Microfluidics for material production

We develop methods to create new functional materials using microfluidic devices. These devices provide capabilities for very precisely mixing fluids to form new materials. All the structures are based on drops which can both encapsulate active materials and serve as templates on which to build new structures. These have interesting properties and great technological potential for encapsulation and controlled release of a wide variety of active materials. We also consider methods to scale up the fabrication of these materials to produce practical quantities. This work is motivated by both fundamental studies and the potential for creating technologically valuable materials, and some of the work has led to industrial applications.

Quadruple Emulsion Templated Multilamellar Phospholipid Vesicles: Multilamellar vesicles are promising delivery vehicles for multiple components of drugs or enzymes for pharmaceuticals and cosmetics. There have been reports of multiple polymersomes for encapsulation and programmed release. However, phospholipids as the natural component of biological membranes have not been successfully used for fabrication of multilamellar vesicles, mainly because of their fragility and small size. In this project we want to develop a microfluidic method to prepare liposomes with double bilayers through quadruple emulsion templates. The resultant biocompatible vehicle will have potential application for separated storage and controlled release of multiple components. Moreover, we also look forward to providing a platform to study physical properties of biomembranes with multilamellar liposome structures. Anqi Chen

Encapsulation and enhanced biocidal effect in biodiesel: A major problem delays wide application of biodiesel is microbial contamination during storage. Most of the microbes live in water phase in the storage tank. The most effective way to kill the microbes is to dose biocide directly to the water phase. However practically people put antimicrobial actives to the biodiesel directly, the extra antimicrobial actives will eventually be combusted with the fuel and emitted to the air causing air pollution. We use microfluidic approach to encapsulate biocide in hydrogel, which acts as a vehicle that delivers biocide to the interface of oil and water then burst release the biocide into water, leaving as little as possible biocide in the oil phase. Hao Pei

Fatty amine encapsulation: Fatty amine is a widely used nonionic surfactant for water in oil emulsion. It’s also been added to the marine engine lubricant as the neutralizing active. It’s a type of very effective acid remover but it is instable in high temperature, like working temperature in the engine. We are interested in protecting the fatty amine from early degradation and controllably releasing it in acidic environment. By encapsulating fatty amine in pH-responsive microcapsules, it is possible to use the capsule shell as the physical barrier to separate the air and the inside fatty amine, thus delay the oxidative degradation. Hao Pei

Smart Janus capsules. Microscopic materials with anisotropic structures or compositions are of great interesting and potentials for various applications. My project focus on fabrication of Janus microcapsules with anisotropic structures or compositions by microfluidics, which could be applied to stimulating responsive, drug delivery and microactuators. Yong Zhao

Nanoliposomes, Phospholipid Liposomes, and Polymersomes for Drug Delivery: In order to improve the delivery of drugs to the target area, a number of different capsules for drugs are being developed. The ideal particle will be safe and stable, able to deliver a targeted dose of drug only to treatment areas. Mingtan Hai

Electrically-Controlled Programmable Microfluidics System: You need to prepare for 3 hours and you collect the droplets for 15 minutes, leave along the time designing in AutoCAD, making wafer, and if some are blocked you need to debug and do it again. Have you ever thought about “make it once, run it immediately”?  You can do it if you have valves that controllable and connect the elements you want it to. Unlike programmable microfluidics project in Stanford, I use electrically controllable valves that largely facilitate the portability of the device, when study today are all using magnetically controlled or vacuum controlled valves which need abundant hardware and limit its usage; Now we have a 3CM*3CM chip that connect to microfluidics chips and control 3*3 grid of valves by computer, as well as a activator grid for valves comprising 64 addressable electrodes served as valves actuators. The goal of it is to demonstrate an electrically controlled “generous purpose” system comprising elements such as cell trap, channels, mixer, and detection mechanism and connected by valve grid via ipad coding. Yanzhe Qin

 

Multilayer Polyelectrolyte Capsule Assembly in Microfluidic Device. In the classical Layer-by-Layer (LbL) technique, polyelectrolyte multi-layer capsules are fabricated by alternatively deposited charged polyelectrolytes onto an oppositely bulk or colloidal template followed by dissolved the template which is high consuming. Droplet-based microfluidics which involves the generation of producing high mono-dispersity drops offers a platform for miniaturizing LbL technique by imparting benefits of time and reagent reduction.  We present a novel deposition method by designing a new microfluidic coating device which utilizes “Z” shape channel to guide discrete droplets. Similar to the game of pinball in which the templates guided and diverted to the downstream direction smoothly by repeated unit rows of fabricated channels. Right now, we achieved four layers of polyelectrolyte deposition on a template in less than 2 minutes by guiding discrete templates through coating and washing solution of flushing and two polyelectrolytes. Liyuan Zhang

Fabrication of multilayered microfluidic devices and its application for double emulsions: Photolithography is an accurate, reproducible and easy method for fabricating micron scale devices. The basic outcome of Photolithography is a single layer, and it is possible to repeat the exposure process and end up with multilayered landscapes. However, some topologies are impossible to achieve using multiple exposures and require a complementary method of stacking up devices after fabrication. We use a simple method for aligning stacks of micron-scale devices that relies on matching locks and keys that are an inherent part of the device. Applications of multilayered devices are numerous. We focus here on the generation of double emulsions that are useful for instance in encapsulation (drug delivery) and particle synthesis. The formation of double emulsions in single layered microfluidic devices demands precise spatial control over surface properties of the device channels. However in the case of axial symmetric microfluidic devices such as capillaries, this is no longer a constraint since there is no direct contact between the double emulsion and the device surface. We show that forming double emulsions in multilayered microfluidic device is similar to their formation in capillaries, alleviating the need for precise spatial control of wettability. Improving the robustness of double emulsion formation in photolithographic devices is important for large scale uses of double emulsions. Assaf Rotem

