DNA strand displacement cascades have been engineered to construct various fascinating DNA circuits. However, biological applications are limited by the insufficient cellular internalization of naked DNA structures, as well as the separated multicomponent feature. In this work, these problems are addressed by the development of a novel DNA nanodevice, termed intelligent layered nanoflare, which integrates DNA computing at the nanoscale, via the self-assembly of DNA flares on a single gold nanoparticle. As a “lab-on-a-nanoparticle”, the intelligent layered nanoflare could be engineered to perform a variety of Boolean logic gate operations, including three basic logic gates, one three-input AND gate, and two complex logic operations, in a digital non-leaky way. In addition, the layered nanoflare can serve as a programmable strategy to sequentially tune the size of nanoparticles, as well as a new fingerprint spectrum technique for intelligent multiplex biosensing. More importantly, the nanoflare developed here can also act as a single entity for intracellular DNA logic gate delivery, without the need of commercial transfection agents or other auxiliary carriers. By incorporating DNA circuits on nanoparticles, the presented layered nanoflare will broaden the applications of DNA circuits in biological systems, and facilitate the development of DNA nanotechnology.

Development of efficient methods for highly sensitive and rapid screening of specific oligonucleotide sequences is essential to the early diagnosis of serious diseases. In this work, an aggregated cationic perylene diimide (PDI) derivative was found to efficiently quench the fluorescence emission of a variety of anionic oligonucleotide-labeled fluorophores that emit at wavelengths from the visible to NIR region. This broad-spectrum quencher was then adopted to develop a multicolor biosensor via a label-free approach for multiplexed fluorescent detection of DNA. The aggregated perylene derivative exhibits a very high quenching efficiency on all ssDNA-labeled dyes associated with biosensor detection, having efficiency values of 98.3 ± 0.9%, 97 ± 1.1%, and 98.2 ± 0.6% for FAM, TAMRA, and Cy5, respectively. An exonuclease-assisted autocatalytic target recycling amplification was also integrated into the sensing system. High quenching efficiency combined with autocatalytic target recycling amplification afforded the biosensor with high sensitivity toward target DNA, resulting in a detection limit of 20 pM, which is about 50-fold lower than that of traditional unamplified homogeneous fluorescent assay methods. The quencher did not interfere with the catalytic activity of nuclease, and the biosensor could be manipulated in either preaddition or postaddition manner with similar sensitivity. Moreover, the proposed sensing system allows for simultaneous and multicolor analysis of several oligonucleotides in homogeneous solution, demonstrating its potential application in the rapid screening of multiple biotargets.

The double-strand DNA (dsDNA) can act as an efficient template for the formation of copper nanoparticles (Cu NPs) with high fluorescence, whereas the single-strand DNA (ssDNA) cannot support the formation of Cu NPs. This difference in fluorescent signal generation can be used for the detection of nuclease cleavage activity. Thus, a label-free strategy for sensitive detection of nuclease has been developed. The sensor contains a complete complementary dsDNA which acts as a template for the formation of Cu NPs and generation of fluorescence signal. The enzyme S1 nuclease was taken as the model analyte. Upon addition of S1 nuclease into the sensing system, the DNA was cleaved into fragments, preventing the formation of the Cu NPs and resulting in low fluorescence. In order to achieve the system's best sensing performance, a series of experimental conditions were optimized. Under the optimized experimental conditions, the sensor exhibits excellent performance (e.g., a detection limit of 0.3 U mL−1 with high selectivity). This possibly makes it an attractive platform for the detection of S1 nuclease and other biomolecules.Highlights► A fluorescent probe based on double-strand DNA-templated formation of copper nanoparticles was developed for label-free nuclease enzyme detection. ► The probe shows a high sensitivity to S1 nuclease activity with a low detection limit of 0.3 U mL−1 observed. ► It also exhibits high selectivity to S1 nuclease over other nucleases.

