(a) A schematic of the microfluidic device integrated with microbridge structures interconnecting droplet-carrying and control channels. Two inlets of the droplet-carrying channel (inlets 1 and 2) are for introduction of reagent (Qr) and oil flow (Qo), and the inlet of the control channel (inlet 3) is for introduction of control oil flow (Qc). A fluidic pressure drop between two channels via 45 microbridges can be used to adjust the interval at the droplet-carrying channel, enabling the flexible and precise temporal control of droplets. (b) Channel design of the microfluidic device and enlarged view of fabricated microbridge structures. All fluidic channel and microbridge structures were fabricated from PDMS using standard soft lithographic methods. The overall thickness of the channel was designed to be 35 μm.
(a) Simulation results of flow characteristics with an increase of the additional flow from the control channel. The cross-sectional images acquired nearby outlet show the concentration distributions of two different flows at a control oil flow rate (Qc) of 20 and 80 μl/h, respectively, maintaining a constant oil flow rate (Qo) of 10 μl/h. An additional oil flow field causes the migration of control oil flow passing through each microbridge due to a fluidic pressure drop between two channels, thereby enhancing the velocity of the droplet-carrying flow and inducing the temporal spacing of droplets. (b) Plot of the concentration distributions along the line from A to B in panel a as the flow rate in the control channel (Qc) increases from 2.5 to 80 μl/h. (c) Plot of the calculated pressure drop between two channels according to the control oil flow rate (Qc) at two different oil flow rate (Qo). (d) Plot of the calculated normalized velocity distribution through the microbridges according to the microbridge number. Each data point represents the y-axial velocity in the center of each microbridge at the two different control oil flow rate (Qc).
Droplet interval control with respect to the control oil flow rate (Qc) in the control channel. Microscopic images of varying droplet interval within droplet-carrying channel with respect to the flow rate in the control channel at the fixed flow rates of aqueous (Qr) and oil phase (Qo) (a) 1 and 10 μl/h, (b) 2 and 10 μl/h, and (c) 4 and 20 μl/h, respectively. White and black dashed circles follow 2nd and 3rd droplet of the train of droplets which was temporally controlled by control oil flow, respectively. Plot of the droplet interval with respect to the control oil flow rate (Qc) and reagent flow rate (Qr) at the condition of droplet generation with an oil flow rate (Qo) of (d) 10 and (e) 20 μl/h.
Microscopic images of the gelated hydrogel beads taken at the channel outlet with respect to the control flow rate (Qc) of (a) 40, (b) 60, and (c) 80 μl/h. (d) Plot of the droplet interval measured at the detection zone with respect to the control oil flow rate at the condition of alginate droplet generation with an oil flow rate (Qo) of 10 μl/h, while the reagent flow (Qr) varied from 1 to 10 μl/h. The results indicate that alginate droplets introduced to the droplet-carrying channel were temporally controlled and polymerized by the additional flow including calcified oleic acid.
Microscopic images of the cell-laden alginate beads with varying interval taken at the channel outlet with respect to the control oil flow rate (Qc) of (a) 40, (b) 60, and (c) 80 μl/h. Dashed circles indicate the U937 cell encapsulated in the alginate bead. The fixed flow rates of alginate solution (Qr) and oleic acid (Qo) were 1 and 10 μl/h, respectively.
Production of combinatorial droplet pairs by droplet synchronization in the microfluidic channel. (a) The layout of the parallel-linked channel for the dynamic control of droplets and the confluence channel for the production and observation of droplet pairing. Non-dyed (blue) and dyed (orange) aqueous phase was introduced to each inlet. Non-dyed and dyed droplets emerged from each T-junction were temporally controlled by changing the flow rate of each control flow (Qc1 and Qc2). Microscopic images of the dynamic control of droplet interval at the microbridge and adjusted droplet pairing ratio (non-dyed: dyed) of (b) 1:2, (c) 1:1, and (d) 2:1 at the confluence channel when (b) Qc1 = 80 μl/h and Qc2 = 10 μl/h, (c) Qc1 = 20 μl/h and Qc2 = 20 μl/h, and (d) Qc1 = 20 μl/h and Qc2 = 60 μl/h, respectively. Each inset in (b)–(d) shows a schematic of pairing sequence in droplet pairs. White and orange arrows in each droplet pairing images indicate non-dyed and dyed droplets, respectively. All conditions of droplet generating flow were fixed as Qr1 = Qr2 = 4 μl/h and Qo = 20 μl/h.
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