Plasmon-enhanced fluorescence imaging with silicon-based silver chips for protein and nucleic acid assay.

Metal-enhanced fluorescence shows great potential for improving the sensitivity of fluoroscopy, which has been widely used in protein and nucleic acid detection for biosensor and bioassay applications. In comparison with the traditional glass-supported metal nanoparticles (MNPs), the introduction of a silicon substrate has been shown to provide an increased surface-enhanced Raman scattering (SERS) effect due to the coupling between the MNPs and the semiconducting silicon substrate. In this work, we further study the fluorescence-enhanced effect of the silicon-supported silver-island (Ag@Si) plasmonic chips. In particular, we investigate their practical application of improving the traditional immunoassay such as the biotin-streptavidin-based protein assay and the protein-/nucleic acid-labeled cell and tissue samples. The protein assay shows a wavelength-dependent enhancement effect of the Ag@Si chip, with an enhancement factor ranging from 1.2 (at 532 nm) to 57.3 (at 800 nm). Moreover, for the protein- and nucleic acid-labeled cell and tissue samples, the Ag@Si chip provides a fluorescence enhancement factor of 3.0-4.1 (at 800 nm) and a significant improvement in the signal/background ratio for the microscopy images. Such a ready accommodation of the fluorescence-enhanced effect for the immunoassay samples with simple manipulations indicates broad potential for applications of the Ag@Si chip not only in biological studies but also in the clinical field.

Highly sensitive and reproducible silicon-based surface-enhanced Raman scattering sensors for real applications.

During the past few decades, thanks to silicon nanomaterials' outstanding electronic/optical/mechanical properties, large surface-to-volume ratio, abundant surface chemistry, facile tailorability and good compatibility with modern semiconductor industry, different dimensional silicon nanostructures have been widely employed for rationally designing and fabricating high-performance surface-enhanced Raman scattering (SERS) sensors for the detection of various chemical and biological species. Among these, two-dimensional silicon nanostructures made of metal nanoparticle-modified silicon wafers and three-dimensional silicon nanostructures made of metal nanoparticle-decorated SiNW arrays are of particular interest, and have been extensively exploited as promising silicon-based SERS-active substrates for the construction of high-performance SERS sensors. With an aim to retrospect these important and exciting achievements, we herein focus on reviewing recent representative studies on silicon-based SERS sensors for sensing applications from a broad perspective and possible future direction, promoting readers' awareness of these novel powerful silicon-based SERS sensing technologies. Firstly, we summarize the two unique merits of silicon-based SERS sensors, and those are high sensitivity and good reproducibility. Next, we present recent advances of two- and three-dimensional silicon-based SERS sensors, especially for real applications. Finally, we discuss the major challenges and prospects for the development of silicon-based SERS sensors.

Ultrasensitive, Specific, Recyclable, and Reproducible Detection of Lead Ions in Real Systems through a Polyadenine-Assisted, Surface-Enhanced Raman Scattering Silicon Chip.

It is of great significance to accurately and reliably detect trace lead(II) (Pb(2+)) ions, preferably at sub-nM level due to the possible long-term accumulation of Pb(2+) in the human body, which may cause serious threats to human health. However, a suitable Pb(2+) sensor meeting the demands is still scanty. Herein, we develop a polyadenine-assisted, surface-enhanced Raman scattering (SERS) silicon chip (0.5 cm × 0.5 cm) composed of core (Ag)-satellite (Au) nanoparticles (Ag-Au NPs)-decorated silicon wafers (Ag-Au NPs@Si) for high-performance Pb(2+) detection. Typically, strong SERS signals could be measured when DNAzyme conjugated on the SERS silicon chip is specifically activated by Pb(2+), cleaving the substrate strand into two free DNA strands. A good linearity exists between the normalized Raman intensities and the logarithmic concentrations of Pb(2+) ranging from 10 pM to 1 µM with a good correlation coefficient, R(2) of 0.997. Remarkably, Pb(2+) ions with a low concentration of 8.9 × 10(-12) M can be readily determined via the SERS silicon chip ascribed to its superior SERS enhancement, much lower than those (∼nM) reported by other SERS sensors. Additionally, the developed chip features good selectivity and recyclability (e.g., ∼11.1% loss of Raman intensity after three cycles). More importantly, the as-prepared chip can be used for accurate and reliable determination of unknown Pb(2+) ions in real systems including lake water, tap water and industrial wastewater, with the RSD value less than 12%.

