Ultrasensitive Probe Research Articles

Chiral CdSe nanoplatelets as an ultrasensitive probe for lead ion sensing.

As opposed to traditional photoluminescence and ultra-violet based optical sensing, we present here a sensing system based on resolved optically active polarization with promising applications. It is based on the ultrathin CdSe nanoplatelets (NPLs) when modified with either l or d-cysteine molecules (l/d-cys) as bio-to-nano ligands. The chiral ligand transfers its chiroptical activity to the achiral nanoplatelets with an anisotropy factor of ∼10-4, which unlocks the chiral excitonic transitions and allows lead ion detection with a limit of detection (LOD) as low as 4.9 nM. Simulations and modelling based on time-dependent density functional theory (TD-DFT) reveal the chiral mechanism of l/d-cys capped CdSe NPLs. The presented CD-based sensing system illustrates an alternative possibility of using chiral CdSe NPLs as competitive chiral sensors for heavy metal ion detection.

A highly specific and ultrasensitive probe for the imaging of inflammation-induced endogenous hypochlorous acid.

A turn-on two-photon fluorescent probe HCA-Green for hypochlorous acid (HOCl) was synthesized using 4-methylamino-1,8-naphthalimide (MNA) as a two-photon fluorophore and p-hydroxyaniline as a leaving-recognition domain. Both the probe and the fluorophore were investigated under one- and two-photon excitation modes. The fluorescence intensity of the probe was enhanced by ∼229-fold and ∼193-fold under one-photon and two-photon excitation, respectively, after reacting with HOCl. A maximal two-photon action cross-section of 50 GM was obtained under excitation at 810 nm. The probe exhibited high sensitivity with a detection limit of 42.3 nM, as well as high selectivity, low cytotoxicity, and good photostability. Two-photon microscopy (TPM) was conducted to visualize HOCl levels in living cells and tissues. The production of endogenous HOCl induced by lipopolysaccharide-mediated inflammation was successfully monitored with this probe.

A far-red to NIR emitting ultra-sensitive probe for the detection of endogenous HOCl in zebrafish and the RAW 264.7 cell line.

Fluorescence imaging is a dynamic tool for monitoring the functions of biomolecules in living systems. Probes with emission in the far-red to near-infrared range have been found to demonstrate great application prospects in bioimaging due to their deep tissue penetration, low background fluorescence, minimum photodamage to the tissue and high sensitivity. The present study aimed to construct a far-red to near-infrared emitting probe (PI) bearing dicyanoisophorone coupled with a phenothiazine moiety. The probe exhibits an instant response towards HOCl with a colour change from red to yellow with a 100 fold fluorescence enhancement at 620 nm with a low detection limit (42 nM). The electron-rich sulfur atom can be oxidised by HOCl; this endows the probe with distinct selectivity over other anions as well as other reactive oxygen species. The probe demonstrates great cell permeability with low toxicity to the cell. Therefore, the probe can be effectively applied in biological systems to monitor the endogenous level of HOCl produced by PMA in living systems and in the fluorescence imaging of endogenous HOCl in zebrafish and the RAW 264.7 cell line.

Ultrasensitive amplification-free detection of protein kinase based on catalyzed assembly and enumeration of gold nanoparticles.

A single-particle enumeration method based on phosphorylation-directed in situ assembly of gold nanoparticles is developed for the ultrasensitive sensing of cellular protein kinase A activity. In comparison to existing strategies, the proposed new method demonstrates five orders of linear range and improves the detection limit up to 10-to-1000 fold without the involvement of target amplification.

An organic neurophysiological tool for neuronal metabolic activity monitoring.

Monitoring cell metabolism in vitro is considered a relevant methodology in several scientific fields ranging from fundamental biology research to neuro-toxicology. In the last 20 years, several in vitro neuro-pharmacological and neuro-toxicological approaches have been developed, with the intent of addressing the increasing demand for real-time, non-invasive in vitro systems capable of continuously and reliably monitoring cellular activity. In this paper, an Organic Charge Modulated Field Effect Transistor-based device is proposed as a promising tool for neuro-pharmacological applications, thanks to its ultra-high pH sensitivity and a simple fabrication technology. The preliminary characterization of this versatile organic device with primary neuronal cultures shows how these remarkable properties can be exploited for the realization of ultra-sensitive metabolic probes, which are both reference-less and low cost. These features, together with the already assessed capability of this sensor to also monitor the electrical activity of electrogenic cells, could provide important advances in the fabrication of multi-sensing lab-on-chip devices, thus opening up interesting perspectives in the neuro-pharmacological field.

