View source for Microfluidic fabrication of smart micro gels from macromolecular precursors

==Introduction==

The authors demonstrate how microfluidic technologies can be used to create 'smart', monodisperse microgels which can shrink or swell in response to changes in the surrounding such as temperature. The choice of material in this study is poly(N-isopropylacrylamide) (pNIPAAM) which has a critical temperature of 32 degrees and is often used to make thermo-responsive microgels. The main idea of this technique is to create a stream of pre-microgel solution and using a second immiscible fluid to pinch on the pre-microgel stream to form monodisperse droplets. Exact size of the droplets can be controlled exquisitely by changing the flow rates, viscosities of fluid, etc.

==Keywords==

[[microfluidics]], [[lab-on-a-chip]], [[microgels]], [[monodisperse]]

==Results==

Figure 1 shows a schematic how monodisperse microgel droplets can be produced, i.e. by using an immiscible fluid to pinch the stream of pre-microgel solution. The pre-microgel solution consists of pre-cursor polymer solutions. As mentioned, the size of the droplets can be controlled to a high degree of precision by changing the flow rate and viscosity of the fluid. The pNIPAAM precursors can be functionalized in many different ways before introducing them into the microfluidic channel, while the microfluidic technology itself can be adapted to form different kind of droplet structures, such as Janus microgels, where two different sides of the droplet consist of polymers functionalized in two different ways. (Figure 2). Encapsulation can also be achieved whereby microgel particles are encapsulated in pNIPAAm (Figure 3). The sensitivity of pNIPAAm to temperature also means that the microgel particle load can be released at a certain temperature (Figure 4). 

[[Image:microgel1.png]]

Figure 1. Microfluidic emulsification of a semidilute solution of crosslinkable pNIPAAm precursors in water (schematic). Subsequent gelation of the monodisperse droplets, achieved through crosslinking the polymer chains by dimerization of pendant reactive side groups, forms monodisperse microgel particles.

[[Image:microgel2.png]]

Figure 2. Microfluidic templating of anisotropic microgels with two distinguishable sides (“Janus microgels”). (A) Optical micrograph of a microfluidic device forming aqueous droplets from three separate semidilute pNIPAAm solutions. In the first junction, these three solutions meet and form a laminar, co-flowing stream. In the second junction, this stream is broken to form monodisperse droplets by flow focusing with parafin oil. For demonstration purposes, two of the three polymer phases are tagged with either red or green fluorescent dyes while the third phase is untagged; however, note that the color in Panel A was added digitally, because the true color of these polymer solutions is visible only through fluorescence. To visualize the flow pattern with greater clarity, the inset micrograph shows a similar experiment with a center phase that is doped with iron oxide nanoparticles. Right after their formation, the droplets enter a wide basin channel, where they are gelled by UV exposure. (B) Fluorescence micrographs of the resultant microgel particles. Varying the flow rates of the two tagged outer polymer phases, the untagged center polymer phase, and the emulsifying oil phase from 105:105:30:500 μL/h (upper row of micrographs) to 30:30:180:500 μL/h (lower row of micrographs) yields particles with different inner morphology. All scalebars denote 100 μm.

[[Image:microgel3.png]]

Figure 3. Microfluidic fabrication of microgel capsules that consist of two miscible yet distinct layers. (A) Schematic of a microfluidic device forming aqueous pNIPAAm droplets that are loaded with a well-defined number of pre-fabricated microgel particles of a similar material, pNIPAAm or polyacrylamide. Subsequent droplet gelation leads to microgels with a distinct core-shell architecture. (B, C) The flow rates of the inner particle phase (red-tagged pNIPAAm), the middle polymer phase (green-tagged pNIPAAm), and the outer oil phase control the number of core particles in each shell (B) as well as the shell-thickness (C). Pictures in the upper row of Panel B show an overlay of the micrographs in the middle and lower row, which depict separate visualizations of the green-tagged pNIPAAm shell and the red-tagged pNIPAAm core. (D) Spatially resolved intensity profiles of the red and green fluorescence in the single-core particle shown in Panel B, evidencing only very little interpenetration of its two phases. The scalebar denotes 100 μm and applies to all micrographs in Panel B and C.


[[Image:microgel4.png]]

Figure 4. Thermo-responsive behavior and controlled release application of pAAm-pNIPAAm core-shell microgels. (A) Fluorescence images (left column) and bright field micro-graphs (right column) of microgels consisting of a 60 mm untagged pAAm core encapsulated in a green-tagged pNIPAAm shell. At ambient temperatures (upper row), the shell is swollen, whereas it collapses at elevated temperatures (lower row). By contrast, the core dimension remains unaffected by the same changes of temperature. (B) Detailed plot of the particle-diameter, d, as a function of temperature, T. Dark blue circles represent the diameter of the entire particle, i.e., pAAm core plus pNIPAAm shell, whereas light blue squares represent only the pAAm core. The dotted lines are guides to the eye. (C) Controlled release of RITC-dextran (M 10,000 g mol-1) from the particles in Panel A. In the course of the first 10 s of this experiment, the temperature remains above 33 C, and the particles remain sealed (left three pictures). As the temperature decreases, a spontaneous release of the active incorporated in the particles is triggered by the swelling of the pNIPAAm shells. All scalebars denote 100 μm.

==Personal Thought==

The most obvious potential use for such microgels is for drug delivery and most important controlled release of the drug load in the human body. The author demonstrates the thermo-sensitive nature of the pNIPAAm polymer which happens to be close to human physiological temperature, hence its huge potential. The benefit of this technology platform is that it is flexible - a huge range microgel structures can be produced. We can imagine an encapsulated microgel which is sensitive to pH, such that it will only release its load at a threshold pH. This can be useful because of the difference in pH in different parts of the human body. Microgels could also engineered to preferentially stick to particular parts of the body and even different cell types by functionalizing the polymer molecules.

==References==

1. S. Seiffert, D.A. Weitz, "Microfluidic fabrication of smart microgels from macromolecular precursors", Polymer 51 (2010) 5883-5889