Shape-Changing Particles: From Materials Design and Mechanisms to Implementation

Abstract

Demands for next-generation soft and responsive materials have sparked recent interest in the development of shape-changing particles and particle assemblies. Over the last two decades, a variety of mechanisms that drive shape change have been explored and integrated into particulate systems. Through a combination of top-down fabrication and bottom-up synthesis techniques, shape-morphing capabilities extend from the microscale to the nanoscale. Consequently, shape-morphing particles are rapidly emerging in a variety of contexts, including photonics, microfluidics, microrobotics, and biomedicine. Herein, the key mechanisms and materials that facilitate shape changes of microscale and nanoscale particles are discussed. Recent progress in the applications made possible by these particles is summarized, and perspectives on their promise and key open challenges in the field are discussed.

1. Introduction

In the last two decades, significant progress has been made in understanding the mechanisms responsible for controllably changing the shape of soft materials to enable new applications. Scientists and engineers have approached this area of research from several different perspectives, including taking inspiration from biological processes. For example, shape-changing phenomena observed in pinecones, seedpods, ice-plant seed capsules, plant tendrils, leaves, and flowers have inspired the design of biomimetic shape-changing material architectures.^[1–4] This has led to the demonstration of sophisticated and highly controlled motions that would be difficult to attain using hard materials alone, an approach that has been dubbed “4D printing” to describe 3D materials that change shape over time.^[5–8] Owing to multidisciplinary research efforts spanning physics, biology, mathematics, materials science, and engineering, a wide variety of shape-changing material platforms have now been realized, with emerging applications in areas including soft robotics, biomedicine, textile, and electronics.^[8,9]

Although most demonstrations of shape change to date have focused on millimeter to centimeter scale structures, emerging fabrication and synthesis techniques have recently enabled their extension to micro and nanoscale objects. Miniaturization of shape-changing structures allows for their integration into new application areas. As soft actuators are being developed at the micrometer scale, their applications are being realized in biomedical science such as in minimally invasive biopsies,^[10,11] targeted drug and cell delivery,^[12–14] and responsive microfluidics.^[15] Since the size of shape-changing structures are approaching the wavelength of visible light, novel approaches to modulate light–matter interactions are being explored with applications in tunable photonics.^[16–18] Small-scale shape-changing architectures are now being considered as smart building blocks of materials that can be assembled and reconfigured on demand.^[19,20]

In this review, we discuss mechanisms that facilitate shape changes in micro- and nanostructures as well as their usefulness in several emerging applications. We refer to these structures as “shape-changing particles.” We examine a variety of shape-transformations, except the simple case of isotropic volume-change. In Section 2, we review numerous mechanisms that have been recently exploited to change the shape of particles in response to stimuli such as temperature, pH, light, and magnetic fields. We discuss the properties of commonly used materials, including liquid crystal elastomers,^[21] responsive hydrogels,^[22] and shape-memory polymers^[23] as well as techniques for fabricating particles from these materials. We highlight various types of shape transformations such as changing the aspect ratio of micro- and nanoscale anisotropic particles,^[24] bending of microcylinders and particle chains,^[25,26] twisting of microribbons,^[27] and folding of microscale sheets.^[28] Finally, we discuss the challenges and opportunities for programmable shape-morphing and the kinetics of shape change that are controlled by particle size and the mode of stimulation. In Section 3, we review recent applications of shape-changing particles, including photonics, microfluidics, microrobotics, drug delivery, and surgery. In each of these categories, we discuss seminal advances that have been enabled by shape-changing particles, and we discuss their benefits compared to conventional approaches. In Section 4, we identify key unresolved challenges in current applications and areas of research that hold promise for advancing the current state of knowledge of dynamic materials design.

2. Mechanisms of Shape Transformation

Various materials and forms of stimulation have been used to facilitate shape transformation in particles. Here, we discuss four categorical approaches. In Section 2.1, we review particles synthesized from polymer networks designed to undergo thermally induced transitions that lead to shape change. In Section 2.2, we summarize mechanisms that selectively change the shape of multicompartmental and multiphasic particles by differential swelling, triggered dewetting, or surfactant reprogramming. In Section 2.3, we discuss photothermal and photochemical mechanisms that take advantage of local deformations caused by light. In Section 2.4, we describe recent efforts to achieve shape change by magnetic fields through the incorporation of magnetically susceptible materials. Each of these categories have distinct characteristics regarding the types of shape transformation that are accessible and their corresponding kinetics, which we discuss from the perspective of helping the reader find a suitable mechanism for their desired application.

2.1. Thermomechanical Shape Change in Polymer Networks

2.1.1. Polymer Particles that Change Shape Irreversibly at Their Glass Transition Temperature

Above the glass transition temperature (T_g), anisotropic particles made from an un-crosslinked polymer network can relax to an equilibrium spherical shape driven by interfacial tension.^[25,29] The fluid-like behavior above T_g enables this shape transformation, and the time required to change shape is determined by the balance between the interfacial tension and viscosity. The time constant is described by $\tau =\frac{L\mu }{\sigma }$, where L is the characteristic particle size, μ is the polymer viscosity, and σ is the interfacial tension. In pioneering work, Yoo et al. prepared ellipsoidal disc-shaped particles from biocompatible poly(lactide-co-glycolide) (PLGA) and demonstrated control in the kinetics of shape change by tuning each of these three parameters (Figure 1a).^[29] The particles were prepared by casting PLGA spheres into a poly(vinyl alcohol) (PVA) film, deforming the film above the T_g of PLGA, and then cooling down the film to room temperature. Anisotropic particles were released from the PVA by placing the films in water to facilitate dissolution. Preparing smaller particles (small L), increasing the temperature, or reducing the molecular weight of the polymer (thereby lowering μ), and lowering the pH (thereby increasing protonation of the carboxylic acid end groups that caused high σ), all increased the rate of shape change. The authors demonstrated control over the time of shape switching from a few minutes to a few weeks.

Figure 1.

a) Elliptical disc-shaped PLGA particles (T_g = 28 °C, aspect ratio = 5) switch shape to spheres at 37 °C. Scale bars: 5 μm. Adapted with permission.^[29] Copyright 2010, The Authors, published by National Academy of Sciences. b) Top: bicompartmental cylinders made from PLGA (blue dye) and PMMA (red dye) before (left) and after shape-changing (right). Scale bars: 20 μm. Bottom: different shapes achieved from multicompartmental cylinders. From left to right: bicompartmental PLGA/(PLGA+PMMA), PVCi/PLGA, tricompartmental PLGA/(PLGA+PVCi)/PLGA, and bicompartmental PS/PLGA. Adapted with permission.^[25] Copyright 2012, The Authors, published by National Academy of Sciences. Scale bars: 10 μm. c) Due to the difference in director field orientations of the LCEs, the disc-shaped particles expand, but the fiber-shaped particles contract at T_NI. Scale bar: 100 μm. Adapted with permission.^[24] Copyright 2011, American Chemical Society. d) Four different shapes of an LCE-hydrogel Janus particle: mushroom-shaped (LCE: elongated, hydrogel: highly swollen), barbell-shaped (hydrogel: less swollen), rod-shaped (hydrogel:dry), and torpedo-shaped (LCE: contracted). Adapted with permission.^[42] Copyright 2018, Wiley-VCH. e) Shape-programming and reversible transformation of shape-memory particles. Scale bars: 10 μm. Reproduced with permission.^[53] Copyright 2014, Royal Society of Chemistry.

Lee et al. achieved a greater degree of shape diversity using multicompartmental microcylinders fabricated by electro-hydrodynamic cojetting (EHD) followed by microsectioning (Figure 1b).^[25] Two or three needles containing distinct polymer solutions were placed side-by-side during the cojetting that resulted in the formation of cylinders with diameters ranging from hundreds of nanometers to hundreds of micrometers. The shapes of the compartments were controlled individually when each of them had a distinct T_g. The authors showed that a bicompartmental microcylinder made from PLGA (T_g = 47–48 °C) and PMMA (T_g = 115–116 °C) changed its shape by only converting the PLGA compartment to a sphere. Using this approach, the authors demonstrated shape switching from cylinders to bullhead- and ring-shaped particles (Figure 1b). In subsequent work, Sitt et al. performed electrospinning with coaxially positioned needles to prepare hollow microcylinders with an outer shell made from PLGA and an inner core made from poly(ethylene oxide) (PEO) that transformed into donut-shaped particles upon heating above the T_g of PLGA.^[30]

When combined with novel micro- and nanofabrication techniques, this method of shape change allows for enhanced shape diversity and control over transformation kinetics. However, since the shape transformation is only driven toward the lowest energy (generally spherical) shapes determined by surface tension, this method is nonreversible.

2.1.2. Reversible Shape Changes of Liquid Crystalline Particles at Nematic-Isotropic Phase Transition Temperatures

Liquid crystal polymers (LCPs) are designed by connecting liquid crystalline mesogens to polymers whereby the mesogens are either a part of the polymer chain (main-chain LCP) or attached pendent to the polymer backbone via spacers (side-chain LCPs).^[31] Particles made from LCPs exhibit reversible, anisotropic shape change at the nematic-to-isotropic phase transition temperature (T_NI). This shape change is attributed to the change in molecular order that causes shrinkage parallel to the preferred orientation of the LC molecules, commonly known as the orientation of the director. Particles that are smaller than a single liquid crystalline domain possess an anisotropic shape in equilibrium due to the monodomain orientation. For example, Yang et al. synthesized ellipsoidal particles from main-chain LCPs in the range of 100–200 nm using a miniemulsion technique and showed that they reversibly switched to spherical configurations upon heating to T_NI.^[32] The lower critical radius (R_c) of the ellipsoidal particles depends on the ratio of the elastic energy cost (elastic modulus μ) that favors the ellipsoidal shape and the interfacial energy (surface tension γ) that favors a spherical shape ($R_c=\frac{\gamma }{\mu }$). Particles larger than a single domain can be fabricated using photolithographic and microfluidic techniques to achieve a uniform director orientation.^[33]

LCPs with low crosslink density, or liquid crystalline elastomers (LCE), are widely used for their ability to enable large contraction or expansion.^[21,34–36] LCE micropillars with a diameter as small as 20 μm have been fabricated by photopolymerization, crosslinking, and magnetic alignment of an LC monomer inside of a microscopic mold fabricated using soft lithography.^[37,38] Highly monodispersed and anisotropic LCE particles were synthesized (Figure 1c) using a microfluidic setup designed by Zentel and co-workers.^[24,39,40] Monodisperse droplets were first prepared by injecting an LC monomer solution combined with a crosslinker and a photoinitiator into a co-flowing stream of immiscible silicone oil. Droplets were then polymerized downstream. To design shape anisotropy, the monodisperse spherical droplets were flowed through a microtube with an inner diameter that determined the degree of anisotropy. As the diameter of the microtube decreased, the particles changed from spheres to oblate discs and then to fibers. The orientation of the nematic director in the spherical and disc-like oblate particles had concentric ring patterns, which resulted in a transition to an elongated cigar-like shape when heated to T_NI. On the other hand, the orientation of the director in the fiber-like prolate particles was aligned with the long fiber axis, which resulted in a reduced particle aspect ratio above T_NI.

