Stimuli-responsive Devices Research Articles

4D-printed shape-programmable [H+]-responsive needles for determination of urea

Four-dimensional printing (4DP) technologies are revolutionizing the fabrication, functionality, and applicability of stimuli-responsive analytical devices. More practically, 4DP technologies are effective in fabricating devices with complex geometric designs and functions, and the degree of shape programming of 4D-printed stimuli-responsive devices can be optimized to become a reliable analytical strategy. Although shape-programming modes play a critical role in determining the analytical characteristics of 4D-printed stimuli-responsive sensing devices, the effect of shape-programming modes on the analytical performance of 4D-printed stimuli-responsive devices remains an unexplored subject. We employed digital light processing three-dimensional printing (3DP) with acrylate-based photocurable resins and 2-carboxyethyl acrylate (CEA)-incorporated photocurable resins for 4DP of the bending, helixing, and twisting needles. Upon immersion in samples with pH values above the pKa of CEA, the electrostatic repulsion among the dissociated carboxyl groups of polyCEA caused swelling of the CEA-incorporated part and [H+]-dependent shape programming. When coupling with the derivatization reaction of the urease-mediated hydrolysis of urea, the decline in [H+] induced shape programming of the needles, offering reliable determination of urea based on the shape-programming angles. After optimizing the experimental conditions, the helixing needles provided the best analytical performance, with the method's detection limit of 0.9 μM. The reliability of this analytical method was validated by determining urea in samples of human urine and sweat, fetal bovine serum, and rat plasma with spike analyses and comparing these results with those obtained from a commercial assay kit. Our demonstration and analytical results suggest the importance of optimizing the shape-programming modes to improve the analytical performance of 4D-printed stimuli-responsive shape-programming sensing devices and emphasize the benefits and applicability of 4DP technologies in advancing the development and fabrication of stimuli-responsive sensing devices for chemical sensing and quantitative chemical analyses.

Non-Centrosymmetric Single Crystalline Biomolecular Nano-Arrays for Responsive Electronics.

Herein, a novel strategy is reported for synthesizing libraries of single crystalline amino acid (AA) nanocrystals with control over size, anisotropy, and polymorphism by leveraging dip-pen nanolithography (DPN) and recrystallization via solvent vapor annealing. The crystals are prepared by first depositing nanoreactors consisting of a solvent with AAs, followed by water vapor-induced recrystallization. This leads to isotropic structures that are non-centrosymmetric with strong piezoelectric (g33 coefficients >1000mVmN-1), ferroelectric, and non-linear optical properties. However, recrystallizing arrays of isotropic DL-alanine nanodot features with a binary solvent (water and ethanol) leads to arrays of 1D piezoelectric nanorods with their long axis coincident with the polar axis. Moreover, positioning nanoreactors containing AAs (the nanodot features) between micro electrodes leads to capillary formation, making the reactors anisotropic and facilitating piezoelectric nanorod formation between the electrodes. This offers a facile route to device fabrication. These as-fabricated devices respond to ultrasonic stimulation in the form of a piezoelectric response. The technique described herein is significant as it provides a rapid way of investigating non-centrosymmetric nanoscale biocrystals, potentially pivotal for fabricating a new class of stimuli-responsive devices such as sensors, energy harvesters, and stimulators.

Hybrid crystalline bioparticles with nanochannels encapsulating acemannan from Aloe vera: Structure and interaction with lipid membranes

Smart nanocarrier-based bioactive delivery systems are a current focus in nanomedicine for allowing and boosting diverse disease treatments. In this context, the design of hybrid lipid-polymer particles can provide structure-sensitive features for tailored, triggered, and stimuli-responsive devices. In this work, we introduce hybrid cubosomes that have been surface-modified with a complex of chitosan-N-arginine and alginate, making them pH-responsive. We achieved high-efficiency encapsulation of acemannan, a bioactive polysaccharide from Aloe vera, within the nanochannels of the bioparticle crystalline structure and demonstrated its controlled release under pH conditions mimicking the gastric and intestinal environments. Furthermore, an acemannan-induced phase transition from Im3m cubic symmetry to inverse hexagonal HII phase enhances the bioactive delivery by compressing the lattice spacing of the cubosome water nanochannels, facilitating the expulsion of the encapsulated solution. We also explored the bioparticle interaction with membranes of varying curvatures, revealing thermodynamically driven affinity towards high-curvature lipid membranes and inducing morphological transformations in giant unilamellar vesicles. These findings underscore the potential of these structure-responsive, membrane-active smart bioparticles for applications such as pH-triggered drug delivery platforms for the gastrointestinal tract, and as modulators and promoters of cellular internalization.

