Abstract

We present a study on the surface-enhanced Raman scattering (SERS) properties of Ag nanoparticle island substrates (NIS) and their applications for target oligonucleotide (OND) detection. It has been found that the surface nanostructure of NIS samples can be controlled with a good degree of reproducibility, and a high SERS enhancement can be achieved when the peak extinction wavelength of NIS is tuned to a spectral window (60nm) between the excitation wavelength and the scattered Raman wavelength. The highest SERS enhancement was obtained from the NIS substrates with a nominal thickness of 50Å. Detection of target OND was performed with a sandwich format in which the target OND was hybridized both to a capture OND immobilized on the NIS substrate, and a detection OND conjugated with a Raman-active dye for SERS signal generation. We compare the detection performance of two strategies based on the use of the detection OND with or without the gold nanoparticle (Au-NP). Our results confirm that, when the detection OND is coupled to the Au-NP, a better sensitivity for the target OND detection, in terms of a wider dynamic range and a lower detection limit (0.4fM versus 1nM without Au-NP), would be achieved.

© 2009 Optical Society of America

1. Introduction

Over the years, different assay readout strategies have been developed to achieve high sensitivity for gene detection and identification [1]. Techniques based on surface plasmon resonance (SPR) [2], surface-enhanced Raman scattering (SERS) [3, 4, 5, 6, 7, 8, 9, 10], quantum dots [11], microcantilevers [12], and atomic force microscopy [13] have been devised for biosensing. Among them, SERS, using both the intrinsic and the extrinsic Raman signals of certain labels for sensing biomolecules, has attracted most intense research interests. Such an expansion is due to several intrinsic merits that SERS offers. For example, SERS provides a high sensitivity and has potential to be used as a multiplexed readout technique [14, 15]. These merits can be attributed to a number of features, including the SERS enhancement factor (EF), which can be optimized to a level as high as 1014 for single molecule identification [15]. Also, when multiple labels are used for detection, the readout spectrum will be less overlapped, thus reducing the cross talk in multiplexed assays, since Raman bands are in general much narrower than those of fluorescence peaks. Moreover, in the SERS assays, it is possible to use one excitation wavelength to read multiple labels. Also, Raman signals are less susceptible to photobleaching than fluorescence [14, 15].

However, the acceptance of SERS as a general analytical tool has been hindered by the lack of well- engineered SERS substrate and systematic development of substrate technology [5, 6, 7]. Generally, SERS activities come from randomly distributed hot spots, which are primarily associated with nanosized col loidal noble metal aggregates deposited on the substrate. Nonetheless, not much information on the conditions to produce efficient SERS has been reported in the literature before.

In this work, we have optimized a strategy to produce an effective SERS platform for biosensing, which can be used for fast and sensitive detection of target DNA. Since SERS signals are essentially derived from the enhanced localized electric field associated with nanosized metal structures, it is most important to increase the density of the nanosized features and to maintain a high degree of reproduc ibility. For these reasons, we adopted a physical vapor deposition (PVD) route to prepare the metal layer because of its simplicity and the possibility of achieving high density of nanosized surface features. An investigation of the SERS properties of NIS prepared under various layer growth rates was performed systematically by studying the correlation between surface nanostructures of the NIS samples, their SERS spectra, and the EF [16, 17, 18]. Our work has revealed that the extinction spectrum or extinction maximum (λmax) of the NIS substrates is very sensitive to the surface nanostructures, which can be tuned by changing the thickness of the deposited metal, with a constant coating rate and vacuum condition of the PVD system.

For the sandwich DNA detection assay, a layer of single stranded capture OND with a thiol group at the 5 end was first immobilized on a NIS substrate so that, upon hybridization with the target OND, the target OND would in turn associate with the detection OND with FAM at the 5 end, through the Watson and Crick base pairing (Scheme 1) [19, 20]. Through this design, a particular Raman spectroscopic fingerprint can be identified after hybrid ization of the detection OND to the target OND according to the specific Raman-active dye [3, 5, 10, 14]. Yet, the common SERS schemes do not achieve the possible maximum EF because the detection OND are not sufficiently close to the SERS surface after hybridization with the target OND. In the present study, we adopted a new strategy that employed a detection OND capped with a gold nanoparticle (Au-NP, 20nm) at the 3 end. The Au-NP acted as a SERS promoter for the dye molecule when the detection OND was captured by the target and capture OND on substrate. We also compared the detection performance of the detection OND with or without Au-NP in terms of dynamic range and detection limit. Our results show that the target OND detection limit on the NIS substrate in the cases with or without Au-NP was found to be 0.4fM and 1nM, respectively.

2. Experimental Section

2A. Materials

Ag (99.99%) was purchased from D. F. Goldsmith (Evanston, Illinois). Glass substrates were obtained from Fisher Scientific (Pittsburgh, Pennsylvania). Tungsten vapor deposition boats were purchased from R. D. Mathis (Long Beach, California). Water (18MΩ.cm) was obtained from an ultrafilter system (Milli-Q, Millipore, Marlborough, Massachusetts). All chemicals and solvents were purchased at the highest purity grade and used without further purification.

6-mercapto-1-hexanol (MCH, 0.981g/mL), NaCl (AR grade, 99%), phosphate buffered solution (PBS, 10mM phosphate), ammonium hydroxide solution (30% NH3 basis), and Rhodamine 6G (Rh6G) were purchased from Sigma Aldrich (USA). Hydrogen peroxide and 96% sulfuric acid were purchased from Pierce (USA). Phosphine moiety [Bis(p-sulfonatophenyl)phenylphosphine] was obtained from STREM Chemicals (USA) and 20nm Au-NP solution was bought from Ted Pella Inc. (2.32nM, USA). All OND (0.2μmol, PAGE purification) were obtained from Tech Dragon (Hong Kong) and diluted to a concentration of 100mM for stock (in a 0.15M NaCl, pH 6.5 PBS). Capture OND p1 and detection OND p4 were modified with a thiol group (SH); detection OND p3 and p4 were labeled with Raman tag FAM. All OND were kept at 20°C and freshly prepared before use. The detailed sequence designs of OND (p1, p2, p3, and p4) are shown in Chart 1.

Chart 1. Sequences of OND used:

  • p1 (Capture OND): (HS)-5-(C6H12)-CGC ATT CAG GAT-3
  • p2 (Target OND): 5-TAC GAG TTG AGA ATC CTG AAT GCG-3
  • p3 (Detection OND): FAM-5-TCT CAA CTC GTA-(C3H6)-3
  • p4 (Detection OND): FAM-5-TCT CAA CTC GTA-(C3H6)-(SH)-3

2B. NIS Substrate Fabrication

Glass substrates were cleaned with piranha solution at 80°C for 1h first, and then a base treatment method with H2ONH4OH30%H2O2 (511) was used to render the surface hydrophilic. The metal films of Ag were deposited in a deposition system (Edwards, UK) with a base pressure of 106Torr. Different thicknesses of Ag, ranging from 10 to 200Å, were coated on the substrates for further study. The deposition rate for each sample was kept at 0.1Å/s with the aid of a quartz crystal microbalance (Maxtek Inc.). Chromium (10Å thick) was deposited on the glass substrates prior to the deposition of Ag in order to improve adhesion. The NIS substrates were stored in a dry, high-vacuum and dark sample chamber at room temperature prior to use within 2 days.

2C. Preparation of Receptor Oligonucleotide Substrates and Hybridization

Scheme 1 illustrates our immobilization strategy via HS–Ag binding and hybridization procedures for a typical sandwich DNA detection. The Ag-coated NIS substrate was immersed in capture OND p1 solution (4μM, 25μl) for approximately 3h, followed by a 1h exposure to MCH solution (1mM, 25μl). The self- assembled monolayers of MCH are between the capture of ONDs and used to block direct exposure of those gaps or unoccupied substrate to target OND. [5, 21, 22]. The substrate was then washed with water several times and dried in the air. The well-prepared capture OND substrate could selectively detect target OND p2 by complementary hybridization. Subsequently, the substrate was covered with target OND p2 solution (concentration 4μM, 25μl) and placed in a 37.5°C hybridization oven for 8h with an H2O saturated airtight container to prevent evaporation of the OND solution. Then a 0.75M NaCl PBS buffer solution was used repeatedly to flush away the excess target OND p2. The substrate was then air dried and ready for complementary hybridization with the detection OND to verify the presence of target OND p2 on the substrate. For this, detection OND p3 or p4 (4μM, 25μl) was added, and the substrate was placed in a humidity container at 37.5°C for 3h for hybridization. After hybridization, the substrate was washed copiously with water and dried by a centrifuge (1000RPM for 2min).

2D. Modification of Au-NPs with Probe Oligonucleotide

As shown in our sandwich assay for DNA detec tion (Scheme 1), Au-NPs modified, FAM-labeled, alkylthiol-capped OND p4 strands were used as probes to monitor the presence of specific target OND p2.

Phosphine was used to increase the stability of Au-NPs before their conjugation with detection OND p4. 10ml of 20nm NPs solution (2.32nM) was concentrated by a factor of 200, by precipitating the NPs using an ultracentrifuge (12,000RPM for 20min). The pellet was resuspended in 50μl of phosphine buffer (1mM phosphine in distilled water) [[8, 9, 14, 23, 24, 25]. The mixture was left overnight on a rocking platform at room temperature to allow sufficient time for surfactant exchange. The final concentration of the phosphine-coated Au particles was about 0.46μM.

On average, there are about 200 OND strands attached on each 20nm Au-NP [14, 23]. Then, OND p4 (4μM) was mixed with the concentrated phosphine-coated Au-NPs (0.46μM) in a molar ratio of 2001 at room temperature for about 12h. OND p4 was puri fied by centrifugation at 12,000RPM for 30min to remove excess reagent; the supernatant was discarded and the red oily precipitate was diluted with 1ml of 0.15M NaCl pH 6.5 PBS. The prepared conjugation solution of Au-NPs with detection OND p4 should be used freshly or stored at 20°C.

2E. SERS Apparatus

We used a Renishaw MicroRaman system (514nm, 50mW) equipped with a 50× objective ( 0.75 NA) and a 2μm pinhole to detect the SERS signal. The accumulation time for the Raman spectrum was typically 30s. Five spots at the same substrate were measured for each sample to minimize measurement errors. For experiments using Rh6G, the spectrum acquired from the blank substrate was used as a reference, and the background spectrum of the substrate coated with captured OND was used in the DNA experiments.

