Semiconducting electrodes for neural interfacing: a review.

In the past 50 years, the advent of electronic technology to directly interface with neural tissue has transformed the fields of medicine and biology. Devices that restore or even replace impaired bodily functions, such as deep brain stimulators and cochlear implants, have ushered in a new treatment era for previously intractable conditions. Meanwhile, electrodes for recording and stimulating neural activity have allowed researchers to unravel the vast complexities of the human nervous system. Recent advances in semiconducting materials have allowed effective interfaces between electrodes and neuronal tissue through novel devices and structures. Often these are unattainable using conventional metallic electrodes. These have translated into advances in research and treatment. The development of semiconducting materials opens new avenues in neural interfacing. This review considers this emerging class of electrodes and how it can facilitate electrical, optical, and chemical sensing and modulation with high spatial and temporal precision. Semiconducting electrodes have advanced electrically based neural interfacing technologies owing to their unique electrochemical and photo-electrochemical attributes. Key operation modalities, namely sensing and stimulation in electrical, biochemical, and optical domains, are discussed, highlighting their contrast to metallic electrodes from the application and characterization perspective.

Micro/Nano-Fabrication of Flexible Poly(3,4-Ethylenedioxythiophene)-Based Conductive Films for High-Performance Microdevices.

With the increasing demands for novel flexible organic electronic devices, conductive polymers are now becoming the rising star for reaching such targets, which has witnessed significant breakthroughs in the fields of thermoelectric devices, solar cells, sensors, and hydrogels during the past decade due to their outstanding conductivity, solution-processing ability, as well as tailorability. However, the commercialization of those devices still lags markedly behind the corresponding research advances, arising from the not high enough performance and limited manufacturing techniques. The conductivity and micro/nano-structure of conductive polymer films are two critical factors for achieving high-performance microdevices. In this review, the state-of-the-art technologies for developing organic devices by using conductive polymers are comprehensively summarized, which will begin with a description of the commonly used synthesis methods and mechanisms for conductive polymers. Next, the current techniques for the fabrication of conductive polymer films will be proffered and discussed. Subsequently, approaches for tailoring the nanostructures and microstructures of conductive polymer films are summarized and discussed. Then, the applications of micro/nano-fabricated conductive films-based devices in various fields are given and the role of the micro/nano-structures on the device performances is highlighted. Finally, the perspectives on future directions in this exciting field are presented.

Machine-learning screening of luminogens with aggregation-induced emission characteristics for fluorescence imaging.

Due to the excellent biocompatible physicochemical performance, luminogens with aggregation-induced emission (AIEgens) characteristics have played a significant role in biomedical fluorescence imaging recently. However, screening AIEgens for special applications takes a lot of time and efforts by using conventional chemical synthesis route. Fortunately, artificial intelligence techniques that could predict the properties of AIEgen molecules would be helpful and valuable for novel AIEgens design and synthesis. In this work, we applied machine learning (ML) techniques to screen AIEgens with expected excitation and emission wavelength for biomedical deep fluorescence imaging. First, a database of various AIEgens collected from the literature was established. Then, by extracting key features using molecular descriptors and training various state-of-the-art ML models, a multi-modal molecular descriptors strategy has been proposed to extract the structure-property relationships of AIEgens and predict molecular absorption and emission wavelength peaks. Compared to the first principles calculations, the proposed strategy provided greater accuracy at a lower computational cost. Finally, three newly predicted AIEgens with desired absorption and emission wavelength peaks were synthesized successfully and applied for cellular fluorescence imaging and deep penetration imaging. All the results were consistent successfully with our expectations, which demonstrated the above ML has a great potential for screening AIEgens with suitable wavelengths, which could boost the design and development of novel organic fluorescent materials.

Silk fibroin fibers-based shape memory membrane with Janus wettability for multitiered wearable protection.

