Microstructure-Driven Self-Transport and Convection of Water on Membrane Surface for Ultra-Fast, Highly Sensitive, Low-Cost Lateral-Flow Assays.

Lateral-flow assay (LFA) is one of the most commonly used detection technologies, in which the chromatographic membranes are currently used as the lateral-flow membrane (e.g., nitrocellulose membrane, NC Mem). However, several disadvantages of existing chromatographic membranes limit the performance of LFA, including relatively low flow velocity of sample solution and relatively more residuals of sample on membrane, which increase detection time and detection noise. Herein, a surface structure membrane (SS Mem) is proposed, which enables fast self-transport of water with a convection manner and realizes low residuals of sample on membrane surface after the flow. On SS Mem, the flow velocity of water is 7.1-fold higher, and the residuals of sample are decreased by 60-67%, comparing those in NC Mem. SS Mem is used as lateral-flow membrane to prepare lateral-flow strips of nanogold LFA and fluorescence LFA for rapid detection of SARS CoV-2 nucleocapsid protein. These LFAs require 210 s per detection, with limits of detection of 3.98 pg mL-1 and 53.3 fg mL-1, sensitivity of 96.5%, and specificity of 90%. The results suggest that SS Mem enables ultrafast, highly sensitive lateral-flow immunoassays and shows great potential as a new type of lateral-flow membrane to broaden the application of LFA.

Intelligent and Multifunctional Graphene Nanomesh Electronic Skin with High Comfort.

As the aging population increases in many countries, electronic skin (e-skin) for health monitoring has been attracting much attention. However, to realize the industrialization of e-skin, two factors must be optimized. The first is to achieve high comfort, which can significantly improve the user experience. The second is to make the e-skin intelligent, so it can detect and analyze physiological signals at the same time. In this article, intelligent and multifunctional e-skin consisting of laser-scribed graphene and polyurethane (PU) nanomesh is realized with high comfort. The e-skin can be used as a strain sensor with large measurement range (>60%), good sensitivity (GF≈40), high linearity range (60%), and excellent stability (>1000 cycles). By analyzing the morphology of e-skin, a parallel networks model is proposed to express the mechanism of the strain sensor. In addition, laser scribing is also applied to etch the insulating PU, which greatly decreases the impedance in detecting electrophysiology signals. Finally, the e-skin is applied to monitor the electrocardiogram, electroencephalogram (EEG), and electrooculogram signals. A time- and frequency-domain concatenated convolution neural network is built to analyze the EEG signal detected using the e-skin on the forehead and classify the attention level of testers.

A Microarray Screening Platform with an Experimental Conditions Gradient Generator for the High-Throughput Synthesis of Micro/Nanosized Calcium Phosphates.

Calcium phosphates (CaP) represent an impressive kind of biomedical material due to their excellent biocompatibility, bioactivity, and biodegradability. Their morphology and structure highly influence their properties and applications. Whilst great progress has been made in research on biomedical materials, there is still a need to develop a method that can rapidly synthesize and screen micro/nanosized biomedical materials. Here, we utilized a microarray screening platform that could provide the high-throughput synthesis of biomedical materials and screen the vital reaction conditions. With this screening platform, 9 × 9 sets of parallel experiments could be conducted simultaneously with one- or two-dimensions of key reaction condition gradients. We used this platform to establish a one-dimensional gradient of the pH and citrate concentration and a two-dimensional gradient of both the Ca/P ratio and pH to synthesize CaP particles with various morphologies. This screening platform also shows the potential to be extended to other reaction systems for rapid high-throughput screening.

Functionalization of Calcium Sulfate/Bioglass Scaffolds with Zinc Oxide Whisker.

There are urgent demands for satisfactory antibacterial activity and mechanical properties of bone scaffolds. In this study, zinc oxide whisker (ZnOw) was introduced into calcium sulfate/bioglass scaffolds. Antimicrobial behavior was analyzed using Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The results showed that the scaffolds presented a strong antibacterial activity after introducing ZnOw, due to the antibacterial factors released from the degradation of ZnO. Moreover, ZnOw was also found to have a distinct reinforcing effect on mechanical properties. This was ascribed to whisker pull-out, crack bridging, crack deflection, crack branching and other toughening mechanisms. In addition, the cell culture experiments showed that the scaffolds with ZnOw had a good biocompatibility.

