Search

Transconductance (gm) is one important figure of merit for benchmarking organic electrochemical transistor (OECT) biosensors, which nevertheless experiences undesired fluctuation instead of keep constant during the target detection of varied concentrations. Light‐matter interplay is recently shown as a potential way to regulate the OECT characteristics, e.g. maximum gm at zero gate bias is achieved. In this work, the challenge of unstable gm is addressed by using a unique metal‐organic framework (MOF)‐derived hollow tube indium sulfide (m‐In2S3) as the photogate. Interestingly, the light irradiation on m‐In2S3 generate a straight transfer curve, leading to a stable gm that is desirable for biological application. Exemplifying by an aptasening, such a device is then tested for protein quantification with a stable sensitivity during the detection. This work features the feasibility of light‐matter interplay to achieve a stable gm in organic electronics. [ABSTRACT FROM AUTHOR]

Designing dynamic assemblies in living cells is crucial for creating organelle‐like structures, yet precisely controlling their morphological transitions in response to specific signals is a significant challenge. In this study, a DNA framework is combined with hybridization chain reaction (HCR) to achieve specific assembly of hyperbranched aggregates in cancer cells. HCR, distinguished for its signal amplification and linear extension capabilities, enables the morphological transition of precursors to be specifically triggered by trace amounts of endogenous microRNA‐21 (miR‐21). The spatial constraints of the framework and the diversity of hairpin orientations significantly accelerate the assembly kinetics of hyperbranched networks, and the resulting micrometer‐scale aggregates possess enhanced intracellular retention capabilities. Introducing Ce6 molecules as a proof of concept, the regulatory function of aggregates can be activated under light irradiation and remains effective over a long period. The probe we constructed demonstrates good stability and biocompatibility, offers easy functionalization, and works inside cells long‐term, making it an ideal candidate material for the construction of organelle‐like structures. [ABSTRACT FROM AUTHOR]

Full utilization of the excited species at both singlet states (1R*) and triplet states (3R*) is crucial to improving electrochemiluminescence (ECL) efficiency but is challenging for organic luminescent materials. Here, an aggregation‐induced delayed ECL (AIDECL) active organic dot (OD) containing a benzophenone acceptor and dimethylacridine donor is reported, which shows high ECL efficiency via reverse intersystem crossing (RISC) of non‐emissive 3R* to emissive 1R*, overcoming the spin‐forbidden radiative decay from 3R*. By introducing dual donor‐acceptor pairs into luminophores, it is found that nonradiative pathway could be further suppressed via enhanced intermolecular weak interactions, and multiple spin‐up conversion channels could be activated. As a consequence, the obtained OD enjoys a 6.8‐fold higher ECL efficiency relative to the control AIDECL‐active OD. Single‐crystal studies and theoretical calculations reveal that the enhanced AIDECL behaviors come from the acceleration of both radiative transition and RISC. This work represents a major step towards purely organic, high‐efficiency ECL dyes and a direction for the design of next‐generation ECL dyes at the molecular level. [ABSTRACT FROM AUTHOR]

The transport behavior of ions in the nanopores has an important impact on the performance of the electrochemical devices. Although the classical Transmission‐Line (TL) model has long been used to describe ion transport in pores, the boundary conditions for the applicability of the TL model remain controversial. Here, we investigated the transport kinetics of different ions, within nanochannels of different lengths, by using transient single‐particle imaging with temporal resolution up to microseconds. We found that the ion transport kinetics within short nanochannels may deviate significantly from the TL model. The reason is that the ion transport under nanoconfinement is composed of multi basic stages, and the kinetics differ much under different stage domination. With the shortening of nanochannels, the electrical double layer (EDL) formation would become the "rate‐determining step" and dominate the apparent ion kinetics. Our results imply that using the TL model directly and treating the in‐pore mobility as an unchanged parameter to estimate the ion transport kinetics in short nanopores/nanochannels may lead to orders of magnitude bias. These findings may advance the understanding of the nanoconfined ion transport and promote the related applications. [ABSTRACT FROM AUTHOR]

Construction of white‐light emitters is of great importance in practical applications but is challenging for metal nanoclusters. Herein, arginine (Arg)‐mediated copper nanoclusters (Cu NCs) assemblies with white‐light emission (WLE) are reported for the first time. The multidentate ligand, Arg, not only effectively tailors the high stability and locally‐excited emission (LES) of aqueous phase Cu NCs, but also bridges 1‐naphthalenol methylcarbamate (NMC) to generate a blue emitter via through‐space interactions (TSIs), resulting in a stable mixed light. Density functional theory calculation and mass spectrum further confirm that Arg can allow for the formation of strong hydrogen‐bonds with the ligand 2,4‐diaminotoluene of Cu NCs, and formation of TSIs‐based complexes with NMC. More importantly, pure white‐light emission (WLE) with Commission Internationale de L'Eclairagecoordination (0.30, 0.31) is observed by regulating the ratio between Arg and the interfacial ligand of NMC. The findings not only provide a new perspective for the construction of WLE emitters via interface modification chemistry but also open a window to gain insight into the mechanism of interface engineering. [ABSTRACT FROM AUTHOR]