Realizing breathable shape memory fiber-based material with antibacterial and waterproof performances is important for multitiered wearable protection to address the increasing concerns of air pollution. Herein, using an alternating electrospinning-electrospraying technology, we develop a fiber-based membrane with Janus wettability based on a silk fibroin nanofibers-substrate (SFNFs), a polyurethane nanospheres-top layer (PUNSs), and a middle layer of PU nanofibers-mat with in-situ grown silver nanoparticles (PUNFs-AgNPs), which serves separately for skin contact, a self-cleaning physical barrier to resist external aerosol/bacteria (PM2.5 filtration efficiency ~ 98.1%), and a bio-barrier that can sterilize harmful particles and inhibit bacteria proliferation (> 95%). This breathable Janus film (SFNFs/PUNFs-AgNPs/PUNSs, SPAP) with an antibacterial filter shows shape memory stretchability enabled by the thermoplastic PU component, which is mechanically adaptive to human body for wearable protection. This work presents a breathable wearable material for air-filtration and anti-bacteria, promising for applications such as wound dressings, medical masks, protection suits, and multifunctional filters. Graphical abstract: An alternating electrospinning-electrospraying technology was proposed to achieve a silk fibroin-based antibacterial membrane with Janus wettability, as well as good skin affinity and breathability, which serves well as physical and bio-barriers for water resistance, PM2.5 filtration (~98.1%) and bacteria inhibition (efficiency of 95%). This shape memory Janus membrane can adapt mechanically to human body curvatures for functional wearable protections. Supplementary Information: The online version contains supplementary material available at 10.1557/s43578-022-00805-w.

Membrane-intercalating conjugated oligoelectrolytes.

By acting as effective biomimetics of the lipid bilayers, membrane-intercalating conjugated oligoelectrolytes (MICOEs) can spontaneously insert themselves into both synthetic lipid bilayers and biological membranes. The modular and intentional molecular design of MICOEs enable a range of applications, such as bioproduction, biocatalysis, biosensing, and therapeutics. This tutorial review provides a structural evolution of MICOEs, which originated from the broader class of conjugated molecules, and analyses the drivers behind this evolutionary process. Various representative applications of MICOEs, accompanied by insights into their molecular design principles, will be reviewed separately. Perspectives on the current challenges and opportunities in research on MICOEs will be discussed at the end of the review to highlight their potential as unconventional and value-added materials for biological systems.

Synthetic Conjugated Oligoelectrolytes Are Effective siRNA Transfection Carriers: Relevance to Pancreatic Cancer Gene Therapy.

Conjugated oligoelectrolyte COE-S6 contains an elongated conjugated core with three cationic charges at each termini of the internal core. As an analogue of bolaamphiphiles, these structural attributes lead to the formation of spherical nanoplexes with Dh = 205 ± 5.0 nm upon mixing with small interfering RNA (siRNA). COE-S6/siRNA nanocomplexes were shown to be protective toward RNase, stimulate endosome escape, and achieve transfection efficiencies comparable to those achieved with commercially available LIP3000. Moreover, COE-S6/siRNA nanocomplexes enabled efficient silencing of the K-ras gene in pancreatic cancer cells and significant inhibition of cancer tumor growth with negligible in vitro toxicities. More importantly, cell invasion and colony formation of the Panc-1 cells were significantly inhibited, and apoptosis of the pancreatic cancer cells was also promoted. We also note that COE-S6 is much less toxic relative to commercial lipid formulations, and it provides optical signatures that can enable subsequent mechanistic work without the need to label nucleotides. COE-S6-based nanoplexes are thus a promising candidate as nonviral vectors for gene delivery.

Electrically Tunable All-PCM Visible Plasmonics.

