Angew: Microfluidic induced assembly of supramolecular hydrogels

Dipeptide hydrogel is a low molecular weight hydrogel material suitable for embedding a variety of organic molecules and inorganic nanoparticles. However, the self-assembly gel process of dipeptide molecules is more difficult to control, and the compounding of the dipeptide molecules with particles often has the problem of uneven distribution. In response to this problem, the team of Professor Julian Thiele from the Leibniz Institute of Polymer Research in Dresden and the team of Professor Li Junbai from the Institute of Chemistry of the Chinese Academy of Sciences published a titled “Embedment of quantum dots and biomolecules in an in -situ formed dipeptide hydrogel using microfluidics" research paper. The author proposes a simple but precise and controllable method to fabricate dipeptide-based hydrogels through supramolecular assembly in microfluidic channels, combining water-soluble quantum dots (QDs), premixed porphyrins and dimethylene Sulfone dipeptide (DMSO) is injected into the Y-shaped microfluidic junction. At the DMSO/water interface, the preparation of dipeptide-based hydrogels can be effectively controlled. Subsequently, the formed hydrogel flows continuously along the tortuous microfluidic channels, gradually completing the gel and QD retention.



First, the author characterizes the morphology of nanofibers formed by different porphyrins. Four types of water-soluble quantum dots CdTe exhibited fluorescence colors ranging from green (520 nm), yellow (570 nm), and orange (610 nm). ), red (710 nm) increases the diameter from less than 10 to 20 and 30 nm. The precursor solutions of Fmoc-FF and TCPP (or TAPP) and QDs suspension are injected into the opposite branch of the microchannel y-junction, and the volume flow is controlled by a high-precision syringe pump. After the water phase and the organic phase are co-injected, DMSO and water form a dynamic co-flowing interface. At the interface, the hydrogel assembles spontaneously through diffusion and mixing of non-covalent interactions. The gelation process is carried out in a continuous tortuous microchannel. The length of the microchannel is optimized to ensure the quantitative conversion of the two precursor phases at the outlet of the flow chamber and remove the polydimethylene in the microfluidic device. After the siloxane (PDMS) cap, the hydrogel structure remains on the glass substrate (Figure 1).





Figure 1 Schematic diagram of the continuous preparation of supramolecular assembly hydrogels by microfluidic technology and the characterization of Fmoc-FF/TCPP/QD-520 hydrogels



Next, the author compared the interaction of two porphyrins (TCPP and TAPP) with premixed Fmoc-FF in the microfluidic channel. Without quantum dots dispersed in water, the optical properties of the hydrogel precursor solutions and the process of their nucleation and hydrogel formation were studied by using absorption and fluorescence spectroscopy. The author proposes a reasonable assembly model to explain the molecular interactions in nanofibers. The stability of nanofibers mainly comes from the hydrophobic interaction and π bond stacking self-assembly based on Fmoc-FF. In addition, various interactions such as the π bond accumulation between porphyrins, the π bond accumulation between Fmoc-FF and porphyrins, the hydrophobic effect, and the electrostatic interaction between Fmoc-FF and TAPP have important effects on the stability of the system. Great contribution (Figure 2).

Figure 2 Schematic diagram of co-assembly of dipeptide and porphyrin, optical detection and analysis of gel forming process

Then, the author selected a series of carboxyl-coated water-soluble CdTe quantum dots as fluorescent inorganic models for coating research. Compared with quantum dots encapsulated in Fmoc-FF/TCPP hydrogel, the normalized fluorescence emission spectrum of quantum dots shows that compared with free quantum dots in water, the maximum emission spectrum after QD encapsulation has a red shift (QD520, QD570, QD610 and QD710 are approximately 2 nm, 10 nm and 14 nm respectively). The emission spectrum of the encapsulated quantum dots is red-shifted due to the aggregation of the quantum dots. The quantum dots are not embedded in the combination of dipeptide fibrils, but only passively trapped in the gaps of the Fmoc-FF/TCPP fibril network, or stay on the surface of the nanofibers (Figure 3).





