Resonance Light Scattering Signals Research Articles

Resonance Light-Scattering Correlation Spectroscopy and Its Application in Analytical Chemistry for Life Science.

Resonance light-scattering correlation spectroscopy (RLSCS) is a new single-particle detection method with its working principle being like fluorescence correlation spectroscopy (FCS). RLSCS is obtained by autocorrelation function analysis on the measured fluctuation of the resonance light scattering (RLS) intensity occurring within a subfemtoliter volume when a single nanoparticle (such as gold nanoparticles (NPs) or silver (SNPs)) freely diffuses through the volume. The RLSCS technique can detect such parameters as concentration, diffusion coefficient (translation and rotation), etc. Compared with the FCS technique, the correlated fluorescence intensity signal in RLSCS is replaced with the RLS signal of the nanoparticles, overcoming some limits of the fluorescent probes such as photobleaching under high-intensity or long-term illumination. In this Account, we showcase RLSCS methods, theoretical models at different optical configurations, and some key applications. First, the RLSCS optical detection system was constructed based on the confocal optics, its theoretical model was proposed, and the diffusion behaviors of the nanoparticles in the solution were studied including the rotational and translational diffusion. And, methods were developed to measure the concentration, size, aspect ratio, and size distribution of the NPs. Second, based on the RLSCS methods, some detection strategies were developed for homogeneous DNA detection, immunoassay, apoptosis assay, self-thermophoresis of the nanomotor, and quantitative assay in single living cells. Meanwhile, a new fluorescence/scattering cross-correlation spectroscopy (FSCCS) method was proposed for monitoring the molecule-particle interaction. This method enriched the conventional fluorescence/fluorescence cross-correlation spectroscopy (FCCS) method. Third, using the EMCCD with high sensitivity and rapid response as an optical detector, two temporospatially resolved scattering correlation spectroscopy methods and their theoretical models were developed: total internal reflection (TIR) configuration-based spatially resolved scattering correlation spectroscopy (SRSCS) and dark-field illumination-based scattering correlation spectroscopy (DFSCS). These methods extended single-spot confocal RLSCS to imaging RLSCS, which makes RLSCS have the ability for multiple channel detection with temporospatial resolution. The method was successfully used for investigating the dynamic behaviors of gold NPs in live cells and obtained its temporospatial concentration distribution and diffusion behaviors. The final section of this Account outlines future directions in the development of RLSCS.

Three-channel smartphone-based aptamer sensor for multiplexed detecting antibiotics in water through resonance light scattering

A more sensitive, low-cost, and miniaturized three-channel smartphone-based aptamer sensor using resonance light scattering (RLS) as a readout method was designed to in-situ detect multiplexed antibiotics in water. In this system, three unlabeled aptamers were used to respectively recognize the targets and a smartphone with a three-channel design was the detector to obtain the corresponding RLS signal of aggregation AuNPs caused by depressed aptamer. The strategy simultaneously tested tobramycin (TOB), kanamycin (KANA), and alternariol (AOH) to verify the sensor performance using three-channel design. This sensor obtained good limit of detection of 24.23 ng/mL for TOB, and 58.03 ng/mL, and 0.18 μg/mL for KANA and AOH, linear ranges of 50–300 ng/mL, 200–1000 ng/mL, and 0.75–3.5 μg/mL, respectively. The recoveries for TOB ranged from 91.6%–105.4% and the coefficient of variation for the relative standard deviation was less than 10%. Compared with commonly used bio-sensors, this sensor has advantages of high-throughput assay and simple operation and realized three antibiotics detection using RLS as a signal output based on a miniaturized smartphone with a three-channel design.

