Nan-Nan Deng

Monodisperse Uni- and Multicompartment Liposomes

Liposomes are self-assembled phospholipid vesicles with great potential in fields ranging from targeted drug delivery to artificial cells. The formation of liposomes using microfluidic techniques has seen considerable progress, but the liposomes formation process itself has not been studied in great detail. As a result, high throughput, high-yielding routes to monodisperse liposomes with multiple compartments have not been demonstrated. Here, we report on a surfactant-assisted microfluidic route to uniform, single bilayer liposomes, ranging from 25 to 190 μm, and with or without multiple inner compartments. The key of our method is the precise control over the developing interfacial energies of complex W/O/W emulsion systems during liposome formation, which is achieved via an additional surfactant in the outer water phase. The liposomes consist of single bilayers, as demonstrated by nanopore formation experiments and confocal fluorescence microscopy, and they can act as compartments for cell-free gene expression. The microfluidic technique can be expanded to create liposomes with a multitude of coupled compartments, opening routes to networks of multistep microreactors.

Monodisperse and Fast-Responsive Poly(N-isopropylacrylamide) Microgels with Open-Celled Porous Structure

A simple and efficient method is developed to fabricate monodisperse and fast-responsive poly(N-isopropylacrylamide) (PNIPAM) microgels with open-celled porous structure. First, numerous fine oil droplets are fabricated by homogeneous emulsification method and are then evenly dispersed inside monodisperse PNIPAM microgels as porogens via the combination of microfluidic emulsification and UV-initiated polymerization methods. Subsequently, the embedded fine oil droplets inside the PNIPAM microgels are squeezed out upon stimuli-induced rapid volume shrinkage of the microgels; as a result, a spongelike open-celled porous structure is formed inside the PNIPAM microgels. The open-celled porous structure provides numerous interconnected free channels for the water transferring convectively inward or outward during the volume phase transition process of PNIPAM microgels; therefore, the response rates of the PNIPAM microgels with open-celled porous structure are much faster than that of the normal ones in both thermo-responsive shrinking and swelling processes. Because of the fast-responsive characteristics, the microgels with open-celled porous structure will provide ever better performances in their myriad applications, such as microsensors, microactuators, microvalves, and so on.

A novel surgery-like strategy for droplet coalescence in microchannels

We report an innovative and efficient surgery-like strategy for achieving the coalescence of surfactant-stabilized droplets in microchannels. As pairs of preformed droplets flow across a micro-lancet, with a suitable surface wettability, in a converging microchannel simultaneously, their surfaces are scratched by the micro-lancet, which causes temporarily local scattering of surfactants, and thus induces their coalescence by joining up their scratched wounds. Our approach shows highly controllable flexibility and stability. We demonstrate this by controlling the coalescence of emulsion droplets with different numbers and complex structures. This surgery-like strategy is totally passive and has great potential in myriad applications including micro-reaction, high-throughput injection, and multiple emulsion formation, etc.

Hydrogel-Based Microactuators with Remote-Controlled Locomotion and Fast Pb2+-Response for Micromanipulation

Hydrogel-based microactuators that enable remote-controlled locomotion and fast Pb(2+)-response for micromanipulation in Pb(2+)-polluted microenvironment have been fabricated from quadruple-component double emulsions. The microactuators are Pb(2+)-responsive poly(N-isopropylacrylamide-co-benzo-18-crown-6-acrylamide) microgels, each with an eccentric magnetic core for magnetic manipulation and a hollow cavity for fast Pb(2+)-response. Micromanipulation of the microactuators is demonstrated by using them for preventing Pb(2+)-leakage from microchannel. The microactuators can be remotely and precisely transported to the Pb(2+)-leaking site under magnetic guide, and then clog the microchannel with Pb(2+)-responsive volume swelling to prevent flowing out of Pb(2+)-contaminated solution. The proposed microactuator structure provides a potential and novel model for developing multifunctional actuators and sensors, biomimetic soft microrobots, microelectro-mechanical systems and drug delivery systems.