4D-Printed Elution-Peak-Guided Dual-Responsive Monolithic Packing for the Solid-Phase Extraction of Metal Ions.

Four-dimensional printing (4DP) technologies are revolutionizing the fabrication of stimuli-responsive devices. To advance the analytical performance of conventional solid-phase extraction (SPE) devices using 4DP technology, in this study, we employed N-isopropylacrylamide (NIPAM)-incorporated photocurable resins and digital light processing three-dimensional printing to fabricate an SPE column with a [H+]/temperature dual-responsive monolithic packing stacked as interlacing cuboids to extract Mn, Co, Ni, Cu, Zn, Cd, and Pb ions. When these metal ions were eluted using 0.5% HNO3 solution as the eluent at a temperature below the lower critical solution temperature of polyNIPAM, the monolithic packing swelled owing to its hydrophilic/hydrophobic transition and electrostatic repulsion among the protonated units of polyNIPAM. These effects resulted in smaller interstitial volumes among these interlacing cuboids and improvements in the elution peak profiles of the metal ions, which, in turn, demonstrated the reduced method detection limits (MDLs; range, 0.2-7.2 ng L-1) during analysis using inductively coupled plasma mass spectrometry. We studied the effects of optimizing the elution peak profiles of the metal ions on the analytical performance of this method and validated its reliability and applicability by analyzing the metal ions in reference materials (CASS-4, SLRS-5, 1643f, and Seronorm Trace Elements Urine L-2) and performing spike analyses of seawater, groundwater, river water, and human urine samples. Our results suggest that this 4D-printed elution-peak-guided dual-responsive monolithic packing enables lower MDLs when packed in an SPE column to facilitate the analyses of the metal ions in complex real samples.

Urea-Functionalized Heterocycles: Structure, Hydrogen Bonding and Applications

Ureido-heterocycles exhibiting different triple- and quadruple H-bonding patterns are useful building blocks in the construction of supramolecular polymers, self-healing materials, stimuli-responsive devices, catalysts and sensors. The heterocyclic group may provide hydrogen bond donor/acceptor sites to supplement those in the urea core, and they can also bind metals and can be modified by pH, redox reactions or irradiation. In the present review, the main structural features of these derivatives are discussed, including the effect of tautomerization and conformational isomerism on self-assembly and complex formation. Some examples of their use as building blocks in different molecular architectures and supramolecular polymers, with special emphasis on biomedical applications, are presented. The role of the heterocyclic functionality in catalytic and sensory applications is also outlined.

Colorimetric photosensing of solvent polarity using photochromic spironaphthoxazine dye and its stimuli-responsive acrylic copolymer: A physico-chemical study

Stimuli-responsive devices containing photoswitchable compounds have received a great deal of attention for constructing portable opto-chemical sensors in detection of solvent polarities. Here, photochromic and solvatochromic behavior of the synthesized spironaphtooxazine (SNO) and its acrylic copolymer (PCSN-3) in various protic and aprotic solvents were investigated experimentally and theoretically; and the results were exploited to fabricate a portable probe for colorimetric and spectroscopic detection of solvent polarity. The incorporation of SNO-based comonomer into the poly(methyl methacrylate) chains was approved by observing its functional groups in FTIR spectra and the efficiency of chemical incorporation was evaluated as 98.2% using 1HNMR analysis. DLS and SEM analyses demonstrated particles sizes of below 100 nm with spherical morphology and narrow size distributions. DFT calculation was used to predict plausible meronaphtooxazine (MNO) conformations and they were compared with the experimental results. UV–vis analyses showed that the maximum absorption intensity of MNO increased up to 20 folds in protic and aprotic solvents at −20 °C compared to those at room temperature. Hansen solubility parameter and solute-solvent interaction for SNO, MNO and PCSN-3 in different protic and aprotic solvents were measured by group contribution method for the first time. It was found that hydrogen bonding and solvent polarity are the determining parameters for solvatochromic behavior of SNO in protic solvents, while dispersibility parameter is dominant in aprotic solvents. Photochromism and solvatochromism of PCSN-3 film in aprotic solvents were studied similar to SNO. Interestingly, PCSN-3 film showed definite visual color change and spectroscopic feature for each solvent after UV irradiation at 365 nm, which establishes a promising solid-state portable probe for colorimetric photosensing of solvents polarity.

