Confined particles in microfluidic devices: a review

Written by Marine Daïeff
Published October 12th 2020
Contact: partnership@elvesys.com, Elvesys SAS, 172 Rue de Charonne 75011 Paris

Introduction to confined particles in microfluidic devices

Microfluidics and microfabrication have been intensively developed during the last decade because their specific scale enables numerous applications in a wide range of fields. The ability to sort out and filter particles or micro-organisms as a function of their properties such as deformability, shape and activity is fundamental for medical, biological and food science applications. Numerous techniques have been developed using microscale filters, external fields (magnetic, acoustic, optical) and sedimentation. The use of inertial [1-2] and viscoelastic effects [3] in order to concentrate particles at specific positions inside channels is also possible, as well as the use of confinement properties.

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This review presents a brief overview of the numerous advantages of confined particles like bubbles, droplets and fibers with various symmetry properties and how confinement can be used for interesting applications such as sorting particles out. Two main advantages presented in this review can arise from this confinement: a better control over the dimensions of the particles formed in situ and a good control over the transport trajectories leading to new strategies for particles sorting.

Figure 1: Generation of confined droplets in a T-junction microfluidic device [4].

Specific properties of confined particles in microfluidic devices

In simple unbounded flows, when the flow boundaries are far from the particle itself and when there is no inertial effect, particles are transported at the velocity of the imposed flow and follow Jeffery orbits [5].

However, when a particle is inserted in a microfluidic device with dimensions comparable to the dimensions of the channel, the particle is confined in a particular system and the situation is completely different. On one side, the walls add boundaries and impose a zero-velocity condition for the flow. On the other side, the particle acts as a moving obstacle for the flow. Two types of confinement can be defined. When particles are confined by the lateral walls of the channel, they experience a lateral confinement. When they are confined by the top and bottom walls of the channel, they experience a transversal confinement. Of course, a particle can be both laterally and transversally confined (Figure 2).

Figure 2: Diverse particles confined and unconfined: (a) fiber perpendicular to a pressure-driven flow, confined by channel walls (left) and cross-section of the fiber with its height comparable to the channel height [6], (b) droplets with high dispersion in size flowing freely in a carrier fluid (A), droplets confined by the channel walls (B) [4], (c) schematic of the streamlines around a droplet confined by the top and bottom walls in a Hele-Shaw cell [7].

Formation of bubbles, droplets and fibers: the advantage of a confined geometry in microfluidic channels

Fluid interfaces confined in microfluidic devices present a different behavior compared to fluid interfaces in unbounded flows, especially because capillary instabilities are inhibited in confined geometries.  As a result, an amazing control of the size, the shape, the uniformity and the rate of formation of bubbles and droplets is possible using microfluidic devices [8]. Three different techniques of formation are mainly used depending on the geometry of the microfluidic device: co-flow, cross-flow and flow-focusing geometries (figure 3a [9]). Studies [4,10,11], projects and technologies like an easy droplet generation pack have been developed during the last decades, demonstrating and using the wonderful advantage of microfluidic devices for the formation of uniform and numerous bubbles and droplets.

In order to study fibers under flow in microfluidic channels and avoid any clogging when introducing them in the channels, the best solution is to fabricate them in situ using a microscope-based projection photolithography method [12-17]. A photosensitive solution chosen to crosslink under UV light is driven in the microfluidic channel by a pressure controller. UV light is projected through a shutter and a mask into the channel under a microscope. When the flow is stopped and under illumination, the targeted fluid region polymerizes within hundreds of milliseconds (Figure 3b). Due to layers along the top and bottom walls with dissolved oxygen permeating through the PDMS, polymerization of the solution is not possible in these regions. The presence of these constant inhibition layers prevents the fibers to be stuck to the walls. The fabrication technique takes advantage of the inhibition layer to create fibers able to freely flow in the middle of the channel. The confinement of the fibers, defined as the ratio between the fiber height and the channel height, is controlled by changing the height of the channel as the inhibition layer is unchanged (Figure 3c). The versatility of the technique enables to fabricate in situ fibers with different mechanical properties, shapes and confinement by adjusting the exposure time, the geometry of the mask and the height of the microchannel.