Single‐cell epigenetics is envisioned to decipher manifold epigenetic phenomena and to contribute to our accurate knowledge about basic epigenetic mechanisms. Engineered nanopipette technology has gained momentum in single‐cell studies; however, solutions to epigenetic questions remain unachieved. This study addresses the challenge by exploring N6‐methyladenine (m6A)‐bearing deoxyribozyme (DNAzyme) confined within a nanopipette for profiling a representative m6A‐modifying enzyme, fat mass and obesity‐associated protein (FTO). Electroosmotic intracellular extraction of FTO could remove the m6A and cause DNAzyme cleavage, leading to the altered ionic current signal. Because the cleavage can release a DNA sequence, we simultaneously program it as an antisense strand against FTO‐mRNA, intracellular injection of which has been shown to induce early stage apoptosis. This nanotool thus features the dual functions of studying single‐cell epigenetics and programmable gene regulation. [ABSTRACT FROM AUTHOR]

Classic tris(bipyridine)ruthenium(II) complex (Ru-bpy) with high electrochemiluminescence (ECL) efficiency still suffers from a serious aggregation-caused quenching (ACQ) problem, which greatly weakens its ECL efficiency to restrict further applications in solid-state ECL imaging and light-emitting devices. Herein, the crystallization-induced enhanced ECL (CIE-ECL) of tris(bipyridine) ruthenium(II) derivatives (Ru-TPE) are reported by decorating Ru-bpy with inherent aggregation-induced emission active tetraphenylethene (TPE), which effectively eliminates the detrimental π-π stacking interactions and thus helps Ru-bpy surmount notorious ACQ effect in the aqueous phase. The Ru-TPE shows negligible ECL emission in solution but produces a strong ECL emission upon crystallization. Surprisingly, the ECL efficiency of Ru-TPE crystals is 20 and 3 times higher than that of its solution and Ru-bpy crystals, respectively. Experimental and structural analysis reveals that such a CIE-ECL effect originates from the restricted intramolecular rotation and ordered molecular packing. Moreover, the high-resolution ECL imaging of a single Ru-TPE crystal is successfully demonstrated. This work provides a new design strategy for achieving high efficiency in solid-state ECL imaging and devices. [ABSTRACT FROM AUTHOR]

Cuproptosis is a new form of programmed cell death and exhibits enormous potential in cancer treatment. However, reducing the undesirable Cu ion release in normal tissue and maximizing the copper‐induced therapeutic effect in cancer sites are two main challenges. In this study, we constructed a photothermally triggered nanoplatform (Au@MSN‐Cu/PEG/DSF) to realize on‐demand delivery for synergistic therapy. The released disulfiram (DSF) chelated with Cu2+ in situ to generate highly cytotoxic bis(diethyldithiocarbamate)copper (CuET), causing cell apoptosis, and the formed Cu+ species promoted toxic mitochondrial protein aggregation, leading to cell cuproptosis. Synergistic with photothermal therapy, Au@MSN‐Cu/PEG/DSF could effectively kill tumor cells and inhibit tumor growth (inhibition rate up to 80.1 %). These results provide a promising perspective for potential cancer treatment based on cuproptosis, and may also inspire the design of advanced nano‐therapeutic platforms. [ABSTRACT FROM AUTHOR]

Tumor‐targeted and stimuli‐activatable nanosensitizers are highly desirable for cancer theranostics. However, designing smart nanosensitizers with multiple imaging signals and synergistic therapeutic activities switched on is challenging. Herein, we report tumor‐targeted and redox‐activatable nanosensitizers (1‐NPs) for sono‐photodynamic immunotherapy of tumors by molecular co‐assembly and redox‐controlled disassembly. 1‐NPs show a high longitudinal relaxivity (r1=18.7±0.3 mM−1 s−1), but "off" dual fluorescence (FL) emission (at 547 and 672 nm), "off" sono‐photodynamic therapy and indoleamine 2,3‐dioxygenase 1 (IDO1) inhibition activities. Upon reduction by glutathione (GSH), 1‐NPs rapidly disassemble and remotely release small molecules 2‐Gd, Zn‐PPA‐SH and NLG919, concurrently switching on (1) dual FL emission, (2) sono‐photodynamic therapy and (3) IDO1 inhibition activities. After systemic injection, 1‐NPs are effective for bimodal FL and magnetic resonance (MR) imaging‐guided sono‐photodynamic immunotherapy of orthotropic breast and brain tumors in mice under combined ultrasound (US) and 671‐nm laser irradiation. [ABSTRACT FROM AUTHOR]

Single‐cell protein therapeutics is expected to promote our in‐depth understanding of how a specific protein with a therapeutic dosage treats the cell without population averaging. However, it has not yet been tackled by current single‐cell nanotools. We address this challenge by the use of a double‐barrel nanopipette, in which one lumen was used for electroosmotic cytosolic protein delivery and the other was customized for ionic evaluation of the consequence. Upon injection of protein DJ‐1 through the delivery lumen, upregulation of the antioxidant protein could protect neural PC‐12 cells against oxidative stress from phorbol myristate acetate exposure, as deduced by targeting of the cytosolic hydrogen peroxide by the detecting lumen. The nanotool developed in this study for single‐cell protein therapeutics provides a perspective for future single‐cell therapeutics involving different therapeutic modalities, such as peptides, enzymes and nucleic acids. [ABSTRACT FROM AUTHOR]

