Shiping Song

Shanghai Institute of Applied Physics, Shanghai, Shanghai Shi, China

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Publications (83)519.58 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Enzyme-linked immunosorbent assay (ELISA) provides a convenient means for the detection of Salmonella enterica serovar Typhimurium (STM), which is important for rapid diagnosis of foodborne pathogens. However, conventional ELISA is limited by antibody-antigen immunoreactions and suffers from poor sensitivity and tedious sample pretreatment. Therefore, development of novel ELISA remains challenging. Herein, we designed a comprehensive strategy for rapid, sensitive and quantitative detection of STM with high specificity by gold nanoparticle-based enzyme-linked antibody-aptamer sandwich (nano-ELAAS) method. STM was captured and pre-concentrated from samples with aptamer-modified magnetic particles, followed by binding with detector antibodies. And then nanoprobes carrying a large amount of reporter antibodies and horseradish peroxidase molecules were used for colorimetric signal amplification. Under the optimized reaction conditions, the nano-ELAAS assay had a quantitative detection range from 1 × 103 to 1 × 108 CFU mL-1, a limit of detection of 1 × 103 CFU mL-1 and a selectivity of > 10-fold for STM in samples containing other bacteria at higher concentration with an assay time less than 3h. In addition, the developed nanoprobes were improved in terms of detection range and/or sensitivity when compared with two commercial enzyme-labeled antibody signal reporters. Finally, the nano-ELAAS method was demonstrated to work well in milk samples, a common source of STM contamination.
    ACS Applied Materials & Interfaces 09/2014; · 5.01 Impact Factor
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    ABSTRACT: Surface-enhanced Raman scattering (SERS) technique has recently been used to design novel nanoprobes called "SERS tags" which hold great promise for the fields of biosensing and nanomedicine. More recent advances have shed new light on the synthesis of uniform nanostructures with interior nanogaps for stable SERS enhancement. However, producing interior nanogap-based SERS nanotags directly and controllably with strong and stable multiplex SERS signals as well as developing multiplex analytical platform to recognize different types of bioactive molecules still remain highly challenging. To address this challenge, we herein develop a novel approach for direct synthesis of nanogap-based universal SERS nanotags by mediating poly adenine (polyA) and encoding non-fluorescent small molecules. The universal nanotags were then functionalized by different types of biological probes and used as SERS nanoprobes to recognize various bioactive molecules. To the best of our knowledge, this is the first example of using SERS nanotags to develop simultaneous multianalysis platform for all of the major types of bioactive analytes, including nucleic acids, proteins and small molecules. Furthermore, the nanotags showed great promise for fluorescence-SERS bimodal bioanalysis and bioimaging.
    Chemical Science 07/2014; · 8.31 Impact Factor
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    ABSTRACT: Reproducible and controllable growth of nanostructures with well-defined physical and chemical properties is a longstanding problem in nanoscience. A key step to address this issue is to understand their underlying growth mechanism, which is often entangled in the complexity of growth environments and obscured by rapid reaction speeds. Herein, we demonstrate that the evolution of size, surface morphology, and the optical properties of gold plasmonic nanostructures could be quantitatively intercepted by dynamic and stoichiometric control of the DNA-mediated growth. By combining synchrotron-based small-angle X-ray scattering (SAXS) with transmission electron microscopy (TEM), we reliably obtained quantitative structural parameters for these fine nanostructures that correlate well with their optical properties as identified by UV/Vis absorption and dark-field scattering spectroscopy. Through this comprehensive study, we report a growth mechanism for gold plasmonic nanostructures, and the first semiquantitative revelation of the remarkable interplay between their morphology and unique plasmonic properties.
