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SFG has been utilized to monitor the surface species present on platinum and rhodium crystal surfaces during catalytic reactions at atmospheric pressures. Ethylene hydrogenation to ethane, cyclohexene hydrogenation to cyclohexane and its dehydrogenation to benzene, and carbon monoxide oxidation to carbon dioxide have been studied while also measuring the turnover rates and the gas phase product distribution by gas chromatography Strongly bound spectators, weakly bound reaction intermediates, and pressure-dependent changes in the chemical bonding of surface species have all been observed. SFG spectra of polyethylene and polypropylene show monolayer sensitivity and reveal temperature-dependent changes of surface structure. For polymer blends, the hydrophobic component segregates to the solid-air interface, and the hydrophilic component segregates at the solid-water interface. Changes in SFG spectra of polymer blends as a function of bulk concentration correlate with changes of contact angle. SFG is an excellent probe of surface-structure and surface-composition changes as the polymer interface is altered.

Untethered microrobots offer the possibility to perform medical interventions in anatomically complex and small regions in the body. Presently, it is necessary to access the upper urinary tract to diagnose and treat Upper Tract Urothelial Carcinoma (UTUC). Diagnostic and treatment challenges include ensuring adequate tissue sampling, accurately grading the disease, achieving completeness in endoscopic treatment, and consistently delivering medications to targeted sites. This work introduces microgrippers (µ-grippers) that are autonomously triggered by physiological temperature for biopsy in the upper urinary tract. The experiments demonstrated that µ-grippers can be deployed using standard ureteral catheters and maneuvered using an external magnetic field. The μ-grippers successfully biopsied tissue samples from ex vivo pig ureters, indicating that the thin-film bilayer springs' autonomous, physiologically triggered actuation exerts enough force to retrieve urinary tract tissue. The quality of these biopsy samples is sufficient for histopathological examination, including hematoxylin and eosin (H&E) and GATA3 immunohistochemical staining. Beyond biopsy applications, the µ-grippers' small size, wafer-scale fabrication, and multifunctionality suggest their potential for statistical sampling in the urinary tract. Experimental data and clinical reports underscore this potential through statistical simulations that compare the efficacy of µ-grippers with conventional tools, such as ureteroscopic forceps and baskets., (© 2024 Wiley‐VCH GmbH.)

The ability to transform matter between numerous physical states or shapes without wires or external devices is a major challenge for robotics and materials design. Organisms can transform their shapes using biomolecules carrying specific information and localize at sites where transitions occur. Here, we introduce gel automata, which likewise can transform between a large number of prescribed shapes in response to a combinatorial library of biomolecular instructions. Gel automata are centimeter-scale materials consisting of multiple micro-segments. A library of DNA activator sequences can each reversibly grow or shrink different micro-segments by polymerizing or depolymerizing within them. We develop DNA activator designs that maximize the extent of growth and shrinking, and a photolithography process for precisely fabricating gel automata with elaborate segmentation patterns. Guided by simulations of shape change and neural networks that evaluate gel automata designs, we create gel automata that reversibly transform between multiple, wholly distinct shapes: four different letters and every even or every odd numeral. The sequential and repeated metamorphosis of gel automata demonstrates how soft materials and robots can be digitally programmed and reprogrammed with information-bearing chemical signals., (© 2024. The Author(s).)

Brain organoids are three-dimensional aggregates of self-organized differentiated stem cells that mimic the structure and function of human brain regions. Organoids bridge the gaps between conventional drug screening models such as planar mammalian cell culture, animal studies, and clinical trials. They can revolutionize the fields of developmental biology, neuroscience, toxicology, and computer engineering. Conventional microinstrumentation for conventional cellular engineering, such as planar microfluidic chips; microelectrode arrays (MEAs); and optical, magnetic, and acoustic techniques, has limitations when applied to three-dimensional (3D) organoids, primarily due to their limits with inherently two-dimensional geometry and interfacing. Hence, there is an urgent need to develop new instrumentation compatible with live cell culture techniques and with scalable 3D formats relevant to organoids. This review discusses conventional planar approaches and emerging 3D microinstrumentation necessary for advanced organoid-machine interfaces. Specifically, this article surveys recently developed microinstrumentation, including 3D printed and curved microfluidics, 3D and fast-scan optical techniques, buckling and self-folding MEAs, 3D interfaces for electrochemical measurements, and 3D spatially controllable magnetic and acoustic technologies relevant to two-way information transfer with brain organoids. This article highlights key challenges that must be addressed for robust organoid culture and reliable 3D spatiotemporal information transfer., (© 2024 Wiley‐VCH GmbH.)

Fetal lung fibroblasts contribute dynamic infrastructure for the developing lung. These cells undergo dynamic mechanical transitions, including cyclic stretch and spreading, which are integral to lung growth in utero. We investigated the role of the nuclear envelope protein emerin in cellular responses to these dynamic mechanical transitions. In contrast to control cells, which briskly realigned their nuclei, actin cytoskeleton, and extracellular matrices in response to cyclic stretch, fibroblasts that were acutely downregulated for emerin showed incomplete reorientation of both nuclei and actin cytoskeleton. Emerin-downregulated fibroblasts were also aberrantly circular in contrast to the spindle-shaped controls and exhibited an altered pattern of filamentous actin organization that was disconnected from the nucleus. Emerin knockdown was also associated with reduced myosin light chain phosphorylation during cell spreading. Interestingly, emerin-downregulated fibroblasts also demonstrated reduced fibronectin fibrillogenesis and production. These findings indicate that nuclear-cytoskeletal coupling serves a role in the dynamic regulation of cytoskeletal structure and function and may also impact the transmission of traction force to the extracellular matrix microenvironment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

The development of biomolecular stimuli-responsive hydrogels is important for biomimetic structures, soft robots, tissue engineering, and drug delivery. DNA polymerization gels are a new class of soft materials composed of polymer gel backbones with DNA duplex crosslinks that can be swollen by sequential strand displacement using hairpin-shaped DNA strands. The extensive swelling can be tuned using physical parameters such as salt concentration and biomolecule design. Previously, DNA polymerization gels have been used to create shape-changing gel automata with a large design space and high programmability. Here we systematically investigate how the swelling response of DNA polymerization gels can be tuned by adjusting the design and concentration of DNA crosslinks in the hydrogels or DNA hairpin triggers, and the ionic strength of the solution in which swelling takes place. We also explore the effect hydrogel size and shape have on the swelling response. Tuning these variables can alter the swelling rate and extent across a broad range and provide a quantitative connection between biochemical reactions and macroscopic material behaviour.

