Correlation between Plasmonic and Thermal Properties of Metallic Nanoparticles.

Here, we investigate the correlation between the heat generated by gold nanoparticles, in particular nanospheres and nanobipyramids, and their plasmonic response manifested by the presence of Localized Surface Plasmon Resonances (LSPRs). Using a tunable laser and a thermal camera, we measure the temperature increase induced by colloidal nanoparticles in an aqueous solution as a function of the excitation wavelength in the optical regime. We demonstrate that the photothermal performances of the nanoparticles are strongly related not only to their plasmonic properties but also to the size and shape of the nanoparticles. The contribution of the longitudinal and transversal modes in gold nanobipyramids is also analyzed in terms of heat generation. These results will guide us to design appropriate nanoparticles to act as efficient heat nanosources.

Portable microfluidic plasmonic chip for fast real-time cardiac troponin I biomarker thermoplasmonic detection.

Acute myocardial infarction is one of the most serious cardiovascular pathologies, impacting patients' long-term outcomes and health systems worldwide. Significant effort is directed toward the development of biosensing technologies, which are able to efficiently and accurately detect an early rise of cardiac troponin levels, the gold standard in detecting myocardial injury. In this context, this work aims to develop a microfluidic plasmonic chip for the fast and accurate real-time detection of the cardiac troponin I biomarker (cTnI) via three complementary detection techniques using portable equipment. Furthermore, the study focuses on providing a better understanding of the thermoplasmonic biosensing mechanism taking advantage of the intrinsic photothermal properties of gold nanoparticles. Specifically, a plasmonic nanoplatform based on immobilized gold nanobipyramids was fabricated, exhibiting optical and thermoplasmonic properties that promote, based on a sandwich-like immunoassay, the "proof-of-concept" multimodal detection of cTnI via localized surface plasmon resonance, surface enhanced Raman spectroscopy and thermoplasmonic effects under simulated conditions. Furthermore, after the integration of the plasmonic nanoplatform in a microfluidic channel, the determination of cTnI in 16 real plasma samples was successfully realized via thermoplasmonic detection. The results are compared with a conventional high-sensitivity enzyme-linked immunosorbent clinical assay (ELISA), showing high sensitivity (75%) and specificity (100%) as well as fast response features (5 minutes). Thus, the proposed portable and miniaturized microfluidic plasmonic chip is successfully validated for clinical applications and transferred to clinical settings for the early diagnosis of cardiac diseases, leading towards the progress of personalized medicine.

Innovative, Flexible, and Miniaturized Microfluidic Paper-Based Plasmonic Chip for Efficient Near-Infrared Metal Enhanced Fluorescence Biosensing and Imaging.

The implementation of metal enhanced fluorescence (MEF) as an efficient detection tool, especially in the near-infrared region of the electromagnetic spectrum, is a rather new direction for diagnostic analytical technologies. In this context, we propose a novel microfluidic plasmonic design based on paper for efficient MEF detection of the "proof-of-concept" biotin-streptavidin recognition interaction. Our design made use of the benefits of gold nanobipyramids (AuBPs), considering the strong enhanced electromagnetic field present at their sharp tips, and filter paper to operate as a natural microfluidic channel due to excellent wicking abilities. The calligraphed plasmonic paper, obtained using a commercial pen filled with AuBPs, was integrated in a robust sandwich optically transparent polydimethylsiloxane chip, exhibiting portability and flexibility while preserving the chip's properties. To place the Alexa 680 fluorophore at an optimal distance from the nanobipyramid substrate, the human IgG-anti-IgG-conjugated biotin sandwich reaction was employed. Thus, upon the capture of Alexa 680-conjugated streptavidin by the biotinylated system, a 1.3-fold average enhancement of the fluorophore's emission was determined by bulk fluorescence measurements. However, the local enhancement factor was considerably higher with values spanning from 5 to 6.3, as proven by mapping the fluorescence emission under both re-scan microscopy and fluorescence lifetime imaging, endorsing the proposed chip's feasibility for bulk MEF biosensing as well as high-resolution MEF bioimaging. Finally, the versatility of our chip was demonstrated by adapting the biosensing protocol for cardiac troponin I biomarker detection, validated using 10 plasma samples collected from pediatric patients and corroborated with a conventional ELISA assay.

