High-Fidelity sEMG Signals Recorded by an on-Skin Electrode Based on AgNWs for Hand Gesture Classification Using Machine Learning.

The human forearm is one of the most densely distributed parts of the human body, with the most irregular spatial distribution of muscles. A number of specific forearm muscles control hand motions. Acquiring high-fidelity sEMG signals from human forearm muscles is vital for human-machine interface (HMI) applications based on gesture recognition. Currently, the most commonly used commercial electrodes for detecting sEMG or other electrophysiological signals have a rigid nature without stretchability and cannot maintain conformal contact with the human skin during deformation, and the adhesive hydrogel used in them to reduce skin-electrode impedance may shrink and cause skin inflammation after long-term use. Therefore, developing elastic electrodes with stretchability and biocompatibility for sEMG signal recording is essential for developing HMI. Here, we fabricated a nanocomposite hybrid on-skin electrode by infiltrating silver nanowires (AgNWs), a one-dimensional (1D) nano metal material with conductivity, into polydimethylsiloxane (PDMS), a silicone elastomer with a similar Young's modulus to that of the human skin. The AgNW on-skin electrode has a thickness of 300 µm and low sheet resistance of 0.481 ± 0.014 Ω/sq and can withstand the mechanical strain of up to 54% and maintain a sheet resistance lower than 1 Ω/sq after 1000 dynamic strain cycles. The AgNW on-skin electrode can record high signal-to-noise ratio (SNR) sEMG signals from forearm muscles and can reflect various force levels of muscles by sEMG signals. Besides, four typical hand gestures were recognized by the multichannel AgNW on-skin electrodes with a recognition accuracy of 92.3% using machine learning method. The AgNW on-skin electrode proposed in this study has great potential and promise in various HMI applications that employ sEMG signals as control signals.

Detection of Bacterial Metabolic Volatile Indole Using a Graphene-Based Field-Effect Transistor Biosensor.

The existence of bacteria is a great threat to food safety. Volatile compounds secreted by bacteria during their metabolic process can be dissected to evaluate bacterial contamination. Indole, as a major volatile molecule released by Escherichia coli (E. coli), was chosen to examine the presence of E. coli in this research. In this work, a graphene field-effect transistor (G-FET) was employed to detect the volatile molecule-indole based on a π-π stacking interaction between the indole and the graphene. The exposure of G-FET devices to the indole provokes a change in electrical signal, which is ascribed to the adsorption of the indole molecule onto the graphene surface via π-π stacking. The adsorption of the indole causes a charge rearrangement of the graphene-indole complex, which leads to changes in the electrical signal of G-FET biosensors with a different indole concentration. Currently, the indole biosensor can detect indole from 10 ppb to 250 ppb and reach a limit of detection of 10 ppb for indole solution detection. We believe that our detection strategy for detecting bacterial metabolic gas molecules will pave a way to developing an effective platform for bacteria detection in food safety monitoring.

Topography induced stiffness alteration of stem cells influences osteogenic differentiation.

Topography-driven alterations in cell morphology tremendously influence cell biological processes, particularly stem cell differentiation. Aligned topography is known to alter the cell shape, which we anticipated to also induce altered physical properties of the cell. Here, we show that topography has a significant influence on single cell stiffness of human bone marrow derived-Mesenchymal Stem Cells (hBM-MSCs) and the osteogenic differentiation of these. Aligned topographies were used to control the cell elongation, depicted as the cell aspect ratio (CAR). Intriguingly, an equal CAR elicited from different topographies, resulted in highly altered differentiation behavior and the underlying single cell mechanics was found to be critical. The cell behavior was found to be focal adhesion-mediated and induced stiffness alterations rather than just influencing the cell elongation. The effect was further corroborated by investigations of the transcriptional regulators YAP. Our study provides insight into how mechanical properties of the cell, which are stimulated by topography, modulate the osteogenesis of hBM-MSCs, which is beneficial for improving the understanding of interactions between stem cells and topography for developing applications of tissue engineering and regenerative medicine.

An ultraflexible polyurethane yarn-based wearable strain sensor with a polydimethylsiloxane infiltrated multilayer sheath for smart textiles.

