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Functional nanoprobes for ultrasensitive detection of biomolecules: an update Jing-Juan Xu,a Wei-Wei Zhao,a Shiping Song,b Chunhai Fan*b and Hong-Yuan Chen*a 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.

Received 27th July 2013

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;

DOI: 10.1039/c3cs60277j

(iii) superquenching nanoprobes: fluorescent background suppression; (iv) nanoscale Raman probes: nanoscale surface-enhanced Raman resonance scattering; (v) nanoFETs: nanomaterial-based electrical

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detection; and (vi) nanoscale enhancers: nanomaterial-induced metal deposition.

a

State Key Laboratory of Analytical Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China. E-mail: [email protected]; Fax: +86 025 83594862; Tel: +86 025 83594862 b Division of Physical Biology, and Bioimaging Center, Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. E-mail: [email protected]

Jing-Juan Xu, born in 1968, graduated from Wuhan University in 1990 and earned her MSc and PhD from Nanjing University in 1997 and 2000. Currently she is the full Professor in the Department of Chemistry at Nanjing University and has published more than 150 scientific papers. She is the recipient of National Outstanding Youth Foundation of China (2010) and the National Nature Science Jing-Juan Xu Award of China (second class). Her research interest focuses on the development of various electrochemical, electrochemiluminescent and photoelectrochemical sensors based on nanostructured materials with enhanced sensitivity and selectivity and the fabrication of Lab-on-chip detectors for biological analysis.

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1. Introduction A biosensor is typically composed of biosignal element, transducer, signal processing and actuator. The essential role of the biosensing configuration is to provide a suitable functional module to identify a specific analyte from a biological mixture by producing

Wei-Wei Zhao

Wei-Wei Zhao was educated at Nanjing University of Aeronautics and Astronautics (NUAA) and received his BS and ME in 2005 and 2008, respectively. Then he moved to Nanjing University, he received his PhD from Nanjing University in 2012 under the supervision of Prof. Hong-Yuan Chen and Jing-Juan Xu. Currently, he works at Nanjing University and his project involves photoelectrochemical DNA detection, immunoassay and biocatalytic sensing. He has published over 20 scientific articles.

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meaningful signals for actuation.1–4 In the past decade, with the ever-growing demands for ultrasensitive biosensing, there have been continuous efforts on developing new bioanalysis methods and signal amplification strategies. In particular, construction of functional nanoprobes has demonstrated its power in realizing high sensitivity and selectivity for the detection of biomolecules.5 Nanoprobes are nanomaterials functionalized with specific biomolecules, which have attracted substantial interest due to their great potential in monitoring biorecognition events and ultrasensitive biodetection.6 For example, nanoparticles (NPs), with comparable dimensions to many biomolecules, have been widely used as components for developing a variety of nanoprobes, because their nanometer-size surfaces offer advantageous physical properties that are chemically tailorable as well.7,8 Among them, Au NPs are most extensively employed because of their unique characteristics and excellent biocompatibility.9–11 Quantum dots

Fig. 1 Schematic illustration for various ultrasensitive biodetection strategies by using biofunctionalized nanomaterials.

Shiping Song completed his PhD in chemistry at Shanghai Institute of Applied Physics in 2004. His research interests include the development of biosensors and biochips based on microtechnology such as microarrays and microfluidics, and nanotechnology such as nanobiohybrid systems (mainly nanobioprobes). He is also interested in the applications of micro- and nano-based biosensors and biochips in life science such as genomics, proteomics and molecular diagnostics.

(QDs) also possess distinct photophysical properties that offer significant advantages as optical or electrochemical labels for biosensing.12–14 The use of these nanomaterials, coupled with specific probe biomolecules, opens almost unlimited possibilities for novel bioassay development. With the capacity of control that can be engineered over the sizes, shapes, compositions and functions of the building blocks with nanoscale precision, nanoprobes offer unprecedented opportunities for bioanalytical science as well as environmental, forensic and healthcare applications sciences. Over the past decade, enormous efforts have been devoted to the exploitation of new nanoprobes and their applications in a plethora of biomolecular detection methods. We have previously summarized the construction and application of different nanoprobes in various detection technologies in 2010.6 Since then, there has been rapid progress in this field, which merits an updated review. Here, with selected examples, we hope to provide a concise summary on recent advances in this direction, particularly in the past two years. Along the same line as in our previous review, we present six sections in this review (see also Fig. 1), each describing a different ultrasensitive biodetection strategy with new

Chunhai Fan was born in 1974 in Zhangjiagang of Jiangsu Province, China. He obtained his BS and PhD from the Department of Biochemistry at Nanjing University in 1996 and 2000. After his postdoctoral research at University of California, Santa Barbara (UCSB), he joined the faculty at Shanghai Institute of Applied Physics (SINAP), Chinese Academy of Sciences (CAS) in 2004. He is now Chunhai Fan Professor and Chief of the Division of Physical Biology and the Center of Bioimaging at SINAP. He is also the associate editor of ACS Applied Materials & Interfaces, and the editorial board member of several international journals. He has published over 200 papers in the areas of biosensors, biophotonics and DNA nanotechnology.

Hong-Yuan Chen was born in 1937 in Sanmen of Zhejiang Province in China. After graduation from Nanjing University in 1961, he has been working in the department of chemistry, Nanjing University. From 1981 to 1984, he worked at Mainz University as a visiting scholar. During 1986–1999, he has been a guest professor or visiting professor in Germany four times. In 2001, he was Hong-Yuan Chen elected as the academician of Chinese Academy of Science. He has authored and co-authored over 650 papers, and several chapters and books. Research interests include electrochemical biosensing, bioelectrochemistry, ultramicroelectrodes and biomolecular-electronic devices and Micro-Total Analysis Systems.

Shiping Song

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functional nanoprobes. While the fundamental signal amplification mechanisms remain largely the same, we have witnessed major improvement in all these six categories.

