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The development of Pt on Ni nanoparticles is critical for the improvement of water splitting reactions. Here, the growth of small, below 2 nm Pt islands on crystalline branched Ni nanoparticles was investigated by tuning the size of the islands using a slow seeded-growth synthesis. Smaller island size results in a greater shift in the hydrogen binding energy on the Pt sites, as characterized by the hydrogen underpotential peak position in the voltammogram. This shift indicates the weakening of the binding to hydrogen, which leads to enhanced alkaline hydrogen evolution reaction activity with smaller Pt island size.

Nanopore sensing is a popular biosensing strategy that is being explored for the quantitative analysis of biomarkers. With low concentrations of analytes, nanopore sensors face challenges related to slow response times and selectivity. Here, we demonstrate an approach to rapidly detect species at ultralow concentrations using an optical nanopore blockade sensor for quantitative detection of the protein vascular endothelial growth factor (VEGF). This sensor relies on monitoring fluorescent polystyrene nanoparticles blocking nanopores in a nanopore array of 676 nanopores. The fluorescent signal is read out using a wide-field fluorescence microscope. Nonspecific blockade events are then distinguished from specific blockade events based on the ability to pull the particles out of the pore using an applied electric field. This allows the detection of VEGF at sub-picomolar concentration in less than 15 min.

The impact of the electrolyte ion size on electrocatalytic reactions that occur within nanoconfined volumes is currently unknown. Herein, the effect of the size of solvated alkali metal ions on the oxygen reduction reaction (ORR) in acidic electrolytes was explored by using nanoparticles that contain isolated Pt nanochannels of 1–2 nm in diameter. The exterior surface of the nanoparticles was passivated to ensure that the ORR occurred only in the nanoconfined volume defined by the nanochannels. A number of alkali metal ions, with different hydrated sizes, were added into the acidic electrolyte, and different electrolyte ionic strengths were used to establish different levels of nanoconfinement. The results show that the ORR activity at comparatively positive applied potentials is not affected by the presence and nature of the alkali metal ions in the electrolyte. At less positive potentials, however, the activity is influenced by the presence of alkali metal ions in the electrolyte, and this is dependent on both the identity of the alkali metal ions and the electrolyte ionic strength. The differences in activities at less positive potentials are attributed to differences in the alkali metal ions’ accessibility to the nanoconfined space with Li+being accessible and decreasing the electrocatalytic activity relative to inaccessible K+ions that cannot enter the nanoconfined channels. This was corroborated by molecular dynamics modeling suggesting that the energy penalty for the alkali metal ions to enter the nanochannels is different for the different alkali metal ions and is affected by the surface charge of the nanochannel walls.

Stochastic optical reconstruction microscopy (STORM) allows wide-field imaging with single-molecule resolution by calculating the coordinates of individual fluorophores from the separation of fluorophore emission in both time and space. Such separation is achieved by photoswitching the fluorophores between a long-lived OFF state and an emissive ON state. Although STORM can image single molecules, molecular counting remains challenging due to undercounting errors from photobleached or overlapping dyes and overcounting artefacts from the repetitive random blinking of dyes. Here we show that fluorophores can be electrochemically switched for STORM imaging (EC-STORM), with excellent control over the switching kinetics, duty cycle and recovery yield. Using EC-STORM, we demonstrate molecular counting by using electrochemical potential to control the photophysics of dyes. The random blinking of dyes is suppressed by a negative potential but the switching-ON event can be activated by a short positive-potential pulse, such that the frequency of ON events scales linearly with the number of underlying dyes. We also demonstrate EC-STORM of tubulin in fixed cells with a spatial resolution as low as ~28 nm and counting of single Alexa 647 fluorophores on various DNA nanoruler structures. This control over fluorophore switching will enable EC-STORM to be broadly applicable in super-resolution imaging and molecular counting.

Controlling the coordination environment of the nanocatalyst surface is a major synthetic challenge to producing electrocatalysts with high activity and high stability. This is particularly important for the methanol oxidation reaction (MOR) in which multiple neighboring metal atoms are needed to prevent CO poisoning. Using a combination of tunable Pt-island size and a spreading process, we can vary the Pt loading on branched Ru nanoparticles, which leads to tunable proportions of Pt–Pt and Pt–Ru neighboring atoms at the surface. The controlled coordination environments are shown to be critical to stripping poisoning CO intermediates and can be precisely tuned to achieve highly active and stable MOR catalysts. These results show a new concept in synthetically controlling the coordination environment around a catalytic site for improved activity and stability that can be applied to other multimetal nanocatalysts.