A Poly Adenine-Mediated Assembly Strategy for Designing Surface-Enhanced Resonance Raman Scattering Substrates in Controllable Manners.

In this article, we introduce a Poly adenine (Poly A)-assisted fabrication method for rationally designing surface-enhanced resonance Raman scattering (SERRS) substrates in controllable and reliable manners, enabling construction of core-satellite SERRS assemblies in both aqueous and solid phase (e.g., symmetric core (Au)-satellite (Au) nanoassemblies (Au-Au NPs), and asymmetric Ag-Au NPs-decorated silicon wafers (Ag-Au NPs@Si)). Of particular significance, assembly density is able to be controlled by varying the length of the Poly A block (e.g., 10, 30, and 50 consecutive adenines at the 5' end of DNA sequence, Poly A10/A30/A50), producing the asymmetric core-satellite nanoassemblies with adjustable surface density of Au NPs assembly on core NPs surface. Based on quantitative interrogation of the relationship between SERRS performance and assemble density, the Ag-Au NPs@Si featuring the strongest SERRS enhancement factor (EF ≈ 10(7)) and excellent reproducibility can be achieved under optimal conditions. We further employ the resultant Ag-Au NPs@Si as a high-performance SERRS sensing platform for the selective and sensitive detection of mercury ions (Hg(2+)) in a real system, with a low detection limit of 100 fM, which is ∼5 orders of magnitude lower than the United States Environmental Protection Agency (USEPA)-defined limit (10 nM) in drinkable water. These results suggest the Poly A-mediated assembly method as new and powerful tools for designing high-performance SERRS substrates with controllable structures, facilitating improvement of sensitivity, reliability, and reproducibility of SERRS signals.

Peptide-Conjugated Fluorescent Silicon Nanoparticles Enabling Simultaneous Tracking and Specific Destruction of Cancer Cells.

We herein introduce a kind of fluorescent silicon nanoparticles (SiNPs) bioprobes, that is, peptides-conjugated SiNPs, which simultaneously feature small sizes (<10 nm), biological functionality, and stable and strong fluorescence (photoluminescent quantum yield (PLQY): ∼28%), as well as favorable biocompatibility. Taking advantage of these merits, we further demonstrate such resultant SiNPs bioprobes are superbly suitable for real-time immunofluorescence imaging of cancer cells. Meanwhile, malignant tumor cells could be specifically destroyed by the peptides-conjugated SiNPs, suggesting potential promise of simultaneous detection and treatment of cancer cells.

Simultaneous capture, detection, and inactivation of bacteria as enabled by a surface-enhanced Raman scattering multifunctional chip.

Herein, we present a multifunctional chip based on surface-enhanced Raman scattering (SERS) that effectively captures, discriminates, and inactivates pathogenic bacteria. The developed SERS chip is made of a silicon wafer decorated with silver nanoparticles and modified with 4-mercaptophenylboronic acid (4-MPBA). It was prepared in a straightforward manner by chemical reduction assisted by hydrogen fluoride etching, followed by the conjugation of 4-MPBA through AgS bonds. The dominant merits of the fabricated SERS chip include excellent reproducibility with a relative standard deviation (RSD) value smaller than 11.0 %, adaptable bacterial-capture efficiency (ca. 60 %) at low concentrations (500-2000 CFU mL(-1) ), a low detection limit (down to a concentration of 1.0×10(2)  cells mL(-1) ), and high antibacterial activity (an antibacterial rate of ca. 97 %). The SERS chip enabled sensitive and specific discrimination of Escherichia coli and Staphylococcus aureus from human blood.