Interaction between meso-tetra-(4-hydroxyphenyl)porphyrin and SDS in aqueous solutions: Premicellar porphyrin-surfactant J-aggregate formation

Interactions between meso-tetra(4-hydroxyphenyl)porphyrin (THPP) and anionic sodium n-dodecyl sulfate (SDS) in a wide surfactant concentration range (0.5–50 mM) have been studied by UV–vis absorption and fluorescence spectroscopy, resonance light scattering (RLS), spin probe EPR spectroscopy and dynamic light scattering (DLS). J-type aggregate formation has been observed for THPP within 2–5 mM surfactant concentration range, accompanied by a significant bathochromic shift of the absorption bands, fluorescence quenching and emergence of an intense RLS signal. Porphyrin binding to the surfactant micelles above the cmc and aggregate formation below the cmc have been observed in SDS solutions containing THPP by DLS and EPR spectroscopy. SEM and optical microscopy revealed a rod-like morphology of the microparticles crystallized from an air dried suspension of THPP J-aggregates. The results obtained contribute to understanding of the mechanism of porphyrin-surfactant interactions both below and above the surfactant cmc.

A highly sensitive dual-readout assay for perfluorinated compounds based CdTe quantum dots

Perfluorooctanoic acid (PFOA) and Perfluorooctane sulfonate (PFOS) are two typical perfluorinated compounds (PFCs) that poss potential ecological toxicity. In this work, a fluorescence and resonance light scattering (RLS) dual-readout strategy for the detection of PFCs at picomole level based on the water-soluble CdTe quantum dots (CdTe QDs) has been proposed. It is found that the CdTe QDs exhibit a quenching in the presence of PFCs and thus serve as useful probes for PFCs. The linear ranges are 0.032–10.0 nM with a limit of detection(LOD) of 32.02 pM for PFOA and 0.044–15.0 nM with a LOD of 43.96 pM for PFOS, respectively. Meanwhile, PFCs can form complexes with CdTe QDs in acid medium, resulting in remarkable RLS signals. The enhanced RLS intensities are in proportion to the concentrations of PFOA and PFOS, respectively. And the linear ranges are 0.048–5.0 nM with a LOD of 47.78 pM for PFOA, and 0.057–5.0 nM with a LOD of 56.72 pM for PFOS, respectively. This dual-mode detection increases the reliability of the measurement. The proposed method is simple, sensitive and cost-effective, with potential applications in environmental monitoring and assessment.

Gold nanoparticles-based resonance light scattering method for the determination of phenothiazine drugs

In this work, a new method was developed for the determination of two phenothiazine drugs, namely thioridazine hydrochloride and chlorpromazine hydrochloride using gold nanoparticles-based resonance light scattering (RLS) technique. The addition of these drugs to gold nanoparticles solution in acidic medium leads to the aggregation of nanoparticles, which, in turn, causes a marked enhancement in RLS intensity at 400 nm. The aggregates were characterized by UV-Vis spectroscopy and transmission electron microscopy. The effects of important experimental factors such as pH, concentration of gold nanoparticles and incubation time on RLS signal were investigated and optimized. Under the optimum conditions, the calibration graphs were linear in the range of 3.6 - 36 and 3.5 - 30 ng/mL, for thioridazine hydrochloride and chlorpromazine hydrochloride, respectively with corresponding limits of detection of 1.1 and 1.0 ng/mL. The results indicate that the nanogold-based RLS is a very sensitive and simple method for the determination of phenothiazine drugs in pharmaceutical samples and human plasma.

Resonance light scattering technique for sensitive detection of heparin using plasmonic Cu2-xSe nanoparticles

Heparin (Hep) is a mucopolysaccharide sulfate anticoagulant drug widely used in clinic and thus the quantification of Hep concentration is of great significance. In this work, a simple resonance light scattering (RLS) method for the determination of Hep concentration using plasmonic copper selenide nanoparticles (Cu2-xSe NPs) was developed. The positively-charged Cu2-xSe NPs capped by cetyltrimethyl ammonium bromide (CTAB) were aggregated by negatively-charged Hep, consequently inducing a significant enhancement in the RLS signals of plasmonic Cu2-xSe NPs. Under the optimal reaction conditions, the increased RLS intensity is linearly correlated with the concentrations of Hep in the range of 0.01–0.60 μg mL−1 (R2 = 0.999), with a low detection limit (LOD) of 4.0 ng mL−1 (3σ). This method offered a simple, sensitive and selective strategy for determining Hep, which can be further successfully applied to quantify Hep in the heparin sodium injection.

