Plant pathogens represent a significant threat to food supplies. Agricultural diagnostics currently function on a paradigm involving either inaccurate visual inspection or burdensome laboratory molecular tests. Several field-ready diagnostic methods have been presented in recent years; however detection of pre-symptomatic or co-occurring infections and in-field sample processing remain challenges. To address these challenges, we developed surface-enhanced Raman scattering (SERS)-sensing hydrogels that uptake pathogenic material (RNA) and produce a measurable response on-site. Our novel reagentless SERS sensor for the detection of tobacco mosaic virus (TMV) was embedded in an environmentally compatible hydrogel material, to produce sensing hydrogels. We demonstrate the diagnostic application of our sensing hydrogels through exposure to TMV infected tobacco plants. This technology offers a field-deployable tool for pre-symptomatic and multiplexed molecular identification of pathogens with the potential to shift the current agricultural diagnostic paradigm.
Point-of-sampling diagnostics has gained interest for its potential to detect trace amounts of analytes in real-time. Several challenges persist with developing accurate and reliable field-testing techniques, including limits of detection, portable and durable instrumentation, and cost effectiveness for routine monitoring. To combat these challenges, our goal is to develop a facile, field deployable Surface-Enhanced Raman Scattering (SERS) sensor for detecting trace amounts of Chemical Warfare Agents (CWAs) and environmental contaminants such as perfluoroalkyl substances (PFAS). In collaboration with the University of Cincinnati, we optimized the ink formulation and printing parameters for AgAu nanostars using a machine learning optimization algorithm to achieve the best SERS performance using the minimal AgAu nanostars. The SERS sensor performance and limits of detection were assessed using CWAs and PFAS. Future work includes exploring the tunability of the LSPR of the AgAu nanostars for compatibility with commercially available handheld Raman spectrometers.
The pandemic has shown that we need sensitive and deployable diagnostic technologies. Surface-enhanced Raman scattering (SERS) sensors can be an ideal solution for developing such advanced Point-of-Need (PON) diagnostic tests but their limitation is the achievable sensitivity, insufficient compared to what is needed for sensing of viral biomarkers. Noncovalent DNA catalysis mechanisms have been recently exploited for catalytic amplification in SERS assays. These advances used catalytic hairpin assembly (CHA) and other DNA self-assembly processes to develop sensing mechanisms with improved sensitivities. We developed and investigated a reagentless SERS sensing mechanism that uses catalytic amplification based on DNA self-assembly. We will discuss the design of this catalytic sensing mechanism and its automation into a design algorithm.
Sandwich-based LFA device was successfully demonstrated to detect salivary lipopolysaccharides of P. gingivalis from human saliva. Although saliva is an attractive biofluid due to non-invasive sampling and excellent availability, isolating targeted biomarkers for analysis in saliva is challenging because of interferences from various biomolecules in saliva, especially by -amylase. Combined pre-treatment using potato starch and syringe filtration has been developed to reduce the interference from -amylase. Pretreated saliva presented a comparable LOD ~46 ng/mL with excellent selectivity versus other LPS and proteins. Future directions include not only the development of aptamer-based LFA but also adapting the Surface Enhanced Raman Scattering (SERS) technology for sensing target analytes in LFA in conjunction with novel silver-coated Au nanostar particles. Our prior research using aptamer in LFA and preliminary results of SERS detection in LFA will be presented to support our future directions.
Understanding biological samples is an important part of disease treatment and prevention. Current methods of biological analysis can be time-consuming and costly. Label-free Surface-Enhanced Raman Scattering (SERS) is a useful vibrational technique that incorporates plasmonic metal nanomaterial to amplify Raman signals. This technique requires little sample preparation and provides high informational chemical insights on the target. Herein, we use SERS to test and analyze biological samples of exosomes and bacteria. Each biological sample has similar biomolecular components that are difficult to differentiate or show small differences after interacting with other chemicals. Thus, herein, we show the incorporation of principal component analysis to understand differences and trends in the spectra. These studies highlight the powerful combination of SERS and machine learning for biological analysis.