In this paper, for the first time, Cu nanoparticles (CuNPs) were prepared by seed-mediated growth method with Au nanoparticles (AuNPs) playing the role of seeds. Carbon nanotubes (CNTs) and AuNPs were first dropped on the surface of glassy carbon (GC) electrode, and then the electrode was immersed into growth solution that contained CuSO4 and hydrazine. CuNPs were successfully grown on the surface of the CNTs. The modified electrode showed a very high electrochemical activity for electrocatalytic oxidation of glucose in alkaline medium, which was utilized as the basis of the fabrication of a nonenzymatic biosensor for electrochemical detection of glucose. The biosensor can be applied to the quantification of glucose with a linear range covering from 1.0 × 10−7 to 5 × 10−3 M and a low detection limit of 3 × 10−8 M. Furthermore, the experiment results also showed that the biosensor exhibited good reproducibility and long-term stability, as well as high selectivity with no interference from other oxidable species.Graphical abstractHighlights► Seed-mediated method was introduced to prepare of the Cu nanoparticles (CuNPs). ► The CuNPs modified electrode shows high electrocatalytic ability to glucose oxidation in alkaline solution. ► The CuNPs modified electrode has been used to construct a novel nonenzymatic glucose biosensor.

Chemotherapy strategies thus far reported can result in both side effects and drug resistance. To address both of these issues at the cellular level, we report a molecular engineering strategy, which employs polymeric aptamers to induce selective cytotoxicity inside target cells. The polymeric aptamers, composed of both multiple cell-based aptamers and a high ratio of dye-labeled short DNA, exploit the target recognition capability of the aptamer, enhanced cell internalization via multivalent effects, and cellular disruption by the polymeric conjugate. Importantly, the polymer backbone built into the conjugate is cytotoxic only inside cells. As a result, selective cytotoxicity is achieved equally in both normal cancer cells and drug-resistant cells. Control assays have confirmed the nontoxicity of the aptamer itself, but they have also shown that the physical properties of the polymer backbone contribute to target cell cytotoxicity. Therefore, our approach may shed new light on drug design and drug delivery.

Many types of fluorescent sensing systems have been reported for biological small molecules. Particularly, several methods have been developed for the recognition of ATP or NAD+, but they only show moderate sensitivity, and they cannot discriminate either ATP or NAD+ from their respective analogues. We have addressed these limitations and report here a dual strategy which combines split DNAzyme-based background reduction with catalytic and molecular beacon (CAMB)-based amplified detection to develop a ligation-triggered DNAzyme cascade, resulting in ultrahigh sensitivity. First, the 8-17 DNAzyme is split into two separate oligonucleotide fragments as the building blocks for the DNA ligation reaction, thereby providing a zero-background signal to improve overall sensitivity. Next, a CAMB strategy is further employed for amplified signal detection achieved through cycling and regenerating the DNAzyme to realize the true enzymatic multiple turnover (one enzyme catalyzes the cleavage of several substrates) of catalytic beacons. This combination of zero-background signal and signal amplification significantly improves the sensitivity of the sensing systems, resulting in detection limits of 100 and 50 pM for ATP and NAD+, respectively, much lower than those of previously reported biosensors. Moreover, by taking advantage of the highly specific biomolecule-dependence of the DNA ligation reaction, the developed DNAzyme cascades show significantly high selectivity toward the target cofactor (ATP or NAD+), and the target biological small molecule can be distinguished from its analogues. Therefore, as a new and universal platform for the design of DNA ligation reaction-based sensing systems, this novel ligation-triggered DNAzyme cascade method may find a broad spectrum of applications in both environmental and biomedical fields.

The use of a nanoscale DNA–Au dendrimer as a signal amplifier was proposed for the universal design of functional DNA-based ultra-sensitive SERS biosensors. This novel design combines the high specificity of functional DNA with the high sensitivity of surface-enhanced Raman scattering (SERS) spectroscopy, resulting in sensitivity superior to that of previously reported sensors.

This work reports the development of a new molecular beacon-based junction sensing system with highly sensitive DNA detection and a strong capability to identify SNPs. The single linear probe typically labels the midsection of the oligonucleotide, but our next-generation junction sensing system uses a hairpin-structured MB with labels on each end of the oligonucleotide to maintain the cleaving activity of our newly designed ssDNA-cleaved endonuclease, Nt.BbvCI, rather than the typical dsDNA-cleaved endonuclease. These design improvements guarantee a true and efficient target-triggered enzymatic recycling amplification process in our sensing system. They also afford a faster and more sensitive response toward target DNA than the first-generation junction sensing system.

