SERS Tags: Novel Optical Nanoprobes for Bioanalysis

CONTENTS1. Introduction1.1. Fundamental Theory of Surface-Enhanced Raman Scattering1.2. Optical Properties of SERS Tags2. Synthesis of SERS Tags2.1. Noble Metal Nanosubstrates2.1.1. Single Particle-Based SERS Substrates2.1.2. Nanoparticle Cluster-Based Substrates2.2. Raman Reporter Molecules2.2.1. Selection Principles and Reporter Types2.2.2. Self-Assembled Monolayer Coverage Strategy2.3. Surface Coating for Protection2.3.1. Biomolecule Coating2.3.2. Polymer Coating2.3.3. Liposome Coating2.3.4. Silica Coating2.4. Attachment of Targeting Molecules3. Bioanalysis Applications3.1. Ionic and Molecular Detection3.2. Pathogen Detection3.3. Live-Cell Imaging3.3.1. Cancer Marker Detection3.3.2. Intercellular Microenvironment Sensing3.4. Tissue SERS Imaging3.5. In Vivo SERS Imaging4. Challenges and Perspectives4.1. Reproducible Signal of SERS Tags4.1.1. Precisely Controlled Hot Spots for Nanosubstrates4.1.2. Calibration of SERS Intensities and Enhancements4.2. Improving Multiplexing Capability4.3. Reduced Size for Subcellular Imaging4.4. Development of Multifunctional Nanoplatforms4.4.1. Magnetic SERS Dots4.4.2. Multimodal Imaging Dots4.4.3. SERS Tag-Based Therapeutic Systems4.5. Biocompatibility5. Conclusions and Remarks</ul

Colorimetric determination of copper ions based on the catalytic leaching of silver from the shell of silver-coated gold nanorods

We have developed a method for the colorimetric determination of copper ions (Cu2+) that is based on the use of silver-coated gold nanorods (Au@Ag NRs). Its outstanding selectivity and sensitivity result from the catalytic leaching process that occurs between Cu2+, thiosulfate (S2O3 (2-)), and the surface of the Au@Ag NRs. The intrinsic color of the Au@Ag NRs changes from bright red to bluish green with decreasing thickness of the silver coating. The addition of Cu2+ accelerates the leaching of silver from the shell caused in the presence of S2O3 (2-). This result in a decrease in the thickness of the silver shell which is accompanied a change in color and absorption spectra of the colloidal solution. The shifts in the absorption maxima are linearly related to the concentrations of Cu2+ over the 3-1,000 nM concentration range (R = 0.996). The method is cost effective and was applied to the determination of Cu2+ in real water samples.We have developed a method for the colorimetric determination of copper ions (Cu2+) that is based on the use of silver-coated gold nanorods (Au@Ag NRs). Its outstanding selectivity and sensitivity result from the catalytic leaching process that occurs between Cu2+, thiosulfate (S2O3 (2-)), and the surface of the Au@Ag NRs. The intrinsic color of the Au@Ag NRs changes from bright red to bluish green with decreasing thickness of the silver coating. The addition of Cu2+ accelerates the leaching of silver from the shell caused in the presence of S2O3 (2-). This result in a decrease in the thickness of the silver shell which is accompanied a change in color and absorption spectra of the colloidal solution. The shifts in the absorption maxima are linearly related to the concentrations of Cu2+ over the 3-1,000 nM concentration range (R = 0.996). The method is cost effective and was applied to the determination of Cu2+ in real water samples

Colorimetric sensing of copper(II) based on catalytic etching of gold nanoparticles

Based on the catalytic etching of gold nanoparticles (AuNPs), a label-free colorimetric probe was developed for the detection of Cu2+ in aqueous solutions. AuNPs were first stabilized by hexadecyltrimethylammonium bromide in NH3-NH4Cl (0.6 M/0.1 M) solutions. Then thiosulfate (S2O32-) ions were introduced and AuNPs were gradually dissolved by dissolved oxygen. With the further addition of Cu2+, Cu(NH3)(4)(2+) oxidized AuNPs to produce Au(S2O3)(2)(3-) and Cu(S2O3)(3)(5-), while the later was oxidized to Cu(NH3)(4)(2+) again by dissolved oxygen. The dissolving rate of AuNPs was thereby remarkably promoted and Cu2+ acted as the catalyst. The process went on due to the sufficient supply of dissolved oxygen and AuNPs were rapidly etched. Meanwhile, a visible color change from red to colorless was observed. Subsequent tests confirmed such a non-aggregation-based method as a sensitive (LOD= 5.0 nM or 032 ppb) and selective (at least 100-fold over other metal ions except for Pb2+ and Mn2+) way for the detection of Cu2+ (linear range, 10-80 nM). Moreover, our results show that the color change induced by 40 nM Cu2+ can be easily observed by naked eyes, which is particularly applicable to fast on-site investigations. (C) 2013 Elsevier B.V. All rights reserved.Based on the catalytic etching of gold nanoparticles (AuNPs), a label-free colorimetric probe was developed for the detection of Cu2+ in aqueous solutions. AuNPs were first stabilized by hexadecyltrimethylammonium bromide in NH3-NH4Cl (0.6 M/0.1 M) solutions. Then thiosulfate (S2O32-) ions were introduced and AuNPs were gradually dissolved by dissolved oxygen. With the further addition of Cu2+, Cu(NH3)(4)(2+) oxidized AuNPs to produce Au(S2O3)(2)(3-) and Cu(S2O3)(3)(5-), while the later was oxidized to Cu(NH3)(4)(2+) again by dissolved oxygen. The dissolving rate of AuNPs was thereby remarkably promoted and Cu2+ acted as the catalyst. The process went on due to the sufficient supply of dissolved oxygen and AuNPs were rapidly etched. Meanwhile, a visible color change from red to colorless was observed. Subsequent tests confirmed such a non-aggregation-based method as a sensitive (LOD= 5.0 nM or 032 ppb) and selective (at least 100-fold over other metal ions except for Pb2+ and Mn2+) way for the detection of Cu2+ (linear range, 10-80 nM). Moreover, our results show that the color change induced by 40 nM Cu2+ can be easily observed by naked eyes, which is particularly applicable to fast on-site investigations. (C) 2013 Elsevier B.V. All rights reserved

