A programmable microfluidic platform for multisample injection, discretization, and droplet manipulation

Abstract

A programmable microfluidic platform enabling on-demand sampling, compartmentalization, and manipulation of multiple aqueous volumes is presented. The system provides random-access actuation of a microtrap array supporting selective discretization of picoliter volumes from multiple sample inputs. The platform comprises two interconnected chips, with parallel T-junctions and multiplexed microvalves within one chip enabling programmable injection of aqueous sample plugs, and nanoliter volumes transferred to a second microtrap array chip in which the plugs are actively discretized into picoliter droplets within a static array of membrane displacement actuators. The system employs two different multiplexer designs that reduce the number of input signals required for both sample injection and discretization. This versatile droplet-based technology offers flexible sample workflows and functionalities for the formation and manipulation of heterogeneous picoliter droplets, with particular utility for applications in biochemical synthesis and cell-based assays requiring flexible and programmable operation of parallel and multistep droplet processes. The platform is used here for the selective encapsulation of differentially labeled cells within a discrete droplet array.

Programmable Control of Nanoliter Droplet Arrays Using Membrane Displacement Traps

“…For example, we have previously reported the design and implementation of an on‐chip multiplexer topology capable of MDT actuation based on the pioneering work of Thorsen et al. [ 113 ] that employs n inputs to control 2 n/2 traps, [ 69 ] offering a promising path toward future arrays with significantly higher trap densities through microfluidic large‐scale integration.…”

“…We previously demonstrated that this simple process can be employed to achieve reliable on-demand droplet capture and ejection from the MDT traps. [47,68,69] In the present work we significantly extend the range of unit operations that can be implemented using MDT technology. An overview showing the configuration of a membrane displacement trap is presented in Figure 1A, and operation of a single trap for droplet capture and release is shown in Figure 1B.…”

“…This design provides precise control over the injected aqueous volumes. [47,69] The independent plug generators allow two different samples to be injected at desired time points. Additional generators may be readily integrated for applications requiring higher levels of sample multiplexing.…”

“…To address this limitation, various pneumatic microfluidic multiplexers have been reported to provide control over large numbers of on-chip elastomer actuators with a minimal number of control inputs, [111][112][113] offering a potential solution to the scaling challenge. For example, we have previously reported the design and implementation of an on-chip multiplexer topology capable of MDT actuation based on the pioneering work of Thorsen et al [113] that employs n inputs to control 2 n/2 traps, [69] offering a promising path toward future arrays with significantly higher trap densities through microfluidic large-scale integration.…”

Deterministic assembly of chromosome ensembles in a programmable membrane trap array

“…In particular, droplet microfluidics [26] provides a straightforward approach for isolating single biological particles, with the number of components within each droplet defined by a Poisson distribution [27,28]. Specific control over individual droplets for higher level manipulation of the discretized volumes, such as trapping, storing, releasing, metering, or merging [29,30] can be achieved by appending additional microfluidic components following droplet formation, such as integrated microvalves [31][32][33][34][35], traps [36][37][38][39][40], or a combination of both [41][42][43][44][45] to yield the desired functionality. However, existing droplet microfluidic platforms are not designed with the goal of enabling efficient assembly of macromolecular sets with precise control over numbers and types within the resulting population.…”