2. Nanoamplifier probes: one nanomaterial loaded with multiple biomolecules Due to the high surface-to-volume ratio and the controllable surface chemistry, NPs coated with different types of biomolecules make it possible to amplify the recognition events of DNA hybridization and antigen–antibody binding. Given its well-understood surface chemistry, Au NPs functionalized with various biomolecules have been popularly employed in detection. For example, spherical nucleic acid–gold NPs (SNA–Au NPs) conjugates, which consisted of a gold NP core and a shell of oligonucleotides, have been exploited in detection of biomolecules.15,16 By using SNA–Au NPs, Mirkin and co-workers designed a ‘‘nanoflare’’ system for simultaneous detection of multiple intracellular targets.17 In a typical setup, highly oriented oligonucleotides are densely packed on the Au NPs, and many of these oligonucleotides can hybridize to their DNA or RNA targets, which are then transduced via a reporter with a distinct fluorophore label. They demonstrated that such a Au NP probe can simultaneously detect two intracellular mRNA targets. By using a scanometric method with SNA–Au NP-based amplification, they could detect miRNAs in serum with a detection limit of 1 fM.18 Recently, by modifying Au NPs surface with a dense shell of recognition sequences hybridized to three short dye-terminated reporter sequences, Tang and co-workers developed a multicolor fluorescence nanoprobe for detecting three tumor-related mRNAs, with a detection limit of 1.2 nM for c-myc mRNA, 1.4 nM for TK1 mRNA and 1.6 nM for GalNAc-T mRNA, respectively.19 More significantly, the use of SNA as probes was extend to the bio-barcode assay (BCA), which leads to a new way for signal amplification strategy with polymerase chain reaction (PCR)-like sensitivity.20,21 Recently, on the basis of integrating the DNA-based hybridization chain reaction with the BCA strategy, Zhang et al. developed a novel electrochemical sandwich-type immunoassay method for human IgG, with a detection limit as low as 0.1 fg mL 1.21 Graphene, a single layer of carbon atoms arranged in the honeycomb lattice, is an emerging two-dimensional carbon nanomaterial with remarkable electronic, physical and chemical properties.22 When incorporated into biosensors, functionalized graphene or graphene oxide (GO) provide an ideal platform for accommodating a large amount of biomolecules that results in substantial signal amplification.23–26 As shown in Fig. 2, Chang et al. constructed a graphene fluorescence resonance energy transfer (FRET) aptasensor for thrombin detection by using GO bound with fluorescein amidite (FAM) labeled aptamers. Because of the high fluorescence quenching efficiency of GO, this sensor reached a detection limit as low as 31.3 pM.23 Taking advantages of the large specific surface area and abundant functional groups of GO, Du et al. fabricated a new

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Fig. 2 Schematic demonstration of graphene FRET aptasensor and the detection mechanism for thrombin. Fluorescence of dye labeled aptamer is quenched when aptamer binds to graphene due to FRET between dyes and graphene. The fluorescence recovers while thrombin combines with aptamers to form quadruplex–thrombin complexes which have much less affinity to graphene, causing FAM far away from the graphene surface [reprinted with permission from ref. 23].

electrochemical immunosensor with a multienzyme amplification strategy for ultrasensitive detection of phosphorylated p53 at Ser392 with a detection limit of 10 pM.27 Based on the biotin– streptavidin interaction, Liu et al. prepared a GO–streptavidin complex and used it to capture biotinylated protein complexes for affinity purification.28 In addition, anodized epitaxial graphene (EG) coated with DNA probe was shown to be a robust platform for label-free DNA detection with electrochemical impedance and differential pulse voltammetry with a linear dynamic detection range of 5.0  10 14 to 1  10 6 M.29 Interfacing carbon nanotubes (CNTs) with DNA or proteins for the development of sensitive detection methods has long been explored in nanotechnology. Recently, Weizmann et al. reported a conductivity-based DNA detection method utilizing CNT–DNA network devices with oligonucleotide-functionalized enzyme probes.30 Biorecognition at the DNA junctions linking CNTs, followed by amplification using enzymatic metallization, led to conductimetric responses. The detection limit for DNA analyte is 10 fM with the ability to discriminate single, double and triple base-pair mismatches.

3. Quantum dots probes: fluorescent nanomaterials with high brightness With unique electronic and optical properties, QDs have been widely explored since the past decade. The rapid development of QDs has promoted advances in optical probing. Compared to conventional organic fluorophores, QDs offer substantial advantages such as broad absorption spectra, narrow emission spectra, long fluorescence lifetime and enhanced photostability. As a result, QDs have been intensively used for sensing various biomolecular interactions.31 Yao et al. developed a novel label-free fluorescent assay for monitoring the activity and inhibition of protein kinases based on the aggregation behavior of unmodified QDs.32 In this assay, kinase-catalyzed peptide phosphorylation was monitored based on the selective aggregation of unmodified QDs by changing the surface charge of QDs. This sensor offered several advantages

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such as quick detection (less than 3 min), no need of QDs modification and visible detection without instrument. Zhu et al. described a QDs-based immunofluorescence (IF) approach to measure the expression of glycans on the cell surface of single cells.33 Compared with conventional IF staining, the QDs-based IF probe exhibited higher brightness and stability against photobleaching. With these merits, high-throughput IF staining was performed to measure the glycan level and its changes after drug treatment at the single cell level. Willner et al. reported the use of self-assembled hemin– G-quadruplex nanostructures for chemiluminescence resonance energy transfer (CRET) detection of aptamer–substrate complexes, metal ions (Hg2+) and DNA.34 Based on their CRET sensing platform (Fig. 3), they realized multiplexed analysis of the different target DNAs using three different sized CdSe–ZnS QDs. Zhong et al. utilized ordered assembling supramolecular DNA–QDs nanowires as ultrahigh-intensity QDs probe to recognize DNA sequences on polystyrene microbeads, which permitted direct detection of target DNA with a detection limit of 50 fM.35 Zhang and co-workers developed a highly sensitive and specific miRNA assay based on two-stage exponential amplification reaction (EXPAR) and a single-QD-based nanosensor.36 Due to the coupling of two-stage EXPAR and QDs, the sensitivity of this miRNA assay was greatly improved, with the detection limit as low as 0.1 aM. By using this ultrasensitive sensor, they could discriminate even single nucleotide differences among the miRNA family. Moreover, QDs also possess a prominent electrochemiluminescent (ECL) property.37 ECL emission of QDs has excellent temporal and spatial controllability and does not involve the problems of scattered light and luminescent impurities. Recently, Chen’s group has demonstrated that ECL resonance energy transfer (ERET) occurred at a relative long distance in comparison with FRET.38

Fig. 3 Multiplexed analysis of the different target DNAs using three different sized CdSe–ZnS QDs emitting at (a) 620 nm, (b) 560 nm and (c) 490 nm, using the CRET sensing platform [reprinted with permission from ref. 34].

