Acoustically-driven thread-based tuneable gradient generators

Abstract

Thread-based microfluidics offer a simple, easy to use, low-cost, disposable and biodegradable alternative to conventional microfluidic systems. While it has recently been shown that such thread networks facilitate manipulation of fluid samples including mixing, flow splitting and the formation of concentration gradients, the passive capillary transport of fluid through the thread does not allow for precise control due to the random orientation of cellulose fibres that make up the thread, nor does it permit dynamic manipulation of the flow. Here, we demonstrate the use of high frequency sound waves driven from a chip-scale device that drives rapid, precise and uniform convective transport through the thread network. In particular, we show that it is not only possible to generate a stable and continuous concentration gradient in a serial dilution and recombination network, but also one that can be dynamically tuned, which cannot be achieved solely with passive capillary transport. Additionally, we show a proof-of-concept in which such spatiotemporal gradient generation can be achieved with the entire thread network embedded in a three-dimensional hydrogel construct to more closely mimic the in vivo tissue microenvironment in microfluidic chemotaxis studies and cell culture systems, which is then employed to demonstrate the effect of such gradients on the proliferation of cells within the hydrogel.

Surface acoustic wave devices for chemical sensing and microfluidics: a review and perspective

“…Ramesan et al expanded on this concept by using cotton thread rather than paper as the sample carrying medium. 182 Using a mesh or network, they could create different channels and produce a concentration gradient from two supply solutions throughout the network (Fig. 15).…”

Thread based electrofluidic platform for direct metabolite analysis in complex samples

“…The second group are based upon single threads, which generally involve much smaller solution volumes, as in these examples the flow within the strands of the thread is confined to one direction. The use of this later platform has been applied to bacteria isolation and quantification [24], chemotaxis studies for cell culture systems [25], immunoassays [26,27], blood typing [28], chemical synthesis [29], and the determination of nucleic acids [30,31], proteins [4,7,29,[31][32][33][34], glucose [29,[35][36][37], drugs [38], small ions [6,8,32,39] and metals [40]. Several detection techniques have been used for these various applications, with the most common, albeit the least sensitive, being simple colorimetric detection.…”

Microfluidic modelling of the tumor microenvironment for anti-cancer drug development

“…There have also been some interesting microfluidic devices which adopt alternative approaches to generate these chemical gradients. For example, a thread network was shown to allow cell growth with different chemical concentrations by absorbing solutions of high and low chemical concentrations [207]. Electric fields can also be used to modulate the chemical gradient in a microfluidic device and this feature may be easily incorporated into existing devices [208].…”