Smart Materials for Microrobots.

Over the past 15 years, the field of microrobotics has exploded with many research groups from around the globe contributing to numerous innovations that have led to exciting new capabilities and important applications, ranging from in vivo drug delivery, to intracellular biosensing, environmental remediation, and nanoscale fabrication. Smart responsive materials have had a profound impact on the field of microrobotics and have imparted small-scale robots with new functionalities and distinct capabilities. We have identified four large categories where the majority of future efforts must be allocated to push the frontiers of microrobots and where smart materials can have a major impact on such future advances. These four areas are the propulsion and biocompatibility of microrobots, the cooperation between individual units and human operators, and finally, the intelligence of microrobots. In this Review, we look critically at the latest developments in these four categories and discuss how smart materials contribute to the progress in the exciting field of microrobotics and will set the stage for the next generation of intelligent and programmable microrobots.

Ease and practicability of the 2017 classification of periodontal diseases and conditions: a study of dental electronic health records.

BACKGROUND: A new classification for Periodontal and Peri-implant Diseases and Conditions was introduced in the 2017 World Workshop. In the past the 1999 Armitage Classification was commonly used in practice. This study aimed to assess the ease and practicability of retroactively diagnosing a subset of patients formerly diagnosed using the 1999 AAP/CDC classification with the 2017 AAP/EFP disease classification. METHODS: A random subset of 10% of all patients referred over a 7-year period (2011-2018) to the Post-Doctoral Periodontics Clinic at Columbia University College of Dental Medicine were reviewed by accessing the Electronic Health Records (EHRs) on axiUm. Patients diagnosed with periodontal disease based on the 1999 AAP/CDC classification (including chronic and aggressive Periodontitis) were reclassified using the 2017 classification (stage: I, II, III and grade: A, B, C). RESULTS: A sample of 336 patient records were examined. 132 were diagnosed with gingivitis, and 204 with periodontitis. Of these 204 patients, 68 (33.3%) were diagnosed with aggressive and 136 (66.7%) with chronic periodontitis. Patients diagnosed with aggressive periodontitis, 10% were reclassified as stage II, 47% as stage III, and 43% as stage IV periodontitis, and 100% were reclassified as grade C. Among patients with chronic periodontitis, 7% were reclassified as stage I, 65% as stage II, 21% as stage III, and 7% as stage IV; 11% of these were reclassified as grade A, 63% grade B, and 26% grade C. CONCLUSIONS: The majority of those originally diagnosed with aggressive (90%) and chronic (80%) periodontitis were reclassified as either molar/incisor pattern stage III grade C or stage IV grade C periodontitis, and stage II or III periodontitis, respectively. The study demonstrated that it is practical to retroactively reassign a diagnosis according to the new 2017 classification using available information included in dental EHRs.

Electrical Propulsion and Cargo Transport of Microbowl Shaped Janus Particles.

Herein the effective electrical propulsion, cargo trapping, and transport capabilities of microbowl-shaped Janus particles (JPs) are demonstrated and evaluated. These active JPs are made by deposition of Au and Ti layers onto sacrificial spherical polystyrene particles, followed by oxidation of the Ti to TiO2 . In contrast to the commonly studied spherical JP, the dual broken symmetry of both geometrical and electrical properties of the microbowl renders a strong dependence of its mobility and cargo loading on the order of the layering of Au and TiO2 . Specifically, an opposite direction of motion is obtained for interchanged layers of Au and TiO2 , using only electrical propulsion as the sole mechanism of motion. The concave side of the microbowl exhibits a negative dielectrophoretic trap of large size wherein trapped cargo is protected from hydrodynamic shearing, leading to an enhanced cargo loading capacity compared to that obtained using common spherical JP. Such enhanced cargo capability of the microbowl along with the ease of engineering it by interchanging the order of the layers are very attractive for future in vitro biological and biomedical applications.

Immediate versus delayed temporization at posterior single implant sites: A randomized controlled trial.