    Angewandte Chemie International Edition in English 06/2014; · 13.45 Impact Factor
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    ABSTRACT: With the rapidly increasing demands for ultrasensitive biodetection, the design and applications of functional nanoprobes have attracted substantial interest for biosensing with optical, electrochemical, and various other means. In particular, given the comparable sizes of nanomaterials and biomolecules, there exists plenty of opportunities to develop functional nanoprobes with biomolecules for highly sensitive and selective biosensing. Over the past decade, numerous nanoprobes have been developed for ultrasensitive bioaffinity sensing of proteins and nucleic acids in both laboratory and clinical applications. In this review, we provide an update on the recent advances in this direction, particularly in the past two years, which reflects new progress since the publication of our last review on the same topic in Chem. Soc. Rev. The types of probes under discussion include: (i) nanoamplifier probes: one nanomaterial loaded with multiple biomolecules; (ii) quantum dots probes: fluorescent nanomaterials with high brightness; (iii) superquenching nanoprobes: fluorescent background suppression; (iv) nanoscale Raman probes: nanoscale surface-enhanced Raman resonance scattering; (v) nanoFETs: nanomaterial-based electrical detection; and (vi) nanoscale enhancers: nanomaterial-induced metal deposition.
    ChemInform 05/2014; 45(18).
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    ABSTRACT: An intelligent microscale electrochemical device (iMED) for one-step, quantitative and multiplexed electrochemical detection of biomarkers for infectious diseases and tumors is developed. A "plug-in-cartridge" technology is introduced and adapted for use in screen-printed electrodes (SPEs) in electrochemical devices. Using this iMED, biomarkers for two types of tumors and one infectious disease are detected at sub-ng/mL levels in less than 30 min.
    Advanced Materials 04/2014; · 14.83 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) have been regarded as promising biomarkers for the diagnosis and prognosis of early-stage cancer as their expression levels are associated with different types of human cancers. However, it is a challenge to produce low-cost miRNA sensors, as well as retain a high sensitivity, both of which are essential factors that must be considered in fabricating nanoscale biosensors and in future biomedical applications. To address such challenges, we develop a complementary metal oxide semiconductor (CMOS)-compatible SiNW-FET biosensor fabricated by an anisotropic wet etching technology with self-limitation which provides a much lower manufacturing cost and an ultrahigh sensitivity. This nanosensor shows a rapid (< 1 minute) detection of miR-21 and miR-205, with a low limit of detection (LOD) of 1 zeptomole (ca. 600 copies), as well as an excellent discrimination for single-nucleotide mismatched sequences of tumor-associated miRNAs. To investigate its applicability in real settings, we have detected miRNAs in total RNA extracted from lung cancer cells as well as human serum samples using the nanosensors, which demonstrates their potential use in identifying clinical samples for early diagnosis of cancer.
    Small 02/2014; · 7.82 Impact Factor
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    ABSTRACT: Molecular computing holds great promise for diagnosis and treatment of diseases at molecular level, nevertheless, designing molecular logic gates to operate programmably and autonomously for molecular diagnostics still remains challenges. We designed logic gates on DNA Origami for microRNA analysis. As a demonstration, two indicators of heart failure, microRNA-21 and microRNA-195, were selected as the logic inputs. The logic gates contain two main modules: computation module and output module, performing in a single DNA Origami nanostructure. The computation module recognizes disease indicators, while output module display different nanoscale symbols, "+" (positive) or "-" (negative), depending on the computing results. We demonstrated that the molecular logic gates worked well with single and two input combinations.
    Analytical Chemistry 01/2014; · 5.70 Impact Factor
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    ABSTRACT: Silicon nanowire field-effect transistors (SiNW-FETs) have recently emerged as a type of powerful nanoelectronic biosensors due to their ultrahigh sensitivity, selectivity, label-free and real-time detection capabilities. Here, we present a protocol as well as guidelines for detecting DNA with complementary metal oxide semiconductor (CMOS) compatible SiNW-FET sensors. SiNWs with high surface-to-volume ratio and controllable sizes were fabricated with an anisotropic self-stop etching technique. Probe DNA molecules specific for the target DNA were covalently modified onto the surface of the SiNWs. The SiNW-FET nanosensors exhibited an ultrahigh sensitivity for detecting the target DNA as low as 1 fM and good selectivity for discrimination from one-base mismatched DNA.