2F. Atomic Force Microscope and UV–Visible Spectrum Measurements

An atomic force microscope (AFM, Digital Instrument, Dimension 3100) and UV–visible–NIR spectrophotometer (Hitachi U-3501) were used for surface characterization. An AFM working in tapping mode under ambient conditions was used to study the surface morphology and structural variation of NIS substrates at different silver thicknesses. The extinction spectra were acquired using a UV–visible/NIR spectrophotometer to study the localized surface plasmon resonance (LSPR) properties of the NIS substrates.

3. Results and Discussion

In this study, we tried to study (1) the physical characteristics of the NIS based on the AFM, extinction spectra, and SERS results, and (2) the applicability and efficiency of these substrates as a DNA detection platform.

3A. Morphology Study and Statistical Analysis of λmax Distribution

An AFM study and following roughness analysis were performed to better understand the morpholog ical variation of the NIS substrates by changing the Ag thickness; the results are shown in Fig. 2. In this study, the PVD deposition conditions, such as deposition rate 0.1Å/s and vacuum 106Torr were kept constant for all depositions. From Fig. 2, it can be seen that a continuous and uniform Ag nanostructured surface began to develop at a thickness of 30Å. As expected, the fine nanostructures started to disappear when the thickness went beyond 110Å, as the size of the NPs increased with the thickness of the silver layer. This can also be revealed from the roughness analysis of the AFM results, as demonstrated in Fig. 2; the roughness, i.e., the nominal size of the NPs, actually increases with the thickness from 2.625 to 55.24nm, while the relative size variation decreases from 78.32% to 12.64% at the same time.

To understand the effect of the thickness on the morphological variation of nanostructures, UV– visible absorption spectra of several thicknesses, i.e., 10, 30, 50, 70, 90, and 110Å, were measured, as shown in Fig. 3. As can be seen, there is a notable trend of redshift in the extinction maximum λmax from 517.5 to 769nm when the thickness of the silver layer increased from 10 to 110Å. For the case of 110Å, the λmax approached the upper limit of the wavelength of our UV–visible spectrophotometer. The FWHMs of the corresponding spectra of different thicknesses vary from 100  to 200nm.

A more systematic statistical study of the extinction spectra and extinction maximum λmax of NIS substrates was conducted to explore the distribution of λmax caused by chip-to-chip variation. In this study, the extinction spectra of 20 NIS substrates of each thickness, i.e., 10, 30, 50, 70, and 90Å, were measured and analyzed with Gaussian fitting. All parameters derived from the Gaussian fitting were reported as the average value ±σ, where σ is the half-width at half-maximum. As shown in Fig. 4, the histograms in Figs. 4A, 4B, 4C, 4D, and 4E show that the average of λmax of thicknesses 10, 30, 50, 70, and 90Å are 517.5±5.1, 548.5±3.7, 554±2.4, 586.5±2.25, and 611±2.15nm, respectively. Figure 4F depicts the redshifting of the average λmax (with corresponding values of σ shown as error bars) for different thicknesses of the silver layer. There was also a notable reduction of 60% in the value of σ as we increased the thickness of the silver layer from 10 to 90Å. This result is consistent with the observation seen from the AFM images and roughness analysis shown in Fig. 2. For very thin layers below 30Å, the nanoislands exhibited quite observable variation in their size, whereas in the samples with larger thicknesses, the islands were more homogeneous, and the surface became more continuous.

3B. SERS Enhancement Factor Calculation

Typically, the enhancement performance can be quantitatively described by an EF of a particular adsorbate vibrational mode. The EF can be obtained by comparing the emission efficiency or signal strength per particular adsorbate molecule of the SERS sample and the normal Raman standard in terms of one vibrational mode. EF can be calculated using the following equation [15, 16, 19, 26]:

EF(1652cm1)=Nvol×IsurfNsurf×Ivol.
In our case, we used Rh6G as the adsorbate, and the Raman vibrational mode 1652cm1 of Rh6G was chosen to quantitatively calculate the EF of our NIS substrates. In the equation, Ivol is the standard Raman signal measured in counts with a 30s integration time, Isurf is the measured SERS signal in counts with an integration time of 30s, Nvol is the maximum number of Rh6G molecules that contributes to the measured standard Raman signal intensity, and Nsurf is the maximum number of Rh6G molecules that contributes to the measured SERS signal. To calculate the number of molecules that have been excited to produce emission by the incident laser spot, parameters such as the area of the focal volume calculated from the NA of the objective lens and the concentration of adsorbate molecules should be taken into account. In our study, we used a Renishaw MicroRaman system (50×, 0.75 NA) to acquire SERS from the NIS substrates and the standard Raman signals from a neat liquid sample of Rh6G (10mM, in distilled deionized water) deposited on the surface of a plastic plate. The focus volume of the 50× objective was found to be 8pl on the basis of 1/e2 analysis [27, 28, 29], using a Rh6G solution concentration of 10mM. The number of molecules contributing to the normal Raman signal measured from the standard was 8×1017mol. The known spot size of the 50× microscope objective was 2μm in diameter. A Rh6G (variant concentration) solution droplet (1μl) spread into a circle of about 3mm in diameter. Assuming that the solution evenly covered the NIS substrate surface after air drying and centrifugation, the number of molecules involved could be obtained by multiplying the exposed surface area by the surface density of the dried adsorbate Rh6G. In the experiment, multipoint measurements and averaging were used in order to reduce the measurement error induced by the “coffee ring” effect, which is a typical consequence of the air-dry method. We must point out that the reported collective enhancement here combines the contributions of resonance (chemical) effect and surface enhancement (electromagnetic) effect. Further experiments are needed in order to specifically isolate these two effects. In terms of the surface enhancement effect, it should be mentioned that only a portion of the molecules under excitation contribute to the measured signal from the NIS substrate because of the uneven distribution of hot spots. This suggests the actual EF for an individual nanoisland can be much higher than the observed value, which represents the average EF of a large collection of nanoislands.

3C. Correlation Among λex, λmax, and λvib

Figure 5 shows the correlation of UV–visible extinction spectra of our NIS samples with different Ag layer thicknesses and their corresponding SERS spectra from the Rh6G. The locations of λex for each thickness are also highlighted in the table to reveal their relative positions to λmax and λvib. The Raman spectra were acquired from dried Rh6G solution of concentration 1μM, using an integration time of 30s. λvib was the Raman-Stokes-shifted wavelength. A strong vibrational mode at 1652cm1, which was associated with the in-plate carbon–carbon (c–c) stretching vibration mode, was chosen for monitoring the EF in our experiments. As shown in Table 1, our results reveal that the strongest SERS intensity occurred when the extinction maximum λmax was located between λex (514nm) and λvib (562nm), especially when the thickness of the Ag film was around 50Å. Apart from this special region, the EF did not go beyond 10 when the SERS signal was measured against the background. Out of the 20 substrates at each thickness that had been studied, the EF was typically 107 when λmax was between the excitation wavelength λex (514nm) and the Stoke-shifted Raman wavelength λvib. The highest measured EF was about 4×108, at an Ag thickness of 50Å. The small variation of EF also suggests that the fabrication of NIS substrates using a PVD method would not introduce a large chip-to-chip or site-to-site variation in substrate surface morphology.

3D. DNA Detection using NIS

Using the optimized NIS (i.e., with an Ag layer thickness of 50Å, fabricated with a base pressure of 106Torr and a coating rate of 0.1Å/s), we performed a series of OND-detection experiments based on the sandwich assay shown in Scheme 1. The capture OND was modified to contain a thiol group (SH) to be embedded onto the Ag surface for hybridization experiments. Compared to other schemes for protein detection using avidin–biotin binding [30, 31], our approach of SH–Ag binding took full advantage of the surface ambient electromagnetic field by drastically reducing the distance between the Raman emitter and the substrate surface (results not shown). Instead of the one from the DNA itself, the Raman spectrum fingerprint of FAM labeled at the 5 end of the detection OND was acquired. This approach offered many advantages, for example, a large pool of dyes for multiplexed detection, reduction in spectra overlapping caused by similar DNA structures, much bigger cross sections and no photobleaching. Also, labeling the 5 end instead of the 3 end of the OND, which is different from the configuration commonly employed by other works [8, 9, 14, 23, 24, 25], would fur ther reduce the distance effect that does not favor SERS. The use of MCH as a blocker in our scheme was also essential to prevent nonspecific binding caused by direct exposure of the silver surface to the target and detection OND.

To find the detection limit of NIS substrates for the identification of target OND, various concentrations of target OND, ranging from micromolar to nanomolar, were employed. Meanwhile, the concentrations of capture and detection OND were kept constant, i.e., 4μM, in all our experiments. At this concentration, the surface binding area would be fully occupied by the capture OND. Our results indicate that the SERS signals from the detection OND p3 did not increase further when the concentration of the target OND was greater than 4μM (data not shown), suggesting that no further binding sites were left when the concentration was approaching 4μM. Result in Fig. 6A demonstrates a continuous but nonlinear decrease of signal when the concentration of the target decreased from 1μM to 1nM. Data at 1638cm1 were extracted from Fig. 6A and plotted in Fig. 6B. From the sigmoidal response curve depicted in Fig. 6B, the detection limit of the target OND was found to be to 1nM and the dynamic range was found in the range from 1μM to 1nM. Further increase in the concentration of the target OND beyond 1μM could not lead to a significant increase in SERS signal.

For the control experiment without the target OND, we used probe p3, which did not complementarily bind to capture OND p1. In such a condition, no SERS signal from FAM was detected (data not shown).

3E. Effect of Conjugation of Au-NPs and Oligonucleotide on DNA Detection

As the NIS substrate could not detect the target OND at a concentration smaller than 1nM, we tried another method to increase the detection limit further for practical application purpose. Works from other groups indicate that formation of a capture-OND–target-OND–detection-OND triplex is essential for single molecule detection [15, 19, 26, 27]. Therefore, in our triplex system, Au-NPs were conjugated to the detection OND. It is noteworthy that each Au-NP, having a diameter of 20nm, is capable of carrying 200 detection OND [14, 23]. Under this situation, both the number of Raman emitters and the possibility of the dye being present in the vicinity of a hot spot increased. These would enhance the SERS signal and the detection capability of the system.

Our experimental results indeed confirmed this enhancement in terms of the SERS intensity. As shown in Figs. 7A and 7B using 4μM of capture and detection OND again, a smaller target OND concentration at 0.4fM was detected. The sigmoidal curve in Fig. 7B also revealed that both the dynamic range and the detection limit were amplified when Au-NPs were attached to the 3 end of the detection OND. Compared to the results in Fig. 6, where no Au-NPs was employed, this scheme offered a wider dynamic range from 4μM to 0.4fM, with a detection limit extended to subfemtomolar concentration. Now, it becomes quite clear that the combined approach of using Au-NPs and NIS substrates is very useful for DNA biosensing in light of their high EF, simplicity, and consistency.