No country for old antibiotics! Antimicrobial peptides (AMPs) as next-generation treatment for skin and soft tissue infection.

In recent years, the unprecedented rise of bacterial antibiotic resistance together with the lack of adequate therapies have made the treatment of skin infections and chronic wounds challenging, urging the scientific community to focus on the development of new and more efficient treatment strategies. In this context, there is a growing interest in the use of natural molecules with antimicrobial features, capable of supporting wound healing i.e., antimicrobial peptides (AMPs), for the treatment of skin and soft tissue infections. In this review, we give a short overview of the bacterial skin infections as well as some of the classic treatments used for topical application. We then summarize the AMPs classes, stressing the importance of the appropriate selection of the peptides based on their characteristics and physicochemical properties in order to maximize the antibacterial efficacy of the therapeutic systems against multi-drug resistant pathogens. Additionally, the present paper provides a comprehensive and rigorous assessment of the latest clinical trials investigating the efficacy of AMPs in the treatment of skin and soft tissue infections, highlighting the relevant outcomes. Seeking to obtain novel and improved compounds with synergistic activity, while also decreasing some of the known side effects of AMPs, we present two employed strategies using AMPs: (i) AMPs-conjugated nanosystems for systemic and topical drug delivery systems and (ii) antibiotics-peptide conjugates as a strategy to overcome antibiotics resistance. Finally, an important property of some of the AMPs used in wound treatment is highlighted: their ability to help in wound healing by generally promoting cell proliferation and migration, and in some cases re-epithelialization and angiogenesis among others. Thus, as the pursuit of improvement is an ongoing effort, this work presents the advances made in the treatment of skin and soft tissue infections along with their advantages and limitations, while the still remaining challenges are addressed by providing future prospects and strategies to overcome them.

NIR photothermal-activable drug-conjugated microcapsules for in vitro targeted delivery and release: An alternative treatment of diabetic retinopathy.

Diabetic retinopathy (DR) is one of the most serious complications of diabetes, which leads to blindness. By addressing the traditional treatment limitations, we developed a novel light-responsive targeted polymeric microcapsule able to encapsulate a near infrared (NIR) photoactive fluorophore - Indocyanine Green, owing to its photothermal properties. Moreover, for an efficient in vitro targeted drug delivery, the fluorescent microsystem was conjugated with a therapeutic agent, i.e., Avastin drug - a Food and Drug Administration approved therapeutic antibody. The microcapsules were fabricated and evaluated in terms of morphology, encapsulation and drug conjugation efficiency and its release capacity. Avastin-conjugated microcapsules with an average dimension of 4.5 ± 0.35 µm were obtained, according to Scanning Electron Microscopy and Re-Scanning Confocal Microscopy (RCM) investigations. The capacity of the microcapsules to operate as effective phototherapeutic agents by generating heat under NIR laser irradiation was evaluated, followed by the investigation of the microcapsule's shell rupture and NIR laser-induced release of Avastin. The biocompatibility of the Avastin-conjugated microcapsules was proven by WST-1 assay. In vitro cellular internalization and localization of the Avastin microcarriers were determined through Conventional fluorescence microscopy, RCM and Transmission Electron Microscopy imaging techniques. Finally, the Avastin-conjugated microcapsules were validated for in vitro targeted drug delivery and release directly under simulated DR conditions, which could certainly become a successful strategy in DR fighting.

Assessing the Efficiency of Triangular Gold Nanoparticles as NIR Photothermal Agents In Vitro and Melanoma Tumor Model.