4D-printed needle panel meters coupled with enzymatic derivatization for reading urea and glucose concentrations in biological samples

On-site analytical techniques continue being developed with advances in modern technology. To demonstrate the applicability of four-dimensional printing (4DP) technologies in the direct fabrication of stimuli-responsive analytical devices for on-site determination of urea and glucose, we used digital light processing three-dimensional printing (3DP) and 2-carboxyethyl acrylate (CEA)–incorporated photocurable resins to fabricate all-in-one needle panel meters. When adding a sample having a value of pH above the pKa of CEA (ca. 4.6–5.0) into the fabricated needle panel meter, the [H+]-responsive layer of the needle, printed using the CEA-incorporated photocurable resins, swelled as a result of electrostatic repulsion among the dissociated carboxyl groups of the copolymer, leading to [H+]-dependent bending of the needle. When coupled with a derivatization reaction (urease-mediated hydrolysis of urea to decrease [H+]; glucose oxidase-mediated oxidization of glucose to increase [H+]), the bending of the needle allowed reliable quantification of urea or glucose when referencing pre-calibrated concentration scales. After method optimization, the method's detection limits for urea and glucose were 4.9 and 7.0 μM, respectively, within a working concentration range from 0.1 to 10 mM. We verified the reliability of this analytical method by determining the concentrations of urea and glucose in samples of human urine, fetal bovine serum, and rat plasma with spike analyses and comparing the results with those obtained using commercial assay kits. Our results confirm that 4DP technologies can allow the direct fabrication of stimuli-responsive devices for quantitative chemical analysis, and that they can advance the development and applicability of 3DP-enabling analytical methods.

Dehydration-Triggered Afterglow Transition in a Mellitate-Based Coordination Polymer

Stimulus-responsive long persistent luminescence (LPL) materials have attracted wide attention due to their potential applications in information storage, anti-counterfeiting, optoelectronic devices, etc. However, LPL coordination polymers with room temperature afterglow transition characteristics have not been explored. Herein, mellitic acid and zinc ions were utilized to synthesize an acid–base stable coordination polymer (1) by an organic solvent-free hydrothermal method. 1 possesses a tightly stacked structure and exhibits dual-emission peaks with blue luminescence and blue-green afterglow. Upon exposure to heating, DMSO immersion, or vacuum, 1h, 1s, and 1v were obtained. The original blue luminescence changes to blue-green, while the afterglow turns yellow-green due to the loss of water molecules from the inner cavity. This is the first example of an LPL coordination polymer that can realize room temperature afterglow transition by dehydration operation. Moreover, the emission spectra of 1 can be recovered by exposing 1h, 1s, or 1v to water vapor, suggesting a reversible dehydration/hydration process. Experimental and density functional theory (DFT) results suggest that the fluorescence of 1 originates from the mixing of intra-ligand and ligand-to-metal charge transfer excited states. The triplet state from intersystem crossing is responsible for the long persistent luminescence of phosphorescence emission. The rational structural design along with the conceptual model of anti-counterfeiting and information encryption based on afterglow transition display the unique advantages of the LPL coordination polymer in realizing convenient multiple stimuli-responsive devices.

Smart Drug-Delivery System of Upconversion Nanoparticles Coated with Mesoporous Silica for Controlled Release.