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An ultrasensitive DNA detection was reported by combining Au NP–QDs-based ERET with an isothermal circular amplification reaction, which can detect DNA concentration as low as 5 aM.39 In additional, several amplification strategies have been adopted to enhance the ECL of QDs for biological applications.40

4. Superquenching nanoprobes: fluorescent background suppression The sensitivity of fluorescent biosensors is limited not only by the low emission intensity (i.e. quantum yield) but also the high background. A typical switchable sensor contains a fluorophore as the donor, and a quencher as the acceptor. The fluorescence variation in response to target binding is mainly dependent on the distance between these two components via energy- or electron-transfer mechanism. Au NPs have long been recognized as superior quenchers to organic ones, with ultrahigh quenching efficiency for background suppression in biosensors.41 Zhu’s group utilized Mn:ZnSe–ZnS core–shell nanocrystals linked with goat anti-human IgG (Mn:ZnSe–ZnS-Ab1) to provide fluorescence emission, and Au NPs with rat anti-human IgG (AuNPs-Ab2) acting as acceptors. Because of the exceptional quenching ability of Au, highly ¨rster resonance energy transfer (FRET) occurred efficient Fo upon binding of the Mn:ZnSe–ZnS-Ab1 with the Au NPs-Ab2 in the presence of human IgG.42 As shown in Fig. 4, Draz et al. described a nanosensor for Hepatitis B virus (HBV) detection. Here, Au NPs fused with HBV surface antigen (HBsAg) epitope served as acceptors, and QDs labeled with Fab antibody as donors. They were assembled into a complex, which afforded efficient energy transfer with quenched fluorescence in the absence of HBV, and fluorescence was only observed when HBV disassembled the complex.43 In addition to their fluorescence quenching ability, AuNPs have also shown surface plasmon resonance (SPR)-based fluorescence enhancement when the fluorophore is placed at an appropriate distance to the surface. Recently, Zhao et al. systematically studied the distance dependence of Au NPs-enhanced fluorescence by capillary electrophoresis. In their experiments, the enhanced fluorescence of the QDs solution was only observed when the distance was in the range from 6.8 to 18.7 nm.44 More recently, GO was also shown to possess ultra-high quenching ability due to its long-range energy transfer property. Wu et al. presented a GO-based fluorescence quenching assay for DNA phosphorylation detection, which did not require either dual labeling of DNA or DNA amplification.45 Similarly, by exploiting the strong adsorption of pyrene-labeled peptide on the surface of GO via p–p interactions and hydrophobic interactions, Lu et al. developed a general approach for monitoring peptide–protein interactions.46 The proximity of the GO to the pyrene moiety could effectively quench the fluorescence of pyrene. In the presence of target protein, the competitive binding of the target protein with GO for peptide resulted in the restoration of fluorescence signal. Zhang et al. developed a rapid, sensitive, selective multiple microRNA (miRNA) detection assay by

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Fig. 4 Schematic of HBV nanocluster plasmonic resonator complex. Because of the affinity interaction between Fab fragments and its specific peptide epitope, the caps (acceptor) and core (donor, green glow) conjugates assemble together resulting in Au NPs plasmonically resonance-quenching QDs emission (central panel). In the presence of HBV, the NPR complex is disassembled; the capping and core conjugates declustered, and PL signal re-emerges to allow virus detection (high green glow, upper central panel). In the absence of HBV, the complex of caps–core conjugates remains clustered, allowing the plasmonic resonance of Au NP caps to quench the photoluminescence (PL) of the QD core (fainter green glow, bottom central panel) [reprinted with permission from ref. 43].

coupling the GO-based quenching with isothermal strand displacement polymerase reaction (ISDPR). Upon the recognition of specific target miRNA, an ISDPR was triggered to produce numerous specific DNA–miRNA duplexes, and strong emission was observed due to the weak interaction between the DNA– miRNA duplex helix and GO.47 In addition to Au NPs and graphene, other nanomaterials have also been explored in this regard. Graphite NPs (GN), a spherical carbon nanomaterial with a diameter ranging from 4 to 5 nm and layer-by-layer stacked graphene sheets, was also employed for fluorescence quenching. Seo and co-workers utilized GN as a fluorescence quencher to design a new molecular beacons, realizing the real-time survivin mRNA detection and quantification.48 Sun and co-workers demonstrated the use of poly(3,4-ethylene dioxythiophene) (PEDOT) NPs as an effective fluorescent quencher for the detection of nucleic acid sequences.49 Recently, Wang’s group firstly observed photoinduced electron transfer (PET) between DNA–Ag fluorescent nanoclusters and G-quadruplex–hemin complexes, accompanied by a quenching in the fluorescence of DNA–Ag NCs. Based on this phenomenon, they developed a nanocluster-based molecular beacon with very low background fluorescence, which was used for the detection of target biomolecules with high selectivity and sensitivity.50

5. Nanoscale Raman probes: nanoscale surface-enhanced Raman resonance scattering Nanoscale surface-enhanced Raman scattering (SERS) has attracted great attention due to its potential in developing novel nanoprobes, i.e. ‘‘SERS tags’’, for ultrasensitive biodetection.51 Over the last few years, there have been many advances toward

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the design and fabrication of novel SERS-active nanostructures. Most methods aim to increase the number of SERS ‘‘hot spots’’ coupling with biorecognition events. Toward this goal, we have witnessed the progress on synthesis or assembly of single nanostructures containing multiple ‘‘hot spots’’, design of reproducible nanometer gap junctions, and the multi-functionalization of nanoprobes for multimodal biodetection. Although gold and silver NPs have been popularly used to develop SERS-based biodetection methods, the use of singleNPs is limited due to their insufficient Raman signal-enhancing capability. Thus, it is important to involve multiple noble NPs for SERS enhancement in a single biorecognition event. Tay et al. fabricated silica-encapsulated Raman-reporter embedded SERS nanoprobes denoted ‘‘nanoaggregate embedded beads’’, which were linked to the Salmonella specific tailspike protein.52 Due to the increased hot spots from multiple Au NPs on one bead, the nanoprobes allowed the detection of a single bacterium. In another example, Yan et al. developed a nano rolling-circle amplification (nanoRCA) technique to increase SERS hot spots in protein microarray analysis.53 In nanoRCA, ssDNAs attached on NPs act as primers to initiate the in situ RCA reaction to produce long ssDNAs, which allowed thousands of SERS nanoprobes to be involved in a single biomolecular recognition event. The strategy offered high-efficient Raman enhancement and was able to detect o10 zM protein molecules in protein microarray analysis. As a major barricade in SERS detection, the number of hot spots is often difficult to be precisely controlled. In order to design nanostructures containing a constant number of hot spots for reproducible SERS enhancement, Singamaneni et al. assembled core–satellite structures comprised of shape-controlled plasmonic NPs through self-assembly using simple molecular cross-linkers.54 The SERS enhancement factor (EF) from the nanostructures was calculated to be B2.5  108. The built-in hot-spots and Raman reporters of the nanostructures make