A Rapid and Ultrasensitive Tetraphenylethylene-Based Probe with Aggregation-Induced Emission for Direct Detection of α-Amylase in Human Body Fluids.

α-Amylase plays a key role in the physiological cycle of the human body; its function is constantly explored and used as an important indicator of some related diseases like acute pancreatitis, acute organophosphorus pesticide poisoning, and anxiety or depression. However, currently, including the assay kit, existing methods suffer from low sensitivity and time consumption or are indirect assays that require the aid of a tool enzyme or inhibitor of competitive substrates; hence, they are not suitable for the low activity and nondestructive sensing of α-amylase in body fluids. A rapid, highly sensitive, and simple direct α-amylase determination in human body fluids is still challenging. In this work, an AIEgen-based small molecule α-amylase sensing system was first established. The probe has no emission signal in aqueous media because of its good solubility, but the insoluble AIE residues can be released after hydrolysis by α-amylase, lighting up fluorescence significantly. In this novel sensing system, the detection limit is calculated to be 0.14 U L-1 in MES buffer with a linear range of 0-45.5 U L-1, having been shortened to 3 min of test time and excellent selectivity to α-amylase compared to other proteins. Moreover, our method is successfully employed to demonstrate the applications in acute pancreatitis diagnosis and psychological stress analysis. The acquisition of this AIE-based method not only provides a simple technique for clinical diagnosis of related diseases but also has a promotional value for the food and pharmaceutical industries.

Progress on the development of DNA-mediated metal nanomaterials for environmental and biological analysis

Nowadays, DNA-mediated metal nanomaterials have received more and more attention due to their distinctive properties of easy synthesis, high stability and good biocompatibility. As a kind of efficient template to mediate the precise synthesis of metal nanomaterials, DNA can not only increase their recognition and biocompatibility, but also precisely control their morphology, structure and further analytical performance. DNA-mediated metal nanomaterials as ultrasensitive and selective probes have unique advantages for in situ rapid analysis of targets in complex samples. Herein, we reviewed the recent progress on synthesis strategies, morphologies, specific properties of DNA-mediated metal nanomaterials including nanoparticles and nanoclusters. Moreover, the applications of DNA-mediated metal nanomaterials to environmental and biological analysis were also summarized. Finally, the developing prospect of DNA-mediated metal nanomaterials in analytical chemistry was discussed and proposed.

MIP-capped terbium MOF-76 for the selective fluorometric detection of cefixime after its preconcentration with magnetic graphene oxide

Herein, a sensitive and reliable fluorometric probe based on the molecular imprinted polymer capped terbium metal-organic frameworks (MIP@TbMOF-76) was introduced for the measurement of cefixime. The MIP@TbMOF-76 composite was prepared by simple co-polymerization of definite monomers and cross-linkers in the presence of TbMOF-76 as support and cefixime as the model template molecules. After the removing of template molecules, the obtained composite had an intense fluorescence emission corresponding to the terbium emission spectra which undergo a sensible diminution in the presence of cefixime. The prepared MIP@TbMOF-76 indicated a great affinity to adsorb cefixime molecules, which could linearly quench the emission intensity. Moreover, an extraction process using magnetic Fe3O4@SiO2 modified graphene oxide (Fe3O4/GO) was applied for the efficient preconcentration of cefixime from aqueous solution to access its very low concentrations. Based on this procedure, an ultrasensitive and selective probe was designed for cefixime. After optimization of key factors, a calibration graph was achieved in the concentration range of 0.8–90 ng mL−1 cefixime, with a detection limit (3 s) of 0.34 ng mL−1. The developed probe had a good precision (RSD% < 3.6) and was acceptably used for the determination of cefixime in pharmaceutical and human urine samples.

Ultrasensitive Graphene Optoelectronic Probes for Recording Electrical Activities of Individual Synapses

The complex neuronal circuitry connected by submicron synapses in our brain calls for technologies that can map neural networks with ultrahigh spatiotemporal resolution to decipher the underlying mechanisms for multiple aspects of neuroscience. Here we show that, through combining graphene transistor arrays with scanning photocurrent microscopy, we can detect the electrical activities of individual synapses of primary hippocampal neurons. Through measuring the local conductance change of graphene optoelectronic probes directly underneath neuronal processes, we are able to estimate millivolt extracellular potential variations of individual synapses during depolarization. The ultrafast nature of graphene photocurrent response allows for decoding of activity patterns of individual synapses with a sub-millisecond temporal resolution. This new neurotechnology provides promising potentials for recording of electrophysiological outcomes of individual synapses in neural networks.