Drug-delivery vehicles have garnered immense interest in recent years due to unparalleled progress made in material science and nanomedicine. However, the development of stimuli-responsive devices with controllable drug-release systems (DRSs) is still in its nascent stage. In this paper, we designed a two-way controlled drug-release system that can be promoted and prolonged, using the external stimulation of near-infrared light (NIR) and protein coating. A hierarchical nanostructure was fabricated using upconversion nanoparticles (UCNPs)-mesoporous silica as the core-shell structure with protein lysozyme coating. The mesoporous silica shell provides abundant pores for the loading of drug molecules and a specific type of photosensitive molecules. The morphology and the physical properties of the nanostructures were thoroughly characterized. The results exhibited the uniform core-shell nanostructures of ~four UCNPs encapsulated in one mesoporous silica nanoparticle. The core-shell nanoparticles were in the spherical shape with an average size of 200 nm, average surface area of 446.54 m2/g, and pore size of 4.6 nm. Using doxorubicin (DOX), a chemotherapy agent as the drug model, we demonstrated that a novel DRS with capacity of smart modulation to promote or inhibit the drug release under NIR light and protein coating, respectively. Further, we demonstrated the therapeutic effect of the designed DRSs using breast cancer cells. The reported novel controlled DRS with dual functionality could have a promising potential for chemotherapy treatment of solid cancers.

Direct Ink Writing of Recyclable Supramolecular Soft Actuators.

Direct ink writing (DIW) of liquid crystal elastomers (LCEs) has rapidly paved its way into the field of soft actuators and other stimuli-responsive devices. However, currently used LCE systems for DIW require postprinting (photo)polymerization, thereby forming a covalent network, making the process time-consuming and the material nonrecyclable. In this work, a DIW approach is developed for printing a supramolecular poly(thio)urethane LCE to overcome these drawbacks of permanent cross-linking. The thermo-reversible nature of the supramolecular cross-links enables the interplay between melt-processable behavior required for extrusion and formation of the network to fix the alignment. After printing, the actuators demonstrated a reversible contraction of 12.7% or bending and curling motions when printed on a passive substrate. The thermoplastic ink enables recyclability, as shown by cutting and printing the actuators five times. However, the actuation performance diminishes. This work highlights the potential of supramolecular LCE inks for DIW soft circular actuators and other devices.

Nanocellulose in wearable sensors

Nanocellulose possesses an advantageous portfolio of properties required in wearable technologies, including deformability, printability, high mechanical resistance, lightweight nature, sustainability and the capability to be modified with electrical or optical properties in order to achieve stimuli responsive devices. Herein, an overview of inspiring examples of wearable sensors based on nanocellulose is offered. Innovative wearables that are relevant to healthcare are highlighted by covering different applications such as real-time body monitoring (ex. strain, pressure), biosignals detection (ex. sweat components), as well as environmental and external signals (ex. UV exposure). In all of them, the nanocellulose potential and benefits are critically discussed. In fact, nanocellulose represents an excellent choice for the development of green, small, comfortable and subtle wearable devices operating in different fields with a steadily growing social acceptance. Nevertheless, there is still a long way to go for the discussed wearables to meet the expectations of completely smart and connected healthcare devices envisioned by the healthcare 4.0 paradigm, which is also underscored.

Atropisomeric Conjugated Diimides: A Class of Thermally Responsive Organic Semiconductors

Atropisomerism has been studied in many research fields; however, it is rarely studied in organic semiconductors. In this work, we report a series of room-temperature-stable atropisomeric conjugated diimides, Syn-NDI and Anti-NDI based on 1,4,5,8-naphthalenetetracarboxylic diimides (NDIs) as well as Syn-PDI and Anti-PDI based on 3,4:9,10-perylenetetracarboxylic diimides (PDIs). For these two pairs of atropisomers, the Syn and Anti conformers can be interconverted when they are in heated solution, whereas in the solid state, only the Syn conformers can converted to Anti conformers when thermally annealed. This feature can be applied to realize thermally responsive organic field-effect transistors (OFETs). Remarkably, when thermally annealed at a certain temperature, the Syn atropisomers can be fast converted to their respective Anti ones, and OFETs originally based on the Syn semiconductors show a dramatic improvement in electron mobility. For OFETs originally based on Syn-NDI, a 100-fold improvement in electron mobility is recorded when Syn-NDI was converted to Anti-NDI, while for OFETs originally based on Syn-PDI, a 5000-fold improvement in electron mobility is recorded when Syn-PDI was converted to Anti-PDI. In contrast, thermal annealing is found to have a negligible effect for OFETs based on Anti semiconductors, with the electron mobility on the same order of magnitude for all Anti semiconductor devices. This is the first time that the atropisomerism has been exploited in organic semiconductors, demonstrating great potential for stimuli-responsive devices.