Lithographic nanopatterning techniques such as photolithography, electron-beam lithography, and nanoimprint lithography (NIL) have revolutionized modern-day electronics and optics. Yet, their application for creating nanobio interfaces is limited by the cytotoxic and two-dimensional nature of conventional fabrication methods. Here, we present a biocompatible and cost-effective transfer process that leverages (a) NIL to define sub-300 nm gold (Au) nanopattern arrays, (b) amine functionalization of Au to transfer the NIL-arrays from a rigid substrate to a soft transfer layer, (c) alginate hydrogel as a flexible, degradable transfer layer, and (d) gelatin conjugation of the Au NIL-arrays to achieve conformal contact with live cells. We demonstrate biotransfer printing of the Au NIL-arrays on rat brains and live cells with high pattern fidelity and cell viability and observed differences in cell migration on the Au NIL-dot and NIL-wire printed hydrogels. We anticipate that this nanolithography-compatible biotransfer printing method could advance bionics, biosensing, and biohybrid tissue interfaces.

Introduction: Advances in microfabrication, automation, and computer engineering seek to revolutionize small-scale devices and machines. Emerging trends in medicine point to smart devices that emulate the motility, biosensing abilities, and intelligence of cells and pathogens that inhabit the human body. Two important characteristics of smart medical devices are the capability to be deployed in small conduits, which necessitates being untethered, and the capacity to perform mechanized functions, which requires autonomous shape-changing., Areas Covered: We motivate the need for untethered shape-changing devices in the gastrointestinal tract for drug delivery, diagnosis, and targeted treatment. We survey existing structures and devices designed and utilized across length scales from the macro to the sub-millimeter. These devices range from triggerable pre-stressed thin film microgrippers and spring-loaded devices to shape-memory and differentially swelling structures., Expert Opinion: Recent studies demonstrate that when fully enabled, tether-free and shape-changing devices, especially at sub-mm scales, could significantly advance the diagnosis and treatment of GI diseases ranging from cancer and inflammatory bowel disease (IBD) to irritable bowel syndrome (IBS) by improving treatment efficacy, reducing costs, and increasing medication compliance. We discuss the challenges and possibilities associated with ensuring safe, reliable, and autonomous operation of these smart devices.

The brain is arguably the most powerful computation system known. It is extremely efficient in processing large amounts of information and can discern signals from noise, adapt, and filter faulty information all while running on only 20 watts of power. The human brain's processing efficiency, progressive learning, and plasticity are unmatched by any computer system. Recent advances in stem cell technology have elevated the field of cell culture to higher levels of complexity, such as the development of three-dimensional (3D) brain organoids that recapitulate human brain functionality better than traditional monolayer cell systems. Organoid Intelligence (OI) aims to harness the innate biological capabilities of brain organoids for biocomputing and synthetic intelligence by interfacing them with computer technology. With the latest strides in stem cell technology, bioengineering, and machine learning, we can explore the ability of brain organoids to compute, and store given information (input), execute a task (output), and study how this affects the structural and functional connections in the organoids themselves. Furthermore, understanding how learning generates and changes patterns of connectivity in organoids can shed light on the early stages of cognition in the human brain. Investigating and understanding these concepts is an enormous, multidisciplinary endeavor that necessitates the engagement of both the scientific community and the public. Thus, on Feb 22-24 of 2022, the Johns Hopkins University held the first Organoid Intelligence Workshop to form an OI Community and to lay out the groundwork for the establishment of OI as a new scientific discipline. The potential of OI to revolutionize computing, neurological research, and drug development was discussed, along with a vision and roadmap for its development over the coming decade., Competing Interests: TH is employed by, and inventor on a patent by Johns Hopkins University on the production of brain organoids, which is licensed to AxoSim, New Orleans, LA, USA, and receives royalty shares. TH also consults to AxoSim. LS is employed by Johns Hopkins University and consults to AxoSim, New Orleans, LA, USA. JS is employed by, and inventor on a patent by the University of Luxembourg on the production of midbrain organoids, which is licensed to OrganoTherapeutics SARL, Esch-sur-Alzette, Luxembourg. JLC and BC were employed by AxoSim Inc., New Orleans, LA, United States. JS is also co-founder and shareholder of OrganoTherapeutics SARL. AM is employed by the University of California, San Diego and is co-founder and has equity interest in TISMOO, a company dedicated to genetic analysis and human brain organogenesis, focusing on therapeutic applications customized for autism spectrum disorders and other neurological disorders origin genetics. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. BK is employed by Cortical Labs Pty Ltd., Melbourne, Australia, and is an inventor on patents for technology related this paper and holds shares in Cortical Labs Pty Ltd., Melbourne, Australia. No specific funding or other incentives were provided for involvement in this publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Morales Pantoja, Smirnova, Muotri, Wahlin, Kahn, Boyd, Gracias, Harris, Cohen-Karni, Caffo, Szalay, Han, Zack, Etienne-Cummings, Akwaboah, Romero, Alam El Din, Plotkin, Paulhamus, Johnson, Gilbert, Curley, Cappiello, Schwamborn, Hill, Roach, Tornero, Krall, Parri, Sillé, Levchenko, Jabbour, Kagan, Berlinicke, Huang, Maertens, Herrmann, Tsaioun, Dastgheyb, Habela, Vogelstein and Hartung.)

Reversible thermoresponsive hydrogels, which swell and shrink (deswell) in the temperature range of 30° to 60°C, provide an attractive material class for operating untethered soft robots in human physiological and ambient conditions. Crawling has been demonstrated previously with thermoresponsive hydrogels but required patterned or constrained gels or substrates to break symmetry for unidirectional motion. Here, we demonstrate a locomotion mechanism for unidirectionally crawling gels driven by spontaneous asymmetries in contact forces during swelling and deswelling of segmented active thermoresponsive poly( N -isopropylacrylamide) (pNIPAM) and passive polyacrylamide (pAAM) bilayers with suspended linkers. Actuation studies demonstrate the consistent unidirectional movement of these gel crawlers across multiple thermal cycles on flat, unpatterned substrates. We explain the mechanism using finite element simulations and by varying experimental parameters such as the linker stiffness and the number of bilayer segments. We elucidate design criteria and validate experiments using image analysis and finite element models. We anticipate that this mechanism could potentially be applied to other shape-changing locomotors.

The delivery of macromolecular drugs via the gastrointestinal (GI) tract is challenging as these drugs display low stability as well as poor absorption across the intestinal epithelium. While permeation-enhancing drug delivery methods can increase the bioavailability of low molecular weight drugs, the effective delivery of high molecular weight drugs across the tight epithelial cell junctions remains a formidable challenge. Here, we describe autonomous microinjectors that are deployed in the GI tract, then efficiently penetrate the GI mucosa to deliver a macromolecular drug, insulin, to the systemic circulation. We performed in vitro studies to characterize insulin release and assess the penetration capability of microinjectors and we measured the in vivo release of insulin in live rats. We found that the microinjectors administered within the luminal GI tract could deliver insulin transmucosally to the systemic circulation at levels similar to those with intravenously administered insulin. Due to their small size, tunability in sizing and dosing, wafer-scale fabrication, and parallel, autonomous operation, we anticipate that these microinjectors will significantly advance drug delivery across the GI tract mucosa to the systemic circulation in a safe manner.

