Programmable Design Research Articles

Progressive cancer targeting by programmable aptamer-tethered nanostructures.

Scientific research in recent decades has affirmed an increase in cancer incidence as a cause of death globally. Cancer can be considered a plurality of various diseases rather than a single disease, which can be a multifaceted problem. Hence, cancer therapy techniques acquired more accelerated and urgent approvals compared to other therapeutic approaches. Radiotherapy, chemotherapy, immunotherapy, and surgery have been widely adopted as routine cancer treatment strategies to suppress disease progression and metastasis. These therapeutic approaches have lengthened the longevity of countless cancer patients. Nonetheless, some inherent limitations have restricted their application, including insignificant therapeutic efficacy, toxicity, negligible targeting, non-specific distribution, and multidrug resistance. The development of therapeutic oligomer nanoconstructs with the advantages of chemical solid-phase synthesis, programmable design, and precise adjustment is crucial for advancing smart targeted drug nanocarriers. This review focuses on the significance of the different aptamer-assembled nanoconstructs as multifunctional nucleic acid oligomeric nanoskeletons in efficient drug delivery. We discuss recent advancements in the design and utilization of aptamer-tethered nanostructures to enhance the efficacy of cancer treatment. Valuably, this comprehensive review highlights self-assembled aptamers as the exceptionally intelligent nano-biomaterials for targeted drug delivery based on their superior stability, high specificity, excellent recoverability, inherent biocompatibility, and versatile functions.

Microscopic Origins of Flow Activation Energy in Biomolecular Condensates.

Material properties of biomolecular condensates dictate their form and function, influencing the diffusion of regulatory molecules and the dynamics of biochemical reactions. The increasing quality and quantity of microrheology experiments on biomolecular condensates necessitate a deeper understanding of the molecular grammar that encodes their material properties. Recent reports have identified a characteristic timescale related to network relaxation dynamics in condensates, which governs their temperature-dependent viscoelastic properties. This timescale is intimately connected to an activated process involving the dissociation of sticker regions, with the energetic barrier referred to as flow activation energy. The microscopic origin of activation energy is a complex function of sequence patterns, component stoichiometry, and external conditions. This study elucidates the microscopic origins of flow activation energy in single and multicomponent condensates composed of model peptide sequences with varying sticker and spacer motifs, with RNA as a secondary component. We dissected the effects of condensate density, RNA stoichiometry, and peptide sequence patterning using extensive sequence-resolved coarse-grained simulations. We found that flow activation energy is closely linked to the lifetime of sticker-sticker pairs under certain conditions, though the presence of multiple competing stickers further complicates this relationship. The insights gained in this study should help establish predictive multiscale models for the material properties and serve as a valuable guide for the programmable design of condensates.

Deep learning of buckling instability in geometrically symmetry-breaking kirigami

Kirigami, subjected to escalating strain, frequently exhibits pronounced instability, coupled with remarkable flexibility and extraordinary extensibility. This behavior holds significant relevance for domains associated with malleable and reconfigurable surfaces, including stretchable electronics and modifiable functional devices. Nonetheless, conventional design methodologies, anchored in geometric symmetry and governed by minimum energy principles, tend to manifest buckling instabilities restricted to symmetric and anti-symmetric modes. To scrutinize the mechanisms of buckling behavior that disrupt geometric symmetry and comprehend the influence of geometry on programmability during reconfiguration, we propose an innovative strategy for kirigami’s design. This strategy capitalizes on advanced deep learning methodologies, employing convolutional neural networks (CNNs) for categorizing buckling modes and recurrent neural networks (RNNs) for prognosticating constitutive relationships. Our approach furnishes a programmable design solution adept at identifying optimal kirigami patterns, characterized by their superior tensile strength and distinct buckling conformations, thereby fulfilling a diverse array of functional necessities. Our results illustrate that the proposed method displays a high level of precision in distinguishing between buckling modes of geometric symmetry and patterns that deviate from such symmetry. The buckling mode space has been extended and rediscovered, allowing unique modes to have the potential to be adopted into functional devices. Additionally, it demonstrates minimal losses in predicting constitutive relationships. Intriguingly, we discovered that tensile responses are geometry-centric and adjustable. Buckling modes showcase a dependency on geometry, with certain geometric parameters either significantly augmenting the sensitivity of buckling modalities or causing the buckling instability modes to become apathetic and unresponsive. Guided by the principle of target-led pattern parameter design, we proffer prospective tactics for the design of kirigami capable of delivering the desired mechanical performance. Moreover, we explore the feasibility of employing alternative biological materials in these designs.