Beyond Color: The New Carbon Ink.

For thousands of years, carbon ink has been used as a black color pigment for writing and painting purposes. However, recent discoveries of nanocarbon materials, including fullerenes, carbon nanotubes, graphene, and their various derivative forms, together with the advances in large-scale synthesis, are enabling a whole new generation of carbon inks that can serve as an intrinsically programmable materials platform for developing advanced functionalities far beyond color. The marriage between these multifunctional nanocarbon inks with modern printing technologies is facilitating and even transforming many applications, including flexible electronics, wearable and implantable sensors, actuators, and autonomous robotics. This review examines recent progress in the reborn field of carbon inks, highlighting their programmability and multifunctionality for applications in flexible electronics and stimuli-responsive devices. Current challenges and opportunities will also be discussed from a materials science perspective towards the advancement of carbon ink for new applications beyond color.

Self-assembled peptide and protein nanostructures for anti-cancer therapy: Targeted delivery, stimuli-responsive devices and immunotherapy.

Self-assembled peptides and proteins possess tremendous potential as targeted drug delivery systems and key applications of these well-defined nanostructures reside in anti-cancer therapy. Peptides and proteins can self-assemble into nanostructures of diverse sizes and shapes in response to changing environmental conditions such as pH, temperature, ionic strength, as well as host and guest molecular interactions; their countless benefits include good biocompatibility and high loading capacity for hydrophobic and hydrophilic drugs. These self-assembled nanomaterials can be adorned with functional moieties to specifically target tumor cells. Stimuli-responsive features can also be incorporated with respect to the tumor microenvironment. This review sheds light on the growing interest in self-assembled peptides and proteins and their burgeoning applications in cancer treatment and immunotherapy.

Cooperatively assembled liquid crystals enable temperature-controlled Förster resonance energy transfer.

Balancing the rigidity of a π-conjugated structure for strong emission and the flexibility of liquid crystals for self-assembly is the key to realizing highly emissive liquid crystals (HELCs). Here we show that (1) integrating organization-induced emission into dual molecular cooperatively-assembled liquid crystals, (2) amplifying mesogens, and (3) elongating the spacer linking the emitter and the mesogen create advanced materials with desired thermal–optical properties. Impressively, assembling the fluorescent acceptor Nile red into its host donor designed according to the aforementioned strategies results in a temperature-controlled Förster resonance energy transfer (FRET) system. Indeed, FRET exhibits strong S-curve dependence as temperature sweeps through the liquid crystal phase transformation. Such thermochromic materials, suitable for dynamic thermo-optical sensing and modulation, are anticipated to unlock new and smart approaches for controlling and directing light in stimuli-responsive devices.

Synthesis and Fluorescent Thermoresponsive Properties of Tetraphenylethylene-Labeled Methylcellulose.

Functional polymer, especially the one based on renewable and sustainable materials, has attracted increasing attention to satisfy the growing demand for the design of stimuli-responsive devices. Methylcellulose (MC) is a water-soluble derivative of cellulose, which has been widely used in many fields for its biocompatibility and biological inertness. In this work, MC is labeled by tetraphenylethylene (TPE) via azide-alkyne click reaction to obtain a fluorescent cellulose-based derivative of MC-TPE. The degree of substitution of MC-TPE is determined to be 0.074, which can be self-assembled into micelles in water with the size of 42±6nm. MC-TPE shows thermoresponsivity and thermoreversibility in size, transmittance, and fluorescence, enabling it to work as a fluorescent thermosensor. Moreover, MC-TPE exhibits nontoxicity and biocompatibility, allowing its application in MCF-7 cell imaging. Therefore, this newly functional natural polymer shows promising potentials in the fields of sensing and bioimaging.

