Design of Hierarchical Beads for Efficient Label‐Free Cell Capture

Defined hierarchical materials promise cell analysis and call for application‐driven design in practical use. The further issue is to develop advanced materials and devices for efficient label‐free cell capture with minimum instrumentation. Herein, the design of hierarchical beads is reported for efficient label‐free cell capture. Silica nanoparticles (size of ≈15 nm) are coated onto silica spheres (size of ≈200 nm) to achieve nanoscale surface roughness, and then the rough silica spheres are combined with microbeads (≈150–1000 µm in diameter) to assemble hierarchical structures. These hierarchical beads are built via electrostatic interaction, covalent bonding, and nanoparticle adherence. Further, after functionalization by hyaluronic acid (HA), the hierarchical beads display desirable surface hydrophilicity, biocompatibility, and chemical/structural stability. Due to the controlled surface topology and chemistry, HA‐functionalized hierarchical beads afford high cell capture efficiency up to 98.7% in a facile label‐free manner. This work guides the development of label‐free cell capture techniques and contributes to the construction of smart interfaces in bio‐systems.     

A High‐Performance Lithium‐Ion Capacitor Based on 2D Nanosheet Materials

Lithium‐ion capacitors (LICs) are promising electrical energy storage systems for mid‐to‐large‐scale applications due to the high energy and large power output without sacrificing long cycle stability. However, due to the different energy storage mechanisms between anode and cathode, the energy densities of LICs often degrade noticeably at high power density, because of the sluggish kinetics limitation at the battery‐type anode side. Herein, a high‐performance LIC by well‐defined ZnMn₂O₄‐graphene hybrid nanosheets anode and N‐doped carbon nanosheets cathode is presented. The 2D nanomaterials offer high specific surface areas in favor of a fast ion transport and storage with shortened ion diffusion length, enabling fast charge and discharge. The fabricated LIC delivers a high specific energy of 202.8 Wh kg^?1 at specific power of 180 W kg^?1, and the specific energy remains 98 Wh kg^?1 even when the specific power achieves as high as 21 kW kg^?1.     

Near‐Infrared Switchable Fullerene‐Based Synergy Therapy for Alzheimer's Disease

C₆₀ has a special dual function; it can act as both a powerful reactive oxygen species (ROS) producer under UV or visible light and an ROS scavenger in the dark. However, ROS has double‐edged effects in living systems. It is still a great challenge for biomedical application to switch and adjust the two opposite properties of C₆₀ in one system. Herein, UCNP@C₆₀‐pep (UCNP: upconversion nanoparticle, pep: Aβ‐target peptide KLVFF) is designed as a near‐infrared‐switchable nanoplatform for synergy therapy of Alzheimer's disease (AD). Under near‐infrared (NIR) light, the Aβ‐targeting hybrid nanoparticles produce ROS and result in Aβ photooxygenation, which can hinder Aβ aggregation and mitigate the attendant cytotoxicity. In the dark, UCNP@C₆₀‐pep shows protective effects against the increased oxidative stress. The ROS‐generating and ROS‐quenching abilities of UCNP@C₆₀‐pep are both beneficial for decreasing Aβ‐induced neurotoxicity and extending the longevity of the commonly used transgenic AD model Caenorhabditis elegans CL2006. Moreover, UCNP@C60‐pep can also be used for upconversion luminescence (UCL) and magnetic resonance imaging (MRI), which has benefits for “image‐guided therapy.” This study may offer a new perspective for the biological applications of C₆₀.     

Graphene‐Based Linear Tandem Micro‐Supercapacitors with Metal‐Free Current Collectors and High‐Voltage Output

Printable supercapacitors are regarded as a promising class of microscale power source, but are facing challenges derived from conventional sandwich‐like geometry. Herein, the printable fabrication of new‐type planar graphene‐based linear tandem micro‐supercapacitors (LTMSs) on diverse substrates with symmetric and asymmetric configuration, high‐voltage output, tailored capacitance, and outstanding flexibility is demonstrated. The resulting graphene‐based LTMSs consisting of 10 micro‐supercapacitors (MSs) present efficient high‐voltage output of 8.0 V, suggestive of superior uniformity of the entire integrated device. Meanwhile, LTMSs possess remarkable flexibility without obvious capacitance degradation under different bending states. Moreover, areal capacitance of LTMSs can be sufficiently modulated by incorporating polyaniline‐based pseudocapacitive nanosheets into graphene electrodes, showing enhanced capacitance of 7.6 mF cm^?2. To further improve the voltage output and energy density, asymmetric LTMSs are fabricated through controlled printing of linear‐patterned graphene as negative electrodes and MnO₂ nanosheets as positive electrodes. Notably, the asymmetric LTMSs from three serially connected MSs are easily extended to 5.4 V, triple voltage output of the single cell (1.8 V), suggestive of the versatile applicability of this technique. Therefore, this work offers numerous opportunities of graphene and analogous nanosheets for one‐step scalable fabrication of flexible tandem energy storage devices integrating with printed electronics on same substrate.     

