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Soft Microcapsules

미세캡슐화 연구는 약물 및 바이오 물질의 생체 내 전달로부터 디스플레이에 이르기까지 폭넓은 분야에서 사용되고 있고, 또한 개발이 필요한 분야이다. 과거의 캡슐화 기술이 벌크상에서의 액적화 기술을 이용했다면, 본 연구실에서는 유체 흐름 및 계면의 정교한 제어를 통해 미세유체소자 내부에서의 액적 제조를 기반으로 한다. 이를 통해, 기존에 달성할 수 없었던, 균일한 크기 및 구조의 캡슐 형성이 가능하며, 100%의 캡슐화 효율을 달성할 수 있다. 무엇보다 중요한 것은, 액적으로부터 캡슐이 형성되는 과정의 화학적∙물리적 프로세스를 제어함으로써, 원하는 기능을 갖는 캡슐이 되도록 디자인을 할 수 있다는 것이다. 이는 본 기술을 통해 형성되는 캡슐의 다양한 응용을 가능케 한다. 예를 들어, 캡슐막을 특정 외부 자극에 민감하도록 설계하면, 원하는 시간과 위치에서 선택적 방출이 가능해지고, 이러한 구조를 이중 내지는 삼중 구조로 만든다면, 여러 가지 약물을 상호오염 없이 보관하고, 이미 프로그램화 된 방식으로 방출패턴을 형성할 수 있게 된다. 

Encapsulation technology has been intensively developed. Recently, these technologies have attracted considerable attention due to their increasing importance in various applications, ranging from drug delivery, cosmetics, and foods to emerging areas of display devices and medicine.  It is not surprising anymore that all commercialized E-papers (for example, “Amazon Kindle”) are based on microcapsules containing oppositely-charged black and white microparticles (called “E-ink”).
Double-emulsion droplet is one of the most attractive geometries in terms of microcapsule fabrication. Recent advances in microfluidics have enabled to make such double-emulsion droplets in precisely controlled manner. In particular, multiple emulsions with controlled numbers of phases and cores have been prepared, which are useful to make microcapsules for controlled release of core materials.

Double-emulsion drops with ultrathin-shell

We have developed a new emulsification technique that creates monodisperse double-emulsion drops with a core-shell geometry having an ultra-thin wall as a middle layer. We create a biphasic flow in a microfluidic capillary device by forming a sheath flow consisting of a thin layer of a fluid with high affinity to the capillary wall flowing along the inner wall of the capillary, surrounding the innermost fluid. This creates double-emulsion drops, using a single step emulsification, having a very thin fluid shell. If the shell is solidified, its thickness can be small as a hundred nanometers or even less. Despite the small thickness of this shell, these structures are nevertheless very stable, giving them great potential for encapsulation. We demonstrate this by creating biodegradable microcapsules of poly (lactic acid) with shell thickness of a few tens of nanometers, which are potentially useful for encapsulation and delivery of drugs, cosmetics, and nutrients.

1. Shin-Hyun Kim, Jin Woong Kim, Jun-Cheol Cho, and David A. Weitz, “Double-emulsion drops with ultra-thin shells for capsule templates,”  Lab on a Chip, 11, 3162–3166 (2011).

Polymersomes templated by double-emulsion drops

Polymersomes are vesicles with membranes composed of bilayers of amphiphilic block-copolymers; they exhibit greatly enhanced stability and controllability by comparison to the more widely used liposomes whose membranes consist of bilayers of phospholipids. Thus, polymersomes have great promise as capsules for drugs, cosmetics, and nutrients, enabling long term storage and controlled release of the actives. However, conventional approaches to make vesicular structures, such as electroformation or bulk hydration of dried amphiphiles, achieve only limited control over size and low efficiency of encapsulation. We have developed double emulsion-based microfluidic approach to overcome such shortcomings of conventional methods. Through dewetting of the amphiphile-laden oil phase from the surface of the innermost water drop of double-emulsion drops, unilamellar vesicle membranes can be efficiently fabricated. In addition, we have produced multiple polymersomes, or polymersomes-in-polymersomes, which have significantly enhanced flexibility and capability, enabling encapsulation and programmed release of multiple distinct components. 