Protein capsules with cross-linked, semipermeable, and enzyme-degradable surface barriers for controlled release.

This paper describes a method for fabricating protein-based capsules with semipermeable and enzyme-degradable surface barriers. It involves the use of a simple fluidic device to generate water-in-oil emulsion droplets, followed by cross-linking of proteins at the water-oil interface to generate a semipermeable surface barrier. The capsules can be readily fabricated with uniform and controllable sizes and, more importantly, show selective permeability toward molecules with different molecular weights: small molecules like fluorescein sodium salt can freely diffuse through the surface barrier while macromolecules such as proteins can not. The proteins, however, can be released by digesting the surface barrier with an enzyme such as pepsin. Taken together, the capsules hold great potential for applications in controlled release, in particular, for the delivery of protein drugs.

Whole-Teflon microfluidic chips.

Although microfluidics has shown exciting potential, its broad applications are significantly limited by drawbacks of the materials used to make them. In this work, we present a convenient strategy for fabricating whole-Teflon microfluidic chips with integrated valves that show outstanding inertness to various chemicals and extreme resistance against all solvents. Compared with other microfluidic materials [e.g., poly(dimethylsiloxane) (PDMS)] the whole-Teflon chip has a few more advantages, such as no absorption of small molecules, little adsorption of biomolecules onto channel walls, and no leaching of residue molecules from the material bulk into the solution in the channel. Various biological cells have been cultured in the whole-Teflon channel. Adherent cells can attach to the channel bottom, spread, and proliferate well in the channels (with similar proliferation rate to the cells in PDMS channels with the same dimensions). The moderately good gas permeability of the Teflon materials makes it suitable to culture cells inside the microchannels for a long time.

Barbed arrow-like structure membrane with ultra-high rectification coefficient enables ultra-fast, highly-sensitive lateral-flow assay of cTnI.

Acute myocardial infarction (AMI) has become a public health disease threatening public life safety due to its high mortality. The lateral-flow assay (LFA) of a typical cardiac biomarker, troponin I (cTnI), is essential for the timely warnings of AMI. However, it is a challenge to achieve an ultra-fast and highly-sensitive assay for cTnI (hs-cTnI) using current LFA, due to the limited performance of chromatographic membranes. Here, we propose a barbed arrow-like structure membrane (BAS Mem), which enables the unidirectional, fast flow and low-residual of liquid. The liquid is rectified through the forces generated by the sidewalls of the barbed arrow-like grooves. The rectification coefficient of liquid flow on BAS Mem is 14.5 (highest to date). Using BAS Mem to replace the conventional chromatographic membrane, we prepare batches of lateral-flow strips and achieve LFA of cTnI within 240 s, with a limit of detection of 1.97 ng mL-1. The lateral-flow strips exhibit a specificity of 100%, a sensitivity of 93.3% in detecting 25 samples of suspected AMI patients. The lateral-flow strips show great performance in providing reliable results for clinical diagnosis, with the potential to provide early warnings for AMI.

A tough and bioadhesive injectable hydrogel formed with maleimidyl alginate and pristine gelatin.

Injectable hydrogels have wide applications in clinical practice. However, the development of tough and bioadhesive ones based on biopolymers, along with biofriendly and robust crosslinking strategies, still represents a great challenge. Herein, we report an injectable hydrogel composed of maleimidyl alginate and pristine gelatin, for which the precursor solutions could self-crosslink via mild Michael-type addition without any catalyst or external energy upon mixing. This hydrogel is tough and bioadhesive, which can maintain intactness as well as adherence to the defect of porcine skin under fierce bending and twisting, warm water bath, and boiling water shower. Besides, it is biocompatible, bioactive and biodegradable, which could support the growth and remodeling of cells by affording an extracellular matrix-like environment. As a proof of application, we demonstrate that this hydrogel could significantly accelerate diabetic skin wound healing, thereby holding great potential in healthcare.

An overview of control strategy and diagnostic technology for foot-and-mouth disease in China.