Selective supramolecular interaction of ethylenediamine functionalized graphene quantum dots: Ultra-sensitive photoluminescence detection for nickel ion in vitro

Graphene quantum dots have attracted the researchers' attention due to its high stability, low cost and controllable photoluminescence performance. In this paper, we report the synthesis of ethylenediamine functionalized graphene quantum dots (E-GQDs). The E-GQDs is synthesized via hydrothermal treatment of the mixed solution of graphene quantum dots and ethylenediamine. The E-GQDs shows remarkable quantum yield (0.83). The quantum yield of E-GQDs is higher than quantum yields of most previously reported GQDs. Moreover, due to the coordination between Ni2+ and ethylenediamine, the PL of E-GQDs quenched via static quenching process. This makes the E-GQDs an alternative for ultra-sensitive PL probe of Ni2+ (detection limit: 3 × 10−8 M) with high antijamming capability. We also demonstrated the good performance of E-GQDs in vitro detection of Ni2+.

Ultrasensitive Simultaneous Detection of Multiplex Disease-Related Nucleic Acids Using Double-Enhanced Surface-Enhanced Raman Scattering Nanosensors.

Developing ultrasensitive probes holds great significance for simultaneous detection of multiplexed cancer-associated nucleic acids. Bimetallic nanoparticles containing silver may be exploited as nanoprobes for disease detection, which can produce stable and strong surface-enhanced Raman scattering (SERS) signals. However, it remains extremely challenging that such SERS nanoprobes are directly synthesized. Herein gold-silver nanosnowmen, grown via a DNA-mediated approach and attached to thiol-containing Raman dyes, are successfully synthesized. Stable SERS-enhanced gold substrates are also prepared and used as the enriching containers, where the capture DNAs are tethered to sense the target genes jointly enhanced by the SERS nanoprobes in a sandwich hybridization assay. This means detection of the target gene can obtain a limit of detection close to 0.839 fM. Such double-enhanced SERS nanosensors are further employed to simultaneously detect the three types of prostate carcinoma-related genes with high sensitivity and specificity, which meanwhile exhibit robust capacity of resisting disturbance in practical samples. Simultaneous and multiplexed detection of cancer-related genes may provide further biomedical applications with new opportunity.

Ultrasensitive dual probe immunosensor for the monitoring of nicotine induced-brain derived neurotrophic factor released from cancer cells

Brain-derived neurotrophic factor (BDNF) was detected in the extracellular matrix of neuronal cells using a dual probe immunosensor (DPI), where one of them was used as a working and another bioconjugate loading probe. The working probe was fabricated by covalently immobilizing capture anti-BDNF (Cap Ab) on the gold nanoparticles (AuNPs)/conducting polymer composite layer. The bioconjugate probe was modified by drop casting a bioconjugate particles composed of conducting polymer self-assembled AuNPs, immobilized with detection anti-BDNF (Det Ab) and toluidine blue O (TBO). Each sensor layer was characterized using the surface analysis and electrochemical methods. Two modified probes were precisely faced each other to form a microfluidic channel structure and the gap between inside modified surfaces was about 19 µm. At optimized conditions, the DPI showed a linear dynamic range from 4.0 to 600.0 pg/ml with a detection limit of 1.5 ± 0.012 pg/ml. Interference effect of IgG, arginine, glutamine, serine, albumin, and fibrinogene were examined and stability of the developed biosensor was also investigated. The reliability of the DPI sensor was evaluated by monitoring the extracellular release of BDNF using exogenic activators (ethanol, K+, and nicotine) in neuronal and non-neuronal cells. In addition, the effect of nicotine onto neuroblastoma cancer cells (SH-SY5Y) was studied in detail.

CaZnOS:Nd3+ Emits Tissue-Penetrating near-Infrared Light upon Force Loading.