Hygiene is becoming a key issue in a world with an increasing global population and an increasing number of antibioticresistant bacteria. In the next few years, a crucial challenge will be finding better methods for disinfection. Currently, these methods are studied with traditional microbiology techniques, where bacteria are grown, exposed to a treatment and further growth is followed for several days. However, this paradigm is slow and does not offer chemical insights in the mechanism of action of disinfecting agents. Without new analytical tools, we risk slowing down the critical research into new disinfecting agents. There is a large body of literature reporting bacterial inhibition mechanisms are diverse and include cell membrane disruption, DNA/RNA damage, ribosome degradation, protein denaturation, etc. Also, it is widely known that bacteria inactivation mechanisms are complex and multiple mechanisms can be involved in a synergetic manner. Current knowledge regarding the mechanism of action for bacteria inhibition is largely based on results from analytical tools that include mass spectrometry, nuclear magnetic resonance spectroscopy and fluorescence spectroscopy in combination with a suite of biochemical assays. All these methods require significant effort and sample preparation/treatment to obtain results. In addition, chemical insights obtained from biochemical assays rely tightly to the initial hypotheses. Herein, we propose to use Raman and surface-enhanced Raman scattering (SERS) to study the mechanism of action for bacteria inhibition. Vibrational spectroscopies have numerous advantages over the current paradigm for this analysis, including low sample preparation requirements and spectra rich in chemical information. These advantages permit to monitor bacteria cultures easily and quickly, while also obtaining chemical insights regarding mechanism of action for bacteria inhibition. In this work, we will show the monitoring of treated bacteria via Raman spectroscopy and how we can use SERS to further streamline this process.
Plant biotechnology and biofuel research is critical in addressing increasing global demands for energy. Further understanding of biomass producing associated metabolic pathways in plants can be used to exploit and increase the production of biomass for energy purposes. In vivo detection of biomarkers associated with plant growth for bioenergy has proved to be limited due to complex sample preparation required by traditional methods. In addition, genetic transformation and biomolecule monitoring inside plant cells is regulated by diameter and size exclusion limits of the plant cell wall (5 - 20 nm). Currently limited methods exist for enabling direct entry into plant cells. Moreover, these methods, such as biolistic particle delivery and electroporation use mechanical force that causes damages to the plant tissue. Nanoparticles could serve as promising platforms for probes to characterize intercellular and intracellular plant biomarkers and pathways. Bi-metallic nanostars are a plasmonics-active nanoplatform capable of high surface-enhanced Raman scattering (SERS) which can enter plant cells and have the future potential for nucleic acid sensing. Imaging technologies such as SERS mapping, confocal imaging, X-ray fluorescence imaging, multi-photon imaging, and transmission electron microscopy have been utilized to determine the compartmentalization and location of the SERS iMS biosensors inside Arabidopsis plants.
Surface-enhanced Raman scattering (SERS) is emerging as an alternative non-invasive detection method in many applications. We recently show the use of SERS nanoprobes to detect tumors in vivo in mice, as well as the use of SERS sensors in vivo in plants for the detection of mIRNA. In spite of these advancements, the translation of SERS to real-world settings has been limited due to issues with observing Raman signal over complex background. For example, it remains challenging to observe SERS under sunlight or under strong illumination (e.g., operating room), using a conventional Raman setup. To this end, we combined a Raman setup with a newly developed dual-wavelength laser to perform shifted-excitation Raman difference spectroscopy (SERDS). Using SERDS, we demonstrate that the use of SERS sensors to detect miRNA in live plants inside a growth chamber, under full illumination. Additionally, we show that SERDS can be used to accurately identify tumors in mice, under ambient light. In both these applications, we demonstrate that the combination of SERS with SERDS improves the sensitivity and accuracy. This work will aid the translation of Raman and SERS to real-world settings.
Our group has integrated surface-enhanced Raman scattering (SERS) silver coated gold nanostars on an optical fiber. Fiber-based sensors are an in-situ technology that can simultaneously bring the sensor and light to the sample without disturbing the environment. This technology is a multi-use method that does not require complex sample preparation. Fiber sensors or optrodes, enable the detection of analytes in samples that are difficult to access. Additionally, optrodes allow for specific detection while evading background signals from non-target regions. The fiber-optrode was used to detect miRNA and illegal food additives.
Further understanding of biomass producing associated metabolic pathways in plants can be used to increase the production of biomass. In vivo detection of these markers has proved to be limited due to complex sample preparation required by traditional methods. Recently the Vo-Dinh group has designed a platform to detect nucleic acid targets in biological systems called inverse molecular sentinels which utilize surface-enhanced Raman scattering. These multimodal probes were shown to detect and image key microRNA within whole plants in vivo. This work lays the foundation for detecting and imaging biological markers in plants with enhanced spatial and temporal resolution.