Foot-and-mouth disease (FMD) is one of most contagious animal diseases. It affects millions of cloven-hoofed animals and causes huge economic losses in many countries of the world. There are seven serotypes of which three (O, A and Asia 1) are endemic in China. Efficient control of FMD in China is crucial for the prevention and control of FMD in Asia and throughout the world. For the control of FMD, a powerful veterinary administration, a well-trained veterinary staff, a system of rapid and accurate diagnostic procedures and, in many countries, compulsory vaccination of susceptible animals are indispensable. This article strives to outline the Chinese animal disease control and prevention system, in particular for FMD, with the emphasis on diagnostic procedures applied in Chinese laboratories. In addition, new technologies for FMD diagnosis, which are currently in the phase of development or in the process of validation in Chinese laboratories, are described, such as lateral flow devices (LFD), Mab-based ELISAs, reverse transcription loop-mediated isothermal amplification (RT-LAMP) and gold nanopariticle immuno-PCR (GNP-IPCR).

Light-activated cellulose nanocrystals/fluorinated polyacrylate-based waterborne coating: Facile preparation, mechanical and self-healing behavior.

The development of environmental-friendly self-healing nanocomposites has attracted much attention. In this paper, the light-activated cellulose nanocrystals/ fluorinated polyacrylate-based waterborne coating based on the reversible cycloaddition reaction of the coumarin groups was prepared via Pickering emulsion polymerization. The cellulose nanocrystals (CNCs) modified by the PDMAEMA-b-PGMA-b-P(HFBA-co-VBMC) copolymer were studied via FT-IR and TGA. In addition, the dispersity and interface behavior of CNCs before and after modification were investigated by DLS and interfacial tension measurements. Afterwards, we focused on the influence of modified CNCs, PDMAEMA-g-CNC-g- P(HFBA-co-VBMC) (MCNC) dosage on the Pickering emulsion, emulsion polymerization and properties of latex film. The droplet diameter of Pickering emulsion gradually reduced with the increase of MCNC dosage. The MCNC dosage for the minimum average size and optimum stability of latex particles was 1.0 wt%. Moreover, the latex film comprising 1.0 wt% MCNC presented not only high tensile stress (6.0 MPa), large elongation at break (567.70 %) and superior oil/water repellency but also excellent self-healing properties. The outstanding self-healing capability of latex film was attributed to the reversible light-activated dimerization of coumarin groups. The preparation method for the advanced performance waterborne cellulose nanocrystals/fluorinated polyacrylate will provide valuable guidance for the development of versatile materials.

Ti3C2Tx MXene and cellulose-based aerogel phase change composite decorated laminated fabric with excellent electro/solar-thermal conversion and high latent heat.

Wearable heaters have attracted growing attention for maintaining a relatively constant temperature of the human body in cold environments with near zero energy consumption. Herein, we developed a multifunctional laminated fabric with fascinating electro/solar-thermal conversion, thermal energy storage and thermal insulation properties. With cotton fabric as the substrate, MXene/polydimethylsiloxane (PDMS) conductive network was decorated on the upper layer, and carbon nanotube (CNT)/cellulose nanofiber (CNF)/paraffin (PA) aerogel phase change composites were assembled on the bottom layer. Attributed to the strong conductivity and light absorption of MXene and the light/thermal response of CNT and PA components, this wearable laminated fabric broke the limitation of intermittent solar photothermal heating, and integrated multiple heating modes to precisely heat the human body. Meanwhile, the low thermal conductivity of aerogel retarded heat loss. The laminated fabric can help people better adapt to a variety of complex and changeable environments such as cold winter, rainy days and nights. This study provides a promising and energy-efficient avenue for the development of all-day personal thermal management fabrics.

Cation-free siRNA-cored nanocapsules for tumor-targeted RNAi therapy.