Brain organoids are important models for mimicking some three-dimensional (3D) cytoarchitectural and functional aspects of the brain. Multielectrode arrays (MEAs) that enable recording and stimulation of activity from electrogenic cells offer notable potential for interrogating brain organoids. However, conventional MEAs, initially designed for monolayer cultures, offer limited recording contact area restricted to the bottom of the 3D organoids. Inspired by the shape of electroencephalography caps, we developed miniaturized wafer-integrated MEA caps for organoids. The optically transparent shells are composed of self-folding polymer leaflets with conductive polymer-coated metal electrodes. Tunable folding of the minicaps' polymer leaflets guided by mechanics simulations enables versatile recording from organoids of different sizes, and we validate the feasibility of electrophysiology recording from 400- to 600-μm-sized organoids for up to 4 weeks and in response to glutamate stimulation. Our studies suggest that 3D shell MEAs offer great potential for high signal-to-noise ratio and 3D spatiotemporal brain organoid recording.

Multicellular organization with precise spatial definition is essential to various biological processes, including morphogenesis, development, and healing in vascular and other tissues. Gradients and patterns of chemoattractants are well-described guides of multicellular organization, but the influences of 3D geometry of soft hydrogels are less well defined. Here, the discovery of a new mode of endothelial cell self-organization guided by combinatorial effects of stiffness and geometry, independent of protein or chemical patterning, is described. Endothelial cells in 2 kPa microwells are found to be ≈30 times more likely to migrate to the edge to organize in ring-like patterns than in stiff 35 kPa microwells. This organization is independent of curvature and significantly more pronounced in 2 kPa microwells with aspect ratio (perimeter/depth) < 25. Physical factors of cells and substrates that drive this behavior are systematically investigated and a mathematical model that explains the organization by balancing the dynamic interaction between tangential cytoskeletal tension, cell-cell, and cell-substrate adhesion is presented. These findings demonstrate the importance of combinatorial effects of geometry and stiffness in complex cellular organization that can be leveraged to facilitate the engineering of bionics and integrated model organoid systems with customized nutrient vascular networks., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Widespread testing and isolation of infected patients is a cornerstone of viral outbreak management, as underscored during the ongoing COVID-19 pandemic. Here, we report a large-area and label-free testing platform that combines surface-enhanced Raman spectroscopy and machine learning for the rapid and accurate detection of SARS-CoV-2. Spectroscopic signatures acquired from virus samples on metal-insulator-metal nanostructures, fabricated using nanoimprint lithography and transfer printing, can provide test results within 25 min. Not only can our technique accurately distinguish between different respiratory and nonrespiratory viruses, but it can also detect virus signatures in physiologically relevant matrices such as human saliva without any additional sample preparation. Furthermore, our large area nanopatterning approach allows sensors to be fabricated on flexible surfaces allowing them to be mounted on any surface or used as wearables. We envision that our versatile and portable label-free spectroscopic platform will offer an important tool for virus detection and future outbreak preparedness.

Microsurgical tools offer a path to less invasive clinical procedures with improved access, reduced trauma, and better recovery outcomes. There are a variety of rigid and flexible endoscopic devices that have significantly advanced diagnostics and microsurgery. However, they rely on wires or tethers for guidance and operation of small end-effector tools. While untethered physiologically responsive microgrippers have been previously shown to excise tissue from deep gastrointestinal locations in animal models, there are challenges associated with guiding them along paths and moving them to specific locations. In this communication, the magnetic dipole moment of untethered thermally responsive grippers is optimized for efficient coupling to external magnetic resonance (MR) fields. Gripper encapsulation in a millimeter sized wax pellet reduces the friction with the surrounding tissue and MR Navigation (MRN) of a 700 µm sized microgripper is realized within narrow channels in tissue phantoms and in an ex vivo porcine esophagus. The results show convincing proof-of-concept evidence that it is possible to sequentially image, move, and guide a submillimeter functional microsurgical tool in tissue conduits using a commercial preclinical MR system, and when combined with prior demonstrations of physiologically responsive in vivo biopsy are an important step towards the clinical translation of untethered microtools., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Extended-release gastrointestinal (GI) luminal delivery substantially increases the ease of administration of drugs and consequently the adherence to therapeutic regimens. However, because of clearance by intrinsic GI motility, device gastroretention and extended drug release over a prolonged duration are very challenging. Here, we report that GI parasite-inspired active mechanochemical therapeutic grippers, or theragrippers, can reside within the GI tract of live animals for 24 hours by autonomously latching onto the mucosal tissue. We also observe a notable sixfold increase in the elimination half-life using theragripper-mediated delivery of a model analgesic ketorolac tromethamine. These results provide first-in-class evidence that shape-changing and self-latching microdevices enhance the efficacy of extended drug delivery., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

Hydrogels with the ability to change shape in response to biochemical stimuli are important for biosensing, smart medicine, drug delivery, and soft robotics. Here, a family of multicomponent DNA polymerization motor gels with different polymer backbones is created, including acrylamide-co-bis-acrylamide (Am-BIS), poly(ethylene glycol) diacrylate (PEGDA), and gelatin-methacryloyl (GelMA) that swell extensively in response to specific DNA sequences. A common mechanism, a polymerization motor that induces swelling is driven by a cascade of DNA hairpin insertions into hydrogel crosslinks. These multicomponent hydrogels can be photopatterned into distinct shapes, have a broad range of mechanical properties, including tunable shear moduli between 297 and 3888 Pa and enhanced biocompatibility. Human cells adhere to the GelMA-DNA gels and remain viable during ≈70% volumetric swelling of the gel scaffold induced by DNA sequences. The results demonstrate the generality of sequential DNA hairpin insertion as a mechanism for inducing shape change in multicomponent hydrogels, suggesting widespread applicability of polymerization motor gels in biomaterials science and engineering., (© 2020 Wiley-VCH GmbH.)

Due to their precisely modifiable microporosity and chemical functionality, Metal-Organic Frameworks (MOFs) have revolutionized catalysis, separations, gas storage, drug delivery, and sensors. However, because of their rigid and brittle powder morphology, it is challenging to build customizable MOF shapes with tunable mechanical properties. Here, we describe a new three-dimensional (3D) printing approach to create stretchable and tough MOF hydrogel structures with tunable mechanical properties. We formulate a printable ink by combining prepolymers of a versatile double network (DN) hydrogel of acrylamide and alginate, a shear-thinning agent, and MOF ligands. Importantly, by simultaneous cross-linking of alginate and in situ growth of the HKUST-1 using copper ions, we are able to create composites with high MOF dispersity in the DN hydrogel matrix with high pore accessibility. We extensively characterize the inks and uncover parameters to tune modulus, strength, and toughness of the 3D prints. We also demonstrate the excellent performance of the MOF hydrogels for dye absorption. Our approach incorporates all of the advantageous attributes of 3D printing while offering a rational approach to merge stretchable hydrogels and MOFs, and our findings are of broad relevance to wearables, implantable and flexible sensors, chemical separations, and soft robotics.