Growing Pt on Ag nanoparticles is a promising approach to forming catalysts that present active sites with both Pt and Ag available to improve the activity for the hydrogen evolution reaction (HER). By carefully controlling the concentration of a Pt precursor, the amount of Pt-decorated particles onto the Ag nanoparticles could be controlled to grow Pt islands between 0.6 and 1.5 nm. As a result, the relative amounts of the Ag–Pt active sites could be tuned. The smallest, 0.6 nm Pt islands on the Ag nanoparticle, with the highest ratio of Ag–Pt to Pt–Pt sites was found to have the highest activity and an accelerated Volmer step. DFT modeling showed that the improved performance was due to increased electron density on Pt from electron donation from neighboring Ag that leads to weaker Pt–H binding and the presence of more oxophilic Ag that can bind −OH on the active site that accelerates the water splitting.

Synthetic hydrogels have been used widely as extracellular matrix (ECM) mimics due to the ability to control and mimic physical and biochemical cues observed in natural ECM proteins such as collagen, laminin, and fibronectin. Most synthetic hydrogels are formed viacovalent bonding resulting in slow gelation which is incompatible with drop-on-demand 3D bioprinting of cells and injectable hydrogels for therapeutic delivery. Herein, we developed an electrostatically crosslinked PEG-based hydrogel system for creating high-throughput 3D in vitro models using synthetic hydrogels to mimic the ECM cancer environment. A 3-arm PEG-based polymer backbone was first modified with either permanent cationic charged moieties (2-(methacryloyloxy)ethyl trimethylammonium) or permanent anionic charged moieties (3-sulfopropyl methacrylate potassium salt). The resulting charged polymers can be conjugated further with various amounts of cell adhesive RGD motifs (0, 25, 75, and 98%) to study the influences of RGD motifs on breast cancer (MCF-7) spheroid formation. Formation, stability, and mechanical properties of hydrogels were tested with, and without, RGD to evaluate the cellular response to material parameters in a 3D environment. The hydrogels can be degraded in the presence of salts at room temperature by breaking the interaction of oppositely charged polymer chains. MCF-7 cells could be released with high viability through brief exposure to NaCl solution. Flow cytometry characterization demonstrated that embedded MCF-7 cells proliferate better in a softer (60 Pa) 3D hydrogel environment compared to those that are stiffer (1160 Pa). As the stiffness increases, the RGD motif plays a role in promoting cell proliferation in the stiffer hydrogel. Flow cytometry characterization demonstrated that embedded MCF-7 cells proliferate better in a softer (60 Pa) 3D hydrogel environment compared to those that are stiffer (1160 Pa). As the stiffness increases, the RGD motif plays a role in promoting cell proliferation in the stiffer hydrogel. Additionally, cell viability was not impacted by the tested hydrogel stiffness range between 60 to 1160 Pa. Taken together, this PEG-based tuneable hydrogel system shows great promise as a 3D ECM mimic of cancer extracellular environments with controllable biophysical and biochemical properties. The ease of gelation and dissolution through salt concentration provides a way to quickly harvest cells for further analysis at any given time of interest without compromising cell viability.

Branched metal nanoparticles have unique catalytic properties because of their high surface area with multiple branches arranged in an open 3D structure that can interact with reacting species and tailorable branch surfaces that can maximize the exposure of desired catalytically active crystal facets. These exceptional properties have led to the exploration of the roles of branch structural features ranging from the number and dimensions of branches at the larger scales to the atomic-scale arrangement of atoms on precise crystal facets. The fundamental significance of how larger-scale branch structural features and atomic-scale surface faceting influence and control the catalytic properties has been at the forefront of the design of branched nanoparticles for catalysis. Current synthetic advances have enabled the formation of branched nanoparticles with an unprecedented degree of control over structural features down to the atomic scale, which have unlocked opportunities to make improved nanoparticle catalysts. These catalysts have high surface areas with controlled size and surface facets for achieving exceedingly high activity and stability. The synthetic advancement has recently led to the use of branched nanoparticles as ideal substrates that can be decorated with a second active metal in the form of islands and single atoms. These decorated branched nanoparticles have new and highly effective catalytic active sites where both branch metal and decorating metal play essential roles during catalysis.