CMOS‐Compatible Silicon Nanowire Field‐Effect Transistors for Ultrasensitive and Label‐Free MicroRNAs Sensing

MicroRNAs (miRNAs) have been regarded as promising biomarkers for the diagnosis and prognosis of early‐stage cancer as their expression levels are associated with different types of human cancers. However, it is a challenge to produce low‐cost miRNA sensors, as well as retain a high sensitivity, both of which are essential factors that must be considered in fabricating nanoscale biosensors and in future biomedical applications. To address such challenges, we develop a complementary metal oxide semiconductor (CMOS)‐compatible SiNW‐FET biosensor fabricated by an anisotropic wet etching technology with self‐limitation which provides a much lower manufacturing cost and an ultrahigh sensitivity. This nanosensor shows a rapid (< 1 minute) detection of miR‐21 and miR‐205, with a low limit of detection (LOD) of 1 zeptomole (ca. 600 copies), as well as an excellent discrimination for single‐nucleotide mismatched sequences of tumor‐associated miRNAs. To investigate its applicability in real settings, we have detected miRNAs in total RNA extracted from lung cancer cells as well as human serum samples using the nanosensors, which demonstrates their potential use in identifying clinical samples for early diagnosis of cancer.     

Reduced Graphene Oxide‐Functionalized High Electron Mobility Transistors for Novel Recognition Pattern Label‐Free DNA Sensors

We designed and constructed reduced graphene oxide (rGO) functionalized high electron mobility transistor (HEMT) for rapid and ultra‐sensitive detection of label‐free DNA in real time. The micrometer sized rGO sheets with structural defects helped absorb DNA molecules providing a facile and robust approach to functionalization. DNA was immobilized onto the surface of HEMT gate through rGO functionalization, and changed the conductivity of HEMT. The real time monitor and detection of DNA hybridization by rGO functionalized HEMT presented interesting current responses: a “two steps” signal enhancement in the presence of target DNA; and a “one step” signaling with random DNA. These two different recognition patterns made the HEMT capable of specifically detecting target DNA sequence. The working principle of the rGO functionalized HEMT can be demonstrated as the variation of the ambience charge distribution. Furthermore, the as constructed DNA sensors showed excellent sensitivity of detect limit at 0.07 fM with linear detect range from 0.1 fM to 0.1 pM. The results indicated that the HEMT functionalized with rGO paves a new avenue to design novel electronic devices for high sensitive and specific genetic material assays in biomedical applications.     

Label‐Free Optofluidic Nanobiosensor Enables Real‐Time Analysis of Single‐Cell Cytokine Secretion

Single‐cell analysis of cytokine secretion is essential to understand the heterogeneity of cellular functionalities and develop novel therapies for multiple diseases. Unraveling the dynamic secretion process at single‐cell resolution reveals the real‐time functional status of individual cells. Fluorescent and colorimetric‐based methodologies require tedious molecular labeling that brings inevitable interferences with cell integrity and compromises the temporal resolution. An innovative label‐free optofluidic nanoplasmonic biosensor is introduced for single‐cell analysis in real time. The nanobiosensor incorporates a novel design of a multifunctional microfluidic system with small volume microchamber and regulation channels for reliable monitoring of cytokine secretion from individual cells for hours. Different interleukin‐2 secretion profiles are detected and distinguished from single lymphoma cells. The sensor configuration combined with optical spectroscopic imaging further allows us to determine the spatial single‐cell secretion fingerprints in real time. This new biosensor system is anticipated to be a powerful tool to characterize single‐cell signaling for basic and clinical research.     