AIMS: We conducted a randomized controlled trial to assess the clinical outcomes of two loading protocols involving either immediate or delayed prosthetic temporization of single implants placed at posterior, healed sites. MATERIALS AND METHODS: Forty-nine patients in need of single implants at premolar or molar sites were randomized to receive a temporary crown either immediately after implant placement or 3 months later. Randomization was stratified by sex, implant location (premolar/molar) and arch (maxilla/mandible). Final implant screw-retained zirconia crowns with angulated screw channels were delivered at 5 months after surgery. Radiographic bone levels (primary outcome), peri-implant mucosal margin levels and peri-implant probing depths were recorded at baseline, 6 and 12 months after surgery. RESULTS: Both treatment arms showed similar patterns of soft tissue and bone re-modelling from the implant platform over 12 months [mean bone level change 1.6 mm (SD 1.0 mm) in the delayed, and 1.2 mm (SD 1.3 mm) in the immediate temporization group], with the majority of changes occurring within the first 6 months. CONCLUSIONS: Immediate or delayed temporization of single implants placed at posterior healed sites resulted in largely similar 1-year outcomes with respect to peri-implant bone levels and soft tissue changes.

Uric acid electrochemical sensing in biofluids based on Ni/Zn hydroxide nanocatalyst.

A highly sensitive sensor for quantification of uric acid (UA) directly in body fluids (saliva and sweat) is reported, working at a potential as low as 0.0 V vs Ag/AgCl. New mixed hydroxide materials exhibiting stable electrocatalytic responses from alkaline to acidic media were prepared, their structure was thoroughly characterized, and the electrochemical properties of the modified FTO (fluorine-doped tin oxide) electrodes were evaluated for UA determination by cyclic voltammetry, chronoamperometry, and batch injection analysis. A very low limit of detection (2.3 × 10-8 mol L-1) with good repeatability (RSD = 3.2% for 30 successive analyses) was achieved based on a fast and simple BIA procedure. Finally, α-Ni0.75Zn0.25(OH)2 screen-printed electrodes (SPE) were developed for the measurement of UA directly in real saliva and sweat samples, without interference of ascorbic acid, acetaminophen, lactate, and glucose at their typical concentrations present in those body fluids, revealing high potential for application as disposable sensors in biological systems. Graphical abstract.

Onion-like Multifunctional Microtrap Vehicles for Attraction-Trapping-Destruction of Biological Threats.

A multifunctional motile microtrap is developed that is capable of autonomously attracting, trapping, and destroying pathogens by controlled chemoattractant and therapeutic agent release. The onion-inspired multi-layer structure contains a magnesium engine core and inner chemoattractant and therapeutic layers. Upon chemical propulsion, the magnesium core is depleted, resulting in a hollow structure that exposes the inner layers and serves as structural trap. The sequential dissolution and autonomous release of the chemoattractant and killing agents result in long-range chemotactic attraction, trapping, and destruction of motile pathogens. The dissolved chemoattractant (l-serine) significantly increases the accumulation and capture of motile pathogens (E. coli) within the microtrap structure, while the internal release of silver ions (Ag+ ) leads to lysis of the pathogen accumulated within the microtrap cavity.

Pacifier Biosensor: Toward Noninvasive Saliva Biomarker Monitoring.

Wearable sensors for noninvasive monitoring of physiological parameters is a growing technology in the clinical field. Especially in neonates, the development of portable and nonharmful monitoring devices is urgently needed because they cannot provide any feedback about discomfort or health complaints. However, in infant monitoring, only wearable sensors measuring physical parameters for vital signs have been developed. Here, we describe the first chemical wearable sensor for newborn monitoring. This fully integrated pacifier operates as a portable wireless device toward noninvasive chemical monitoring in the infant's saliva. The infant's mouth movements on the pacifier result in efficient saliva pumping and promote unidirectional flow from the mouth to the electrochemical chamber. The integrated electrochemical detection chamber, containing the enzymatic biosensor, is located outside of the oral cavity. The capabilities of the platform were studied for glucose detection in diabetic adults and compared to their blood levels with good correlation, demonstrating the sensor's good performance. This baby-friendly device integrates saliva sampling with electrochemical sensing, along with miniaturized wireless electronics on a single pacifier platform. Such integration simplifies the infant's health monitoring in a real-time and selective fashion, representing the first wearable sensor focusing on chemical saliva sensing in newborns. This initial demonstration of glucose monitoring introduces new possibilities for metabolites monitoring in infants and neonates using saliva as a noninvasive sample.