Gene expression monitoring within whole plants is critical for many applications ranging from plant biology to biofuel development. Herein, we report a unique multimodal method for in vivo imaging and biosensing of nucleic acid biotargets, specifically microRNA, within whole plant leaves by integrating three complementary techniques: surface-enhanced Raman scattering (SERS), X-ray fluorescence (XRF), and plasmonics-enhanced two-photon luminescence (TPL). The method described utilizes plasmonic nanostar-based inverse molecular sentinel (iMS) nanoprobes, which not only provide large Raman signal enhancement upon target binding, but also allow for localization and quantification by XRF and plasmonics-enhanced TPL. This report lays the foundation for the use of plasmonic nanoprobes for in vivo functional imaging of nucleic acid biotargets in whole plants.
Molecular analysis has revolutionized many applications, including bio-safety, bio-engineering and biofuel research; however, there are limited practical tools for in situ detection during field work. New technology is needed to translate molecular advances from laboratory settings into the practical realm. The unique characteristics of plasmonic nanosensors have made them ideal candidates for field-ready sensing applications. Herein, we discuss the development of a fiber-based plasmonic sensor capable of direct detection (i.e., no washing steps required) of miRNA targets, which are detected by immerging the sensor in the sample solution. This sensor is composed of an optical fiber that is decorated with plasmonic nanoprobes based on silver-coated gold nanostars to detect target nucleic acids using the surface-enhanced Raman scattering sensing mechanism of nanoprobes referred to as inverse molecular sentinels. The fiber sensors were tested in extracts from leaves of plants that were induced to have different miRNA expression levels. The results indicate that the fiber sensors developed have the potential to be a powerful tool for field analysis.
The ability to monitor gene expression within living plants is of importance in many applications ranging from plant biology research to biofuel development; however, no method currently exists without requiring sample extraction. Herein, we report a multimodal imaging method based on plasmonic nanoprobes for in vivo imaging and biosensing of microRNA biotargets within whole plant leaves. This method integrates three different but complementary techniques: surfaceenhanced Raman scattering (SERS), X-ray fluorescence (XRF), and plasmonics-enhanced two-photon luminescence (TPL). The multimodal method utilizes plasmonic nanostars, which not only provide large Raman signal enhancement, but also allow for localization and quantification by XRF and plasmonics-enhanced TPL, owing to gold content and high two-photon luminescence cross-sections. For the sensing mechanism, inverse molecular sentinel (iMS) nanoprobes are used for SERS bioimaging of microRNA within Arabidopsis thaliana leaves to provide a dynamic SERS map of detected microRNA targets while also quantifying nanoprobe concentrations using XRF and TPL. This report lays the foundation for the use of plasmonic nanoprobes for in vivo functional imaging of nucleic acid biotargets in whole plants, a tool that will allow the study of these biotargets with previously unmet spatial and temporal resolution.
Early detection of molecular targets can greatly impact the clinical diagnosis and outcome of many diseases such as cancer. Methods utilizing optical detection systems and Surface-Enhanced Raman Scattering (SERS)-labeled nanoparticles provide a way of selectively targeting and obtaining signals unique to the target diseases as well as in-vivo applications for biomass and biofuel research with plants. However, these modalities are often limited to surface level detection due to attenuation from layers of highly scattering and absorbing tissue. In this work, we utilize surface-enhanced spatially offset Raman spectroscopy (SESORS) to probe through thick tissue to overcome this limitation. This modality combines high SERS signals generated by nanoparticles with a depth resolved detection technique called spatially offset Raman spectroscopy (SORS). We show the detection and recovery of SERS signal in layered systems comprising of optically mimicking gel as well as bone material.
The knowledge over gene expression dynamics and location in plants is crucial for applications ranging from basic biological research to agricultural biotechnology (e.g., biofuel development). However, current methods cannot provide in vivo dynamic detection of genomic targets in plants. This limitation is due to the complex sample preparation needed by current methods for nucleic acids detection, which disrupt spatial and temporal resolution. We report the development of a unique multimodal method based on plasmonics-active nanoprobes, referred to inverse molecular sensitnels capable of in vivo imaging and biosensing of microRNA biotargets within whole plant using surface-enhanced Raman scattering (SERS) detection. This work lays the foundations for in vivo functional imaging of RNA biotargets in plants with previously unmet spatial and temporal resolution for many applications ranging from agricultural biotechnology to biofuel research.