4. Conclusion

In this investigation, we have accomplished two goals. First, through a systematic study of deposition conditions and spectral characteristics of NIS substrates, we demonstrated that it is necessary to correlate the excitation wavelength, extinction maximum, and Raman-scattered wavelength in order to optimize the SERS performance of the NIS substrate for the detection of target OND [16, 17, 18]. It has become clear that NIS substrates offer practical and consistent SERS surfaces for a wide range of detections. Our experimental results using adsorbate Rh6G reveal that high signal-to-noise SERS spectra can be obtained when the extinction maximum wavelength of the silver-coated substrate is properly tuned to an 60nm spectral window between the excitation wavelength and the Stokes-shifted wavelength through varying the silver film thickness. The experimental SERS EF was typically from 107 to 108, with the highest level being 4×108, which occurs at a silver thickness of 50Å. Second, we have shown that a combined approach based on the use of NIS substrates and Au-NPs, which results in the formation of duplex and triplex configurations among the captured OND and target OND, can provide stronger SERS signals. Our experiments also demonstrate that both the dynamic range and the detection limit can be optimized by using Au-NP for the detecting OND. The dynamic range achieved in the present case is from 4μM to 0.4fM, while the detection limit is 0.4fM. The approach we report here renders that SERS is useful for cases where the target DNA concentration is extremely low. We also anticipate that our approach can be extended to a multiplexed platform for detecting disease-related genes by using different Raman-active dyes.

We acknowledge J. Li and Daniel H. C. Ong for helpful discussions. This work has been supported by a Research Grants Council (RGC) grant under Competitive Earmarked Research Grant (CERG) project 411907. Partial funding support from the Shun Hing Institute for Advanced Engineering, The Chinese University of Hong Kong (CUHK), and a research studentship from CUHK for W. Yuan are also gratefully acknowledged.

Tables Icon

Table 1. Enhancement Factors of Vibration Mode 1652cm1 (λvib: 562nm) Obtained from Rh6G at Different Ag Layer Thicknesses Versus Their Corresponding Extinction Maxima λmax a

 

Fig. 1 Immobilization strategy via HS–Ag binding and hybridization procedure for a typical sandwich DNA detection.

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Fig. 2 AFM images (2μm×2μm) of nanoparticle island (NIS) substrates with different Ag thicknesses from 10 to 200Å on top of 10Å Cr, rough analysis of corresponding AFM images is also shown. All substrates were fabricated by PVD with a coating rate of 0.1   Å/s and a vacuum of 106Torr.

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Fig. 3 UV–visible extinction spectra of NIS substrates with different Ag thicknesses; λmax stands for extinction maximum.

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Fig. 4 Statistical study of extinction maximum λmax of NIS substrates with different Ag thicknesses: A, 10Å; B, 30Å; C, 50Å; D, 70Å; and E, 90Å, where σ is the half-width at half-maximum of the Gaussian-fitted curves. F shows the redshifting trend of the average λmax with increasing Ag thickness; error bars indicate the values of σ.

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Fig. 5 UV–visible extinction spectra of NIS samples with different Ag thicknesses and their corresponding SERS spectra of Rh6G obtained from Ag thicknesses of 10, 30, 50, 70, and 90Å, respectively; the bottom trace shows the typical background spectrum of the blank substrate.

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Fig. 6 A: SERS results of target oligonucleotide detection (concentrations from 1μM to 1nM). The spectra shown were given by the detection OND p3 with Raman label FAM; B: corresponding sigmoidal response curve of vibration mode 1652cm1 of FAM, which was normalized by maximum intensity; the bottom trace shows the background spectrum of the substrate coated with the receptor OND.

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Fig. 7 Target OND detection with the aid of Au-NPs-capped detection OND p4 with Raman label FAM. A, SERS spectra of target OND (concentrations from 4μM to 0.4fM), B, normalized sigmoidal response curve of vibration mode 1652cm1 of FAM versus the change of target concentrations; the bottom trace shows the background spectrum of the substrate coated with the receptor OND.

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1. E. P. Diamandis and T. K. Christopoulous, eds., Immunoassay (Academic, 1996).

2. G. J. Wegner, H. J. Lee, and R. M. Corn, “Characterization and optimization of peptide arrays for the study of epitope- antibody interactions using surface plasmon resonance imaging,” Anal. Chem. 74, 5161–5168 (2002). [CrossRef]   [PubMed]  

3. M. B. Wabuyele and T. Vo-Dinh, “Detection of human immunodeficiency virus type 1 DNA sequence using plasmonics nanoprobes,” Anal. Chem. 77, 7810–7815 (2005). [CrossRef]   [PubMed]  

4. J. M. Song, P. M. Kasili, G. D. Griffin, and T. Vo-Dinh, “Detection of cytochrome c in a single cell using an optical nanobiosensor,” Anal. Chem 76, 2591–2594 (2004). [CrossRef]   [PubMed]  

5. M. Culha, D. Stokes, L. R. Allain, and T. Vo-Dinh, “Surface- enhanced Raman scattering substrate based on a self- assembled monolayer for use in gene diagnostics,” Anal. Chem. 75, 6196–6201 (2003). [CrossRef]   [PubMed]  

6. X. Zhang, J. Zhao, A. V. Whitney, J. W. Elam, and R. P. Van Duyne, “Ultrastable substrates for surface-enhanced Raman spectroscopy: Al2O3 overlayers fabricated by atomic layer deposition yield improved anthrax biomarker detection,” J. Am. Chem. Soc. 128, 10304–10309 (2006). [CrossRef]   [PubMed]  

7. X. Zhang, M. A. Young, O. Lyandres, and R. P. Van Duyne, “Rapid detection of an anthrax biomarker by surface- enhanced Raman spectroscopy,” J. Am. Chem. Soc. 127, 4484–4489 (2005). [CrossRef]   [PubMed]  

8. J. Driskell, K. M. Kwarta, R. J. Lipert, and M. D. Porter, “Low-level detection of viral pathogens by a surface-enhanced Raman scattering based immunoassay,” Anal. Chem. 77, 6147–6154 (2005). [CrossRef]   [PubMed]  

9. D. S. Grubisha, R. J. Lipert, H. Park, J. Driskell, and M. D. Porter, “Femtomolar detection of prostate-specific antigen: an immunoassay based on surface-enhanced Raman scattering and immunogold labels,” Anal. Chem. 75, 5936–5943 (2003). [CrossRef]   [PubMed]  

10. S. E. J. Bell and N. M. S. Sirimuthu, “Surface-enhanced Raman spectroscopy (SERS) for sub-micromolar detection of DNA/RNA mononucleotides,” J. Am. Chem. Soc. 128, 15580–15581 (2006). [CrossRef]   [PubMed]  

11. W. C. W. Chan and S. Nie, “Quantum dot bioconjugates for ultrasensitive nonisotopic detection,” Science 281, 2016–2018 (1998). [CrossRef]   [PubMed]  

12. G. Wu, R. H. Datar, K. M. Hansen, T. Thundat, R. J. Cote, and A. Majumdar, “Bioassay of prostate-specific antigen (PSA) using microcantilevers,” Nat. Biotechnol. 19, 856–860 (2001). [CrossRef]   [PubMed]  

13. V. W. Jones, J. R. Kenseth, M. D. Porter, C. L. Mosher, and E. Henderson, “Microminiaturized immunoassays using atomic force microscopy and compositionally patterned antigen arrays,” Anal. Chem. 70, 1233–1241 (1998). [CrossRef]   [PubMed]  

14. Y-W. Cao, R-C. Jin, and C. A. Mirkin, “Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection,” Science 297, 1536–1540 (2002). [CrossRef]   [PubMed]  

15. S. Nie and S. R. Emory, “Probing single molecules and single nanoparticles by surface-enhanced Raman scattering,” Science 275, 1102–1106 (1997). [CrossRef]   [PubMed]  

16. C. L. Haynes and R. P. Van Duyne, “Plasmon-sampled surface-enhanced Raman excitation spectroscopy,” J. Phys. Chem. B 107, 7426–7433 (2003). [CrossRef]  

17. A. D. McFarland, M. A. Young, J. A. Dieringer, and R. P. Van Duyne, “Wavelength-scanned surface-enhanced Raman excitation spectroscopy,” J. Phys. Chem. B 109, 11279–11285 (2005). [CrossRef]  

18. G. C. Schatz and R. P. Van Duyne, Handbookof Vibrational Spectroscopy, J.P. M.R. ChalmersGriffiths, eds. (Wiley, 2002), Vol. 1, pp. 759–774.

19. K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99, 2957–2976 (1999). [CrossRef]  

20. L. A. Gearheart, H. J. Ploehn, and C. J. Murphy, “Oligonucleotide adsorption to gold nanoparticles: a surface-enhanced Raman spectroscopy study of intrinsically bent DNA,” J. Phys. Chem. B 105, 12609–12615 (2001). [CrossRef]  

21. R. Levicky, T. M. Herne, M. J. Tarlov, and S. K. Satija, “Using self-assembly to control the structure of DNA monolayers on gold: a neutron reflectivity study,” J. Am. Chem. Soc. 120, 9787–9792 (1998). [CrossRef]  

22. A. B. Steel, T. M. Herne, and M. J. Tarlov, “Electrochemical quantitation of DNA immobilized on gold,” Anal. Chem. 70, 4670–4677 (1998). [CrossRef]   [PubMed]  

23. G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47–52 (2006). [CrossRef]  

24. C-C. You, A. Chompoosor, and V. M. Rotello, “The biomacromolecule-nanoparticle interface,” Nanotoday 2, 34–43 (2007). [CrossRef]  

25. P. Alivisatos, “The use of nanocrystals in biological detection,” Nat. Biotechnol. 22, 47–52 (2004). [CrossRef]   [PubMed]  

26. K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, “Single molecule detection using surface-enhanced Raman scattering,” Phys. Rev. Lett. 78, 1667–1670 (1997). [CrossRef]  

27. S. Nie and R. N. Zare, “Optical detection of single molecules,” Annu. Rev. Biophys. Biomol. Struct. 26, 567–596 (1997). [CrossRef]   [PubMed]  

28. V. Westphal and S. W. Hell, “Nanoscale resolution in the focal plane of an optical microscope,” Phys. Rev. Lett. 94, 143903–143910 (2005). [CrossRef]   [PubMed]  