A label-free resonance light scattering biosensor for nucleic acids using triple-helix molecular switch and G-quadruplex nanowires

In this work, a label-free resonance light scattering (RLS) biosensor based on triple-helix molecular switch (THMS) and G-quadruplex nanowires (G-wires) for HAV DNA and microRNA-31 detection was developed. The target can combine with the loop sequences of triple-helix, and opened the triple-helix structure as well as liberated the G-rich sequences which were self-assembled into G-wires in the presence of K+ and Mg2+, causing an obvious enhancement of RLS intensity. Meanwhile, the RLS signal at 304 nm was linear with the logarithm of target concentration in the range of 50 pM to 300 nM, and the limit of detection is as low as 7.1 pM for HAV DNA and microRNA-31, respectively. Moreover, qualitative analysis of HAV DNA and microRNA-31 was successfully achieved in human serum samples and cancer cell lysates. The biosensor holds a great promise for universal RLS sensing platform for sensitive detection of various targets just by changing the sequence of the THMS in the loop and be a biosensing platform for early clinical diagnosis and biomedical research.

Ultrasensitive graphene quantum dots-based catalytic hairpin assembly amplification resonance light scattering assay for p53 mutant DNA detection

In this work, a simple, enzyme-free and ultrasensitive resonance light scattering (RLS) method was developed based on graphene quantum dots (GQDs) with a catalytic hairpin assembly amplification strategy for selective detection of mutant DNA. This method contains two probes, GQDs-H1 and GQDs-H2. Two partially complementary hairpins (H1 and H2) are ingeniously and rationally designed, and they can't spontaneously hybridize with each other in the absence of target. When the target is added, the target binds with GQDs-H1 and forms GQDs-H1: target intermediates. Then, GQDs-H2 hybridizes with the GQDs-H1: target and frees the target, triggering another reaction cycle. A large amount of GQDs-H1:H2-GQDs aggregates are formed, which obviously increase the RLS signals. A limit of detection of 0.8 pmol L−1 and two linear ranges of 1.0 pmol L−1–1.5 nmol L−1 and 1.5–50.0 nmol L−1 for target detection are obtained. This detection method is simple, available, and low-cost. It can be potentially applied to other DNA detection and broadens the sensing application of GQDs for the detection of other significant disease-related markers.

Cationic porphyrins with large side arm substituents as resonance light scattering ratiometric probes for specific recognition of nucleic acid G-quadruplexes.

Specific G-quadruplex-probing is crucial for both biological sciences and biosensing applications. Most reported probes are focused on fluorescent or colorimetric recognition of G-quadruplexes. Herein, for the first time, we reported a new specific G-quadruplex-probing technique—resonance light scattering (RLS)-based ratiometric recognition. To achieve the RLS probing of G-quadruplexes in the important physiological pH range of 7.4-6.0, four water soluble cationic porphyrin derivatives, including an unreported octa-cationic porphyrin, with large side arm substituents were synthesized and developed as RLS probes. These RLS probes were demonstrated to work well for ratiometric recognition of G-quadruplexes with high specificity against single- and double-stranded DNAs, including long double-stranded ones. The working mechanism was speculated to be based on the RLS signal changes caused by porphyrin protonation that was promoted by the end-stacking of porphyrins on G-quadruplexes. This work adds an important member in G-quadruplex probe family, thus providing a useful tool for studies on G-quadruplex-related events concerning G-quadruplex formation, destruction and changes in size, shape and aggregation. As a proof-of-concept example of applications, the RLS probes were demonstrated to work well for label-free and sequence-specific sensing of microRNA. This work also provides a simple and useful way for the preparation of cationic porphyrins with high charges.