Single cell manipulation is important in biosensing, biorobotics, and quantitative cell analysis. Although microbeads, droplets, and microrobots have been developed previously, it is still challenging to simultaneously excise, capture, and manipulate single cells in a biocompatible manner. Here, we describe untethered single cell grippers, that can be remotely guided and actuated on-demand to actively capture or excise individual or few cells. We describe a novel molding method to micropattern a thermally responsive wax layer for biocompatible motion actuation. The multifingered grippers derive their energy from the triggered release of residual differential stress in bilayer hinges composed of silicon oxides. A magnetic layer enables remote guidance through narrow conduits and fixed tissue sections ex vivo . Our results provide an important advance in high-throughput single cell scale biopsy tools important to lab-on-a-chip devices, microrobotics, and minimally invasive surgery.

Nanotherapies based on micelles, liposomes, polymersomes, nanocapsules, magnetic nanoparticles, and noble metal nanoparticles have been at the forefront of drug delivery in the past few decades. Some of these nanopharmaceuticals have been commercially applied to treat a wide range of diseases, from dry eye syndrome to cancer. However, the majority involve particles that are passive, meaning that they do not change shape, and they lack motility; the static features can limit their therapeutic efficacy. In this review, we take a critical look at an emerging field that seeks to utilize active matter for therapeutics. In this context, active matter can be broadly referred to as micro or nanosized constructs that energetically react with their environment or external fields and translate, rotate, vibrate or change shape. Essentially, the recent literature suggests that such particles could significantly augment present-day drug delivery, by enhancing transport and increasing permeability across anatomical barriers by transporting drugs within solid tumor microenvironments or disrupting cardiovascular plaque. We discuss examples of such particles and link the transport and permeability properties of active matter to potential therapeutic applications in the context of two major diseases, namely cancer and heart disease. We also discuss potential challenges, opportunities, and translational hurdles., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Recent advancements in 3D printing have revolutionized biomedical engineering by enabling the manufacture of complex and functional devices in a low-cost, customizable, and small-batch fabrication manner. Soft elastomers are particularly important for biomedical applications because they can provide similar mechanical properties as tissues with improved biocompatibility. However, there are very few biocompatible elastomers with 3D printability, and little is known about the material properties of biocompatible 3D printable elastomers. Here, we report a new framework to 3D print a soft, biocompatible, and biostable polycarbonate-based urethane silicone (PCU-Sil) with minimal defects. We systematically characterize the rheological and thermal properties of the material to guide the 3D printing process and have determined a range of processing conditions. Optimal printing parameters such as printing speed, temperature, and layer height are determined via parametric studies aimed at minimizing porosity while maximizing the geometric accuracy of the 3D-printed samples as evaluated via micro-CT. We also characterize the mechanical properties of the 3D-printed structures under quasistatic and cyclic loading, degradation behavior and biocompatibility. The 3D-printed materials show a Young's modulus of 6.9 ± 0.85 MPa and a failure strain of 457 ± 37.7% while exhibiting good cell viability. Finally, compliant and free-standing structures including a patient-specific heart model and a bifurcating arterial structure are printed to demonstrate the versatility of the 3D-printed material. We anticipate that the 3D printing framework presented in this work will open up new possibilities not only for PCU-Sil, but also for other soft, biocompatible and thermoplastic polymers in various biomedical applications requiring high flexibility and strength combined with biocompatibility, such as vascular implants, heart valves, and catheters., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A patent application has been filed on aspects of the described work., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Changes in structure and function of small muscular arteries play a major role in the pathophysiology of pulmonary hypertension, a burgeoning public health challenge. Improved anatomically mimetic in vitro models of these microvessels are urgently needed because nonhuman vessels and previous models do not accurately recapitulate the microenvironment and architecture of the human microvascular wall. Here, we describe parallel biofabrication of photopatterned self-rolled biomimetic pulmonary arterial microvessels of tunable size and infrastructure. These microvessels feature anatomically accurate layering and patterning of aligned human smooth muscle cells, extracellular matrix, and endothelial cells and exhibit notable increases in endothelial longevity and nitric oxide production. Computational image processing yielded high-resolution 3D perspectives of cells and proteins. Our studies provide a new paradigm for engineering multicellular tissues with precise 3D spatial positioning of multiple constituents in planar moieties, providing a biomimetic platform for investigation of microvascular pathobiology in human disease., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Two-dimensional transition-metal dichalcogenide (TMD) crystals are a versatile platform for optoelectronic, catalytic and quantum device studies. However, the ability to tailor their physical properties through explicit synthetic control of their morphology and dimensionality is a major challenge. Here we demonstrate a gas-phase synthesis method that substantially transforms the structure and dimensionality of TMD crystals without lithography. Synthesis of MoS 2 on Si(001) surfaces pre-treated with phosphine yields high-aspect-ratio nanoribbons of uniform width. We systematically control the width of these nanoribbons between 50 and 430 nm by varying the total phosphine dosage during the surface treatment step. Aberration-corrected electron microscopy reveals that the nanoribbons are predominantly 2H phase with zig-zag edges and an edge quality that is comparable to, or better than, that of graphene and TMD nanoribbons prepared through conventional top-down processing. Owing to their restricted dimensionality, the nominally one-dimensional MoS 2 nanocrystals exhibit photoluminescence 50 meV higher in energy than that from two-dimensional MoS 2 crystals. Moreover, this emission is precisely tunable through synthetic control of crystal width. Directed crystal growth on designer substrates has the potential to enable the preparation of low-dimensional materials with prescribed morphologies and tunable or emergent optoelectronic properties.

The stiffness, microcurvature, and meso-curvature of cellular microenvironments can significantly alter cell and tissue function. However, it is challenging to produce in vitro tissue models that feature tunability in shape, stiffness, and curvature simultaneously in a high-throughput and cost-effective manner. One of the significant challenges is the fragility of micropatterns in soft and biocompatible hydrogels. Here, we describe an approach that combines reflow photolithography, soft lithography, and strain engineering to create soft anatomically mimetic gelatin cell culture models. The models can be mechanically tuned to have stiffnesses as low as 400 Pa to as high as 50 kPa featuring hierarchical curvature at two length scales: the cellular length scale of 12 to 120 μm, and the mesoscale of 1-4 mm. We characterize the microstructured gels using optical microscopy and rheometry, highlighting tunability in the hierarchical curvature, modulus, and shape. Also, collagen-based gelatin offers high-level biocompatibility and bypasses the need for additional surface modification to enhance cell adhesion. We anticipate that this approach could advance anatomically accurate in vitro 3D cell culture models of relevance to biofabrication, cell biology, and drug screening.

