Shiping Song

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

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Publications (90)636.69 Total impact

  • Lanying Li · Yanli Wen · Li Xu · Qin Xu · Shiping Song · Xiaolei Zuo · Juan Yan · Weijia Zhang · Gang Liu
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    ABSTRACT: Mercury (II) ion (Hg(2+)) contamination can be accumulated along the food chain and cause serious threat to the public health. Plenty of research effort thus has been devoted to the development of fast, sensitive and selective biosensors for monitoring Hg(2+). Thymine was demonstrated to specifically combine with Hg(2+) and form a thymine-Hg(2+)-thymine (T-Hg(2+)-T) structure, with binding constant even higher than T-A Watson-Crick pair in DNA duplex. Recently, various novel Hg(2+) biosensors have been developed based on T-rich Mercury-Specific Oligonucleotide (MSO) probes, and exhibited advanced selectivity and excellent sensitivity for Hg(2+) detection. In this review, we explained recent development of MSO-based Hg(2+) biosensors mainly in 3 groups: fluorescent biosensors, colorimetric biosensors and electrochemical biosensors.
    Biosensors & Bioelectronics 09/2015; 75:433-445. DOI:10.1016/j.bios.2015.09.003 · 6.41 Impact Factor
  • Shixing Chen · Fuwu Li · Chunhai Fan · Shiping Song
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    ABSTRACT: In recent years, graphene has received widespread attention owing to its extraordinary electrical, chemical, optical, mechanical and structural properties. Lately, considerate interests have been focused on exploring potential applications of graphene in life science, particularly in disease-related molecular diagnostics. Especially, the coupling of functional molecules with graphene as nanoprobes offers an excellent platform to realize the detection of biomarkers, such as nucleic acid, protein and other bioactive molecules, with high performance. This article reviews emerging graphene-based nanoprobes in electrical, optical and other assay methods and their application for various strategies of molecular diagnostics. Especially, this review focuses on the construction of graphene-based nanoprobes and their special advantages for the detection of various bioactive molecules. Properties of graphene-based materials and their functionalization are also comprehensively discussed in view of the development of nanoprobes. Finally, future challenges and perspectives of graphene-based nanoprobes are discussed.
    The Analyst 07/2015; 140(19). DOI:10.1039/C5AN00848D · 4.11 Impact Factor
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    ABSTRACT: In this work, we investigated the interactions between graphene oxide (GO) and conjugated polyelectrolytes (CPEs) with different backbone and sidechain structures. By studying the mechanism of fluorescence quenching of CPEs by GO, we find that the charge and the molecular structure of CPEs plays important roles for GO-CPEs interactions. Among them, electrostatic interaction, π-π interaction and cation-π bonding are dominant driving forces. By using a cationic P2, we have developed a sensitive homogeneous sensor for DNA and RNA detection with a detection limit of 50 pM DNA and RNA, which increased the sensitivity by 40 fold as compared to GO-free CPE-based sensors. This GO-assisted CPE sensing strategy is also generic, and shows high potential for biosensor designs based on aptamers, proteins, peptides and other biological probes.
    Analytical Chemistry 03/2015; 87(7). DOI:10.1021/ac504658a · 5.64 Impact Factor
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    ABSTRACT: A novel three-dimensional (3D) superstructure based on the growth and origami folding of DNA on gold nanoparticles (AuNPs) was developed. The 3D superstructure contains a nanoparticle core and dozens of two-dimensional DNA belts folded from long single-stranded DNAs grown in situ on the nanoparticle by rolling circle amplification (RCA). We designed two mechanisms to achieve the loading of molecules onto the 3D superstructures. In one mechanism, ligands bound to target molecules are merged into the growing DNA during the RCA process (merging mechanism). In the other mechanism, target molecules are intercalated into the double-stranded DNAs produced by origami folding (intercalating mechanism). We demonstrated that the as-fabricated 3D superstructures have a high molecule-loading capacity and that they enable the high-efficiency transport of signal reporters and drugs for cellular imaging and drug delivery, respectively.
    Angewandte Chemie International Edition 01/2015; 54(8). DOI:10.1002/anie.201408247 · 11.26 Impact Factor
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    ABSTRACT: Prostate-specific antigen (PSA) is one of the most important biomarkers for the early diagnosis and prognosis of prostate cancer. Although many efforts has been made to achieve significant progress for the detection of PSA, challenges including relative low sensitivity, complicated operation, sophisticated instruments and high-cost remain unsolved. Here, we have developed a strategy combining rolling circle amplification (RCA)-based DNA belts and magnetic beads based enzyme-linked immunosorbent assay (ELISA) for the highly sensitive and specific detection of PSA. At first, a 96-base circular DNA template was designed and prepared for the following RCA. Single stranded DNA (ssDNA) products from RCA were used as scaffold strand for DNA origami, which was hybridized with three staple strands of DNA. The resulting DNA belts were conjugated with multiple enzymes for signal amplification and then employed to magnetic bead based ELISA for PSA detection. Through our strategy, as low as 50 aM of PSA can be detected with excellent specificity.