29. W. Denk, J. H. Stricker, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248, 73–76 (1990). [CrossRef]   [PubMed]  

30. M. Howarth, D. J-F. Chinnapen, K. Gerrow, P. C. Dorrestein, M. R. Grandy, N. L. Kelleher, A. El-Husseini, and A. Y. Ting, “A monovalent streptavidin with a single femtomolar biotin binding site,” Nat. Methods 3, 267–273 (2006). [CrossRef]   [PubMed]  

31. P. R. Langer, A. A. Waldrop, and D. C. Ward, “Enzymatic synthesisof biotin-labeled polynucleotides: novel nucleic acid affinity probes,” Proc. Natl. Acad. Sci. USA 78, 6633–6637 (1981). [CrossRef]  

References

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  1. E. P. Diamandis and T. K. Christopoulous, eds., Immunoassay (Academic, 1996).
  2. G. J. Wegner, H. J. Lee and R. M. Corn, “Characterization and optimization of peptide arrays for the study of epitope-antibody interactions using surface plasmon resonance imaging,” Anal. Chem. 74, 5161-5168 (2002).
    [CrossRef] [PubMed]
  3. M. B. Wabuyele and T. Vo-Dinh, “Detection of human immunodeficiency virus type 1 DNA sequence using plasmonics nanoprobes,” Anal. Chem. 77, 7810-7815 (2005).
    [CrossRef] [PubMed]
  4. J. M. Song, P. M. Kasili, G. D. Griffin, and T. Vo-Dinh, “Detection of cytochrome c in a single cell using an optical nanobiosensor,” Anal. Chem 76, 2591-2594 (2004).
    [CrossRef] [PubMed]
  5. M. Culha, D. Stokes, L. R. Allain, and T. Vo-Dinh, “Surface-enhanced Raman scattering substrate based on a self-assembled monolayer for use in gene diagnostics,” Anal. Chem. 75, 6196-6201 (2003).
    [CrossRef] [PubMed]
  6. X. Zhang, J. Zhao, A. V. Whitney, J. W. Elam, and R. P. Van Duyne, “Ultrastable substrates for surface-enhanced Raman spectroscopy: Al2O3 overlayers fabricated by atomic layer deposition yield improved anthrax biomarker detection,” J. Am. Chem. Soc. 128, 10304-10309 (2006).
    [CrossRef] [PubMed]
  7. X. Zhang, M. A. Young, O. Lyandres, and R. P. Van Duyne, “Rapid detection of an anthrax biomarker by surface-enhanced Raman spectroscopy,” J. Am. Chem. Soc. 127, 4484-4489 (2005).
    [CrossRef] [PubMed]
  8. J. Driskell, K. M. Kwarta, R. J. Lipert, and M. D. Porter, “Low-level detection of viral pathogens by a surface-enhanced Raman scattering based immunoassay,” Anal. Chem. 77, 6147-6154 (2005).
    [CrossRef] [PubMed]
  9. D. S. Grubisha, R. J. Lipert, H. Park, J. Driskell, and M. D. Porter, “Femtomolar detection of prostate-specific antigen: an immunoassay based on surface-enhanced Raman scattering and immunogold labels,” Anal. Chem. 75, 5936-5943(2003).
    [CrossRef] [PubMed]
  10. S. E. J. Bell and N. M. S. Sirimuthu, “Surface-enhanced Raman spectroscopy (SERS) for sub-micromolar detection of DNA/RNA mononucleotides,” J. Am. Chem. Soc. 128, 15580-15581 (2006).
    [CrossRef] [PubMed]
  11. W. C. W. Chan and S. Nie, “Quantum dot bioconjugates for ultrasensitive nonisotopic detection,” Science 281, 2016-2018(1998).
    [CrossRef] [PubMed]
  12. G. Wu, R. H. Datar, K. M. Hansen, T. Thundat, R. J. Cote, and A. Majumdar, “Bioassay of prostate-specific antigen (PSA) using microcantilevers,” Nat. Biotechnol. 19, 856-860 (2001).
    [CrossRef] [PubMed]
  13. V. W. Jones, J. R. Kenseth, M. D. Porter, C. L. Mosher, and E. Henderson, “Microminiaturized immunoassays using atomic force microscopy and compositionally patterned antigen arrays,” Anal. Chem. 70, 1233-1241 (1998).
    [CrossRef] [PubMed]
  14. Y-W. Cao, R-C. Jin, and C. A. Mirkin, “Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection,” Science 297, 1536-1540 (2002).
    [CrossRef] [PubMed]
  15. S. Nie and S. R. Emory, “Probing single molecules and single nanoparticles by surface-enhanced Raman scattering,” Science 275, 1102-1106 (1997).
    [CrossRef] [PubMed]
  16. C. L. Haynes and R. P. Van Duyne, “Plasmon-sampled surface-enhanced Raman excitation spectroscopy,” J. Phys. Chem. B 107, 7426-7433 (2003).
    [CrossRef]
  17. A. D. McFarland, M. A. Young, J. A. Dieringer, and R. P. Van Duyne, “Wavelength-scanned surface-enhanced Raman excitation spectroscopy,” J. Phys. Chem. B 109, 11279-11285(2005).
    [CrossRef]
  18. G. C. Schatz and R. P. Van Duyne, Handbook of Vibrational Spectroscopy, J. M. Chalmers and P. R. Griffiths, eds. (Wiley, 2002), Vol. 1, pp. 759-774.
  19. K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99, 2957-2976 (1999).
    [CrossRef]
  20. L. A. Gearheart, H. J. Ploehn, and C. J. Murphy, “Oligonucleotide adsorption to gold nanoparticles: a surface-enhanced Raman spectroscopy study of intrinsically bent DNA,” J. Phys. Chem. B 105, 12609-12615 (2001).
    [CrossRef]
  21. R. Levicky, T. M. Herne, M. J. Tarlov, and S. K. Satija, “Using self-assembly to control the structure of DNA monolayers on gold: a neutron reflectivity study,” J. Am. Chem. Soc. 120, 9787-9792 (1998).
    [CrossRef]
  22. A. B. Steel, T. M. Herne, and M. J. Tarlov, “Electrochemical quantitation of DNA immobilized on gold,” Anal. Chem. 70, 4670-4677 (1998).
    [CrossRef] [PubMed]
  23. G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47-52 (2006).
    [CrossRef]
  24. C-C. You, A. Chompoosor, and V. M. Rotello, “The biomacromolecule-nanoparticle interface,” Nanotoday 2, 34-43 (2007).
    [CrossRef]
  25. P. Alivisatos, “The use of nanocrystals in biological detection,” Nat. Biotechnol. 22, 47-52 (2004).
    [CrossRef] [PubMed]
  26. K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, “Single molecule detection using surface-enhanced Raman scattering,” Phys. Rev. Lett. 78, 1667-1670 (1997).
    [CrossRef]
  27. S. Nie and R. N. Zare, “Optical detection of single molecules,” Annu. Rev. Biophys. Biomol. Struct. 26, 567-596 (1997).
    [CrossRef] [PubMed]
  28. V. Westphal and S. W. Hell, “Nanoscale resolution in the focal plane of an optical microscope,” Phys. Rev. Lett. 94, 143903-143910 (2005).
    [CrossRef] [PubMed]
  29. W. Denk, J. H. Stricker, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248, 73-76 (1990).
    [CrossRef] [PubMed]
  30. M. Howarth, D. J-F. Chinnapen, K. Gerrow, P. C. Dorrestein, M. R. Grandy, N. L. Kelleher, A. El-Husseini, and A. Y. Ting, “A monovalent streptavidin with a single femtomolar biotin binding site,” Nat. Methods 3, 267-273 (2006).
    [CrossRef] [PubMed]
  31. P. R. Langer, A. A. Waldrop, and D. C. Ward, “Enzymatic synthesis of biotin-labeled polynucleotides: novel nucleic acid affinity probes,” Proc. Natl. Acad. Sci. USA 78, 6633-6637(1981).
    [CrossRef]

2007 (1)

C-C. You, A. Chompoosor, and V. M. Rotello, “The biomacromolecule-nanoparticle interface,” Nanotoday 2, 34-43 (2007).
[CrossRef]

2006 (4)

M. Howarth, D. J-F. Chinnapen, K. Gerrow, P. C. Dorrestein, M. R. Grandy, N. L. Kelleher, A. El-Husseini, and A. Y. Ting, “A monovalent streptavidin with a single femtomolar biotin binding site,” Nat. Methods 3, 267-273 (2006).
[CrossRef] [PubMed]

G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47-52 (2006).
[CrossRef]

X. Zhang, J. Zhao, A. V. Whitney, J. W. Elam, and R. P. Van Duyne, “Ultrastable substrates for surface-enhanced Raman spectroscopy: Al2O3 overlayers fabricated by atomic layer deposition yield improved anthrax biomarker detection,” J. Am. Chem. Soc. 128, 10304-10309 (2006).
[CrossRef] [PubMed]

S. E. J. Bell and N. M. S. Sirimuthu, “Surface-enhanced Raman spectroscopy (SERS) for sub-micromolar detection of DNA/RNA mononucleotides,” J. Am. Chem. Soc. 128, 15580-15581 (2006).
[CrossRef] [PubMed]

2005 (5)

M. B. Wabuyele and T. Vo-Dinh, “Detection of human immunodeficiency virus type 1 DNA sequence using plasmonics nanoprobes,” Anal. Chem. 77, 7810-7815 (2005).
[CrossRef] [PubMed]

X. Zhang, M. A. Young, O. Lyandres, and R. P. Van Duyne, “Rapid detection of an anthrax biomarker by surface-enhanced Raman spectroscopy,” J. Am. Chem. Soc. 127, 4484-4489 (2005).
[CrossRef] [PubMed]

J. Driskell, K. M. Kwarta, R. J. Lipert, and M. D. Porter, “Low-level detection of viral pathogens by a surface-enhanced Raman scattering based immunoassay,” Anal. Chem. 77, 6147-6154 (2005).
[CrossRef] [PubMed]

A. D. McFarland, M. A. Young, J. A. Dieringer, and R. P. Van Duyne, “Wavelength-scanned surface-enhanced Raman excitation spectroscopy,” J. Phys. Chem. B 109, 11279-11285(2005).
[CrossRef]

V. Westphal and S. W. Hell, “Nanoscale resolution in the focal plane of an optical microscope,” Phys. Rev. Lett. 94, 143903-143910 (2005).
[CrossRef] [PubMed]

