Controlling the non-linear emission of upconversion nanoparticles to enhance super-resolution imaging performance.

Upconversion nanoparticles (UCNPs) exhibit unique optical properties such as photo-emission stability, large anti-Stokes shift, and long excited-state lifetimes, allowing significant advances in a broad range of applications from biomedical sensing to super-resolution microscopy. In recent years, progress on nanoparticle synthesis led to the development of many strategies for enhancing their upconversion luminescence, focused in particular on heavy doping of lanthanide ions and core-shell structures. In this article, we investigate the non-linear emission properties of fully Yb-based core-shell UCNPs and their impact on the super-resolution performance of stimulated excitation-depletion (STED) microscopy and super-linear excitation-emission (uSEE) microscopy.

A Metal-Polymer Hybrid Biomimetic System for use in the Chemodynamic-Enhanced Photothermal Therapy of Cancers.

This article reports the fabrication of a smart biomimetic enzyme system, which incorporates a pH-responsive chemodynamic therapy (CDT) combined with a photothermal (PTT) therapy approach in resolving the high recurrence rate of deadly cancers. The resulting enzyme system comprises copper sulfide (CuS) nanoparticle (NP) cores as Fenton-like catalysts, and a photothermal-active generation 5 poly(amidoamine) (G5) dendrimer as a template for the entrapment of Cu NPs and the compression of glucose oxidase (GOD). GOD is introduced to produce H O necessary in the sequential Fenton-like reaction, and this generates hydroxyl radicals that kill the cancerous cells.

A Robust Intrinsically Green Fluorescent Poly(Amidoamine) Dendrimer for Imaging and Traceable Central Nervous System Delivery in Zebrafish.

Intrinsically fluorescent poly(amidoamine) dendrimers (IF-PAMAM) are an emerging class of versatile nanoplatforms for in vitro tracking and bio-imaging. However, limited tissue penetration of their fluorescence and interference due to auto-fluorescence arising from biological tissues limit its application in vivo. Herein, a green IF-PAMAM (FGP) dendrimer is reported and its biocompatibility, circulation, biodistribution and potential role for traceable central nervous system (CNS)-targeted delivery in zebrafish is evaluated, exploring various routes of administration.

Unravelling Structural Dynamics within a Photoswitchable Single Peptide: A Step Towards Multimodal Bioinspired Nanodevices.

The majority of the protein structures have been elucidated under equilibrium conditions. The aim herein is to provide a better understanding of the dynamic behavior inherent to proteins by fabricating a label-free nanodevice comprising a single-peptide junction to measure real-time conductance, from which their structural dynamic behavior can be inferred. This device contains an azobenzene photoswitch for interconversion between a well-defined cis, and disordered trans isomer.

A Bimane-Based Peptide Staple for Combined Helical Induction and Fluorescent Imaging.

The thiol-selective fluorescent imaging agent, dibromobimane, has been repurposed to crosslink cysteine- and homocysteine-containing peptides, with the resulting bimane linker acting as both a structural constraint and a fluorescent tag. Macrocyclisation was conducted on nine short peptides containing two cysteines and/or homocysteines, both on-resin and in buffered aqueous solution, to give macrocycles ranging in size from 16 (i,i+2) to 31 (i,i+7) atoms. The structures were defined by CD, NMR structure calculations by using Xplor-NIH, NMR secondary shift and J analyses to reveal helical structure in the i,i+4 (1, 2), and i,i+3 (5) constrained peptides.

Plasmon-Enhanced Four-Wave Mixing Imaging for Microdroplet-Based Single-Cell Analysis.

A high-throughput single-cell analytical technique based on the microdroplet array integrated with the plasmon-enhanced-four-wave mixing (PE-FWM) imaging was developed, which is applicable for the highly sensitive and automatic assessment of the surface receptors of cells. The metal nanoprobes were prepared by simply decorating metal nanoparticles with capturing molecules (antibody or molecules with surface identification function). Owing to the multifrequency selection of lasers via resonating their plasmonic bands, these metal nanoprobes are highly recognizable under the FWM imaging and display high photostability above fluorescent dyes.

Constructing Dual-Molecule Junctions to Probe Intermolecular Crosstalk.