Magnetite/Ceria Nanoparticle Assemblies for Extracorporeal Cleansing of Amyloid‐β in Alzheimer's Disease

Accumulation of amyloid‐β (Aβ) peptides in the brain is regarded as a major contributor to the pathogenesis and progression of Alzheimer's disease (AD). However, development of clinically relevant techniques to reduce Aβ levels in AD patients is hindered by low efficiency and/or side effects. Here, an extracorporeal Aβ cleansing system, where multifunctional magnetite/ceria nanoparticle assemblies are used to remove Aβ peptides from flowing blood by specific capture and magnetic separation, is reported. The magnetite nanoparticles in the nanoassembly core enable the magnetic isolation of the captured Aβ peptides by generating a large attraction force under an external magnetic field. The ceria nanoparticles in the nanoassembly shell relieve oxidative stress by scavenging reactive oxygen species that are produced by immune response during the process. Blood Aβ cleansing treatment of 5XFAD transgenic mice not only demonstrates the decreased Aβ levels both in the blood and in the brain but also prevents the spatial working memory deficits, suggesting the potential of the method for AD prevention and therapy.     

The Regulatory Functionality of Exosomes Derived from hUMSCs in 3D Culture for Alzheimer's Disease Therapy

Reducing amyloid‐β (Aβ) accumulation could be a potential therapeutic approach for Alzheimer's disease (AD). Particular functional biomolecules in exosomes vested by the microenvironment in which the original cells resided can be transferred to recipient cells to improve pathological conditions. However, there are few reports addressing whether exosomes derived from cells cultured on scaffolds with varying dimension can reduce Aβ deposition or ameliorate cognitive decline for AD therapy. Herein, both 3D graphene scaffold and 2D graphene film are used as the matrix for human umbilical cord mesenchymal stem cell culture, from which the supernatants are obtained to isolate exosomes. The levels of 195 kinds of miRNAs and proteins, including neprilysin, insulin‐degrading enzyme and heat shock protein 70, in 3D‐cultured exosomes (3D‐Exo) are dramatically different from those obtained from 2D culture. Hence, 3D‐Exo could up‐regulate the expression of α‐secretase and down‐regulate the β‐secretase to reduce Aβ production in both AD pathology cells and transgenic mice, through their special cargo. With rescuing Aβ pathology, 3D‐Exo exerts enhanced therapeutic effects on ameliorating the memory and cognitive deficits in AD mice. These findings provide a novel clinical application for scaffold materials and functional exosomes derived from stem cells.     

Label‐Free Imaging of Nanoparticle Uptake Competition in Single Cells by Hyperspectral Stimulated Raman Scattering

Imaging and quantification of nanoparticles in single cells in their most natural condition are expected to facilitate the biotechnological applications of nanoparticles and allow for better assessment of their biosafety risks. However, current imaging modalities either require tedious sample preparation or only apply to nanoparticles with specific physicochemical characteristics. Here, the emerging hyperspectral stimulated Raman scattering (SRS) microscopy, as a label‐free and nondestructive imaging method, is used for the first time to investigate the subcellular distribution of nanoparticles in the protozoan Tetrahymena thermophila. The two frequently studied nanoparticles, polyacrylate‐coated α‐Fe₂O₃ and TiO₂, are found to have different subcellular distribution pattern as a result of their dissimilar uptake routes. Significant uptake competition between these two types of nanoparticles is further discovered, which should be paid attention to in future bioapplications of nanoparticles. Overall, this study illustrates the great promise of hyperspectral SRS as an analytical imaging tool in nanobiotechnology and nanotoxicology.     

Reaction Kinetics‐Mediated Control over Silver Nanogap Shells as Surface‐Enhanced Raman Scattering Nanoprobes for Detection of Alzheimer's Disease Biomarkers

It is very challenging to accurately quantify the amounts of amyloid peptides Aβ40 and Aβ42, which are Alzheimer's disease (AD) biomarkers, in blood owing to their low levels. This has driven the development of sensitive and noninvasive sensing methods for the early diagnosis of AD. Here, an approach for the synthesis of Ag nanogap shells (AgNGSs) is reported as surface‐enhanced Raman scattering (SERS) colloidal nanoprobes for the sensitive, selective, and multiplexed detection of Aβ40 and Aβ42 in blood. Raman label chemicals used for SERS signal generation modulate the reaction rate for AgNGSs production through the formation of an Ag‐thiolate lamella structure, enabling the control of nanogaps at one nanometer resolution. The AgNGSs embedded with the Raman label chemicals emit their unique SERS signals with a huge intensity enhancement of up to 10⁷ and long‐term stability. The AgNGS nanoprobes, conjugated with an antibody specific to Aβ40 or Aβ42, are able to detect these AD biomarkers in a multiplexed manner in human serum based on the AgNGS SERS signals. Detection is possible for amounts as low as 0.25 pg mL^?1. The AgNGS nanoprobe‐based sandwich assay has a detection dynamic range two orders of magnitude wider than that of a conventional enzyme‐linked immunosorbent assay.