Highly fluorescent, photostable, and ultrasmall silicon drug nanocarriers for long-term tumor cell tracking and in-vivo cancer therapy.

Silicon nanoparticle (SiNP) nanocarriers feature strong fluorescence, ultrasmall size, robust photostability, and tunable drug-loading capacity. Using SiNP nanocarriers, the first example of long-term cancer cell tracking is successfully demonstrated. Furthermore, in vivo experiments show that tumor-bearing mice treated with SiNP nanocarriers survive over 20 d without observable tumor growth, demonstrating the high-efficacy chemotherapy of the Si nanocarriers.

Surface-enhancement Raman scattering sensing strategy for discriminating trace mercuric ion (II) from real water samples in sensitive, specific, recyclable, and reproducible manners.

It is of essential importance to precisely probe mercury(II) (Hg(2+)) ions for environment-protection analysis and detection. To date, there still remain major challenges for accurate, specific, and reliable detection of Hg(2+) ions at subppt level. We herein employ gold nanoparticles (AuNPs) decorated silicon nanowire array (SiNWAr) as active surface-enhanced Raman scattering (SERS) substrates to construct a high-performance sensing platform assisted by DNA technology, enabling ultrasensitive detection of trace Hg(2+) in ∼64 min and with low sample consumption (∼30 µL). Typically, strong SERS signals could be detected when the single-stranded DNA structure converts to the hairpin structure in the presence of Hg(2+) ions, due to the formation of thymine (T)-Hg(2+)-T. As a result, Hg(2+) ions with a low concentration of 1 pM (0.2 ppt) can be readily discriminated, much lower than those (∼nM) reported for conventional analytical strategies. Water samples spiked with various Hg(2+) concentrations are further tested, exhibiting a good linear relationship between the normalized Raman intensities and the logarithmic concentrations of Hg(2+) ranging from 1 pM to 100 nM, with a correlation coefficient of R(2) = 0.998. In addition, such SERS sensor features excellent selectivity, facilely distinguishing Hg(2+) ions from various interfering substances. Moreover, this presented SERS sensor possesses good recyclability, preserving adaptable reproducibility during 5-time cyclic detection of Hg(2+). Furthermore, unknown Hg(2+) concentration in river water can be readily determined through our sensing strategy in accurate and reliable manners, with the RSD value of ∼9%.

Silicon nanohybrid-based surface-enhanced Raman scattering sensors.

Nanomaterial-based surface-enhanced Raman scattering (SERS) sensors are highly promising analytical tools, capable of ultrasensitive, multiplex, and nondestructive detection of chemical and biological species. Extensive efforts have been made to design various silicon nanohybrid-based SERS substrates such as gold/silver nanoparticle (NP)-decorated silicon nanowires, Au/Ag NP-decorated silicon wafers (AuNP@Si), and so forth. In comparison to free AuNP- and AgNP-based SERS sensors, the silicon nanohybrid-based SERS sensors feature higher enhancement factors (EFs) and excellent reproducibility, since SERS hot spots are efficiently coupled and stabilized through interconnection to the semiconducting silicon substrates. Consequently, in the past decade, giant advancements in the development of silicon nanohybrid-based SERS sensors have been witnessed for myriad sensing applications. In this review, the representative achievements related to the design of high-performance silicon nanohybrid-based SERS sensors and their use for chemical and biological analysis are reviewed in a detailed way. Furthermore, the major opportunities and challenges in this field are discussed from a broad perspective and possible future directions.

Stem-loop DNA-assisted silicon nanowires-based biochemical sensors with ultra-high sensitivity, specificity, and multiplexing capability.

A class of stem-loop DNA-assisted silicon nanowires (SiNWs)-based fluorescent biosensor is presented in this report. Significantly, the sensor enables rapid and sensitive detection of DNA targets with a concentration as low as 1 pM. Moreover, the large planar surface of SiNWs facilitates simultaneous assembly with different DNA strands, which is favorable for multiplexed DNA detection. On the other hand, the SiNWs-based sensor is highly efficacious for detecting heavy metal ions. Mercury ions (Hg(2+)) of low concentrations (e.g., 5 pM) are readily identified from its mixture with over 10 kinds of interfering metal ions, even in real water samples. Given that SiNWs can be fabricated in a facile, reproducible and low-cost manner, this kind of SiNWs-based high-performance sensor is expected to be a practical analytical tool for a variety of biological and environment-protection applications.