1. Shin-Hyun Kim, Ho Cheung Shum, Jin Woong Kim, Jun-Cheol Cho, and David A. Weitz, “Multiple Polymersomes for Programmed Release of Multiple Components,”  Journal of the American Chemical Society, 133,  15165–15171 (2011).

Multiple-emulsion drops with high order

We have developed a facile one-step emulsification approach to make monodisperse multiple emulsion drops of high order using stable biphasic flows in confining channels. Through controlled surface modification of glass capillary devices, immiscible multiphase streams flow through a single orifice, forming layered coaxial interfaces. Breakup of the interfaces is achieved in dripping or jetting modes, determined by the flow rates. In the dripping mode, breakup is triggered by inserting a drop in the core of the emulsion, facilitating the production of monodisperse triple or quadruple emulsion drops with an onion-like configuration. In addition, by using the jetting breakup mode, the number of drop in the core can be manipulated. This class of multiple emulsion drops has great potential as advanced microcapsules. we have explicitly showed production of model active magnetic inks for display applications. Other examples of potential useful microcapsules include double microcapsules or microcapsules in microcapsules, which are both potentially useful for drug carriers, as they enable sequential release of multi-component drugs while avoiding cross-contamination; they could be valuable in growth-factor delivery and cancer therapy. Furthermore, multiple emulsion drops can act as microreactors which can contain several different reagents. Therefore, this novel approach to make multiple emulsion drops is promising for a wide range of applications owing to its high degree of controllability, its stability, and its simplicity.

1. Shin-Hyun Kim and David A. Weitz, “One-step Emulsification of Multiple Concentric Shells with Capillary Microfluidic Devices,”  Angewandte Chemie International Edition, 50, 8731 –8734 (2011)

Optofluidic encapsulation technique
We have demonstrate the optofluidic encapsulation of CCAs using a double emulsion with a photocurable middle phase. The optofluidic encapsulation of CCAs produced highly monodisperse spherical CCAs with all identical core structures in a controlled manner. In particular, the spherical CCAs gained structural stability immediately after they were produced by in situ photoinduced polymerization of the encapsulating shells. Because CCAs tend to lose stability in an aqueous phase containing ions and other impurities or in an electric field, encapsulation of a CCA with a spherical shell of low permeabilities of ions and molecules can afford long-time stability to the CCA. In addition, the shell inhibits evaporation of water molecules even when the encapsulated CCA is exposed to the atmosphere. More importantly, spherical CCAs show different optical properties from conventional film-type CCAs because the densest plane of the fcc structure, the (111) plane, is the entire spherical inner wall of the shell.

Double-emulsion drops which are drops in drops are useful templates to produce microcapsules. Surprisingly, densely confined core droplets within an oily shell drop rearrange into a unique configuration depending on the number of core droplets by minimization of interfacial energy. In addition, the shell phase drains out of the films between the outer envelope and the overhanging surfaces of the core droplets, resulting in highly thin shell. With these structural advantages of droplet clusters, strong mechanical durability and thin shell phase, we create microparticles of multicompartments by in situ photopolymerization of shell phase of multi-cored double emulsion drops. In particular, the microcapsules can be functionalized through delicate control of surface chemistry of colloids embedded in the capsule membranes in two different approaches; first, perforati
on of the membrane with well defined nanohole array for controlled release and second, construction of the metal nanoarchitectures on the membranes for photo-responsive release.

1. Shin-Hyun Kim, Seog-Jin Jeon, and Seung-Man Yang, “Optofluidic Encapsulation of Crystalline Colloidal Arrays with Spherical Membranes,” Journal of the American Chemical Society, 130, 6040-6046 (2008) 

2. Shin-Hyun Kim, Hyerim Hwang, Che Ho Lim, Jae Won Shim and Seung-Man Yang, “Packing of emulsion droplets: Structural and functional motifs for multi-cored microscapsules,” Advanced Functional Materials,  21, 1608-1615 (2011).