A modified microfluidic setup was later used to design more complex LCE particle morphologies. Particles were prepared by co-flowing LC monomer with another immiscible monomer in a side-by-side capillary configuration that resulted in a Janus particle, half of which was comprised of LCE and the other half was comprised of a nonfunctional, hydrophilic polyacrylamide network.^[41] Another Janus particle morphology was designed by combining LCEs with thermoresponsive poly(N-isopropyl-acrylamide) (PNIPAm) hydrogels to enable the triggering of shape change of each compartment individually (Figure 1d).^[42] At room temperature, below the T_NI of the LCE and the lower critical solution temperature (LCST) of the PNIPAm, the particles displayed mushroom shapes with a rod-like LCE side and a swollen, spherical hydrogel side. Above the LCST, deswelling of the hydrogel compartment caused isotropic shrinking in its volume, resulting in a rod without a swollen end. When heated above T_NI, the LCE compartment shrank anisotropically at the thermotropic transition, resulting in a torpedo-like shape.

Recent efforts have enabled the preparation of smaller LCE particles with a lower T_NI. Marshall et al. embedded LC monomer droplets in a stretchable thermoplastic polymer matrix and then applied mechanical stretching, photopolymerization, and crosslinking to achieve highly anisotropic LCE particles with a diameter of a few micrometers. A monomer solution was added to lower the transition temperature to 58 °C, above which the ellipsoidal particles changed their shapes to spheres.^[43] In another effort to reduce the size of the particles and to design shape complexity, microparticles as small as 10 μm were prepared via thiol-ene dispersion polymerization and were stretched or compressed in a PVA film followed by crosslinking. Both prolate spheroids and oblate disc-like particles were programmed to change their shapes to spheres at T_NI = 70 °C.^[44] Recently, shape-programming of LCE particles has been demonstrated by employing covalent adaptable network (CAN) that allows for modification of a polymer network in the presence of a stimulus. A photoinitiated addition-fragmentation chain-transfer (AFT) exchange reaction was used to program the particles to prolate shapes at low temperature and then the shape was erased by initiating the reaction at high temperature. The authors also demonstrated switchable patterning of particle surfaces using nanoimprint lithography and the AFT exchange reaction.^[45]

An advantage of LCP particles is that their shape transformation is rapid and reversible; however, the direction of shape change is constrained by the director orientation of the LCPs and must be programmed to achieve a target structure. In a recent work by Guo et al., the director field was programmed in a 3D microstructure of liquid crystal network (LCN) using two-photon polymerization. First, microchannels were fabricated to align the LCN director field of a monomer with a resolution of ≈5 μm, and then the monomer was photo-crosslinked to fabricate 3D structures with a target geometry (i.e., coils and rings). This approach provides a pathway toward programmable shape-change but requires a two-step fabrication procedure.^[46]

2.1.3. Shape-Memory Particles for Programmable One-Way and Two-Way Shape Change

Materials made from shape-memory polymers can be designed to maintain a programmable temporary shape and then recover their original shapes in response to temperature.^[47] Typically, the temporary shape is programmed by applying external stress and then fixing the deformed state by triggering physical or chemical crosslinking. Once the temporary shape is exposed to an external stimulus such as high temperature that removes the temporary crosslinks, the original shape is restored. This mechanism is known as a one-way shape memory effect that is irreversible. However, a two-way reversible shape memory effect has been realized in recent years. This type of material can be made using several mechanisms such as by introducing two domains with different melting temperatures or by using thermoreversible noncovalent interactions.^[48] The two-way shape memory effect allows for switching between two shapes reversibly in multiple cycles without requiring the shape-programming step to be implemented every time.

One-way shape-memory microparticles were prepared by Wischke et al. with a diameter of about 35 μm from a multi-block copolymer of poly(ω-pentadecalactone) (PPDL) and poly(ε-caprolactone) (PCL).^[49] A temporary ellipsoidal shape was achieved by stretching at high temperatures (70 °C) and subsequent cooling (0 °C) to result in the formation of temporary netpoints in the PCL domain. After heating again to 70 °C, the spherical shape was recovered due to removal of the temporary netpoints, and the presence of permanent standpoints provided by the hard PPDL domain. Consistent shape recovery was observed for particles with a size of about 5 μm. The authors showed that the crystallinity of the domains reduces in particles smaller than 1 μm and argued that this could affect the number of netpoints in nanoscale particles and their shape recovery. A one-way shape memory effect was also observed for microscale objects with different geometries, including microwires^[50] and micro-cuboids.^[51] Recently, Elliott et al. showed a glass transition based shape memory effect in complex 3D microarchitectures with the shapes of a flower and a cubic lattice that had features of less than 800 nm characteristic dimension.^[52]

Gong et al. demonstrated two-way shape-memory particles with a diameter of 5 μm made from a star-shaped crosslinked network of six-arm-poly(ethylene glycol)-PCL (6A PEG-PCL).^[53] A temporary ellipsoidal shape was realized after heating (60 °C), stretching in a PVA film, and cooling (0 °C). Afterward, cyclic heating and cooling between 43 and 0 °C was applied and the shape reversibly switched between a sphere and an ellipsoid (Figure 1e). The reversible shape memory effect was attributed to the two different domains in the PEG-PCL network, i.e., free molecular chains and crosslinked molecular chains. The crosslinked molecular regions exhibited temperature sensitive reversible crystallization between 43 and 0 °C that resulted in the two-way shape memory effect.

2.2. Selective Shape-Modification of Multicompartmental Particles

By selectively changing the swelling or wetting properties of one compartment of a particle, the shape of an entire particle can be modified. This section summarizes the mechanisms based on selective shape-modification of multicompartmental particles.

2.2.1. Selective Swelling in Biphasic and Janus Particles Changes Particle Geometry

Biphasic and Janus particles containing compartments with distinct swelling behaviors change their shapes when an external stimulus selectively swells or deswells one of the compartments. Biphasic spherical particles with concave patches have been synthesized by Zheng et al. that consist of a highly crosslinked organosilica: a 3-(trimethoxysilyl)propyl methacrylate (TPM) shell and polystyrene (PS) patches (Figure 2a).^[54] The synthesis was performed by encapsulating PS clusters with pre-defined geometry into TPM, swelling in toluene, and finally solidifying the TPM shell by free radical polymerization. The PS patches buckled into the shell during the removal of toluene, which resulted in a concave patch geometry. The number of patches was determined by the initial cluster morphology during encapsulation, and the concavity or convexity of the patches was tuned by the amount of toluene added during synthesis. The authors demonstrated selective swelling of the PS patches by placing the particles into a THF/water solvent, as gradual absorption of THF by the concave patches resulted in convex protrusions. Selective swelling was also achieved by controlling temperature when the particles were placed in a thermal-responsive water/N-methylpiperidine (NMP) binary mixture. At a temperature of 42 °C, liquid demixing caused more absorption of NMP by the PS patches; as a result, the concave patches protruded in 30 min. A pH-responsive shape-shifting Janus particle design was implemented by Tu et al.^[55] One side of these particles contained a hydrophobic monomer (styrene) and the other side contained a pH-responsive hydrophilic repeat unit (acrylic acid, AA). The AA unit swelled at high pH and consequently, the particle changed shape from an oblate spheroid to a dumbbell when the pH was increased from 2.2 to 11.0.

Figure 2.

a) Illustrations and optical microscopy images of di-patch particles with concave patch shapes that change into convex patches when dispersed into different solvents (i.e., water, 15% v/v THF/water, and 30% v/v THF/water, from left to right). Scale bars: 1 μm. Adapted with permission.^[54] Copyright 2017, Wiley-VCH. b) Snap-buckling inversion of bilayer particles (i.e., silica-tethered and silica-free) triggered by changes in pH. Scale bars: 4 μm. Adapted with permission.^[68] Copyright 2015, Wiley-VCH. c) Optical microscopy images of origami machines before (left) and after folding into different 3D architecture (center) with corresponding paper models of the target geometry (right). Adapted with permission.^[69] Copyright 2018, The Authors, published by National Academy of Sciences. d) Demonstration of dewetting from a colloidal cube in response to a change in pH (left). Light-triggered dewetting from a peanut-shaped particle using its photocatalytic property (right). Reproduced under the terms of the CC-BY Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0).^[71] Copyright 2016, The Authors, published by Springer Nature. Scale bars: 1 μm. e) Electron microscopy images of a particle morphology switch due to the temperature- and surfactant-dependent absorption of solvent. Scale bars: 2 μm. Adapted with permission.^[72] Copyright 2018, American Chemical Society.

Block copolymers (BCPs) have recently been employed to construct biphasic particles.^[56–58] Klinger et al. synthesized block copolymer PS-b-poly(2-vinylpyridine) (PS-b-P2VP) particles with shape-switching abilities via selective swelling.^[59] During synthesis, the particle morphology varied from an onion to an ellipsoid and then to an inverted onion, depending on the composition of the surfactant mixture (HO-CTAB/CTAB) that controlled the interfacial tension. The authors crosslinked the P2VP phase in the ellipsoidal particles and demonstrated that the selective swelling of the P2VP phase at low pH causes dramatic (up to 250%), but reversible, elongation along the long axis of the particles.

2.2.2. Differential Swelling in Multilayered Particles Causes Particle Bending, Buckling, and Folding

Multilayered geometries in which each layer has distinct swelling properties have been widely employed in the transformation of 2D sheets into 3D curved shapes.^[60–66] In bilayer structures, the swelling mismatch between the two layers and the condition of sustained strain at the interface between the layers causes deformations such as bending and wrinkling.^[2] The radius of curvature of a bilayer structure can be calculated from the thickness ratio and the stiffness ratio of the two layers using a model developed by Timoshenko.^[67] By implementing this concept, Lee et al. fabricated bicompartmental microcylinders made from an organogel (i.e., poly(vinyl cinnamate), PVCi) and a hydrogel (i.e., poly(ethylene imine), PEI).^[25] Upon submersion in water, the hydrogel side swelled and the interfacial stress caused bending in one direction. When the PVCi side was crosslinked and the bicompartmental cylinder was placed in dioxane, the PVCi side swelled and caused bending in the other direction. Shape switching in both directions was reversible, and a three-way shape toggling behavior was observed when the solvent was changed from 100% dioxane to 100% water.

Swelling-induced snap-buckling inversion in curved bilayer particles has been shown to change shape in less than 200 ms (Figure 2b).^[68] This timescale is significantly shorter than other mechanisms based on heat and mass transfer, which usually occur over a few seconds, making it useful for microrobotics applications. The mechanically bistable microparticles fabricated by Epstein et al. had a crosslinked poly(acrylic acid) (PAA) hydrogel layer that expands at high pH and contracts at low pH, and a mechanochemically inactive PVCi organogel layer. The swelling of the PAA layer caused deformation in the curved bilayer. At a critical mismatch strain between the layers, buckling inversion took place, resulting in a jump from positive to negative curvature. The same behavior was observed for a curved bilayer that was tethered to a spherical colloidal particle.^[68] As these particles switch shape at timescales faster than diffusion, they have been proposed as candidates to study novel self-assembly dynamics.