Photothermal therapy (PTT) is gaining a lot of interest as a cancer treatment option with minimal side effects due to the efficient photothermal agents employed. They are based on nanomaterials that, upon laser irradiation, absorb photon energy and convert it into heat to induce hyperthermia, which destroys the cancer cells. Here, the unique light-to-heat conversion features of three different gold nanotriangular nanoparticles (AuNTs) are evaluated with respect to their absorption properties to select the most efficient nanoheater with the highest potential to operate as an efficient photothermal agent. AuNTs with LSPR response in- and out- of resonance with the 785 nm near-infrared (NIR) excitation wavelength are investigated. Upon 15 min laser exposure, the AuNTs that exhibit a plasmonic response in resonance with the 785 nm laser line show the highest photothermal conversion efficacy of 80%, which correlates with a temperature increase of 22 °C. These photothermal properties are well-preserved in agarose-based skin biological phantoms that mimic the melanoma tumoral tissue and surrounding healthy tissue. Finally, in vitro studies on B16.F10 melanoma cells prove by fluorescence staining and MTT assay that the highest phototoxic effect after NIR laser exposure is induced by AuNTs with LSPR response in resonance with the employed laser line, thus demonstrating their potential implementation as efficient photothermal agents in PTT.

Hybrid polymeric therapeutic microcarriers for thermoplasmonic-triggered release of resveratrol.

Diabetic retinopathy (DR) is a severe ocular complication that causes retinal damage, being one of the leading causes of blindness globally, thus the development of new strategies to prevent and treat DR as well as other degenerative diseases is highly desired. This work is focused on the design and fabrication of an ingenious model of polymeric microcapsules (MC) for controlled drug delivery in human retina cells able to carry therapeutic resveratrol (RSV) molecules in tandem with active anisotropic gold bipyramidal nanoparticles (AuBPs) as efficient photothermal agents. Specifically, MC were developed via a Layer-by-Layer deposition technique, by successively adding oppositely charged polyelectrolytes on a RSV-conjugated calcium carbonate (CaCO3) core. For the monitorization and localization of the as-formed spherical fluorescent MC inside human retina pigmented epithelial (RPE) D407 cells, fluorescein isothiocyanate, a Food and Drug Administration approved fluorophore, was attached between the polyelectrolytes layers. High-performance liquid chromatography analysis revealed a loading efficiency of over 90% of RSV on the CaCO3 core and demonstrates its release upon NIR irradiation as a consequence of the thermoplasmonic effect of MC. The cytotoxicity of the RSV-carrying MC inside human retina cells was assessed by WST-1 assay. Finally, cellular internalization and localization of the MC inside living RPE cells were monitored via Conventional Fluorescence and Re-Scanning Confocal Fluorescence Microscopy. This research seeks to take use of the novel MC and implement them as potential intraocular RSV delivery vehicles for the therapy of DR.

Cardiac Troponin Biosensor Designs: Current Developments and Remaining Challenges.

Acute myocardial infarction (AMI) is considered as one of the main causes of death, threating human lives for decades. Currently, its diagnosis relies on electrocardiography (ECG), which has been proven to be insufficient. In this context, the efficient detection of cardiac biomarkers was proposed to overcome the limitations of ECG. In particular, the measurement of troponins, specifically cardiac troponin I (cTnI) and cardiac troponin T (cTnT), has proven to be superior in terms of sensitivity and specificity in the diagnosis of myocardial damage. As one of the most life-threatening conditions, specific and sensitive investigation methods that are fast, universally available, and cost-efficient to allow for early initiation of evidence-based, living-saving treatment are desired. In this review, we aim to present and discuss the major breakthroughs made in the development of cTnI and cTnT specific biosensor designs and analytical tools, highlighting the achieved progress as well as the remaining challenges to reach the technological goal of simple, specific, cheap, and portable testing chips for the rapid and efficient on-site detection of cardiac cTnI/cTnT biomarkers in order to diagnose and treat cardiovascular diseases at an incipient stage.

Antibody-functionalized theranostic protein nanoparticles for the synergistic deep red fluorescence imaging and multimodal therapy of ovarian cancer.