    Methods 07/2013; · 3.64 Impact Factor
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    ABSTRACT: Biochemical and biomedical applications of graphene are critically dependent on the interaction between biomolecules and the nanomaterial. In this work, we developed a graphene-based signal-amplification nanoprobe by combining anti-immunoglobulin G (anti-IgG) and horseradish peroxidase (HRP) with graphene oxide (GO). The structure and function of HRP in the nano-interface of GO were firstly investigated, which demonstrated that the enzyme retained 78% of its native activity and 77% of its native α-helix content. HRP and anti-IgG were then co-adsorbed onto GO to form bifunctional nanoprobes. The nanoprobes provide both improved binding ability and signal-amplification ability. Comparing with conventional bioconjugates such as enzyme-linked antibody, co-adsorption could avoid chemical conjugation between biomolecules, keeping their bioactivity well. As an example for their application, the nanoprobes were used to obtain amplified signals in a sandwich-type immunoassay for cancer marker, instead of conventional colorimetric conjugates. This approach provided a detection limit of 10pg/mL alpha-fetoprotein (AFP), which was much more sensitive than conventional enzyme-linked immunosorbent assay (ELISA) methods. The easily fabricated GO-based nanoprobes have the potential to become universal probes for molecular diagnostics.
    Biosensors & bioelectronics 06/2013; 50C:251-255. · 5.43 Impact Factor
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    ABSTRACT: Schistosomiasis control remains to be an important and challenging task in the world. However, lack of quick, simple, sensitive and specific sero-diagnostic test is still a hurdle in the control practice. The commonly employed enzyme-linked immuno-sorbent assay (ELISA) relies on the native soluble egg antigen (SEA) that is limited in supply. Here we developed an electrochemical immunosensor array (ECISA) assay with an interfacial co-assembly strategy. A recombinant Schistosoma japonicum (Sj) calcium-binding protein (SjE16) was used as a principal antigen, while the SEA as a minor, co-assembling agent, with a ratio of 8:1 (SjE16: SEA, Sj16EA), which was co-immobilized on a disposable 16-channel screen-printed carbon electrode array. A portable electrochemical detector was employed to detect antibodies in serum samples. The sensitivity of ECISA reached 100% with minimal cross-reactions. Therefore, we have demonstrated that this rapid, sensitive and specific ECISA technique has the potential to perform large-scale on-site screening of Sj infection.
    Scientific Reports 05/2013; 3:1789. · 5.08 Impact Factor
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    ABSTRACT: Several single-stranded scaffold DNA, obtained from rolling circle amplification (RCA), are folded by different staples to form DNA nanoribbons. These DNA nanoribbons are rigid, simple to design, and cost-effective drug carriers, which are readily internalized by mammalian cells and show enhanced immunostimulatory activity.
    Small 04/2013; · 7.82 Impact Factor
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    ABSTRACT: We report a highly sensitive competitive-type assay for multiplexing electrochemical detection of clenbuterol in pig urine using a 16-sensor array. In this design, the clenbuterol was first conjugated with bovine serum albumin (BSA), and then the conjugates were immobilized on the electrode surface to compete with the free clenbuterol in the sample for specific antibody. Under the optimal conditions, the reproducibility of the clenbuterol electrochemical immunosensor was evaluated to be 3.4 % (coefficient of variation, CV) and the limit of detection was estimated to be 1.3 pg/mL. The very low detection limit was probably derived from the higher efficiency of the competitive immunoreaction caused by appropriate quantities of the clenbuterol immobilized on the 16-sensor array and the suitable amount of anti-clenbuterol antibody in the assay system.