Wirelessly detecting of spatiotemporal mechanical stimuli by a bio-inspired neural sensor via temperature signals

Traditional artificial sensory systems, inspired by biological sensory nervous systems, require the integration of distributed units and wired connections to realize the perception of external mechanical stimuli, which brings disadvantages such as complex connections, complicated structures, and interference between signals. Herein, we propose a bio-inspired artificial neural sensor with a highlighted ability of wirelessly detecting spatiotemporal mechanical stimuli, which is fabricated by carbon nanotube and polymer composites. Because the resistance of the sensor varies in respond to external mechanical stimuli, the consequential temperature changes caused by Joule heating effect can be wirelessly detected, realizing the recognition of different mechanical stimuli and multi-positional sensing. The great durability (>1400 cycles) allow the sensor to withstand long-lasting mechanical stimuli. In addition, the artificial neural sensor enables programmable design in device shapes and functions, and it needs no energy consumption without stimulus. We demonstrate a series of touch-interaction applications based on the neural sensor, such as human–computer interaction, encrypted information transmission, and remote control. We hope that this artificial neural sensor will facilitate the development of complex bionic sensing systems, virtual reality, and metaverse.

Tuning quantum dots emission on DNA tetrahedron/silica nanosphere/graphene oxide nanointerface for ratiometric fluorescence assay of Pb2+ in multiplex samples

BackgroundAssembling framework nucleic acid (FNA) nanoarchitectures and tuning luminescent quantum dots (QDs) for fluorescence assays represent a versatile strategy in analytical territory. Rationally, FNA constructs could offer a preferential orientation to efficiently recognize the target and improve detection sensitivity, meanwhile, regulating size-dependent multicolor emissions of QDs in one analytical setting for ratiometric fluorescence assay would greatly simplify operation procedures. Nonetheless, such FNA/QDs-based ratiometric fluorescence nanoprobes remain rarely explored. ResultsWe designed a sensitive and signal amplification-free fluorescence aptasensor for lead ions (Pb2+) that potentially cause extensive contamination to environment, cosmetic, food and pharmaceuticals. Red and green emission CdTe quantum dots (rQDs and gQDs) were facilely prepared. Moreover, silica nanosphere encapsulating rQDs served as quantitative internal reference and scaffold to anchor a predesigned FNA and DNA sandwich containing Pb2+ binding aptamer and gQD modified DNA signal reporter. On binding of Pb2+, the gQD-DNA signal reporter was set free, resulting in fluorescence quenching at graphene oxide (GO) interface. Owing to the rigid structure of FNA, the fluorescence signal reporter orderly arranged at the silica nanosphere could sensitively respond to Pb2+ stimulation. The dose-dependent fluorescence signal-off mode enabled ratiometric analysis of Pb2+ without cumbersome signal amplification. Linear relationship was established between fluorescence intensity ratio (I555/I720) and Pb2+ concentration from 10 nM to 2 μM, with detection limit of 1.7 nM (0.43 ppb), well addressing the need for Pb2+ routine monitoring. The designed nanoprobe was applied to detection of Pb2+ in soil, cosmetic, milk, drug, and serum samples, with the sensitivity comparable to conventional ICP-MS technique. SignificanceGiven the programmable design of FNA and efficient recognition of target, flexible tuning of QDs emission, and signal amplification-free strategy, the present fluorescence nanoprobe could be a technical criterion for other heavy metal ions detection in a straightforward manner.