Selective isolation of individual target cells from a heterogeneous population is technically challenging; however, the ability to retrieve single cells can have high significance in various aspects of biological research. Here, we present a new photoelectrochemical surface based on a transparent electrode that is compatible with high-resolution fluorescence microscopy for isolating individual rare cells from complex biological samples. This is underpinned by two important factors: (i) careful design of the electrode by patterning discrete Au disks of micron dimension on amorphous silicon–indium tin oxide films and (ii) orthogonal surface chemistry, which modifies the patterned electrode with self-assembly layers of different functionalities, to selectively capture target cells on the Au disks and resist cell binding to the amorphous silicon surface. The co-stimulation of the surface using light from a microscope and an electric potential triggers the reductive desorption of the alkanethiol monolayer from the Au disks to release the single cells of interest from the illuminated regions only. Using circulating tumor cells as a model, we demonstrate the capture of cancer cells on an antibody-coated surface and selective release of single cancer cells with low expression of epithelial cell adhesion molecules.

Nanopore sensors have received significant interest for the detection of clinically important biomarkers with single-molecule resolution. These sensors typically operate by detecting changes in the ionic current through a nanopore due to the translocation of an analyte. Recently, there has been interest in developing optical readout strategies for nanopore sensors for quantitative analysis. This is because they can utilize wide-field microscopy to independently monitor many nanopores within a high-density array. This significantly increases the amount of statistics that can be obtained, thus enabling the analysis of analytes present at ultralow concentrations. Here, we review the use of optical nanopore sensing strategies for quantitative analysis. We discuss optical nanopore sensing assays that have been developed to detect clinically relevant biomarkers, the potential for multiplexing such measurements, and techniques to fabricate high density arrays of nanopores with a view toward the use of these devices for clinical applications.

Developing alternatives to platinum-based electrocatalysts for the hydrogen evolution reaction (HER) is an important challenge for realizing the green transition. This is especially the case for alkaline conditions where Pt-based catalysts have very poor stability. Here, we demonstrate a new solvothermal synthesis method with facile allotropism control for selectively obtaining hexagonal-close-packed (hcp) and face-centered cubic (fcc) ruthenium nanoparticles. Both samples are highly active and durable HER catalysts in alkaline conditions outperforming state-of-the-art Pt/C. However, the samples show markedly different stabilities. The hcp sample shows exceptional stability for 12 hours constant operation at 10 mA cm−2with an overpotential that only increases 6 mV whereas the fcc sample increases 50 mV and the commercial Pt/C more than 350 mV. The significant variation in the stability of two Ru allotropes could be attributed to the difference in their crystal symmetries. Thus, this study underlines the importance of controlling the crystal structure of nanoparticle electrocatalysts and underlines the potential of using relatively cheaper Ru as an alternative to Pt for HER in alkaline conditions.

The synthesis and characterization of carbon black supported rhodium and iridium heterobimetallic catalysts, termed hybrid catalysts, and their application in the hydrosilylation of alkynes is described. An aryl diazonium grafting procedure was applied to simultaneously immobilize Rh and Ir pyrazole–triazole complexes with tethers of varying lengths to carbon black, yielding the hybrid catalysts. The complexes differ in metal centre oxidation state and co-ligands, which are CO or Cp*Cl for the Rh complexes and Cp*Cl for the Ir complexes. The immobilization results in simultaneous surface binding and modification of the Rh complexes bearing CO-ligands. In this process, the CO ligands are removed and the overall structure of the catalytically active complex is altered. Analysis of the hybrid catalysts by XPS and SEM/EDX shows that the catalysts bear both surface bound Rh- and Ir-complexes. The Rh content is substantially higher than the Ir content. This is due to more efficient binding of the modified Rh complexes to the carbon black, as they feature two potential binding sites. Synchrotron based X-ray absorption spectroscopy (XAS) at the Rh K- and Ir L3edges further confirms the presence of the surface bound metal complexes. There is no indication that the presence of a secondary metal affects the electronic structure of the adjacent metal in the systems under investigation, for either the long or short tether derivatives. The performance of the different catalysts was assessed for promoting the hydrosilylation of alkynes, an important industrially relevant reaction. All catalysts are highly efficient. The modified Rh sites are α-selective in the product formation on activation of terminal alkynes, while the RhCp*Cl and IrCp*Cl sites are β(Z)-selective. When operating at mild conditions with high metal loadings, the surface bound Rh catalyst is the active species, while the Ir sites are inactive. At a lower overall surface coverage or higher temperature, the Ir sites become active, which allows engineering of the regioselectivity by adjusting surface coverages and metal loadings.