    Electroanalysis 04/2013; 25(4). · 2.82 Impact Factor
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    ABSTRACT: There are still challenges for the development of multifunctional carbon nanotubes (CNTs). Here, a multiwalled carbon nanotube (MWCNT)-based rolling circle amplification system (CRCAS) is reported which allows in situ rolling circle replication of DNA primer on the surface of MWCNTs to create a long single-strand DNA (ssDNA) where a large number of nanoparticles or proteins could be loaded, forming a nano-biohybridized 3D structure with a powerful signal amplification ability. In this strategy, the binding ability of proteins, hybridization, replication ability of DNA, and the catalytical ability of enzymes are integrated on a single carbon nanotube. The CRCAS is then used to develop colorimetric and chemiluminescent assays for the highly sensitive and specific detection of cancer protein markers, alpha-fetoprotein (AFP) and prostate specific antigen (PSA). The colorimetric CRCAS assay is 4000 times more sensitive than a conventional enzyme-linked immunosorbent assay (ELISA), and its concentration range is 10 000 times wider. Control experiments show that as low as 10 pg mL(-1) AFP or PSA could be detected even in the presence of interfering protein markers with a more than 10(5) -fold greater concentration in the sample, demonstrating the high specificity of the CRCAS assay. The limit of detection of the chemiluminescent CRCAS assays for AFP and PSA are 5 fg mL(-1) (70 aM) and 10 fg mL(-1) (0.29 fM), respectively, indicating that the sensitivity is much higher than that of the colorimetric CRCAS assay. Importantly, CRCAS works well with real biological samples.
    Small 03/2013; · 7.82 Impact Factor
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    ABSTRACT: We herein report a power-free microfluidic chip for fluorescent DNA detection with high single-nucleotide polymorphism discrimination, using a DNA intercalator and graphene oxide.
    Chemical Communications 03/2013; · 6.38 Impact Factor
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    ABSTRACT: A novel electrochemical DNA biosensor for single-nucleotide polymorphism (SNP) analysis was developed. In this work, an oligonucleotide-incorporated nonfouling surface (ONS) was constructed to resist nonspecific absorption. The biosensor was developed using a 16-electrode array for high-throughput SNP analysis. The proposed strategy was primarily based on specific oligonucleotide ligation. Fully matched target DNA templated the ligation between a capture probe assembled on gold electrodes and a tandem signal probe with a biotin moiety that could capture avidin-horseradish peroxidase and sequentially generate a catalysed amperometric signal. A pre-core mutation in the hepatitis B virus (HBV) genome at G1896A and two adjacent polymorphisms in the human CYP2C19 genome at C680T and G681A were analysed. Polymerase chain reaction (PCR) products were used as real-life samples and analysed. Our results showed that 10% of a single-mismatched mutant gene was clearly distinguished with a current signal 16 times higher than that of the blank sample, demonstrating the selectivity and practicability of the multiplexed electrochemical DNA biosensor.
    Biosensors & bioelectronics 11/2012; 42C:516-521. · 5.43 Impact Factor
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    ABSTRACT: Although "hot spots" have been proved to contribute to surface enhanced Raman scattering (SERS), less attention was paid to increase the number of the "hot spot" to directly enhance the Raman signals in bioanalytical systems. Here we report a new strategy based on nano rolling-circle amplification (nanoRCA) and nano hyperbranched rolling-circle amplification (nanoHRCA) to increase "hot spot" groups for protein microarrays. First, protein and ssDNA are coassembled on gold nanoparticles, making the assembled probe have both binding ability and hybridization ability. Second, the ssDNAs act as primers to initiate in situ RCA reaction to produced long ssDNAs. Third, a large number of SERS probes are loaded on the long ssDNA templetes, allowing thousands of SERS probes involved in each biomolecular recognition event. The strategy offered high-efficiency Raman enhancement and could detect less than 10 zeptomolar protein molecules in protein microarray analysis.
    Analytical Chemistry 10/2012; · 5.70 Impact Factor
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    ABSTRACT: In this work, we report a novel strategy of electrochemical DNA (E-DNA) sensor based on surface initiated enzymatic polymerization (SIEP). This DNA sensor employs a capture DNA probe labeled with thiol at its 3' terminal to be immobilized at gold electrode via gold-thiol chemistry. Oligo (ethylene glycol) -terminated thiols (SH-OEGs) are then used to prepare an oligonucleotide-incorporated nonfouling surface (ONS). After the sequence-specific recognition of target DNA, terminal deoxynucleotidyl transferase (TdT) is employed to catalyze the sequential addition of deoxynucleotides (dNTPs) at the 3'-OH group of target DNA without template. During the TdT-mediated extension reaction, by using biotinlated 2'-deoxyadenosine 5'-triphosphate (biotin-dATP), biotin labels are incorporated into the SIEP-generated long single-stranded DNA (ssDNA). Specific binding of avidin-horseradish peroxidase (Av-HRP) to the biotin label leads to enzyme turnover-based signal transduction. By using this new strategy, we demonstrated the high picomolar sensitivity and a broad detection range of six orders of magnitude.