Waterproof fiber-based strain sensors with a high gauge factor and outstanding stability are essential for smart textiles, wearable devices and biomedical electronics. In this work, we demonstrate a highly flexible, stretchable, sensitive, and waterproof core-sheath structure strain sensor with a relatively wide strain-sensing range fabricated by a simple approach. Such a core-sheath structure is composed of a superelastic core material polyurethane (PU) yarn; a highly conductive multilayer sheath material, namely, graphene nanosheets/thin gold film/graphene nanosheets (GNSs/Au/GNSs); and a thin polydimethylsiloxane (PDMS) wrapping layer. The combination of the PU yarn, multilayer GNSs/Au/GNSs, and PDMS wrapping layer enables the strain sensor to achieve high flexibility and stretchability, high sensitivity, broad strain-sensing range, and good waterproof property simultaneously due to the infiltration of PDMS into the multilayer during stretching. Particularly, the yarn strain sensor exhibits a high gauge factor (GF: 661.59), outstanding stability with an applied strain of 50% for approximately 10 000 stretch/release cycles, and superior water resistance. Moreover, it can be readily integrated into textiles, including medical textile bandages and textile gloves, for monitoring various human motions (e.g., phonation, pulse, finger bending, and walking) and effectively control a hand robot. Therefore, strain sensors show considerable potential in textile, wearable, and biomedical electronics for healthcare-related applications, such as disease diagnosis, preventive healthcare, and rehabilitation care, and robot controlling-related applications (e.g., controlling a hand robot to catch some objects).

Interaction of Sp1 and APP promoter elucidates a mechanism for Pb2+ caused neurodegeneration.

A ubiquitously expressed transcription factor, specificity protein 1 (Sp1), interacts with the amyloid precursor protein (APP) promoter and likely mediates APP expression. Promoter-interaction strengths variably regulate the level of APP expression. Here, we examined the interactions of finger 3 of Sp1 (Sp1-f3) with a DNA fragment containing the APP promoter in different ionic solutions using atomic force microscope (AFM) spectroscopy. Sp1-f3 molecules immobilized on an Si substrate were bound to the APP promoter, which was linked to the AFM tips via covalent bonds. The interactions were strongly influenced by Pb2+, considering that substituting Zn2+ with Pb2+ increased the binding affinity of Sp1 for the APP promoter. The results revealed that the enhanced interaction force facilitated APP expression and that APP overexpression could confer a high-risk for disease incidence. An increased interaction force between Sp1-f3 and the APP promoter in Pb2+ solutions was consistent with a lower binding free energy, as determined by computer-assisted analysis. The impact of Pb2+ on cell morphology and related mechanical properties were also detected by AFM. The overexpression of APP caused by the enhanced interaction force triggered actin reorganization and further resulted in an increased Young's modulus and viscosity. The correlation with single-force measurements revealed that altered cellular activities could result from alternation of Sp1-APP promoter interaction. Our AFM findings offer a new approach in understanding Pb2+ associated neurodegeneration.

Reversible reconfiguration of high-order DNA nanostructures by employing G-quartet toeholds as adhesive units.

G-quadruplex structures are becoming useful alternative interaction modules for the assembly of DNA nanomaterials because of their unique inducibility by cations. In this study, we demonstrated a new strategy for the assembly of polymeric DNA nanoarchitectures in the presence of cations, such as K+ and Na+, by employing G-quartet toeholds at the edges of discrete mini-square DNA building blocks as adhesive units. In comparison with the Watson-Crick base-paired duplex linkers, G-quadruplex arrays embedded in the self-assembled DNA system exhibit higher thermal stability. The morphology of these doughnut-shaped or spherical-shaped DNA nanostructures is highly regulated by the orientation of the folded G-quadruplexes either in parallel or antiparallel orientation in response to different cations. Furthermore, this G-quadruplex-mediated assembly strategy is able to manipulate the cycling of DNA assemblies between discrete and polymeric states by means of introducing cations and chelating agents sequentially. This property enables the reversible manipulation of the DNA-based nanosystems for at least 4 cycles. The G-quadruplex array embedded in this self-assembled DNA system can become a scaffold for functional molecules, as a number of organic molecules and proteins exhibit specific binding to these G-quadruplex structures. Besides, embedded G-quadruplexes are also considered as functional components of nanoscale electronic materials due to their electron transport through the stacked orientation of the G-quartet. Therefore, this work is an important step towards obtaining reversible, responsive G-quadruplex-induced DNA-based nanomaterials with versatile functionalities which will be highly useful in further electronic, biomedical and drug-delivery applications.

Cholesterol Modulates the Formation of the Aß Ion Channel in Lipid Bilayers.