2004 (2)

P. Alivisatos, “The use of nanocrystals in biological detection,” Nat. Biotechnol. 22, 47-52 (2004).
[CrossRef] [PubMed]

J. M. Song, P. M. Kasili, G. D. Griffin, and T. Vo-Dinh, “Detection of cytochrome c in a single cell using an optical nanobiosensor,” Anal. Chem 76, 2591-2594 (2004).
[CrossRef] [PubMed]

2003 (3)

M. Culha, D. Stokes, L. R. Allain, and T. Vo-Dinh, “Surface-enhanced Raman scattering substrate based on a self-assembled monolayer for use in gene diagnostics,” Anal. Chem. 75, 6196-6201 (2003).
[CrossRef] [PubMed]

D. S. Grubisha, R. J. Lipert, H. Park, J. Driskell, and M. D. Porter, “Femtomolar detection of prostate-specific antigen: an immunoassay based on surface-enhanced Raman scattering and immunogold labels,” Anal. Chem. 75, 5936-5943(2003).
[CrossRef] [PubMed]

C. L. Haynes and R. P. Van Duyne, “Plasmon-sampled surface-enhanced Raman excitation spectroscopy,” J. Phys. Chem. B 107, 7426-7433 (2003).
[CrossRef]

2002 (2)

G. J. Wegner, H. J. Lee and R. M. Corn, “Characterization and optimization of peptide arrays for the study of epitope-antibody interactions using surface plasmon resonance imaging,” Anal. Chem. 74, 5161-5168 (2002).
[CrossRef] [PubMed]

Y-W. Cao, R-C. Jin, and C. A. Mirkin, “Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection,” Science 297, 1536-1540 (2002).
[CrossRef] [PubMed]

2001 (2)

G. Wu, R. H. Datar, K. M. Hansen, T. Thundat, R. J. Cote, and A. Majumdar, “Bioassay of prostate-specific antigen (PSA) using microcantilevers,” Nat. Biotechnol. 19, 856-860 (2001).
[CrossRef] [PubMed]

L. A. Gearheart, H. J. Ploehn, and C. J. Murphy, “Oligonucleotide adsorption to gold nanoparticles: a surface-enhanced Raman spectroscopy study of intrinsically bent DNA,” J. Phys. Chem. B 105, 12609-12615 (2001).
[CrossRef]

1999 (1)

K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99, 2957-2976 (1999).
[CrossRef]

1998 (4)

V. W. Jones, J. R. Kenseth, M. D. Porter, C. L. Mosher, and E. Henderson, “Microminiaturized immunoassays using atomic force microscopy and compositionally patterned antigen arrays,” Anal. Chem. 70, 1233-1241 (1998).
[CrossRef] [PubMed]

W. C. W. Chan and S. Nie, “Quantum dot bioconjugates for ultrasensitive nonisotopic detection,” Science 281, 2016-2018(1998).
[CrossRef] [PubMed]

R. Levicky, T. M. Herne, M. J. Tarlov, and S. K. Satija, “Using self-assembly to control the structure of DNA monolayers on gold: a neutron reflectivity study,” J. Am. Chem. Soc. 120, 9787-9792 (1998).
[CrossRef]

A. B. Steel, T. M. Herne, and M. J. Tarlov, “Electrochemical quantitation of DNA immobilized on gold,” Anal. Chem. 70, 4670-4677 (1998).
[CrossRef] [PubMed]

1997 (3)

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, “Single molecule detection using surface-enhanced Raman scattering,” Phys. Rev. Lett. 78, 1667-1670 (1997).
[CrossRef]

S. Nie and R. N. Zare, “Optical detection of single molecules,” Annu. Rev. Biophys. Biomol. Struct. 26, 567-596 (1997).
[CrossRef] [PubMed]

S. Nie and S. R. Emory, “Probing single molecules and single nanoparticles by surface-enhanced Raman scattering,” Science 275, 1102-1106 (1997).
[CrossRef] [PubMed]

1990 (1)

W. Denk, J. H. Stricker, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248, 73-76 (1990).
[CrossRef] [PubMed]

1981 (1)

P. R. Langer, A. A. Waldrop, and D. C. Ward, “Enzymatic synthesis of biotin-labeled polynucleotides: novel nucleic acid affinity probes,” Proc. Natl. Acad. Sci. USA 78, 6633-6637(1981).
[CrossRef]

Alivisatos, A. P.

G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47-52 (2006).
[CrossRef]

Alivisatos, P.

P. Alivisatos, “The use of nanocrystals in biological detection,” Nat. Biotechnol. 22, 47-52 (2004).
[CrossRef] [PubMed]

Allain, L. R.

M. Culha, D. Stokes, L. R. Allain, and T. Vo-Dinh, “Surface-enhanced Raman scattering substrate based on a self-assembled monolayer for use in gene diagnostics,” Anal. Chem. 75, 6196-6201 (2003).
[CrossRef] [PubMed]

Bear, D. G.

G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47-52 (2006).
[CrossRef]

Bell, S. E. J.

S. E. J. Bell and N. M. S. Sirimuthu, “Surface-enhanced Raman spectroscopy (SERS) for sub-micromolar detection of DNA/RNA mononucleotides,” J. Am. Chem. Soc. 128, 15580-15581 (2006).
[CrossRef] [PubMed]

Cao, Y-W.

Y-W. Cao, R-C. Jin, and C. A. Mirkin, “Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection,” Science 297, 1536-1540 (2002).
[CrossRef] [PubMed]

Chan, W. C. W.

W. C. W. Chan and S. Nie, “Quantum dot bioconjugates for ultrasensitive nonisotopic detection,” Science 281, 2016-2018(1998).
[CrossRef] [PubMed]

Chen, F. F.

G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47-52 (2006).
[CrossRef]

Chinnapen, D. J-F.

M. Howarth, D. J-F. Chinnapen, K. Gerrow, P. C. Dorrestein, M. R. Grandy, N. L. Kelleher, A. El-Husseini, and A. Y. Ting, “A monovalent streptavidin with a single femtomolar biotin binding site,” Nat. Methods 3, 267-273 (2006).
[CrossRef] [PubMed]

Chompoosor, A.

C-C. You, A. Chompoosor, and V. M. Rotello, “The biomacromolecule-nanoparticle interface,” Nanotoday 2, 34-43 (2007).
[CrossRef]

Corn, R. M.

G. J. Wegner, H. J. Lee and R. M. Corn, “Characterization and optimization of peptide arrays for the study of epitope-antibody interactions using surface plasmon resonance imaging,” Anal. Chem. 74, 5161-5168 (2002).
[CrossRef] [PubMed]

Cote, R. J.

G. Wu, R. H. Datar, K. M. Hansen, T. Thundat, R. J. Cote, and A. Majumdar, “Bioassay of prostate-specific antigen (PSA) using microcantilevers,” Nat. Biotechnol. 19, 856-860 (2001).
[CrossRef] [PubMed]

Culha, M.

M. Culha, D. Stokes, L. R. Allain, and T. Vo-Dinh, “Surface-enhanced Raman scattering substrate based on a self-assembled monolayer for use in gene diagnostics,” Anal. Chem. 75, 6196-6201 (2003).
[CrossRef] [PubMed]

Dasari, R. R.

K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99, 2957-2976 (1999).
[CrossRef]

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, “Single molecule detection using surface-enhanced Raman scattering,” Phys. Rev. Lett. 78, 1667-1670 (1997).
[CrossRef]

Datar, R. H.

G. Wu, R. H. Datar, K. M. Hansen, T. Thundat, R. J. Cote, and A. Majumdar, “Bioassay of prostate-specific antigen (PSA) using microcantilevers,” Nat. Biotechnol. 19, 856-860 (2001).
[CrossRef] [PubMed]

Denk, W.

W. Denk, J. H. Stricker, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248, 73-76 (1990).
[CrossRef] [PubMed]

Dieringer, J. A.

A. D. McFarland, M. A. Young, J. A. Dieringer, and R. P. Van Duyne, “Wavelength-scanned surface-enhanced Raman excitation spectroscopy,” J. Phys. Chem. B 109, 11279-11285(2005).
[CrossRef]

Dorrestein, P. C.

M. Howarth, D. J-F. Chinnapen, K. Gerrow, P. C. Dorrestein, M. R. Grandy, N. L. Kelleher, A. El-Husseini, and A. Y. Ting, “A monovalent streptavidin with a single femtomolar biotin binding site,” Nat. Methods 3, 267-273 (2006).
[CrossRef] [PubMed]

Driskell, J.

J. Driskell, K. M. Kwarta, R. J. Lipert, and M. D. Porter, “Low-level detection of viral pathogens by a surface-enhanced Raman scattering based immunoassay,” Anal. Chem. 77, 6147-6154 (2005).
[CrossRef] [PubMed]

D. S. Grubisha, R. J. Lipert, H. Park, J. Driskell, and M. D. Porter, “Femtomolar detection of prostate-specific antigen: an immunoassay based on surface-enhanced Raman scattering and immunogold labels,” Anal. Chem. 75, 5936-5943(2003).
[CrossRef] [PubMed]

Elam, J. W.

X. Zhang, J. Zhao, A. V. Whitney, J. W. Elam, and R. P. Van Duyne, “Ultrastable substrates for surface-enhanced Raman spectroscopy: Al2O3 overlayers fabricated by atomic layer deposition yield improved anthrax biomarker detection,” J. Am. Chem. Soc. 128, 10304-10309 (2006).
[CrossRef] [PubMed]

El-Husseini, A.

M. Howarth, D. J-F. Chinnapen, K. Gerrow, P. C. Dorrestein, M. R. Grandy, N. L. Kelleher, A. El-Husseini, and A. Y. Ting, “A monovalent streptavidin with a single femtomolar biotin binding site,” Nat. Methods 3, 267-273 (2006).
[CrossRef] [PubMed]

Emory, S. R.

S. Nie and S. R. Emory, “Probing single molecules and single nanoparticles by surface-enhanced Raman scattering,” Science 275, 1102-1106 (1997).
[CrossRef] [PubMed]

Feld, M. S.

K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99, 2957-2976 (1999).
[CrossRef]

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, “Single molecule detection using surface-enhanced Raman scattering,” Phys. Rev. Lett. 78, 1667-1670 (1997).
[CrossRef]

Gearheart, L. A.

L. A. Gearheart, H. J. Ploehn, and C. J. Murphy, “Oligonucleotide adsorption to gold nanoparticles: a surface-enhanced Raman spectroscopy study of intrinsically bent DNA,” J. Phys. Chem. B 105, 12609-12615 (2001).
[CrossRef]

Gerion, D.