Localized bending in bilayer geometries has been exploited to design microorigami particles that fold in response to stimuli. Miskin et al. fabricated micrometer-sized origami machines with hinges that are made of 2 nm thick bilayers prepared from graphene and silicon dioxide. Using photolithography, 2 μm rigid panels were fabricated on top of the bilayer in different configurations that enabled the thin sheet to fold into different 3D geometries, such as boxes, helices with a controllable pitch, and origami with bidirectional folds (Figure 2c).^[69] Xu et al. designed another graphene origami microstructure in which each panel was folded selectively by the functionalization of the graphene layer with polydopamine and subsequently with thermoresponsive PNIPAm.^[70]

2.2.3. Manipulation of Wetting and Surface Anchoring for Irreversible and Reversible Shape Change

Engineering the shape of the interface between a particle and its surrounding solvent provides a route to control particle shape. A morphology switch triggered by dewetting in biphasic colloidal particles was demonstrated by Youssef et al. (Figure 2d).^[71] The authors designed biphasic structures by nucleating oil droplets on solid hydrophilic particles with hydrophobic monolayers on their surfaces. Different materials (i.e., PS, silica, hematite, and titania) were used as the solid seed particles, and the initial morphology was determined by the type of particle. For example, when a PS seed particle was used, the oil droplet partially wetted the particle, creating a well-defined contact angle, whereas hematite seed particles became encapsulated by the oil droplet. To induce dewetting and shape change, the hydrophobic layer was chemically etched or degraded by light. When the hematite colloidal sample was irradiated by green or blue light in the presence of a small amount of hydrogen peroxide, hydroxyl radicals formed, causing degradation of the hydrophobic layer and triggered dewetting of the particles. This dewetting was irreversible.

A reversible transition was observed in the colloidal system prepared by Liu et al. in which non-crosslinked PS microspheres were dispersed in a thermoresponsive mixture comprising water and 2,6-dimethylpyridine (DMP) (Figure 2e).^[72] When heated above the phase separation temperature, DMP was absorbed by the particle surfaces, resulting in shapes that were determined by the relative magnitudes of the interfacial tensions (i.e., between PS and water, DMP and water, and PS and DMP). As the interfacial tension depended on temperature and surfactant concentration, changes in these parameters resulted in reversible switching between different morphologies. The authors demonstrated diverse morphological transitions from spheres to convex-convex shapes, plano-convex shapes, and concave-convex shapes.

Responsive surfactants provide a promising way to control surface anchoring conditions and have been used to facilitate shape change in particles and droplets.^[73–75] Lee et al. used photocleavable surfactants that change amphiphilicity and interfacial activity under light irradiation.^[76] Upon UV irradiation (λ = 254 nm), the surfactant 5-hexyloxy-2-nitrobenzyl-16-N,N,N-trimethylhexadecan-1-ammonium bromide (N-CTAB) transforms into HOOC-CTAB, which caused preferential interactions between the P2VP domain of the BCP particles (PS-b-P2VP). As a result, with longer irradiation times, the spherical onion-shaped particles turned into prolate ellipsoids and then into inverse spherical onion shapes. Wavelength-dependent shape changes were demonstrated by using another surfactant composed of a coumarin ester group (C-CTAB), which turns into HOOC-CTAB at a wavelength of 420 nm.

Viscoelastic droplets can adapt nonspherical shapes when their elastic energy dominates the interfacial tension. The impact of elasticity on changing particle shapes was observed by Denkov et al. in linear hydrocarbon droplets that undergo multiple shape transformations as they are slowly cooled down to their freezing temperature.^[77] A rotator phase forms near the highly curved surfaces of a droplet by freely rotating molecules that maintain their positional long-range order. As a result, a nonisotropic elastic stress is generated to deform the liquid droplet into different shapes (i.e., regular octahedra, polygonal platelets, and thin fibers) during the freezing transition. In another work by Poulichet et al., shape transformation of a droplet was realized using only elastocapillary effects without requiring the application of an external stimulus.^[78] In their work, a rod-shaped petrolatum (petroleum jelly) droplet below a threshold radius of curvature was shown to selectively wrap around a cylinder as it wet the hydrophobized part of the cylinder surface.

2.3. Light-Driven Shape Change

2.3.1. Photothermal Effects

By incorporating light-absorbing materials into particles, temperature can be increased locally with illumination to change particle morphology. The most common light-absorbing agents include gold nanoparticles or nanorods, carbon nanotubes, graphene, and iron oxide nanoparticles. Since both inclusion of photothermal agents and light intensity can be spatially varied, a wide range of shape-changing structures and dynamics are possible.^[79]

Downs et al. used the photothermal effect to achieve a number of desired shape-changing morphologies in a multicompartmental hydrogel (Figure 3a).^[26] The authors i) prepared droplets containing monomer, crosslinker, and photoinitiator, ii) dispersed the droplets in a lipid-containing oil, and then iii) manually assembled the droplets into a network. After photopolymerization, the bilayer between neighboring droplets ruptured, resulting in a continuous hydrogel structure. The size of the individual hydrogel compartments was selectively tuned using photothermal heating by including nanoparticles in the droplets before polymerization. The authors demonstrated selective shrinking of a compartment and bending of a bilayer droplet chain upon illumination with green light. Hydrogel nanocomposite actuators were synthesized by Kim et al. by spatially patterning gold nanoparticles in a temperature-responsive hydrogel sheet (Figure 3b).^[80] When illuminated with light, the in-plane variation of the nanoparticle concentration produced a nonuniform temperature profile in the hydrogel and caused wrinkling of the hydrogel film along its azimuthal direction. The number of wrinkles was controlled by tuning the thickness of the hydrogel film and the size of the gold-patterned region.

Figure 3.

a) Shape change of a hydrogel droplet network containing gold nanoparticles (AuNPs). Upon selective illumination with light, the AuNP-containing droplets shrank, resulting in partial curling of the network. Scale bars 250 μm. Adapted with permission.^[26] Copyright 2020, The Authors, published by Springer Nature. b) AuNP-incorporated hydrogel nanocomposite is shown to wrinkle due to photothermal heating. The number of wrinkles increases with decreasing film thickness. Scale bars: 200 μm. Adapted with permission.^[80] Copyright 2019, Wiley-VCH. c) Bending of an LCE microcylinder in a CLC host obtained by laser scanning along directions shown by the red arrows. The green arrows represent the direction of the CLC host. Adapted with permission.^[83] Copyright 2013, American Physical Society. d) Symmetry-breaking modes of deformation in azo polymer Janus particles, caused by different angles between the orientation of polarized light and the axis of symmetry of the particles. Scale bars: 1 μm. Adapted with permission.^[88] Copyright 2016, American Chemical Society. e) Actuation of artificial cilia under illumination of UV light. Scale bars: 500 μm. Adapted with permission.^[90] Copyright 2009, Springer Nature.

LCE particles containing photothermal agents have also been employed to control and enhance particle actuation. Microrobots with a diameter in the range of 200–400 μm were fabricated by Palagi et al. by adding azobenzene dye into an LCE particle. When illuminated with spatially and temporarily structured light produced by a digital micromirror array, the local isotropic-to-nematic transition resulted in deformations at different parts of the microrobot. Using this concept, periodic body deformations of a cylindrical microrobot was realized that gave rise to self-propulsion.^[81] Photothermal actuation in LCE microstructures was carefully examined by Liu et al. with LCE micropillar arrays that included gold nanospheres and gold nanorods. The authors showed that more rapid photothermal actuations and higher actuation strains can be achieved with gold nanorods compared to nanospheres.^[82] LCE microparticles doped with gold nanocrystals were designed by Evans et al.; when dispersed in an aqueous cholesteric liquid crystal (CLC) solution, photothermal heating caused by unidirectional laser scanning caused particle bending and contraction (Figure 3c).^[83] The aspect ratio of the cylinders were modified both reversibly and irreversibly by bidirectional laser scanning. Similar shape transitions were observed in LCE microparticles dispersed in glycerol.^[84]

Photothermal heating can be implemented in nonequilibrium conditions by applying rapid temporal modulation of light. Mourran et al. designed a ribbon-shaped hydrogel microswimmer with embedded gold nanorods that exhibited bending and torsional motion.^[27] The authors showed that although L-shaped ribbons exhibited isotropic shrinkage at high temperatures under equilibrium conditions, the same ribbon exhibited bending motions when the light irradiation switched between an “on” and “off” state within 50 ms. The authors also demonstrated that the bending deformation modes in a hydrogel ribbon coated with a thin layer of gold nanorods can be designed to generate swimming motions.

Photothermal heating can also be used to change the shapes of plasmonic nanoparticles. A few studies have shown that high energy laser pulses can generate thermally induced shape transformations of gold nanoparticles.^[85,86] An experiment performed by Link et al. showed that femtosecond laser pulses can efficiently, but irreversibly, transform gold nanorods to gold nanospheres.^[85] Another experiment by Inasawa et al. measured the threshold energy of a pulsed laser that can cause gold ellipsoids with a size of 38 nm to change their shapes to spheres. The authors attributed the shape transformation to the surface melting phenomenon that takes place at a temperature of 940 °C, which is about 100 °C lower than the melting temperature of gold.^[86]

2.3.2. Photochemical Effects

Photochemically active molecules undergo deformation in their molecular structure in response to light that drives microscopic changes in particle shape. Azobenzene is a commonly used, photochemically active molecule that switches its shape reversibly from an extended trans to a bent cis state when light is absorbed. By synthesizing particles from azobenzene-based polymers, photochemical shape change can be induced. Li et al. have synthesized poly[6-(4-methoxy-4’-oxy-azobenzene) hexyl methacrylate] (PMMAzo) particles using microfluidics and emulsion-solvent evaporation.^[87] The spherical particles elongated upon irradiation with visible light (λ = 450 nm) along the polarization direction of a linearly polarized beam of light. Particles with a diameter of 9 μm showed much higher deformation rates compared to particles with a diameter of 80 μm. The authors switched the orientation of polarized light with respect to the initial orientation and achieved unique morphologies such as lance-shaped and rice-shaped particles. To explore further shape diversity, Janus particles composed of an azopolymer and PMMA were synthesized.^[88] As the orientation of polarized light was varied with respect to the symmetric axis of the Janus particles, a number of symmetry-breaking deformations were observed, including transitions to droplet-like, mushroom-like, and snail-like shapes (Figure 3d).