The misfolding of amyloid beta (Aß) is one of the predominant hallmarks in the pathology of Alzheimer's disease (AD). In this study, we showed that the formation of the Aß ion channel on the membrane depended on the cholesterol concentration. From a mechanical aspect, we found that cholesterol levels affected the stability and assembly of lipid bilayers. Measurements on planar lipid bilayers indicated that a small amount of cholesterol interacted with Aß proteins and promoted the insertion process. Conversely, high cholesterol integrated the lipid bilayer and exerted an opposite effect on Aß insertion. The Aß ion channel was then detected by graphene-based field-effect transistors. Results demonstrated that the Aß ion channel promoted a Ca2+ flux in the presence of 15% cholesterol but prevented a Ca2+ flux in high cholesterol. Thus, cholesterol had a complex impact on the Aß ion channel that can be described as two different effects. First, a small amount of cholesterol interacted with Aß and facilitated the Aß ion channel formation in the membrane. Second, a large amount of cholesterol did not induce the ion flux in the membrane, which can be explained by the cholesterol damage to the regular distribution of the lipid bilayer. Overall, this study suggested a possible approach to consider cholesterol levels for the treatment of AD patients.

Extracellular Nanomatrix-Induced Self-Organization of Neural Stem Cells into Miniature Substantia Nigra-Like Structures with Therapeutic Effects on Parkinsonian Rats.

Substantia nigra (SN) is a complex and critical region of the brain wherein Parkinson's disease (PD) arises from the degeneration of dopaminergic neurons. Miniature SN-like structures (mini-SNLSs) constructed from novel combination of nanomaterials and cell technologies exhibit promise as potentially curative cell therapies for PD. In this work, a rapid self-organization of mini-SNLS, with an organizational structure and neuronal identities similar to those of the SN in vivo, is achieved by differentiating neural stem cells in vitro on biocompatible silica nanozigzags (NZs) sculptured by glancing angle deposition, without traditional chemical growth factors. The differentiated neurons exhibit electrophysiological activity in vitro. Diverse physical cues and signaling pathways that are determined by the nanomatrices and lead to the self-organization of the mini-SNLSs are clarified and elucidated. In vivo, transplantation of the neurons from a mini-SNLS results in an early and progressive amelioration of PD in rats. The sculptured medical device reported here enables the rapid and specific self-organization of region-specific and functional brain-like structures without an undesirable prognosis. This development provides promising and significant insights into the screening of potentially curative drugs and cell therapies for PD.

Facile construction of a DNA tetrahedron in unconventional ladder-like arrangements at room temperature.

A DNA tetrahedron as the most classical and simplest three-dimensional DNA nanostructure has been widely utilized in biomedicine and biosensing. However, the existing assembly approaches usually require harsh thermal annealing conditions, involve the formation of unwanted by-products, and have poor size control. Herein, a facile strategy to fabricate a discrete DNA tetrahedron as a single, thermodynamically stable product in a quantitative yield at room temperature is reported. This system does not require a DNA trigger or thermal annealing treatment to initiate self-assembly. This DNA tetrahedron was made of three chemically ligated triangular-shaped DNAs in unconventional ladder-like arrangements, with measured heights of ∼4.16 ± 0.04 nm, showing extra protections for enzymatic degradation in biological environment. They show substantial cellular uptake in different cell lines via temperature, energy-dependent and clathrin-mediated endocytosis pathways. These characteristics allow our DNA tetrahedron to be used as vehicles for the delivery of very small and temperature-sensitive cargos. This novel assembly strategy developed for DNA tetrahedra could potentially be extended to other highly complex polyhedra; this indicated its generalizability.

Simulation of Graphene Field-Effect Transistor Biosensors for Bacterial Detection.

Foodborne illness is correlated with the existence of infectious pathogens such as bacteria in food and drinking water. Probe-modified graphene field effect transistors (G-FETs) have been shown to be suitable for Escherichia coli (E. coli) detection. Here, the G-FETs for bacterial detection are modeled and simulated with COMSOL Multiphysics to understand the operation of the biosensors. The motion of E. coli cells in electrolyte and the surface charge of graphene induced by E. coli are systematically investigated. The comparison between the simulation and experimental data proves the sensing probe size to be a key parameter affecting the surface charge of graphene induced by bacteria. Finally, the relationship among the change in source-drain current (∆Ids), graphene-bacteria distance and bacterial concentration is established. The shorter graphene-bacteria distance and higher bacterial concentration give rise to better sensing performance (larger ∆Ids) of the G-FETs biosensors. The simulation here could serve as a guideline for the design and optimization of G-FET biosensors for various applications.

Biophysical Characteristics of Human Neuroblastoma Cell in Oligomeric $\beta $ -Amyloid (1-40) Cytotoxicity.