G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47-52 (2006).
[CrossRef]

Gerrow, K.

M. Howarth, D. J-F. Chinnapen, K. Gerrow, P. C. Dorrestein, M. R. Grandy, N. L. Kelleher, A. El-Husseini, and A. Y. Ting, “A monovalent streptavidin with a single femtomolar biotin binding site,” Nat. Methods 3, 267-273 (2006).
[CrossRef] [PubMed]

Grandy, M. R.

M. Howarth, D. J-F. Chinnapen, K. Gerrow, P. C. Dorrestein, M. R. Grandy, N. L. Kelleher, A. El-Husseini, and A. Y. Ting, “A monovalent streptavidin with a single femtomolar biotin binding site,” Nat. Methods 3, 267-273 (2006).
[CrossRef] [PubMed]

Gray, J. W.

G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47-52 (2006).
[CrossRef]

Griffin, G. D.

J. M. Song, P. M. Kasili, G. D. Griffin, and T. Vo-Dinh, “Detection of cytochrome c in a single cell using an optical nanobiosensor,” Anal. Chem 76, 2591-2594 (2004).
[CrossRef] [PubMed]

Grubisha, D. S.

D. S. Grubisha, R. J. Lipert, H. Park, J. Driskell, and M. D. Porter, “Femtomolar detection of prostate-specific antigen: an immunoassay based on surface-enhanced Raman scattering and immunogold labels,” Anal. Chem. 75, 5936-5943(2003).
[CrossRef] [PubMed]

Hansen, K. M.

G. Wu, R. H. Datar, K. M. Hansen, T. Thundat, R. J. Cote, and A. Majumdar, “Bioassay of prostate-specific antigen (PSA) using microcantilevers,” Nat. Biotechnol. 19, 856-860 (2001).
[CrossRef] [PubMed]

Haynes, C. L.

C. L. Haynes and R. P. Van Duyne, “Plasmon-sampled surface-enhanced Raman excitation spectroscopy,” J. Phys. Chem. B 107, 7426-7433 (2003).
[CrossRef]

Hell, S. W.

V. Westphal and S. W. Hell, “Nanoscale resolution in the focal plane of an optical microscope,” Phys. Rev. Lett. 94, 143903-143910 (2005).
[CrossRef] [PubMed]

Henderson, E.

V. W. Jones, J. R. Kenseth, M. D. Porter, C. L. Mosher, and E. Henderson, “Microminiaturized immunoassays using atomic force microscopy and compositionally patterned antigen arrays,” Anal. Chem. 70, 1233-1241 (1998).
[CrossRef] [PubMed]

Herne, T. M.

R. Levicky, T. M. Herne, M. J. Tarlov, and S. K. Satija, “Using self-assembly to control the structure of DNA monolayers on gold: a neutron reflectivity study,” J. Am. Chem. Soc. 120, 9787-9792 (1998).
[CrossRef]

A. B. Steel, T. M. Herne, and M. J. Tarlov, “Electrochemical quantitation of DNA immobilized on gold,” Anal. Chem. 70, 4670-4677 (1998).
[CrossRef] [PubMed]

Howarth, M.

M. Howarth, D. J-F. Chinnapen, K. Gerrow, P. C. Dorrestein, M. R. Grandy, N. L. Kelleher, A. El-Husseini, and A. Y. Ting, “A monovalent streptavidin with a single femtomolar biotin binding site,” Nat. Methods 3, 267-273 (2006).
[CrossRef] [PubMed]

Itzkan, I.

K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99, 2957-2976 (1999).
[CrossRef]

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, “Single molecule detection using surface-enhanced Raman scattering,” Phys. Rev. Lett. 78, 1667-1670 (1997).
[CrossRef]

Jett, S. D.

G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47-52 (2006).
[CrossRef]

Jin, R-C.

Y-W. Cao, R-C. Jin, and C. A. Mirkin, “Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection,” Science 297, 1536-1540 (2002).
[CrossRef] [PubMed]

Jones, V. W.

V. W. Jones, J. R. Kenseth, M. D. Porter, C. L. Mosher, and E. Henderson, “Microminiaturized immunoassays using atomic force microscopy and compositionally patterned antigen arrays,” Anal. Chem. 70, 1233-1241 (1998).
[CrossRef] [PubMed]

Kasili, P. M.

J. M. Song, P. M. Kasili, G. D. Griffin, and T. Vo-Dinh, “Detection of cytochrome c in a single cell using an optical nanobiosensor,” Anal. Chem 76, 2591-2594 (2004).
[CrossRef] [PubMed]

Kelleher, N. L.

M. Howarth, D. J-F. Chinnapen, K. Gerrow, P. C. Dorrestein, M. R. Grandy, N. L. Kelleher, A. El-Husseini, and A. Y. Ting, “A monovalent streptavidin with a single femtomolar biotin binding site,” Nat. Methods 3, 267-273 (2006).
[CrossRef] [PubMed]

Kenseth, J. R.

V. W. Jones, J. R. Kenseth, M. D. Porter, C. L. Mosher, and E. Henderson, “Microminiaturized immunoassays using atomic force microscopy and compositionally patterned antigen arrays,” Anal. Chem. 70, 1233-1241 (1998).
[CrossRef] [PubMed]

Kneipp, H.

K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99, 2957-2976 (1999).
[CrossRef]

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, “Single molecule detection using surface-enhanced Raman scattering,” Phys. Rev. Lett. 78, 1667-1670 (1997).
[CrossRef]

Kneipp, K.

K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99, 2957-2976 (1999).
[CrossRef]

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, “Single molecule detection using surface-enhanced Raman scattering,” Phys. Rev. Lett. 78, 1667-1670 (1997).
[CrossRef]

Kunchakarra, S.

G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47-52 (2006).
[CrossRef]

Kwarta, K. M.

J. Driskell, K. M. Kwarta, R. J. Lipert, and M. D. Porter, “Low-level detection of viral pathogens by a surface-enhanced Raman scattering based immunoassay,” Anal. Chem. 77, 6147-6154 (2005).
[CrossRef] [PubMed]

Langer, P. R.

P. R. Langer, A. A. Waldrop, and D. C. Ward, “Enzymatic synthesis of biotin-labeled polynucleotides: novel nucleic acid affinity probes,” Proc. Natl. Acad. Sci. USA 78, 6633-6637(1981).
[CrossRef]

Lee, H. J.

G. J. Wegner, H. J. Lee and R. M. Corn, “Characterization and optimization of peptide arrays for the study of epitope-antibody interactions using surface plasmon resonance imaging,” Anal. Chem. 74, 5161-5168 (2002).
[CrossRef] [PubMed]

Lee, L. P.

G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47-52 (2006).
[CrossRef]

Levicky, R.

R. Levicky, T. M. Herne, M. J. Tarlov, and S. K. Satija, “Using self-assembly to control the structure of DNA monolayers on gold: a neutron reflectivity study,” J. Am. Chem. Soc. 120, 9787-9792 (1998).
[CrossRef]

Lipert, R. J.

J. Driskell, K. M. Kwarta, R. J. Lipert, and M. D. Porter, “Low-level detection of viral pathogens by a surface-enhanced Raman scattering based immunoassay,” Anal. Chem. 77, 6147-6154 (2005).
[CrossRef] [PubMed]

D. S. Grubisha, R. J. Lipert, H. Park, J. Driskell, and M. D. Porter, “Femtomolar detection of prostate-specific antigen: an immunoassay based on surface-enhanced Raman scattering and immunogold labels,” Anal. Chem. 75, 5936-5943(2003).
[CrossRef] [PubMed]

Liu, G. L.

G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47-52 (2006).
[CrossRef]

Lyandres, O.

X. Zhang, M. A. Young, O. Lyandres, and R. P. Van Duyne, “Rapid detection of an anthrax biomarker by surface-enhanced Raman spectroscopy,” J. Am. Chem. Soc. 127, 4484-4489 (2005).
[CrossRef] [PubMed]

Majumdar, A.

G. Wu, R. H. Datar, K. M. Hansen, T. Thundat, R. J. Cote, and A. Majumdar, “Bioassay of prostate-specific antigen (PSA) using microcantilevers,” Nat. Biotechnol. 19, 856-860 (2001).
[CrossRef] [PubMed]

McFarland, A. D.

A. D. McFarland, M. A. Young, J. A. Dieringer, and R. P. Van Duyne, “Wavelength-scanned surface-enhanced Raman excitation spectroscopy,” J. Phys. Chem. B 109, 11279-11285(2005).
[CrossRef]

Mirkin, C. A.

Y-W. Cao, R-C. Jin, and C. A. Mirkin, “Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection,” Science 297, 1536-1540 (2002).
[CrossRef] [PubMed]

Mosher, C. L.

V. W. Jones, J. R. Kenseth, M. D. Porter, C. L. Mosher, and E. Henderson, “Microminiaturized immunoassays using atomic force microscopy and compositionally patterned antigen arrays,” Anal. Chem. 70, 1233-1241 (1998).
[CrossRef] [PubMed]

Mukherjee, B.

G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47-52 (2006).
[CrossRef]

Murphy, C. J.

L. A. Gearheart, H. J. Ploehn, and C. J. Murphy, “Oligonucleotide adsorption to gold nanoparticles: a surface-enhanced Raman spectroscopy study of intrinsically bent DNA,” J. Phys. Chem. B 105, 12609-12615 (2001).
[CrossRef]

Nie, S.

W. C. W. Chan and S. Nie, “Quantum dot bioconjugates for ultrasensitive nonisotopic detection,” Science 281, 2016-2018(1998).
[CrossRef] [PubMed]

S. Nie and S. R. Emory, “Probing single molecules and single nanoparticles by surface-enhanced Raman scattering,” Science 275, 1102-1106 (1997).
[CrossRef] [PubMed]

S. Nie and R. N. Zare, “Optical detection of single molecules,” Annu. Rev. Biophys. Biomol. Struct. 26, 567-596 (1997).
[CrossRef] [PubMed]

Park, H.

D. S. Grubisha, R. J. Lipert, H. Park, J. Driskell, and M. D. Porter, “Femtomolar detection of prostate-specific antigen: an immunoassay based on surface-enhanced Raman scattering and immunogold labels,” Anal. Chem. 75, 5936-5943(2003).
[CrossRef] [PubMed]

Perelman, L. T.

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, “Single molecule detection using surface-enhanced Raman scattering,” Phys. Rev. Lett. 78, 1667-1670 (1997).
[CrossRef]

Ploehn, H. J.