Gold coated magnetic nanoparticles (Au@MNPs), modified with DNA sequences give dispersible electrodes that can detect ultralow amounts of microRNAs and other nucleic acids but, as with most other sensors, they require calibration. Herein we show how to adapt a calibration free approach for electrochemical aptamer-based sensors on bulk electrodes to microRNA (miR-21) detection with methylene blue terminated DNA modified Au@MNPs. The electrochemical square wave voltammetry signal from the DNA-Au@MNPs when collected at a bulk electrode under magnetic control, decreases upon capture of miR-21. We show that the square wave voltammogram has concentration dependent and independent frequencies that can be used to give a calibration free signal.

Understanding the underlying mechanisms of migration and metastasis is a key focus of cancer research. There is an urgent need to develop in vitro3D tumor models that can mimic physiological cell–cell and cell–extracellular matrix interactions, with high reproducibility and that are suitable for high throughput (HTP) drug screening. Here, we developed a HTP 3D bioprinted migration model using a bespoke drop-on-demand bioprinting platform. This HTP platform coupled with tunable hydrogel systems enables (i) the rapid encapsulation of cancer cells within in vivotumor mimicking matrices, (ii) in situand real-time measurement of cell movement, (iii) detailed molecular analysis for the study of mechanisms underlying cell migration and invasion, and (iv) the identification of novel therapeutic options. This work demonstrates that this HTP 3D bioprinted cell migration platform has broad applications across quantitative cell and cancer biology as well as drug screening.

Adsorption of a biofouling layer on the surface of biosensors decreases the electrochemical activity and hence shortens the service life of biosensors, particularly implantable and wearable biosensors. Real-time quantification of the loss of activity is important for in situassessment of performance while presenting an opportunity to compensate for the loss of activity and recalibrate the sensor to extend the service life. Here, we introduce an electrochemical noise measurement technique as a tool for the quantification of the formation of a biofouling layer on the surface of gold. The technique uniquely affords thermodynamic and kinetic information without applying an external bias (potential and/or current), hence allowing the system to be appraised in its innate state. The technique relies on the analysis of non-faradaic current and potential fluctuations that are intrinsically generated by the interaction of charged species at the electrode surface, i.e., gold. An analytical model is extended to explain the significance of parameters drawn from statistical analysis of the noise signal. This concept is then examined in buffered media in the presence of albumin, a common protein in the blood and a known source of a fouling layer in biological systems. Results indicate that the statistical analysis of the noise signal can quantify the loss of electrochemical activity, which is also corroborated by impedance spectroscopy as a complementary technique.

How nanoparticles distribute in living cells and overcome cellular barriers are important criteria in the design of drug carriers. Pair-correlation microscopy is a correlation analysis of fluctuation in the fluorescence intensity obtained by a confocal line scan that can quantify the dynamic properties of nanoparticle diffusion including the number of mobile nanoparticles, diffusion coefficient, and transit time across a spatial distance. Due to the potential heterogeneities in nanoparticle properties and the complexity within the cellular environment, quantification of averaged auto- and pair-correlation profiles may obscure important insights into the ability of nanoparticles to deliver drugs. To overcome this issue, we used phasor analysis to develop a data standardizing method, which can segment the scanned line into several subregions according to diffusion and address the spatial heterogeneity of nanoparticles moving inside cells. The phasor analysis is a fit-free method that represents autocorrelation profiles for each pixel relative to free diffusion on the so-called phasor plots. Phasor plots can then be used to select subpopulations for which the auto- and pair-correlation analysis can be performed separately. We demonstrate the phasor analysis for pair-correlation microscopy for investigating 16 nm, Cy5-labeled silica nanoparticles diffusing across the plasma membrane and green fluorescent proteins (GFP) diffusing across nuclear envelope in MCF-7 cells.