In addition to azopolymers, azo molecular glasses, which are low-molecular-weight amorphous organic materials containing azo chromophores, exhibit distinct shape-changing behaviors.^[89] Huang et al. synthesized azo molecular glass particles with a diameter of 14 μm that turned into mushroom-like particles upon irradiation with light (λ = 488 nm). Distinct from the azopolymer particles, photoinduced elongation only occurred on the upper part of the azo molecular glass particles, while the lower part remained unchanged. This effect was attributed to the limited penetration depth of light inside of the particles. Additionally, it was shown that with irradiation times exceeding 3 h, the elongated cap started to deform toward the substrate, which was caused by the refraction of light in the curved caps of the microspheres. The authors also demonstrated that with irradiation of circularly polarized light, the microspheres transformed into a similar mushroom-like structure, with a less elongated cap.

Shape deformations in azobenzene-incorporated LCE structures have been widely explored since the trans to cis isomerization can influence the order parameter of the LCE host. Van Oosten et al. designed flap-bending actuators that mimic the motions of cilia, both on millimeter and micrometer scales (Figure 3e).^[90] Using inkjet printing, the authors fabricated structures with two connected parts incorporating two distinct azobenzene dyes that activate at different wavelengths of light (i.e., one with UV light and another with visible light). The LCE matrix was pre-designed in a splay-bend configuration across its thickness, which caused bending upon isomerization of the azobenzene dyes. By illuminating with UV or visible light, the structures were bent either across their full length, or just partially, mimicking cilia-like motions.

Photochemical reactions have also been used for changing the shape of plasmonic nanoparticles. Silver nanoprisms were transformed into nanodisks when kept in the dark for 24 h and were reversibly transformed back to nanoprisms upon light irradiation for 20 min.^[91] This shape change was attributed to a competitive reaction between the photochemical reduction of Ag⁺ onto the surfaces of the silver nanoparticles and the slower oxidation of the nanoparticles by 4,4′-(phenylphosphinidene)bis(benzenesulfonic acid) dipotassium salt. In later work, shape evaluation from discs to hexagons and then from hexagons to nanoprisms was demonstrated upon longer periods of illumination.^[92]

2.4. Magnetic Field-Induced Shape Change

Magnetically active materials experience a ferromagnetic or paramagnetic torque in response to an externally applied uniform magnetic field or a body-force in the presence of a field gradient.^[93] Structures can be prepared to respond to magnetic fields by incorporating magnetic nanoparticles such as superparamagnetic iron oxide nanoparticles (SPIONs), NdFeB micro-particles, FePt nanoparticles, or by coating thin films made of nickel, cobalt, iron, and other magnetic materials.^[94] The use of magnetic fields has been proven successful in achieving programmable, directional, and rapid shape changes.^[95–99]

Oscillating magnetic fields can cause time-varying torques and thus deformations of elastomeric bodies, which can be used to generate swimming motions. Dreyfus et al. designed an artificial swimmer resembling the motion of a flagellum in which an oscillating magnetic field caused deformation of a self-assembled chain of superparamagnetic particles.^[100] In these microswimmers, the particles with a diameter of 1 μm were first assembled into a chain configuration using DNA linkers. In the presence of a polarizing magnetic field, the particles acquired magnetic dipoles; the dipolar interactions between the beads in the chain and the interaction between the dipoles and the external magnetic field resulted in magnetic torque. The component of the magnetic field along the chain remained constant, while the component perpendicular to the chain oscillated in time. Since this oscillation was trans-verse to the magnetic field, the free end of the chain successively bent to follow the magnetic field, creating a propagating undulation that gave rise to propulsion. Another design of a magnetic microswimmer was prepared by Li et al. containing a central gold body segment and two nickel arm segments that were connected by flexible porous silver hinges (Figure 4a).^[101] This swimmer also responded to an oscillating magnetic field that was applied perpendicular to its central body. As a result, the magnetic moment of the two arms tended to align with the magnetic field and oscillate in an antiphase manner, causing a swimming motion resembling the freestyle stroke. A “micros-callop” like swimmer robot has been demonstrated by Velev and co-workers where cobalt-coated patchy microcubes assembled into linear chains under a magnetic field directed by their magnetic patches.^[102] Upon removing the external magnetic field, the residual magnetic polarization remained as a magnetic dipole and allowed the microcubes to self-fold to minimize their magnetic interaction energy. Thus, by switching the magnetic field “on” and “off”, “opening” and “closing” strokes were realized, respectively (Figure 4b). The authors later showed that these origami clusters can self-propel in non-Newtonian fluids when driven by reciprocal strokes of different opening and closing speeds by a time-varying magnetic field.^[103]

Figure 4.

a) Schematic illustration (left) and microscopy images (right) showing the deformation of a two-armed swimmer body in response to an oscillating magnetic field. Scale bar: 2 μm. Adapted with permission.^[101] Copyright 2017, American Chemical Society. b) Opening and closing of assemblies of magnetic microcubes by turning an applied magnetic field on and off, respectively. Scale bar: 10 μm. Adapted with permission.^[103] Copyright 2020, American Chemical Society. c) Magnetic nanoparticles assemble in parallel with an applied magnetic field prior to photopolymerization; after photopolymerization, the direction of the alignment rotates when a magnetic field is applied in another direction (left). A microactuator made from four different parts with four different alignment axes recoils under a magnetic field. Scale bar: 100 μm (middle). Magnetic tweezers designed with a pure polymer region and a magnetic assembly region. Scale bar: 50 μm (right). Adapted with permission.^[104] Copyright 2011, Springer Nature. d) Left: Schematic illustration of a micromachine comprising five panels with two magnetization types, shown in red and green, and magnetization directions (top). Electron microscopy image of the panels (bottom). Scale bars: 500 nm. Right: Programming of the panels using magnetic fields B₁ and B₂ with magnitudes such that B₁ activates both Type I and Type II panels, but B₂ activates only Type II panels (top). Folding of a pre-programmed micromachine (bottom). The geometry of the fold depends on the configuration with which it was magnetized. Scale bar: 10 μm. Adapted with permission.^[28] Copyright 2019, The Authors, published by Springer Nature.

Bending and folding deformations have been achieved using magnetic fields by incorporating magnetic materials into soft polymer and hydrogel matrices. A programmable magnetic microactuator was designed by Kim et al. directing the self-assembly of SPIONs into chains embedded in a polymer matrix (Figure 4c).^[104] During the fabrication of the microactuators (or microrobots), a photocurable resin monomer solution along with SPIONs was flowed into a microfluidic channel, where an external magnetic field was used to assemble the nanoparticles into a chain. Once the resin was photopolymerized, nanoparticles were immobilized and when an external magnetic field was applied along a different direction, the chains induced a cooperative torque to rotate along the direction of the magnetic field. Applying this principle, different parts of the microrobot were bent in different orientations by designing the initial alignment of the particle chains. A magnetic tweezer and a crawling microrobot were developed using these deformations.

Nanomagnet micromachines were fabricated by Cui et al. that can encode shape-morphing information and transform into diverse morphing geometries when a magnetic field of differing strengths is applied along different directions (Figure 4d).^[28] The micromachines were designed with rigid panels containing arrays of nanomagnets and soft spring hinges connecting the panels. The direction of magnetization of each panel was controlled by tuning the orientation and size of individual nanomagnets. First, when exposed to a polarizing magnetic field at different angles, panels only acquired magnetization in the direction of the longest axis of the nanomagnets, allowing each panel to be magnetized in specific directions. Second, even when the nanomagnets were aligned in the same direction, the authors demonstrated the panels could be polarized in opposite directions by adjusting the size, and thus hysteresis of the nanomagnets such that they polarize in response to magnetic fields of different amplitudes. By selecting an external magnetic field with the appropriate direction and amplitude, one or both types of the magnetization were activated, and as a result, panels with distinct magnetization types were individually programmed. Using these principles, the authors programmed the micromachine panels in different configurations and demonstrated the folding of a box in different geometries. Additional complex and programmed micromachines were made, including a microscale bird with diverse and programmable motions such as flapping, hovering, turning, and slide-slipping.

2.5. Discussion

2.5.1. Challenges and Opportunities of Changing Shape at the Micro and Nanoscale

Much progress has been made in demonstrating numerous shape-changing modes at the micro and nanoscale as discussed in the previous section. The actuation mechanisms each have their own advantages and limitations that have been critically analyzed in the literature.^[94] Here, we discuss potential future directions in the development of micro and nanoscale shape-changing particles that will involve enhancing programmability and efficiency and reducing cost.

Higher degrees of programmability will allow for the transformation of an arbitrary 3D shape to another target shape, enhancing programmability so that a particle with an arbitrary 3D shape can be fabricated and transformed into another target shape. The top-down and bottom-up technologies methods of fabricating and programming 3D nanostructures with arbitrary shapes using stimuli-responsive materials are emerging. Direct laser writing (DLW) using two-photon polymerization is a promising top-down fabrication method that allows for precise control over shape in 3D with a resolution of less than 200 nm.^[7] In the case of micro and nanoparticles, it is challenging to maintain the stability of freestanding 3D nanostructures using deformable and stimuli-responsive materials. Several approaches have been developed to overcome this challenge. Zhang et al. introduced a dual-3D fabrication strategy in which the voxel size and voxel distribution can be precisely controlled to achieve tunable deformability in 3D using only one photopolymer.^[105] Jin et al. have designed compound 3D micromachines with carefully positioned active components made from hydrogel bilayers that allow for large deformations in structures with sizes less than 100 μm (Figure 5a).^[106] An in-gel writing method has been developed that enables writing of stable freestanding structures made from a stiff material inside of a deformable hydrogel body.^[107] Polymeric ionic liquids have been proposed as deformable material for DLW to achieve higher writing resolution.^[108] The top-down method of DLW is good for precise control over geometry and shape transformation; however, it is expensive and not suitable for fast and large-scale particle fabrication.

Figure 5.

a) Schematic Illustration of a 4D printing strategy that allows for precise spatial control over hydrogel crosslinking density in a 3D micromachine. Reproduced under the terms of the CC-BY Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0).^[106] Copyright 2019, The Authors, published by Elsevier. b) Schematic illustration of a dynamic plasmonic structure that changes its chirality in response to a certain wavelength of light. Reproduced under the terms of the CC-BY Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0).^[112] Copyright 2016, The Authors, published by Springer Nature. c) Illustration of a reconfigurable assembly in which colloidal Janus particles transition from a crystalline bilayer configuration to a chain configuration in response to changes in temperature. Adapted with permission.^[113] Copyright 2020, American Chemical Society. d) Time required to facilitate complete changes in particle shape as a function of size for several key materials and mechanisms. An effective particle size was defined by $\sqrt[3]{V}$, where V is the volume calculated from the references listed in brackets.