L. A. Gearheart, H. J. Ploehn, and C. J. Murphy, “Oligonucleotide adsorption to gold nanoparticles: a surface-enhanced Raman spectroscopy study of intrinsically bent DNA,” J. Phys. Chem. B 105, 12609-12615 (2001).
[CrossRef]

Porter, M. D.

J. Driskell, K. M. Kwarta, R. J. Lipert, and M. D. Porter, “Low-level detection of viral pathogens by a surface-enhanced Raman scattering based immunoassay,” Anal. Chem. 77, 6147-6154 (2005).
[CrossRef] [PubMed]

D. S. Grubisha, R. J. Lipert, H. Park, J. Driskell, and M. D. Porter, “Femtomolar detection of prostate-specific antigen: an immunoassay based on surface-enhanced Raman scattering and immunogold labels,” Anal. Chem. 75, 5936-5943(2003).
[CrossRef] [PubMed]

V. W. Jones, J. R. Kenseth, M. D. Porter, C. L. Mosher, and E. Henderson, “Microminiaturized immunoassays using atomic force microscopy and compositionally patterned antigen arrays,” Anal. Chem. 70, 1233-1241 (1998).
[CrossRef] [PubMed]

Rotello, V. M.

C-C. You, A. Chompoosor, and V. M. Rotello, “The biomacromolecule-nanoparticle interface,” Nanotoday 2, 34-43 (2007).
[CrossRef]

Satija, S. K.

R. Levicky, T. M. Herne, M. J. Tarlov, and S. K. Satija, “Using self-assembly to control the structure of DNA monolayers on gold: a neutron reflectivity study,” J. Am. Chem. Soc. 120, 9787-9792 (1998).
[CrossRef]

Schatz, G. C.

G. C. Schatz and R. P. Van Duyne, Handbook of Vibrational Spectroscopy, J. M. Chalmers and P. R. Griffiths, eds. (Wiley, 2002), Vol. 1, pp. 759-774.

Sirimuthu, N. M. S.

S. E. J. Bell and N. M. S. Sirimuthu, “Surface-enhanced Raman spectroscopy (SERS) for sub-micromolar detection of DNA/RNA mononucleotides,” J. Am. Chem. Soc. 128, 15580-15581 (2006).
[CrossRef] [PubMed]

Song, J. M.

J. M. Song, P. M. Kasili, G. D. Griffin, and T. Vo-Dinh, “Detection of cytochrome c in a single cell using an optical nanobiosensor,” Anal. Chem 76, 2591-2594 (2004).
[CrossRef] [PubMed]

Steel, A. B.

A. B. Steel, T. M. Herne, and M. J. Tarlov, “Electrochemical quantitation of DNA immobilized on gold,” Anal. Chem. 70, 4670-4677 (1998).
[CrossRef] [PubMed]

Stokes, D.

M. Culha, D. Stokes, L. R. Allain, and T. Vo-Dinh, “Surface-enhanced Raman scattering substrate based on a self-assembled monolayer for use in gene diagnostics,” Anal. Chem. 75, 6196-6201 (2003).
[CrossRef] [PubMed]

Stricker, J. H.

W. Denk, J. H. Stricker, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248, 73-76 (1990).
[CrossRef] [PubMed]

Tarlov, M. J.

A. B. Steel, T. M. Herne, and M. J. Tarlov, “Electrochemical quantitation of DNA immobilized on gold,” Anal. Chem. 70, 4670-4677 (1998).
[CrossRef] [PubMed]

R. Levicky, T. M. Herne, M. J. Tarlov, and S. K. Satija, “Using self-assembly to control the structure of DNA monolayers on gold: a neutron reflectivity study,” J. Am. Chem. Soc. 120, 9787-9792 (1998).
[CrossRef]

Thundat, T.

G. Wu, R. H. Datar, K. M. Hansen, T. Thundat, R. J. Cote, and A. Majumdar, “Bioassay of prostate-specific antigen (PSA) using microcantilevers,” Nat. Biotechnol. 19, 856-860 (2001).
[CrossRef] [PubMed]

Ting, A. Y.

M. Howarth, D. J-F. Chinnapen, K. Gerrow, P. C. Dorrestein, M. R. Grandy, N. L. Kelleher, A. El-Husseini, and A. Y. Ting, “A monovalent streptavidin with a single femtomolar biotin binding site,” Nat. Methods 3, 267-273 (2006).
[CrossRef] [PubMed]

Van Duyne, R. P.

X. Zhang, J. Zhao, A. V. Whitney, J. W. Elam, and R. P. Van Duyne, “Ultrastable substrates for surface-enhanced Raman spectroscopy: Al2O3 overlayers fabricated by atomic layer deposition yield improved anthrax biomarker detection,” J. Am. Chem. Soc. 128, 10304-10309 (2006).
[CrossRef] [PubMed]

X. Zhang, M. A. Young, O. Lyandres, and R. P. Van Duyne, “Rapid detection of an anthrax biomarker by surface-enhanced Raman spectroscopy,” J. Am. Chem. Soc. 127, 4484-4489 (2005).
[CrossRef] [PubMed]

A. D. McFarland, M. A. Young, J. A. Dieringer, and R. P. Van Duyne, “Wavelength-scanned surface-enhanced Raman excitation spectroscopy,” J. Phys. Chem. B 109, 11279-11285(2005).
[CrossRef]

C. L. Haynes and R. P. Van Duyne, “Plasmon-sampled surface-enhanced Raman excitation spectroscopy,” J. Phys. Chem. B 107, 7426-7433 (2003).
[CrossRef]

G. C. Schatz and R. P. Van Duyne, Handbook of Vibrational Spectroscopy, J. M. Chalmers and P. R. Griffiths, eds. (Wiley, 2002), Vol. 1, pp. 759-774.

Vo-Dinh, T.

M. B. Wabuyele and T. Vo-Dinh, “Detection of human immunodeficiency virus type 1 DNA sequence using plasmonics nanoprobes,” Anal. Chem. 77, 7810-7815 (2005).
[CrossRef] [PubMed]

J. M. Song, P. M. Kasili, G. D. Griffin, and T. Vo-Dinh, “Detection of cytochrome c in a single cell using an optical nanobiosensor,” Anal. Chem 76, 2591-2594 (2004).
[CrossRef] [PubMed]

M. Culha, D. Stokes, L. R. Allain, and T. Vo-Dinh, “Surface-enhanced Raman scattering substrate based on a self-assembled monolayer for use in gene diagnostics,” Anal. Chem. 75, 6196-6201 (2003).
[CrossRef] [PubMed]

Wabuyele, M. B.

M. B. Wabuyele and T. Vo-Dinh, “Detection of human immunodeficiency virus type 1 DNA sequence using plasmonics nanoprobes,” Anal. Chem. 77, 7810-7815 (2005).
[CrossRef] [PubMed]

Waldrop, A. A.

P. R. Langer, A. A. Waldrop, and D. C. Ward, “Enzymatic synthesis of biotin-labeled polynucleotides: novel nucleic acid affinity probes,” Proc. Natl. Acad. Sci. USA 78, 6633-6637(1981).
[CrossRef]

Wang, Y.

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, “Single molecule detection using surface-enhanced Raman scattering,” Phys. Rev. Lett. 78, 1667-1670 (1997).
[CrossRef]

Ward, D. C.

P. R. Langer, A. A. Waldrop, and D. C. Ward, “Enzymatic synthesis of biotin-labeled polynucleotides: novel nucleic acid affinity probes,” Proc. Natl. Acad. Sci. USA 78, 6633-6637(1981).
[CrossRef]

Webb, W. W.

W. Denk, J. H. Stricker, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248, 73-76 (1990).
[CrossRef] [PubMed]

Wegner, G. J.

G. J. Wegner, H. J. Lee and R. M. Corn, “Characterization and optimization of peptide arrays for the study of epitope-antibody interactions using surface plasmon resonance imaging,” Anal. Chem. 74, 5161-5168 (2002).
[CrossRef] [PubMed]

Westphal, V.

V. Westphal and S. W. Hell, “Nanoscale resolution in the focal plane of an optical microscope,” Phys. Rev. Lett. 94, 143903-143910 (2005).
[CrossRef] [PubMed]

Whitney, A. V.

X. Zhang, J. Zhao, A. V. Whitney, J. W. Elam, and R. P. Van Duyne, “Ultrastable substrates for surface-enhanced Raman spectroscopy: Al2O3 overlayers fabricated by atomic layer deposition yield improved anthrax biomarker detection,” J. Am. Chem. Soc. 128, 10304-10309 (2006).
[CrossRef] [PubMed]

Wu, G.

G. Wu, R. H. Datar, K. M. Hansen, T. Thundat, R. J. Cote, and A. Majumdar, “Bioassay of prostate-specific antigen (PSA) using microcantilevers,” Nat. Biotechnol. 19, 856-860 (2001).
[CrossRef] [PubMed]

Yin, Y.

G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47-52 (2006).
[CrossRef]

You, C-C.

C-C. You, A. Chompoosor, and V. M. Rotello, “The biomacromolecule-nanoparticle interface,” Nanotoday 2, 34-43 (2007).
[CrossRef]

Young, M. A.

A. D. McFarland, M. A. Young, J. A. Dieringer, and R. P. Van Duyne, “Wavelength-scanned surface-enhanced Raman excitation spectroscopy,” J. Phys. Chem. B 109, 11279-11285(2005).
[CrossRef]

X. Zhang, M. A. Young, O. Lyandres, and R. P. Van Duyne, “Rapid detection of an anthrax biomarker by surface-enhanced Raman spectroscopy,” J. Am. Chem. Soc. 127, 4484-4489 (2005).
[CrossRef] [PubMed]

Zare, R. N.

S. Nie and R. N. Zare, “Optical detection of single molecules,” Annu. Rev. Biophys. Biomol. Struct. 26, 567-596 (1997).
[CrossRef] [PubMed]

Zhang, X.

X. Zhang, J. Zhao, A. V. Whitney, J. W. Elam, and R. P. Van Duyne, “Ultrastable substrates for surface-enhanced Raman spectroscopy: Al2O3 overlayers fabricated by atomic layer deposition yield improved anthrax biomarker detection,” J. Am. Chem. Soc. 128, 10304-10309 (2006).
[CrossRef] [PubMed]

X. Zhang, M. A. Young, O. Lyandres, and R. P. Van Duyne, “Rapid detection of an anthrax biomarker by surface-enhanced Raman spectroscopy,” J. Am. Chem. Soc. 127, 4484-4489 (2005).
[CrossRef] [PubMed]

Zhao, J.