The realization of electrically tunable plasmonic resonances in the ultraviolet (UV) to visible spectral band is particularly important for active nanophotonic device applications. However, the plasmonic resonances in the UV to visible wavelength range cannot be tuned due to the lack of tunable plasmonic materials. Here, we experimentally demonstrate tunable plasmonic resonances at visible wavelengths using a chalcogenide semiconductor alloy such as antimony telluride (Sb2Te3), by switching the structural phase of Sb2Te3 from amorphous to crystalline. We demonstrate the excitation of a propagating surface plasmon with a high plasmonic figure of merit in both amorphous and crystalline phases of Sb2Te3 thin films. We show polarization-dependent and -independent plasmonic resonances by fabricating one and two-dimensional periodic nanostructures in Sb2Te3 thin films, respectively. Moreover, we demonstrate electrically tunable plasmonic resonances using a microheater integrated with the Sb2Te3/Si device. The developed electrically tunable Sb2Te3-based plasmonic devices could find applications in the development of active color filters.

Nanocarbons for Biology and Medicine: Sensing, Imaging, and Drug Delivery.

Nanocarbons with different dimensions (e.g., 0D fullerenes and carbon nanodots, 1D carbon nanotubes and graphene nanoribbons, 2D graphene and graphene oxides, and 3D nanodiamonds) have attracted enormous interest for applications ranging from electronics, optoelectronics, and photovoltaics to sensing, bioimaging, and therapeutics due to their unique physical and chemical properties. Among them, nanocarbon-based theranostics (i.e., therapeutics and diagnostics) is one of the most intensively studied applications, as these nanocarbon materials serve as excellent biosensors, versatile drug/gene carriers for specific targeting in vivo, effective photothermal nanoagents for cancer therapy, and promising fluorescent nanolabels for cell and tissue imaging. This review provides a systematic overview of the latest theranostic applications of nanocarbon materials with a comprehensive comparison of the characteristics of different nanocarbon materials and their influences on theranostic applications. We first introduce the different carbon allotropes that can be used for theranostic applications with their respective preparation and surface functionalization approaches as well as their physical and chemical properties. Theranostic applications are described separately for both in vitro and in vivo systems by highlighting the protocols and the studied biosystems, followed by the toxicity and biodegradability implications. Finally, this review outlines the design considerations for nanocarbon materials as the key unifying themes that will serve as a foundational first principle for researchers to study, investigate, and generate effective, biocompatible, and nontoxic nanocarbon materials-based models for cancer theranostics applications. Finally, we summarize the review with an outlook on the challenges and novel theranostic protocols using nanocarbon materials for hard-to-treat cancers and other diseases. This review intends to present a comprehensive guideline for researchers in nanotechnology and biomedicine on the selection strategy of nanocarbon materials according to their specific requirements.

PEGylated CuInS2/ZnS quantum dots inhibit neurite outgrowth by downregulating the NGF/p75NTR/MAPK pathway.

The widespread application of cadmium-free CuInS2/ZnS QDs has raised great concern regarding their potential toxicity to humans. To date, toxicological data related to CuInS2/ZnS QDs are scarce. Neurons play extraordinary roles in regulating the activities of organs and systems, and serious consequences occur when neurons are damaged. Currently, the potential toxicity of CuInS2/ZnS QDs on neurons has not been fully elucidated. Here, we investigate the neurotoxicity of PEGylated CuInS2/ZnS (CuInS2/ZnS-PEG) QDs on neuron-like PC12 cells. We found that CuInS2/ZnS-PEG QDs were taken up by PC12 cells, but at a concentration range from 0 to 100 µg/mL, they did not affect the survival rate of the PC12 cells. In addition, we found that CuInS2/ZnS-PEG QDs significantly inhibited neurite outgrowth from and the differentiation of PC12 cells in the presence of NGF, while COOH-modified CuInS2/ZnS QDs or free PEG did not have a similar effect. Further studies showed that CuInS2/ZnS-PEG QDs obviously downregulated the expression of low-affinity NGF receptor (p75NTR) and subsequently negatively regulated the downstream MAPK cascade by dephosphorylating ERK1/2 and AKT. Taken together, these results suggest that CuInS2/ZnS-PEG QDs disturb NGF signal transduction from external stimuli to relevant internal signals, thus affecting normal biological processes such as neurite outgrowth and cell differentiation.

Thermodynamic perspectives on liquid-liquid droplet reactors for biochemical applications.