A facile and on-demand optimizing strategy for polyurethane elastomers via programmable hydrogen bonding

Polyurethane elastomers address important significance in a wide range of applications. The mechanical properties including strength and toughness are of great importance, which are closely related to their unique hydrogen bonding structure. Unfortunately, the poor designability of hydrogen bonding structure in existing polyurethane severely restricts the on-demand regulation of their properties. Herein, a facile, universal and efficient modifying strategy based on stimuli-responsive polyphenol aggregates was proposed. Through precisely manipulated heat-induced aggregate division and/or photo-induced interfacial hydrogen bonding upgrading, programmable strengthening and toughening effect on the derived polyurethane elastomers could be achieved with high precision. Typically, the tensile strength and toughness of our proposed polyurethane elastomers could be enhanced by 3.23 and 2.22 times comparing with neat samples, respectively. The relevant results were supported by various characterizations and mathematical modeling. In addition, our polyurethane exhibited unique selective biocompatibility, rapid self-healing capability and recyclability, which could fulfill varieties of functions. Our proposed modifying strategy by using polyphenol aggregates can not only programmatically optimize the comprehensive properties of polyurethane, but also inspire programmable regulation of polymer performance through programmable design of its certain microstructure in the future.

Blockchain empowerment: Investigating integration with software-defined networks and its impact on IoT privacy

The swift expansion of Internet of Things (IoT) devices has brought forth exceptional prospects for automation and data-driven decisions. Software-Defined Networking (SDN) is an instance of network architecture that divides network devices into a control plane and a data plane. SDN provides a dynamic and adaptable method of managing the growing complexity of IoT devices with its programmable design and centralized control. A network's capacity to handle an increasing number of IoT devices is facilitated by SDN's improved scalability. Custom network policies and services that are suited to the distinctive requirements of various IoT applications it can be established because of SDN's programmability. SDN and blockchain integration can improve network transaction and configuration security. Here, blockchain technology is decentralized. There is not just one point of failure, which lowers the possibility of malicious attacks and illegal access. The study demonstrates that IoT environments can be enhanced more efficiently, transparently and safely by integrating blockchain technology with SDN. A summary of SDN is presented and then block-chain technologies are examined with a focus on consensus protocols. After that, it explores the difficulties of implementing blockchain-based SDN into practice, concentrating on security issues. Furthermore, this study explores the mutual effects of IoT and blockchain, emphasizing the complementary relationship between the two developing technologies. This review highlights that block-chain as well as SDNs could work together to strengthen IoT privacy and establish a more robust digital future.

Femtosecond Laser Microfabrication of Artificial Compound Eyes

Over millions of years of evolution, arthropods have intricately developed and fine-tuned their highly sophisticated compound eye visual systems, serving as a valuable source of inspiration for human emulation and tracking. Femtosecond laser processing technology has attracted attention for its excellent precision, programmable design capabilities, and advanced three-dimensional processing characteristics, especially in the production of artificial bionic compound eye structures, showing unparalleled advantages. This comprehensive review initiates with a succinct introduction to the operational principles of biological compound eyes, providing essential context for the design of biomimetic counterparts. It subsequently offers a concise overview of crucial manufacturing methods for biomimetic compound eye structures. In addition, the application of femtosecond laser technology in the production of biomimetic compound eyes is also briefly introduced. The review concludes by highlighting the current challenges and presenting a forward-looking perspective on the future of this evolving field.

Bilayer Gradient Hydrogel with Topological Crosslinking for High‐Sensitivity Tactile Perception and Information Encryption

AbstractHuman fingers possess stable high sensitivity and a wide range of tactile perception, attributed to the gradient microstructure and the interlocking collagen fiber on the skin's surface. However, challenges persist in achieving simultaneous enhancement of multiple functionalities in artificial skin. Inspired by the unique structure of the skin, a two‐step process involving ion diffusion‐induced and strong‐weak topological crosslinking is synergistically employed to fabricate a bilayer gradient hydrogel. Zn2+ initially diffuses to induce the formation of weak bonds, imparting elasticity. Subsequently, Fe3+/Zn2+ diffusion constructs a strong‐weak topologically crosslinked network, enhancing the toughness of the gel while reducing the brittleness associated with robust bonds. Due to its distinctive design, the gel employs an adaptive energy dissipation strategy subjected to large and small stress, ensuring high sensitivity (3.31 kPa−1, 0–2 kPa), wide sensing range (0.4–40.6 kPa), and exceptional stability (500 cycles). This flexible approach enables programmable design in three dimensions, including ion diffusion type, direction, and shape. This gel can detect the gentle brushing of feathers and human body movements. It utilizes significant differences generated by magnitudes of stress to perform binary information encryption. This study introduces a novel strategy for preparing skin‐like gels, offering promising potential for expanding their applications in complex scenarios.