    Biosensors & bioelectronics 09/2012; · 5.43 Impact Factor
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    ABSTRACT: We have developed a surface-enhanced Raman scattering (SERS)-active substrate based on gold nanoparticle-decorated chemical vapor deposition (CVD)-growth graphene and used it for multiplexing detection of DNA. Due to the combination of gold nanoparticles and graphene, the Raman signals of dye were dramatically enhanced by this novel substrate. With the gold nanoparticles, DNA capture probes could be easily assembled on the surface of graphene films which have a drawback to directly immobilize DNA. This platform exhibits extraordinarily high sensitivity and excellent specificity for DNA detection. A detection limit as low as 10 pM is obtained. Importantly, two different DNA targets could be detected simultaneously on the same substrate just using one light source.
    Analytical Chemistry 04/2012; 84(10):4622-7. · 5.70 Impact Factor
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    ABSTRACT: A portable and power-free microfluidic device was designed for rapid and sensitive detection of lead (Pb(2+)). 11-mercaptoundecanoic acid (MUA)-functionalized gold nanoparticles (MUA-AuNPs) aggregated in the presence of Pb(2+) for the chelation mechanism. When we performed this analysis on a polydimethylsiloxane (PDMS) microfluidic chip, the aggregations deposited onto the surface of chip and formed dark lines along the laminar flows in the zigzag microchannels. This visual result can be observed by the naked eye through a microscope or just a drop of water as a magnifier. Ten μM Pb(2+) was successfully detected.
    Sensors 01/2012; 12(7):9467-75. · 2.05 Impact Factor
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    ABSTRACT: It was found that stannous chloride (SnCl(2)), as a popular inorganic reducing reagent, could obviously enhance the electrochemiluminescence (ECL) of tris(2,2'-bipyridyl) ruthenium(II) (Ru(bpy)(3)(2+)) in aqueous solution. Some factors affecting the ECL reactions between Ru(bpy)(3)(2+) and Sn(2+), including pH, concentrations of coreactant, and electrode materials, were investigated by comparison with a classic ECL coreactant tripropylamine (TPA). The Ru(bpy)(3)(2+)-Sn(2+) ECL coreactant system produces stronger and more stable ECL signals, can keep its excellent ECL activity over a wider pH range and has more choices in using electrode materials than the Ru(bpy)(3)(2+)-TPA ECL coreactant system. The ECL mechanism of the Ru(bpy)(3)(2+)-Sn(2+) coreactant system was also studied in detail.
    Dalton Transactions 12/2011; 41(5):1630-4. · 3.81 Impact Factor

Publication Stats

2k Citations
519.58 Total Impact Points


  • 2005–2014
    • Shanghai Institute of Applied Physics
      Shanghai, Shanghai Shi, China
  • 2013
    • Ludong University
      Shan-tang, Jiangxi Sheng, China
  • 2006–2013
    • Chinese Academy of Sciences
      Peping, Beijing, China
  • 2012
    • Fudan University
      • Lab of Advanced Materials
      Shanghai, Shanghai Shi, China
  • 2011–2012
    • Shanghai Institute of Measurement and Testing Technology
      Shanghai, Shanghai Shi, China
    • Nanjing University of Science and Technology
      Nan-ching, Jiangsu Sheng, China
    • Second Military Medical University, Shanghai
      Shanghai, Shanghai Shi, China
  • 2010
    • Shanghai Academy of Social Science
      Shanghai, Shanghai Shi, China
  • 2009
    • East China University of Science and Technology
      Shanghai, Shanghai Shi, China
    • Nanjing University
      Nan-ching, Jiangsu Sheng, China
    • Sichuan University
      • College of Life Sciences
      Hua-yang, Sichuan, China
  • 2008
    • Shanghai Jiao Tong University
      • School of Life Science and Biotechnology
      Shanghai, Shanghai Shi, China