Rational utilization of the rich light‐bio‐matter interplay taking place in single‐cell analysis represents a new technological direction in the field. The light‐fueled operation is expected to achieve advanced photoelectrochemical (PEC) single‐cell analysis with unknown possibilities. Here, a PEC nanoreactor capable of single‐cell sampling and near zero‐background Faradaic detection of intracellular microRNA (miR) is devised by the construction of a small reaction chamber accommodating the target‐triggered hybridization chain reaction for binding the metallointercalator of [Ru(bpy)2(dppz)]2+ as the signal reporter. Light stimulation of the dsDNA/metallointercalator adduct will induce the generation of photocurrents, underpinning a zero‐biased and near zero‐background PEC method toward Faradaic detection of non‐electrogenic miR at the single‐cell level. Using this nanotool, lower miR concentration in the near‐nucleus region than that in the main cytosol was revealed. [ABSTRACT FROM AUTHOR]

Saccharides play critical roles in many forms of cellular activities. Saccharide structures are however complicated and similar, setting a technical hurdle for direct identification. Nanopores, which are emerging single molecule tools sensitive to minor structural differences between analytes, can be engineered to identity saccharides. A hetero‐octameric Mycobacterium smegmatis porin A nanopore containing a phenylboronic acid was prepared, and was able to clearly identify nine monosaccharide types, including D‐fructose, D‐galactose, D‐mannose, D‐glucose, L‐sorbose, D‐ribose, D‐xylose, L‐rhamnose and N‐acetyl‐D‐galactosamine. Minor structural differences between saccharide epimers can also be distinguished. To assist automatic event classification, a machine learning algorithm was developed, with which a general accuracy score of 0.96 was achieved. This sensing strategy is generally suitable for other saccharide types and may bring new insights to nanopore saccharide sequencing. [ABSTRACT FROM AUTHOR]

Acidic catecholamine metabolites, which could serve as diagnostic markers for many diseases, demonstrate an importance of accurate sensing. However, they share a highly similar chemical structure, which is a challenge in the design of sensing strategies. A nanopore may be engineered to sense these metabolites in a single molecule manner. To achieve this, a recently developed programmable nano‐reactor for stochastic sensing (PNRSS) technique adapted with a phenylboronic acid (PBA) adaptor was applied. Three acidic catecholamine metabolites, including 3,4‐dihydroxyphenylacetic acid (DOPAC), 3,4‐dihydroxymandelic acid (DHMA) and 3‐methoxy‐4‐hydroxymandetic acid (VMA) were investigated by PNRSS. Specifically, DHMA, which contains an α‐hydroxycarboxylate moiety and an adjacent cis‐hydroxyl groups on its benzene ring, reports two binding modes simultaneously resolvable by PNRSS. Assisted with the high resolution of PNRSS, direct regulation of these two binding modes by pH can also be observed. A custom machine learning algorithm was also developed to achieve automatic event classification. [ABSTRACT FROM AUTHOR]

Since the concept of surface plasmon amplification by stimulated emission of radiation (SPASER) was proposed in 2003, great progresses have been made on two kinds of plasmonic nanolasers, namely SPASER device and SPASER nanoparticle. In comparison, SPASER nanoparticle, with ultra‐narrow emission line, small size, and good biocompatibility, is a kind of promising luminescent nanoprobe and has a bright application prospect in biomedical imaging and sensing. Hence, it is gradually becoming an attractive research hotspot in the world. However, as the research on SPASER nanoparticle is still in its infancy, there are still lots of problems to be solved before it is widely applied. In this paper, the latest research advances of SPASER nanoparticles and their biological applications are reviewed. Besides existing problems, challenges and opportunities of SPASER nanoparticles as next generation luminescent nanoprobes are discussed as well. [ABSTRACT FROM AUTHOR]

A novel electrochemiluminescence (ECL) Janus emitter realizes dual‐mode biosensing for multiple disease‐related biomarkers from cells. Each Janus emitter consists of ruthenium (II) complex and luminol polymer doped hemispheres that are spatially separated but function simultaneously, generating intense dual‐ECL emissions. This design effectively eliminates optical and electrochemical interferences between different ECL mono‐luminophores in comparison with the homogenous nanostructures, thereby improving ECL efficiency and detection sensitivity. Accordingly, the ECL Janus emitters provide a proof of concept for the construction of the ratiometric ECL sensing of H2O2. Furthermore, this Janus emitter enables simultaneous identification and quantification of the intracellular cancer‐related dual microRNAs. This work not only inspires the development of ECL Janus emitters, but also highlights their potential in bioanalysis and clinical diagnosis in the future. [ABSTRACT FROM AUTHOR]

Photonic (bio)electronic circuits and devices have been an enduring goal in modern photonics and electronics. Organic photoelectrochemical transistor (OPECT) interfacing light with biological world creates a substantial opportunity to this end due to the immense light−bio−matter interplay. Through modulating the invisible ionic circuit of organic electrochemical transistor (OECT) with a bipolar electrode (BPE) accommodating different semiconductor combinations, the unique photonic electronics toward logic and sensor applications are realized. Six combinations of BPEs are produced by the representative n‐type CdS/TiO2 and p‐type BiOI/NiO semiconductors, and the corresponding photonic characteristics and operation rationale are systematically investigated and explained. Designation of opto‐logic circuits and feasibility as a sensory platform are subsequently demonstrated. This work not only represents new photonic bioelectronics but also provides a generic mechanism for the design and development of advanced opto‐logics and bio‐analytics. [ABSTRACT FROM AUTHOR]