Understanding and controlling charge transport across multiple parallel molecules are fundamental to the creation of innovative functional electronic components, as future molecular devices will likely be multimolecular. The smallest possible molecular ensemble to address this challenge is a dual-molecule junction device, which has potential to unravel the effects of intermolecular crosstalk on electronic transport at the molecular level that cannot be elucidated using either conventional single-molecule or self-assembled monolayer (SAM) techniques. Herein, we demonstrate the fabrication of a scanning tunneling microscopy (STM) dual-molecule junction device, which utilizes noncovalent interactions and allows for direct comparison to the conventional STM single-molecule device.

Rationally designed peptide-based inhibitor of Aβ42 fibril formation and toxicity: a potential therapeutic strategy for Alzheimer's disease.

Amyloid beta peptide (Aβ42) aggregation in the brain is thought to be responsible for the onset of Alzheimer's disease, an insidious condition without an effective treatment or cure. Hence, a strategy to prevent aggregation and subsequent toxicity is crucial. Bio-inspired peptide-based molecules are ideal candidates for the inhibition of Aβ42 aggregation, and are currently deemed to be a promising option for drug design.

Unravelling electron transfer in peptide-cation complexes: a model for mimicking redox centres in proteins.

Metalloproteins are crucial to many biological processes, such as photosynthesis, respiration, and efficient electron transport. Zinc is the most common transition metal found in proteins and is critical for structure, function and stability, however the effects from the electronic properties of a bound zinc ion on electron transfer are not clearly defined. Here, a series of β-strand and 310-helical peptides, capable of binding Zn2+via suitably positioned His residues, was synthesized and their ability to undergo electron transfer in the presence and absence of Zn2+ studied by electrochemical and computational means.

A hypoxia-activated antibacterial prodrug.

A prodrug based on a known antibacterial compound is reported to target Staphylococcus aureus and Escherichia coli under reductive conditions. The prodrug was prepared by masking the N-terminus and side chain amines of a component lysine residue as 4-nitrobenzyl carbamates. Activation to liberate the antibacterial was demonstrated on treatment with a model reductant, tin(II) chloride.

Time-resolved microfluidic flow cytometer for decoding luminescence lifetimes in the microsecond region.

Time-resolved luminescence detection using long-lived probes with lifetimes in the microsecond region have shown great potential in ultrasensitive and multiplexed bioanalysis. In flow cytometry, however, the long lifetime poses a significant challenge to measure wherein the detection window is often too short to determine the decay characteristics. Here we report a time-resolved microfluidic flow cytometer (tr-mFCM) incorporating an acoustic-focusing chip, which allows slowing down of the flow while providing the same detection conditions for every target, achieving accurate lifetime measurement free of autofluorescence interference.

Backbone-Constrained Peptides: Temperature and Secondary Structure Affect Solid-State Electron Transport.

The primary sequence and secondary structure of a peptide are crucial to charge migration, not only in solution (electron transfer, ET), but also in the solid-state (electron transport, ETp). Hence, understanding the charge migration mechanisms is fundamental to the development of biomolecular devices and sensors. We report studies on four Aib-containing helical peptide analogues: two acyclic linear peptides with one and two electron-rich alkene-based side chains, respectively, and two peptides that are further rigidified into a macrocycle by a side bridge constraint, containing one or no alkene.

Luminescent Porous Silicon Nanoparticles for Continuous Wave and Time-Gated Photoluminescence Imaging.

Luminescent porous silicon nanoparticles (LpSiNPs) display red-orange photoluminescence (PL) that provides large penetration depth for precise deep-tissue imaging and diagnostics. Herein, we describe in detail the fabrication process of porous silicon nanoparticles (pSiNPs), activation of photoluminescence, quantum yield measurement, and PL imaging. LpSiNPs perform as imaging probe for both the continuous wave and time-gated PL imaging.

3D sub-diffraction imaging in a conventional confocal configuration by exploiting super-linear emitters.

Sub-diffraction microscopy enables bio-imaging with unprecedented clarity. However, most super-resolution methods require complex, costly purpose-built systems, involve image post-processing and struggle with sub-diffraction imaging in 3D. Here, we realize a conceptually different super-resolution approach which circumvents these limitations and enables 3D sub-diffraction imaging on conventional confocal microscopes.

A highly efficient porous rod-like Ce-doped ZnO photocatalyst for the degradation of dye contaminants in water.