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Fig. 5 Nanogap-engineerable Raman-active nanodumbbells for single-molecule biodetection. (a) Nanoscale silver–shell growth-based gapengineering in the formation of the SERS-active nanostructures. (b) The HRTEM images of the nanostructures with B3 nm, B5 nm and B10 nm Ag shell thicknesses (b1, b2 and b3), respectively. (c) The corresponding SERS spectra taken from the nanostructures with B3 nm, B5 nm and B10 nm Ag shell thicknesses (c1, c2 and c3), respectively [reprinted with permission from ref. 56].

them good candidates for SERS nanoprobes. In a simpler approach, Lu and co-workers directly synthesized popcorn-shaped gold nanoprobes conjugated with monoclonal antibodies and aptamers.55 Due to the presence of several hot spots in one nano-popcorn, the nanoprobes provided a significant enhancement of the Raman signal intensity by several orders of magnitude (2.5  109) and allowed the recognition of human prostate cancer cells at the level of 50 cells. Another major advance has been made to design reproducible nanometer gap junctions to fabricate single nanostructures with high SERS signals. As shown in Fig. 5, Nam and co-workers developed a synthetic method for SERS-active gold–silver core– shell nanodumbbells, where the nanoscale gap between two NPs could be precisely controlled.56 They demonstrated that Raman signals were highly reproducible from single-DNA-tethered nanodumbbells, holding great promise for reproducible single-molecule biodetection. Besides the design of such exterior nanogaps, they designed well-defined gold core–shell nanostructures with interior nanogaps, which also generated highly stable and reproducible SERS signals.57 The uniform nanogap could be precisely loaded with a quantifiable amount of Raman reporters, generating SERS signals with a linear relationship with probe concentration. The gold nanostructures had EF narrowly distributed between 1.0  108 and 5.0  109, resulting in high sensitivity toward single-molecule detection. There is also a trend to develop multi-functionalized nanoprobes for multimodal biodetection. Cui and co-workers developed a two-mode SERS-fluorescence spectral encoding method by using organic–metal–QD hybrid NPs with a nanolayered structure.58 This encoding system served as a powerful tool for high-throughput bioanalysis. Similarly, Du and co-workers reported QD-decorated Ag@SiO2 NPs embedded with Raman reporters for simultaneous SERS and surface-enhanced fluorescence (SEF) detection of biomolecules.59 Metal NPs exhibit strong plasmonic effects in addition to SERS. For example, Long and co-workers used dark-field microscopy (DFM) to follow the in situ formation of Ag, Au and Cu NPs on stable protein 1 integrated in hybrid bilayer membranes.60

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The plasmon resonance Rayleigh scattering spectral shifts enabled the nanoprobes to sense biorecognition events at the single NP level. Zheng et al. developed catalysis-based nanoplasmonic gold nanoprobes for highly sensitive and specific detection of DNA and small molecules.61,62 Also, it was able to develop multimodal detection methods by combining SERS with resonance scattering spectroscopy.63 It is important to point out that the resonance scattering properties on the surface of noble NPs might enhance SERS signals if Raman reporters and appropriate incident light were coupled. Studies on this direction may open a new avenue for the use of metal NPs for developing multimodal SERS-plasmonic nanoprobes.

6. NanoFETs: nanomaterial-based electrical detection Electrical detection represents an interesting alternative to optical detection for the development of rapid and low-cost biosensing devices. Nanomaterials play a significant role in new developments in many facets of electrical biosensing, including the design of a specific biosensing interface, the realization of efficient signal transduction of biorecognition events, the improvement in the sensitivity and the reduction of response time.64,65 Since the development of silicon nanowires (SiNWs) fieldeffect transistors (FETs) by Lieber and co-workers in 2001,64 Si NWs, with their unique nanoscale dimensions and large surface-to-volume ratio, have been popularly employed for developing ultrasensitive FET-type biosensors. They have proven to be one of the most promising high-throughput sensing platforms with superior sensing performance in terms of excellent sensitivity, miniaturization of the sensing device and high scalability of process/fabrication. Recently, Gao et al. developed a new SiNWs-based FET biosensor array for ultrasensitive label-free and real-time detection of nucleic acids.66 DNA probes were covalently immobilized on Si NWs, which exhibited concentrationdependent conductance changes in response to the specific

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target DNA sequences. This nanosensor was able to identify and distinguish single-nucleotide polymorphism with a remarkable detection limit of 1 fM for target DNA. With this nanosensor, two pathogenic strain virus DNA sequences (H1N1 and H5N1) of avian influenza could be simultaneously detected. In an effort to further increase the sensitivity, triangle cross-section SiNWs were used to interrogate the detection of nucleic acids.67 It was found that the back-gated SiNW-based FET biosensor manifested ultrahigh sensitivity for rapid detection of target DNA as low as 0.1 fM. Since all previously reported SiNWs-based FET biosensors employed ‘‘line-like’’ detectors, the sensitivity of these nanosensors were limited by the relatively large active region at the micrometer level (1–2 mm). To address this problem, Lieber and co-workers designed a ‘‘point-like’’ detector that has the active NW detector length comparable to the NW diameter.68 The encoded ultrashort-channel NW-based FET biosensor could accomplish fast response for cellular signals with peak widths of B500 ms, revealing highly efficient signal transduction for both extra- and intracellular events. Carbon nanomaterials (e.g. CNTs and graphene)-based FET electrical biosensing also hold enormous potential for realizing direct, label-free, real-time electrical biomolecular detection in a multiplex manner. Owing to their high conductivity, even a very small amount of target binding to their surface may alter the electrical properties of these nanomaterials.69 Star and co-workers functionalized CNTs with porphyrin-based glycoconjugates, based on which they developed a CNTs-based FETs biosensor for probing the interactions between glycoconjugates and bacterial lectins.70 Later, using pyrene- and porphyrinbased glycoconjugates to functionalize either CNTs or chemically converted graphene (CCG), they developed new FET biosensors to study the interactions between glycoconjugates and three different lectins.71 In another study, Johnson et al. functionalized CNTs with single-chain variable fragment (scFv) protein, and demonstrated that the immobilized scFv protein could retain the biological binding activity for a prostate cancer biomarker-osteopontin (OPN). This CNTs-based FET biosensor could realize the highly sensitive and selective detection of OPN with a detection limit of B30 fM.72 It still remains a great challenge to detect single-molecule events in biology. To this end, Shepard et al. covalently attached a single stranded probe DNA sequence to a point defect in CNTs, which realized the label-free detection of DNA hybridization at the single-molecule level.73 Fang et al. demonstrated individual DNA aptamer-functionalized CNTs as point contacts to form a single-molecule FET biosensor,74 exhibiting a realtime, label-free, reversible detection system of DNA–thrombin interactions with high selectivity and real single-molecule sensitivity (Fig. 6). The first graphene-based FET electrical biosensor for the detection of DNA and bacterium was demonstrated by Berry and co-workers in 2008.75 After that, Ohno et al. demonstrated a label-free aptamer-modified graphene-based FET biosensor for selective detection of immunoglobulin E with a dissociation constant of 47 nM.76 Lee and co-workers developed a grapheneencapsulated NPs-based FET biosensor for selective and