Wetting-induced coalescence of nanoliter drops as microreactors in microfluidics.

Controllable one-to-one coalescence of surfactant-stabilized nanoliter water drops is successfully achieved from wetting-induced drop engulfing in microfluidics by surrounding one of the drops with a thin layer of immiscible wetting fluid. This wetting layer can spread over the other drop to drain away the liquid film between the two drops, thereby inducing coalescence. This innovative approach is totally spontaneous and highly potential in a myriad of fields, such as quantitative analysis, microreaction, and high-throughput injection. To demonstrate this potential, we successfully perform the drop-coalescence-triggered microreaction in microchannels for pH indicator and syntheses of functional materials including micro- and nanoparticles.

Microfluidic formation of monodisperse coacervate organelles in liposomes

Abstract Coacervates have been widely studied as model compartments in protocell research. Complex coacervates composed of disordered proteins and RNA have also been shown to play an important role in cellular processes. Herein, we report on a microfluidic strategy for constructing monodisperse coacervate droplets encapsulated within uniform unilamellar liposomes. These structures represent a bottom‐up approach to hierarchically structured protocells, as demonstrated by storage and release of DNA from the encapsulated coacervates as well as localized transcription.

Spontaneous transfer of droplets across microfluidic laminar interfaces

The precise manipulation of droplets in microfluidics has revolutionized a myriad of drop-based technologies, such as multiple emulsion preparation, drop fusion, drop fission, drop trapping and drop sorting, which offer promising new opportunities in chemical and biological fields. In this paper, we present an interfacial-tension-directed strategy for the migration of droplets across liquid-liquid laminar streams. By carefully controlling the interfacial energies, droplets of phase A are able to pass across the laminar interfaces of two immiscible fluids from phase B to phase C due to a positive spreading coefficient of phase C over phase B. To demonstrate this, we successfully perform the transfer of water droplets across an oil-oil laminar interface and the transfer of oil droplets across an oil-water laminar interface. The whole transfer process is spontaneous and only takes about 50 ms. We find that the fluid dynamics have an impact on the transfer processes. Only if the flowrate ratios are well matched will the droplets pass through the laminar interface successfully. This interfacial-tension-directed transfer of droplets provides a versatile procedure to make new structures and control microreactions as exemplified by the fabrication of giant unilamellar vesicles and cell-laden microgels.

Trojan‐Horse‐Like Stimuli‐Responsive Microcapsules

Abstract Multicompartment microcapsules, with each compartment protected by a distinct stimuli‐responsive shell for versatile controlled release, are highly desired for developing new‐generation microcarriers. Although many multicompartmental microcapsules have been created, most cannot combine different release styles to achieve flexible programmed sequential release. Here, one‐step template synthesis of controllable Trojan‐horse‐like stimuli‐responsive microcapsules is reported with capsule‐in‐capsule structures from microfluidic quadruple emulsions for diverse programmed sequential release. The nested inner and outer capsule compartments can separately encapsulate different contents, while their two stimuli‐responsive hydrogel shells can individually control the content release from each capsule compartment for versatile sequential release. This is demonstrated by using three types of Trojan‐horse‐like stimuli‐responsive microcapsules, with different combinations of release styles for flexible programmed sequential release. The proposed microcapsules provide novel advanced candidates for developing new‐generation microcarriers for diverse, efficient applications.

Macromolecularly Crowded Protocells from Reversibly Shrinking Monodisperse Liposomes

The compartmentalization of cell-free gene expression systems in liposomes provides an attractive route to the formation of protocells, but these models do not capture the physical (crowded) environment found in living systems. Here, we present a microfluidics-based route to produce monodisperse liposomes that can shrink almost 3 orders of magnitude without compromising their stability. We demonstrate that our strategy is compatible with cell-free gene expression and show increased protein production rates in crowded liposome protocells.