At the micro and nanoscale, self-assembled structures that change their shape in response to stimuli provide a more scalable alternative for production of programmable shape-changing particles. Nanometer-scale structures with arbitrary 3D architectures can be self-assembled using DNA origami – by folding large scaffolds of DNA strands into different shapes by hybridizing with other staple strands.^[109,110] Willner et al. designed DNA nanoscissors that open and close with UV and visible light illumination, respectively, driven by the duplex formation of azobenzene-tethered DNA.^[111] Gold nanorods were attached to the opposite sides of the nanoscissors to form a 3D chiral structure that changes its chirality according to the “open” and “closed” states of the nanoscissors (Figure 5b).^[112] Reconfigurable self-assembly at the micrometer scale was shown by the temperature-driven transition of DNA-coated Janus particles between different geometries – crystalline bilayers, small clusters, and chains (Figure 5c).^[113] Thus, instead of the conventional shape-changing approach of programming heterogeneity inside of a particle, self-assembly allows for programming of the interactions between small particles to assemble into different shapes. Recently, a number of advanced synthesis methods have been implemented to create helical^[114] and cone-shaped^[115] particles as well as colloidal “molecules” with clusters and chains^[116] and chiral arrangements.^[117,118] These developments add new possibilities for reconfigurable self-assembly as a route to achieve shape-changing micro and nanostructures.

2.5.2. Shape-Changing Kinetics for Target Applications

The required time for changing shape is an important parameter to consider when designing particles for certain applications. As particle size decreases, many shape-changing mechanisms such as hydrogel swelling, polymer relaxation, and heat diffusion across the particle body can proceed more rapidly. For example, the expected timescale for heat transfer can be roughly estimated from $\tau ~\frac{d^2}{D}$, where d is the relevant particle length and D_t is the thermal diffusivity of the material. We observed that this general tendency stands for different mechanisms, as shown in Figure 5d. The fastest shape transformations in the range of 10–100 ms have been demonstrated by oscillatory magnetic field-driven microswimmers (purple area in Figure 5d)^[100,101] as well as photothermal actuators (red area in Figure 5d).^[120,121] Thus, particles that change shape by magnetic fields, photothermal effects, or swelling-induced snap-buckling are especially promising for next-generation soft microrobots. Temperature-driven relaxation of shape-memory polymers and phase transition of LCPs (orange area in Figure 5d)^[37,42,51] as well as mechanisms based on anisotropic swelling of the particle body (green area in Figure 5d)^{[65,66,68,105,106]} take place over 1–10 s. Although comparatively slower, this timescale is appropriate for many biomedical devices. The time required for photo chemical mechanisms can vary significantly depending on the kinetics of the reaction and the mechanical properties of the material. While photochemical deformation of azopolymer particles^[87–89] and actuation of block copolymer particles via photo-switchable surfactants^[76] (gray area in Figure 5d) may take up to an hour, azobenzene-incorporated LCE microstructures exhibit much faster shape transformations, on the order of 20 ms.^[122] While the miniaturization of particles allows for faster transformation kinetics, it often requires the application of high intensity light and magnetic fields. In future work, transformation efficiency will become a crucial parameter to consider when designing shape-changing particles at the micro and nanoscale.

3. Emerging Applications of Shape-Morphing Particles

Shape-changing particles have the potential to impact numerous application areas because of their ability to be incorporated into virtually any material system in which responsiveness to the environment is desirable. Recently, there has been much progress in applying responsive and even active shape-morphing materials at the micro and nanoscale. These applications fall into the broad categories of optics, microrobotics, biomedical technologies, and microfluidics. In this section, we review recent demonstrations of shape-changing particles in each of these application areas.

3.1. Photonics and Plasmonics

Shape-changing particles and reconfigurable particle assemblies have proven useful in designing tunable photonic and plasmonic materials. The study of colloidal self-assembly was initially motivated by the potential of colloidal systems to produce photonic bandgap materials.^[123,124] Although such bandgap materials can now be fabricated using top-down methods, colloidal self-assembly has been proven suitable for the production of materials with structural color.^[125–127] Reconfigurable assemblies have been implemented to achieve responsive structural color with applications in camouflage, smart coatings, and anti-counterfeiting.^[128,129] In addition to self-assembled structures, soft materials such as LCPs and hydrogels are used in the fabrication of photonic materials such as waveguides, optical fibers, and photonic crystals.^[130,131] LCEs and LCNs in particular have been proposed for light-driven motors and actuators, artificial muscles, and smart surfaces.^[21]

Advances made in tunable optics, photonics, and plasmonics at the microscale could enable new capabilities in microrobotics and microdevices. The fabrication of shape-morphing particles within the body of a microscale robot could provide a platform for tunable photonic components, such as waveguides and filters. Color-changing capabilities discussed in this section might have uses in sensing applications. For example, optical displays on microdevices could provide readouts in biological and environmental sensing. These topics are addressed in the following sections. Further discussions of the advantages of using light to actuate or manipulate microscale devices can be found in recent reviews.^[94,132]

3.1.1. Tunable Structural Color

Colloidal particles embedded in a soft material can show structural color dependent on the separation distance between particles. Materials that bend, expand, and contract can change interparticle distances and therefore the optical properties of embedded crystals. Kwon and co-workers created optically tunable microactuators from magnetic nanocomposites (Figure 6a).^[133] These materials consisted of superparamagnetic colloidal nanoclusters embedded in a photocurable polymer resin (PEG diacrylate, PEGDA). During fabrication, the nanoclusters were assembled into chains using an applied magnetic field. By changing the magnetic field strength during polymerization, the authors varied the initial and subsequent colors of microactuators. These actuators were tethered so that bending under an applied magnetic field varied interparticle distance and thus color. Using silver nanoparticles in LCE films, Guo and co-workers created thermally driven bilayer structures (Figure 6b). Localized surface plasmon resonance (LSPR) of nanoparticle arrays conferred color-changing capabilities upon thermal actuation of LCE films (bending and compressing). Alterations of the embedded colloidal crystal resulted in blue-shifting and varying reflectance.^[134] Cho and co-workers added negatively charged spherical gold nanoparticles to positively charged, thermoreversible hydrogel particles (Figure 6c).^[135] All of the above examples rely on crystals within responsive materials and the capability of these materials to vary interparticle separation.

Figure 6.

a) Array of magnetochromatic actuators of different colors. The magnetic field is parallel to the actuator, and magnetic particles are perpendicular, resulting in out-of-plane bending. Each actuator contains different photonic crystals that give rise to different colors upon actuation. Scale bar: 50 μm. Adapted with permission.^[133] Copyright 2013, Wiley-VCH. b) Chameleon-like color change of a nanocomposite film comprising silver nanoparticles embedded in LCE from 30 to 130 °C. Reproduced with permission.^[134] Copyright 2016, Royal Society of Chemistry. c) Color-changing of hydrogel particles depend on gold nanoparticle (Au NP) spacing. SEM images of gel particles (left) and corresponding UV–vis spectra (right). Reproduced with permission.^[135] Copyright 2014, American Chemical Society. d) TEM images and fluorescence photographs of BCP particles responsive to pH and temperature. The two images show a single particle switching between two different BCP phases: spherical (top) and lamellar (bottom). Reproduced with permission.^[18] Copyright 2019, American Chemical Society. e) BCP ellipsoids containing iron oxide nanoparticles under a magnetic field, illustrating reconfigurable optics using anisotropic colloidal particles. The iron oxide nanoparticles were tethered to the surfaces of particles after emulsion polymerization. Reproduced with permission.^[16] Copyright 2020, American Chemical Society. f) Optical microscopy images of capsules with rigid (i) and flexible (ii) silicone shells in solutions with different osmolarities. Flexible capsules show tunable optical properties. Particle sizes were ≈100 μm. Adapted with permission.^[136] Copyright 2014, Springer Nature.

Besides changing separation distance between particles, tuning single particle geometry is another way to achieve tunable optical properties. To our knowledge, there are very few examples of shape-shifting particles within crystal structures. However, several recent publications show that shape-shifting at the single-particle scale also results in optically tunable materials. Block copolymers (BCPs) in particular have been used to synthesize many different nonspherical particle shapes. Kim and co-workers engineered dual-responsive surfactants for shape-shifting BCP nanoparticles. These particles were made responsive to pH and temperature for possible applications in biosensing and could reversibly shift from football-like (prolate ellipsoid) to lens-like shapes (Figure 6d). The authors incorporated different fluorescent dyes into the BCP domains and showed that the shapeshifting modulates the distance between the dye molecules as well as the efficiency of Förster resonance energy transfer (FRET) between them, resulting in a colorimetric readout.^[18] Swager and co-workers took advantage of the molecular properties of bottlebrush copolymers to synthesize ellipsoidal particles with high aspect ratios. The assembly of these elongated particles gave rise to structural colors in solution, and the authors subsequently tethered magnetic nanoparticles to the ellipsoids to make a magnetoresponsive, optically switchable solution (Figure 6e). This work demonstrates the link between macromolecular architecture and microparticle geometry with applications in assembly-driven optics.^[16] The Schenning group made films from CLC polymers containing side-chain mesogens that allowed for differential swelling within the material upon exposure to water. Varying degrees of swelling and therefore different colors could be patterned into the material using an inkjet printer with submillimeter precision. This type of system could be adapted for particle fabrication.^[129] The Weitz and Manoharan groups demonstrated that colloidal crystals could be encapsulated in flexible, elastomeric silicone microshells, allowing for optical control using osmotic pressure gradients (Figure 6f). These capsules showed reversible color-switching capabilities.^[136]

3.1.2. Reconfigurable and Shape-Driven Self-Assembly

Both the structure and the dynamics of a self-assembly process are determined by the shape of the building blocks and the interactions between them. By using shape-shifting particles as the building blocks of self-assembly, reconfigurable structures and unusual dynamics can be observed.^[137] Glotzer and co-workers have shown computationally that shape-shifting of particles in colloidal crystals can result in assemblies normally inaccessible to static particle shapes, highlighting the potential of such assemblies in a variety of applications.^[19] In another study, Nguyen and Glotzer computationally showed that shape-changing nanorods could generate different assemblies by simply changing their length. These assemblies included square grids at long lengths, honeycomb and pentagonal structures at intermediate lengths, and smectic A phases at short lengths.^[138] Recently, several experiments have demonstrated reconfiguration of assemblies using shape-changing particles. The shape-shifting patchy particles designed by Weck and colleagues have been used to assemble into supracolloidal chains as well as branched and cyclic structures, as the patches shift from concave to convex in response to changes in the solvent. The patch-patch interactions were mediated by liquid-induced capillary bridging from the absorption of N-methylpiperidine into PS.^[54] The biphasic particles synthesized by Sacanna and co-workers were assembled into a crystalline lattice, and stimulated dewetting was shown to drive their reconfiguration in the lattice structure.^[71] Interestingly, reconfiguration of self-assembled particle clusters could also have applications in information storage and computation.^[139]

Shape-driven interactions and assembly will be useful for controlling interparticle behaviors such as communication, locomotion, swarming, clustering, and separation. Capillary interactions at air–water interfaces have been shown to drive the assembly of shape-morphing microgels. Hayward and co-workers developed a method for maskless grayscale photolithography, which can be used to fabricate shape-programmed gel particles.^[140,141] Thermoresponsive PNIPAm sheets were fabricated into minimal surfaces with a specified number of wrinkles for controlled buckling into radially symmetric shapes. The buckling of hydrogel particles and subsequent deformation of the air–liquid interface resulted in their reversible self-assembly. Shape was used to determine valence and bond angle to form higher-order, reversible assemblies.^[141]