Figure 3 TEM, fluorescence and rheological characteristics detection of different hydrogels



In addition to studying the general interaction of quantum dots loaded into the Fmoc-FF/porphyrin-based hydrogel system, the author further studied the dynamic encapsulation of quantum dots in hydrogels prepared by microfluidics. Therefore, Fmoc-FF/TCPP in DMSO and QDs in the water are injected from inflow ports 1 and 2. Then, diffusion-type mixing occurred in the meandering flow channel, and its repeated thinning also affected the study of flow direction on fiber formation. Especially in the curved section, the unique structure of Fmoc-FF is composed of traditional twisted nanofibers and straight nanofibers. The authors attribute this complex morphology to the unique three-dimensional hybrid profile in these microchannel cross-sections (Figure 4).





Figure 4 Two-dimensional geometric structure of the microchannel



After that, the author removed the PDMS part of the microchannel in the microfluidic device, and characterized the morphology of the Fmoc-FF/TCPP/QD hydrogel at different internal positions to study the quantum dot capture process during the formation of nanofibers. The author also added additional collection ports to the PDMS part of the flow pool containing microchannels at different positions of the outflow channel to characterize the different flow history and mixing state of Fmoc-FF/TCPP/QD. The emission wavelength of quantum dots depends on the particle size. Quantum dots and redshifted suspensions indicate polymerization formation, confirming that by using quantum dots microfluidic to be more evenly distributed in the hydrogel matrix, it can be used as a supramolecular hydrogel that causes uniform loading of injectable Glue (Figure 5).





Figure 5 SEM and optical characteristic inspection of different hydrogel assembled micro devices



Finally, in order to study the functional interaction between porphyrin and quantum dots in the hybrid hydrogel, the author used Foster resonance energy transfer (FRET) to study the interaction between the organic part and the inorganic part in the hydrogel system. These measurements also provide a reference for the supramolecular assembly of Fmoc-FF/TCPP/QDs hydrogels prepared by microfluidics. The author also compared the fluorescence signals of Fmoc-FF hydrogels with different concentration ratios. Excess TCPP is deposited on the outside of the nanofibers in the form of aggregates, and the fluorescence intensity is reduced by the self-aggregation induced quenching. On the other hand, for fixed concentrations of Fmoc-FF and TCPP, when TCPP is excited at 270 nm, the emission peaks at 660 nm and 720 nm increase due to the increase in energy injection (Figure 6). Therefore, adjusting the concentration ratio of different components in the hydrogel system is essential to enhance the observed FRET effect, and the FRET effect can be controlled by the inflow rate of the microfluid and the hydrogel precursor solution.





Figure 6 Schematic diagram of energy transfer of Fmoc-FF/porphyrin/quantum dot quantum dot hydrogel



In this study, the author developed a new method of continuous flow microfluidic technology for continuous preparation of dipeptide-based hydrogels and hydrogel/quantum dot mixtures. In the microchannel of the microfluidic system, the Fmoc-FF-based hydrogel formed by supramolecular assembly can capture inorganic quantum dots and organic porphyrins of different sizes in a uniform tissue. Combining the "bottom-up" self-assembly with the "top-down" microfluidic control can precisely control the joint assembly of multiple components and avoid the common heterogeneity in the process of macroscopic mixing and gel formation. In addition, the energy transfer through FRET was confirmed in the supramolecular hybrid system designed by the author, which showed the energy transfer from inorganic quantum dots to organic TCPP, further indicating that the distance between them is very small, and low molecular weight dipeptide gel Advantages in efficient capture and integration. The formation of dipeptide-based multi-component hydrogels has opened up new possibilities for the application of these hybrid gels in biomedical equipment, photodynamic therapy or continuous bioprinting.


Information source: EFL EngineeringForLife

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