Although nanotechnology has led to important advances in in vitro diagnostics, the development of nanosensors for in vivo molecular detection remains very challenging. Here, we demonstrated the proof‐of‐principle of in vivo detection of nucleic acid targets using a promising type of surface‐enhanced Raman scattering (SERS) nanosensor implanted in the skin of a large animal model (pig). The in vivo “smart tattoo” nanosensor used in this study employs the “inverse molecular sentinel” (iMS) detection scheme, which is a label-free homogeneous biosensing system based on a non-enzymatic DNA strand-displacement process and conformational change of stem-loop (hairpin) oligonucleotide probes upon target binding. In this study, plasmonics‐active nanostar was utilized as an efficient in vivo SERS sensing platform due to their tunable absorption bands in the near infrared region of the “tissue optical window. The results of this study illustrate the usefulness of SERS iMS nanosensors as an implantable skin‐based in vivo biosensing platform, providing a foundation for developments in continuous health status sensing, disease biomarker monitoring, and other clinical translation applications.
Direct detection of genetic biomarkers in tissue and body fluids without complex target extraction and amplification processes can revolutionize nucleic acid-based diagnostics by enabling the use of this technology at the point-of-care. The development of point-of-care diagnostics is important to increase access to early treatment in underserved populations in low to middle income countries, which are disproportionally affected by infectious diseases and increasingly affected by certain types of cancer. The main obstacle to the development of such technologies is the low concentration of target sequences that makes this goal challenging. We report a method for direct detection of pathogen RNA in blood lysate using a bioassay using surface-enhanced Raman spectroscopy (SERS)-based detection assay that can be integrated in a “lab-in-a-stick” portable device. We could directly detect synthetic target with a limit of detection of 200 fM and, more importantly, we detected P. falciparum malaria parasite RNA directly in infected red blood cells lysate. Additionally, this paper will discuss the use of the developed assay for the identification of head and neck squamous cell carcinoma (HNSCC), which is an increasingly prevalent malignancy in low to middle income countries.
While the use of nanomaterials in medical diagnostics has received increasing interest, in vivo detection of nanoparticles using optical techniques is still a challenge. Among other techniques, surface-enhanced Raman scattering (SERS)-labeled nanoparticles offer many potential applications in the field of disease diagnostics and biomedical monitoring, due to the advantages offered by SERS. We have previously developed a unique plasmonics-active nanoplatform, gold nanostars (GNS) for in vitro and in vivo multiplexed detection and diagnostics. To date conventional optical setups are typically limited in obtaining SERS signals at the sample surface, due to the strong attenuation caused by the highly scattering and absorbing tissue. Herein, we utilize spatially offset Raman spectroscopy (SORS) to overcome this depth limitation and obtain specific spectrochemical signatures of SERS-labeled nanoparticles, such as gold nanostars, beneath thick material and bone. In particular, we developed an optical setup for inverse spatially offset Raman spectroscopy to improve the robustness of the method developed. The efficacy of this method, referred to as inverse Surface-Enhanced Spatially Offset Raman Spectroscopy (SESORS) is demonstrated through the detection of layer-specific and subsurface SERS signals beneath different layers and substrates: (1) 4-mm tissue phantom, (2) 4-mm paraffin film, and (3) 5 mm bone of a macaque skull. Additionally, we show the possibility of recovering the pure SERS signal that belongs to a specific layer within a two-layer system using scaled subtraction. We will discuss the use of inverse SESORS in applications relevant to biomedical research.
Detection of surface-enhanced Raman scattering (SERS) tagged nanoparticles in-vivo is critical for its potential application in cancer diagnostics, inflammation monitoring, and glucose quantification. However, traditional optical methods are typically limited to surface level detection due to attenuation from layers of highly scattering and absorbing tissue. To break through this depth limitation, we utilize surface-enhanced spatially offset Raman spectroscopy (SESORS), a recent development for probing deep tissue that combines the high SERS signals generated by nanoparticles with a depth resolved detection technique called spatially offset Raman spectroscopy (SORS). We create a series of tissue phantoms that optically mimic tissue and embedded SERS tagged gold nanostars within them to demonstrate the ability of SESORS to distinguish signals from different layers by simply offsetting the excitation spot from the collection spot. We also show the ability to recover the subsurface SERS signal by a scaled subtraction between the spectra obtained at the 0 mm offset position and the spectra obtained at 10 mm offset position, demonstrating the ability of SESORS to isolate the subsurface SERS spectra of tagged nanoparticles.