On the basis of the remarkable difference in affinity of graphene (GO) with ssDNA containing a different number of bases in length, we for the first time report a GO–DNAzyme based biosensor for amplified fluorescence “turn-on” detection of Pb2+. A FAM-labeled DNAzyme–substrate hybrid acted as both a molecular recognition module and signal reporter and GO as a superquencher. By taking advantage of the super fluorescence quenching efficiency of GO, our proposed biosensor exhibits a high sensitivity toward the target with a detection limit of 300 pM for Pb2+, which is lower than previously reported for catalytic beacons. Moreover, with the choice of a classic Pb2+-dependent GR-5 DNAzyme instead of 8-17 DNAzyme as the catalytic unit, the newly designed sensing system also shows an obviously improved selectivity than previously reported methods. Moreover, the sensing system was used for the determination of Pb2+ in river water samples with satisfying results.

Fluorescence catalytic beacons have emerged as a general platform for sensing applications. However, almost all such sensing systems need covalent modification of the DNAzymes with fluorophore–quencher pairs, which may require elaborate design of the synthetic routes and many heavy and complicated synthetic steps and result in increased cost and lower synthesis yield. Here we report the construction of fluorescent cascadic catalytic beacons. With separation of the molecular recognition module from the signal reporter, this new design both avoids DNAzyme modifications and improves sensitivity through an endonuclease-based cascadic enzymatic signal amplification. This allows detection of l-histidine with high sensitivity (LOD = 200 nM) and excellent specificity. The proposed sensing system has also been used for detection of l-histidine in cellular homogenate with satisfactory results.

This letter described the design and synthesis of a novel fluorescein-appended rhodamine spirolactam derivative and its preliminary application as a ratiometric fluorescent cellular imaging probe for Zn2+. The ratiometric fluorescent signal change of the probe is based on an intramolecular fluorescence resonance energy transfer (FRET) mechanism modulated by a specific metal ion induced ring-opening process of the rhodamine spirolactam (acting as a trigger). In the new developed sensing system, the emission peaks of the two fluorophores are well-resolved, which can avoid the emission spectra overlap problem generally met by spectra-shift type probes and benefits for observation of fluorescence signal change at two different emission wavelengths with high resolution. It also benefits for a large range of emission ratios, thereby a high sensitivity for Zn2+detection. Under optimized experimental conditions, the probe exhibits a stable response for Zn2+ over a concentration range from 2.0 × 10−7 to 2.0 × 10−5 M, with a detection limit of 4.0 × 10−8 M. Most importantly, the novel probe has well solved the problem of serious interferences from other transition metal ions generally met by previously reported typical fluorescent probes for Zn2+ with the di(2-picolyl)amine moiety as the receptor (in this case, the fluorescence response induced by Cd2+is even comparable to that of Zn2+) and shows a reversible and fast response toward Zn2+. All these unique features make it particularly favorable for ratiometric cellular imaging investigations. It has been preliminarily used for ratiometric imaging of Zn2+ in living cells with satisfying resolution.

The catalytic beacon has emerged as a general platform for sensing metal ions and organic molecules. However, few reports have taken advantage of the true potential of catalytic beacons in signal amplification through multiple enzymatic turnovers, as existing designs require either equal concentrations of substrate and DNAzyme or an excess of DNAzyme in order to maintain efficient quenching, eliminating the excess of substrate necessary for multiple turnovers. On the basis of the large difference in the melting temperatures between the intramolecular molecular beacon stem and intermolecular products of identical sequences, we here report a general strategy of catalytic and molecular beacon (CAMB) that combines the advantages of the molecular beacon for highly efficient quenching with the catalytic beacon for amplified sensing through enzymatic turnovers. Such a CAMB design allows detection of metal ions such as Pb2+ with a high sensitivity (LOD = 600 pM). Furthermore, the aptamer sequence has been introduced into DNAzyme to use the modified CAMB for amplified sensing of adenosine with similar high sensitivity. These results together demonstrate that CAMB provides a general platform for amplified detection of a wide range of targets.

Mesoporous SBA-15 silica is an excellent support for constructing fluorescent surface sensors. In this letter, we reported a two-step surface reaction involved strategy to construct efficient fluorescent surface sensors for metal ions by clicking fluoroionophores onto azide-functionalized SBA-15. Our experimental results indicate that such a strategy exhibits an obviously higher loading efficiency within commercial SBA-15 than a previously reported strategy. As a proof-of-concept, a newly designed alkyne-functionalized Hg2+ fluoroionophore was grafted onto SBA-15 to form a fluorescent Hg2+ surface sensor. It shows improved sensitivity and selectivity than the fluoroionophore itself working in the solution phase with a detection limit of 2.0 × 10−8 M for Hg2+.