Beta amyloid ( ) peptide, which is a common neuropathological hallmark deposit in the brain of patients with Alzheimer's disease, typically comprises 39-43 amino acid residues. peptides exist as isoforms of and with various lengths. In this research, atomic force microscopy (AFM) was applied to investigate aggregations in Hank's Balanced Salt Solution. Toxic effect of oligomer was investigated in live SH-SY5Y neuroblastoma cells by characterizing cell morphology and cell mechanics using high-resolution AFM scanning. oligomer-induced cytoskeleton reorganization was also observed under confocal microscopy, and it can account for reduction in Young's modulus of cells. Meanwhile, phosphorylation of tau increased after oligomer treatment, possibly resulting in microtubule disassembly. This paper demonstrates the linkage between cellular mechanical changes and neurodegeneration mediated by . The method used implies promising applications of real-time monitoring of cellular mechanical properties given the toxic effects of on living neuronal cells.

Graphene Field-Effect Transistors for the Sensitive and Selective Detection of Escherichia coli Using Pyrene-Tagged DNA Aptamer.

This study reports biosensing using graphene field-effect transistors with the aid of pyrene-tagged DNA aptamers, which exhibit excellent selectivity, affinity, and stability for Escherichia coli (E. coli) detection. The aptamer is employed as the sensing probe due to its advantages such as high stability and high affinity toward small molecules and even whole cells. The change of the carrier density in the probe-modified graphene due to the attachment of E. coli is discussed theoretically for the first time and also verified experimentally. The conformational change of the aptamer due to the binding of E. coli brings the negatively charged E. coli close to the graphene surface, increasing the hole carrier density efficiently in graphene and achieving electrical detection. The binding of negatively charged E. coli induces holes in graphene, which are pumped into the graphene channel from the contact electrodes. The carrier mobility, which correlates the gate voltage to the electrical signal of the APG-FETs, is analyzed and optimized here. The excellent sensing performance such as low detection limit, high sensitivity, outstanding selectivity and stability of the graphene biosensor for E. coli detection paves the way to develop graphene biosensors for bacterial detection.

A turn-on fluorescent probe based on coumarin-anhydride for highly sensitive detection of hydrazine in the aqueous solution and gas states.

In this paper, a new coumarin-based fluorescent probe for hydrazine was rationally designed and successfully synthesized based on the Gabriel reaction. This novel probe enabled highly sensitive and selective detection of hydrazine. The detection limit was 43.6 nM (1.49 ppb). It displayed distinct changes in the intensity of both absorption and emission spectra upon the addition of hydrazine and remarkable color changes can be visually observed. The sensing mechanism of this probe toward hydrazine was characterized by 1H NMR and mass spectroscopy. Moreover, with the help of theoretical calculations, the sensing capability of this probe for hydrazine detection was described: the electron structure was modulated by a three-substituted group of coumarin once upon the addition of hydrazine. In addition, a test paper experiment indicated its great potential in environment monitoring.

Development of the Electric Equivalent Model for the Cytoplasmic Microinjection of Small Adherent Cells.

A novel approach utilizing current feedback for the cytoplasmic microinjection of biological cells is proposed. In order to realize the cytoplasmic microinjection on small adherent cells (diameter < 30 µm and thickness < 10 µm), an electrical model is built and analyzed according to the electrochemical properties of target cells. In this study, we have verified the effectiveness of the current measurement for monitoring the injection process and the study of ion channel activities for verifying the cell viability of the cells after the microinjection.

A highly versatile platform based on geometrically well-defined 3D DNA nanostructures for selective recognition and positioning of multiplex targets.

We develop a versatile recognition system based on 3D triangular-shaped DNA nanotubes by integrating three different aptamer sequences along the three edges. This would allow multiple binding activities to be combined into a single system. The versatility of this nanotube platform can also provide a framework for spatial orientation and positioning of different aptamer-binding ligands in a 'pea-pod' architecture.

Compressive Video Recovery Using Block Match Multi-Frame Motion Estimation Based on Single Pixel Cameras.

Compressive sensing (CS) theory has opened up new paths for the development of signal processing applications. Based on this theory, a novel single pixel camera architecture has been introduced to overcome the current limitations and challenges of traditional focal plane arrays. However, video quality based on this method is limited by existing acquisition and recovery methods, and the method also suffers from being time-consuming. In this paper, a multi-frame motion estimation algorithm is proposed in CS video to enhance the video quality. The proposed algorithm uses multiple frames to implement motion estimation. Experimental results show that using multi-frame motion estimation can improve the quality of recovered videos. To further reduce the motion estimation time, a block match algorithm is used to process motion estimation. Experiments demonstrate that using the block match algorithm can reduce motion estimation time by 30%.