X. Zhang, J. Zhao, A. V. Whitney, J. W. Elam, and R. P. Van Duyne, “Ultrastable substrates for surface-enhanced Raman spectroscopy: Al2O3 overlayers fabricated by atomic layer deposition yield improved anthrax biomarker detection,” J. Am. Chem. Soc. 128, 10304-10309 (2006).
[CrossRef] [PubMed]

Anal. Chem (1)

J. M. Song, P. M. Kasili, G. D. Griffin, and T. Vo-Dinh, “Detection of cytochrome c in a single cell using an optical nanobiosensor,” Anal. Chem 76, 2591-2594 (2004).
[CrossRef] [PubMed]

Anal. Chem. (7)

M. Culha, D. Stokes, L. R. Allain, and T. Vo-Dinh, “Surface-enhanced Raman scattering substrate based on a self-assembled monolayer for use in gene diagnostics,” Anal. Chem. 75, 6196-6201 (2003).
[CrossRef] [PubMed]

J. Driskell, K. M. Kwarta, R. J. Lipert, and M. D. Porter, “Low-level detection of viral pathogens by a surface-enhanced Raman scattering based immunoassay,” Anal. Chem. 77, 6147-6154 (2005).
[CrossRef] [PubMed]

D. S. Grubisha, R. J. Lipert, H. Park, J. Driskell, and M. D. Porter, “Femtomolar detection of prostate-specific antigen: an immunoassay based on surface-enhanced Raman scattering and immunogold labels,” Anal. Chem. 75, 5936-5943(2003).
[CrossRef] [PubMed]

G. J. Wegner, H. J. Lee and R. M. Corn, “Characterization and optimization of peptide arrays for the study of epitope-antibody interactions using surface plasmon resonance imaging,” Anal. Chem. 74, 5161-5168 (2002).
[CrossRef] [PubMed]

M. B. Wabuyele and T. Vo-Dinh, “Detection of human immunodeficiency virus type 1 DNA sequence using plasmonics nanoprobes,” Anal. Chem. 77, 7810-7815 (2005).
[CrossRef] [PubMed]

V. W. Jones, J. R. Kenseth, M. D. Porter, C. L. Mosher, and E. Henderson, “Microminiaturized immunoassays using atomic force microscopy and compositionally patterned antigen arrays,” Anal. Chem. 70, 1233-1241 (1998).
[CrossRef] [PubMed]

A. B. Steel, T. M. Herne, and M. J. Tarlov, “Electrochemical quantitation of DNA immobilized on gold,” Anal. Chem. 70, 4670-4677 (1998).
[CrossRef] [PubMed]

Annu. Rev. Biophys. Biomol. Struct. (1)

S. Nie and R. N. Zare, “Optical detection of single molecules,” Annu. Rev. Biophys. Biomol. Struct. 26, 567-596 (1997).
[CrossRef] [PubMed]

Chem. Rev. (1)

K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99, 2957-2976 (1999).
[CrossRef]

J. Am. Chem. Soc. (4)

R. Levicky, T. M. Herne, M. J. Tarlov, and S. K. Satija, “Using self-assembly to control the structure of DNA monolayers on gold: a neutron reflectivity study,” J. Am. Chem. Soc. 120, 9787-9792 (1998).
[CrossRef]

S. E. J. Bell and N. M. S. Sirimuthu, “Surface-enhanced Raman spectroscopy (SERS) for sub-micromolar detection of DNA/RNA mononucleotides,” J. Am. Chem. Soc. 128, 15580-15581 (2006).
[CrossRef] [PubMed]

X. Zhang, J. Zhao, A. V. Whitney, J. W. Elam, and R. P. Van Duyne, “Ultrastable substrates for surface-enhanced Raman spectroscopy: Al2O3 overlayers fabricated by atomic layer deposition yield improved anthrax biomarker detection,” J. Am. Chem. Soc. 128, 10304-10309 (2006).
[CrossRef] [PubMed]

X. Zhang, M. A. Young, O. Lyandres, and R. P. Van Duyne, “Rapid detection of an anthrax biomarker by surface-enhanced Raman spectroscopy,” J. Am. Chem. Soc. 127, 4484-4489 (2005).
[CrossRef] [PubMed]

J. Phys. Chem. B (3)

C. L. Haynes and R. P. Van Duyne, “Plasmon-sampled surface-enhanced Raman excitation spectroscopy,” J. Phys. Chem. B 107, 7426-7433 (2003).
[CrossRef]

A. D. McFarland, M. A. Young, J. A. Dieringer, and R. P. Van Duyne, “Wavelength-scanned surface-enhanced Raman excitation spectroscopy,” J. Phys. Chem. B 109, 11279-11285(2005).
[CrossRef]

L. A. Gearheart, H. J. Ploehn, and C. J. Murphy, “Oligonucleotide adsorption to gold nanoparticles: a surface-enhanced Raman spectroscopy study of intrinsically bent DNA,” J. Phys. Chem. B 105, 12609-12615 (2001).
[CrossRef]

Nanotoday (1)

C-C. You, A. Chompoosor, and V. M. Rotello, “The biomacromolecule-nanoparticle interface,” Nanotoday 2, 34-43 (2007).
[CrossRef]

Nat. Biotechnol. (2)

P. Alivisatos, “The use of nanocrystals in biological detection,” Nat. Biotechnol. 22, 47-52 (2004).
[CrossRef] [PubMed]

G. Wu, R. H. Datar, K. M. Hansen, T. Thundat, R. J. Cote, and A. Majumdar, “Bioassay of prostate-specific antigen (PSA) using microcantilevers,” Nat. Biotechnol. 19, 856-860 (2001).
[CrossRef] [PubMed]

Nat. Methods (1)

M. Howarth, D. J-F. Chinnapen, K. Gerrow, P. C. Dorrestein, M. R. Grandy, N. L. Kelleher, A. El-Husseini, and A. Y. Ting, “A monovalent streptavidin with a single femtomolar biotin binding site,” Nat. Methods 3, 267-273 (2006).
[CrossRef] [PubMed]

Nat. Nanotechnol. (1)

G. L. Liu, Y. Yin, S. Kunchakarra, B. Mukherjee, D. Gerion, S. D. Jett, D. G. Bear, J. W. Gray, A. P. Alivisatos, L. P. Lee, and F. F. Chen, “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nat. Nanotechnol. 1, 47-52 (2006).
[CrossRef]

Phys. Rev. Lett. (2)

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, “Single molecule detection using surface-enhanced Raman scattering,” Phys. Rev. Lett. 78, 1667-1670 (1997).
[CrossRef]

V. Westphal and S. W. Hell, “Nanoscale resolution in the focal plane of an optical microscope,” Phys. Rev. Lett. 94, 143903-143910 (2005).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. (1)

P. R. Langer, A. A. Waldrop, and D. C. Ward, “Enzymatic synthesis of biotin-labeled polynucleotides: novel nucleic acid affinity probes,” Proc. Natl. Acad. Sci. USA 78, 6633-6637(1981).
[CrossRef]

Science (4)

W. Denk, J. H. Stricker, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248, 73-76 (1990).
[CrossRef] [PubMed]

Y-W. Cao, R-C. Jin, and C. A. Mirkin, “Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection,” Science 297, 1536-1540 (2002).
[CrossRef] [PubMed]

S. Nie and S. R. Emory, “Probing single molecules and single nanoparticles by surface-enhanced Raman scattering,” Science 275, 1102-1106 (1997).
[CrossRef] [PubMed]

W. C. W. Chan and S. Nie, “Quantum dot bioconjugates for ultrasensitive nonisotopic detection,” Science 281, 2016-2018(1998).
[CrossRef] [PubMed]

Other (2)

G. C. Schatz and R. P. Van Duyne, Handbook of Vibrational Spectroscopy, J. M. Chalmers and P. R. Griffiths, eds. (Wiley, 2002), Vol. 1, pp. 759-774.

E. P. Diamandis and T. K. Christopoulous, eds., Immunoassay (Academic, 1996).

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Figures (7)

Fig. 1
Fig. 1

Immobilization strategy via HS–Ag binding and hybridization procedure for a typical sandwich DNA detection.

Fig. 2
Fig. 2

AFM images ( 2 μ m × 2 μ m ) of nanoparticle island (NIS) substrates with different Ag thicknesses from 10 to 200 Å on top of 10 Å Cr, rough analysis of corresponding AFM images is also shown. All substrates were fabricated by PVD with a coating rate of 0.1     Å / s and a vacuum of 10 6 Torr .

Fig. 3
Fig. 3

UV–visible extinction spectra of NIS substrates with different Ag thicknesses; λ max stands for extinction maximum.

Fig. 4
Fig. 4

Statistical study of extinction maximum λ max of NIS substrates with different Ag thicknesses: A,  10 Å ; B,  30 Å ; C,  50 Å ; D,  70 Å ; and E,  90 Å , where σ is the half-width at half-maximum of the Gaussian-fitted curves. F shows the redshifting trend of the average λ max with increasing Ag thickness; error bars indicate the values of σ.

Fig. 5
Fig. 5

UV–visible extinction spectra of NIS samples with different Ag thicknesses and their corresponding SERS spectra of Rh6G obtained from Ag thicknesses of 10, 30, 50, 70, and 90 Å , respectively; the bottom trace shows the typical background spectrum of the blank substrate.

Fig. 6
Fig. 6

A: SERS results of target oligonucleotide detection (concentrations from 1 μM to 1 nM ). The spectra shown were given by the detection OND p3 with Raman label FAM; B: corresponding sigmoidal response curve of vibration mode 1652 cm 1 of FAM, which was normalized by maximum intensity; the bottom trace shows the background spectrum of the substrate coated with the receptor OND.

Fig. 7
Fig. 7

Target OND detection with the aid of Au-NPs-capped detection OND p4 with Raman label FAM. A, SERS spectra of target OND (concentrations from 4 μM to 0.4 fM ), B, normalized sigmoidal response curve of vibration mode 1652 cm 1 of FAM versus the change of target concentrations; the bottom trace shows the background spectrum of the substrate coated with the receptor OND.

Tables (1)

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Table 1 Enhancement Factors of Vibration Mode 1652 cm 1 ( λ vib : 562 nm ) Obtained from Rh6G at Different Ag Layer Thicknesses Versus Their Corresponding Extinction Maxima λ max a

Equations (1)

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EF ( 1652 cm 1 ) = N vol × I surf N surf × I vol .

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