Liquid-liquid droplet reactors have garnered significant interest in biochemical applications with the obvious benefits of reduced reagent consumption, well controlled droplet size and confinement of biochemical reactions away from external interference. This Tutorial Review provides a succinct overview of widely employed liquid-liquid droplet reactors, namely single emulsions, multiple emulsions and all-aqueous emulsions, under the scope of thermodynamics, with a particular emphasis on how their intrinsic interfacial properties may endow mass transport for a variety of demands. Beyond spatially compartmentalizing a thermodynamic system, the artificial interface of droplet reactors has shown initial promising for multi-step or complex reactions. Moving forward, the artificial interface shall be tailored further towards "functional" to imitate the "intelligent" interface surrounding natural vesicles or cells.

Recent advances in copper sulphide-based nanoheterostructures.

Due to the high mobility of copper ions in numerous structurally-related phases, copper sulphide (Cu2-xS, 0 ≤x≤ 1) has been widely used as a starting template to fabricate various heterostructures via cation exchange. Such nanoheterostructures can possess unique combinations of physical properties that could be useful in diverse applications. Controllable methods of fabricating copper sulphide nanoheterostructures of increasing complexity have been rapidly emerging over the past few years. In this tutorial review, we discuss recent progress in heterostructure fabrication methods using copper sulphide. We primarily focus on important reports of cation exchange-based approaches and then summarize some key emerging applications that can employ these copper-sulphide-based nanoheterostructures.

Carbon Allotrope-Based Optical Fibers for Environmental and Biological Sensing: A Review.

Recently, carbon allotropes have received tremendous research interest and paved a new avenue for optical fiber sensing technology. Carbon allotropes exhibit unique sensing properties such as large surface to volume ratios, biocompatibility, and they can serve as molecule enrichers. Meanwhile, optical fibers possess a high degree of surface modification versatility that enables the incorporation of carbon allotropes as the functional coating for a wide range of detection tasks. Moreover, the combination of carbon allotropes and optical fibers also yields high sensitivity and specificity to monitor target molecules in the vicinity of the nanocoating surface. In this review, the development of carbon allotropes-based optical fiber sensors is studied. The first section provides an overview of four different types of carbon allotropes, including carbon nanotubes, carbon dots, graphene, and nanodiamonds. The second section discusses the synthesis approaches used to prepare these carbon allotropes, followed by some deposition techniques to functionalize the surface of the optical fiber, and the associated sensing mechanisms. Numerous applications that have benefitted from carbon allotrope-based optical fiber sensors such as temperature, strain, volatile organic compounds and biosensing applications are reviewed and summarized. Finally, a concluding section highlighting the technological deficiencies, challenges, and suggestions to overcome them is presented.

AIE Featured Inorganic-Organic Core@Shell Nanoparticles for High-Efficiency siRNA Delivery and Real-Time Monitoring.

RNA interference (RNAi) is demonstrated as one of the most powerful technologies for sequence-specific suppression of genes in disease therapeutics. Exploration of novel vehicles for small interfering RNA (siRNA) delivery with high efficiency, low cytotoxicity, and self-monitoring functionality is persistently pursued. Herein, by taking advantage of aggregation-induced emission luminogen (AIEgen), we developed a novel class of Ag@AIE core@shell nanocarriers with regulable and uniform morphology. It presented excellent efficiencies in siRNA delivery, target gene knockdown, and cancer cell inhibition in vitro. What's more, an anticancer efficacy up to 75% was achieved in small animal experiments without obvious toxicity. Attributing to the unique AIE properties, real-time intracellular tracking of siRNA delivery and long-term tumor tissue imaging were successfully realized. Compared to the commercial transfection reagents, significant improvements were obtained in biocompatibility, delivery efficiency, and reproducibility, representing a promising future of this nanocarrier in RNAi-related cancer therapeutics.

Tunable hybridization induced transparency for efficient terahertz sensing.