A novel tyrosinase biosensor based on hydroxyapatite nanoparticles (nano-HA)-chitosan nanocomposite has been developed for the detection of phenolic compounds. The uniform and size controlled nano-HA was synthesized by hydrothermal method, and its morphological characterization was examined by transmission electron microscope (TEM). Tyrosinase was then immobilized on a nano-HA-chitosan nanocomposite-modified gold electrode. Electrochemical impedance spectroscopy and cyclic voltammetry were used to characterize the sensing film. The prepared biosensor was applied to determine phenolic compounds by monitoring the reduction signal of the biocatalytically produced quinone species at −0.2 V (vs. saturated calomel electrode). The effects of the pH, temperature and applied potential on the biosensor performance were investigated, and experimental conditions were optimized. The biosensor exhibited a linear response to catechol over a wide concentration range from 10 nM to 7 μM, with a high sensitivity of 2.11 × 103 μA mM−1 cm−2, and a limit of detection down to 5 nM (based on S/N = 3). The apparent Michaelis–Menten constants of the enzyme electrode were estimated to be 3.16, 1.31 and 3.52 μM for catechol, phenol and m-cresol, respectively. Moreover, the stability and reproducibility of this biosensor were evaluated with satisfactory results.

A highly selective electrochemical biosensor for the ultrasensitive detection of Hg2+ in aqueous solution has been developed based on the strong and specific binding of Hg2+ by two DNAthymine bases (T–Hg2+–T) and the use of AuNP-functionalized reporter DNA to achieve signal amplification.

In this paper, we unveil a novel naphthalimide−porphyrin hybrid based fluorescence probe (1) for ratiometric detection of Hg2+ in aqueous solution and living cells. The ratiometric signal change of the probe is based on a carefully predesigned molecule containing two independent Hg2+-sensitive fluorophores with their maximal excitation wavelengths located at the same range, which shows reversibly specific ratiometric fluorescence responses induced by Hg2+. In the new developed sensing system, the emissions of the two fluorophores are well-resolved with a 125 nm difference between two emission maxima, which can avoid the emission spectra overlap problem generally met by spectra-shift type probes and is especially favorable for ratiometric imaging intracellular Hg2+. It also benefits from a large range of emission ratios and thereby a high sensitivity for Hg2+ detection. Under optimized experimental conditions, the probe exhibits a stable response for Hg2+ over a concentration range from 1.0 × 10−7 to 5.0 × 10−5 M, with a detection limit of 2.0 × 10−8 M. The response of the probe toward Hg2+ is reversible and fast (response time less than 2 min). Most importantly, the ratiometric fluorescence changes of the probe are remarkably specific for Hg2+ in the presence of other abundant cellular metal ions (i.e., Na+, K+, Mg2+, and Ca2+), essential transition metal ions in celsl (such as Zn2+, Fe3+, Fe2+, Cu2+, Mn2+, Co2+, and Ni2+), and environmentally relevant heavy metal ions (Ag+, Pb2+, Cr3+, and Cd2+), which meets the selective requirements for biomedical and environmental monitoring application. The recovery test of Hg2+ in real water samples demonstrates the feasibility of the designed sensing system for Hg2+ assay in practical samples. It has also been used for ratiometric imaging of Hg2+ in living cells with satisfying resolution, which indicates that our novel designed probe has effectively avoided the general emission spectra overlap problem of other ratiometric probes.

The design and synthesis of a novel rhodamine spirolactam derivative and its application in fluorescent detections of Cu2+in aqueous solution and living cells are reported. The signal change of the chemosensor is based on a specific metal ion induced reversible ring-opening mechanism of the rhodamine spirolactam. It exhibits a highly sensitive “turn-on” fluorescent response toward Cu2+ in aqueous solution with an 80-fold fluorescence intensity enhancement under 10 equiv of Cu2+added. This indicates that the synthesized chemosensor effectively avoided the fluorescence quenching for the paramagnetic nature of Cu2+ via its strong binding capability toward Cu2+. With the experimental conditions optimized, the probe exhibits a dynamic response range for Cu2+ from 8.0 × 10−7 to 1.0 × 10−5 M, with a detection limit of 3.0 × 10−7 M. The response of the chemosensor for Cu2+ is instantaneous and reversible. Most importantly, both the color and fluorescence changes of the chemosensor are remarkably specific for Cu2+ in the presence of other heavy and transition metal ions (even those that exist in high concentration), which meet the selective requirements for biomedical and environmental monitoring application. The proposed chemosensor has been used for direct measurement of Cu2+ content in river water samples and imaging of Cu2+ in living cells with satisfying results, which further demonstrates its value of practical applications in environmental and biological systems.