Hairpin DNA-assisted silicon/silver-based surface-enhanced Raman scattering sensing platform for ultrahighly sensitive and specific discrimination of deafness mutations in a real system.

Surface-enhanced Raman scattering (SERS) is well-recognized as a powerful analytical tool for ultrahighly sensitive detection of analytes. In this article, we present a kind of silicon-based SERS sensing platform made of a hairpin DNA-modified silver nanoparticles decorated silicon wafer (AgNPs@Si). In particular, the AgNPs@Si with a high enhancement factor (EF) value of ~4.5 × 10(7) is first achieved under optimum reaction conditions (i.e., pH = 12, reaction time = 20 min) based on systematic investigation. Such resultant AgNPs@Si is then employed for construction of a silicon-based SERS sensing platform through surface modification of hairpin DNA, which is superbly suitable for highly reproducible, multiplexed, and ultrasensitive DNA detection. A detection limit of 1 fM is readily achieved in a very reproducible manner along with high specificity. Most significantly, for the first time, we demonstrate that the silicon-based SERS platform is highly efficacious for discriminating deafness-causing mutations in a real system at the femtomolar level (500 fM), which is about 3-4 orders of magnitude lower than that (~5 nM) ever reported by conventional detection methods. Our results raise the exciting potential of practical SERS applications in biology and biomedicine.

A silicon-based antibacterial material featuring robust and high antibacterial activity.

In this article, we present a kind of silicon-based antibacterial material made of silver nanoparticle (AgNP)-decorated silicon wafers (AgNP@Si), which is facilely and rapidly (30 min) synthesized via a one-step reaction. Significantly, such a resultant silicon-based antibacterial material features stable and high antibacterial activity, preserving >99% antibacterial efficiency against E. coli during 30 day storage.

Silicon nanowire-based therapeutic agents for in vivo tumor near-infrared photothermal ablation.

The first example of silicon nanowire (SiNW)-based in vivo tumor phototherapy is presented. Gold nanoparticle (AuNP)-decorated SiNWs are employed as high-performance NIR hyperthermia agents for highly efficacious in vivo tumour ablation. Significantly, the overall survival time of SiNW-treated mice is drastically prolonged, with 100% of mice being alive and tumor-free for over 8 months, which is the longest survival time ever reported for tumor-bearing mice treated with nanomaterial-based NIR hyperthermia agents.

Photostable water-dispersible NIR-emitting CdTe/CdS/ZnS core-shell-shell quantum dots for high-resolution tumor targeting.

Near-infrared (NIR, 700-900 nm) fluorescent quantum dots are highly promising as NIR bioprobes for high-resolution and high-sensitivity bioimaging applications. In this article, we present a class of NIR-emitting CdTe/CdS/ZnS core-shell-shell quantum dots (QDs), which are directly prepared in aqueous phase via a facile microwave synthesis. Significantly, the prepared NIR-emitting QDs possess excellent aqueous dispersibility, strong photoluminescence, favorable biocompatibility, robust storage-, chemical-, and photo-stability, and finely tunable emission in the NIR range (700-800 nm). The QDs are readily functionalized with antibodies for use in immunofluorescent bioimaging, yielding highly spectrally and spatially resolved emission for in vitro and in vivo imaging. In comparison to the large size of 15-30 nm of the conventional NIR QDs, the extremely small size (≈ 4.2 nm or 7.5 nm measured by TEM or DLS, respectively) of our QDs offers great opportunities for high-efficiency and high-sensitivity targeted imaging in cells and animals.

Aqueous synthesized near-infrared-emitting quantum dots for RGD-based in vivo active tumour targeting.