Among women, ovarian cancer is the fifth most frequent type of cancer, and despite benefiting from current standard treatment plans, 90% of patients relapse in the subsequent 18 months and, eventually, perish. As a result, via embracing nanotechnological advancements in the field of medical science, researchers working in the areas of cancer therapy and imaging are looking for the next breakthrough treatment strategy to ensure lower cancer recurrence rates and improved outcomes for patients. Herein, we design a novel phototheranostic agent with optical features in the biological window of the electromagnetic spectrum via encapsulating a newly synthesized phthalocyanine dye within biocompatible protein nanoparticles, allowing the targeted fluorescence imaging and synergistic dual therapy of ovarian cancer. The nanosized agent displays great biocompatibility and enhanced aqueous biostability and photothermal activity, as well as high reactive-oxygen-species generation efficiency. To achieve the active targeting of the desired malignant tissue and suppress the rapid clearance of the photosensitive agent from the peritoneal cavity, the nanoparticles are biofunctionalized with an anti-folate receptor antibody. A2780 ovarian cancer cells are employed to confirm the improved targeting capabilities and the in vitro cytotoxic efficiency of the theranostic nanoparticles after exposure to a 660 nm LED lamp; upon measurement via MTT and flow cytometry assays, a significant 95% decrease in the total number of viable cells is seen. Additionally, the therapeutic performance of our newly designed nanoparticles was evaluated in vivo, via real-time thermal monitoring and histopathological assays, upon the irradiation of tumour-bearing mice with a 660 nm LED lamp (0.05 W cm-2). Foremost, separately from steady-state fluorescence imaging, we found that, via utilizing FLIM investigations, the differences in fluorescence lifetimes of antibody biofunctionalized and non-functionalized nanoparticles can be correlated to different intracellular localization and internalization pathways of the fluorescent agent, which is relevant for the development of a cutting-edge method for the detection of cancer cells that overexpress folate receptors at their surfaces.

Fluorescent Phthalocyanine-Encapsulated Bovine Serum Albumin Nanoparticles: Their Deployment as Therapeutic Agents in the NIR Region.

In recent times, researchers have aimed for new strategies to combat cancer by the implementation of nanotechnologies in biomedical applications. This work focuses on developing protein-based nanoparticles loaded with a newly synthesized NIR emitting and absorbing phthalocyanine dye, with photodynamic and photothermal properties. More precisely, we synthesized highly reproducible bovine serum albumin-based nanoparticles (75% particle yield) through a two-step protocol and successfully encapsulated the NIR active photosensitizer agent, achieving a good loading efficiency of 91%. Making use of molecular docking simulations, we confirm that the NIR photosensitizer is well protected within the nanoparticles, docked in site I of the albumin molecule. Encouraging results were obtained for our nanoparticles towards biomedical use, thanks to their negatively charged surface (-13.6 ± 0.5 mV) and hydrodynamic diameter (25.06 ± 0.62 nm), favorable for benefitting from the enhanced permeability and retention effect; moreover, the MTT viability assay upholds the good biocompatibility of our NIR active nanoparticles. Finally, upon irradiation with an NIR 785 nm laser, the dual phototherapeutic effect of our NIR fluorescent nanoparticles was highlighted by their excellent light-to-heat conversion performance (photothermal conversion efficiency 20%) and good photothermal and size stability, supporting their further implementation as fluorescent therapeutic agents in biomedical applications.

Versatile Polypeptide-Functionalized Plasmonic Paper as Synergistic Biocompatible and Antimicrobial Nanoplatform.

Nowadays, thanks to nanotechnological progress, which itself guides us more and more closely toward not only the efficient design of innovative nanomaterials or nanostructures, but to the improvement of their functionality, we benefit from an important asset in the battle against pathogenic illnesses. Herein, we report a versatile biocompatible plasmonic nanoplatform based on a Whatman paper incorporating positively-charged gold nanospherical particles via the immersion approach. The morphological characterization of the as-engineered-plasmonic paper was examined by SEM (scanning electron microscopy) and HRTEM (high-resolution transmission electron microscopy) investigations, while its surface chemical modification with a synthetic polypeptide, specifically RRWHRWWRR-NH2 (P2), was proved by monitoring the plasmonic response of loaded gold nanospheres and the emission signal of P2 via fluorescence spectroscopy. The as-functionalized plasmonic paper is non-cytotoxic towards BJ fibroblast human cells at bactericidal concentrations. Finally, the antimicrobial activity of the P2-functionalized plasmonic paper on both planktonic bacteria and biofilms was tested against two reference strains: Gram-positive Bacteria, i.e., Staphylococcus aureus and the Gram-negative Bacteria, i.e., Escherichia coli, determining microbial inhibition of up to 100% for planktonic bacteria. In line with the above presented nanoplatform's proper design, followed by their functionalization with active antimicrobial peptides, new roads can be open for determining antibiotic-free treatments against different relevant pathogens.