Highly Sensitive Surface-Enhanced Raman Scattering Sensing of Heparin Based on Antiaggregation of Functionalized Silver Nanoparticles

We report a simple and sensitive surface-enhanced Raman scattering (SERS) platform for the detection of heparin, based on antiaggregation of 4-mercaptopyridine (4-MPY) functionalized silver nanoparticles (Ag NPs). Here, protamine was employed as a medium for inducing the aggregation of negatively charged 4-MPY functionalized Ag NPs through surface electrostatic interaction, which resulted in significantly enhanced Raman signal of the Raman reporter. However, in the presence of heparin, the interaction between heparin and protamine decreased the concentration of free protamine, which dissipated the aggregated 4-MPY functionalized Ag NPs and thus decreased Raman enhancement effect. The degree of aggregation and Raman enhancement effect was proportional to the concentration of added heparin. Under optimized assay conditions, good linear relationship was obtained over the range of 0.5-150 ng/mL (R-2 = 0.998) with a minimum detectable concentration of 0.5 ng/mL in standard aqueous solution. Furthermore, the developed method was also successfully applied for detecting heparin in fetal bovine serum samples with a linear range of 1-400 ng/mL.We report a simple and sensitive surface-enhanced Raman scattering (SERS) platform for the detection of heparin, based on antiaggregation of 4-mercaptopyridine (4-MPY) functionalized silver nanoparticles (Ag NPs). Here, protamine was employed as a medium for inducing the aggregation of negatively charged 4-MPY functionalized Ag NPs through surface electrostatic interaction, which resulted in significantly enhanced Raman signal of the Raman reporter. However, in the presence of heparin, the interaction between heparin and protamine decreased the concentration of free protamine, which dissipated the aggregated 4-MPY functionalized Ag NPs and thus decreased Raman enhancement effect. The degree of aggregation and Raman enhancement effect was proportional to the concentration of added heparin. Under optimized assay conditions, good linear relationship was obtained over the range of 0.5-150 ng/mL (R-2 = 0.998) with a minimum detectable concentration of 0.5 ng/mL in standard aqueous solution. Furthermore, the developed method was also successfully applied for detecting heparin in fetal bovine serum samples with a linear range of 1-400 ng/mL

Enhanced Nigrostriatal Neuron-specific, Long-term Expression by Using Neural-specific Promoters in Combination with Targeted Gene Transfer by Modified Helper Virus-free HSV-1 Vector Particles

Background: Direct gene transfer into neurons has potential for developing gene therapy treatments for specific neurological conditions, and for elucidating neuronal physiology. Due to the complex cellular composition of specific brain areas, neuronal type-specific recombinant gene expression is required for many potential applications of neuronal gene transfer. One approach is to target gene transfer to a specific type of neuron. We developed modified Herpes Simplex Virus (HSV-1) particles that contain chimeric glycoprotein C (gC) – glial cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) proteins. HSV-1 vector particles containing either gC – GDNF or gC – BDNF target gene transfer to nigrostriatal neurons, which contain specific receptors for GDNF or BDNF. A second approach to achieve neuronal type-specific expression is to use a cell type-specific promoter, and we have used the tyrosine hydroxylase (TH) promoter to restrict expression to catecholaminergic neurons or a modified neurofilament heavy gene promoter to restrict expression to neurons, and both of these promoters support long-term expression from HSV-1 vectors. To both improve nigrostriatal-neuron specific expression, and to establish that targeted gene transfer can be followed by long-term expression, we performed targeted gene transfer with vectors that support long-term, neuronal-specific expression. Results: Helper virus-free HSV-1 vector packaging was performed using either gC – GDNF or gC – BDNF and vectors that contain either the TH promoter or the modified neurofilament heavy gene promoter. Vector stocks were injected into the midbrain proximal to the substantia nigra, and the rats were sacrificed at either 4 days or 1 month after gene transfer. Immunofluorescent costaining was performed to detect both recombinant gene products and nigrostriatal neurons. The combination of targeted gene transfer with neuronal-specific promoters improved nigrostriatal neuron-specific expression (83 to 93%) compared to either approach alone, and supported long-term (1 month) expression at levels similar to those observed using untargeted gene transfer. Conclusion: Targeted gene transfer can be used in combination with neuronal-specific promoters to achieve a high level of nigrostriatal neuron-specific expression. Targeted gene transfer can be followed by long-term expression. Nigrostriatal neuron-specific expression may be useful for specific gene therapy approaches to Parkinson's disease or for genetic analyses of nigrostriatal neuron physiology