The local structure and geometry of catalytic interfaces can influence the selectivity of chemical reactions. Selectivity is often critical for the practical realization of reactions such as the electroreduction of carbon dioxide (CO 2 ). Previously developed strategies to manipulate the structure and geometry of catalysts for electroreduction of CO 2 involve complex processes or fail to efficiently alter the selectivity. Here, using a prestrained polymer, we uniaxially and biaxially compress a 60 nm gold film to form a nano-folded electrocatalyst for CO 2 reduction. We observe two kinds of folds and can tune the ratio of loose to tight folds by varying the extent of prestrain in the polymer. We characterize the nano-folded catalysts using X-ray diffraction, scanning, and transmission electron microscopy. We observe grain reorientation and coarsening in the nano-folded gold catalysts. We measure an enhancement of Faradaic efficiency for carbon monoxide formation with the biaxially compressed nano-folded catalyst by a factor of about nine as compared to the flat catalyst (up to 87.4%). We rationalize this observation by noting that an increase of the local pH in the tight folds of the catalyst outweighs the effects of alterations in grain characteristics. Together, our studies demonstrate that nano-folded geometries can significantly alter grain characteristics, mass transport, and catalytic performance.

Two-dimensional layered materials (2DLMs) have been extensively studied in a variety of planar optoelectronic devices. Three-dimensional (3D) optoelectronic structures offer unique advantages including omnidirectional responses, multipolar detection, and enhanced light-matter interactions. However, there has been limited success in transforming monolayer 2DLMs into reconfigurable 3D optoelectronic devices due to challenges in microfabrication and integration of these materials in truly 3D geometries. Here, we report an origami-inspired self-folding approach to reversibly transform monolayer molybdenum disulfide (MoS 2 ) into functional 3D optoelectronic devices. We pattern and integrate monolayer MoS 2 and gold (Au) onto differentially photo-cross-linked thin polymer (SU8) films. The devices reversibly self-fold due to swelling gradients in the SU8 films upon solvent exchange. We fabricate a wide variety of optically active 3D MoS 2 microstructures including pyramids, cubes, flowers, dodecahedra, and Miura-oris, and we simulate the self-folding mechanism using a coarse-grained mechanics model. Using finite-difference time-domain (FDTD) simulation and optoelectronic characterization, we demonstrate that the 3D self-folded MoS 2 structures show enhanced light interaction and are capable of angle-resolved photodetection. Importantly, the structures are also reversibly reconfigurable upon solvent exchange with high tunability in the optical detection area. Our approach provides a versatile strategy to reversibly configure 2D materials in 3D optoelectronic devices of broad relevance to flexible and wearable electronics, biosensing, and robotics.

Poly(tetrafluoroethylene) (PTFE) is a unique polymer with highly desirable properties such as resistance to chemical degradation, biocompatibility, hydrophobicity, antistiction, and low friction coefficient. However, due to its high melt viscosity, it is not possible to three-dimensional (3D)-print PTFE structures using nozzle-based extrusion. Here, we report a new and versatile strategy for 3D-printing PTFE structures using direct ink writing (DIW). Our approach is based on a newly formulated PTFE nanoparticle ink and thermal treatment process. The ink was formulated by mixing an aqueous dispersion of surfactant-stabilized PTFE nanoparticles with a binding gum to optimize its shear-thinning properties required for DIW. We developed a multistage thermal treatment to fuse the PTFE nanoparticles, solidify the printed structures, and remove the additives. We have extensively characterized the rheological and mechanical properties and processing parameters of these structures using imaging, mechanical testing, and statistical design of experiments. Importantly, several of the mechanical and structural properties of the final-printed PTFE structures resemble that of compression-molded PTFE, and additionally, the mechanical properties are tunable. We anticipate that this versatile approach facilitates the production of 3D-printed PTFE components using DIW with significant potential applications in engineering and medicine.

Inspired by biological organisms, soft engineered robots seek to augment the capabilities of rigid robots by providing safe, compliant, and flexible interfaces for human-machine interactions. Soft robots provide significant advantages in applications ranging from pick-and-place, prostheses, wearables, and surgical and drug-delivery devices. Conventional soft robots are typically composed of elastomers or gels, where changes in material properties such as stiffness or swelling control actuation. However, soft materials have limited electronic and optical performance, mechanical rigidity, and stability against environmental damage. Atomically thin two-dimensional layered materials (2DLMs) such as graphene and transition metal dichalcogenides have excellent electrical, optical, mechanical, and barrier properties and have been used to create ultrathin interconnects, transistors, photovoltaics, photocatalysts, and biosensors. Importantly, although 2DLMs have high in-plane stiffness and rigidity, they have high out-of-plane flexibility and are soft from that point of view. In this Perspective, we discuss the use of 2DLMs either in their continuous monolayer state or as composites with elastomers and hydrogels to create soft three-dimensional (3D) robots, with a focus on origami-inspired approaches. We classify the field, outline major methods, and highlight challenges toward seamless integration of hybrid materials to create multifunctional robots with the characteristics of soft devices.

Biological samples such as cells have complex three-dimensional (3D) spatio-molecular profiles and often feature soft and irregular surfaces. Conventional biosensors are based largely on 2D and rigid substrates, which have limited contact area with the entirety of the surface of biological samples making it challenging to obtain 3D spatially resolved spectroscopic information, especially in a label-free manner. Here, we report an ultrathin, flexible skinlike biosensing platform that is capable of conformally wrapping a soft or irregularly shaped 3D biological sample such as a cancer cell or a pollen grain, and therefore enables 3D label-free spatially resolved molecular spectroscopy via surface-enhanced Raman spectroscopy (SERS). Our platform features an ultrathin thermally responsive poly( N-isopropylacrylamide)-graphene-nanoparticle hybrid skin that can be triggered to self-fold and wrap around 3D micro-objects in a conformal manner due to its superior flexibility. We highlight the utility of this 3D biosensing platform by spatially mapping the 3D molecular signatures of a variety of microparticles including silica microspheres, spiky pollen grains, and human breast cancer cells.

The distribution of periodic patterns of materials with radial or bilateral symmetry is a universal natural design principle. Among the many biological forms, tubular shapes are a common motif in many organisms, and they are also important for bioimplants and soft robots. However, the simple design principle of strategic placement of 3D printed segments of swelling and nonswelling materials to achieve widely different functionalities is yet to be demonstrated. Here, we report the design, fabrication, and characterization of segmented 3D printed gel tubes composed of an active thermally responsive swelling gel (poly N-isopropylacrylamide) and a passive thermally nonresponsive gel (polyacrylamide). Using finite element simulations and experiments, we report a variety of shape changes including uniaxial elongation, radial expansion, bending, and gripping based on two gels. Actualization and characterization of thermally induced shape changes are of key importance to robotics and biomedical engineering. Our studies present rational approaches to engineer complex parameters with a high level of customization and tunability for additive manufacturing of dynamic gel structures.