Photoelectrochemical (PEC) cytosensors, a combination of the PEC process and the living‐cell assay, have emerged as a powerful tool in the analytical and biological science. This mini review provides a brief introduction of this arena and summaries the key steps about the development of PEC cytosensors with representative examples, followed by future prospects based on our own opinions. [ABSTRACT FROM AUTHOR]

A large collection of unique molecular barcodes is useful in the simultaneous sensing or screening of molecular analytes. Though the sequence of DNA has been widely applied to encode for molecular barcodes, decoding of these barcodes is normally assisted by sequencing. We here demonstrate a barcode system based solely on self‐assembly of synthetic nucleic acids and direct nanopore decoding. Each molecular barcode is composed of "n" distinct information nodes in a non‐binary manner and can be sequentially scanned and decoded by a Mycobacterium smegmatis porin A (MspA) nanopore. Nanopore events containing step‐shaped features were consistently reported. 14 unique information nodes were developed which in principle could encode for 14n unique molecular barcodes in a barcode containing "n" information nodes. These barcode probes were adapted to detect different antibody proteins or cancer‐related microRNAs, suggesting their immediate application in a wide variety of sensing applications. [ABSTRACT FROM AUTHOR]

We report a photodynamic therapy driven by electrochemiluminescence (ECL). The luminescence generated by Ru(bpy)32+ and co‐reactant tripropylamine (TPA) pair acts as both optical readout for ECL imaging, and light source for the excitation of photosensitizer to produce reactive oxygen species (ROS) in photodynamic therapy (PDT) system. The ECL‐driven PDT (ECL‐PDT) relies on the effective energy transfer from ECL emission to photosensitizer chlorin e6 (Ce6), which sensitizes the surrounding O2 into ROS. The dynamic process of gradual morphological changes, the variation of cell‐matrix adhesions, as well as the increase of cell membrane permeability in the process of ECL‐PDT were monitored under ECL microscopy (ECLM) with good spatiotemporal resolution. Combining real‐time imaging with ECL‐PDT, this new strategy provides not only new insights into dynamic cellular processes, but also promising potential of ECL in clinical applications. [ABSTRACT FROM AUTHOR]

Single‐nanoparticle electrochemistry offers electrochemical behaviors of individual entities beyond the ensemble system. An electric double layer (EDL) exists on any charged particle–liquid interface because of counter‐ion accumulation, while direct measuring of the interfacial ion migration remains a challenge. Herein, a plasmonic‐based transient microscopic method, with a temporal resolution of 1–2 μs, was demonstrated to directly track the ion migration dynamics on single charged nanoparticles. We found that the dynamics of EDL formation might deviate significantly from the prediction made by using the classical resistance–capacitance (RC) model under nanoscale and transient conditions. Under ultrafast charging, due to the limit migration rate of ions in the solution, the actual time scale of the EDL formation could be up to 5 times slower than the predicted value from the RC model. We then proposed a new theoretical model to describe the transient dynamics of EDL formation. These results may expand our current knowledge about nano‐electrochemistry and transient electrochemistry. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: SPASER nanoparticle (NP), with small size, ultranarrow spectral‐line and good biocompatibility, is a potential biomedical nanoprobe. However, owning to the striking light absorption capacity of Au‐resonator, huge energy could accumulate under strong pumping‐laser, which would lead to poor photo‐stability and unexpected photo‐damage to SPASER NP, and is harmful to its future practical application but hasn't been systematically studied in experiment. In this paper, our experimental and theoretical researches revealed that the photo‐stability of SPASER NP is largely determined by its structure parameters: smaller Au‐core diameter, thicker silica‐shell will contribute to better photo‐stability. And the possibility and extent of photo‐damage of SPASER NP depend on not only its intrinsic stability but also the external pumping‐laser. Notably, the strong pumping condition for two‐level SPASER system could lead to heating‐melting‐evaporation or even phase‐explosion of SPASER NP, resulting in obvious photo‐damage, while, the weak pumping condition for three‐level SPASER system is quite friendly. This study provides reliable bases for the structural‐properties optimization of SPASER NPs, which is of great significance for its future application as a novel luminescence probe. [ABSTRACT FROM AUTHOR]

Though great advances are achieved in the area of organic electrochemical transistor (OECT) biosensors, general issues of shared electrolyte by the channel and gate electrode remain unsolved. On the other hand, to date binding‐free OECT detection of cellular membrane proteins is not reported. On the basis of the advanced technique of organic photoelectrochemical transistor (OPECT), herein the H‐cell‐supported OPECT device that can easily circumvent the issues of abovementioned shared electrolyte and its application toward binding‐free detection of membrane alkaline phosphatase (ALP) of HeLa cells is demonstrated. In such a configuration, usage of a Nafion perfluorinated membrane equipped H‐cell can well retain the ionic circuit of the device but prevent the diffusion of various molecules and minimize the possible interference. In the detection, ALP catalytic chemistry enables the sensitization of the TiO2 nanotubes electrode, triggering enhanced de‐doping of the poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) and thus resulting in altered channel currents proportionate to the membrane ALP. This work not only provides a new perspective for binding‐free detection of membrane protein but also represents a general protocol for H‐cell‐supported OECT/OPECT biosensors with enhanced accuracy. [ABSTRACT FROM AUTHOR]