Hybridization induced transparency (HIT) resulting from the coupling between the material absorption resonance and the artificial structure (metamaterial) resonance provides an effective means of enhancing the sensitivity in the terahertz spectroscopic technique-based sensing applications. However, the application of this method is limited by the versatility to the samples with different volumes, because the samples usually have a refractive index larger than unity and their presence with different thicknesses will lead to a shift of the structure resonance, mismatching the material absorption. In this work, we demonstrate that by using InSb coupled rod structures, whose electromagnetic response in the terahertz band can be easily controlled by using ambient parameters like the temperature or magnetic field, the HIT effect can be easily tuned so that without the needs to change the rod geometry, one can realize efficient terahertz sensing with different sample thickness.

New Generation Cadmium-Free Quantum Dots for Biophotonics and Nanomedicine.

This review summarizes recent progress in the design and applications of cadmium-free quantum dots (Cd-free QDs), with an emphasis on their role in biophotonics and nanomedicine. We first present the features of Cd-free QDs and describe the physics and emergent optical properties of various types of Cd-free QDs whose applications are discussed in subsequent sections. Selected specific QD systems are introduced, followed by the preparation of these Cd-free QDs in a form useful for biological applications, including recent advances in achieving high photoluminescence quantum yield (PL QY) and tunability of emission color. Next, we summarize biophotonic applications of Cd-free QDs in optical imaging, photoacoustic imaging, sensing, optical tracking, and photothermal therapy. Research advances in the use of Cd-free QDs for nanomedicine applications are discussed, including drug/gene delivery, protein/peptide delivery, image-guided surgery, diagnostics, and medical devices. The review then considers the pharmacokinetics and biodistribution of Cd-free QDs and summarizes current studies on the in vitro and in vivo toxicity of Cd-free QDs. Finally, we provide perspectives on the overall current status, challenges, and future directions in this field.

Functionalized Fiber End Superstructure Fiber Bragg Grating Refractive Index Sensor for Heavy Metal Ion Detection.

We present a novel superstructure fiber Bragg grating fiber end sensor capable of detecting variations in refractive index (RI) of liquids and potentially that of gases, and demonstrated an application in the detection of heavy metal ions in water. The sensor is capable of sensing RI variations in the range of 1.333 to 1.470 with good sensitivity of up to 230 dB/RIU achieved for the RI range of 1.370 to 1.390. The sensor is capable of simultaneously measuring variations in ambient temperature along with RI. A simple chemical coating was employed as a chelating agent for heavy metal ion detection at the fiber end to demonstrate an possible application of the sensor. The coated fiber sensor can conclusively detect the presence of heavy metal ions with concentrations upwards of 100 ppm. RI sensing capability of the sensor is neither affected by temperature nor strain and is both robust and easily reproducible.

Novel Magnetic-Luminescent Janus Nanoparticles for Cell Labeling and Tumor Photothermal Therapy.

Magnetic-luminescent nanocomposites have multiple uses including multimodal imaging, magnetic targeted drug delivery, and cancer imaging-guided therapies. In this work, dumbbell-like MnFe2 O4 -NaYF4 Janus nanoparticles are synthesized via a two-step thermolysis approach. These synthesized nanoparticles exhibit stability in aqueous solutions and very low cytotoxicity after poly(acryl amide) modification. High cellular uptake efficiency is observed for the folic acid-conjugated MnFe2 O4 -NaYF4 in human esophagus carcinoma cells (Eca-109) due to the upconversion luminescence properties as well as the folate targeting potential. The MnFe2 O4 -NaYF4 also strongly absorbs light in the near-infrared range and rapidly converts to heat energy. It is demonstrated that Eca-109 cells incubated with MnFe2 O4 -NaYF4 are killed with high efficiency after 808 nm laser irradiation. Furthermore, the growth of tumors in mice (grown from Eca-109 cells) is highly inhibited by the photothermal effects of MnFe2 O4 -NaYF4 efficiently. Histological analysis reveals no pathological change and inflammatory response in heart, liver, spleen, lung, or kidney. The low toxicity, excellent luminescence, and highly efficient photothermal therapy properties of MnFe2 O4 -NaYF4 Janus nanoparticles illustrated in this work support their vast potential for nanomedicine and cancer therapy.

