Comparison of Gap-Enhanced Raman Tags and Nanoparticle Aggregates with Polarization Dependent Super-Resolution Spectral SERS Imaging.

Strongly confined electric fields resulting from nanogaps within nanoparticle aggregates give rise to significant enhancement of surface-enhanced Raman scattering (SERS). Nanometer differences in gap sizes lead to drastically different confined field strengths; so much attention has been focused on the development and understanding of nanostructures with controlled gap sizes. In this work, we report a novel petal gap-enhanced Raman tag (GERT) consisting of a bipyramid core and a nitrothiophenol (NTP) spacer to support the growth of hundreds of small petals and compare its SERS emission and localization to a traditional bipyramid aggregate. To do this, we use super resolution spectral SERS imaging that simultaneously captures the SERS images and spectra while varying the incident laser polarization. Intensity fluctuations inherent of SERS enabled super resolution algorithms to be applied, which revealed subdiffraction limited differences in the localization with respect to polarization direction for both particles. Interestingly, however, only the traditional bipyramid aggregates experienced a strong polarization dependence in their SERS intensity and in the plasmon-induced conversion of NTP to dimercaptoazobenzene (DMAB), which was localized with nanometer precision to regions of intense electromagnetic fields. The lack of polarization dependence (validated through electromagnetic simulations) and surface reactions from the bipyramid-GERTs suggests that the emissions arising from the bipyramid-GERTs are less influenced by confined fields.

Accurate Quantification and Imaging of Cellular Uptake Using Single-Particle Surface-Enhanced Raman Scattering.

Understanding the uptake, distribution, and stability of gold nanoparticles (NPs) in cells is of fundamental importance in nanoparticle sensors and therapeutic development. Single nanoparticle imaging with surface-enhanced Raman spectroscopy (SERS) measurements in cells is complicated by aggregation-dependent SERS signals, particle inhomogeneity, and limited single-particle brightness. In this work, we assess the single-particle SERS signals of various gold nanoparticle shapes and the role of silica encapsulation on SERS signals to develop a quantitative probe for single-particle level Raman imaging in living cells. We observe that silica-encapsulated gap-enhanced Raman tags (GERTs) provide an optimized probe that can be quantifiable per voxel in SERS maps of cells. This approach is validated by single-particle inductively coupled mass spectrometry (spICP-MS) measurements of NPs in cell lysate post-imaging. spICP-MS also provides a means of measuring the tag stability. This analytical approach can be used not only to quantitatively assess nanoparticle uptake on the cellular level (as in previous digital SERS methods) but also to reliably image the subcellular distribution and to assess the stability of NPs in cells.

Non-heme Iron Single-Atom Nanozymes as Peroxidase Mimics for Tumor Catalytic Therapy.

Single-atom nanozymes (SAzymes) open new possibilities for the development of artificial enzymes that have catalytic activity comparable to that of natural peroxidase (POD). So far, most efforts have focused on the structural modulation of the Fe-N4 moiety to mimic the metalloprotein heme center. However, non-heme-iron POD with much higher activity, for example, HppE, has not been mimicked successfully due to its structural complexity. Herein, carbon dots (CDs)-supported SAzymes with twisted, nonplanar Fe-O3N2 active sites, highly similar to the non-heme iron center of HppE, was synthesized by exploiting disordered and subnanoscale domains in CDs. The Fe-CDs exhibit an excellent POD activity of 750 units/mg, surpassing the values of conventional SAzymes with planar Fe-N4. We further fabricated an activatable Fe-CDs-based therapeutic agent with near-infrared enhanced POD activity, a photothermal effect, and tumor-targeting ability. Our results represent a big step in the design of high-performance SAzymes and provide guidance for future applications for synergistic tumor therapy.

Electrochemical fluorescence switching of enhanced green fluorescent protein.

Switchable fluorescent proteins, for which fluorescence can be switched ON and OFF, are widely used for molecule tracking and super resolution imaging. However, the robust use of the switchable fluorescent proteins is still limited as either the switching is not repeatable, or such switching requires irradiation with coupled lasers of different wavelengths. Herein, we report an electrochemical approach to reversible fluorescence switching for enhanced green fluorescent proteins (EGFP) on indium tin oxide coated glass. Our results demonstrate that negative and positive electrochemical potentials can efficiently switch the fluorescent proteins between the dim (OFF) and bright (ON) states at the single molecule level. The electrochemical fluorescence switching is fast, reversible, and may be performed up to hundreds of cycles before photobleaching occurs. These findings highlight that this method of electrochemical fluorescence switching can be incorporated into advanced fluorescence microscopy.

Single-atom nanozymes: From bench to bedside.

Single-atom nanozymes (SANs) are the new emerging catalytic nanomaterials with enzyme-mimetic activities, which have many extraordinary merits, such as low-cost preparation, maximum atom utilization, ideal catalytic activity, and optimized selectivity. With these advantages, SANs have received extensive research attention in the fields of chemistry, energy conversion, and environmental purification. Recently, a growing number of studies have shown the great promise of SANs in biological applications. In this article, we present the most recent developments of SANs in anti-infective treatment, cancer diagnosis and therapy, biosensing, and antioxidative therapy. This text is expected to better guide the readers to understand the current state and future clinical possibilities of SANs in medical applications.