Enzymatic/Immunoassay Dual-Biomarker Sensing Chip: Towards Decentralized Insulin/Glucose Detection.

Performing bioassay formats based on enzyme and antibody recognition reactions with a single detection chip remains an unmet challenge owing to the different requirements of such bioassays. Herein, we describe a dual-marker biosensor chip, integrating enzyme and antibody-based assays for simultaneous electrochemical measurements of insulin (I) and glucose (G). Simultaneous G/I sensing has been realized by addressing key fabrication and operational challenges associated with the different assay requirements and surface chemistry. The I immunosensor relies on a peroxidase-labeled sandwich immunoassay, while G is monitored through reaction with glucose oxidase. The dual diabetes biomarker chip offers selective and reproducible detection of picomolar I and millimolar G concentrations in a single microliter sample droplet within less than 30 min, including direct measurements in whole blood and saliva samples. The resulting integrated enzymatic-immunoassay biosensor chip opens a new realm in point-of-care multiplexed biomarker detection.

Vertical Gold Nanowires Stretchable Electrochemical Electrodes.

Conventional electrodes produced from gold or glassy carbon are outstanding electrochemical platforms for biosensing applications due to their chemical inertness and wide electrochemical window, but are intrinsically rigid and planar in nature. Hence, it is challenging to seamlessly integrate them with soft and curvilinear biological tissues for real-time wearable or implantable electronics. In this work, we demonstrate that vertically gold nanowires (v-AuNWs) possess an enokitake-like structure, with the nanoparticle (head) on one side and nanowires (tail) on the opposite side of the structure, and can serve as intrinsically stretchable, electrochemical electrodes due to the stronger nanowire-elastomer bonding forces preventing from interfacial delamination under strains. The exposed head side of the electrode comprising v-AuNWs can achieve a detection limit for H2O2 of 80 µM, with a linear range of 0.2-10.4 mM at 20% strain, with a reasonably high sensitivity using chronoamperometry. This excellent electrochemical performance in the elongated state, in conjunction with low-cost wet-chemistry fabrication, demonstrates that v-AuNWs electrodes may become a next-generation sensing platform for conformally integrated, in vivo biodiagnostics.

Micromotors Spontaneously Neutralize Gastric Acid for pH-Responsive Payload Release.

The highly acidic gastric environment creates a physiological barrier for using therapeutic drugs in the stomach. While proton pump inhibitors have been widely used for blocking acid-producing enzymes, this approach can cause various adverse effects. Reported herein is a new microdevice, consisting of magnesium-based micromotors which can autonomously and temporally neutralize gastric acid through efficient chemical propulsion in the gastric fluid by rapidly depleting the localized protons. Coating these micromotors with a cargo-containing pH-responsive polymer layer leads to autonomous release of the encapsulated payload upon gastric-acid neutralization by the motors. Testing in a mouse model demonstrate that these motors can safely and rapidly neutralize gastric acid and simultaneously release payload without causing noticeable acute toxicity or affecting the stomach function, and the normal stomach pH is restored within 24 h post motor administration.

Superfast Near-Infrared Light-Driven Polymer Multilayer Rockets.

A gold nanoshell-functionalized polymer multilayer nanorocket performs self-propulsion upon the irradiation with NIR light in the absence of chemical fuel. Theoretical simulations reveal that the NIR light-triggered self-thermophoresis drives the propulsion of the nanorocket. The nanorocket also displays -efficient NIR light-triggered propulsion in -biofluids and thus holds considerable promise for various potential biomedical applications.

Ultrasound-modulated bubble propulsion of chemically powered microengines.

The use of an ultrasound (US) field for rapid and reversible control of the movement of bubble-propelled chemically powered PEDOT/Ni/Pt microengines is demonstrated. Such operation reflects the US-induced disruption of normal bubble evolution and ejection, essential for efficient propulsion of catalytic microtubular engines. It offers precise speed control, with sharp increases and decreases of the speed at low and high US powers, respectively. A wide range of speeds can thus be generated by tuning the US power. Extremely fast changes in the motor speed (<0.1 s) and reproducible "On/Off" activations are observed, indicating distinct advantages compared to motion control methods based on other external stimuli. Such effective control of the propulsion of chemically powered microengines, including remarkable "braking" ability, holds considerable promise for diverse applications.