Mechanoluminescent (ML) materials are mechano-optical converters that can emit light under an external mechanical stimulus. All the existing ML materials can only emit light from near ultraviolet to red, which is outside the near-infrared (NIR) windows desired for biomechanical imaging. No studies have been done on doping rare earth (RE) ions with photoluminescence (PL) in the NIR region into a compound to form a ML material that emits NIR light in response to an external force. Here, we show that doping RE ions with a NIR PL into an inorganic compound does not usually result in the formation of a NIR ML material, which can only be achieved in the combination of Nd3+ ions and a CaZnOS compound among the combinations we studied. The newly discovered NIR ML material (CaZnOS:Nd3+) is biocompatible and can efficiently convert mechanical stress into NIR light over the first and second tissue-penetrating bioimaging window. Its NIR ML emission appeared at a very low force threshold (even when the material was shaken slightly), increased sensitively and linearly with the increase in the force (up to >5 kN), and could penetrate the tissue as deep as >22 mm to enable biomechanical detection. Such a force-responsive behavior is highly reproducible. Hence, CaZnOS:Nd3+ is a new potential ultrasensitive biomechanical probe and expands the ML application horizons into in vivo bioimaging.

An ultrasensitive biological probe enhanced RT-IPCR assay for detecting benzo[a]pyrene in environmental samples based on the specific polyclonal antibody.

Benzo[a]pyrene (BaP), a type of polycyclic aromatic hydrocarbon, is widely distributed in the environment. In this study, BaP immunogen and coating antigen were respectively prepared by different methods, and the specific antibody targeting the BaP analyte was obtained. Moreover, gold nanoparticles modified with the specific polyclonal antibody and thiol-capped DNA were prepared as biological probes. Based on the work above, an ultrasensitive biological probe enhanced real-time immuno-polymerase chain reaction (BP-rt-iPCR) assay was developed to detect BaP in several environmental samples. Under optimal conditions, the proposed method was used to detect BaP with a linearity ranging from 5 pg/l to 50 ng/l. The limit of detection was 1.63 pg/l. The recovery rates of the spiked samples ranged from 92.12% to 109.76% and the coefficients of variation were 7.53%-11.06%. This immunoassay was successfully used to detect BaP in environmental samples, and the BaP detection results were consistent with those obtained using high performance liquid chromatography, indicating that the BP-rt-iPCR method is accurate and reliable, and has great potential to detect trace amounts of BaP.

Electrospun nanofibers decorated with bio-sonochemically synthesized gold nanoparticles as an ultrasensitive probe in amalgam-based mercury (II) detection system

In this study, bio-ultrasound-assisted synthesized gold nanoparticles using Gracilaria canaliculata algae have been immobilized on a polymeric support and used as a glassy probe chemosensor for detection and rapid removal of Hg2+ ions. The function of the suggested chemosensor has been explained based on gold-amalgam formation and its catalytic role on the reaction of sodium borohydride and rhodamine B (RhB) with fluorescent and colorimetric sensing function. The catalyzed reduction of RhB by the gold amalgam led to a distinguished color change from red and yellow florescence to colorless by converting the amount of Hg2+ deposited on Au-NPs. The detection limit of the colorimetric and fluorescence assays for Hg2+ was 2.21 nM and 1.10 nM respectively. By exposing the mentioned colorless solution to air for at least 2 h, unexpectedly it was observed that the color and fluorescence of RhB were restored. Have the benefit of the above phenomenon a recyclable and portable glass-based sensor has been provided by immobilizing the Au-NPs and RB on the glass slide using electrospinning. Moreover, the introduced combinatorial membrane has facilitated the detection and removal of Hg2+ ions in various Hg (II)-contaminated real water samples with efficiency of up to 99%.

Controlled Pore Sizes in Monolayer C2N Act as Ultrasensitive Probes for Detection of Gaseous Pollutants (HF, HCN, and H2S)

Porous two-dimensional monolayers have gained interest both in theoretical and experimental research because of their controlled pore size and evenly distributed holes within the basal plane. Herein, we have investigated the efficient trapping of three pollutants (HF, HCN, and H2S) on the recently synthesized porous two-dimensional nitrogeneted holey carbon (C2N-h2D) monolayer using periodic density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations. The differential binding positions/orientations of HF, HCN, and H2S in the cavity of C2N depend on their adsorption energy and charge transfer efficiency. H2S serves as a charge donor while HF and HCN act as charge acceptors. Our AIMD simulations demonstrate that the C2N monolayer is thermally stable at room temperature. Adsorption occurs through physisorption, and no chemical bond is formed between the molecule and the C2N surface irrespective of the site of interaction. Electrostatic interactions and hydrogen bonding facilitate stro...

Dealloyed Intra-Nanogap Particles with Highly Robust, Quantifiable Surface-Enhanced Raman Scattering Signals for Biosensing and Bioimaging Applications.

