8:45 AM - SM06.08.01
Ultra-Fast Microfluidic Droplet and Jet Gelation to Produce Rod-Shaped Microgels
Andreas Krüger1,Luis Guerzoni1,Onur Bakirman1,Laura De Laporte1
DWI - Leibniz Institute for Interactive Materials1
Over the last years, anisotropic microgels became a spotlight subject in the research fields of material design and tissue engineering. They have the ability to function as crucial microscopic building blocks for macroscopic injectable constructs1. Due to their geometry, magneto-responsive, rod-shaped microgels can align into 3D anisotropic hybrid hydrogels in a low-invasive manner, resulting in oriented cell growth and extension of functional nerves2-3. Ideally, monodisperse microgels with a large range in stiffness, dimensions, aspect ratio’s, and (bio)chemistries should be produced in a high-throughput, continuous manner. However, currently, none of the existing methods fulfills all these requirements.
To overcome these limitations, we developed a microfluidic gelation system operable in both droplet and in-jet gelation modes to produce anisometric rod-shaped microgels with adjustable size and mechanical properties. The microgels are crosslinked via a light trigger, employing a pulse with modulation (PWM) light controller with variable pulse length, frequency, and output intensity of any light source coupled to the PWM. The systems presented here are equipped with a UV-LED (365 nm) for droplet gelation or a laser (405 nm) in the case of in-jet gelation. As precursor solution, poly (ethylene oxide)-diacrylate (PEG-DA), supplemented with the water soluble photoinitiator lithium phenyl-2,4,6-trimethylbenzoyl-phosphinate (LAP), is used. Characteristically, droplet gelation is limited to the fabrication of microgels with a diameter equal to the channel diameter of the microfluidic chip; the length and thus aspect ratio is varied by the ratio of the flow rates of the inner and outer phases. Here, microgels with various polymer concentrations, ranging between 50 and 9 wt% PEG-DA, are produced, leading to elastic moduli between 300 kPa and 3 kPa, respectively. Via a single pulse irradiation method, we elucidated that the required gelation time increased from 0.8 s to 70 s, respectively.
As ultra-fast gelation is possible after droplet formation, the system was further developed to in-jet gelation in order to achieve rod-shaped microgels with a diameter smaller than the channel diameter of the chip. Stable microfluidic jets are realized with diameters 10 times smaller as the channel diameter by adjusting the flow ratio of the inner and outer phases. A continuous laser signal results in continuous jet gelation, leading to hydrogel fibers with a diameter equal to the jet diameter. To produce short, anisometric microgels, the 405 nm laser is operated at different pulse modes to crosslink alternating compartments of the jets. The non-crosslinked compartments dissolve after leaving the chip, while the crosslinked parts maintain their shape and swell, depending on the polymer concentration. For a 80 µm channel diameter, ~ 500 microgels/s are produced with a rod diameter of ~ 8 µm, while the length is adjusted between 2200 and 64 µm by varying the pulse length. In order to achieve oscillated gelation in the jet without losing jet stability a non-reactive, a linear filler (400 kDA PEG-OH) is mixed with the PEG-DA.
In summary, as promising alternative to established methods, a modular light controller is combined with either UV-LED droplet gelation or laser-initiated in-jet gelation to realize continuous fabrication of rod-shaped microgels with adjustable diameters, aspect ratios and stiffness. The mechanical properties, swelling behavior, can microgel dimensions are adjusted by changing the prepolymer concentration, flow ratio, channel size, and pulse length. This method offers the opportunity to fabricate elevated amounts of tailored anisometric microgels from different prepolymer systems and crosslinking chemistries, to be used in a wide variety of applications.
1. Krüger, A.J.D et al, Chem Comm 2018, 54 (50), 6943-6946.
2. Rose, J. C et al, Nano Lett 2017, 17 (6), 3782-3791.
3. Rose, J. C et al, Biomater 2018, 163, 128-141.