Shiping Song

Chinese Academy of Sciences, Peping, Beijing, China

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Publications (96)668.49 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Detection of nucleic acid and protein targets related to human health and safety has attracted widespread attention. Surface-enhanced Raman scattering (SERS) is a powerful tool for biomarker detection because of its ultrahigh detection sensitivity and unique fingerprinting spectra. In this review, we first introduce the development of nanostructure-based SERS-active substrates and SERS nanotags, which greatly influence the performance of SERS biosensors. We then focus on recent advances in SERS biosensors for DNA, microRNA and protein determination, including label-free, labeled and multiplex analysis approaches as well as in vivo imaging. Finally, the prospects and challenges of such nanostructure-based SERS biosensors are discussed.
    No preview · Article · Jan 2016 · Journal of Materials Chemistry B
  • Na LU · AnRan GAO · PengFei DAI · ShiPing SONG · ChunHai FAN · YueLin WANG · Tie LI

    No preview · Article · Jan 2016 · Chinese Journal
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    ABSTRACT: Cellular imaging technologies employing metallic surface-enhanced Raman scattering (SERS) tags have gained much interest toward clinical diagnostics, but they are still suffering from poor controlled distribution of hot spots and reproducibility of SERS signals. Here, we report the fabrication and characterization of high narrow nanogap-containing Au@Au core-shell SERS nanoparticles (GCNPs) for the identification and imaging of proteins overexpressed on the surface of cancer cells. First, plasmonic nanostructures are made of gold nanoparticles (∼15 nm) coated with gold shells, between which a highly narrow and uniform nanogap (∼1.1 nm) is formed owing to polyA anchored on the Au cores. The well controlled distribution of Raman reporter molecules, such as 4,4'-dipyridyl (44DP) and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), are readily encoded in the nanogap and can generate strong, reproducible SERS signals. In addition, we have investigated the size-dependent SERS activity of GCNPs and found that with the same laser wavelength, the Raman enhancement discriminated between particle sizes. The maximum Raman enhancement was achieved at a certain threshold of particle size (∼76 nm). High narrow nanogap-containing Au@Au core-shell SERS tags (GCTs) were prepared via the functionalization of hyaluronic acid (HA) on GCNPs, which recognized the CD44 receptor, a tumor-associated surface biomarker. And it was shown that GCTs have a good targeting ability to tumour cells and promising prospects for multiplex biomarker detection.
    No preview · Article · Dec 2015 · Nanoscale
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    ABSTRACT: Oligonucleotide-based technologies for biosensing or bio-regulation produce huge amounts of rich high-dimensional information. There is a consequent need for flexible means to combine diverse pieces of such information to form useful derivative outputs, and to display those immediately. Here we demonstrate this capability in a DNA-based system that takes two input numbers, represented in DNA strands, and returns the result of their multiplication, writing this as a number in a display. Unlike a conventional calculator, this system operates by selecting the result from a library of solutions rather than through logic operations. The multiplicative example demonstrated here illustrates a much more general capability - to generate a unique output for any distinct pair of DNA inputs. The system thereby functions as a lookup table and could be a key component in future, more powerful data-processing systems for diagnostics and sensing.
    Preview · Article · Dec 2015 · Nature Communications
  • 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.
    No preview · Article · Sep 2015 · Biosensors & Bioelectronics
  • 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.
    No preview · Article · Jul 2015 · The Analyst
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    ABSTRACT: A DNA tetrahedral nanostructure-based electrochemical biosensor was developed to detect avian influenza A (H7N9) virus through recognizing a fragment of the hemagglutinin gene sequence. The DNA tetrahedral probe was immobilized onto a gold electrode surface based on self-assembly between three thiolated nucleotide sequences and a longer nucleotide sequence containing complementary DNA to hybridize with the target single-stranded (ss)DNA. The captured target sequence was hybridized with a biotinylated-ssDNA oligonucleotide as a detection probe, and then avidin-horseradish peroxidase was introduced to produce an amperometric signal through the interaction with 3,3',5,5' tetramethylbenzidine substrate. The target ssDNA was obtained by asymmetric polymerase chain reaction (PCR) of the cDNA template, reversely transcribed from the viral lysate of influenza A (H7N9) virus in throat swabs. The results showed that this electrochemical biosensor could specifically recognize the target DNA fragment of influenza A (H7N9) virus from other types of influenza viruses, such as influenza A (H1N1) and (H3N2) viruses, and even from single-base mismatches of oligonucleotides. Its detection limit could reach a magnitude of 100 fM for target nucleotide sequences. Moreover, the cycle number of the asymmetric PCR could be reduced below three with the electrochemical biosensor still distinguishing the target sequence from the negative control. To the best of our knowledge, this is the first report of the detection of target DNA from clinical samples using a tetrahedral DNA probe functionalized electrochemical biosensor. It displays that the DNA tetrahedra has a great potential application as a probe of the electrochemical biosensor to detect avian influenza A (H7N9) virus and other pathogens at the gene level, which will potentially aid the prevention and control of the disease caused by such pathogens.
    No preview · Article · Apr 2015 · ACS Applied Materials & Interfaces
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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.
    No preview · Article · Mar 2015 · Analytical Chemistry
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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.
    No preview · Article · Jan 2015 · Angewandte Chemie International Edition
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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.
    No preview · Article · Oct 2014 · ACS Applied Materials & Interfaces
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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.
    No preview · Article · Oct 2014 · ACS Applied Materials & Interfaces
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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.
    Full-text · Article · Sep 2014 · ACS Applied Materials & Interfaces
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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.
    No preview · Article · Aug 2014 · Angewandte Chemie International Edition in English
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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.
    Full-text · Article · Jul 2014 · Chemical Science
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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.
    No preview · Article · Jul 2014 · Advanced Materials
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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.
    No preview · Article · May 2014 · ChemInform
  • 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.
    No preview · Article · May 2014 · Small
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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.
    Full-text · Article · Mar 2014 · Nano Research
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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.
    No preview · Article · Jan 2014 · Analytical Chemistry
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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.
    No preview · Article · Sep 2013 · Small

Publication Stats

6k Citations
668.49 Total Impact Points

Institutions

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