Multifunctional Hyperbolic Nanogroove Metasurface for Submolecular Detection.

Metasurface serves as a promising plasmonic sensing platform for engineering the enhanced light-matter interactions. Here, a hyperbolic metasurface with the nanogroove structure in the subwavelength scale is designed. This metasurface is able to modify the wavefront and wavelength of surface plasmon wave with the variation of the nanogroove width or periodicity. At the specific optical frequency, surface plasmon polaritons are tightly confined and propagated with a diffraction-free feature due to the epsilon-near-zero effect. Most importantly, the groove hyperbolic metasurface can enhance the plasmonic sensing with an ultrahigh phase sensitivity of 30 373 deg RIU-1 and Goos-Hänchen shift sensitivity of 10.134 mm RIU-1 . The detection resolution for refractive index change of glycerol solution is achieved as 10-8 RIU based on the phase measurement. The detection limit of bovine serum albumin (BSA) molecule is measured as low as 0.1 × 10-18 m (1 × 10-19 mol L-1 ), which corresponds to a submolecular detection level (0.13 BSA mm-2 ). As for low-weight biotin molecule, the detection limit is estimated below 1 × 10-15 m (1 × 10-15 mol L-1 , 1300 biotin mm-2 ). This enhanced plasmonic sensing performance is two orders of magnitude higher than those with current state-of-art plasmonic metamaterials and metasurfaces.

An Aptamer Bio-barCode (ABC) assay using SPR, RNase H, and probes with RNA and gold-nanorods for anti-cancer drug screening.

With modifications to an ultra-sensitive bio-barcode (BBC) assay, we have developed a next generation aptamer-based bio-barcode (ABC) assay to detect cytochrome-c (Cyto-c), a cell death marker released from cancer cells, for anti-cancer drug screening. An aptamer is a short single-stranded DNA selected from a synthetic DNA library that is capable of binding to its target with high affinity and specificity based on its unique DNA sequence and 3D structure after folding. Similar to the BBC assay, Cyto-c is captured by a micro-magnetic particle (MMP) coated with capturing antibodies (Ab) and an aptamer specifically against Cyto-c to form sandwich structures ([MMP-Ab]-[Cyto-c]-[Aptamer]). After washing and melting, our aptamers, acting as a DNA bio-barcode, are released from the sandwiches and hybridized with the probes specially designed for RNase H for surface plasmon resonance (SPR) sensing. In an aptamer-probe duplex, RNase H digests the RNA in the probe and releases the intact aptamer for another round of hybridization and digestion. With signal enhancement effects from gold-nanorods (Au-NRs) on probes for SPR sensing, the detection limit was found to be 1 nM for the aptamer and 80 pM for Cyto-c. Without the time-consuming DNA amplification steps by PCR, the detection process of this new ABC assay can be completed within three hours. As a proof-of-concept, phenylarsine oxide was found to be a potent agent to kill liver cancer cells with multi-drug resistance at the nano-molar level. This approach thus provides a fast, sensitive and robust tool for anti-cancer drug screening.

Ultra-small v-shaped gold split ring resonators for biosensing using fundamental magnetic resonance in the visible spectrum.

Strong light localization within metal nanostructures occurs by collective oscillations of plasmons in the form of electric and magnetic resonances. This so-called localized surface plasmon resonance (LSPR) has gained much interest in the development of low-cost sensing platforms in the visible spectrum. However, demonstrations of LSPR-based sensing are mostly limited to electric resonances due to the technological limitations for achieving magnetic resonances in the visible spectrum. In this work, we report the first demonstration of LSPR sensing based on fundamental magnetic resonance in the visible spectrum using ultrasmall gold v-shaped split ring resonators. Specifically, we show the ability for detecting adsorption of bovine serum albumin and cytochrome c biomolecules at monolayer levels, and the selective binding of protein A/G to immunoglobulin G.