DLP 3D Printed “Intelligent” Microneedle Array (iμNA) for Stimuli Responsive Release of Drugs and Its in Vitro and ex Vivo Characterization

We demonstrate a new fabrication technology to realize “intelligent”, transdermal, minimally invasive microneedle array ( i $\mu $ NA) by crosslinking a hydrogel, Polyethylene Glycol Diacrylate (PEGDA) by photo-polymerization using Digital Light Processing (DLP) based 3D printing. The photo-polymerization conditions have been optimized so that the mutually exclusive requirements of excellent mechanical strength while retaining hydrogel properties of PEGDA are met which would allow swelling/delivery of therapeutic cargo of diclofenac sodium via diffusion. An array having 100 microneedles arranged in a $10\times 10$ array was successfully 3D printed which efficiently penetrated human skin during ex vivo characterization. In vitro drug release studies demonstrated that the PEGDA based i $\mu $ NA behaves as a stimuli responsive device showing distinct release characteristics from external stimuli such as temperature and pH. [2020-0133]

Dielectric Response Triggered by a Non-ferroelectric Phase Transition in Poly(Vinylidene Fluoride)/Poly(Ethylene Glycol)/Halloysite Composites

Thermoresponsive dielectric materials have attracted the interest of researchers as they exhibit very important application prospects in stimuli-responsive smart devices. In this contribution polyethylene glycol (PEG), impregnated in halloysite nanotubes (HNTs), was incorporated into poly(vinylidene fluoride) (PVDF) for tailoring the thermoresponsive dielectric properties based on a non-ferroelectric phase transition. The PVDF/PEG/HNTs displayed a remarkable rise of dielectric constant between 20 and 30 °C. The mechanism is related to the enhanced orientational polarization effect triggered by the solid–liquid phase transition of the PEG. This make it possible to design stimuli-responsive smart materials through a simple, low-cost and efficient strategy. The present work provides an alternative and innovative routine for tailoring thermal-induced dielectric behaviors via a non-ferroelectric phase transition by introducing PEG into a high-dielectric-constant polymer matrix.

Recent avenues in Novel Patient-Friendly Techniques for the Treatment of Diabetes.

Diabetes is one of the most common chronic metabolic disorders which affect the quality of human life worldwide. As per the WHO report, between 1980 to 2014, the number of diabetes patients increases from 108 million to 422 million, with a global prevalence rate of 8.5% per year. Diabetes is the prime reason behind various other diseases like kidney failure, stroke, heart disorders, glaucoma, etc. It is recognized as the seventh leading cause of death throughout the world. The available therapies are painful (insulin injections) and inconvenient due to higher dosing frequency. Thus, to find out a promising and convenient treatment, extensive investigations are carried out globally by combining novel carrier system (like microparticle, microneedle, nanocarrier, microbeads etc.) and delivery devices (insulin pump, stimuli-responsive device, inhalation system, bioadhesive patch, insulin pen etc.) for more precise diagnosis and painless or less invasive treatment of disease. The review article is made with an objective to compile information about various upcoming and existing modern technologies developed to provide greater patient compliance and reduce the undesirable side effect of the drug. These devices evade the necessity of daily insulin injection and offer a rapid onset of action, which sustained for a prolonged duration of time to achieve a better therapeutic effect. Despite numerous advantages, various commercialized approaches, like Afrezza (inhalation insulin) have been a failure in recent years. Such results call for more potential work to develop a promising system. The novel approaches range from the delivery of non-insulin blood glucose lowering agents to insulin-based therapy with minimal invasion are highly desirable.

Electrospinning Piezoelectric Fibers for Biocompatible Devices.

The field of nanotechnology has been gaining great success due to its potential in developing new generations of nanoscale materials with unprecedented properties and enhanced biological responses. This is particularly exciting using nanofibers, as their mechanical and topographic characteristics can approach those found in naturally occurring biological materials. Electrospinning is a key technique to manufacture ultrafine fibers and fiber meshes with multifunctional features, such as piezoelectricity, to be available on a smaller length scale, thus comparable to subcellular scale, which makes their use increasingly appealing for biomedical applications. These include biocompatible fiber-based devices as smart scaffolds, biosensors, energy harvesters, and nanogenerators for the human body. This paper provides a comprehensive review of current studies focused on the fabrication of ultrafine polymeric and ceramic piezoelectric fibers specifically designed for, or with the potential to be translated toward, biomedical applications. It provides an applicative and technical overview of the biocompatible piezoelectric fibers, with actual and potential applications, an understanding of the electrospinning process, and the properties of nanostructured fibrous materials, including the available modeling approaches. Ultimately, this review aims at enabling a future vision on the impact of these nanomaterials as stimuli-responsive devices in the human body.