Soft-robotic devices such as polymeric microgrippers offer the possibility for pick and place of fragile biological cargo in hard-to-reach conduits with potential applications in drug delivery, minimally invasive surgery, and biomedical engineering. Previously, millimeter-sized self-folding thermomagnetically responsive soft grippers have been designed, fabricated, and utilized for pick-and-place applications but there is a concern that such devices could get lost or left behind after their utilization in practical clinical applications in the human body. Consequently, strategies need to be developed to ensure that these soft-robotic devices are biodegradable so that they would disintegrate if left behind in the body. In this paper, we describe the photopatterning of bilayer gels composed of a thermally responsive high-swelling poly(oligoethylene glycol methyl ether methacrylate ( M n = 500)-bis(2-methacryloyl)oxyethyl disulfide), P(OEGMA-DSDMA), and a low-swelling poly(acrylamide- N, N'-bis(acyloyl)cystamine) hydrogel, in the shape of untethered grippers. These grippers can change shape in response to thermal cues and open and close due to the temperature-induced swelling of the P(OEGMA-DSDMA) layer. We demonstrate that the grippers can be doped with magnetic nanoparticles so that they can be moved using magnetic fields or loaded with chemicals for potential applications as drug-eluting theragrippers. Importantly, they are also biodegradable at physiological body temperature (∼37 °C) on the basis of cleavage of disulfide bonds by reduction. This approach that combines thermoresponsive shape change, magnetic guidance, and biodegradability represents a significant advance to the safe implementation of untethered shape-changing biomedical devices and soft robots for medical and surgical applications.

The ability to concentrate the electrical field into sub-wavelength volumes is a key benefit sought and, to a certain degree, found within the discipline of plasmonics. This ability is restricted only by the ohmic loss in noble metals and, recently, in the infrared region, metals are beginning to face a challenge from emerging alternative media: phononic (i.e., relying on surface phonon polaritons) and photonic (i.e., relying on high refractive index) all-dielectric structures, and highly doped semiconductors, all of them having smaller intrinsic loss than metals. In this Letter, we compare the degree of enhancement and its spectral selectivity for different media and confirm that, while one can obtain sharper resonant features with all-dielectric structures, the magnitude of the field enhancement is invariably higher with metals such as gold and copper, primarily due to a higher density of electrons. On the whole, depending on the application, metals and dielectrics have their own unique advantages.

Interfacing nano/microscale elements with biological components in 3D contexts opens new possibilities for mimicry, bionics, and augmentation of organismically and anatomically inspired materials. Abiotic nanoscale elements such as plasmonic nanostructures, piezoelectric ribbons, and thin film semiconductor devices interact with electromagnetic fields to facilitate advanced capabilities such as communication at a distance, digital feedback loops, logic, and memory. Biological components such as proteins, polynucleotides, cells, and organs feature complex chemical synthetic networks that can regulate growth, change shape, adapt, and regenerate. Abiotic and biotic components can be integrated in all three dimensions in a well-ordered and programmed manner with high tunability, versatility, and resolution to produce radically new materials and hybrid devices such as sensor fabrics, anatomically mimetic microfluidic modules, artificial tissues, smart prostheses, and bionic devices. In this critical Review, applications of small scale devices in 3D hybrid integration, biomicrofluidics, advanced prostheses, and bionic organs are discussed., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Miniaturized grippers that possess an untethered structure are suitable for a wide range of tasks, ranging from micromanipulation and microassembly to minimally invasive surgical interventions. In order to robustly perform such tasks, it is critical to properly estimate their overall configuration. Previous studies on tracking and control of miniaturized agents estimated mainly their 2D pixel position, mostly using cameras and optical images as a feedback modality. This paper presents a novel solution to the problem of estimating and tracking the 3D position, orientation and configuration of the tips of submillimeter grippers from marker-less visual observations. We consider this as an optimization problem, which is solved using a variant of the Particle Swarm Optimization algorithm. The proposed approach has been implemented in a Graphics Processing Unit (GPU) which allows a user to track the submillimeter agents online. The proposed approach has been evaluated on several image sequences obtained from a camera and on B-mode ultrasound images obtained from an ultrasound probe. The sequences show the grippers moving, rotating, opening/closing and grasping biological material. Qualitative results obtained using both hydrogel (soft) and metallic (hard) grippers with different shapes and sizes ranging from 750 microns to 4 mm (tip to tip), demonstrate the capability of the proposed method to track the agent in all the video sequences. Quantitative results obtained by processing synthetic data reveal a tracking position error of 25 ± 7 μ m and orientation error of 1.7 ± 1.3 degrees. We believe that the proposed technique can be applied to different stimuli responsive miniaturized agents, allowing the user to estimate the full configuration of complex agents from visual marker-less observations.

With the discovery of graphene, significant research has focused on the synthesis, characterization, and applications of ultrathin materials. Graphene has also brought into focus other ultrathin materials composed of organics, polymers, inorganics, and their hybrids. Together, these ultrathin materials have unique properties of broad significance. For example, ultrathin materials have a large surface area and high flexibility which can enhance conformal contact in wearables and sensors leading to improved sensitivity. When porous, the short transverse diffusion length in these materials allows rapid mass transport. Alternatively, when impermeable, these materials behave as an ultrathin barrier. Such controlled permeability is critical in the design of encapsulation and drug delivery systems. Finally, ultrathin materials often feature defect-free and single-crystal-like two-dimensional atomic structures resulting in superior mechanical, optical, and electrical properties. A unique property of ultrathin materials is their low bending rigidity, which suggests that they could easily be bent, curved, or folded into 3D shapes. In this Account, we review the emerging field of 2D to 3D shape transformations of ultrathin materials. We broadly define ultrathin to include materials with a thickness below 100 nm and composed of a range of organic, inorganic, and hybrid compositions. This topic is important for both fundamental and applied reasons. Fundamentally, bending and curving of ultrathin films can cause atomistic and molecular strain which can alter their physical and chemical properties and lead to new 3D forms of matter which behave very differently from their planar precursors. Shape change can also lead to new 3D architectures with significantly smaller form factors. For example, 3D ultrathin materials would occupy a smaller space in on-chip devices or could permeate through tortuous media which is important for miniaturized robots and smart dust applications. Our Account highlights several differences between ultrathin and traditional shape change materials. The latter is typically associated with hydrogels, liquid crystals, or shape memory elastomers. As compared to bulk materials, ultrathin materials can much more easily bend and fold due to the significantly reduced bending modulus. Consequently, it takes much less energy to alter the shape of ultrathin materials, and even small environmental stimuli can trigger a large response. Further, the energy barriers between different configurations are small which allow a variety of conformations and enhances programmability. Finally, due to their ultrathin nature, the shape changes are typically not slowed down by sluggish mass or thermal transport, and thus, responses can be much faster than those of bulk materials. The latter point is important in the design of high-speed actuators. Consequently, ultrathin materials could enable low-power, rapid, programmable, and complex shape transformations in response to a broad range of stimuli such as pH, temperature, electromagnetic fields, or chemical environments. The Account also includes a discussion of applications, important challenges, and future directions.