Uniformly controlling a large number of metal nanostructures with a plasmonically enhanced signal to generate quantitative optical signals and the widespread use of these structures for surface-enhanced Raman scattering (SERS)-based biosensing and bioimaging applications are of paramount importance but are extremely challenging. Here, we report a highly controllable, facile selective-interdiffusive dealloying chemistry for synthesizing the dealloyed intra-nanogap particles (DIPs) with a ∼2 nm intragap in a high yield (∼95%) without the need for an interlayer. The SERS signals from DIPs are highly quantitative and polarization-independent with polarized laser sources. Remarkably, all the analyzed particles displayed the SERS enhancement factors (EFs) of ≥1.1 × 108 with a very narrow distribution of EFs. Finally, we show that DIPs can be used as ultrasensitive SERS-based DNA detection probes for detecting 10 aM to 1 pM target concentrations and highly robust, quantitative real-time cell imaging probes for long-term imaging with low laser power and short exposure time.

Ultra-sensitive probe of spectral line structure and detection of isotopic oxygen

We discuss a new method of investigating and obtaining quantitative behavior of higher harmonic (> 2f) wavelength modulation spectroscopy (WMS) based on the signal structure. It is shown that the spectral structure of higher harmonic WMS signals, quantified by the number of zero crossings and turnings points, can have increased sensitivity to ambient conditions or line-broadening effects from changes in temperature, pressure, or optical depth. The structure of WMS signals, characterized by combinations of signal magnitude and spectral locations of turning points and zero crossings, provides a unique scale that quantifies lineshape parameters and, thus, useful in optimization of measurements obtained from multi-harmonic WMS signals. We demonstrate this by detecting weaker rotational–vibrational transitions of isotopic atmospheric oxygen (16O18O) in the near-infrared region where higher harmonic WMS signals are more sensitive contrary to their signal-to-noise ratio considerations. The proposed approach based on spectral structure provides the ability to investigate and quantify signals not only at linecenter but also in the wing region of the absorption profile. This formulation is particularly useful in tunable diode laser spectroscopy and ultra-precision laser-based sensors where absorption signal profile carries information of quantities of interest, e.g., concentration, velocity, or gas collision dynamics, etc.

Gold nanostar-enhanced chemiluminescence probe for highly sensitive detection of Cu(II) ions

Gold nanostars have interesting and unique surface plasmonic properties originating from their multi-branched shape with sharp tips. We demonstrate here the first use of gold nanostars in chemiluminescence (CL) field by studying their effect on H2O2-IO4− reaction. Nanostars, prepared by seed-mediated growth in poly(vinylpyrrolidone) solution in DMF, remarkably enhance the CL intensity of this reaction. On the basis of some evidence- we show that the enhancing effect of gold nanostars is most probably due to the coupling of CL emission to surface plasmons of nanostar tips. We applied the gold nanostar-based CL system as an ultrasensitive and selective probe for detection of nM levels of Cu(II) ions. The probe has a linear calibration range from 2.0nM to 9.0μM with a detection limit of 0.9nM. The developed CL method was validated by analysis of a certified reference material and applied for real environmental and biological samples.

Improving sensitivity of magnetic resonance imaging by using a dual-targeted magnetic iron oxide nanoprobe

Developing an ultrasensitive and high-efficient molecular imaging probe for detection of malignant tumors is extremely needed in clinical and remains a big challenge. Here, we report a novel bispecific nanoprobe for dual-targeted T2-weighed magnetic resonance imaging (MRI) of COLO-205 colorectal cancer in vivo. First, the magnetic iron oxide nanoparticles (Fe3O4@OA) were synthesized by a thermal decomposition method. Then, PEGylation of the hydrophobic Fe3O4@OA was implemented by amphiphilic DSPE-PEG2000-COOH, producing water-soluble nanoparticles (Fe3O4@PEG). Lastly, arginine-glycine-asparticacid-tumornecrosis factor-related apoptosis-inducing ligand (RGD-TRAIL), a bispecific fusion protein, was conjugated with the nanoparticle to construct molecularly multi-targeted nanoprobe, which was defined as Fe3O4@RGD-TRAIL. This Fe3O4@RGD-TRAIL was proven to exhibit extremely high relaxation property (r2=534mM−1s−1) and saturation magnetization value (Ms=92 emu/g Fe). In vitro studies showed its dual-targeting combination capacity, favorable biocompatibility and strong ability to resist against the non-specific phagocytosis. Owing to these excellent advantages, high sensitive and efficient imaging of tumor was achieved in vivo. Therefore, this RGD-TRAIL conjugated nanoprobe could be developed as a multi-targeted contrast enhancement agent for magnetic resonance molecular imaging in detection of cancer.