Figure 3: Techniques for the formation of particles directly in microfluidic devices: (a) illustrations of the three main geometries for droplet generation: co-flowing streams (top), cross-flow streams (middle) and flow focusing geometry with elongational streams (bottom) [9], (b) stop-flow lithography set-up for in situ fabrication of polymeric fibers. A photosensitive solution is illuminated by UV light through a fiber-shaped mask. The targeted fluid region is polymerized [12], (c) sketch showing how the confinement of the particle is controlled by tuning the height of the microfluidic channel [16].

Manipulation of confined bubbles and droplets in microfluidic devices

Taking advantage of the precise control and high uniformity of the volume and frequency of droplets production, droplets have been widely studied. This review choses to present four different studies related to droplets and bubbles properties and transport in microfluidic devices where confinement leads to specific features.

In the scope of droplet-based lab-on-chip devices, one needs to understand the conditions controlling coalescence and non-coalescence behavior of confined droplets without the need of external fields [18]. For efficient coalescence, it is necessary to control the local curvature of the droplet and keep the speed of collision low. If the system does not meet the right criteria, splitting and slipping is observed (Figure 4a).

Concerning the creation of droplets, most of the microfluidic devices use the help of hydrodynamic forces. In order to simplify the device operations, using only the geometry properties of microfluidic devices to create droplets is a real advantage. Generation and self-propulsion of droplets is possible by incorporating height variations to the system and hence a gradient of confinement [19] (Figure 4d).

Confined bubbles can be used to sort particles as a function of their size [20]. Particles with a diameter smaller than the thickness of the bubble-wall gap move through the thin film without colliding with the bubble interface. The others are captured by the bubble (Figure 4b). By adjusting the speed of the bubble, it is possible to change easily the thickness of the lubrification film.

The dynamics of transported droplets confined in Hele-Shaw geometries are rich and interesting to study and control in order to develop a way to mix and transport entities in microfluidic devices. When a pair of droplets or an assembly of three droplets are transported, the dynamics become more complex with phenomena such as rebound, pair exchange and reorientation processES (Figure 4c). When the assembly is laterally confined, oscillations between side walls are observed [7]. Some similarities with the transport of rigid fibers described in the next section can be observed.

Figure 4: Manipulation of confined bubbles and droplets in microfluidic devices: (a) droplet collision at  microfluidic T-junction with immediate or late coalescence, splitting and slipping depending on the speed and size of the droplets [18], (b) separation of particles by size using the motion of a confined bubble [20], (c) dynamics of pair of droplets transported in Hele-Shaw cells: experiments (A) and calculation (B). The pair of droplets rotates and tends to align with the flow [7], (d) generation and manipulation of droplets using a gradient of confinement instead of hydrodynamic forces. The geometry of the device controls the size of the droplet [19].

Transport of confined rigid particles in microfluidic devices

Transport dynamics are very unique in confined geometries and depend on the level of symmetry of the fibers. Elongated fibers with two axes of symmetry follow different and really specific trajectories compared to fibers with one or zero axis of symmetry.

In Hele-Shaw cells, when an elongated fiber with two axes of symmetry undergoes a transversal confinement, its velocity is reduced. Due to viscous friction introduced by the top and bottom walls, the fiber is not transported at the speed of the imposed flow any more. Moreover, it has been shown that the velocity of the fiber depends on its orientation [16]. A fiber perpendicular to the flow moves faster than one parallel to the flow. As a result, for a transported fiber with an initial orientation different from 0° and 90°, a drift motion is observed in the lateral direction towards the channel walls. The importance of the drift motion increases with transversal confinement (Figure 5a). As a result, the trajectories can be tuned by transversal confinement and it is then possible to sort particles according to their confinement.