3.2. Soft and Microscale Robotics

The miniaturization of robotic systems to the microscale requires a materials approach that integrates capabilities such as sensing, information processing, and actuation into the same structure. Soft microrobots offer many advantages over hard structures, including dexterity and adaptability, which can be especially useful for biological applications. Shape-morphing of soft materials can be easily programmed, enabling capabilities such as swimming, gripping, and deformation-based release of encapsulated payloads. The diversity of actuation mechanisms and materials increases the number of possible applications from soft robotics to biomedical sensors.^[22] Certain LCEs have recently been shown to be biocompatible, broadening the scope of their potential applications.^[142] Soft microrobots have been researched for targeted drug delivery, minimally invasive surgery, single-cell manipulation, lab-on-a-chip devices, desktop micromanufacturing, and environmental remediation.^[143] For these applications, microrobots must be capable of self-propulsion, which can be accomplished using magnetic fields,^[103] electric fields,^[144] optical fields,^[145] acoustic fields,^[146] and chemical fuels.^[147] For biomedical and biological applications, light, acoustic fields, and magnetic fields offer the most promising actuation mechanisms because of their biocompatibility and high spatiotemporal resolution.^[94]

3.2.1. Mechanical Self-Propulsion

In nature, microorganisms and eukaryotic cells display many types of shape-driven locomotion from the crawling of amoebas to the beating of flagella.^[148] The design of shape-shifting active materials takes inspiration from nature to drive motion and other complex behaviors. Motion of soft materials at the microscale has been achieved using LCEs, ionic polymers, thermoresponsive polymers, and oscillating chemical reactions.^[149,150] In particular, LCEs and hydrogels have been used extensively in the fabrication of soft robotic components, and these technologies laid the groundwork for microscale devices.^[94,151] On the millimeter scale, walking, jumping, crawling, and even flying have been demonstrated with soft or microscale robots using elastomers and hydrogels.^[152,153] Dickey, Velev, and co-workers made a hydrogel walker consisting of two sections, each of which was made from a differently charged polyelectrolyte material.^[154] The walker could move forward and backward in response to electric fields. Osmotic pressure differences from the movement of ions in solution bent each polyelectrolyte appendage, offering a relatively simple way to actuate the material. Chu and co-workers developed a similar hydrogel walker system capable of cargo transport.^[155] Sitti and co-workers designed and made a millimeter-scale robot from an elastomeric material containing magnetic microparticles. This robot was capable of multiple types of locomotion in water and air.^[98] Shape-morphing LCPs have been studied and reviewed extensively,^[21,156] and recent advances show that these materials can be used in microfabrication and microparticle synthesis, as discussed in the previous section.

In this section, we discuss soft microparticles that self-propel as a result of mechanical actuation. Numerous responsive microgels have been used to fabricate self-propelling devices. Hayward and co-workers designed light-responsive hydrogel nanocomposites that exhibit different modes of motion. Thermoresponsive polymers (i.e., poly(diethyl acrylamide) or PDEAM) were used to fabricate hydrogel sheets containing a gold salt. Photolithography and subsequent patterned photo-catalysis of the salt with UV light allowed for in-gel synthesis of gold nanoparticles. These nanocomposite gels contained precisely defined patterns of nanoparticles, which could be heated for controlled wrinkling and buckling. These light-responsive gel surfers were shown to tractably assemble, repel, and undergo rotational and translational motion (Figure 7a).^[80] Using various hydrogel systems, Möller and co-workers fabricated a variety of robotic microgels. The motion of these gels is driven by their ability to twist and bend in response to stimuli such as heat and light. PNIPAm ribbons were fabricated and coated with thin gold layers. Plasmonic heating from a laser source resulted in the twisting of these ribbons into helices, achieving bidirectional rotation with high spatial resolution.^[120] Using the particle replication in nonwetting templates, or PRINT, technique pioneered by DeSimone’s group,^[157] PNIPAm nanocomposites containing gold nanorods were fabricated. L-shaped robots were designed, prepared, and shown to translate by nonreciprocal bending.^[27] This group also fabricated microgel rotors tethered to microbeads capable of nonreciprocal motion in response to light. Photothermal heating and bending of the rotor led to biomimetic motions under nonequilibrium conditions (Figure 7b).^[158] Nonreciprocal motion is necessary for net displacement in Newtonian fluids at small Reynold’s number; therefore, this type of system could be useful in soft microrobots. In addition to hydrogels and polymers, LCEs have been used in the fabrication of soft microrobots. Fischer’s group developed a method for fabricating LCE microrobots that swim in response to structured light. They used this method to fabricate a millirobot and smaller disc-shaped robots. Using structured light, the authors were able to induce traveling waves in the LCE material, driving rotational and translational motion of the disc robots (Figure 7c).^[81]

Figure 7.

a) i) Nanocomposite gel surfers with three binding sites. ii) Self-assembly of square-shaped nanocomposite gel surfers. Scale bars: 200 μm. Reproduced with permission.^[80] Copyright 2019, Wiley-VCH. b) i) Spiral rotor at different temperatures. ii) Superimposed images of a spiral rotor under stroboscopic irradiation. iii) Superimposed trajectories of a spiral rotor under stroboscopic irradiation. Adapted under the terms of the CC-BY Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0).^[158] Copyright 2019, The Authors, published by Wiley-VCH. c) Schematic illustration (i) and microscopy images (ii) of light-controlled disc-shaped microrobots. Scale bar: 200 μm. Adapted with permission.^[81] Copyright 2016, Springer Nature. d) Shape-switching of microtubes controlled by temperature. Such devices were loaded with magnetic particles such that directed motion was achieved with magnetic fields. Scale bar: 500 μm. Adapted with permission.^[162] Copyright 2015, American Chemical Society. e) Schematic illustration (i) and microscopy image (ii) of directed propulsion of microrobot powered by an infrared LED. Scale bar: 1 mm. Reproduced with permission.^[170] Copyright 2020, The Authors, published by Springer Nature.

In addition to propulsion in aqueous environments, there are also several examples of microrobots that locomote in air. Wiersma and colleagues used DLW to fabricate an LCE microrobot with a rectangular body and four legs. This particular design was capable of walking, rotating, and jumping in response to laser pulses that caused the LCE body to cyclically expand and contract.^[159] Crawling was achieved using chemical oscillations that drive phase transitions and crawling-type motions in active gels. The most popular chemical oscillator is driven by the Belousov–Zhabotinsky (BZ) reaction, which was used to produce amoeba-like movements by autonomous sol-gel transitions in a polymer fluid on an incline. This work by Yoshida and co-workers showed how oscillations from a BZ reaction could be used to drive the formation and dissociation of micelles in a gel, resulting in autonomous motion.^[160] Self-oscillating gels are a promising platform for motile, shape-morphing particles, and recent developments in this field have been reviewed elsewhere.^[149] Microparticles containing oscillating chemical reactions are particularly exciting because of previous work showing that these systems can be engineered to perform computation or communication.^[161] Such chemical systems could pave the way for engineering particle assemblies with collective behavior.

3.2.2. Functional Self-Folding for Propulsion and Delivery

The self-folding of thin films can also confer propulsive capabilities. This technique is commonly used in hydrogel materials because of their ability to swell reversibly.^[4] Pané and co-workers fabricated hydrogel bilayers that are responsive to near-infrared light and magnetic fields. These bilayers could reversibly change shape from a flat to rolled conformation. This was accomplished by adding PNIPAm nanocomposites on top of layers of PEDGA. The top nanocomposite could be made light-responsive by adding graphene oxide (GO) nanoparticles. Alternatively, the nanocomposite was made magnetic through the inclusion of iron oxide nanoparticles. Shape-morphing occurred due to the thermoresponsive swelling of PNIPAm, switching the shape from cylindrical to flat. The flat shape was used to stop propulsion and enhance drug release out of the bilayer. The authors also fabricated helical gel bilayers that unfolded and stopped moving in response to temperature changes using the same material system (Figure 7d).^[162] Rolled structures could also be useful in microsurgical procedures. Schmidt and colleagues showed how microdrillers consisting of polymer sheets coated with a layer of Ti/Cr/Fe were rolled into cylinders with sharp metallic tips. The motion of these cylindrical drillers was controlled by the interplay of fluid viscosity and the frequency of a rotating magnetic field, which provided sufficient strength to penetrate model biological tissues.^[163] On the nanoscale, Wilson and co-workers synthesized polymersomes that reversibly switched from spherical to stomatocyte-like configurations. This type of shape-shifting allowed particles to encapsulate two complementary enzymes, glucose oxidase (GOx) and catalase. These nanomotors used glucose as a fuel for self-propulsion at biologically relevant concentrations. Such systems could be useful as drug delivery vehicles or as nanoreactors.^[164]

Steering, control, and automation remain significant challenges for the field of microrobotics. These challenges could be overcome by on-board electronic and/or photonic circuits, which are necessary for wireless communication, independently addressable robots, and signal processing. The Cohen and McEuen groups have made rapid progress in recent years. Cohen, McEuen, and co-workers pioneered new atomic layer deposition (ALD) and microfabrication strategies,^[165,166] paving the way for advances in novel microactuator designs. The groups have fabricated self-folding microorigami devices by patterning SU-8 panels on ALD SiN_x:SiO₂ bilayers,^[167] and they fabricated pH-responsive microorigami structures by adding graphene between the silicon and SU-8 panels.^[69] Both versions of these origami devices rely on strain differentials between the material layers to drive bending in the regions uncovered by rigid SU-8 panels. Building on these technologies, the McEuen and Cohen groups have also fabricated microrobotic structures capable of reversible shape-morphing and even locomotion. Low voltage, shape-memory microactuators were fabricated using rigid SU-8 panels on Pt:TiO₂ bilayers.^[168] These actuators were electrically connected to a silver electrode and immersed in an electrolyte solution. Upon application of ≈1 V, electrochemical reactions at the platinum interface induced shape-morphing that could be reversed, allowing for read-write-erase-like actuation. Finally, this electrochemical actuation mechanism was used in the fabrication and actuation of deployable microrobots, which could be made to walk on four legs using just laser light.^[169] The above-mentioned fabrication methods are amenable to semiconductor processing, which allows for scalability and manufacturability. Schmidt and co-workers designed motile twin-jet engine microsystems with two rolled hydrogel tubes separated by a flat surface on which a receiver coil was fabricated for wireless energy transfer. Each rolled tube contained a platinum layer for catalytic self-propulsion in a hydrogen peroxide solution. The authors also added a thermoresponsive arm to enable grab-release functions (Figure 7e).^[170] It is likely that future generations of microrobots will be fabricated with electronic and photonic components.^[171] Circuits could be added to microrobotic structures made from standard photolithography or DLW and be made from responsive materials.^[172] For example, tunable photonics have been demonstrated using LCNs. Wiersma and co-workers added LCN components to waveguides and resonators fabricated by DLW. The LCN could be used to actuate a whispering gallery-mode resonator or as a resonator itself.^[17] This represents a growing and likely impactful direction within microrobotics research.