Accurate detection of hepatic hydrogen sulfide (H2S) to monitor H2S‐related enzymes' activity is critical for acute hepatitis diagnosis, but remains a challenge due to the dynamic and transient nature of H2S. Here, we report a H2S‐activatable near‐infrared afterglow/MRI bimodal probe F1‐GdNP, which shows an "always‐on" MRI signal and "off‐on" afterglow signal toward H2S. F1‐GdNP shows fast response, high sensitivity and specificity toward H2S, permitting afterglow imaging of H2S and evaluation of cystathionine γ‐lyase (CSE)'s activity in living mice. We further employ the high spatial‐resolution MRI signal of F1‐GdNP to track its delivery and accumulation in liver. Importantly, F1‐GdNP offers a high signal‐to‐background ratio (SBR=86.2±12.0) to sensitively report on the increased hepatic H2S level in the acute hepatitis mice via afterglow imaging, which correlated well with the upregulated CSE activity in the liver, showcasing the good potential of F1‐GdNP for monitoring of acute hepatitis process in vivo. [ABSTRACT FROM AUTHOR]

With reduced background and high sensitivity, photoelectrochemistry (PEC) may be applied as an intracellular nanotool and open a new technological direction of single‐cell study. Nevertheless, the present palette of single‐cell tools lacks such a PEC‐oriented solution. Here a dual‐functional photocathodic single‐cell nanotool capable of direct electroosmotic intracellular drug delivery and evaluation of oxidative stress is devised by engineering a target‐specific organic molecule/NiO/Ni film at the tip of a nanopipette. Specifically, the organic molecule probe serves simultaneously as the biorecognition element and sensitizer to synergize with p‐type NiO. Upon intracellular delivery at picoliter level, the oxidative stress effect will cause structural change of the organic probe, switching its optical absorption and altering the cathodic response. This work has revealed the potential of PEC single‐cell nanotool and extended the boundary of current single‐cell electroanalysis. [ABSTRACT FROM AUTHOR]

Recent developments concerning large protein nanopores suggest a new approach to structure profiling of native folded proteins. In this work, the large vestibule of Mycobacterium smegmatis porin A (MspA) and calmodulin (CaM), a Ca2+‐binding protein, were used in the direct observation of the protein structure. Three conformers, including the Ca2+‐free, Ca2+‐bound, and target peptide‐bound states of CaM, were unambiguously distinguished. A disease related mutant, CaM D129G was also discriminated by MspA, revealing how a single amino acid replacement can interfere with the Ca2+‐binding capacity of the whole protein. The binding capacity and aggregation effect of CaM induced by different ions (Mg2+/Sr2+/Ba2+/Ca2+/Pb2+/Tb3+) were also investigated and the stability of MspA in extreme conditions was evaluated. This work demonstrates the most systematic single‐molecule investigation of different allosteric conformers of CaM, acknowledging the high sensing resolution offered by the MspA nanopore trap. [ABSTRACT FROM AUTHOR]

A novel mass spectrometric method for probing the flash chemistry of electrogenerated reactive intermediates was developed based on rapid collision mixing of electrosprayed microdroplets by using a theta‐glass capillary. The two individual microchannels of the theta‐glass capillary are asymmetrically or symmetrically fabricated with a carbon bipolar electrode to produce intermediates in situ. Microdroplets containing the newly formed intermediates collide with those of the invoked reactants at sub‐10 microsecond level, making it a powerful tool for exploring their ultrafast initial transformations. As a proof‐of‐concept, we present the identification of the key radical cation intermediate in the oxidative dimerization of 8‐methyl‐1,2,3,4‐tetrahydroquinoline and also the first disclosure of previously hidden nitrenium ion involved reaction pathway in the C−H/N−H cross‐coupling between N,N′‐dimethylaniline and phenothiazine. [ABSTRACT FROM AUTHOR]

Pretargeted imaging has emerged as a promising approach to advance nuclear imaging of malignant tumors. Herein, we combine the enzyme‐mediated fluorogenic reaction and in situ self‐assembly with the inverse electron demand Diels–Alder (IEDDA) reaction to develop an activatable pretargeted strategy for multimodality imaging. The trans‐cyclooctene (TCO) bearing small‐molecule probe, P‐FFGd‐TCO, can be activated by alkaline phosphatase and in situ self‐assembles into nanoaggregates (FMNPs‐TCO) retained on the membranes, permitting to (1) amplify near‐infrared (NIR) fluorescence (FL) and magnetic resonance imaging (MRI) signals, and (2) enrich TCOs to promote IEDDA ligation. The Gallium‐68 (68Ga) labeled tetrazine can readily conjugate the tumor‐retained FMNPs‐TCO to enhance radioactivity uptake in tumors. Strong NIR FL, MRI, and positron emission tomography (PET) signals are concomitantly achieved, allowing for pretargeted multimodality imaging of ALP activity in HeLa tumor‐bearing mice. [ABSTRACT FROM AUTHOR]