Assay of miRNA in cell samples using enhanced resonance light scattering technique based on self aggregation of magnetic nanoparticles.

miRNAs are regarded as potential biomarkers correlated with the development and progression of many diseases. However, it is a challenge to construct a sensitive method to detect them without using time-consuming radioactive labeling or complex amplification strategies. A facile resonance light scattering (RLS) system was developed for the detection of miRNA employing magnetic nanoparticles (MNPs) as RLS probes. MNPs were coated with streptavidin. DNA probes were modified on the surface of MNPs based on the specific interaction of streptavidin and biotin forming MNPs@DNA probes. MNPs@DNA probes dispersed in homogeneous media causing low RLS signal. miRNA hybridized with DNA probes resulting in the aggregation of MNPs and inducing the enhancement of RLS intensity. miRNAs were determined successfully with limit of detection at 0.9picomole per liter (pM). The potential clinical application of the present biosensor was also demonstrated by measuring miRNAs in human normal and cancer cells, and human serum samples.

Resonance light scattering aptasensor for urinary 8-hydroxy-2'-deoxyguanosine based on magnetic nanoparticles: a preliminary study of oxidative stress association with air pollution.

An aptamer based method is described for the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG) using resonance light scattering (RLS). Magnetic nanoparticles (MNPs) were employed as RLS probes. The probe DNA was placed on the surface of MNPs, which produces a rather low RLS signal. If, however, probe DNA hybridizes with the aptamer against 8-OHdG, a sandwich structure will be formed. This results in a significant enhancement of RLS intensity. The aptamer was used as the recognition element to capture 8-OHdG. 8-OHdG has a stronger affinity for the aptamer than probe DNA, and the conformation of the aptamer therefore switches from a double-stranded to a G-quadruplex structure. As a result, MNPs labeled with probe DNA are released, and RLS intensity decreases. The method allows 8-OHdG to be detected with a linear response in the 32 pM - 12.0nM concentration range and an 11 pM limit of detection (at 3.29SB/m, according to the recent recommendation of IUPAC). The MNPs can be reused 5 times by applying an external magnetic field for collection. The method was successfully applied to analyze human urine samples for its content of 8-OHdG. It was also found that the levels of 8-OHdG noticeably increased with the increase of the Air Quality Index. Conceivably, the method is a viable tool to investigate the relationship between 8-OHdG levels and the effect of air pollution. Graphical abstract A reusable sensing strategy was constructed to detect urinary 8-OHdG based on "turn-off" resonance light scattering. The LOD was as low as 11 pM. This study showed some preliminary data for the association between oxidative stress and air pollution.

Simply and sensitively simultaneous detection hepatocellular carcinoma markers AFP and miRNA-122 by a label-free resonance light scattering sensor

In this study, an intelligent and label-free sensor is utilized for the first time to one-spot simultaneous detection hepatocellular carcinoma markers AFP and miRNA-122 by a resonance light scattering (RLS) sensor. cDNA1 hybridizes with cDNA2 to form double-stranded DNA (dsDNA). The construction of dsDNA and methyl violet is used to form the RLS sensor via the electronic interaction. When AFP or miRNA-122 is present, the cDNA (cDNA1 or cDNA2) can bindings of target, thereby RLS intensity changed proportionally with the concentration of AFP or that of miRNA-122. The detection limits of AFP and miRNA-122 are 0.94 μg/L and 98 pM respectively, and their good linear which ranges from 5 to 100 μg/L and 200 pM to 10 nM are achieved using the assay. In the presence of miRNA-122 and AFP mixtures, AFP bound to the AFP aptamer to increase the RLS signal, and miRNA-122 bound to the miRNA-122 complementary strand to decrease the RLS signal. The RLS signal changed in response to changing AFP and miRNA-122 concentrations, so that one-spot simultaneous detection of alpha fetal protein and miRNA-122 is achieved. This method has potential practical applications in the research of hepatocellular carcinoma.