3.3. Shape-Shifting Biomedical Microdevices

3.3.1. Gripping, Encapsulation, and Microsurgery

Developments in microrobotics will play a key role in the miniaturization of medical tools for surgery and other procedures. The push for smaller surgical and biomedical tools may lead to minimally invasive, safer treatments. Such tools could someday be capable of cutting, stapling, and performing other complex tasks. Over the last decade, there have been significant developments in self-folding gels and polymers for gripping and releasing encapsulated cargo. These microgrippers are typically polymers capable of self-folding from sheet-like to enclosed structures. Such devices are capable of handling payloads such as cells, pharmaceutical drugs, and bioactive molecules. One promising application of soft grippers is microbiopsy. Biopsy requires high force to separate cells from tissue, requiring hard and soft materials within the same device. The Gracias group has made a number of important contributions to this field. This group designed and fabricated magnetically responsive microgrippers and demonstrated feasibility by conducting ex vivo studies on porcine liver samples and in vivo studies in a porcine biliary tree. Excised tissues were shown to yield high quality DNA and RNA readouts.^[10] The same group has systematically investigated the influence of shape and size on the actuation and transport of microgrippers, finding that these parameters could be useful in different applications from biopsy to navigation.^[173] The same group also showed that microgrippers made from poly(oligoethylene glycol methyl ether methacrylate-bis(2-methacryloyl)oxyethyl disulfide) and poly(acrylamide-N,N′-bis(acyloyl)cystamine) are biodegradable (Figure 8a).^[174] Interestingly, the Gracias group used thermoresponsive wax and food-grade butter in their magnetic grippers for enhanced biocompatibility. These grippers fold once inside of the body and excise one or several cells at a time (Figure 8b).^[11] Recently, Sitti and co-workers developed biodegradable milligrippers made from porcine extracellular matrix-derived collagen. SPIONs were embedded in the hydrogel for programmable shape transformations and locomotion. Interestingly, permanent magnets were used during fabrication for the assembly of SPIONs into chains, which determined the direction of actuation.^[175] Recent improvements in the design and large-scale manufacturing of gripper technologies make this an exciting application area for minimally invasive medical procedures.^[176]

Figure 8.

a) i) Fluorescence video snapshots of a bilayer degrading after 20 days. The bilayer is composed of P(OEGMA-DSDMA) as a swellable, thermoresponsive layer and a low-swelling poly(acrylamide-N,N′-bis(acyloyl)cystamine) hydrogel layer. ii) Optical video snapshots of the degradation of a bilayer gripper in 500 × 10⁻³ m ascorbic acid and 500 × 10⁻³ m hydrogen peroxide at pH = 3 and 37 °C. Scale bars: 2 mm. Adapted with permission.^[174] Copyright 2015, American Chemical Society. b) i–iv) Approach and capture of a suspended MDA-MB-231 cell using 70 μm thermoresponsive grippers guided by magnetic fields. v) Microgripper transporting cell. vi) Microgripper releasing cell. Adapted with permission.^[11] Copyright 2020, American Chemical Society. c) Encapsulation and drug release from microrobots. i) Drug release by hydrogel bilayer tubes and microrobot assembled by three bilayers. Circles correspond to bilayer tubes and squares correspond to microrobots made up of three hydrogel bilayers; ii) microrobot disassembly by temperature elevation. Particles are ≈1 mm in size. Reproduced with permission.^[182] Copyright 2019, Mary Ann Liebert, Inc. d) Schematic illustration (top) and epifluorescence images (bottom) of microrobots, showing drug release by the enzymatic degradation of the network. Adapted with permission.^[183] Copyright 2019, American Chemical Society. e) Magnetically actuated soft microrobots. The red areas have a high pH, and the blue areas have a low pH. i–vi) A microrobot with an encapsulated bead is driven from a high to low pH region, releasing cargo in response to changes in pH. Adapted with permission.^[12] Copyright 2016, IOP Publishing. f i) Actuation of a cantilever system made of poly(dimethylsiloxane) (PDMS) around which actuators were polymerized. ii) Bending of lever arms due to reversible actuator swelling. Scale bar: 50 μm. iii) Compression of a tumor spheroid. The forward movement of the piston from actuator strain on the piston body. Scale bar: 100 μm. Adapted with permission.^[190] Copyright 2019, Royal Society of Chemistry. g) i) Schematic illustration of 3D microrobotic assembly of various microgels on multiple posts. ii) Schematic illustration of the microgel assembly. iii) Microscopy image (top) and SEM image (bottom) of assembled microgels, as illustrated in (i). Adapted under the terms of the CC-BY Creative Commons Attribution 3.0 Unported license (https://creativecommons.org/licenses/by/3.0).^[191] Copyright 2015, the Royal Society of Chemistry.

3.3.2. Biosensing, Drug Delivery, and Cellular Transport

In addition to the above actuation mechanisms, chemomechanical materials can be employed to respond to chemical changes in the environment. Actuation in response to chemicals or biomolecules is particularly relevant to implantable or ingestible biomedical devices. Chemomechanical actuation has several advantages, including the miniaturization of responsive materials and the diversity of chemicals and chemical interactions by which they selectively transduce energy.^[177] For example, shape-morphing gels can be made responsive to glucose, pH, and other chemicals.^[178,179] Oscillating or networked reactions are capable of driving phase transitions, volumetric changes, and motion in gels. Additionally, recent advances in systems chemistry offer new routes by which molecular networks could improve upon chemical communication and shape-morphing within materials.^[180] Biomolecule-responsive gels have significant potential as future biomaterials. Nucleic acids, enzymes, and protein receptors all show highly specific supramolecular chemistries, and the incorporation of biomolecular receptors into shape-morphing materials offers the ability to perform quantitative biodetections by their actuation. Schulman, Gracias, and colleagues demonstrated hybridization-triggered shape-morphing of DNA-crosslinked polyacrylamide hydrogels. These gels were fabricated using standard photolithography without significant damage to the DNA cross-links, and swelling was induced by the introduction of hairpin DNA sequences that polymerized and extended cross-links via hybridization. This molecular system was used to selectively bend and swell different regions within hydrogel structure.^[181]

Shape-morphing gels have been studied for their ability to modulate diffusion since drug release can be influenced by the structure of the gels. Capsule-like microdevices have also been devised by Nelson and colleagues. These capsules were Matry-oshka-inspired containers for modulated delivery, switching from sheets to rolled conformations. Each capsule was made as a sheet containing one or more hydrogel bilayers (i.e., comprising poly(N-isopropylacrylamide-co-acrylamide) and PEGDA), and the bilayers contained magnetic nanoparticles for locomotion and heating. The authors found that shape and number of layers contributed to drug release, translational motion, and rotational motion near boundaries (Figure 8c).^[182] Sitti and co-workers designed and fabricated biodegradable microrobots made from gelatin methacryloyl, which can be broken down by matrix metalloproteinases (MMPs) for controlled swelling, morphing, and drug release. The authors combined this material with iron oxide nanoparticles for magnetic actuation. Since cancer cells upregulate MMPs during metastasis, this design could be used to achieve actuation in the vicinity of solid tumors (Figure 8d).^[183] Gracias and co-workers designed drug-eluting microgrippers made from hydrogel bilayers consisting of PNIPAm as the soft material and poly(propylene fumarate) (PPF) as the hard layer. These devices were able to cling to the walls of a porcine GI tract for improved delivery upon collapse of the PNIPAm network. Such devices could prove useful in the treatment of diseases such as inflammatory bowel disease and colorectal cancers.^[184] Lastly, Park and co-workers showed that hydrogel microrobots made from PEGDA and poly(2-hydroxyethyl methacrylate) (PHEMA) were capable of encapsulating and delivering drug-containing beads as a proposed cancer treatment (Figure 8e). This material system is pH-responsive, and so the authors proposed that such microrobots would be able to target the highly acidic tumor microenvironment.^[12]

Another application of shape-morphing particles is cell transplantation. There have been recent examples of monolithic, rigid particles used in cell delivery.^[14,185,186] However, few examples have combined soft materials with cell transport capabilities. Peeters and colleagues used a unique hydrogel bilayer system for self-folding to encapsulate cardiomyocytes. The responsive layer was made from PNIPAm with PLA-b-PEG-b-PLA diacrylate as a crosslinker, and the stiff layer was a mixture of a triblock copolymer PLA-b-PEG-b-PLA diacrylate and PMMA. There was no cytotoxicity from these materials, and cyclic folding was successful with encapsulated cells.^[187]

The transport and manipulation of microobjects has been achieved using hydrogel devices and actuators. Shape-morphing gels can be used within microfluidic systems as pick-and-place devices for the assembly of objects into structures.^[188,189] In the next section, we discuss specific applications of shape-changing particles in the context of microfluidics. Sakar and co-workers designed and synthesized optomechanical microactuators to control micromachines and grippers. These actuators were made from gold nanorods inside of PNIPAm gels, and light-induced swelling was shown to bend and move PEGDA microstructures. The authors demonstrated the capability of this system to move and compress cellular spheroids under physiological conditions in addition to other modes of actuation (Figure 8f). Compressive stress drives cancer cells toward meta-static phenotypes, so these devices could be useful in studying cancer.^[190] Sitti and co-workers fabricated microgrippers capable of controlled motion in three dimensions. The authors used the grippers to grab and place microgel particles onto posts to assemble complex, 3D gel structures, achieving up to ten layers of gels (Figure 8g). This micromanipulation system has many possible applications in microfluidic devices, including tissue engineering and preparation of optical microdevices.^[191]

3.4. Microfluidics and Complex Emulsions

3.4.1. Microfluidics

Microfluidic devices have been researched extensively over the past few decades because of their promise in miniaturizing analytical tools for chemical and biological investigations.^[192,193] Shape-morphing components within such devices have shown utility in fluid- and micromanipulation.^[194] Although these components are typically tethered to the walls of a microvalve, shape-morphing particle-like technologies described below demonstrate the progress and potential of shape-morphing in microfluidic devices. These devices work with small volumes of fluid to decrease sample size, achieve high-throughput screening, and automate analysis. The integration of valves, pumps, and mixers into microfluidic devices promises to enhance functional capabilities. Several recent examples showed that particle technologies can improve control over microscale flow. Bhatia and co-workers showed that magnetic micropropellers can induce convection-enhanced transport of diffusion-limited, therapeutic nanoparticles.^[195] The DeMello and Nelson groups showed that magnetic microparticles can be used in a microfluidic circuit to push, steer, or otherwise manipulate droplets.^[196] Finally, the Fischer group showed that arrays of Janus micromotors tethered to a surface can generate complex, bulk flows directly above the active surface.^[197]

Inspired by the work of Beebe and West, many of these technologies rely on responsive hydrogels to direct flow through a device.^[198] Schenning and co-workers optimized the molecular structure of spiropyran-derived photoswitches for incorporation into hydrogel valves, demonstrating reversible and repeatable actuation on a timescale of minutes (Figure 9a).^[199] Light is a promising stimulus because of its potential for fast actuation compared to temperature and pH. Therefore, there is a considerable opportunity for the molecular engineering of photoswitches to be included within bulk materials for a variety of applications, including microfluidics.^[200] Tabeling and co-workers fabricated microvalves and microcages in microfluidic devices from PNIPAm gels (Figure 9b). Heating the PNIPAm microstructures caused swelling to enable capturing or blocking of fluids, providing a potentially cheaper alternative to pneumatic valves and droplet technologies. Cell capture and nucleic acid amplification were demonstrated as possible applications of these microcages. The cages could reversibly rise and lower, confining molecules and cells in small fluid volumes for faster assay times.^[15] Ionogels have also been investigated as microvalves due to their improved toughness, porosity, and mechanical stability.^[201–203]

Figure 9.

a) Schematic illustration of a molecular photoswitch as a microfluidic valve (left). Microfluidic valve polymerized in situ, opening in response to illumination from a blue LED and allowing fluid colored green to flow (right). Adapted with permission.^[199] Copyright 2015, The American Chemical Society. b) Two valves in microfluidic channels, each 400 μm wide. i,ii) Opening and closing of each valve allows different colored dyes to pass. iii) Fluorescence image of the valves switching. One valve is closing and the other opening to change composition of fluid flow. iv) Evolution of the fluid interface as valves open and close. 2Ai per w is a measure of the interface position Ai from the symmetry axis divided by half the channel width w. Adapted under the terms of the CC-BY Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0).^[15] Copyright 2018, The Authors, published by Springer Nature.