Over the past two decades, fluorescent quantum dots (QDs) have been highly attractive for a myriad of bioapplications due to their unique optical properties. For bioimaging applications, QD-based in vivo specific tumour targeting is vitally important in the biological and biomedical fields. Aqueous synthesized QDs (aqQDs) exhibit excellent aqueous dispersibility without requiring any post-treatment and have small hydrodynamic diameters (generally <5 nm), which are highly useful for bioimaging applications. We herein present the first example of in vivo active tumour targeting using water-dispersed near-infrared-emitting aqQDs modified with Arg-Gly-Asp (RGD) peptides. In vitro and in vivo studies (e.g., tumour cell labelling, histological analysis, and active tumour targeting) demonstrate that the prepared RGD-decorated aqQDs exhibit highly bio-specific properties, enabling sensitive and specific targeting of tumour sites in both cells and living animals. Our results suggest that the new class of RGD-decorated aqQDs are highly promising as fluorescent bioprobes for a wide range of biological applications.

Surface-enhanced Raman scattering-based sensing in vitro: facile and label-free detection of apoptotic cells at the single-cell level.

Surface-enhanced Raman scattering (SERS) is well recognized as a powerful analytical tool, enabling ultrahigh sensitive detection of analytes at low concentrations, even down to single-molecule level. Of particular note, in comparison to sufficient investigations on SERS-based detection of biomolecules (e.g., DNA and protein), there has been relatively scanty information regarding in vitro and in vivo detection. In this Article, we demonstrate a kind of SERS-active substrate, i.e., AgNPs-decorated silicon wafer (AgNPs@Si), as a high-performance in vitro sensing platform for single-cell detection of apoptotic cells. The AgNPs@Si yields highly reproducible SERS signals with an enhancement factor of ∼10(7). Remarkably, cellular experiments show that facile, noninvasive, label-free, and sensitive detection of apoptotic cells is readily realized using the high-performance SERS-active platform. Three kinds of apoptotic cells treated with apoptosis inducer are facilely and sensitively detected at the single-cell level, suggesting the exciting potential of AgNPs@Si for SERS-based in vitro analysis and detection.

Microwave-assisted synthesis of biofunctional and fluorescent silicon nanoparticles using proteins as hydrophilic ligands.

Protective shell: A microwave-assisted method allows rapid production of biofunctional and fluorescent silicon nanoparticles (SiNPs), which can be used for cell labeling. Such SiNPs feature excellent aqueous dispersibility, are strongly fluorescent, storable, photostable, stable at different pH values, and biocompatible. The method opens new avenues for designing multifunctional SiNPs and related silicon nanostructures.

In vivo distribution, pharmacokinetics, and toxicity of aqueous synthesized cadmium-containing quantum dots.

Fluorescent Ⅱ-Ⅳ Quantum dots (QDs) have demonstrated to be highly promising biological probes for various biological and biomedical applications due to their many attractive merits, such as robust photostabilty, strong photoluminescence, and size-tunable fluorescence. Along with wide ranging bioapplications, concerns about their biosafety have attracted increasingly intensive attentions. In comparison to full investigation of in vitro toxicity, there has been only scanty information regarding in vivo toxicity of the QDs. Particularly, while in vivo toxicity of organic synthesized QDs (orQDs) have been investigated recently, there exist no comprehensive studies concerning in vivo behavior of aqueous synthesized QDs (aqQDs) up to present. Herein, we investigate short- and long-term in vivo biodistribution, pharmacokinetics, and toxicity of the aqQDs. Particularly, the aqQDs are initially accumulated in liver after short-time (0.5-4 h) post-injection, and then are increasingly absorbed by kidney during long-time (15-80 days) blood circulation. Moreover, obviously size-dependent biodistribution is observed: aqQDs with larger sizes are more quickly accumulated in the spleen. Furthermore, histological and biochemical analysis, and body weight measurement demonstrate that there is no overt toxicity of aqQDs in mice even at long-time exposure time. Our studies provide invaluable information for the design and development of aqQDs for biological and biomedical applications.