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Fig. 6 Scheme for a CNT-based FET biosensor for a real time, label-free, reversible electrical detection of DNA and/or protein activities. (A) Representation of the device structure. (B) Schematic representation of the sensing mechanism showing how single-molecule devices can detect proteins at the single-molecule level. (C) Device characteristics of a representative device rejoined by aptamer before cutting (black), after cutting (red), after DNA connection (green), and after treatment with 260 nm thrombin (blue). VD = 50 mV [reprinted with permission from ref. 74].

sensitive detection of two biomarkers for breast cancer, e.g. Human Epidermal growth factor Receptor 2 (HER2) and epidermal growth factor receptor (EGFR).77 To further improve the sensitivity of graphene-based FET biosensor, Li et al. utilized chemical vapor deposition (CVD)-grown graphene nanosheets to construct an FET-type DNA biosensor, and achieved single-base specificity with a detection limit as low as 10 pM.78 Recently, Garrido et al. reported a CVD-grown graphene arrayed FET biosensor for extracellular detection of action potentials from electrogenic cells.79 This sensor features high signal-to-noise ratios due to the low-noise characteristic of graphene FETs and the large transconductive sensitivity of these devices. Chen et al. reported a graphene-based FET biosensor through direct growth of vertically-oriented graphene (VG) sheets by the plasma-enhanced CVD method.80 Au NPs–antibody conjugates were deposited onto the VG surface. The binding of probe and target proteins produced a significant change in conductivity. The VG-based FET sensor showed a low detection limit of 13 pM for proteins with good specificity, short response time and negligible interfering signals. These studies suggest that the graphene FETs might pave the way for a true breakthrough in bioelectronics.

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7. Nanoscale enhancers: nanomaterial-induced metal deposition Metal deposition provides a relative easy and straightforward approach for signal amplification.81–83 Au NPs are often employed as seeds for the deposition of gold, silver and copper. Non-metal nanomaterials, e.g. graphene, were also found to induce metal deposition. With metal deposition, detectable signals are dramatically amplified, leading to a significant signal enhancement of up to several orders of magnitude and thus considerably lower detection limits for quantification of analytes with optical,81 electrical,82 or other readouts.83 Ju and co-workers reported an electrochemical immunoassay method for biomarker detection by incorporating metal seeds and enzyme to mediated metal deposition.84–86 They designed a streptavidin-functionalized silver-NP-enriched CNT as the trace tag, which was combined with Ag NPs-promoted Ag deposition for ultrasensitive multiplexed measurements of tumor markers.84 Similarly, they used alkaline phosphatase (ALP)/Au NPs deposited silver85 and Au NPs-catalyzed Ag deposition to amplify the detection signal.86 By using GO as an alternative, Zhang et al. reported the detection of bacteria with GO sheet-mediated silver enhancement.87 Deng and co-workers developed an electrochemical immunosensor for the detection of protein biomarker with the GO enhancer.88 Metal deposition can also change the conductivity across a microelectrode gap. For example, Xu and co-workers proposed a novel wireless electrochemiluminescence (ECL) strategy for visualizing prostate-specific antigen (PSA) with bipolar electrodes (BPEs). The strategy could eliminate the background signal and enable a sensitive measurement of PSA by observing the ECL lightspots on BPEs.89 The metal deposition-based enhancement can also be coupled to other techniques. As shown in Fig. 7, Wu and co-workers exploited a highly sensitive signal-enhanced liquid crystals (LC) biosensing platform for the detection of DNA with silver deposition.90 Lv and co-workers demonstrated a highly sensitive inductively coupled

Fig. 7 Stepwise assembly of the signal-enhanced LC DNA biosensing substrate based on enzymatic silver deposition. (a) Cleaned glass slide; (b) self-assembled APS/DMOAP film; (c) immobilization of capture DNA probe; (d) hybridization with target DNA; (e) hybridization with biotinylated detection DNA probe; (f) association with streptavidin alkaline phosphatase and reduction of silver ions by ascorbic acid [reprinted with permission from ref. 90].

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plasma mass spectrometric (ICPMS) immunoassay through the catalytic precipitation of silver onto immunogold tags, which combined the inherent high sensitivity of ICPMS with the signal enhancement of immunogold–silver amplification.83 On the basis of the localized surface plasmon resonance-based photoelectrochemistry, Zhao et al. used the glucose oxidase catalytic growth of Au NP seeds to develop a plasmonic photoelectrochemical (PEC) biosensing towards glucose determination.91 By using copper-enhanced gold NPs, Khayamian and co-workers reported an enhanced chemiluminescent (CL) immunoassay for sensitive detection of human growth hormone (hGH).81 Thaxton et al. employed gold deposition to dramatically increase the light scattering properties of their SNA–Au NP probes.92 By coupling gap-tailorable gold–silver core–shell nanodumbbells to SERS, Lim et al. explored a signal amplified Raman sensing for imaging and sensing applications.56 They also extensively studied factors that influence the performance of this innovative single-particle AFMcorrelated Raman measurement method.93

8. Conclusions and perspectives The growing demands for ultrasensitive biosensing have motivated a large number of studies on the design and development of functional nanoprobes. Over the past decade, we have witnessed substantial progress in tailoring various functional nanomaterials with different biomolecules and their versatile applications in bioassays. A wide range of transduction approaches have been explored, including fluorescence, SERS, plasmonics, electrochemistry and photoelectrochemistry, as well as acoustic and gravimetric techniques.94,95 In particular, it is worthwhile to mention micro/nanomechanical resonators, which have great potential for label-free biomolecular detection with unprecedented sensitivity.96–102 Examples on these can be found in a recent review by Kwon et al.103 Although there have been many reported biosensors that exhibit advantages in terms of simplicity, selectivity, sensitivity and multiplexing ability, it remains a hurdle to implement these ultrasensitive biosensors in real-world applications. ELISA and PCR remain to be the gold standards for protein and nucleic acids assays in clinical diagnosis. In particular, the stability of functional nanoprobes has been the major barricade that prevents their widespread applications. Hence, aside from continuous efforts to find new and better nanomaterials for the development of bio-nanoprobes, we should take greater efforts to face real challenges in hospitals and other medical situations. By taking clinical applications as an example, new assays should meet the criteria for diagnostic purpose and show superior performance for specific biomolecule detection in complex settings. In this regard, the fundamental studies of the mechanism and interfacial properties between bio/nano interfaces are crucial for the advancement of this field.104,105 It is particularly important to elaborate the interfacial design for nanoprobes to combat strong non-specific adsorption due to the high background in serum or whole blood. The assay time is another critical parameter in certain clinical assays,