Lead selenide (PbSe) has been studied as a promising material for room temperature midwave infrared detection. We have investigated pure PbSe, as well as tin (Tn) and cadmium (Cd)-doped PbSe, nanocrystalline materials produced using physical vapor transport methods on glass and high-resistivity silicon substrates. The morphologies were investigated by scanning electron microscopy and energy-dispersive x-ray analysis. Pure PbSe layers consisted of nanocrystals that change into cubes and cuboids upon annealing. Cuboids generally grew in [100] orientation and ultimately developed in nanorods. Growth on silicon and glass substrates showed different morphologies of pure PbSe material. Parabolic and elongated morphologies resulted in nanowires on the top of thin layers of PbSe nanofilm, which acted as the substrate. Under low gradient annealing conditions (<20 K/cm), elongated morphologies grew into nanorods. Annealing of these samples resulted in coarse nanomorphologies with higher resistivity. In the case of Tn-doped PbSe, annealing dissolved a Tn-rich phase observed in as-grown films. Cd- and iodine-doped films produced through the addition of Cd selenide and Cd iodide, respectively, showed higher resistivity than similarly treated pure PbSe films. Annealing of as-grown materials in the presence of oxygen or iodine showed increased resistivity and significant changes in optical characteristics.
The development of rapid, easy-to-use and highly sensitive DNA detection methods has received increasing interest for medical diagnostics and research purposes. Our laboratory has developed several chip-based DNA biosensors including molecular sentinel-on-chip (MSC), multiplex MSC, and inverse molecular sentinel-on-chip (iMS-on-Chip). These sensors use surface-enhanced Raman scattering (SERS) plasmonic chips, functionalized with DNA probes for single-step DNA detection. The sensing mechanisms is based on the hybridization of target sequences and DNA probes, resulting in a displacement of a SERS reporter from the chip surface. This distance increase results in change in SERS signal intensity from the reporter, thus indicating the capture, and therefore the presence, of the target nucleic acid sequence. The nucleic acid probes and the SERS chip, which compose the sensing platform, were designed for single-step DNA detection. The target sequences are detected by delivery of a sample solutions on a functionalized chip and characterization of the SERS signals, after 1 - 2 hr incubation. These techniques avoid labeling of the target sequence or washing to remove unreacted components, making them easy-to-use and cost effective. The use of SERS chip for medical diagnostics was demonstrated by detecting genetic biomarkers for respiratory viral infection and the DNA of dengue virus 4.
Single cell analysis can aid the study of molecular events responsible for cellular functions and unveil their connections to the biological functions of an organism. Biosensors based on surface enhanced Raman spectroscopy (SERS) can be used to this end and offer several advantages over other sensing platforms, such as sensitivity and multiplexed capabilities, among others. While SERS nanosensors/nanoparticles have been used for analysis in single cells, the delivery of such biosensors relies on cellular uptake, which requires long incubation time and has different efficiencies among cell lines. Nanosensors based on tapered optical fibers, instead, can be inserted in single cells and detect target molecules in subcellular compartment. The combination of these sensing devices with the transduction mechanism of nucleic acid based nanoprobes (i.e. inverse molecular sentinels) will permit the more direct detection of nucleic acids within single cells. This paper presents the development of tapered fiber-based biosensors for the detection of nucleic acid biomarkers in plant cells. The use of inverse molecular sentinels in plant cell was demonstrated. Sensors based on tapered fibers were fabricated and used to measure SERS from a single cell.
The utility of peptide-based molecular sensing for the development of novel biosensors has resulted in a significant increase in their development and usage for sensing targets like chemical, biological, energetic and toxic materials. Using peptides as a molecular recognition element is particularly advantageous because there are several mature peptide synthesis protocols that already exist, peptide structures can be tailored, selected and manipulated to be highly discerning towards desired targets, peptides can be modified to be very stable in a host of environments and stable under many different conditions, and through the development of bifunctionalized peptides can be synthesized to also bind onto desired sensing platforms (various metal materials, glass, etc.). Two examples of the several Army relevant biological targets for peptide-based sensing platforms include Ricin and Abrin. Ricin and Abrin are alarming threats because both can be weaponized and there is no antidote for exposure. Combining the sensitivity of SERS with the selectivity of a bifunctional peptide allows for the emergence of dynamic hazard sensor for Army application.