Highly ordered Ni nanowire arrays (NiNWAs) were synthesized for the first time using a template-directed electropolymerization strategy with a nanopore polycarbonate (PC) membrane template, and their morphological characterization were examined by scanning electron microscopy (SEM) and transmission electron microscope (TEM). A NiNWAs based electrode shows very high electrochemical activity for electrocatalytic oxidation of glucose in alkaline medium, which has been utilized as the basis of the fabrication of a nonenzymatic biosensor for electrochemical detection of glucose. The biosensor can be applied to the quantification of glucose with a linear range covering from 5.0 × 10−7 to 7.0 × 10−3 M, a high sensitivity of 1043 μA mM−1 cm−2, and a low detection limit of 1 × 10−7 M. The experiment results also showed that the sensor exhibits good reproducibility and long-term stability, as well as high selectivity with no interference from other oxidable species.

Quinolin-8-ol p-[10′,15′,20′-triphenyl-5′-porphyrinyl]benzoate (1) was synthesized for the first time and developed as a ratiometric fluorescent chemosensor for recognition of Hg2+ ions in aqueous ethanol with high selectivity. The 1–Hg2+ complexation quenches the fluorescence of porphyrin at 646 nm and induces a new fluorescent enhancement at 603 nm. The fluorescent response of 1 towards Hg2+ seems to be caused by the binding of Hg2+ ion with the quinoline moiety, which was confirmed by the absorption spectra and 1H NMR spectrum. The fluorescence response fits a Hill coefficient of 1 (1.0308), indicating the formation of a 1:1 stoichiometry for the 1–Hg2+ complex. The analytical performance characteristics of the chemosensor were investigated. The sensor shows a linear response toward Hg2+ in the concentration range of 3 × 10−7 to 2 × 10−5 M with a limit of detection of 2.2 × 10−8 M. Chemosensor 1 shows excellent selectivity to Hg2+ over transition metal cations except Cu2+, which quenches the fluorescence of 1 to some extent when it exists at equal molar concentration. Moreover, the chemosensor are pH-independent in 5.0–9.0 and show excellent selectivity for Hg2+ over transition metal cations.

A porphyrin derivative (1), containing two 2-(oxymethyl)pyridine units has been designed and synthesized as chemosensor for recognition of metal ions. Unlike many common porphyrin derivatives that show response to different heavy metal ions, compound 1 exhibits unexpected ratiometric fluorescence response to Zn2+ with high selectivity. The response of the novel chemosensor to zinc was based on the porphyrin metallation with cooperating effect of 2-(oxymethyl)pyridine units. The change of fluorescence of 1 was attributed to the formation of an inclusion complex between porphyrin ring and Zn2+ by 1:1 complex ratio (K = 1.04 × 105), which has been utilized as the basis of the fabrication of the Zn2+-sensitive fluorescent chemosensor. The analytical performance characteristics of the proposed Zn2+-sensitive chemosensor were investigated. The sensor can be applied to the quantification of Zn2+ with a linear range covering from 3.2 × 10−7 to 1.8 × 10−4 M and a detection limit of 5.5 × 10−8 M. The experiment results show that the response behavior of 1 to Zn2+ is pH-independent in medium condition (pH 4.0–8.0) and show excellent selectivity for Zn2+ over transition metal cations.