New tools for single‐cell interrogation enable deeper understanding of cellular heterogeneity and associated cellular behaviors and functions. Information of RNA expression in single cell could contribute to our knowledge of the genetic regulatory circuits and molecular mechanism of disease development. Although significant progresses have been made for intracellular RNA analysis, existing methods have a trade‐off between operational complexity and practical feasibility. We address this challenge by combining the ionic current rectification property of nanopipette reactor with duplex‐specific nuclease‐assisted hybridization chain reaction for signal amplification to realize a simple and practical intracellular nanosensor with minimal invasiveness, which enables single‐cell collection and electrochemical detection of intracellular RNA with cell‐context preservation. Systematic studies on differentiation of oncogenic miR‐10b expression levels in non‐malignant breast cells, metastatic breast cancer cells as well as non‐metastatic breast cancer cells were then realized by this nanotool accompanied by assessment of different drugs effects. This work has unveiled the ability of electrochemistry to probe intracellular RNA and opened new opportunities to study the gene expression and heterogeneous complexity under physiological conditions down to single‐cell level. [ABSTRACT FROM AUTHOR]

Stimuli‐responsive smart photosensitizer (PS) nanoassemblies that allow enhanced delivery and controlled release of PSs are promising for imaging‐guided photodynamic therapy (PDT) of tumors. However, the lack of high‐sensitivity and spatial‐resolution signals and fast washout of released PSs from tumor tissues have impeded PDT efficacy in vivo. Herein, we report tumor targeting, redox‐responsive magnetic and fluorogenic PS nanoassemblies (NP‐RGD) synthesized via self‐assembly of a cRGD‐ and disulfide‐containing fluorogenic and paramagnetic small molecule (1‐RGD) for fluorescence/magnetic resonance bimodal imaging‐guided tumor PDT. NP‐RGD show high r1 relaxivity but quenched fluorescence and PDT activity; disulfide reduction by glutathione (GSH) promotes efficient disassembly into a small‐molecule probe (2‐RGD) and an organic PS (PPa‐SH), which could further bind with intracellular albumin, allowing prolonged retention and cascade activation of fluorescence and PDT to ablate tumors. [ABSTRACT FROM AUTHOR]

The ordered assembly of molecules within a specific space of nanoscale, such as a surface, holds great promise in advanced micro‐/nanostructure fabrication for various applications. Herein, we demonstrate the evanescent wave (EW)‐guided organization of small molecules into a long‐range ordered nanowire (NW) array. Experiment and simulation revealed that the orientation and periodicity of the NW array were feasibly regulated by altering the propagation direction and the wavelength of EW. The generality of this approach was demonstrated by using different molecule precursors. While existing studies on EW often took advantages of its near‐field property for optical sensing, this work demonstrated the photochemical power of EW in the guided‐assembly of small molecules for the first time. It also provides an enlightening avenue to periodic structure with fluorescence, promising for super‐resolution microscopy and important devices applicable to optical and bio‐related fields. [ABSTRACT FROM AUTHOR]

We report a new mass spectrometric method for detecting electrogenerated intermediates. This approach is based on simultaneous activation of electrospray ionization and redox reaction on a wireless bipolar ultramicroelectrode, which is fabricated in the tip of a quartz nanopipette. The hollow structure of the ultramicroelectrode permits rapid transferring the transient species from electrode–electrolyte interfaces into the gas phase for mass spectrometric identification on the time scale of microseconds. The long‐sought fleeting intermediates including TPrA.+, whose lifetime in solution is only 200 μs, and catecholamine o‐semiquinone radicals, the second‐order rate constant of which is typically 109 m−1 s−1, were successfully identified, helping clarify the previously hidden reaction pathways. Accordingly, our method may have wide applicability in exploring the dynamics of many electrochemical reactions, especially their ultrafast initial steps. [ABSTRACT FROM AUTHOR]

The inside walls of a nanopipette tip are decorated by a Pt deposit that is used as an open bipolar electrochemiluminescence (ECL) device to achieve intracellular wireless electroanalysis. The synergetic actions of nanopipette and of bipolar ECL lead to the spatial confinement of the voltage drop at the level of the Pt deposit, which generates ECL emission from luminol. The porous structure of Pt deposit permits the electrochemical transport of intracellular molecules into the nanopipette that is coupled with enzymatic reactions. Thus, the intracellular concentrations of hydrogen peroxide or glucose are measured in vivo as well as the intracellular sphingomyelinase activity. In comparison with the classic bipolar ECL, the remarkably low potential applied in our approach is restricted inside the nanopipette and it minimizes the potential bias of the voltage on the cellular activity. Accordingly, this wireless ECL approach provides a new direction for analysis of single living cells. [ABSTRACT FROM AUTHOR]

O6‐carboxymethylguanine (O6‐CMG) is a highly mutagenic alkylation product of DNA, triggering transition mutations relevant to gastrointestinal cancer. However, precise localization of a single O6‐CMG with conventional sequencing platforms is challenging. Here nanopore sequencing (NPS), which directly senses single DNA bases according to their physiochemical properties, was employed to detect O6‐CMG. A unique O6‐CMG signal was observed during NPS and a single‐event call accuracy of >95 % was achieved. Moreover, O6‐CMG was found to be a replication obstacle for Phi29 DNA polymerase (Phi29 DNAP), suggesting this lesion could cause DNA sequencing biases in next generation sequencing (NGS) approaches. [ABSTRACT FROM AUTHOR]