Non-invasive mouthguard biosensor for continuous salivary monitoring of metabolites.

The present work describes the first example of a wearable salivary metabolite biosensor based on the integration of a printable enzymatic electrode on a mouthguard. The new mouthguard enzymatic biosensor, based on an immobilized lactate oxidase and a low potential detection of the peroxide product, exhibits high sensitivity, selectivity and stability using whole human saliva samples. Such non-invasive mouthguard metabolite biosensors could tender useful real-time information regarding a wearer's health, performance and stress level, and thus hold considerable promise for diverse biomedical and fitness applications.

Molecularly imprinted polymer-based catalytic micromotors for selective protein transport.

We demonstrate an attractive nanomachine "capture and transport" target isolation strategy based on molecularly imprinted polymers (MIPs). MIP-based catalytic microtubular engines are prepared by electropolymerization of the outer polymeric layer in the presence of the target analyte (template). Tailor-made selective artificial recognition sites are thus introduced into the tubular microtransporters through complementary nanocavities in the outer polymeric layer. The new microtransporter concept is illustrated using bilayer poly(3,4-ethylenedioxythiophene) (PEDOT)/Pt-Ni microengines and fluorescein isothiocyanate (FITC)-labeled avidin (Av-FITC) as the template. The avidin-imprinted polymeric layer selectively concentrates the fluorescent-tagged protein target onto the moving microengine without the need for additional external functionalization, allowing "on-the-fly" extraction and isolation of Av-FITC from raw serum and saliva samples along with real-time visualization of the protein loading and transport. The new micromachine-MIP-based target isolation strategy can be extended to the capture and transport of other important target molecules, leading toward diverse biomedical and environmental applications.

Cargo-towing fuel-free magnetic nanoswimmers for targeted drug delivery.

Fuel-free nanomotors are essential for future in-vivo biomedical transport and drug-delivery applications. Herein, the first example of directed delivery of drug-loaded magnetic polymeric particles using magnetically driven flexible nanoswimmers is described. It is demonstrated that flexible magnetic nickel-silver nanoswimmers (5-6 µm in length and 200 nm in diameter) are able to transport micrometer particles at high speeds of more than 10 µm s(-1) (more than 0.2 body lengths per revolution in dimensionless speed). The fundamental mechanism of the cargo-towing ability of these magnetic (fuel-free) nanowire motors is modelled, and the hydrodynamic features of these cargo-loaded motors discussed. The effect of the cargo size on swimming performance is evaluated experimentally and compared to a theoretical model, emphasizing the interplay between hydrodynamic drag forces and boundary actuation. The latter leads to an unusual increase of the propulsion speed at an intermediate particle size. Potential applications of these cargo-towing nanoswimmers are demonstrated by using the directed delivery of drug-loaded microparticles to HeLa cancer cells in biological media. Transport of the drug carriers through a microchannel from the pick-up zone to the release microwell is further illustrated. It is expected that magnetically driven nanoswimmers will provide a new approach for the rapid delivery of target-specific drug carriers to predetermined destinations.

Spatial configuration of hepatitis E virus antigenic domain.

Hepatitis E virus (HEV) is a human pathogen that causes acute hepatitis. When an HEV capsid protein containing a 52-amino-acid deletion at the C terminus and a 111-amino-acid deletion at the N terminus is expressed in insect cells, the recombinant HEV capsid protein can self-assemble into a T=1 virus-like particle (VLP) that retains the antigenicity of the native HEV virion. In this study, we used cryoelectron microscopy and image reconstruction to show that anti-HEV monoclonal antibodies bind to the protruding domain of the capsid protein at the lateral side of the spikes. Molecular docking of the HEV VLP crystal structure revealed that Fab224 covered three surface loops of the recombinant truncated second open reading frame (ORF2) protein (PORF2) at the top part of the spike. We also determined the structure of a chimeric HEV VLP and located the inserted B-cell tag, an epitope of 11 amino acids coupled to the C-terminal end of the recombinant ORF2 protein. The binding site of Fab224 appeared to be distinct from the location of the inserted B-cell tag, suggesting that the chimeric VLP could elicit immunity against both HEV and an inserted foreign epitope. Therefore, the T=1 HEV VLP is a novel delivery system for displaying foreign epitopes at the VLP surface in order to induce antibodies against both HEV and the inserted epitope.