ICG-loaded gold nano-bipyramids with NIR activatable dual PTT-PDT therapeutic potential in melanoma cells.

A great amount of effort is directed towards the progress of cancer treatment approaches aspiring to develop non-invasive, targeted and highly efficient therapies. In this context, Photothermal (PTT) and Photodynamic (PDT) Therapies were proven as promising. This work aims to integrate the therapeutic activities of two near-infrared (NIR) photoactive biomaterials - gold nano-bipyramids (AuBPs) and Indocyanine Green (ICG) - into one single targeted hybrid nanosystem able to operate as dual PTT-PDT agent with higher efficiency compared with each one alone. Firstly, different aspect ratio' AuBPs were systematically investigated in water solution for their intrinsic ability to efficiently generate toxic reactive oxygen species, namely oxygen singlet (1O2), under NIR laser irradiation, as this effect is less investigated in literature. Interestingly, the photodynamic activity of AuBPs measured by monitoring the photooxidation of 9,10-Anthracenediyl-bis(methylene)dimalonic acid (ABDA) - a well-known 1O2 sensor, is important, counting for 30 % decrease in ABDA optical absorbance for the most active AuBPs, well-correlating with the previously determined photothermal conversion efficiency. Furthermore, ICG was successfully grafted onto the Poly-lactic acid (PLA) coating of plasmonic nanoparticles and, consequently, the as-designed fully integrated hybrid nanosystem shows improved PTT-PDT performance in solution. Specifically, by triggering simultaneous PTT-PDT activities, the 1O2 amount is doubled, while the heating monitoring shows higher and faster increase in temperature compared to AuBPs alone. Finally, the efficiency of the combined PTT-PDT therapeutic activity was validated in vitro against B16-F10 cell line by covalent conjugation of the nanosystem with Folic Acid, which ensures the cellular recognition by overexpression of folate receptor.

Calligraphed Selective Plasmonic Arrays on Paper Platforms for Complementary Dual Optical "ON/OFF Switch" Sensing.

Designing innovative (nano)detection platforms, respecting their low-cost and fabrication simplicity, capable to chemically detect multiple target analytes by employing the same engineered device, is still a great challenge in the multiplexed biosensor development. In this scientific context, in the current manuscript, we exploit the low-cost plasmonic calligraphy as a versatile approach to directly draw continuous plasmonic lines on Whatman paper using a regular ballpoint pen successively filled with two different anisotropic nanoparticles shapes (gold bipyramids-AuBPs and gold nanorods-AuNRs) as colloidal inks. After the efficient immobilization of the positively-charged AuBPs and AuNRs onto the paper fibres, proved by Scanning Electron Microscopy (SEM) investigations, the specificity of our as-calligraphed-paper platform is ensured by coating the selected lines with a thin layer of anionic poly(styrene sulfonate) polyelectrolyte, creating, consequently, a well-defined plasmonic array of charge-selective regions. Finally, the functionality of the well-isolated and as-miniaturized active plasmonic array is, subsequently, tested using the anionic Rose-Bengal and cationic Rhodamine 6G target analytes and proved by complementary dual optical "ON/OFF Switch" sensing (i.e. Surface-enhanced Raman Scattering sensing/metal-enhanced fluorescence sensing) onto the same plasmonic line, developing thus a simple multiplexed plasmonic array platform, which could further facilitate the well-desired biomarker detection in complex mixtures.

Microfluidic platform for integrated plasmonic detection in laminal flow.