A mild and simple method was developed to synthesize a highly efficient photocatalyst comprised of Ce-doped ZnO rods and optimal synthesis conditions were determined by testing samples with different Ce/ZnO molar ratios calcined at 500 °C for 3 hours via a one-step pyrolysis method. The photocatalytic activity was assessed by the degradation of a common dye pollutant found in wastewater, rhodamine B (RhB), using a sunlight simulator. The results showed that ZnO doped with 3% Ce exhibits the highest RhB degradation rate.

Droplets for Sampling and Transport of Chemical Signals in Biosensing: A Review.

The chemical, temporal, and spatial resolution of chemical signals that are sampled and transported with continuous flow is limited because of Taylor dispersion. Droplets have been used to solve this problem by digitizing chemical signals into discrete segments that can be transported for a long distance or a long time without loss of chemical, temporal or spatial precision. In this review, we describe Taylor dispersion, sampling theory, and Laplace pressure, and give examples of sampling probes that have used droplets to sample or/and transport fluid from a continuous medium, such as cell culture or nerve tissue, for external analysis.

Microfabricated needle for hydrogen peroxide detection.

A microfabricated needle-like probe has been designed and applied for hydrogen peroxide (HO) sampling and detection using a commercial, single-step fluorescent HO assay. In this work, droplets of the assay reagent are generated and sent to the needle tip using a mineral-oil carrier fluid. At the needle tip, the sample is drawn into the device through 100 μm long hydrophilic capillaries by negative pressure.

Time-Gated Luminescent In Situ Hybridization (LISH): Highly Sensitive Detection of Pathogenic .

We describe simple direct conjugation of a single TEGylated Europium chelate to DNA that binds to intracellular rRNA and is then detected using a homogeneous luminescent in situ hybridisation (LISH) technique. As a proof-of-principle, was selected as a model for our study to show the ability of this probe to bind to intracellular 16S ribosomal rRNA. A highly purified Europium chelate conjugated oligonucleotide probe complementary to an rRNA sequence-specific was prepared and found to be soluble and stable in aqueous solution.

High-Throughput, Off-Chip Microdroplet Generator Enabled by a Spinning Conical Frustum.

Although droplet-based microfluidics has been broadly used as a versatile tool in biology, chemistry, and nanotechnology, its rather complicated microfabrication process and the requirement of specialized hardware and operating skills hinder researchers fully unleashing the potential of this powerful platform. Here, we develop an integrated microdroplet generator enabled by a spinning conical frustum for the versatile production of near-monodisperse microdroplets in a high-throughput and off-chip manner. The construction and operation of this generator are simple and straightforward without the need of microfabrication, and we demonstrate that the generator is able to passively and actively control the size of the produced microdroplets.

A Novel Ruthenium-based Molecular Sensor to Detect Endothelial Nitric Oxide.

Nitric oxide (NO) is a key regulator of endothelial cell and vascular function. The direct measurement of NO is challenging due to its short half-life, and as such surrogate measurements are typically used to approximate its relative concentrations. Here we demonstrate that ruthenium-based [Ru(bpy)(dabpy)] is a potent sensor for NO in its irreversible, NO-bound active form, [Ru(bpy)(T-bpy)].

Stacked Nanoporous Anodic Alumina Gradient-Index Filters with Tunable Multispectral Photonic Stopbands as Sensing Platforms.

This study presents the development and optical engineering of stacked nanoporous anodic alumina gradient-index (NAA-GIFs) filters with tunable multispectral photonic stopbands for sensing applications. The structure of these photonic crystals (PC) is formed by stacked layers of NAA produced with sinusoidally modified effective medium. The progressive modification of the sinusoidal period during the anodization process enables the generation and precise tuning of the characteristic photonic stopbands (PSB) (i.

The role of N-terminal heterocycles in hydrogen bonding to α-chymotrypsin.

A series of dipeptide aldehydes containing different N-terminal heterocycles was prepared and assayed in vitro against α-chymotrypsin to ascertain the importance of the heterocycle in maintaining a β-strand geometry while also providing a hydrogen bond donor equivalent to the backbone amide nitrogen of the surrogate amino acid. The dipeptide containing a pyrrole constraint (10) was the most potent inhibitor, with >30-fold improved activity over dipeptides which lacked a nitrogen hydrogen bond donor (namely thiophene 11, furan 12 and pyridine 13). Molecular docking studies of 10 bound to α-chymotrypsin demonstrates a hydrogen bond between the pyrrole nitrogen donor and the backbone carbonyl of Gly located in the S pocket which is proposed to be critical for overall binding.