Cellular level robotic surgery: Nanodissection of intermediate filaments in live keratinocytes.

We present the nanosurgery on the cytoskeleton of live cells using AFM based nanorobotics to achieve adhesiolysis and mimic the effect of pathophysiological modulation of intercellular adhesion. Nanosurgery successfully severs the intermediate filament bundles and disrupts cell-cell adhesion similar to the desmosomal protein disassembly in autoimmune disease, or the cationic modulation of desmosome formation. Our nanomechanical analysis revealed that adhesion loss results in a decrease in cellular stiffness in both cases of biochemical modulation of the desmosome junctions and mechanical disruption of intercellular adhesion, supporting the notion that intercellular adhesion through intermediate filaments anchors the cell structure as focal adhesion does and that intermediate filaments are integral components in cell mechanical integrity. The surgical process could potentially help reveal the mechanism of autoimmune pathology-induced cell-cell adhesion loss as well as its related pathways that lead to cell apoptosis.

Probing for chemotherapy-induced peripheral neuropathy in live dorsal root ganglion neurons with atomic force microscopy.

Chemotherapy-induced peripheral neuropathy (CIPN) remains a major reason for cancer patients to withdraw from their lifesaving therapy. CIPN results in irreversible sensory and motor impairments; however, the epidemiology is largely unknown. Here, we report for the first time that chemotherapy drug vincristine not only reduced axonal regeneration in primary dorsal root ganglion neuron but also induced substantial changes in cell mechanical properties detected by atomic force microscopy (AFM). Confocal imaging analysis revealed vincristine-induced microtubule depolymerization. By using AFM for high-resolution live cell imaging and quantitative analysis, we observed significant changes in cell surface roughness and stiffness of vincristine-treated neurons. Elastic modulus was decreased (21-45%) with increasing dosage of vincristine. Further study with paclitaxel, another well-known CIPN drug, confirmed the link between cell mechanics and cytoskeleton organization. These data support that our system can be used for probing potential CIPN drugs that are of enormous benefit to new chemotherapy drug development. FROM THE CLINICAL EDITOR: This study concludes that reduced cell elasticity in dorsal root ganglion neurons accompanies the development of chemotherapy-induced peripheral neuropathy, providing a model system that enables testing of upcoming chemotherapy agents for this particularly inconvenient and often treatment-limiting complication.

Cellular biophysical dynamics and ion channel activities detected by AFM-based nanorobotic manipulator in insulinoma ß-cells.

Distinct biochemical, electrochemical and electromechanical coupling processes of pancreatic ß-cells may well underlie different response patterns of insulin release from glucose and capsaicin stimulation. Intracellular Ca(2+) levels increased rapidly and dose-dependently upon glucose stimulation, accompanied with about threefold rapid increases in cellular stiffness. Subsequently, cellular stiffness diminished rapidly and settled at a value about twofold of the baseline. Capsaicin caused a similar transient increase in intracellular Ca(2+) changes. However, cellular stiffness increased gradually to about twofold until leveling off. The current study characterizes for the first time the biophysical properties underlying glucose-induced biphasic responses of insulin secretion, distinctive from the slow and single-phased stiffness response to capsaicin despite similar changes in intracellular Ca(2+) levels. The integrated AFM nanorobotics and optical investigation enables the fine dissection of mechano-property from ion channel activities in response to specific and non-specific agonist stimulation, providing novel biomechanical markers for the insulin secretion process. FROM THE CLINICAL EDITOR: This study characterizes the biophysical properties underlying glucose-induced biphasic responses of insulin secretion. Integrated AFM nanorobotics and optical investigations provided novel biomechanical markers for the insulin secretion process.

Cellular-level surgery using nano robots.

The atomic force microscope (AFM) is a popular instrument for studying the nano world. AFM is naturally suitable for imaging living samples and measuring mechanical properties. In this article, we propose a new concept of an AFM-based nano robot that can be applied for cellular-level surgery on living samples. The nano robot has multiple functions of imaging, manipulation, characterizing mechanical properties, and tracking. In addition, the technique of tip functionalization allows the nano robot the ability for precisely delivering a drug locally. Therefore, the nano robot can be used for conducting complicated nano surgery on living samples, such as cells and bacteria. Moreover, to provide a user-friendly interface, the software in this nano robot provides a "videolized" visual feedback for monitoring the dynamic changes on the sample surface. Both the operation of nano surgery and observation of the surgery results can be simultaneously achieved. This nano robot can be easily integrated with extra modules that have the potential applications of characterizing other properties of samples such as local conductance and capacitance.