A self-powered "sense-act-treat" system that is based on a biofuel cell and controlled by boolean logic.

Bio-logic-al: an autonomous, integrated "sense-act-treat" system that is based on an enzymatic biofuel cell has been developed. The system couples a biocomputing logic-detection method with a drug-release system to provide a logic-activated therapeutic intervention in response to a simulated abnormal physiological state, without the need for an external power source, control electronics, or microelectromechanical actuators.

Facile preparation of carbon nanotube/poly(ethyl 2-cyanoacrylate) composite electrode by water-vapor-initiated polymerization for enhanced amperometric detection.

A carbon nanotube/poly(ethyl 2-cyanoacrylate) (CNT/PECA) composite electrode was developed for enhanced amperometric detection. The composite electrode was fabricated on the basis of water-vapor-initiated polymerization of a mixture of CNTs and ethyl 2-cyanoacrylate in the bore of a piece of fused silica capillary. The morphology and structure of the composite were investigated by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis. The results indicate that the CNTs were well dispersed and embedded throughout the PECA matrix to form an interconnected CNT network. The analytical performance of this unique CNT-based detector has been demonstrated by separating and detecting six flavones in combination with capillary electrophoresis. The advantages of the CNT/PECA composite detector include lower operating potential, higher sensitivity, low expense of fabrication, satisfactory resistance to surface fouling, and enhanced stability; these properties indicate great promise for a wide range of applications.

Wearable electrochemical biosensors in North America.

Tremendous research and commercialization efforts around the world are focused on developing novel wearable electrochemical biosensors that can noninvasively and continuously screen for biochemical markers in body fluids for the prognosis, diagnosis and management of diseases, as well as the monitoring of fitness. Researchers in North America are leading the development of innovative wearable platforms that can comfortably comply to the human body and efficiently sample fluids such as sweat, interstitial fluids, tear and saliva for the electrochemical detection of biomarkers through various sensing approaches such as potentiometric ion selective electrodes and amperometric enzymatic sensors. We start this review with a historical timeline overviewing the major milestones in the development of wearable electrochemical sensors by North American institutions. We then describe how such research efforts have led to pioneering developments and are driving the advancement and commercialization of wearable electrochemical sensors: from minimally invasive continuous glucose monitors for chronic disease management to non-invasive sweat electrolyte sensors for dehydration monitoring in fitness applications. While many countries across the globe have contributed significantly to this rapidly emerging field, their contributions are beyond the scope of this review. Furthermore, we share our perspective on the promising future of wearable electrochemical sensors in applications spanning from remote and personalized healthcare to wellness.

Rapid delivery of drug carriers propelled and navigated by catalytic nanoshuttles.

This paper reports the first proof-of-concept of using catalytic nanoshuttles to pick up, transport, and release common drug carriers including biocompatible and biodegradable polymeric particles and liposomes. The rapid transport of a wide size range of drug-loaded particles (100 nm-3.0 µm) with a speed approximately three orders of magnitude faster than that of the particles transported by Brownian motion demonstrates the high propulsion power of the nanoshuttles. The nanoshuttles' navigation ability is illustrated by the transport of the drug carriers through a microchannel from the pick-up to the release microwell. Such ability of nanomotors to rapidly deliver drug-loaded polymeric particles and liposomes to their target destination represents a novel approach towards transporting drug carriers in a target-specific manner. This also potentially addresses the obstacles of current nanoparticle drug delivery, such as off-targeting of particles. While an initial concept of actively transporting therapeutic particles is demonstrated in vitro in this paper, future efforts will focus on practical in vivo motor-based targeted drug delivery in connection to fuel-free nanovehicles.