Cation-associated cytotoxicity limits the systemic administration of RNA delivery in vivo, demanding the development of non-cationic nanosystems. In this study, cation-free polymer-siRNA nanocapsules with disulfide-crosslinked interlayer, namely T-SS(-), were prepared via the following steps: 1) complexation of siRNA with a cationic block polymer cRGD-poly(ethylene glycol)-b-poly[(2-aminoethanethiol)aspartamide]-b-poly{N'-[N-(2-aminoethyl)-2-ethylimino-1-aminomethyl]aspartamide}, abbreviated as cRGD-PEG-PAsp(MEA)-PAsp(C=N-DETA), 2) interlayer crosslinking via disulfide bond in pH 7.4 solution, and 3) removal of cationic DETA pendant at pH 5.0 via breakage of imide bond. The cationic-free nanocapsules with siRNA cores not only showed great performance (such as efficient siRNA encapsulation, high stability in serum, cancer cell targeting via cRGD modification, and GSH-triggered siRNA release), but also achieved tumor-targeted gene silencing in vivo. Moreover, the nanocapsules loaded with siRNA against polo-like kinase 1 (siRNA-PLK1) significantly inhibited tumor growth without showing cation-associated toxicity side effects and remarkably improved the survival rate of PC-3 tumor-bearing mice. The cation-free nanocapsules could potentially serve as a safe and effective platform for siRNA delivery. STATEMENT OF SIGNIFICANCE: Cation-associated toxicity limits the clinical translation of cationic carriers for siRNA delivery. Recently, several non-cationic carriers, such as siRNA micelles, DNA-based nanogels, and bottlebrush-architectured poly(ethylene glycol), have been developed to deliver siRNA. However, in these designs, siRNA as a hydrophilic macromolecule was attached to the nanoparticle surface instead of being encapsulated. Thus, it was easily degraded by serum nuclease and often induced immunogenicity. Herein, we demonstrate a new type of cation-free siRNA-cored polymeric nanocapsules. The developed nanocapsules not only showed capacities including efficient siRNA encapsulation, high stability in serum, and cancer cell targeting via cRGD modification, but also achieved an efficient tumor-targeted gene silencing in vivo. Importantly, unlike cationic carriers, the nanocapsules exhibited no cation-associated side effects.

Temperature-responsive polymer/carbon nanotube hybrids: smart conductive nanocomposite films for modulating the bioelectrocatalysis of NADH.

A temperature-sensitive polymer/carbon nanotube interface with switchable bioelectrocatalytic capability was fabricated by self-assembly of poly(N-isopropylacrylamide)-grafted multiwalled carbon nanotubes (MWNT-g-PNIPAm) onto the PNIPAm-modified substrate. Electron microscopy and electrochemical measurements revealed that these fairly thick (>6 µm) and highly porous nanocomposite films exhibited high conductivity and electrocatalytic activity. The morphological transitions in both the tethered PNIPAm chains on a substrate and those polymers wrapping around the MWNT surface resulted in the opening, closing, or tuning of its permeability, and simultaneously an electron-transfer process took place through the channels formed in the nanostructure in response to temperature change. By combining the good electron-transfer and electrochemical catalysis capabilities, the large surface area, and good biocompatibility of MWNTs with the responsive features of PNIPAm, reversible temperature-controlled bioelectrocatalysis of 1,4-dihydro-ß-nicotinamide adenine dinucleotide with improved sensitivity has been demonstrated by cyclic voltammetry and electrochemical impedance spectroscopy measurements. The mechanism behind this approach was studied by Raman spectroscopy, in situ attenuated total reflection FTIR spectroscopy, and contact angle measurements. The results also suggested that the synergetic or cooperative interactions of PNIPAm with MWNTs gave rise not only to an increase in surface wettability, but also to the enhancement of the interfacial thermoresponsive behavior. This bioelectrocatalytic "smart" system has potential applications in the design of biosensors and biofuel cells with externally controlled activity. Furthermore, this concept might be proposed for biomimetics, interfacial engineering, bioelectronic devices, and so forth.

Semiconducting polymer dots as fluorescent probes for in vitro biosensing.