A new fluorescent chemosensor for sensing Co(II) using di(2-picolyl)amino (DPA) as a recognition group and quinazoline as a reporting group has been synthesized and characterized. The quinazoline derivative contains an intramolecular hydrogen bond, which would undergo excited-state intramolecular proton transfer (ESIPT) at illumination. The fluorescence quenching is attributed to cation-induced inhibition of ESIPT, which constitutes the basis for the determination of Co(II) with the prepared chemosensor. The fluorophore forms 1:1 cobalt(II) complex with the logarithm of apparent dissociation constant log Ka = 6.8. The analytical performance characteristics of the proposed Co(II)-sensitive sensor were investigated. The chemosensor exhibits a linear response toward Co(II) in the concentration range 3.2 × 10−8 to 1.4 × 10−6 M, with a working pH range from 7.0 to 9.5 and high selectivity.

The design and synthesis of a porphyrin-appended terpyridine, 5-(4-([2,2′:6′,2″]-terpyridin-4-yl-carboxyamidyl)phenyl)-10,15,20-triphenylporphyrin (H2TPPTPy) and its application as potential fluoroionophore for recognition of metal ions are reported. For preparation of the fluoroionophore, a novel simple strategy with improved total yield has been applied for the synthesis of 2,2′:6′,2″-terpyridine-4′-carboxylic acid as a ligand. H2TPPTPy shows chelation-enhanced fluorescence effect with cadmium ion via the interruption of photoinduced electron transfer (PET) process, which has been utilized as the basis of the fabrication of the Cd(II)-sensitive fluorescent chemosensor. The analytical performance characteristics of the proposed Cd(II)-sensitive chemosensor were investigated. It shows a linear response toward Cd(II) in the concentration range of 3.2 × 10−6 to 3.2 × 10−4 M with a limit of detection of 1.2 × 10−6 M. The chemosensor shows good selectivity for Cd(II) over a large number of cations, such as alkali, alkali earth and transitional metal ions except Cu(II) and Zn(II). The sensor has been used for determination of Cd(II) in water samples with satisfactory recoveries.

A new highly selective silver(I) electrode was prepared with a PVC membrane using 5,10,15-tris(pentafluorophenyl)corrole as an electroactive material, 2-nitrophenyl octyl ether (o-NPOE) as a plasticizer and sodium tetraphenylborate (NaTPB) as an additive in the percentage ratio of 3:3:62:32 (corrole:NaTPB:o-NPOE:PVC, w:w). The electrode exhibited linear response with a near Nernstian slope of 54.8 mV/decade within the concentration range of 5.1 × 10−6 to 1.0 × 10−1 M silver ions, with a working pH range from 4.0 to 8.0, and a fast response time of <30 s. Selectivity coefficients for Ag(I) relative to a number of interfering ions were investigated. The electrode is highly selective for Ag(I) ions over a large number of mono-, bi-, and tri-valent cations. Common interferents like Hg2+ and Cd2+ show very low interfering effect on the silver assay, which is valuable property of the proposed electrode. Several electroactive materials and solvent mediators have been compared and the experimental conditions were optimized. The sensor was applied to the determination of silver in real ore samples with satisfied results.

The synthesis of a new compound, 10-(4-aminophenyl)-5,15-dimesitylcorrole, and its application for the preparation of optical chemical pH sensors is described. The dye materials were immobilized in a sol–gel glass matrix and characterised upon exposure to aqueous buffer solutions. The response of the sensor is based on the fluorescence intensity changing of corrole owing to multiple steps of protonation and deprotonation. Due to its containing several proton sensitive centers, the 10-(4-aminophenyl)-5,15-dimesitylcorrole based optode shows a wider response range toward pH than that of tetraphenylporphyrin (TPPH2) and 5,10,15-tris(pentafluorophenyl)corrole (H3(tpfc)). It shows a linear pH response in the range of 2.17–10.30. The effect of the composition of the sensor membrane has been studied and the experimental conditions were optimized. The optode showed good reproducibility and reversibility, and common co-existing inorganic ions did not show obvious interference to its pH measurement.

The use of a nanoscale DNA–Au dendrimer as a signal amplifier was proposed for the universal design of functional DNA-based ultra-sensitive SERS biosensors. This novel design combines the high specificity of functional DNA with the high sensitivity of surface-enhanced Raman scattering (SERS) spectroscopy, resulting in sensitivity superior to that of previously reported sensors.

A highly selective electrochemical biosensor for the ultrasensitive detection of Hg2+ in aqueous solution has been developed based on the strong and specific binding of Hg2+ by two DNAthymine bases (T–Hg2+–T) and the use of AuNP-functionalized reporter DNA to achieve signal amplification.