Tunable 3D droplet self-assembly for ultra-high-density digital micro-reactor arrays

Abstract

We present a tunable three-dimensional (3D) self-assembled droplet packing method to achieve high-density micro-reactor arrays for greater imaging efficiency and higher-throughput chemical and biological assays. We demonstrate the capability of this platform's high-density imaging method by performing single molecule quantification using digital polymerase chain reaction, or digital PCR, in multiple self-assembled colloid-like crystal lattice configurations. By controlling chamber height to droplet diameter ratios we predictively control three-dimensional packing configurations with varying degrees of droplet overlap to increase droplet density and imaging sensor area coverage efficiency. Fluorescence imaging of the densely packed 3D reactor arrays, up to three layers high, demonstrates high throughput quantitative analysis of single-molecule reactions. Now a greater number of microreactors can be observed and studied in a single picture frame without the need for confocal imaging, slide scanners, or complicated image processing techniques. Compared to 2D designs, tunable 3D reactor arrays yield up to a threefold increase in density and use 100% of the sensor's imaging area to enable simultaneous imaging a larger number of reactions without sacrificing digital quantification performance. This novel approach provides an important advancement for ultra-high-density reactor arrays.

Microfluidic Induced Controllable Microdroplets Assembly in Confined Channels

“…The crystalline lattice of droplet packing model in theory for predicting high density monodispersed droplets assembly patterns by controlling the confined channel depth or droplet size has been demonstrated by Lee et al [10]. By changing only the depth of the microchannel In Figure 6, there were more data points found in the bottom-left area than top-right area because of the stable droplet generation and fluidic flow at low flow rates rather than high flow rates.…”

“…Monodispersed photonic electro-responsive Janus microspheres have been created with the assistance of a microfluidic device, showing structural colors of the nanoparticle crystals [24]. Furthermore, highly ordered structures of fluidic particles (gas-bubbles or liquid-droplets) have been observed in microfluidic devices, which could afford unique fluidic hydrodynamics and boundary restriction, and be applied for imaging, bioassaying, data storaging and environment monitoring [10,21,22,30,31].…”

“…Direct self-assembly implies an approach to precisely control over rearrangement process to obtain their devised and desired self-organization structures and configurations, while retaining the key elements of spontaneous self-organization [4,5]. Materials with self-assembled structures have received tremendous and increasing attention because of their potential applications in various fields, such as sensors [6], electrical or optical switchers [7], photonic devices [8], data storage materials [9] and bioassays [10].…”

“…Moreover, in the microfluidic device, the fluidic properties and flow profiles, the microstructure size and shapes could be tuned properly. Therefore, the self-assembly process could be induced by capillary force or hydrodynamic force inside the microfluidic devices [10,20,21].…”

All-aqueous multiphase microfluidics

“…71 Hierarchical assembly of materials can be guided by either allaqueous phases or their interface. In the assembly of functional biomimetic units, droplet networks constructed through 3-D printing 72 and droplet-packing in chambers 73 bring new promises. Meanwhile, hierarchical assembly of nano-particles has been investigated at the interfaces of two miscible aqueous phases.…”