Materials fabricated containing molecular photoswitches have many advantages as microscale actuators. Optical actuation is remote, precise, and efficient. Additionally, little to no waste is generated. Finally, light-responsive materials can easily be made responsive to other stimuli. Disadvantages of such systems include a limited set of appropriate chemistries depending on application and the inability of certain wavelengths to penetrate tissues in biomedical applications. Also, the actuator must be made transparent to the optical stimulus; however, this is unlikely to be an issue in microfluidic devices.^[204]

3.4.2. Droplets and Complex Emulsions

Shape-shifting emulsions and liquid droplets have also been used in microfluidic and lab-on-a-chip applications. Droplets can release chemicals, form fluid networks, and participate in chemical communication.^[22,205,206] Additionally, droplets can be shaped with microfluidics to generate particle systems for microscale reaction networks. Gryzbowski and co-workers used dimers made from gold and lead sulfide or iron oxide nanoparticles tethered to different surfactant molecules to stabilize droplets of water and ethylene glycol in solutions of dichlorobenzene and toluene.^[73] By changing the metallic component and surfactant molecules, droplets of varying hydrophobicity and magnetic susceptibility were produced. The nanoparticle surfactants conferred light-responsivity to the droplets, which self-assembled into hexagonally close-packed structures upon illumination. Light was used to drive rotational motion and assembly, while electric fields were capable of welding droplets together into nonspherical shapes that persisted for days after removal of electric fields. The authors demonstrated that droplets carrying different chemicals could be welded together into nonspherical micro-reactors capable of being mixed using light (Figure 10a).^[73] One application of these droplets could be the fabrication of nonspherical polymer particles by adding photopolymerizable gels to the droplet mixtures. The ferromagnetic liquid droplets pioneered by Russell and co-workers showed fluid characteristics of liquids and magnetic properties of solids.^[74] These droplets acted like micromixers in response to rotating magnetic fields and separated from nonmagnetic droplets.^[74] Combining many droplets into fluid networks can enable possible applications as material templates or microreactors. Prileszky and Furst used a microfluidic device to produce droplets of petrolatum and hexadecane that could be assembled into fluid networks in a fashion similar to additive manufacturing.^[207] This method produced droplets that were more stable than those formed using glass capillaries.^[208,209] Droplet “threads”, or networks, folded on themselves like polymer chains, depending on the aspect ratio of the droplets with thermal control over porosity and shape (Figure 10b). The internal microstructures of such droplets resisted flow and stabilized nonspherical conformations. Spicer and co-workers used an extrusion-based method to produce rod-shaped droplets consisting of wax crystals (i.e., petrolatum) in hexadecane. When the droplets were heated, they collapsed from rod-like structures into spheres and other shapes like rings and swirl shapes. The wax crystals formed an endoskeleton whose structure determined intermediate morphological states during collapse (Figure 10c).^[209] One possible application of such a system is improved wetting since these particles were shown to wrap around obstacles such as bubbles and solid particles during their collapse, increasing the available interfacial surface area.

Figure 10.

a) A sequence of reactions initiated by fusing dumbbell-shaped reactors. Reactors are oriented by an external magnetic field and electrostatically welded to connect. Mixing is accomplished by laser light. Reproduced with permission.^[73] Copyright 2016, Springer Nature. b) Droplet superstructures shaped like scorpion tails (i) and flexible chains (ii) were manufactured by varying flow rate. Scale bar: 250 μm. Adapted with permission.^[207] Copyright 2016, American Chemical Society. c) Collapse of rod-shaped endoskeletal droplets is shown to depend on points of initial structural failure, resulting in various shapes. Pet/Hex refers to the petrolatum/hexadecane mixtures, of which the particles were composed. Folding and collapse were dictated by the initial particle shape. Scale bar: 200 μm. Adapted with permission.^[209] Copyright 2015, American Chemical Society. d) Reconfigurable four-phase emulsions containing hydrocarbon oil (H), silicone oil (Si), and fluorinated oil (F) in water (W). Zonyl and SDS are selective surfactants for the oil components shown, which tune the morphology of the emulsion. Scale bar: 50 μm. Reproduced with permission.^[75] Copyright 2015, Springer Nature.

Droplets containing multiple liquid compartments or “complex emulsions” have the potential to enhance storage and delivery of immiscible components within a continuous liquid phase. Such a technology has utility in cosmetics, vaccines, pesticides, and other aerosol formulations.^[207–211] Complex emulsions also provide convenient models of biological cells in which biomolecules separate into liquid phases or liquid-phase organelles.^[212] Swager and co-workers created three- and four-phase emulsions by tuning the interfacial tension and phase separation of hexane-perfluorohexane droplets in a surfactant solution (Figure 10d).^[75] The authors created double emulsions (i.e., hexane in perfluorohexane as well as the inverse) and also Janus-like morphologies. Combining this chemical system with stimuli-responsive surfactants, morphological transitions were shown to occur upon light exposure and changes to pH.^[213] Finally, the authors polymerized Janus-like droplets into nonspherical shapes with this system.

4. Outlook

We have highlighted methods for preparing shape-shifting particles at the micro to nanoscale. We have also reviewed recent applications of shape-shifting particle technologies in small-scale robotics, optical materials, biomedical devices, and microfluidics. Although progress in developing these materials for specific applications has been promising, there are a number of areas where further advancement is needed. For biomedical applications, it will be necessary for materials to be biocompatible. For drug delivery in particular, shape-induced release must be capable of reliable dosing. For delivery to tumors and other hard-to-reach locations within the body, behaviors such as interparticle communication and swarming might be necessary.^[214] Particles may have to navigate through biological barriers and up pressure gradients. This will require the programming of collective actions such as dynamic assemblies, separations, navigation, and networked systems.^[215,216] Engineering collective behaviors for practical applications remains an engineering challenge; however, we anticipate that autonomous multiparticle systems will be necessary for the development of many technologies outlined in this article. Biological cells use chemotaxis for directed motion within confined biological spaces, and such chemotactic capabilities would be useful in shape-morphing particles, though integrating such sensitivity into particles remains a challenge. As we have seen, shape-shifting capabilities can tune the valence of individual particles and change the strength of interparticle forces. Therefore, shape-dependent assembly will have an important role in engineering multiparticle systems.

Progress in these fields is relatively recent, and we anticipate that other applications not mentioned here will become prominent in the coming years. For example, self-propelling micro and nanorobots have been researched extensively for environmental monitoring and remediation.^[217–219] Although there are no examples of shape-changing particles in this context to our knowledge, advances in particle chemical and biological sensing could impact this field. Within microrobotics, much effort has been focused on self-propulsion, but these materials must also be made to interact intelligently with the environment or inside of biological organisms. This will also require advances in chemical sensing and actuation. It is conceivable that some of the shape-shifting materials described in this review could be beneficial to research in artificial cells and other chemical systems.^[220] Regarding applications related to photonics and plasmonics, shape-shifting nanostructures that incorporate plasmonic particles may be useful for designing tunable optical metamaterials.^[221,222]

Although the potential applications are numerous, there are several challenges that must be addressed before real world shape-shifting particles can be deployed. The biggest challenge is arguably scale-up and manufacturing. This remains a challenge in many areas of nanotechnology; however, particles and materials that require multiple fabrication steps or very small feature sizes significantly increase production time and costs.^[124] Challenges on the fundamental side of particle fabrication and actuation include the kinetics of shape-shifting, optimization of particle shapes, and complete reversibility. Actuation must also be made as simple and robust as possible for practical use. Many of these actuation mechanisms outlined in this review are cumbersome and involve manual steps such as changes in solvent or pH. This leaves researchers with the task of engineering materials in such a way that changes in shape happen autonomously.

Considerable progress has been made in developing soft particles that can alter their shape in response to a variety of stimuli. In the future, we expect that more progress will be made in controlling actuation kinetics, nanofabrication procedures, and sensing capabilities for materials that intelligently interact with environmental and biological systems. Shape-shifting particles will continue to offer an exciting platform for fundamental and applied research in many fields.

Biographies

Nabila Tanjeem is a postdoctoral research associate in the Department of Chemical and Biological Engineering at the University of Colorado Boulder. She received her M.S. and Ph.D. in Applied Physics from Harvard University where she studied the effect of geometric constraints on colloidal self-assembly. Her ongoing research focuses on understanding synchronization in photo-responsive active particles and engineering self-limiting assembly of curved colloidal particles.

Montana B. Minnis is a graduate student in the Department of Chemical and Biological Engineering at the University of Colorado Boulder working in the labs of Professors Wyatt Shields and Ryan Hayward where he is a National Defense Science and Engineering Graduate (NDSEG) Fellow. He received his undergraduate degree in chemical engineering at the University of Oklahoma. His research interests include colloidal self-assembly and engineering active particle systems for drug delivery.

Ryan C. Hayward is the James and Catherine Patten Professor of Chemical and Biological Engineering and Affiliated Faculty of Materials Science and Engineering at the University of Colorado Boulder. He received his Ph.D. in chemical engineering from the University of California Santa Barbara. His group studies responsive and active materials, as well as methods to define nano- and microscale structures through frustrated self-assembly.

Charles Wyatt Shields IV is an Assistant Professor in the Department of Chemical and Biological Engineering at the University of Colorado Boulder. He received his M.S. and Ph.D. in biomedical engineering from Duke University where he was a NSF Graduate Research Fellow working in the fields of soft matter physics and biorecognition. His research group is developing new field-responsive and active matter systems as vehicles for next-generation biosensing, drug delivery, and immunoengineering.