Cell sorting in microfluidics (1. DLD)


Microfluidic devices have been used to separate a variety of target cells and particles from samples like blood, urine or cerebral spinal fluid.

One approach to this separation uses an impressive, passive microfluidic technique called deterministic lateral displacement (DLD for short). The beauty lies in its simplicity: Once you have built your array, the sorting is basically a by-product of the sample flowing through the device. Your perfectly tailored microfluidic environment can run continuously, separating your desired targets (e.g. circulating tumour cells, parasites, marker DNA, exosomes, etc.…) from anything else in your sample.

So, why is it not widely used?

Well, it is not that simple (of course!)

Naive model

First of all, even the simplified „naive model“ (as Timm Krueger and I love to call it) takes a bit time to think through there:

The figure above illustrates the top view of a typical deterministic lateral displacement (DLD) geometry. Rightmost panel shows geometric details. G is the gap size, λ is the pillar array pitch (here, identical for x and y directions), D is the post diameter, and Δλ is the row shift. The row shift fraction in this example is ε=Δλ/λ= 1/4, and the tilt angle is α= tan−1(ε). The shifted post arrangement separates the fluid flow into distinct flow lanes (shown in different shadings) separated by a periodic pattern of stagnation streamlines (centre panel). The leftmost panel shows these flow lanes (N=1/ε= 4, here) through a single gap. The width of the “first”(pillar adjacent) flow lane β through each pillar gap gives a first-order approximation of the critical separation radius. Pic and text reproduced from [1]: https://pubs.acs.org/doi/10.1021/acsnano.0c05186.

So, basically, your sample flows through an array, that is tilted in respect to the main flow. The smaller the tilt, the more lanes your flow is divided into. The more lanes, the smaller is each lane – especially around a post of the array. Now, if your particle is significantly bigger than the lane it travels in, it gets pushed into another layer and cannot follow the flow anymore. In this picture, it gets bumped to the right (spoiler: look at the last picture of this post. There a parasite gets bumped downward, while blood cells can continue to flow along horizontally).

Plethora of parameters

Secondly, there is a number of parameters that influence the DLD performance:

Overview of parameters influencing the performance of deterministic lateral displacement (DLD), a powerful microfluidic technique. Reprinted from [1]: https://pubs.acs.org/doi/10.1021/acsnano.0c05186.
A simplified overview of these interdependent parameters are shown in the causal loop diagram above: only the most common and important factors are included. For many applications, additional factors (like sample biochemistry, or sample viscosity) also play a role. Interrelations are shown as arrows. Arrows with a green plus (+) sign indicate that an increase (or decrease) in the upstream factor causes an increase (or decrease) in the downstream one. Arrows with a red minus (−) sign indicate that increasing (or reducing) the upstream factor reduces (or increases) the downstream one. Arrows without signs indicate a complex or unclear relation between factors. Factors are divided into four groups: (1) device geometry, (2) device material, (3)sample/particle properties, and (4)flow/operational properties (colours are used solely for classification). Clogging plays a special role because it is affected by various factors. The central circle labelled “DLD” stands for all desired outcomes of the application (e.g., separation efficiency,critical size). Images and text are based on [1]: https://pubs.acs.org/doi/10.1021/acsnano.0c05186.

BUT: Although it is complicated, it is not impossible:

Above, you see a DLD device separating red blood cells (red) from a trypanosome (blue) simply based on shape and size. No electricity needed. The flow of the sample through the device is all that is needed.

If this sounds intriguing, and you wonder whether DLD is right for you, contact us!

We will get you sorted!

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