Ultrasensitive detection of thrombin based on MoS2-aptamer biosensors by resonance light scattering technique

Abstract Rapid and sensitive detection of thrombin has very important significance in biomedical and bioanalytical applications. In this study, a label-free and simple resonance light scattering (RLS) sensor based on MoS2 nanomaterial is developed for ultrasensitive and highly selective detection of thrombin. In the presence of thrombin, the thrombin aptamer can transform into a G-quartet structure and combine with thrombin, resulting in dissociation of the random DNA (rDNA) in the solution. Once MoS2 is introduced, the free rDNA can be adsorbed on the surface of MoS2 to form a stable DNA1–thrombin–MoS2 complex, which increases RLS signals. The sensor shows two linear ranges of 10 pM to 500 pM and 1 nM to 60 nM, and a detection limit of 0:71 pMfor detection of thrombin. Our sensor is a promising tool for clinical diagnosis of thrombin in human serum. Moreover, this work can offer new opportunities for the development of convenient sensor for detecting other proteins.

Reduced graphene oxide as a resonance light-scattering probe for thrombin detection using dual-aptamer-based dsDNA

This paper describes a reduced graphene oxide (RGO)-based resonance light-scattering (RLS) method for thrombin detection by using double strand DNA (dsDNA) as a binding element. dsDNA is obtained by hybridizing DNA1 and DNA2, which respectively consist of one aptamer of thrombin and the complementary strand of the other aptamer of thrombin. When thrombin is added, the specific binding of two aptamers to thrombin results in a complex (DNA1–thrombin–DNA2) and triggers the release of the complementary strand of two aptamers from dsDNA. The released ssDNA can be self-assembled on the surface of RGO to form a stable DNA1–thrombin–DNA2–RGO complex, which increases RLS signals. This simple and rapid method has enabled the detection of thrombin in the picomolar level in buffer and human serum samples. This study is the first to use RGO as a platform in RLS sensor, which can extend the application of RGO.

A reusable aptasensor of thrombin based on DNA machine employing resonance light scattering technique

The design of molecular nanodevices attracted great interest in these years. Herein, a reusable, sensitive and specific aptasensor was constructed based on an extension-contraction movement of DNA interconversion for the application of human thrombin detection. The present biosensor was based on resonance light scattering (RLS) using magnetic nanoparticles (MNPs) as the RLS probe. MNPs coated with streptavidin can combine with biotin labeled thrombin aptamers. The combined nanoparticles composite is monodispersed in aqueous medium. When thrombin was added a sandwich structure can form on the surface of MNPs, which induced MNPs aggregation. RLS signal was therefore enhanced, and there is a linear relationship between RLS increment and thrombin concentration in the range of 60pM–6.0nM with a limit of detection at 3.5pM (3.29SB/m, according to the recent recommendation of IUPAC). The present aptasensor can be repeatedly used for at least 6 cycling times by heat to transfer G-quadruplex conformation to single strand of DNA sequence and release thrombin. MNPs can be captured by applying the external magnetic field. Furthermore, the proposed biosensor was successfully applied to detect thrombin in human plasma.

The detection of uranium(VI) with a synthesized ditopic bidentate ligand as probe by resonance light scattering

In order to detect the uranium(VI) in environmental water sample by means of establishing a novel resonance light scattering (RLS) method, we synthesized and characterized a ditopic bidentate ligand and studied its chelation with the uranyl(VI) ion. The chelating reaction can form supramolecular dimers and polymers, producing a strong RLS signal, which is used for quantitative analysis of uranium(VI) in aqueous solution. The linear range was 0.01–1.0 nmol mL−1 and the detection limit was 0.003 nmol mL−1 under the optimal conditions. The method has been used for the detection of uranium(VI) in environmental water samples and the recoveries were 98.0–101.0%.

Aptamer-based Resonance Light Scattering for Sensitive Detection of Acetamiprid.