Semiconducting polymer dots (Pdots) have emerged as novel fluorescent probes with excellent characteristics, such as ultrahigh molar extinction coefficient, easy tunable absorption and emission bands, high brightness, and excellent photostability. Combined with good biocompatibility properties, much effort has been devoted to Pdots for in vivo biological imaging and therapy applications, such as deep-tissue fluorescent imaging, photodynamic therapy, photothermal therapy, and nanocarriers of genes or chemical drugs. Many reviews have been presented in these fields. On the other hand, a large number of studies employing Pdots for in vitro biosensing applications have been reported during the past few years, and there are barely any relevant reports to summarize the progress in this area. Hence, it is necessary to review these studies to promote the comprehensive application of Pdots. Herein, we introduce the properties and functionalization of Pdots, and systematically summarize the progress in the in vitro applications of Pdots, including the detection of DNAs, microRNAs, proteins, enzymatic activity, and some biological small molecules and ions. Finally, we share our perspectives on the future direction of this field.

Osteon-mimetic 3D nanofibrous scaffold enhances stem cell proliferation and osteogenic differentiation for bone regeneration.

The scaffold microstructure is important for bone tissue engineering. Failure to synergistically imitate the hierarchical microstructure of the components of bone, such as an osteon with concentric multilayers assembled by nanofibers, hinders the performance for guiding bone regeneration. Here, a 2D bilayer nanofibrous membrane (BLM) containing poly(lactide-co-glycolide) (PLGA)/polycaprolactone (PCL) composite membranes in similar compositions (PCL15 and PCL20), but possessing different degrees of shrinkage, was fabricated via sequential electrospinning. Upon incubation in phosphate buffered saline (PBS) (37 °C), the 2D BLM spontaneously deformed into a 3D shape induced by PCL crystallization within the PLGA matrix, and the PCL15 and PCL20 layer formed a concave and convex surface, respectively. The 3D structure contained curved multilayers with an average diameter of 776 ± 169 µm, and on the concave and convex surface the nanofiber diameters were 792 ± 225 and 881 ± 259 nm, respectively. The initial 2D structure facilitated the even distribution of seeded cells. Adipose-derived stem cells from rats (rADSCs) proliferated faster on a concave surface than on a convex surface. For the 3D BLM, the osteogenic differentiation of rADSCs was significantly higher than that on 2D surfaces, even without osteogenic supplements, which resulted from the stretched cell morphology on the curved sublayer leading to increased expression of lamin-A. After being implanted into cranial defects in Sprague Dawley (SD) rats, 3D BLM significantly accelerated bone formation. In summary, 3D BLM with an osteon-like structure provides a potential strategy to repair bone defects.

Au@Ag Nanorods-PDMS Wearable Mouthguard as a Visualized Detection Platform for Screening Dental Caries and Periodontal Diseases.

The development of easy-to-use, low-cost, and visualized detection platforms for screening human dental caries and periodontal diseases is in urgent demand. In this work, a Au@Ag nanorods-poly(dimethylsiloxane) (Au@Ag NRs-PDMS) wearable mouthguard, which can visualize the tooth lesion sites through the color change of it at the corresponding locations, is presented. The Au@Ag NRs-PDMS composite exhibits a distinct color response to hydrogen sulfide (H2 S) gas generated by bacterial decay at the lesion sites. Moreover, the Au@Ag NRs-PDMS mouthguard is demonstrated to own desired mechanical properties, excellent chemical stability, as well as good biocompatibility, and can accurately locate the lesion sites in human oral cavity. These findings suggest that the mouthguard has the potential to be utilized on a large scale to help people self-monitor their oral health in daily life, and treat oral diseases locally.

A prototypic system of parallel electrophoresis in multiple capillaries coupled with microwell arrays.

We present a microfluidic system that can be directly coupled with microwell array and perform parallel electrophoresis in multiple capillaries simultaneously. The system is based on an array of glass capillaries, fixed in a polydimethylsiloxane (PDMS) microfluidic scaffold, with one end open for interfacing with microwells. In this capillary array, every two adjacent capillaries act as a pair to be coupled with one microwell; samples in the microwells are introduced and separated by simply applying voltage between two electrodes that are placed at the other ends of capillaries; thus no complicated circuit design is required. We evaluate the performance of this system and perform multiple CE with direct sample introduction from microwell array. Also with this system, we demonstrate the analysis of cellular contents of cells lysed in a microwell array. Our results show that this prototypic system is a promising platform for high-throughput analysis of samples in microwell arrays.

