Purification of complex samples: Implementation of a modular and reconfigurable droplet-based microfluidic platform with cascaded deterministic lateral displacement separation modules

Abstract

Particle separation in microfluidic devices is a common problematic for sample preparation in biology. Deterministic lateral displacement (DLD) is efficiently implemented as a size-based fractionation technique to separate two populations of particles around a specific size. However, real biological samples contain components of many different sizes and a single DLD separation step is not sufficient to purify these complex samples. When connecting several DLD modules in series, pressure balancing at the DLD outlets of each step becomes critical to ensure an optimal separation efficiency. A generic microfluidic platform is presented in this paper to optimize pressure balancing, when DLD separation is connected either to another DLD module or to a different microfluidic function. This is made possible by generating droplets at T-junctions connected to the DLD outlets. Droplets act as pressure controllers, which perform at the same time the encapsulation of DLD sorted particles and the balance of output pressures. The optimized pressures to apply on DLD modules and on T-junctions are determined by a general model that ensures the equilibrium of the entire platform. The proposed separation platform is completely modular and reconfigurable since the same predictive model applies to any cascaded DLD modules of the droplet-based cartridge.

A Review on Deterministic Lateral Displacement for Particle Separation and Detection

“…The use of sparse pillar arrays with only several pillar structures and the sieve-based lateral displacement is able to improve the throughput rate in DLD, but it requires an additional adjustment on the array design to balance the pressure to prevent the disruption of the particle separation [94][95][96][97]. Stacking and parallelization of microfluidic DLD devices to multiply the throughput rate have also been reported [37,[98][99][100]. For example, [17].b The application of paper pump to drive the particle separation in an open DLD channel [69].…”

“…To design a cascade array, the resistance of the side channels must be comparable to the resistance of the main channel to provide the same flow rate for each channel. The cascade array can also be designed as a modular device that can be combined in a series or parallel manner for the separation of polydisperse particles [ 36 , 37 ].…”

A Review on Microdevices for Isolating Circulating Tumor Cells

“…A capture efficiency of >80% was reported on breast and colon cancer cells. Another example was to use deterministic lateral displacement (DLD) to separate two populations of particles around a specific size [58]. DLD is a size-based fractionation technique.…”

Controlled protein adsorption on a silica microparticle

“…Microfluidics is an emerging technology in engineering and medical and life sciences, which can be effectively employed for purification [18], biological sample preparation/analysis [19], cell sorting [20], DNA separation [21], etc. Microfluidics' popularity arises from the miniaturization of device dimensions, lowering the sample volume and manufacturing costs, and the ability to construct high‐throughput devices [22].…”