Dummy Molecularly Imprinted Polymers-Capped CdTe Quantum Dots for the Fluorescent Sensing of 2,4,6-Trinitrotoluene

Molecularly imprinted polymers (MIPs) with trinitrophenol (TNP) as a dummy template molecule capped with CdTe quantum dots (QDs) were prepared using 3-aminopropyltriethoxy silane (APTES) as the functional monomer and tetraethoxysilane (TEOS) as the cross linker through a seedgrowth method via a sol gel process (i.e., DMIP@QDs) for the sensing of 2,4,6-trinitrotoluene (TNT) on the basis of electron-transfer-induced fluorescence quenching. With the presence and increase of TNT in sample solutions, a Meisenheimer complex was formed between TNT and the primary amino groups on the surface of the QDs. The energy of the QDs was transferred to the complex, resulting in the quenching of the QDs and thus decreasing the fluorescence intensity, which allowed the TNT to be sensed optically. DMIP@QDs generated a significantly reduced fluorescent intensity within less than 10 min upon binding TNT. The fluorescence-quenching fractions of the sensor presented a satisfactory linearity with TNT concentrations in the range of 0.8-30 mu M, and its limit of detection could reach 0.28 mu M. The sensor exhibited distinguished selectivity and a high binding affinity to TNT over its possibly competing molecules of 2,4-dinitrophenol (DNP), 4-nitrophenol (4-NP), phenol, and dinitrotoluene (DNT) because there are more nitro groups in TNT and therefore a stronger electron-withdrawing ability and because it has a high similarity in shape and volume to TNP. The sensor was successfully applied to determine the amount of TNT in soil samples, and the average recoveries of TNT at three spiking levels ranged from 90.3 to 97.8% with relative standard deviations below 5.12%. The results provided an effective way to develop sensors for the rapid recognition and determination of hazardous materials from complex matrices.Molecularly imprinted polymers (MIPs) with trinitrophenol (TNP) as a dummy template molecule capped with CdTe quantum dots (QDs) were prepared using 3-aminopropyltriethoxy silane (APTES) as the functional monomer and tetraethoxysilane (TEOS) as the cross linker through a seedgrowth method via a sol gel process (i.e., DMIP@QDs) for the sensing of 2,4,6-trinitrotoluene (TNT) on the basis of electron-transfer-induced fluorescence quenching. With the presence and increase of TNT in sample solutions, a Meisenheimer complex was formed between TNT and the primary amino groups on the surface of the QDs. The energy of the QDs was transferred to the complex, resulting in the quenching of the QDs and thus decreasing the fluorescence intensity, which allowed the TNT to be sensed optically. DMIP@QDs generated a significantly reduced fluorescent intensity within less than 10 min upon binding TNT. The fluorescence-quenching fractions of the sensor presented a satisfactory linearity with TNT concentrations in the range of 0.8-30 mu M, and its limit of detection could reach 0.28 mu M. The sensor exhibited distinguished selectivity and a high binding affinity to TNT over its possibly competing molecules of 2,4-dinitrophenol (DNP), 4-nitrophenol (4-NP), phenol, and dinitrotoluene (DNT) because there are more nitro groups in TNT and therefore a stronger electron-withdrawing ability and because it has a high similarity in shape and volume to TNP. The sensor was successfully applied to determine the amount of TNT in soil samples, and the average recoveries of TNT at three spiking levels ranged from 90.3 to 97.8% with relative standard deviations below 5.12%. The results provided an effective way to develop sensors for the rapid recognition and determination of hazardous materials from complex matrices

Simple Way To Fabricate Novel Paper-Based Valves Using Plastic Comb Binding Spines

A novel strategy for fabricating the paper-based valves on microfluidic paper-based analytical devices (mu PADs) was described to control fluid in a user-friendly way. Initial prototypes of 3D mu PADs manipulate the spatial distribution of fluid within the device. The movable paper channel in a different layer could be achieved using the channel's connection or disconnection to realize the valve function using plastic comb binding spines (PCBS). The entire valve manipulation process was similar to a desk calendar that can be flipped over and turned back. It is notable that this kind of PCBS valve can control a fluid in a simple and easy way without the timing setting or any trigger, and this advantage makes it user-friendly for untrained users to carry out the complex and high throughput operations. The reusable plastic comb binding spines greatly reduce the cost of fabricating paper-based valves. To evaluate the performance, the actual samples of Fe (II) and nitrite were successfully analyzed. We hope this method will introduce a new approach to fabrication of paper-based valves on mu PADs in the future