Research in advance for FMD novel vaccines.

Foot-and-Mouth Disease (FMD), as a major global animal disease, affects millions of animals worldwide and remains the main sanitary barrier to the international and national trade of animals and animal products. Inactivated vaccination is the most effective measure for prevention of FMD at present, but fail to induce long-term protection and content new requires for production of FMD vaccines. As a number of Researchers hope to obtain satisfactory novel vaccines by new bio-technology, novel vaccines have been studied for more than thirty years. Here reviews the latest research progress of new vaccines, summarizes some importance and raises several suggestions for the future of FMD vaccine.

A highly sensitive detection for foot-and-mouth disease virus by gold nanopariticle improved immuno-PCR.

BACKGROUND: Foot-and-mouth disease (FMD) is one of the most contagious of all artiodactyl animal diseases, and its infection has an obvious ability to spread over long distances and to contribute to epidemics in FMD-free areas. A highly sensitive and specific method is required to detect FMDV. In this study, we evaluated the usefulness of a bio-barcode assay (BCA) technique for detecting clinical samples of FMDV. METHODS: Highly sensitive gold nanopariticle (GNP) improved immuno -PCR (GNP-IPCR) which derived from the bio-barcode assay (BCA) was designed for the detection of FMDV. The target viral particles were captured by a polyclonal antibody coated on ELISA microplate, followed by adding GNP which was dually modified with oligonucleotides and a FMDV specific monoclonal antibody (MAb) 1D11 to form a sandwiched immune complex. After the formation of immuno-complex, the signal DNA was released by heating, and consequently characterized by PCR and real time PCR. RESULTS: The detection limit of GNP-PCR could reach to 10 fg/ml purified FMDV particles, and the assay can detect clinical samples of FMDV with highly sensitivity, while detect limit of conventional ELISA is 100 ng/ml in this study. CONCLUSION: GNP-IPCR may provide a highly sensitive method for the detection of FMDV.

Simvastatin intervention mitigates hypercholesterolemia-induced alveolar bone resorption in rats.

Simvastatin promotes bone formation and increases bone mineral density in patients with hyperlipidemia and ameliorates hypercholesterolemia-induced microstructure changes in the jaw bone of animals. However, whether and how treatment with simvastatin can modulate the hypercholesterolemia-induced alveolar bone resorption is unclear. The present study aimed to examine the therapeutic efficacy and potential mechanisms of simvastatin application in hypercholesterolemia-induced alveolar bone resorption. The association between hyperlipidemia and alveolar bone resorption in 100 patients with periodontitis was examined. Additionally, male Sprague-Dawley rats were fed a standard rodent chow (NC) for 32 weeks or a high cholesterol diet (HCD) for 24 weeks. The HCD-fed rats were randomized, continually fed with HCD and treated with vehicle saline (HC) or simvastatin by gavage (5 mg/kg; SIM, n=10/group) for 8 weeks. The morphological changes to alveolar bone resorption in rats were analyzed by linear measurements. The relative levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand RANKL, nuclear factor-κB (NF-κB), microtubule-associated protein 1 light chain 3 (LC3) and p62 in the alveolar bone tissues were determined by reverse transcription-quantitative PCR and/or immunohistochemistry. Sulcus bleeding index (SBI), clinical attachment loss (CAL), probing depth (PD) and the distance of cemantoenamel junction-alveolar bone crest (CEJ-ABC) in patients with hyperlipidemia were significantly greater than that in the controls (P<0.001). The levels of hyperlipidemia were positively correlated with the values of SBI, CAL, PD and CEJ-ABC in this population. Compared with the NC rats, higher levels of alveolar bone resorption, NF-κB expression, higher ratios of RANKL/OPG mRNA transcripts and LC3 to p62 expression were detected in the alveolar bone tissues of HC group. Simvastatin intervention significantly mitigated hypercholesterolemia-induced alveolar bone loss and RANKL mRNA transcription, but increased the ratios of LC3/p62 protein expression in the alveolar bone tissues of rats. Hyperlipidemia is associated with alveolar bone resorption and simvastatin treatment alleviated the hypercholesterolemia-related alveolar bone loss by down-regulating the NF-κB expression.