Self-assembled materials and supramolecular chemistry within microfluidic environments: from common thermodynamic states to non-equilibrium structures

Abstract

Self-assembly is a crucial component in the bottom-up fabrication of hierarchical supramolecular structures and advanced functional materials. Control has traditionally relied on the use of encoded building blocks bearing suitable moieties for recognition and interaction, with targeting of the thermodynamic equilibrium state. On the other hand, nature leverages the control of reaction-diffusion processes to create hierarchically organized materials with surprisingly complex biological functions. Indeed, under non-equilibrium conditions (kinetic control), the spatio-temporal command of chemical gradients and reactant mixing during self-assembly (the creation of non-uniform chemical environments for example) can strongly affect the outcome of the self-assembly process. This directly enables a precise control over material properties and functions. In this tutorial review, we show how the unique physical conditions offered by microfluidic technologies can be advantageously used to control the self-assembly of materials and of supramolecular aggregates in solution, making possible the isolation of intermediate states and unprecedented non-equilibrium structures, as well as the emergence of novel functions. Selected examples from the literature will be used to confirm that microfluidic devices are an invaluable toolbox technology for unveiling, understanding and steering self-assembly pathways to desired structures, properties and functions, as well as advanced processing tools for device fabrication and integration.

Fig. 1. Microfluidic technologies enable selection of different pathways in self-assembly processes, yielding structurally different assemblies and/or thermodynamic states at either thermodynamic equilibrium or non-equilibrium states (i.e. metastable, slowly relaxing to equilibrium, or kinetically trapped structures). At the same time, the microfluidic approach allows for exquisite control over the processing of self-assembled materials on surfaces, e.g. enabling direct printing of fibre-like structures, formation of thin films, and formation of localized patterns.

Fig. 2. (A) Schematic illustration of the microfluidic device for TTF assembly. (B and C) Scanning electron microscopy (SEM) images of TTF-Au structures collected outside the chip and synthesized at a FFR of 0.1 and 14, respectively. (D) and (E) Bi-dimensional X-ray images of samples prepared with different FRRs (10 and 14 respectively). The green numbers indicate the reflexion peak related to the π–π stacking distance between TTF molecules in the generated structures. Reproduced from ref. 19 with permission from Wiley-VCH Verlag GmbH & Co., copyright 2010.

Fig. 3. (A) Schematic drawing of the 3D hydrodynamic flow focusing device used for the shape control synthesis of TTF-Au structures. (B) and (C) SEM images of the structures collected at a FRR of 20 and 0.2, respectively. Adapted from ref. 22 with permission from American Chemical Society, copyright 2014.

Fig. 4. (A) General view of the microfluidic nebulator used. (B) Zoom-in illustration of the 3D channel geometry present in the microfluidic device used in this study. The blue inlets indicate the microfluidic channels where the liquids are injected inside the device while only air is introduced in the other inlets. (C) and (D) High-resolution transmission electron microscope (HRTEM) images of CaCO₃ and fenofibrate nanoparticles produced with this microfluidic method, respectively. The insets in (C) and (D) are the Fourier transform of the HRTEM micrographs presented, indicating the amorphous nature of the materials generated. Adapted from ref. 23 with permission from The American Association for the Advancement of Science, copyright 2015.

Fig. 5. (A) Illustration of the microfluidic setup used in the experiments. (B and C) Transmission electron microscope (TEM) images of the CP synthesized in flask mixing experiments and with the continuous-flow microfluidic device at different FRRs, respectively. Adapted from ref. 24 with permission from Wiley-VCH Verlag GmbH & Co., copyright 2016.

Fig. 6. Illustration of the microfluidic device used for the synthesis and printing of the COF. Adapted from ref. 25 with permission from The Royal Society of Chemistry.

Fig. 7. (A) Microfluidic setup used to create water in oil droplets. The oil phase contains the BTC ligand and the water phase contains Cu(ii) ions. At the interphase, a HKUST-1 film is generated (blue). (B) and (C) SEM images showing the homogeneity of the HKUST-1 shell and the capsules, respectively. Adapted from ref. 27 with permission from Springer Nature, copyright 2011.

Fig. 8. (A) Schematic illustration of the digital microfluidic device used in this experiment and of its functioning. (B) SEM image showing the array of HKUST-1 crystals fabricated by this technology. (C) Details of a single HKUST-1 crystal. Adapted from ref. 30 with permission from Wiley-VCH Verlag GmbH & Co., copyright 2012.

Fig. 9. (A) Schematic illustration of the device used for the synthesis of silver acetylides. (B) Microphotographs showing the distribution and morphology of silver acetylide crystals formed along the microchannel. Adapted from ref. 31 with permission from Wiley-VCH Verlag GmbH & Co., copyright 2015.

Fig. 10. (A) Schematic view of the two-layer microfluidic platform employed in the study. (B–D) A sequence of optical microscope images showing the Ag(i)Cys CP assembled at the reactant interface; its reduction to Ag(0); and the subsequent formation of Ag(i)TCNQ (cross polarized image), respectively. Adapted from ref. 32 with permission from American Chemical Society, copyright 2014.

Fig. 11. (A) Optical image of a large TCNQ crystal grown in the fluidic channel and trapped with a pneumatic clamp, and a line of generated silver metal. (B) Polarized optical image of the Ag(i) doped TCNQ crystal. The white areas correspond to the pure TCNQ, while the rest of the crystal shown is the Ag-TCNQ complex. (C) I/V sweep of the Ag(i)TCNQ complex and (D) of the intermediate region measured with CAFM. Adapted from ref. 33 with permission from The Royal Society of Chemistry.