Spacer-Programmed Two-Dimensional DNA Origami Assembly.

Two-dimensional (2D) DNA origami assembly represents a powerful approach to the programmable design and construction of advanced 2D materials. Within the context of hybridization-mediated 2D DNA origami assembly, DNA spacers play a pivotal role as essential connectors between sticky-end regions and DNA origami units. Here, we demonstrated that programming the spacer length, which determines the binding radius of DNA origami units, could effectively tune sticky-end hybridization reactions to produce distinct 2D DNA origami arrays. Using DNA-PAINT super-resolution imaging, we unveiled the significant impact of spacer length on the hybridization efficiency of sticky ends for assembling square DNA origami (SDO) units. We also found that the assembly efficiency and pattern diversity of 2D DNA origami assemblies were critically dependent on the spacer length. Remarkably, we realized a near-unity yield of ∼98% for the assembly of SDO trimers and tetramers via this spacer-programmed strategy. At last, we revealed that spacer lengths and thermodynamic fluctuations of SDO are positively correlated, using molecular dynamics simulations. Our study thus paves the way for the precision assembly of DNA nanostructures toward higher complexity.

Multistable States and Snap-Through Instabilities in an Interconnected Dielectric Elastomer Actuators System

Abstract Snap-through instabilities in single and interconnected dielectric elastomer actuators have demonstrated their potential in enabling many functionalities such as large deformation, high-speed actuation, and enhanced flowrates in fluid pumps. However, the nonlinear nature of dielectric elastomers and the complex interplay of mechanics in interconnected inflated actuators, make the modeling of such systems challenging. In this paper, we present a methodology to analytically model the instabilities in a system of three interconnected homogeneous spherical dielectric elastomer actuators through graphical and numerical approaches. The simulation results reveal the presence of a locus of initial stable states that the interconnected actuators can achieve at zero voltage. In specific loading conditions, the system exhibits multiple stable states which can be cyclically transitioned between by selectively applying voltage to specific actuators. In other conditions, the system may undergo two successive instabilities when the voltage applied to a single actuator in the system is increased monotonically. These results retrieve existing experimental results theoretically for the first time and identify a new behavior of cascading instabilities in inflated dielectric elastomer actuators. We hope this work will pave the way for programmable design of multistable systems to unravel new capabilities in dielectric elastomer actuators and soft robotics.

Controlled Self-Assembly of Natural Polyphenols Driven by Multiple Molecular Interactions.

Nature has exhibited a high degree of control over the structures and functions. Supramolecules have been utilized to mimic the subtle assembly in nature. However, sophisticated synthesis of molecular skeletons or programmable design of the driving forces raises great challenges in fabricating high-level superstructures in a controlled manner. Natural polyphenols show great promises as building blocks for a diverse of assemblies with controlled structures and functionalities. The intrinsically embedded phenolic groups (i. e., catechol and galloyl groups) are readily forming multiple molecular interactions, including coordination, hydrogen bonding, and π-π interactions with various materials of inorganic particles, organic compounds, synthetic polymers, and biomacromolecules, providing the self-assembled structures or nanocoating on surfaces. Subsequent assembly occurred by further bonding of polyphenols to construct supraparticles. To gain control over the self-assembly, the key lies in the interplay among the molecular interactions with one or two being dominant. In this Perspective, we introduce the representative polyphenol-based assemblies and their derived supraparticles to exhibit the effective harness of the controlled self-assembly by polyphenols.