Untethered, millimeter-scale, stimuli-responsive shape change structures are critical to the function of autonomous devices, smart materials, and soft robotics. Temperature in a range compatible with physiological or ambient environmental conditions is an excellent cue to trigger actuation of soft structures for practical biomimetic applications. Previously, a range of thermally responsive self-folding soft structures has been described and utilized in a variety of applications from tissue engineering to minimally invasive surgery. In order to extend these concepts to more complex devices, thermally responsive bilayer structures composed of poly[oligo (ethylene glycol) methyl ether methacrylate] (POEGMA) gels that swell at three different temperatures are described. The lower critical solution temperature and volume transition temperature of POEGMA are tuned by varying the side chain length and the extent of copolymerization. The swelling properties of the POEGMA gels are characterized and a multilayer photopatterning process is described that is used to create soft biomimetic structures that change shape in a sequential manner while displaying multistate behaviors., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Microelectrode arrays (MEAs) have proved to be useful tools for characterizing electrically active cells such as cardiomyocytes and neurons. While there exist a number of integrated electronic chips for recording from small populations or even single cells, they rely primarily on the interface between the cells and 2D flat electrodes. Here, an approach that utilizes residual stress-based self-folding to create individually addressable multielectrode interfaces that wrap around the cell in 3D and function as an electrical shell-like recording device is described. These devices are optically transparent, allowing for simultaneous fluorescence imaging. Cell viability is maintained during and after electrode wrapping around the cel and chemicals can diffuse into and out of the self-folding devices. It is further shown that 3D spatiotemporal recordings are possible and that the action potentials recorded from cultured neonatal rat ventricular cardiomyocytes display significantly higher signal-to-noise ratios in comparison with signals recorded with planar extracellular electrodes. It is anticipated that this device can provide the foundation for the development of new-generation MEAs where dynamic electrode-cell interfacing and recording substitutes the traditional method using static electrodes.

Untethered miniature robotics have recently shown promising results in several scenarios at the microscale, such as targeted drug delivery, microassembly, and biopsy procedures. However, the vast majority of these small-scale robots have very limited manipulation capabilities, and none of the steering systems currently available enable humans to intuitively and effectively control dexterous miniaturized robots in a remote environment. In this paper, we present an innovative micro teleoperation system with haptic assistance for the intuitive steering and control of miniaturized self-folding soft magnetic grippers in 2-D space. The soft grippers can be wirelessly positioned using weak magnetic fields and opened/closed by changing their temperature. An image-guided algorithm tracks the position of the controlled miniaturized gripper in the remote environment. A haptic interface provides the human operator with compelling haptic sensations about the interaction between the gripper and the environment, as well as enables the operator to intuitively control the target position and grasping configuration of the gripper. Finally, magnetic and thermal control systems regulate the position and grasping configuration of the gripper. The viability of the proposed approach is demonstrated through two experiments involving 26 human subjects. Providing haptic stimuli elicited statistically significant improvements in the performance of the considered navigation and micromanipulation tasks. Note to Practitioners -The ability to accurately and intuitively control the motion of miniaturized grippers in remote environments can open new exciting possibilities in the fields of minimally-invasive surgery, micromanipulation, biopsy, and drug delivery. This paper presents a micro teleoperation system with haptic assistance through which a clinician can easily control the motion and open/close capability of miniaturized wireless soft grippers. It introduces the underlying autonomous magnetic and thermal control systems, their interconnection with the master haptic interface, and an extensive evaluation in two real-world scenarios: following of a predetermined trajectory, and pick-and-place of a microscopic object.

The design and control of untethered microrobotic agents has drawn a lot of attention in recent years. This technology truly possesses the potential to revolutionize the field of minimally invasive surgery and microassembly. However, miniaturization and reliable actuation of micro-fabricated grippers are still challenging at sub-millimeter scale. In this study, we design, manufacture, characterize, and control four similarly-structured semi-rigid thermoresponsive micro-grippers. Furthermore, we develop a closed loop-control algorithm to demonstrate and compare the performance of the said grippers when moving in hard-to-reach and unpredictable environments. Finally, we analyze the grasping characteristics of three of the presented designs. Overall, not only does the study demonstrate motion control in unstructured dynamic environments-at velocities up to 3.4, 2.9, 3.3, and 1 body-lengths/s with 980, 750, 250, and 100 μm-sized grippers, respectively-but it also aims to provide quantitative data and considerations to help a targeted design of magnetically-controlled thin micro-grippers.

Graphene and other two-dimensional materials have unique physical and chemical properties of broad relevance. It has been suggested that the transformation of these atomically planar materials to three-dimensional (3D) geometries by bending, wrinkling, or folding could significantly alter their properties and lead to novel structures and devices with compact form factors, but strategies to enable this shape change remain limited. We report a benign thermally responsive method to fold and unfold monolayer graphene into predesigned, ordered 3D structures. The methodology involves the surface functionalization of monolayer graphene using ultrathin noncovalently bonded mussel-inspired polydopamine and thermoresponsive poly( N -isopropylacrylamide) brushes. The functionalized graphene is micropatterned and self-folds into ordered 3D structures with reversible deformation under a full control by temperature. The structures are characterized using spectroscopy and microscopy, and self-folding is rationalized using a multiscale molecular dynamics model. Our work demonstrates the potential to design and fabricate ordered 3D graphene structures with predictable shape and dynamics. We highlight applicability by encapsulating live cells and creating nonlinear resistor and creased transistor devices.

Shape-changing hydrogels that can bend, twist, or actuate in response to external stimuli are critical to soft robots, programmable matter, and smart medicine. Shape change in hydrogels has been induced by global cues, including temperature, light, or pH. Here we demonstrate that specific DNA molecules can induce 100-fold volumetric hydrogel expansion by successive extension of cross-links. We photopattern up to centimeter-sized gels containing multiple domains that undergo different shape changes in response to different DNA sequences. Experiments and simulations suggest a simple design rule for controlled shape change. Because DNA molecules can be coupled to molecular sensors, amplifiers, and logic circuits, this strategy introduces the possibility of building soft devices that respond to diverse biochemical inputs and autonomously implement chemical control programs., (Copyright © 2017, American Association for the Advancement of Science.)

