flow.

Słowa kluczowe:

microfluidics, droplets

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This report provides practical guidelines for the use of inexpensive electromagnetic valves characterized by large dead volumes (tens to hundreds of μL) for the generation of small (nL) droplets on demand in microfluidic chips. We analyze the role of the ratio of resistances and of the elastic capacitance of the fluidic connectors between the reservoir of the liquid, the valve and the microfluidic chip in the reliable and precise formation of micro droplets on demand. We also demonstrate and examine the use of conventional electromagnetic squeeze valves in the generation of small droplets on demand with a similar set of design rules.

Słowa kluczowe:

microfluidics, droplets

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We demonstrate a strategy for construction of high-throughput microfluidic systems generating gradations of chemistry in micro-droplets. The productivity of the systems that we propose is limited only by the maximum rate of the droplet formation, and does not need to be limited by the rate of mixing. Multilayer polycarbonate chips transform two miscible input streams A and B into N streams of droplets, containing mixtures [A]i, [B]i. Exemplary devices generate linear ([B]i ∝ i) and logarithmic gradations (ln[B]i ∝ i). We also analyze the use of the same strategy for the generation of concentration gradation in the streams of droplets comprising mixtures of liquids of different viscosities. The devices preserve the required distribution of compositions, while allowing the volume of the droplets to be tuned over almost two orders of magnitude (i.e. between 3 and 80 nL).

Słowa kluczowe:

Microfluidics, Generation of gradients, Droplet, Viscosity

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We introduce a novel type of droplet generator that produces droplets of a volume set by the geometry of the droplet generator and not by the flow rates of the liquids. The generator consists of a classic T-junction with a bypass channel. This bypass directs the continuous fluid around the forming droplets, so that they can fill the space between the inlet of the dispersed phase and the exit of the bypass without breaking. Once filled, the dispersed phase blocks the exit of the bypass and is squeezed by the continuous fluid and broken off from the junction. We demonstrate the fixed-volume droplet generator for (i) the formation of monodisperse droplets from a source of varying flow rates, (ii) the formation of monodisperse droplets containing a gradation of solute concentration, and (iii) the parallel production of monodisperse droplets.

Słowa kluczowe:

droplet generator, droplets, microfluidics

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Even at moderate values of Reynolds number [e.g., Re=O(1) ] a curved interface between liquids can induce an abrupt transition between topologically different configurations of laminar flow. Here we show for the first time direct evidence of a sharp transition in the speed of flow of a droplet upon a small increase of the value of the capillary number above a threshold and the associated change of topology of flow. The quantitative results on the dependence of the threshold capillary number on the contrast of viscosities and on the direction of transition cannot be explained by any of the existing theories and call for a new description.

Słowa kluczowe:

speed of droplets, microfluidics, droplets

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Microfluidic droplet-on-demand systems allow the controllable construction of multiple droplets of previously unattainable morphologies. Guided by the diagrams of the possible topologies of double droplets we investigate in detail the vistas to control the morphology of Janus droplets. We also explore and control new morphologies of multiple Janus droplets, i.e., arbitrarily long chains of alternating immiscible segments. Theoretical calculations together with the control offered by the use of automation allow the design of both the topology and the geometry (e.g. curvatures of the interfaces) of the multiple droplets. The ability to rationally design convex–convex, convex–concave and concave–convex segments may be useful in material science, while the ability to tune the distances between the interfaces in the chains of droplets may have applications in designing artificial biochemical signalling networks.

Słowa kluczowe:

multiple droplets, microfluidics

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Oscillations of the input rates of flow have a significant impact on the dynamics of formation of droplets in microfluidic systems and on the quality of generated emulsions.

Słowa kluczowe:

microfluidics, T-junction, droplet generation, syringe pump

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We report a microfluidic technique for high-throughput generation of droplets of nanolitre volume in parallel channels with online control of the volumes, volume fraction and distribution of droplet volumes with the use of two external valves.

Słowa kluczowe:

microfluidics, droplet generation, droplets

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Droplet microfluidic techniques offer an attractive compromise between the throughput (of i.e. reactions per second) and the number of input/output controls needed to control them. Reduction of the number of controls follows from the confinement to essentially one-dimensional flow of slugs in channels which—in turn—relies heavily on the speed of flow of droplets. This speed is a complicated function of numerous parameters, including the volume of droplets (or length L of slugs), their viscosity μd, viscosity μc and rate of flow of the continuous phase, interfacial tension and geometry of the cross-section of the channel. Systematic screens of the impact of these parameters on the speed of droplets remain an open challenge. Here we detail an automated system that screens the speeds of individual droplets at a rate of up to 2000 experiments per hour, with high precision and without human intervention. The results of measurements in channels of square cross-section (of width w = 360 μm) for four different values of the contrast of viscosities λ = μd/μc = 0.3, 1, 3, and 33, wide ranges of values of the capillary number Ca ∈ (10−4, 10−1), and wide ranges of lengths of droplets l = L/w ∈ (0.8, 30) show that the speed of droplets depends significantly both on l and on λ. The dependence on Ca is very strong for λ > 1, while it is less important both for λ ≤ 1 and for λ ≫ 1.

Słowa kluczowe:

microfluidics, capillary flow, droplets

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Electrostatic forces are the strongest interactions in soft matter physics, yet they are usually screened by ions present in the solutions. Here we demonstrate that the extent of ionic polarization of liquid-liquid interfaces can be dynamically controlled via appropriate choice of the strength and frequency of the external electric field. Results of microfluidic experiments on electro-coalescence of droplets of aqueous solutions of salt provide guidelines for optimization of the process.

Słowa kluczowe:

electro-coalescence, droplets, microfluidics

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We demonstrate a new droplet on demand (DOD) technique and an integrated system for scanning of arbitrary combinations of 3 miscible solutions in ∼1.5 μL droplets at 3 Hz. The DOD system uses standard electromagnetic valves that are external to the microfluidic chip. This feature makes up for modularity, simplicity of assembly and compatibility with virtually any microfluidic chip and yields an on-chip footprint of less than 1 mm2. A novel protocol for formation of DOD enables generation of an arbitrarily large range of volumes of droplets at a maximum operational frequency of ∼30 Hz. The integrated system that we demonstrate can be used to scan up to 10000 conditions of chemical and biochemical reactions per hour using ∼10 mL of solutions in total.

Słowa kluczowe:

microfluidics, automation, droplet on demand, droplet

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Słowa kluczowe:

microfluidics, lab on a chip, droplets, T-junction

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Techniques operating on droplets and treating them as single reactors are very promising due to their advantage: i) lack of dispersion, ii) fast mixing, iii) superior control on kinetics of reactions, iv) easy to paralelization v) small volume The challenge is to control the size and the content of each droplet simultaneously.
We present concept of microfluidic modules that taking advantage of the capillary back pressure allow to trap, dose and realize precise portion of liquid. The precision is encrypted in the geometry of the device and large mismatch of shear stresses and capillary forces. This mismatch guaranties reproducibility over a wide range of rates of flow that need not be controlled precisely. We also demonstrate that these modules allow to built systems that perform complicated protocols precisely while nor precise control.

Słowa kluczowe:

microfluidics, droplets

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