This review describes the recent advances in plasmonic nanostructures for various sensing applications. In particular, significant advances in surface-enhanced Raman, surface plasmon resonance, and metal-enhanced fluorescence-sensing methodologies associated with the introduction of plasmonic nanostructures, made over the past decade, are highlighted. Plasmonic properties of the various nanostructures employed for each sensing technique are also tabulated to provide a systematic overview of the state-of-the-art in each sensing field. This review is not intended to be a comprehensive compilation of the literature but rather a critical review of the recent significant advances in plasmonic nanostructures for each sensing regime.
Surface enhanced Raman spectroscopy (SERS) has several advantages as a transduction method for many types of optical sensors, due to its sensitivity and potential for multiplexed detection. Over the years, SERS probes have been developed to be capable of extreme sensitivities, with single molecule SERS having been achieved in randomly located hot-spots of colloidal aggregates. However, these structures suffer from significant irreproducibility, due to the randomness of the aggregation. Alternatively, strategies such as ordered 2D arrays or enhancement based on single probes (e.g. immunno-nanosensors, nanostars) have high reproducibilities but limited enhancement factors. In our laboratory a widely applicable enhancing geometry based on metal thin films interleaved with dielectric spacers that takes advantage of interaction into the volume of the probe (perpendicularly to the surface) to enhance the signal independently from the underlying structure has been developed. Preliminary evidence into the mechanism of this enhancement suggests that the dielectric spacer material and thickness play a key role in the magnitude of the resulting enhancement. In this paper we investigate the thickness dependence of the multilayer enhancement using substrates fabricated using ultrathin oxide deposited by atomic layer deposition as spacers. The SERS enhancement measured for substrates based on semiconductor and dielectric materials have been characterized in order to understand the origin of this dependence. In addition a model to describe the mechanism by which the spacer properties influence the multilayer enhancement will also be discussed.
A great deal of research has been performed on developing room temperature mid wave infrared (MWIR) and long wave infrared (LWIR) detectors to replace very costly mercury cadmium telluride based detectors. Among the more studied materials for high operating temperature detectors, PbSe and PbSe-type heavy metal selenides have been grown in the bulk, thin film and nano crystal morphologies. To better understand the effects of the substrate on the properties of these thin films, we have deposited lead selenide by physical vapor transport (PVT) method on highresistivity Si substrates and studied the characteristics of the film. Growth on silicon and glass substrates showed different morphologies compared to pure lead selenide material. It was seen that materials grown on a glass substrate possessed different morphology after annealing. FTIR was used to calculate bandgap information comparison with undoped PbSe. We will describe the details of the growth method, effect of substrate on nucleation and morphology of the pure and lead selenide material and band gap comparisons between substrates.
Photonic nanosensors (e.g. PEBBLES, quantum dots-based sensors, etc.) have begun to allow the study of these
previously inaccessible environments. Unfortunately, many current techniques suffer from biocompatibility issues,
limited ability to monitor multiple species simultaneously and/or complicated fabrication chemistries. Recently SERS
immuno-nanoprobes have demonstrated the capability to overcome many of these limitations. Such intracellular SERS
nanosensors require optimized substrate geometry to achieve the sensitivity necessary to detect the trace analyte
concentrations present. To address this, we have developed a novel multilayered SERS substrate nanoarchitecture that is
capable of enhancing SERS signals by over two orders of magnitude relative to comparable single layer substrates.
These structures are fabricated using different deposition techniques (PVD, ALD, etc) in which multiple films of Ag
(between 10-125 nm thick) are alternately deposited with ultrathin dielectric layers (tens of Å). This geometry allows
surface plasmons from different metal layers to be generated. The resulting multilayer enhancement increases the
sensitivity while also improving the robustness of the nanoprobes. In this paper, we investigate and characterize SERS
immuno-nanoprobes fabricated using this multilayered geometry and discuss the effect of the dielectric spacer (Ag2O,
TiO2, Ta2O5) work functions and conductive band offsets on the multilayer enhancement.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.