In this work, we propose a novel approach to design robust microfluidic devices with integrated plasmonic transducers allowing portability, reduced analysis time through dynamic measurements and high sensitivity. Specifically, the strategy we apply involves two steps: (i) the controlled deposition of gold bipyramidal nanoparticles (AuBPs) onto a functionalized solid glass substrate and (ii) the integration of the as-fabricated plasmonic substrate into a polydimethylsiloxane (PDMS) microfluidic circuit. The localized surface plasmon resonance (LSPR) sensitivity of the plasmonic-microfluidic device was evaluated by monitoring the optical responses at refractive index changes, proving a bulk sensitivity of 243 nm RIU-1 for the longitudinal LSPR band of isolated AuBPs and 150 nm RIU-1 for the band assigned to end-to-end linked nanoparticles. A strong electric field generated in the gaps between AuBPs-due to the generation of the so-called extrinsic 'hot-spots'-was subsequently proved by the volumetric surface enhanced Raman scattering (SERS) detection of molecules in continuous flow conditions by loading the analyte into the microfluidic channel via a syringe pump. In conclusion, our miniaturized portable microfluidic system aims to detect and identify, in real-time with high accuracy, analyte molecules in laminal flow, thus providing a groundwork for further complex biosensing applications.

Assessment of the photothermal conversion efficiencies of tunable gold bipyramids under irradiation by two laser lines in a NIR biological window.

In this work, we present a thorough study on the evaluation of the photothermal conversion efficiencies of gold nanobipyramids (AuBPs) under irradiation by two phototherapeutic laser lines at 785 and 808 nm. Due to fine tunability of the longitudinal localized surface plasmon resonance (LSPR) of AuBPs along the entire biological window, AuBPs have great potential to be applied as efficient photothermal agents in specific hyperthermia applications. Aiming to identify the most suitable AuBPs for each laser line, here we synthetized AuBPs of six different aspect ratios with longitudinal LSPR ranging from 662 to 929 nm and compared their intrinsic photothermal properties in colloidal solutions under laser irradiation at various experimental parameters such as sample volume, optical density and laser power. In addition, the experimental plasmonic resonances of the as-prepared AuBPs were perfectly simulated and their theoretical extinction and absorption cross-sections provided by finite-difference time-domain technique. Finally, we found photothermal conversion efficiencies ranging from 40% to 97% for all AuBPs systems under both NIR irradiation laser lines concluding that for the 785 nm excitation wavelength the AuBPs with longitudinal LSPR at 802 nm are most efficient, whereas in the case of the 808 nm laser line the AuBPs with optical response at 812 nm exhibit the best thermal performance. These studies are crucial for designing AuBPs as effective phototherapy agents acting alone or in combination with other plasmon-based or plasmon-assisted therapies.

Multimodal Biosensing on Paper-Based Platform Fabricated by Plasmonic Calligraphy Using Gold Nanobypiramids Ink.

In this work, we design new plasmonic paper-based nanoplatforms with interesting capabilities in terms of sensitivity, efficiency, and reproducibility for promoting multimodal biodetection via Localized Surface Plasmon Resonance (LSPR), Surface Enhanced Raman Spectroscopy (SERS), and Metal Enhanced Fluorescence (MEF). To succeed, we exploit the unique optical properties of gold nanobipyramids (AuBPs) deposited onto the cellulose fibers via plasmonic calligraphy using a commercial pen. The first step of the biosensing protocol was to precisely graft the previously chemically-formed p-aminothiophenol@Biotin system, as active recognition element for target streptavidin detection, onto the plasmonic nanoplatform. The specific capture of the target protein was successfully demonstrated using three complementary sensing techniques. As a result, while the LSPR based sensing capabilities of the nanoplatform were proved by successive 13-18 nm red shifts of the longitudinal LSPR associated with the change of the surface RI after each step. By employing the ultrasensitive SERS technique, we were able to indirectly confirm the molecular identification of the biotin-streptavidin interaction due to the protein fingerprint bands assigned to amide I, amide III, and Trp vibrations. Additionally, the formed biotin-streptavidin complex acted as a spacer to ensure an optimal distance between the AuBP surface and the Alexa 680 fluorophore for achieving a 2-fold fluorescence emission enhancement of streptavidin@Alexa 680 on the biotinylated nanoplatform compared to the same complex on bare paper (near the plasmonic lines), implementing thus a novel MEF sensing nanoplatform. Finally, by integrating multiple LSPR, SERS, and MEF nanosensors with multiplex capability into a single flexible and portable plasmonic nanoplatform, we could overcome important limits in the field of portable point-of-care diagnostics.

Designing Efficient Low-Cost Paper-Based Sensing Plasmonic Nanoplatforms.