Herein we report a reflection‐mode total internal reflection microscopy (TIRM) to measure the extinction spectrum of individual dielectric, plasmonic, or light‐absorbing nanoparticles, and to differentiate absorption and scattering components from the total optical output. These capabilities were enabled via illuminating the sample with evanescent wave of which the lightpath length was comparable with the size of single nanoparticles, leading to a dramatically improved reflectance change (ΔI/I0) up to tens of percent. It was further found that scattering and absorption of light contributed to bright and dark centroids, respectively, in the optical patterns of single nanoparticles, allowing to distinguish scattering and absorption components from the extinction spectrum by the use of an appropriate image processing method. In addition, wide‐field feature of TIRM enabled the studies on tens of nanoparticles simultaneously with gentle illumination. Nanoparticles, saved from extinction: An ultrathin (ca. 100 nm) evanescent wave is used to illuminate single nano‐objects (Iin) and to collect the reflected light (Iout). This total internal reflection‐based extinction spectroscopy (TIRES) extracts the extinction spectrum from the wavelength‐dependent TIR patterns of a single nanoparticle. [ABSTRACT FROM AUTHOR]

Single nanoparticle collision (SNC) technology has attracted increasing attention to explore single nanoparticle electrochemistry. By improving the temporal resolution of electrochemical recording, several recent studies have uncovered the intermittent electron transfer processes during the SNC of single silver nanoparticles. The electrode current curve displayed multiple current peaks that were completely separated, instead of a single peak. In the present work, we employed surface plasmon resonance microscopy to monitor the collision and oxidation processes of single silver nanoparticles. Simultaneous optical and electrochemical recordings provided comprehensive capability to correlate the physical movement of nanoparticles (from optical signal) and the electron transfer activity (from electrochemical signal). While previous studies hypothesized the physical detachment of nanoparticles from the electrode due to electrostatic repulsion or Brownian motion, the optical imaging revealed that nanoparticles often remained in physical touch with the electrode even though no electron transfer was occurring. These results demonstrated that the electrical contact between nanoparticle and electrode, which could be rather stochastic due to thermal motion and micro‐convection, played critical roles in regulating the multi‐peak behavior of single silver nanoparticles. In touch: surface plasmon resonance microscopy is utilized to monitor collision and oxidation processes of single silver nanoparticles. Simultaneous optical and electrochemical recordings reveal that nanoparticles often remain in physical touch with the electrode even though no electron transfer is occurring. The electrical contact plays critical roles in regulating the multi‐peak behavior of single silver nanoparticles. [ABSTRACT FROM AUTHOR]

Abstract: Ionic current rectification (ICR) based nanopipettes allow accurate monitoring of cellular behavior in single living cells. Herein, we proposed a 30 nm nanopipette functionalized with G‐quadruplex DNAzyme as an efficient biomimetic recognizer for ROS generation at subcellular level via the changes of current–voltage relationship. Taking advantages of the ultra‐small tip, the nanopipette could penetrate into a single living cell repeatedly or keep measuring for a long time without compromising the cellular functions. Coupled with precision nanopositioning system, generation of ROS in mitochondria in response to cell inflammation was determined with high spatial resolution. Meanwhile, the changes of aerobic metabolism in different cell lines under drug‐induced oxidative stress were monitored continuously. We believe that the ICR‐nanopipette could be developed as a powerful approach for the study of cellular activities via electrochemical imaging in living cells. [ABSTRACT FROM AUTHOR]

Abstract: Noble metal nanoparticles are promising catalysts in electrochemical reactions, while understanding the relationship between the structure and reactivity of the particles is important to achieve higher efficiency of electrocatalysis, and promote the development of single‐molecule electrochemistry. Electrogenerated chemiluminescence (ECL) was employed to image the catalytic oxidation of luminophore at single Au, Pt, and Au‐Pt Janus nanoparticles. Compared to the monometal nanoparticles, the Janus particle structure exhibited enhanced ECL intensity and stability, indicating better catalytic efficiency. On the basis of the experimental results and digital simulation, it was concluded that a concentration difference arose at the asymmetric bimetallic interface according to different heterogeneous electron‐transfer rate constants at Au and Pt. The fluid slip around the Janus particle enhanced local redox reactions and protected the particle surface from passivation. [ABSTRACT FROM AUTHOR]

γ-Glutamyl transpeptidase (GGT) is a cell-membrane-bound enzyme that is involved in various physiological and pathological processes and is regarded as a potential biomarker for many malignant tumors, precise detection of which is useful for early cancer diagnosis. Herein, a new GGT-activatable near-infrared (NIR) fluorescence imaging probe (GANP) by linking of a GGT-recognitive substrate γ-glutamate (γ-Glu) and a NIR merocyanine fluorophore (mCy-Cl) with a self-immolative linker p-aminobenzyl alcohol (PABA) is reported. GANP was stable under physiological conditions, but could be efficiently activated by GGT to generate ≈100-fold enhanced fluorescence, enabling high sensitivity (detection limit of ≈3.6 mU L−1) and specificity for the real-time imaging of GGT activity as well as rapid evaluation of the inhibition efficacy of GGT inhibitors in living tumor cells. Notably, the deep tissue penetration ability of NIR fluorescence could further allow GANP to image GGT in frozen tumor tissue slices with large penetration depth (>100 μm) and in xenograft tumors in living mice. This GGT activatable NIR fluorescence imaging probe could facilitate the study and diagnosis of other GGT-correlated diseases in vivo. [ABSTRACT FROM AUTHOR]

