Viscoelastic Particle Encapsulation Using a Hyaluronic Acid Solution in a T-Junction Microfluidic Device

Abstract

The encapsulation of particles and cells in droplets is highly relevant in biomedical engineering as well as in material science. So far, however, the majority of the studies in this area have focused on the encapsulation of particles or cells suspended in Newtonian liquids. We here studied the particle encapsulation phenomenon in a T-junction microfluidic device, using a non-Newtonian viscoelastic hyaluronic acid solution in phosphate buffer saline as suspending liquid for the particles. We first studied the non-Newtonian droplet formation mechanism, finding that the data for the normalised droplet length scaled as the Newtonian ones. We then performed viscoelastic encapsulation experiments, where we exploited the fact that particles self-assembled in equally-spaced structures before approaching the encapsulation area, to then identify some experimental conditions for which the single encapsulation efficiency was larger than the stochastic limit predicted by the Poisson statistics.

Keywords: droplet microfluidics; non-newtonian liquids; viscoelasticity.

Figure 1

(a) Schematic representation of the T-junction device employed in this work. The dispersed viscoelastic phase entered the device via Inlet 1. The trapezoidal structures were added in order to break down potential particle aggregates, in agreement with previous works [43]. After the trapezoidal structure, particles first aligned on the channel centreline and then self-ordered before approaching the encapsulation area. The continuous phase entered the device via Inlet 2, and the droplets containing flowing particles were formed at the T-junction. (b) Image of the Microfluidic device employed in this study next to a 1 pound coin. The device was made of Polymethylemethacrylate bonded on a glass slide using a double-sided tape (see main text for more details) (c) Shear viscosity $\eta$ as a function of the shear rate $\dot{\gamma }$ for the hyaluronic acid solution at 0.1 wt% in phosphate buffer saline. The solutions displays shear-thinning properties above a value of the shear rate equal to $\dot{\gamma }\simeq 30{\mathrm{s}}^{-1}$.

Figure 2

Droplet generation formation and scaling in a T-junction microfluidic device. (a) Experimental snapshots of droplet generation at various continuous phase (oil) flow rates $Q_{oil}$. For the Newtonian case, phosphate buffer saline (PBS) is employed as the dispersed phase. For the non-Newtonian case, hyaluronic acid (HA) at a mass concentration of 0.1 wt% is used as dispersed phase. Satellite droplet formation is only observed in the non-Newtonian case. The volumetric flow rate of the dispersed phase is $8\mathsf{\mu }$L/min in both cases. (b,c) Normalised droplet size $L/W$, where L is the droplet length and $W=100\mathsf{\mu }$m is the channel width (see experimental snapshot in (a)), as a function of the ratio $Q_{PBS}$/$Q_{oil}$ for the Newtonian droplets (b) and $Q_{HA}$/$Q_{oil}$ for the non-Newtonian droplets (c). $Q_{PBS}$ and $Q_{HA}$ are the flow rates of PBS and HA, respectively, while $Q_{oil}$ is the flow rate of the mineral oil. The solid line in (b,c) is $L/W=1+2\left(Q_{PBS}/Q_{oil}\right)$, meaning that the non-Newtonian data in (c) collapse on the master curve for Newtonian droplets. (d) Frequency of non-Newtonian droplet generation as a function of the product $Q_{HA}{Q}_{oil}$. Data points collapse on the master curve $f_{drop}=A{\left(Q_{HA}\times Q_{oil}\right)}^B$ with $A=1.64\pm 0.18$ and $B=2/3$. The parameter A was obtained by fitting the entire data set with flow rate values in the units of $\mathsf{\mu }$L/min, while B was fixed to $B=2/3$ according to the previously introduced by Shahrivar and Del Giudice [27] for xanthan gum solutions.

Figure 3

Viscoelastic particle encapsulation for a hyaluronic acid (HA) dispersed phase and a mineral oil continuous phase. (a–d) Histograms of relative frequency as a function of particles per droplet for a fixed oil flow rate $Q_{oil}$. For each fixed $Q_{oil}$ value, the flow rate of the HA $Q_{HA}$ was in the range 2 to 10 $\mathsf{\mu }$L/min. The Poisson statistics value obtained for $k=n=1$ is represented by the solid symbols. A single particle encapsulation efficiency above the Poisson stochastic value is obtained for $Q_{oil}$ = $Q_{HA}=4\mathsf{\mu }$L/min (b) and $Q_{oil}$ = $Q_{HA}=8\mathsf{\mu }$L/min (c).