The surgical biopsy is one of the most widely utilized medical procedures for diagnosis of a number of diseases. In order to enable less invasive biopsies, we have previously developed and applied residual stress and physiologically activated sub-millimeter sized untethered grippers. Here, we report a controlled, pneumatic system and methodology for pressurized delivery of untethered microgrippers (μ-grippers) to improve the efficacy of tissue excision. The approach is compatible with current minimally invasive laparoscopic and endoscopic methods. Using a model experimental system, we observed that pneumatic delivery significantly improves the efficiency of the tissue attachment-μ-grippers attach up to 30-fold better on vertically oriented tissues, and up to 3.5-fold better on horizontally oriented tissues as compared to experiments without pressurized delivery. Hence, the use of pneumatics in the delivery of untethered microdevices could significantly enhance their efficiency in minimally invasive biopsy procedures.

Untethered microtools that can be precisely navigated into deep in vivo locations are important for clinical procedures pertinent to minimally invasive surgery and targeted drug delivery. In this mini-review, untethered soft grippers are discussed, with an emphasis on a class of autonomous stimuli-responsive gripping soft tools that can be used to excise tissues and release drugs in a controlled manner. The grippers are composed of polymers and hydrogels and are thus compliant to soft tissues. They can be navigated using magnetic fields and controlled by robotic path-planning strategies to carry out tasks like pick-and-place of microspheres and biological materials either with user assistance, or in a fully autonomous manner. It is envisioned that the use of these untethered soft grippers will translate from laboratory experiments to clinical scenarios and the challenges that need to be overcome to make this transition are discussed., Competing Interests: Conflict of Interest Statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The multilayer hyperbolic metamaterials are known to be capable of imaging with sub-wavelength resolution. In this work performance of these "hyperbolic lenses" is analyzed in depth by employing commonly used transfer matrix method as well as the eigen-mode approach, the latter offering a clear physical insight into the operation of hyperbolic imagers and revealing their fundamental limitations. The resolution of multilayer structures is shown to decrease with the number of layers not only due to increased loss but also because of the severe suppression of large spatial frequencies caused by the cancellation between symmetric and antisymmetric eigen-modes. Additionally, the resolution is strongly affected by the granularity and fill ratio. In the end, hyperbolic metamaterials can create an image with subwavelength resolution only at very close distance to the object and hence limiting their utility.

Soft miniaturized untethered grippers can be used to manipulate and transport biological material in unstructured and tortuous environments. Previous studies on control of soft miniaturized grippers employed cameras and optical images as a feedback modality. However, the use of cameras might be unsuitable for localizing miniaturized agents that navigate within the human body. In this paper, we demonstrate the wireless magnetic motion control and planning of soft untethered grippers using feedback extracted from B-mode ultrasound images. Results show that our system employing ultrasound images can be used to control the miniaturized grippers with an average tracking error of 0.4±0.13 mm without payload and 0.36±0.05 mm when the agent performs a transportation task with a payload. The proposed ultrasound feedback magnetic control system demonstrates the ability to control miniaturized grippers in situations where visual feedback cannot be provided via cameras.

Reported is a new shell-based spectroscopic platform, named mechanical trap surface-enhanced Raman spectroscopy (MTSERS), for simultaneous capture, profiling, and 3D microscopic mapping of the intrinsic molecular signatures on the membrane of single live cells. By leveraging the functionalization of the inner surfaces of the MTs with plasmonic gold nanostars, and conformal contact of the cell membrane, MTSERS permits excellent signal enhancement, reliably detects molecular signatures, and allows non-perturbative, multiplex 3D surface imaging of analytes, such as lipids and proteins on the surface of single cells. The demonstrated ability underscores the potential of MTSERS to perform 3D spectroscopic microimaging and to furnish biologically interpretable, quantitative, and dynamic molecular maps in live cell populations., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The use of small, maneuverable, untethered and reconfigurable robots could provide numerous advantages in various micromanipulation tasks. Examples include microassembly, pick-and-place of fragile micro-objects for lab-on-a-chip applications, assisted hatching for in-vitro fertilization and minimally invasive surgery. This study assesses the potential of soft untethered magnetic grippers as alternatives or complements to conventional tethered or rigid micromanipulators. We demonstrate closed-loop control of untethered grippers and automated pick-and-place of biological material on porcine tissue in an unstructured environment. We also demonstrate the ability of the soft grippers to recognize and sort non-biological micro-scale objects. The fully autonomous nature of the experiments is made possible by the integration of planning and decision-making algorithms, as well as by closed-loop temperature and electromagnetic motion control. The grippers are capable of completing pick-and-place tasks of biological material at an average velocity of 1.8 ±0.71 mm/s and a drop-off error of 0.62 ±0.22 mm. Color-sensitive sorting of three micro-scale objects is completed at a velocity of 1.21 ±0.68 mm/s and a drop-off error of 0.85 ±0.41 mm. Our findings suggest that improved autonomous untethered grippers could augment the capabilities of current soft-robotic instruments especially in advancedtasks involving manipulation.

A significant need in nanotechnology is the development of methods to mass-produce three-dimensional (3D) nanostructures and their ordered assemblies with patterns of functional materials such as metals, ceramics, device grade semiconductors, and polymers. While top-down lithography approaches can enable heterogeneous integration, tunability, and significant material versatility, these methods enable inherently two-dimensional (2D) patterning. Bottom-up approaches enable mass-production of 3D nanostructures and their assemblies but with limited precision, and tunability in surface patterning. Here, we demonstrate a methodology to create Self-folding Nanostructures with Imprint Patterned Surfaces (SNIPS). By a variety of examples, we illustrate that SNIPS, either individually or in ordered arrays, are mass-producible and have significant tunability, material heterogeneity, and patterning precision.

In vivo, mammalian cells proliferate within 3D environments consisting of numerous microcavities and channels, which contain a variety of chemical and physical cues. External environments often differ between normal and pathological states, such as the unique spatial constraints that metastasizing cancer cells experience as they circulate the vasculature through arterioles and narrow capillaries, where they can divide and acquire elongated cylindrical shapes. While metastatic tumors cause most cancer deaths, factors impacting early cancer cell proliferation inside the vasculature and those that can promote the formation of secondary tumors remain largely unknown. Prior studies investigating confined mitosis have mainly used 2D cell culture systems. Here, we mimic aspects of metastasizing tumor cells dividing inside blood capillaries by investigating single-cell divisions of living human cancer cells, trapped inside 3D rolled-up, transparent nanomembranes. We assess the molecular effects of tubular confinement on key mitotic features, using optical high- and super-resolution microscopy. Our experiments show that tubular confinement affects the morphology and dynamics of the mitotic spindle, chromosome arrangements, and the organization of the cell cortex. Moreover, we reveal that membrane blebbing and/or associated processes act as a potential genome-safety mechanism, limiting the extent of genomic instability caused by mitosis in confined circumstances, especially in tubular 3D microenvironments. Collectively, our study demonstrates the potential of rolled-up nanomembranes for gaining molecular insights into key cellular events occurring in tubular 3D microenvironments in vivo.