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e.g. it is a necessity to detect cardiac markers in minutes rather than hours. Given that, it is also important to increase the binding affinity of biomolecules, possibly by reducing the size of the interface to facilitate mass transport. Many diseases are complex and cannot be reliably reflected by the level a single biomarkers. While both DNA and protein microarrays have been popular techniques, bioassays for trans-level biomarkers are still rare. We envision that a biosensing device that can simultaneously monitor the levels of DNA, RNA, protein and small molecule markers in a single miniaturized and user-friendly format will offer the promise of new biomedical diagnostic platforms.

Acknowledgements We appreciate the financial support from NSFC and Ministry of Science and Technology of China. Our research activities involved in this review were partially supported by 973 Program (2012CB932600, 2013CB933800), NSFC (21025522 21135003, 21121091 and 21305063) and the Natural Science Funds (BK20130553) of Jiangsu Province.

Notes and references 1 D. Li, S. P. Song and C. H. Fan, Acc. Chem. Res., 2010, 43, 631–641. 2 Z. Matharu, A. J. Bandodkar, V. Guptac and B. D. Malhotra, Chem. Soc. Rev., 2012, 41, 1363–1402. 3 H. N. Kim, W. X. Ren, J. S. Kim and J. Yoon, Chem. Soc. Rev., 2012, 41, 3210–3244. 4 X. M. Zhou and D. Xing, Chem. Soc. Rev., 2012, 41, 4643–4656. 5 J. P. Lei and H. X. Ju, Chem. Soc. Rev., 2012, 41, 2122–2134. 6 S. P. Song, Y. Qin, Y. He, Q. Huang, C. H. Fan and H. Y. Chen, Chem. Soc. Rev., 2010, 39, 4234–4243. 7 L. B. Wang, L. G. Xu, H. Kuang, C. L. Xu and N. A. Kotov, Acc. Chem. Res., 2012, 45, 1916–1926. 8 N. C. Tansil and Z. Gao, Nano Today, 2006, 1, 28–37. 9 K. Saha, S. S. Agasti, C. Kim, X. Li and V. M. Rotello, Chem. Rev., 2012, 112, 2739–2779. 10 H. Jansa and Q. Huo, Chem. Soc. Rev., 2012, 41, 2849–2866. 11 U. H. F. Bunz and V. M. Rotello, Angew. Chem., Int. Ed., 2010, 49, 3268–3279. 12 R. Gill, M. Zayats and I. Willner, Angew. Chem., Int. Ed., 2008, 47, 7602–7625. 13 M. F. Frasco and N. Chaniotakis, Sensors, 2009, 9, 7266–7286. 14 J. J. Li and J. J. Zhu, Analyst, 2013, 138, 2506–2515. 15 J. I. Cutler, E. Auyeung and C. A. Mirkin, J. Am. Chem. Soc., 2012, 134, 1376–1391. 16 A. E. Prigodich, A. H. Alhasan and C. A. Mirkin, J. Am. Chem. Soc., 2011, 133, 2120–2123. 17 A. E. Prigodich, P. S. Randeria, W. E. Briley, N. J. Kim, W. L. Daniel, D. A. Giljohann and C. A. Mirkin, Anal. Chem., 2012, 84, 2062–2066.

This journal is © The Royal Society of Chemistry 2014

Review Article

18 A. H. Alhasan, D. Y. Kim, W. L. Daniel, E. Watson, J. J. Meeks, C. S. Thaxton and C. A. Mirkin, Anal. Chem., 2012, 84, 4153–4160. 19 N. Li, C. Y. Chang, W. Pan and B. Tang, Angew. Chem., Int. Ed., 2012, 51, 7426–7430. 20 J. M. Nam, C. S. Thaxton and C. A. Mirkin, Science, 2003, 301, 1884–1886. 21 B. Zhang, B. Q. Liu, D. Q. Tang, R. Niessner, G. N. Chen and D. Knopp, Anal. Chem., 2012, 84, 5392–5399. 22 M. Pumera, A. Ambrosi, A. Bonanni, E. L. K. Chng and H. L. Poh, TrAC, Trends Anal. Chem., 2010, 29, 954–965. 23 H. X. Chang, L. H. Tang, Y. Wang, J. H. Jiang and J. H. Li, Anal. Chem., 2010, 82, 2341–2346. 24 X. H. Wang, C. Y. Wang, K. G. Qu, Y. J. Song, J. S. Ren, D. Miyoshi, N. Sugimoto and X. G. Qu, Adv. Funct. Mater., 2010, 20, 3967–3971. 25 D. Chen, H. B. Feng and J. H. Li, Chem. Rev., 2012, 112, 6027–6053. ´ez and A. Merkoçi, Adv. Mater., 2012, 24, 26 E. Morales-Narva 3298–3308. 27 D. Du, L. M. Wang, Y. Y. Shao, J. Wang, M. H. Engelhard and Y. H. Lin, Anal. Chem., 2011, 83, 746–752. 28 Z. F. Liu, L. H. Jiang, F. Galli, I. Nederlof, R. C. L. Olsthoorn, G. E. M. Lamers, T. H. Oosterkamp and J. P. Abrahams, Adv. Funct. Mater., 2010, 20, 2857–2865. 29 E. Dubuisson, Z. Y. Yang and K. P. Loh, Anal. Chem., 2011, 83, 2452–2460. 30 Y. Weizmann, D. M. Chenoweth and T. M. Swager, J. Am. Chem. Soc., 2011, 133, 3238–3241. 31 A. Francesc, T. Esteve and A. F. Antonio, Biosens. Bioelectron., 2013, 41, 12–29. 32 X. H. Xu, X. Liu, Z. Nie, Y. L. Pan, M. L. Guo and S. Z. Yao, Anal. Chem., 2011, 83, 52–59. 33 J. T. Cao, Z. X. Chen, X. Y. Hao, P. H. Zhang and J. J. Zhu, Anal. Chem., 2012, 84, 10097–10104. 34 R. Freeman, X. Q. Liu and I. Willner, J. Am. Chem. Soc., 2011, 133, 11597–11604. 35 H. Zhong, R. Zhang, H. Zhang and S. S. Zhang, Chem. Commun., 2012, 48, 6277–6279. 36 Y. Zhang and C. Y. Zhang, Anal. Chem., 2012, 84, 224–231. 37 S. Y. Deng and H. X. Ju, Analyst, 2013, 138, 43–61. 38 J. Wang, Y. Shan, W. W. Zhao, J. J. Xu and H. Y. Chen, Anal. Chem., 2011, 83, 4004–4011. 39 H. Zhou, J. Liu, J. J. Xu and H. Y. Chen, Chem. Commun., 2011, 47, 8358–8360. 40 J. P. Lei and H. X. Ju, TrAC, Trends Anal. Chem., 2011, 30, 1351–1359. 41 M. Swierczewska, S. Lee and X. Y. Chen, Phys. Chem. Chem. Phys., 2011, 13, 9929–9941. 42 D. Zhu, X. X. Jiang, C. Zhao, X. L. Sun, J. R. Zhang and J. J. Zhu, Chem. Commun., 2010, 46, 5226–5228. 43 M. S. Draz, B. A. Fang, L. J. Li, Z. Chen, Y. J. Wang, Y. H. Xu, J. Yang, K. Killeen and F. Q. F. Chen, ACS Nano, 2012, 6, 7634–7643. 44 Y. Q. Li, L. Y. Guan, H. L. Zhang, J. Chen, S. Lin, Zh. Y. Ma and Y. D. Zhao, Anal. Chem., 2011, 83, 4103–4109.