Spatially Segregated Wettability in Microfluidic Devices and Scale-up: In order to make water-in-oil-in-water double emulsions with microfluidic devices, the channels of the device must have spatially segregated wettability – in other words the wettability should be such that the first junction of the device wets the shell phase, and the second junction wets the oil phase. We use tandem emulsification to achieve spatially segregated wettability, and also explore methods of achieving segregated wettability in thermoplastic devices through careful engineering of device geometry and functionalization techniques. We also scale-up the production of double emulsions with sizes close to the millimeter-range and with viscous shells, shown here. Saraf Nawar

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Encapsulation of high-viscosity biologics and on-demand release. The goal of this project is to encapsulate highly viscous antibody for subcutaneous injection and to realize triggered release in human body environment. To do this, we develop a microfluidics approach to fabricate microcapsules based on water-in-oil-in-water double emulsion template. The biologics is encapsulated in biocompatible and photocurable polymer, which transforms into crosslinked polymeric shells upon UV illumination. By tuning the flowrate of middle phase and inner phase, we are able to fabricate microcapsules with non-uniform shell thickness. The structural inhomogeneities lead to inhomogeneous deformation in shell upon external osmotic pressure change, enabling capsule rupture at the thinnest part of the shell. Liangliang Qu

qu-liangliang-icon-fig2.jpgEncapsulated Reactive Small Molecules. The goal of this project is to encapsulate the polyurethane precursors, polydiisocyanates and polyols, in separate polymeric shells and to release them simultaneously upon external stimuli so as to form polyurethane network in desired position. The most challenging part of this project is that it is difficult to find an effective way to encapsulate polydiisocynantes due to their high reactivity. Our strategy here is to form polyurethane shell via interfacial polymerization. Liangliang Qu
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Encapsulation of neutralizing agents for marine lubricants. Fatty amines (FAs) are used as effective acid neutralizing agents in marine lubricants, however they suffer thermal degradation in marine engine. The goal of this project is to protect FAs from early oxidation and thermal degradation and release them when entering into contact with organic acid. The challenge of encapsulating FAs is that FAs prefer to stay at interface due to very low surface tension. Our strategy is to trap FAs in the crosslinked polymer network as a core and generate protective shells by using pH-responsive polymer. Liangliang Qu

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Reversibly responsive and selective microcapsules: Microcapsules have been established as efficient carrier vehicles for sensitive actives. Capsules with radii of 10s-100s of microns and thin shells offer a large cargo space while utilizing only a small amount of encapsulant. Many encapsulation systems are designed for single use and one way applications only, however. We develop microcapsule based encapsulation systems that allow for repeated uptake and release of cargo utilizing responsive and non-destructive permeability change of the capsule shell. We achieve this by using reversibly stimuli-responsive functional polymer shells, such as pH-responsive block copolymers, hydrogels, etc. The responsive nature of the polymers is complemented with selectivity by morphological and chemical design, allowing for discrimination of permeates by charge, size, or chemical functionality, leading to encapsulation systems with application areas far beyond the traditional ones, including purification and separation. Joerg Werner

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OEG-based thermoresponsive microparticles by microfluidics: Polymeric microgels and microcapsules with temperature triggered property changes have promising applications in the fields of controlled release, cell laden, cosmetics, etc. Till now, PNiPAM is the mostly used polymer for thermoresponsive microparticles fabrication by microfluidics. However, the irreversible phase transition and the ambiguous biocompatibility due to the presence of amide groups in its structures limit its applications. As an alternative, oligoethylene glycol (OEG)-based dendronized polymers have several superior characteristics, including good biocompatibility, excellent antifouling property, fully reversible thermoresponsiveness, tunable LCSTs and switchable shielding effect, which will be used for microparticles fabrication in this project. We aim to develop novel thermoresponsive particles with excellent properties for materials applications. Wen Li

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Ultrahigh drug loaded carriers: An advanced approach that can precisely control over the preparation process to generate homogeneously size distributed particles with ultrahigh mass fraction of therapeutics, controlled payload release profiles, as well as high throughput productivity is strongly desirable. With the help of microfluidics, I am aiming to develop a versatile and robust approach to efficiently synthesize optimal core/shell structured vectors. After characterization, the obtained optimal vectors will be utilized for cancer therapy or spinal cord injury treatment. Dongfei Liu

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Integrated enrichment detection system for bioassay. Circulating tumor DNA (ctDNA) and microRNA (miRNA) biomarkers as liquid biopsy open up a new field for molecular diagnosis for cancer and other diseases. The clinical samples used to test for these targets are from patients biofluids. These samples are a complex collection with trace level analytes thus the process of separation, purification and enrichment are important as sample pretreatment. Microfluidic system provides a means of separation, enrichment as well as detection. We intend to develop a microfluidic system integrated enrichment, amplification and detection functional modules for the high sensitive determination of ctDNA or microRNA. This proposed microfluidic system will provide enormous potential for applications of clinical diagnosis. Peng Zuo