A series of Rh- and Ir-hybrid catalysts with varying tether lengths has been prepared by immobilization of RhI, RhIIIand IrIIIcomplexes on carbon black viaradical grafting. The performance of the different catalysts was assessed for the hydrosilylation of phenylacetylene with Et3SiH. The efficiency of the catalysts was dependent on the length of the tethers to the surface. The RhIII- and IrIIIhybrids afforded the β(Z)-vinylsilanes, as observed for the analogous homogeneous RhIIIcatalyst. No distinct product selectivity was observed when using the homogeneous RhIprecursors as catalysts. However, on using the RhIIIhybrid catalysts derived from the RhIprecursors to promote hydrosilylation, the major products were the α-vinylsilanes and the origin of the difference in reactivity was found to be a chemical modification of the catalysts during immobilization. Substrate scope is demonstrated for a number of alkynes, and feasible mechanisms supported by DFT calculations are proposed.

Porous materials can be modified with physical barriers to control the transport of ions and molecules through channels via an external stimulus. Such capability has brought attention toward drug delivery, separation methods, nanofluidics, and point-of-care devices. In this context, gated platforms on which access to an electrode surface of species in solution can be reversibly hindered/unhindered on demand are appearing as promising materials for sensing and microfluidic switches. The preparation of a reversible gated device usually requires mesoporous materials, nanopores, or molecularly imprinted polymers. Here, we show how the breath-figure method assembly of graphene oxide can be used as a simple strategy to produce gated electrochemical materials. This was achieved by forming an organized porous thin film of graphene oxide onto an ITO surface. Localized brushes of thermoresponsive poly(N-isopropylacrylamide) were then grown to specific sites of the porous film by in situ reversible addition-fragmentation chain-transfer polymerization. The gating mechanism relies on the polymeric chains to expand and contract depending on the thermal stimulus, thus modulating the accessibility of redox species inside the pores. The resulting platform was shown to reversibly hinder or facilitate the electron transfer of solution redox species by modulating temperature from the room value to 45 °C or vice versa.

Incorporation of fluorinated moieties in polymeric nanoparticles has been shown in many instances to increase their uptake by living cells and, hence, has proven to be a useful approach to enhancing delivery to cells. However, it remains unclear how incorporation of fluorine affects critical transport processes, such as interactions with membranes, intracellular transport, and tumor penetration. In this study, we investigate the influence of fluorine on transport properties using a series of rationally designed poly(oligo(ethylene glycol) methyl ether acrylate)-block-perfluoropolyether (poly(OEGA)m-PFPE) copolymers. Copolymers with different fluorine contents were prepared and exhibit aggregate in solution in a manner dependent on the fluorine content. Doxorubicin-conjugated poly(OEGA)20-PFPE nanoparticles with lower fluorine content exist in solution as unimers, leading to greater exposure of hydrophobic PFPE segments to the cell surface. This, in turn, results in greater cellular uptake, deeper tumor penetration, as well as enhanced therapeutic efficacy compared to that with the micelle-state nanoaggregates (poly(OEGA)10-PFPE and poly(OEGA)5-PFPE) with higher fluorine content but with less PFPE exposed to the cell membranes. Our results demonstrate that the aggregation behavior of these fluorinated polymers plays a critical role in internalization and transport in living cells and 3D spheroids, providing important design criteria for the preparation of highly effective delivery agents.