Chem. Soc. Rev.

View Article Online

Published on 17 December 2013. Downloaded by Lomonosov Moscow State University on 22/12/2013 10:16:33.

Review Article

45 W. H. Wu, H. Y. Hu, F. Li, L. H. Wang, J. M. Gao, J. X. Lu and C. H. Fan, Chem. Commun., 2011, 47, 1201–1203. 46 C. H. Lu, J. Li, X. L. Zhang, A. X. Zheng, H. H. Yang, X. Chen and G. N. Chen, Anal. Chem., 2011, 83, 7276–7282. 47 H. F. Dong, J. Zhang, H. X. Ju, H. T. Lu, S. Y. Wang, S. Jin, K. H. Hao, H. W Du and X. J. Zhang, Anal. Chem., 2012, 84, 4587–4593. 48 Y. X. Piao, F. Liu and T. S. Seo, ACS Appl. Mater. Interfaces, 2012, 4, 6785–6789. 49 Y. W. Zhang, S. Liu, L. Wang, Y. L. Luo, J. Q. Tian, A. M. Asiri, A. O. Al-Youbi and X. P. Sun, ACS Comb. Sci., 2012, 14, 191–196. 50 L. B. Zhang, J. B. Zhu, S. J. Guo, T. Li, J. Li and E. K. Wang, J. Am. Chem. Soc., 2013, 135, 2403–2406. 51 Y. Wang, B. Yan and L. Chen, Chem. Rev., 2013, 113, 1391–1428. 52 L. L. Tay, P. J. Huang, J. Tanha, S. Ryan, X. Wu, J. Hulse and L. K. Chau, Chem. Commun., 2012, 48, 1024–1026. 53 J. Yan, S. Su, S. He, Y. He, B. Zhao, D. Wang, H. Zhang, Q. Huang, S. Song and C. Fan, Anal. Chem., 2012, 84, 9139–9145. 54 N. Gandra, A. Abbas, L. Tian and S. Singamaneni, Nano Lett., 2012, 12, 2645–2651. 55 W. Lu, A. K. Singh, S. A. Khan, D. Senapati, H. Yu and P. C. Ray, J. Am. Chem. Soc., 2010, 132, 18103–18114. 56 D. K. Lim, K. S. Jeon, H. M. Kim, J.-M. Nam and Y. D. Suh, Nat. Mater., 2009, 9, 60–67. 57 D. K. Lim, K. S. Jeon, J. H. Hwang, H. Kim, S. Kwon, Y. D. Suh and J. M. Nam, Nanoscale Res. Lett., 2011, 6, 452–460. 58 Z. Wang, S. Zong, W. Li, C. Wang, S. Xu, H. Chen and Y. Cui, J. Am. Chem. Soc., 2012, 134, 2993–3000. 59 X. Zhang, X. Kong, Z. Lv, S. Zhou and X. Du, J. Mater. Chem. B, 2013, 1, 2198–2204. 60 L. X. Qin, Y. Li, D. W. Li, C. Jing, B. Q. Chen, W. Ma, A. Heyman, O. Shoseyov, I. Willner, H. Tian and Y. T. Long, Angew. Chem., Int. Ed., 2012, 51, 140–144. 61 X. X. Zheng, Q. Liu, C. Jing, Y. Li, D. Li, W. J. Luo, Y. Q. Wen, Y. He, Q. Huang, Y. T. Long and C. H. Fan, Angew. Chem., Int. Ed., 2011, 50, 11994–11998. 62 Q. Liu, C. Jing, X. X. Zheng, Z. Gu, D. Li, D. W. Li, Q. Huang, Y. T. Long and C. H. Fan, Chem. Commun., 2012, 48, 9574–9576. 63 Y. Li, C. Jing, L. Zhang and Y. T. Long, Chem. Soc. Rev., 2012, 41, 632–642. 64 Y. Cui, Q. Wei, H. Park and C. M. Lieber, Science, 2001, 293, 1289–1292. 65 J. C. Claussen, A. Kumar, D. B. Jaroch, M. H. Khawaja, A. B. Hibbard, D. M. Porterfield and T. S. Fisher, Adv. Funct. Mater., 2012, 22, 3399–3405. 66 A. Gao, N. Lu, P. F. Dai, T. Li, H. Pei, X. L. Gao, Y. B. Gong, Y. L. Wang and C. H. Fan, Nano Lett., 2011, 11, 3974–3978. 67 A. Gao, N. Lu, Y. C. Wang, P. F. Dai, T. Li, X. L. Gao, Y. L. Wang and C. H. Fan, Nano Lett., 2012, 12, 5262–5268. 68 T. Cohen-Karni, D. Casanova, J. F. Cahoon, Q. Qing, D. C. Bell and C. M. Lieber, Nano Lett., 2012, 12, 2639–2644.

Chem. Soc. Rev.