    ACS Applied Materials & Interfaces 10/2014; 6(22). DOI:10.1021/am505913d · 6.72 Impact Factor
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    ABSTRACT: Microarrays of biomolecules have greatly promoted the development of the fields of genomics, proteomics, and clinical assays because of their remarkably parallel and high-throughput assay capability. Immobilization strategies for biomolecules on a solid support surface play a crucial role in the fabrication of high-performance biological microarrays. In this study, rationally designed DNA tetrahedra carrying three amino groups and one single-stranded DNA extension were synthesized by the self-assembly of four oligonucleotides, followed by high-performance liquid chromatography purification. We fabricated DNA tetrahedron-based microarrays by covalently coupling the DNA tetrahedron onto glass substrates. After their biorecognition capability was evaluated, DNA tetrahedron microarrays were utilized for the analysis of different types of bioactive molecules. The gap hybridization strategy, the sandwich configuration, and the engineering aptamer strategy were employed for the assay of miRNA biomarkers, protein cancer biomarkers, and small molecules, respectively. The arrays showed good capability to anchor capture biomolecules for improving biorecognition. Addressable and high-throughput analysis with improved sensitivity and specificity had been achieved. The limit of detection for let-7a miRNA, prostate specific antigen, and cocaine were 10 fM, 40 pg/mL, and 100 nM, respectively. More importantly, we demonstrated that the microarray platform worked well with clinical serum samples and showed good relativity with conventional chemical luminescent immunoassay. We have developed a novel approach for the fabrication of DNA tetrahedron-based microarrays and a universal DNA tetrahedron-based microarray platform for the detection of different types of bioactive molecules. The microarray platform shows great potential for clinical diagnosis.
    ACS Applied Materials & Interfaces 10/2014; 6(20). DOI:10.1021/am5047735 · 6.72 Impact Factor
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    Wenhe Wu · Jun Li · Dun Pan · Jiang Li · Shiping Song · Mingge Rong · Zixi Li · Jimin Gao · Jianxin Lu
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    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; 6(19). DOI:10.1021/am5045828 · 6.72 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 08/2014; 53(32). DOI:10.1002/anie.201402937 · 13.45 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; 5(11). DOI:10.1039/C4SC01792G · 9.21 Impact Factor
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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 07/2014; 26(27). DOI:10.1002/adma.201400451 · 17.49 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). DOI:10.1002/chin.201418299
  • Na Lu · Anran Gao · Pengfei Dai · Shiping Song · Chunhai Fan · Yuelin Wang · Tie Li
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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 05/2014; 10(10). DOI:10.1002/smll.201302990 · 8.37 Impact Factor
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    ABSTRACT: Uniform silver-containing metal nanostructures with well-defined nanogaps hold great promise for ultrasensitive surface-enhanced Raman scattering (SERS) analyses. Nevertheless, the direct synthesis of such nanostructures with strong and stable SERS signals remains extremely challenging. Here, we report a DNA-mediated approach for the direct synthesis of gold-silver nano-mushrooms with interior nanogaps. The SERS intensities of these nano-mushrooms were critically dependent on the area of the nanogap between the gold head and the silver cap. We found that the formation of nanogaps was finely tunable by controlling the surface density of 6-carboxy-X-rhodamine (ROX) labeled single-stranded DNA (ssDNA) on the gold nanoparticles. We obtained nano-mushrooms in high yield with a high SERS signal enhancement factor of ∼1.0 × 109, much higher than that for Au-Ag nanostructures without nanogaps. Measurements for single nanomushrooms show that these structures have both sensitive and reproducible SERS signals.
    Nano Research 03/2014; 8(3):731-742. DOI:10.1007/s12274-014-0556-2 · 7.01 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; 86(4). DOI:10.1021/ac403661z · 5.64 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 09/2013; 9(18). DOI:10.1002/smll.201300458 · 8.37 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 08/2013; 9(15). DOI:10.1002/smll.201202957 · 8.37 Impact Factor
  • Na Lu · Anran Gao · Pengfei Dai · Tie Li · Yi Wang · Xiuli Gao · Shiping Song · Chunhai Fan · Yuelin Wang
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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; 63(3). DOI:10.1016/j.ymeth.2013.07.012 · 3.65 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. DOI:10.1016/j.bios.2013.06.039 · 6.41 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. DOI:10.1038/srep01789 · 5.58 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). DOI:10.1002/elan.201200166 · 2.14 Impact Factor

Publication Stats

5k Citations
636.69 Total Impact Points


  • 2006–2015
    • Shanghai Institute of Applied Physics
      Shanghai, Shanghai Shi, China
  • 2014
    • University of Cologne
      Köln, North Rhine-Westphalia, Germany
  • 2008–2014
    • Chinese Academy of Sciences
      • Biophysics Laboratory
      Peping, Beijing, China
  • 2010–2011
    • Shanghai Institute of Measurement and Testing Technology
      Shanghai, Shanghai Shi, China
    • Shanghai Academy of Social Science
      Shanghai, Shanghai Shi, China