An improved re-entrant honeycomb with programmable densification and multistage energy-absorbing performance

Recently, auxetic metamaterials have turned into an area of growing interest, because of their deformation uniqueness, design flexibility, and functional diversity. To achieve their programmable design of densification and energy absorption, the variable stiffness factor method (VSF) emerged. However, the energy absorption capacity of the metamaterials designed by this method has a significant reduction. In this work, to remedy this defect, several different lightweight specimens are proposed and fabricated to extend the stage of energy absorption and retain the tunability. Then quasi-static compression tests and finite element methods are carried out to analyze the mechanical properties of the designed boundary-constrained structure (BCS) and X-shape constrained structure (XCS). The accuracy of the densification points and energy absorption capacity of the two structures at different VSF values are also studied. The results show that the densification points of the designed structures can be adjusted quantitatively, and their deformation modes are more stable than conventional structures during compression. Furthermore, their specific energy absorption is four and five times higher than that of non-lightweight structures with VSF = 40%, respectively. These findings contribute to advancing the implementation of auxetics in applications of multistage protective structures.

Transient freeform thermal metamaterials via inverse-design

Thermal metamaterials have gained significant interest because of their unconventionally tailored properties. Analytical transformation optics and numerical optimization method dealing with structural parameters have motivated unique and beneficial potential applications for thermal management. Nevertheless, analytical design methods are expected to possess and complex artificial mathematical derivation. Moreover, a self-driven standard strategy that meets the demands of different design requirements is unavailable. Herein, we report an inverse-design strategy using topology optimization for freeform thermal metamaterials in a transient state. The design of thermal metamaterials in transient state is converted to an inverse heat conduction problem, in which the sensitivity analysis and the adjoint problem are defined over the strong-form. The thermal conductivity and volumetric heat capacity of thermal metadevices are evolved simultaneously relying on the conjugate gradient method. Thermal metadevices with irregular shapes are specifically designed to verify the feasibility and universality of the paradigm. This study constructs a standard programmable design strategy for transient freeform thermal metamaterials and further suggests conducting more explorations in other Laplace fields, such as DC and magnetostatics.

Research on 3D Equipment Modeling Technology of 500 KV Substation

A three-dimensional simulation system for a flexible wire layout of a 500 KV substation is developed by using a hierarchical design method in this work. Firstly, the scenario model and device model for the 500 KV substation are established as the physical models. Then, the data model, flexible wire mathematical model, and connection model are established to form the rule models for the 500 KV substation. Finally, the three-dimensional simulation diagram of the 500 KV substation soft wire layout is generated by system integration. The system can quickly and accurately generate the three-dimensional simulation drawing of 500 KV substation soft wire by only seven structural parameter setting modules, achieving the purpose of programmable design. The simulation system software is proved to be feasible and correct by the data of several 500 KV substations.

Cage-shaped self-folding mechanical metamaterials

Self-folding is an effective design method for mechanical metamaterials with complex configurations and multiple material components. However, existing self-folding mechanical metamaterials are typically limited to a single transformation, limiting their potential for various deformation modes and diverse application scenarios. In this paper, we present a cage-shaped, self-folding mechanical metamaterial. This metamaterial exhibits multiple deformation modes from an initially flat state upon heating to different temperatures and subsequently remains stable upon cooling. The constituent self-folding elements of the metamaterial comprise temperature-responsive materials to achieve different folding thresholds. Theoretical models are developed to quantify the mechanical properties of the metamaterial, enabling programmable design of its mechanical performance. We also demonstrate that the cage-shaped mechanical metamaterial has tunable mechanical properties, multi-stage load-bearing, and decoupling of mechanical performance, providing the possibility of multifunctional applications in various fields.

Research on a Variable-Stiffness Joint and Its Application in Actuators

Variable-stiffness actuators can flexibly adjust the overall or local stiffness of a structure, thus enabling reconstruction, adaptation, and locking capabilities that can meet a wide range of task requirements. However, the programmable design and manufacture of three-dimensional (3D) variable-stiffness actuators has become a challenge. In this paper, we present a method to develop the 3D structure of variable-stiffness actuators that combines variable-stiffness joints with 3D printing technology. The variable-stiffness joints were obtained by arranging steel needles wrapped with enameled copper wire inside the grooves of a polylactic acid (PLA) structure and bonding the three components with silicone glue. First, a variable-stiffness joint was used as a variable-stiffness node and subjected to 3D printing to realize multiple 3D variable-stiffness designs and manufacture a programmable structure. Then, using the repulsive force between paired magnets, we developed a driving actuator for the 3D variable-stiffness structure, enabling the expansion and deployment functions of the structure. In addition, an electromagnetically driven mechanical gripper was designed based on variable-stiffness joints to effectively decrease the driving energy in applications where objects are held for extended periods using variable-stiffness control. Our study provides practical solutions and guidance for the development of 3D variable-stiffness actuators, contributing to the achievement of more innovative and practical actuators.