In this work, an aptasensor-based resonance light-scattering (RLS) method was developed for the sensitive and selective detection of acetamiprid. The ABA (acetamiprid binding aptamer)-stabilized gold nanoparticles (ABA-AuNPs) were used as a probe. Highly specific single-strand DNA (ssDNA, i.e, aptamers) that bind to acetamiprid with high affinity were employed to discriminate other pesticides, such as edifenphos, kanamycin, metribuzin et. al. The sensing approach is based on a specific interaction between acetamiprid and ABA. Aggregation of AuNPs was specifically induced by the desorption of the ABA from the surface of AuNPs, which caused the RLS signal intensity to be enhanced at 700 nm. The alteration of AuNPs' aggregation has been successfully optimized by controlling several conditions. Under the optimal conditions, the RLS intensity changes (I/I0) of AuNPs were linearly correlated with the acetamiprid concentration in the range of 0 - 100 nM. The detection limit is 1.2 nM (3σ). This method had also been used for acetamiprid detection in lake water samples.

Determination of trace uranium (VI) using its self-assembly with a tetradentate–monodentate ditopic ligand by resonance light scattering

ABSTRACTWe describe here a resonance light scattering (RLS) method for uranium (VI) detection by using phosphorylethanol-amido-salophen (PAS) as optical probe. PAS is a tetradentate–monodentate ditopic ligand in which the tetradentate and monodentate ligands are salophen moiety and phosphate group, respectively. PAS can chelate uranyl with its salophen moiety. The chelated uranyl can connect phosphate group in another PAS through coordination reaction. This causes the self-assembly of PAS with uranyl to form a metallo-supramolecular polymer, resulting in a production of strong RLS signal. The RLS method was established based on the self-assemble. The RLS intensity is linearly related to the concentration of uranium (VI) in the 0.8–32 ng mL−1 range, with a detection limit of 0.24 ng mL−1 detection limit under optimal conditions. The method was successfully applied to determine uranium (VI) in environmental water samples with the recoveries between 97.1% and 102.6%.

"Click on the bidirectional switch": the aptasensor for simultaneous detection of lysozyme and ATP with high sensitivity and high selectivity.

A bifunctional and simple aptasensor was designed to one-spot simultaneously detect two analytes, lysozyme and ATP. The aptasensor was obtained by the electronic interaction between methyl violet (MV) and dsDNA. The dsDNA was obtained by hybridization of ATP aptamer and lysozyme aptamer. And we used the resonance light scattering (RLS) technique to detect the concentration of lysozyme and ATP. During the procedure of detection, the aptasensor works like a bidirectional switch, the corresponding side of the dsDNA will open when the target (lysozyme or ATP) “click” the aptamer, which results in corresponding RLS signal change. By the combination of the RLS technique, it is found that the changed RLS intensity was proportional to the concentration of lysozyme and ATP. The mixtures of ATP and lysozyme also met two binary function relations. The results indicated that the aptasensor could achieve simultaneous detection of ATP and lysozyme, the detection limits of ATP and lysozyme could reach 10−11 M and 10−12 M, respectively. The aptasensor shows potential application for small molecule and protein detection by RLS, it could extend the application of RLS technique.

Effect of morphine, oxycodone and thebaine on resonance light scattering properties of human serum albumin: Investigation possibility of morphine determination in the presence of the two other drugs

This work reports on the resonance light scattering (RLS) technique for studying the interaction of human serum albumin (HSA) with three opiates drugs (i.e. morphine (MO), oxycodone (OX) and thebaine (TH)). RLS is very sensitive to the interaction caused by weak binding forces such as intermolecular electrostatic attraction, hydrogen bonding, hydrophobic interaction, and aggregation interaction of biological macromolecules. The results of this work showed that the investigated drugs, with similar chemical structures, have different affinities to interact with HSA and enhance its RLS signal in following order: MO>OX>TH. Furthermore, the results showed that using the proposed method, MO could be determined in the presence of TH (up to ten-fold concentration ratio), OX (up to seven-fold concentration ratio) and both of OX and TH (up to three-fold concentration ratio) in the concentration range of 0.1–10.0μgmL−1 with detection limit of 43μgL−1.