Judiciously integrated nanostructured materials/cellular interfaces could be applied for various applications including physiological monitoring. Physiological H2S is the third most important endogenously generated gasotransmitter and is believed to be related with many diseases. This work reports the novel photoelectrochemical (PEC) probing of cellular interfaces and the evaluation of cellular H2S production based on in situ-generated CdS-enhanced TiO2 nanotube (NT) heterostructures. We chose the TiO2 NT array in particular, owing to its structure of regular oriented vertical NTs (which permits fast directional charge transport) and its substantial inner cavity (which guarantees the highly efficient guest loading and molecule capture). HepG2 cells directly grown on and interfacing with the TiO2 NTs are then used for the activation of the TiO2 NTs through the CdS generated in situ on the TiO2 NTs. Owing to the aforementioned unique properties of TiO2 NTs, even small amounts of in situ-generated CdS could be detected and result in apparent electrical signals. To the best of our knowledge, such TiO2 NT-based in situ PEC probing of cellular interfaces and evaluation of H2S cellular production have not previously been reported. [ABSTRACT FROM AUTHOR]

A crack-free sub-nanometer composite structure for the study of ion transfer was constructed by in situ growth of ZIF-90 [Zn(ICA)2, ICA=Imidazole-2-carboxaldehyde] on the tip of a glass nanopipette. The potential-driven ion transfer through the sub-nanometer channels in ZIF-90 is strongly influenced by the pH of the solution. A rectification ratio over 500 is observed in 1 m KCl solution under alkaline conditions (pH 11.58), which is the highest value reported under such a high salt concentration. Fluorescence experiments show the super-high rectification ratio under alkaline conditions results from the strong electrostatic interaction between ions and the sub-nanometer channels of ZIF-90. In addition to providing a general pathway for further study of mass-transfer process through sub-nanometer channels, the approach enable all kinds of metal-organic frameworks (MOFs) to be used as ionic permselectivity materials in nanopore-based analysis. [ABSTRACT FROM AUTHOR]

Electrochemical surface stress is important in nanomaterials because of their large surface-to-volume ratios, which lead to unique mechanical and electrocatalytic properties, but directly measuring this quantity has been challenging. Here we report on experimental determination of the surface stress, and associated electrochemical processes of a single gold nanowire with an optical imaging technique. We show that surface stress changes linearly and reversibly with the potential between 0 and 0.8 V versus Ag/AgCl, but abruptly with large hysteresis, associated with the oxidation and reduction of the nanowire, between 0.8 and 1.5 V. The potential derivative of the surface stress closely resembles the cyclic voltammograms. We described the observations in terms of anion adsorption and surface oxidation/reduction. This work demonstrates a new approach to study electrochemical processes and the associated surface stress changes of nanomaterials. [ABSTRACT FROM AUTHOR]

Bipolar electrochemistry is based on the gradient distribution of free-electron density along an electrically isolated electrode, which causes a positive electrode potential at one end and a negative potential at the other, allowing for wide applications in analytical chemistry and materials science. To take full advantage of its wireless and high-throughput features, various types of optical probes, such as pH indicators and fluorescence and electrochemiluminescence reagents, have often been used to indirectly monitor the interfacial electron transfer through chromogenic or fluorogenic reactions. Herein, we report the first probe-free imaging approach that can directly visualize the distribution of the interfacial potential in bipolar electrodes, providing essential information for the validation and development of the theory and applications of bipolar electrochemistry. This approach is based on the sensitive dependence of surface plasmon resonance imaging on the local electron density in the electrode, which enables the direct mapping of potential with a spatial resolution close to the optical diffraction limit, a temporal resolution of 50 ms, and a sensitivity of 10 mV. In addition, in contrast to previous optical readouts that relied on faradaic reactions, the present work achieved the impedance-based measurements under non-faradaic conditions. It is anticipated that this technique will greatly expand the application of bipolar electrochemistry as a platform for chemical and biosensing. [ABSTRACT FROM AUTHOR]

Single-cell analysis techniques are essential for understanding the microheterogeneity and functions of cells. Low-copy-number proteins play important roles in cell functioning, but their measurement in single cells remains challenging. Herein, we report an approach, called plasmonic immunosandwich assay (PISA), for probing low-copy-number proteins in single cells. This approach combined in vivo immunoaffinity extraction and plasmon-enhanced Raman scattering (PERS). Target proteins were specifically extracted from the cells by microprobes modified with monoclonal antibody or molecularly-imprinted polymer (MIP), followed by labeling with Raman-active nanotags. The PERS detection, with Raman intensity enhanced by 9 orders of magnitude, provided ultrasensitive detection at the single-molecule level. Using this approach, we found that alkaline phosphatase and survivin were expressed in distinct levels in cancer and normal cells, and that extended culture passage resulted in reduced expression of survivin. We further developed acupuncture needle-based PISA for probing low-copy-number proteins in living bodies. [ABSTRACT FROM AUTHOR]