Biomolecule-Driven Two-Factor Authentication Strategy for Access Control of Molecular Devices.

The rise of DNA nanotechnology is promoting the development of molecular security devices and marking an essential change in information security technology, to one that can resist the threats resulting from the increase in computing power, brute force attempts, and quantum computing. However, developing a secure and reliable access control strategy to guarantee the confidentiality of molecular security devices is still a challenge. Here, a biomolecule-driven two-factor authentication strategy for access control of molecular devices is developed. Importantly, the two-factor is realized by applying the specificity and nicking properties of the nicking enzyme and the programmable design of the DNA sequence, endowing it with the characteristic of a one-time password. To demonstrate the feasibility of this strategy, an access control module is designed and integrated to further construct a role-based molecular access control device. By constructing a command library composed of three commands (Ca, Cb, Ca and Cb), the authorized access of three roles in the molecular device is realized, in which the command Ca corresponds to the authorization of role A, Cb corresponds to the authorization of role B, and Ca and Cb corresponds to the authorization of role C. In this way, when users access the device, they not only need the correct factor but also need to apply for role authorization in advance to obtain secret information. This strategy provides a highly robust method for the research on access control of molecular devices and lays the foundation for research on the next generation of information security.

Detection of antibiotic-resistance genes in bacterial pathogens using a Cas12a/3D DNAzyme colorimetric paper sensor

The rapid detection of antibiotic-resistant genes in bacterial pathogens is critical in combating global health crises. Herein, we report a CRISPR/Cas12a-based colorimetric paper sensor, where the trans-cleavage activity of Cas12a was post-amplified by rolling circle replication, resulting in the generation of a 3D DNAzyme. The 3D DNAzyme adhered strongly to the paper surface, creating a highly bioactive paper sensor containing high densities of functional DNAzymes. This assay was effective for the rapid detection of the antibiotic-resistant gene, NDM-1, with high sensitivity. In the absence of the NDM-1 gene, the 3D DNAzyme catalyzed a colorimetric reaction, resulting in a blue-colored signal while in the presence of NDM-1, collateral cleavage activity of Cas12a was activated, leading to cleavage of the circle template, thus preventing the generation of the 3D DNAzyme and producing no colorimetric signal. This paper sensor provides rapid and low-cost detection of antibiotic-resistant genes carried by various pathogenic microorganisms with femtomolar-level sensitivity and results that are visible to the naked eye. The entire analysis requires less than 90 minutes of assay time. Due to the highly programmable design of the CRISPR probe, the platform has significant potential for quick responses to new global epidemics.

Unravelling the Drug Encapsulation Ability of Functional DNA Origami Nanostructures: Current Understanding and Future Prospects on Targeted Drug Delivery.

Rapid breakthroughs in nucleic acid nanotechnology have always driven the creation of nano-assemblies with programmable design, potent functionality, good biocompatibility, and remarkable biosafety during the last few decades. Researchers are constantly looking for more powerful techniques that provide enhanced accuracy with greater resolution. The self-assembly of rationally designed nanostructures is now possible because of bottom-up structural nucleic acid (DNA and RNA) nanotechnology, notably DNA origami. Because DNA origami nanostructures can be organized precisely with nanoscale accuracy, they serve as a solid foundation for the exact arrangement of other functional materials for use in a number of applications in structural biology, biophysics, renewable energy, photonics, electronics, medicine, etc. DNA origami facilitates the creation of next-generation drug vectors to help in the solving of the rising demand on disease detection and therapy, as well as other biomedicine-related strategies in the real world. These DNA nanostructures, generated using Watson-Crick base pairing, exhibit a wide variety of properties, including great adaptability, precise programmability, and exceptionally low cytotoxicity in vitro and in vivo. This paper summarizes the synthesis of DNA origami and the drug encapsulation ability of functionalized DNA origami nanostructures. Finally, the remaining obstacles and prospects for DNA origami nanostructures in biomedical sciences are also highlighted.