For particles with fore-rear asymmetry and only one axis of symmetry in confined microfluidic channels, the trajectory depends on their geometry but they all present the same behavior with a reorientation process. With pairs of droplets of different sizes (Figure 4c [7]), rigid asymmetric dumbbell particles (Figure 5b [21]) or T-shaped particles (Figure 5c (c) [22]), it has been observed a rotation to align the mirror axis with the flow and with the biggest block upstream. The timescale for the dynamics is strongly dependent on the particle shape [23].

In practical situations, it is more likely to have particles with small asymmetries with respect to all axes. It is then important to study the trajectories of particles with no axis of symmetry in confined microfluidic channels. For completely asymmetric particles such as L-shaped fibers, it has been observed a reorientation process until an equilibrium orientation followed by a drift motion and finally interactions with the lateral walls (Figure 5c (d), (e) and (f) [22]). Comparable dynamics have been demonstrated using numerical approach [24].

When the lateral walls of the channel are close to the particle, lateral confinement is added to the previous situation. Oscillations between the walls are reported for straight and rigid fibers [25] (Figure 5c (a) and (b)), dumbbell particles [21] and pairs of droplets [7].

All these studies show that the fundamental transport dynamics depend on the level of symmetry, shape and confinement of the particles. It is then possible to control precisely the particle trajectories with applications in targeted delivery, particle sorting or capture inside microchannels.

Figure 5: Transport of confined rigid particles in microfluidic devices: (a) trajectory of straight and rigid fibers (two axes of symmetry) with different orientations (parallel, perpendicular or oriented with an angle of 45°). Each position is recorded with an interval of time indicated in the picture. The confinements are 0.4 and 0.8 for the top and bottom rows respectively [16], (b)  trajectory of a particle with one axis of symmetry. A rotation occurs and the particle aligns its mirror axis with the flow with its biggest block upstream [21], (c) trajectories of fibers with different geometries, from two axes of symmetry (straight fibers) to no axis of symmetry (L-shaped fibers) showing oscillation, rotation and drift [22,25].

Transport of confined flexible fiber particles in microfluidic devices

When flexibility property is added to a confined fiber, the fiber still acts as a moving obstacle and experiences friction with the top and bottom walls of the channel, but a coupling between fiber deformation and transport is introduced. It leads to more complex dynamics as the perturbation of the flow induces non-homogeneous pressure and force distribution along the fiber. If a fiber is being transported perpendicularly to the flow direction it deforms into a C-shape before undergoing a reorientation process and aligning with the flow direction. For confinement above a value of 0.6, a strong influence is observed: the greater the confinement, the stronger the deformation (Figure 6 [6]). Understanding the deformation and transport of complex flexible particles in confined flows is of great interest because of their similarities with red blood cells and vesicles.

Figure 6: Transport of confined flexible fibers in microfluidic devices: superposition of images of a transported flexible fiber with different initial orientations. The fiber undergoes deformation and reorientation processes [6].

Other applications taking advantage of confinement in microfluidic devices

Controlling the dimensions and transport properties of particles in microfluidic channels is not the only way to take advantage of confinement. In many applications in biology and chemistry, the detection of drugs has to be fast and efficient, reactions with small volumes need to be performed and deliveries of well controlled volumes are necessary.

To overcome these challenges, one can use a perpendicular flow in order to confine a medium sample to biosensor surfaces and hence improve the detection rate (Figure 7a [26]). The confinement of a solution or organism in a droplet, called encapsulation, has proven to be very useful [27-28] and enables a wide range of applications such as the detection of bacteria [29] or single cell encapsulation in antibody therapy. In the scope of improvements in this field, existing techniques are combined [30] and new ones are developed – for example to improve the physical properties of nanocomplexes inside droplets (Figure 7b [31]).

Figure 7: Other ways to take advantage of confinement: (a) efficient delivery of a medium to a biosensor surface [26], (b) encapsulation of DNA and polycation solution into individual droplets [31].

To conclude, taking advantage of the confinement in microfluidic devices enables to fabricate particles with well controlled properties and to study their transport dynamics. This knowledge enables to create new techniques and imagine new applications to make improvements in the medical, biological and chemical fields.

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