High-Throughput Surface-Enhanced Raman Scattering for Screening Chemical Sensor Candidates Enabled by Bipolar Electrochemistry.

A variety of hydrothermal or electrochemical methods have been explored to prepare noble metal nanostructures as surface-enhanced Raman scattering (SERS) substrates. However, most of those metallic nanoarrays are structurally homogeneous, which makes it laborious to select the high-performance substrates for particular Raman sensing purposes. Here, a high-throughput SERS imaging strategy is demonstrated for the first time for screening chemical sensors with sub-nanomolar sensitivities. Bipolar electrochemistry was applied to generate Au or Au-Ag gradient nanoarrays with diverse chemical compositions, morphologies, and particle dimensions ranging from several nanometers to micrometers. The selected "hot-spots" on the Au-Ag alloy nanoarray exhibited a 660-fold enhancement in SERS intensity compared to those on the pure Au gradient nanoarray. The SERS screening of 4-aminothiophenol, 4-nitrothiophenol, and 4-mercaptobenzoic acid was carried out that provided a limit of detection (LOD) between 1 and 5 pM. The distinctive LODs among three thiophenolic Raman probes are ascribed to the differences in the affinity of the probe to the alloy, orientation of the metal-ligand monolayer, or plasmonic environment of the nanoarray surface. As a continuous, rapid, and cost-effective manner to fabricate transitional nanostructures and screen out SERS responsive sites, this method not only facilitates controllable synthesis of noble metal nanoarrays but has the potential to provide an alternative tool for ultrasensitive chemical sensing on a wide range of bimetallic substrates.

Observing the Reversible Single Molecule Electrochemistry of Alexa Fluor 647 Dyes by Total Internal Reflection Fluorescence Microscopy.

Alexa Fluor 647 is a widely used fluorescent probe for cell bioimaging and super-resolution microscopy. Herein, the reversible fluorescence switching of Alexa Fluor 647 conjugated to bovine serum albumin (BSA) and adsorbed onto indium tin oxide (ITO) electrodes under electrochemical potential control at the level of single protein molecules is reported. The modulation of the fluorescence as a function of potential was observed using total internal reflectance fluorescence (TIRF) microscopy. The fluorescence intensity of the Alexa Fluor 647 decreased, or reached background levels, at reducing potentials but returned to normal levels at oxidizing potentials. These electrochemically induced changes in fluorescence were sensitive to pH despite that BSA-Alexa Fluor 647 fluorescence without applied potential is insensitive to pH between values of 4-10. The observed pH dependence indicated the involvement of electron and proton transfer in the fluorescence switching mechanism.

A mononuclear manganese(II) complex demonstrates a strategy to simultaneously image and treat oxidative stress.

A manganese(II) complex with a ligand containing an oxidizable quinol group serves as a turn-on sensor for H2O2. Upon oxidation, the relaxivity of the complex in buffered water increases by 0.8 mM(-1) s(-1), providing a signal that can be detected and quantified by magnetic resonance imaging. The complex also serves as a potent antioxidant, suggesting that this and related complexes have the potential to concurrently visualize and alleviate oxidative stress.

Three-dimensional hierarchically porous all-carbon foams for supercapacitor.

Three-dimensional hierarchically porous carbon-CNT-graphene ternary all-carbon foams (3D-HPCFs) with 3D macro- and mesoporous structures, a high specific surface area (1286 m(2) g(-1)), large bimodal mesopores (5.1 and 2.7 nm), and excellent conductivity have been fabricated through multicomponent surface self-assembly of graphene oxide (GO)-dispersed pristine CNTs (GOCs) supported on a commercial sponge. The commercial sponge with a 3D interconnected macroporous framework not only is used as a support for GOCs and subsequently multicomponent self-assembly but also serves as a 3D scaffold to buffer electrolytes to reduce ion transport resistance and ion diffusion distance, while the GO acts as "surfactant" to directly disperse pristine CNTs, preserving the excellent electronic structure of pristine CNTs, and the CNTs also prevent the aggregation of graphene as well as improve the whole conductivity. Benefiting from the aforementioned characteristics, the 3D-HPCFs-based supercapacitors show outstanding specific capacitance, high rate capability, and excellent cycling stability, making them potentially promising for high-performance energy storage devices.

Detection of ferrocenemethanol and molecular oxygen based on electrogenerated chemiluminescence quenching at a bipolar electrode.

Small molecules, such as ferrocenemethanol (FcMeOH) and O2, that are capable of quenching the Ru(bpy)3(2+) excited state via energy or electron transfer can be quantitatively detected in a bipolar electrochemical cell based on the attenuation of steady-state electrogenerated chemiluminescence (ECL). FcMeOH quenches ECL generated by the Ru(bpy)3(2+) oxalate coreactant system, exhibiting a linear dependence on [FcMeOH] with a Stern-Volmer slope of 921 M(-1), corresponding to a quenching rate constant of 2 × 10(9) M(-1) s(-1). We used the bipolar ECL quenching platform to measure dissolved O2 and validated the results using a standard Clark electrode. The detection limit for local [O2] measured using ECL quenching was found to be 300 ppb. This work opens up the possibility of utilizing ECL quenching at bipolar electrodes for a wide range of applications.