Fig. 12. (A) Schematic illustration of the setup used for the photolithographic patterning and the subsequent in situ growth of the CaCO₃. (B and C) Optical microscopy images of CaCO₃/polymer composite microstructures before (B) and after (C) growth of the CaCO₃. (D) Raman mapping of the composite post of (C) with different positions (1–4) obtained by integrating over the wavenumber ranges of CaCO₃ (1050–1150 cm^–1, red), organic (2800–3000 cm^–1, blue), and water (3000–3700 cm^–1, green), respectively. Mapping data were normalized to the strongest intensity of the CaCO₃. (E) SEM image of the outer side surface of the composite posts. Adapted from ref. 35 with permission from Wiley-VCH Verlag GmbH & Co., copyright 2016.

Fig. 13. (A) Chemical structure of ZnTCPP in the anionic and protonated forms. (B) Exemplary SEM image of the amorphous aggregates formed under flask mixing. (C) Schematic illustration of the setup used in this experiment. (D) SEM image of the multi-layered flakes formed by microfluidic mixing. (E) Schematic representation of the 2D hydrogen-bonded network formed under kinetic control (fast protonation). Adapted from ref. 36 with permission from The Chemical Society of Japan, copyright 2015.

Fig. 14. (A) Chemical structure of PBI. (B) Synchrotron XRD patterns of the PBI assemblies formed under different flow conditions, i.e. different solvent compositions at the first cross-point, reported in (C). (C) Schematic representation of the double cross point microfluidic setup used. Blue and pink sets of numbers correspond to different experiments yielding respectively H- and J-aggregates. Note that the solvent composition at the outlet is the same for both the experiments. Adapted from ref. 37 with permission from The Chemical Society of Japan, copyright 2015.

Fig. 15. (A) Chemical structure of GMP. (B) Chemical structure of the bis-cationic linker porphyrin. (C) Schematic illustration of the microfluidic setup used in the experiment and of the hierarchical growth of GMP microfibers by stepwise activation of non-covalent intermolecular interactions by spatial and temporal control. Adapted from ref. 38 with permission from Wiley-VCH Verlag GmbH & Co., copyright 2013.

Fig. 16. (A) Chemical structure of H₂TPPS₄, CTAB and of the chiral amphiphile (S)-C16. (B) TEM image of exemplary aggregates formed by flask synthesis. (C) Schematic illustration of the microfluidic setup used in this example and representative TEM image of the well-aligned rod-like aggregates formed under microfluidic mixing. (D) Circular dichroism spectra showing the effect of microfluidic versus flask mixing on the chirality of the formed H₂TPPS₄/CTAB heteroaggregates, i.e. on the efficiency of the chiral induction. Adapted from ref. 39 with permission from American Chemical Society, copyright 2016.

Fig. 17. (A) Chemical structure of OPV (half molecule is shown for clarity). (B) Schematic illustration of the microfluidic setup used in the experiment. (C) Time dependent IR spectra of the samples prepared by microfluidic mixing. (D) AFM images showing the morphological change with time of the assemblies formed under microfluidic mixing. Adapted from ref. 40 with permission from The Chemical Society of Japan, copyright 2015.

Fig. 18. (A) Chemical structure of the (S)-Zn–porphyrin, and equilibrium between stacks, S (in the blue circle), and dimers, D (in the red circle), in the presence of pyridine (green polyhedron). (B) Schematic representation of the H-cell used. The differential diffusion of the different species results in different stack-to-dimer ratios as detected at the residual and extraction stream. These correspond to two metastable compositions of the system which equilibrate with time to two different thermodynamic states. Adapted from ref. 41 with permission from The Royal Society of Chemistry.

Fig. 19. (A) Chemical structure of FF. (B) Schematic illustration of a single FF tube trapped between the micro-scale pillars. (C) Illustration of the FF nanotube growth. (D) Imaging of FF nanotubes at different times under subcritical (1.6 mM, 10 s interval), critical (2.43 mM, 60 s interval), and supercritical (3.20 mM, 100 s interval) concentration conditions. Adapted from ref. 42 with permission from Springer Nature, copyright 2016.

Fig. 20. (A) Schematic illustration of the fluidic-directed synthesis of 1D peptide–OPV fibers by using planar extensional flow, and fluorescence microscopy micrograph showing the emitting fiber grown at the reactive interface. (B) Schematic illustration and micrograph showing the formation of two aligned fibers obtained by modulating the flow rates, i.e. changing the position of the reactive interface. Adapted from ref. 44 with permission from Wiley-VCH Verlag GmbH & Co., copyright 2013.

Fig. 21. (A) Illustration of the formation of a ternary inclusion complex between the host CB[8] and two different planar guests. (B) Schematic representation of the Au nanoparticles functionalized with methylviologen (guest) and of the copolymer functionalized with naphthol moieties (guest). (C) Schematic representation of the microdroplet generation process using a microfluidic T-junction device, showing the wiggled channel used for rapid mixing of reactant solution, and schematic representation of the microcapsule formation and of the following dehydration step. Adapted from ref. 46 with permission from The American Association for the Advancement of Science, copyright 2012.

Fig. 22. (A) Illustration of the formation of the ternary inclusion complex between the host CB[8] and two different guests. Adapted from ref. 45 with permission from American Chemical Society, copyright 2017. (B) Schematic representation of the supramolecular assembly of the two polymers P1 and P2 at the interface of chloroform-in-water droplets. (C) Fluorescence micrographs demonstrating the interfacial assembly of P2 (Rhodamine-tagged, red) within the droplet and P1 (Fluorescein-tagged, green) present in the external media. Adapted from ref. 47 with permission from Springer Nature, copyright 2014.

From right to left: Andrew deMello, Josep Puigmartí-Luis, Carlos Franco Pujante, Alessandro Sorrenti and Semih Sevim

S. Furukawa

S. Pané