Chem Soc Rev

69 W. Yang, K. R. Ratinac, S. P. Ringer, P. Thordarson, J. J. Gooding and F. Braet, Angew. Chem., Int. Ed., 2010, 49, 2114–2138. 70 H. Vedala, Y. N. Chen, S. Cecioni, A. Imberty, S. Vidal and A. Star, Nano Lett., 2011, 11, 170–175. 71 Y. N. Chen, H. Vedala, G. P. Kotchey, A. Audfray, S. Cecioni, A. Imberty, S. Vidal and A. Star, ACS Nano, 2012, 6, 760–770. 72 M. B. Lerner, J. D’Souza, T. Pazina, J. Dailey, B. R. Goldsmith, M. K. Robinson and A. T. C. Johnson, ACS Nano, 2012, 6, 5143–5149. 73 S. Sorgenfrei, C. Y. Chiu, R. L. Gonzalez, Jr., Y. J. Yu, P. Kim, C. Nuckolls and K. L. Shepard, Nat. Nanotechnol., 2011, 6, 126–132. 74 S. Liu, X. Y. Zhang, W. X. Luo, Z. X. Wang, X. F. Guo, M. L. Steigerwald and X. H. Fang, Angew. Chem., Int. Ed., 2011, 50, 2496–2502. 75 N. Mohanty and V. Berry, Nano Lett., 2008, 8, 4469–4476. 76 Y. Ohno, K. Maehashi and K. Matsumoto, J. Am. Chem. Soc., 2010, 132, 18012–18013. 77 S. Myung, A. Solanki, C. Kim, J. Park, K. S. Kim and K.-B. Lee, Adv. Mater., 2011, 23, 2221–2225. 78 X. C. Dong, Y. M. Shi, W. Huang, P. Chen and L. J. Li, Adv. Mater., 2010, 22, 1649–1653. 79 L. H. Hess, M. Jansen, V. Maybeck, M. V. Hauf, M. Seifert, ¨usser and J. A. M. Stutzmann, I. D. Sharp, A. Offenha Garrido, Adv. Mater., 2011, 23, 5045–5049. 80 S. Mao, K. Yu, J. B. Chang, D. A. Steeber, L. E. Ocola and J. H. Chen, Sci. Rep., 2013, 3, 1–6. 81 F. Hasanpour, T. Khayamian, A. A. Ensafi, H. Rahmani and B. Rezaei, Luminescence, 2013, 28, 780. 82 T. Yasukawa, Y. Yoshimoto, T. Goto and F. Mizutani, Biosens. Bioelectron., 2012, 37, 19–23. 83 R. Liu, X. Liu, Y. R. Tang, L. Wu, X. D. Hou and Y. Lv, Anal. Chem., 2011, 83, 2330–2336. 84 G. S. Lai, J. Wu, H. X. Ju and F. Yan, Adv. Funct. Mater., 2011, 21, 2938–2943. 85 G. S. Lai, F. Yan, J. Wu, C. Leng and H. X. Ju, Anal. Chem., 2011, 83, 2726–2732. 86 D. J. Lin, J. Wu, M. Wang, F. Yan and H. X. Ju, Anal. Chem., 2012, 84, 3662–3668. 87 Y. Wan, Y. Wang, J. J. Wu and D. Zhang, Anal. Chem., 2011, 83, 648–653. 88 F. L. Qu, H. M. Lu, M. H. Yang and C. Y. Deng, Biosens. Bioelectron., 2011, 26, 4810–4814. 89 M. S. Wu, D. J. Yuan, J. J. Xu and H. Y. Chen, Chem. Sci., 2013, 4, 1182–1188. 90 H. Tan, S. Y. Yang, G. L. Shen, R. Q. Yu and Z. Y. Wu, Angew. Chem., 2010, 122, 8790–8793. 91 W. W. Zhao, C. Y. Tian, J. J. Xu and H. Y. Chen, Chem. Commun., 2012, 48, 895–897. 92 A. H. Alhasan, D. Y. Kim, W. L. Daniel, E. Watson, J. J. Meeks, C. S. Thaxton and C. A. Mirkin, Anal. Chem., 2012, 84, 4153–4160. 93 J. H. Lee, J. M. Nam, K. S. Jeon, D. K. Lim, H. Kim, S. Kwon, H. Lee and Y. D. Suh, ACS Nano, 2012, 6, 9574–9584.

This journal is © The Royal Society of Chemistry 2014

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Published on 17 December 2013. Downloaded by Lomonosov Moscow State University on 22/12/2013 10:16:33.

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¨nge, B. E. Rapp and M. Rapp, Anal. Bioanal. Chem., 94 K. La 2008, 391, 1509–1519. ´. S. Paulo and 95 J. Tamayo, P. M. Kosaka, J. J. Ruz, A M. Calleja, Chem. Soc. Rev., 2013, 42, 1287–1311. 96 A. K. Naik, M. S. Hanay, W. K. Hiebert, X. L. Feng and M. L. Roukes, Nat. Nanotechnol., 2009, 4, 445–450. 97 T. P. Burg, M. Godin, S. M. Knudsen, W. Shen, G. Carlson, J. S. Foster, K. Babcock and S. R. Manalis, Nature, 2007, 446, 1066–1069. 98 K. M. Goeders, J. S. Colton and L. A. Bottomley, Chem. Rev., 2008, 108, 522–542. 99 T. Y. Kwon, K. Eom, J. H. Park, D. S. Yoon, T. S. Kim and H. L. Lee, Appl. Phys. Lett., 2007, 90, 223903.

This journal is © The Royal Society of Chemistry 2014

Review Article

100 P. S. Waggoner, M. Varshney and H. G. Craighead, Lab Chip, 2009, 9, 3095–3099. ´ndez, E. Gil-Santos, H. D. Tong, 101 D. Ramos, M. Arroyo-Herna C. V. Rijn, M. Calleja and J. Tamayo, Anal. Chem., 2009, 81, 2274–2279. 102 M. Varshney, P. S. Waggoner, C. P. Tan, K. Aubin, R. A. Montagna and H. G. Craighead, Anal. Chem., 2008, 80, 2141–2148. 103 K. Eoma, H. S. Park, D. S. Yoon and T. Kwon, Phys. Rep., 2011, 503, 115–163. 104 B. Liu, Z. Sun, X. Zhang and J. Liu, Anal. Chem., 2013, 85, 7987–7993. 105 J. Liu, Phys. Chem. Chem. Phys., 2012, 14, 10485–10496.

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Functional nanoprobes for ultrasensitive detection of biomolecules: an update.

With the rapidly increasing demands for ultrasensitive biodetection, the design and applications of functional nanoprobes have attracted substantial i...
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