Paper-based platforms can be a promising choice as portable sensors due to their low-cost and facile fabrication, ease of use, high sensitivity, specificity and flexibility. By combining the qualities of these 3D platforms with the optical properties of gold nanoparticles, it is possible to create efficient nanodevices with desired biosensing functionalities. In this work, we propose a new plasmonic paper-based dual localized surface plasmon resonance⁻surface-enhanced Raman scattering (LSPR-SERS) nanoplatform with improved detection abilities in terms of high sensitivity, uniformity and reproducibility. Specifically, colloidal gold nanorods (GNRs) with a well-controlled plasmonic response were firstly synthesized and validated as efficient dual LSPR-SERS nanosensors in solution using the p-aminothiophenol (p-ATP) analyte. GNRs were then efficiently immobilized onto the paper via the immersion approach, thus obtaining plasmonic nanoplatforms with a modulated LSPR response. The successful deposition of the nanoparticles onto the cellulose fibers was confirmed by LSPR measurements, which demonstrate the preserved plasmonic response after immobilization, as well as by dark-field microscopy and scanning electron microscopy investigations, which confirm their uniform distribution. Finally, a limit of detection for p-ATP as low as 10-12 M has been achieved by our developed SERS-based paper nanoplatform, proving that our optimized plasmonic paper-based biosensing design could be further considered as an excellent candidate for miniaturized biomedical applications.

Gold NanoBipyramids Performing as Highly Sensitive Dual-Modal Optical Immunosensors.

In this work, we demonstrate the feasibility of gold bipyramidal-shaped nanoparticles (AuBPs) to be used as active plasmonic nanoplatforms for the detection of the biotin-streptavidin interaction in aqueous solution via both Localized Surface Plasmon Resonance and Surface Enhanced Raman Scattering (LSPR/SERS). Our proof of concept exploits the precise attachment of the recognition element at the tips of AuBPs, where the electromagnetic field is stronger, which is beneficial to the surface sensitivity of longitudinal LSPR on the local refractive index and to the electromagnetic enhancement of SERS activity, too. Indeed, successive red shifts of the longitudinal LSPR associated with increased local refractive index reveal the attachment of para-aminothiophenol (p-ATP) chemically labeled Biotin to the Au surface and the specific capture of the target protein by biotin-functionalized AuBPs. Finite-Difference Time-Domain simulations based on the reconstructed index of refraction confirm LSPR measurements. However, the molecular identification of the biotin-streptavidin interaction remains elusive by LSPR investigation alone. Remarkably, we succeeded to complement the LSPR detection with reliable SERS measurements which permitted to (a) certify the molecular identification of biotin-streptavidin interaction and (b) extend the limit of detection of streptavidin in solution toward 10-12 M. Finally, to further probe the possibility to implement the AuBPs as dual LSPR-SERS based immunoassays in solution for real clinical diagnostics, we additionally investigated the AuBP's performance to transduce the specific antihuman IgG- human IgG binding event, providing thus a reference design for building unique plasmonic immunoassays for dual-optical detection of target proteins in aqueous solution.

A simple and efficient design to improve the detection of biotin-streptavidin interaction with plasmonic nanobiosensors.

In this manuscript we propose a simple and efficient strategy to improve the sensitivity of localized surface plasmon resonance (LSPR) shift-based biosensors using biotin-streptavidin recognition interaction as a proof-of-concept. Specifically, biotin molecules are immobilized on a low-cost plasmonic LSPR biosensor based on annealed self-assembled spherical gold nanoparticles (AuNSs) and successively incubated with increasing concentrations of streptavidin, achieving a limit of detection (LOD) of 5nM. Interestingly, when the detection is performed by the same biotin-functionalized plasmonic AuNSs substrate but against streptavidin previously conjugated to gold nanorods, the LSPR shift is 26-fold enhanced. Moreover, we confirm these results through numerical simulations and demonstrate that the proposed sensing architecture can operate as transducer not only to confirm the adsorption of bioanalyte but also to provide the chemical identity of the capture and targeted molecules from their vibrational Raman fingerprints. Therefore, we are confident that the development of such plasmonic biosensors that use metallic labels for improving the sensitivity of detection could become highly promising for future point-of-care diagnostic assays, pushing sensitivity towards single-molecule detection limit.