Spatial control of surface functionalization and interactions is essential for microarray-based analysis. This study reports the fabrication of two-dimensional molecular films with site-specific functionalities, forming microarrays at discrete locations. Arrays of microsized gold disks were produced on a silicate membrane using microfabrication. On these arrays, orthogonal self-assembly of molecules was performed that can specifically bind to gold or silicate. The gold array elements were functionalized with a range of alkanethiols and the silicate with polymeric poly-l-lysine-grafted-poly(ethylene glycol) (PLL-PEG). The surface functionalization on the gold disk array and the surrounding substrate was characterized at each step using X-ray photoelectron spectroscopy (XPS) to show that alkanethiols are specifically attached to the gold. PLL-PEG was used to provide resistance against nonspecific protein and cell adsorption and attached exclusively to the silicate. The effectiveness of the surface chemistry was validated by the selective self-assembly of a gold nanoparticle monolayer array on the gold regions. In a more sophisticated example, selective adhesion of MCF-7 cells to anti-EpCAM antibody modified gold areas of the gold–silicate surface was demonstrated to give a cell microarray. This study provides a general approach to fabricate chemical patterns on silicon-based devices with the convergence of microfabrication and material-specific surface modification, which may be useful to expand the functionalities and potential applications for patterned biomolecular films. Importantly, the ability to pattern surfaces with different surface chemistries is not limited to planar surfaces using this orthogonal surface-coupling approach.

We report the development of metal–organic framework (MOF)-based probes for the direct and rapid detection and quantification of perfluorooctanoic acid (PFOA) by mass spectrometry. Four water-resistant MOFs—ZIF-8, UiO-66, MIL88-A, and Tb2(BDC)3—were coated on poly(dopamine) precoated stainless steel needles and used to rapidly preconcentrate PFOA from water for direct analysis by nanoelectrospray ionization mass spectrometry. The analytical performance of each MOF for detecting PFOA was correlated with both the calculated binding energy of the MOF for PFOA and the relative change in the surface area of the MOF upon exposure to PFOA. MOF-functionalized probes can be used for the rapid (<5 min) and sensitive quantification of PFOA molecules at low ng L–1levels in environmental water samples (i.e., tap water, rainwater, and seawater) with no sample preparation. The limit of detection of PFOA in ultrapure water was 11.0 ng L–1. Comparable accuracy to an accredited analytical method was achieved, despite the MOF-functionalized probe approach being ∼40 times quicker and requiring ∼10 times less sample. These features indicate that MOF-coated probes are promising for the direct and rapid monitoring of polyfluorinated substances and other pollutants in the field.

Controlling which facets are exposed in nanocrystals is crucial to understanding different activity between ordered and disordered alloy electrocatalysts. We modify the degree of ordering of Pt3Sn nanocubes, while maintaining the shape and size, to enable a direct evaluation of the effect of the order on ORR catalytic activity. We demonstrate a 2.3-fold enhancement in specific activity by 60- and 30%-ordered Pt3Sn nanocubes compared to 95%-ordered. This was shown to be likely due to surface vacancies in the less-ordered particles. The greater order, however, results in higher stability of the electrocatalyst, with the more disordered nanoparticles showing the dissolution of tin and platinum species during electrocatalysis.

Heterojunctions are typically used to generate large photovoltages and to influence the direction of flow of charge carriers on photovoltaic and photocatalytic devices. Herein, we propose how heterojunctions can be used as a pathway for tuning the peak position of redox active monolayers. This was possible by exploring the principle of contact between materials in heterojunctions leading to a common equilibrium Fermi level for both sides of the heterojunction. The phenomenon was demonstrated with thin layers of intrinsic amorphous silicon deposited on platinum, indium tin oxide, and either n-type or p-type crystalline silicon electrodes. At fixed light-intensity conditions, the potential required for electron transfer of a model redox probe was modulated according to the substrate on which the amorphous silicon was deposited. This allowed us to alter the peak position of a redox process occurring on the electrolyte side of the junction despite it being isolated from the underlying conducting material. We show how such an effect can be explored in a potential range that encompasses any of the redox monolayers electroactive in aqueous electrolytes.

The direct growth of Pt islands on lattice mismatched Ni nanoparticles is a major synthetic challenge and a promising strategy to create highly strained Pt atoms for electrocatalysis. By using very mild reaction conditions, Pt islands with tunable strain were formed directly on Ni branched particles. The highly strained 1.9 nm Pt-island on branched Ni nanoparticles exhibited high specific activity and the highest mass activity for hydrogen evolution (HER) in a pH 13 electrolyte. These results show the ability to synthetically tune the size of the Pt islands to control the strain to give higher HER activity.