pH-Modulated Nanoarchitectonics for Enhancement of Multivalency-Induced Vesicle Shape Deformation at Receptor-Presenting Lipid Membrane Interfaces.

Multivalent ligand-receptor interactions between receptor-presenting lipid membranes and ligand-modified biological and biomimetic nanoparticles influence cellular entry and fusion processes. Environmental pH changes can drive these membrane-related interactions by affecting membrane nanomechanical properties. Quantitatively, however, the corresponding effects on high-curvature, sub-100 nm lipid vesicles are scarcely understood, especially in the multivalent binding context. Herein, we employed the label-free localized surface plasmon resonance (LSPR) sensing technique to track the multivalent attachment kinetics, shape deformation, and surface coverage of biotin ligand-functionalized, zwitterionic lipid vesicles with different ligand densities on a streptavidin receptor-coated supported lipid bilayer under varying pH conditions (4.5, 6, 7.5). Our results demonstrate that more extensive multivalent interactions caused greater vesicle shape deformation across the tested pH conditions, which affected vesicle surface packing as well. Notably, there were also pH-specific differences, i.e., a higher degree of vesicle shape deformation was triggered at a lower multivalent binding energy in pH 4.5 than in pH 6 and 7.5 conditions. These findings support that the nanomechanical properties of high-curvature lipid membranes, especially the membrane bending energy and the corresponding responsiveness to multivalent binding interactions, are sensitive to solution pH, and indicate that multivalency-induced vesicle shape deformation occurs slightly more readily in acidic pH conditions relevant to biological environments.

Chemical design principles of next-generation antiviral surface coatings.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has accelerated efforts to develop high-performance antiviral surface coatings while highlighting the need to build a strong mechanistic understanding of the chemical design principles that underpin antiviral surface coatings. Herein, we critically summarize the latest efforts to develop antiviral surface coatings that exhibit virus-inactivating functions through disrupting lipid envelopes or protein capsids. Particular attention is focused on how cutting-edge advances in material science are being applied to engineer antiviral surface coatings with tailored molecular-level properties to inhibit membrane-enveloped and non-enveloped viruses. Key topics covered include surfaces functionalized with organic and inorganic compounds and nanoparticles to inhibit viruses, and self-cleaning surfaces that incorporate photocatalysts and triplet photosensitizers. Application examples to stop COVID-19 are also introduced and demonstrate how the integration of chemical design principles and advanced material fabrication strategies are leading to next-generation surface coatings that can help thwart viral pandemics and other infectious disease threats.

Scalable Fabrication of Quasi-One-Dimensional Gold Nanoribbons for Plasmonic Sensing.

Plasmonic nanostructures have a wide range of applications, including chemical and biological sensing. However, the development of techniques to fabricate submicrometer-sized plasmonic structures over large scales remains challenging. We demonstrate a high-throughput, cost-effective approach to fabricate Au nanoribbons via chemical lift-off lithography (CLL). Commercial HD-DVDs were used as large-area templates for CLL. Transparent glass slides were coated with Au/Ti films and functionalized with self-assembled alkanethiolate monolayers. Monolayers were patterned with lines via CLL. The lifted-off, exposed regions of underlying Au were selectively etched into large-area grating-like patterns (200 nm line width; 400 nm pitch; 60 nm height). After removal of the remaining monolayers, a thin In2O3 layer was deposited and the resulting gratings were used as plasmonic sensors. Distinct features in the extinction spectra varied in their responses to refractive index changes in the solution environment with a maximum bulk sensitivity of ∼510 nm/refractive index unit. Sensitivity to local refractive index changes in the near-field was also achieved, as evidenced by real-time tracking of lipid vesicle or protein adsorption. These findings show how CLL provides a simple and economical means to pattern large-area plasmonic nanostructures for applications in optoelectronics and sensing.

Elucidating How Different Amphipathic Stabilizers Affect BSA Protein Conformational Properties and Adsorption Behavior.

Natural proteins such as bovine serum albumin (BSA) are readily extracted from biological fluids and widely used in various applications such as drug delivery and surface coatings. It is standard practice to dope BSA proteins with an amphipathic stabilizer, most commonly fatty acids, during purification steps to maintain BSA conformational properties. There have been extensive studies investigating how fatty acids and related amphiphiles affect solution-phase BSA conformational properties, while it is far less understood how amphipathic stabilizers might influence noncovalent BSA adsorption onto solid supports, which is practically relevant to form surface coatings. Herein, we systematically investigated the binding interactions between BSA proteins and different molar ratios of caprylic acid (CA), monocaprylin (MC), and methyl caprylate (ME) amphiphiles-all of which have 8-carbon-long, saturated hydrocarbon chains with distinct headgroups-and resulting effects on BSA adsorption behavior on silica surfaces. Our findings revealed that anionic CA had the greatest binding affinity to BSA, which translated into greater solution-phase conformational stability and reduced adsorption-related conformational changes along with relatively low packing densities in fabricated BSA adlayers. On the other hand, nonionic MC had moderate binding affinity to BSA and could stabilize BSA conformational properties in the solution and adsorbed states while also enabling BSA adlayers to form with higher packing densities. We discuss physicochemical factors that contribute to these performance differences, and our findings demonstrate how rational selection of amphiphile type and amount can enable control over BSA adlayer properties, which could lead to improved BSA protein-based surface coatings.

Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide.

Zika virus is a mosquito-borne virus that is associated with neurodegenerative diseases, including Guillain-Barré syndrome1 and congenital Zika syndrome2. As Zika virus targets the nervous system, there is an urgent need to develop therapeutic strategies that inhibit Zika virus infection in the brain. Here, we have engineered a brain-penetrating peptide that works against Zika virus and other mosquito-borne viruses. We evaluated the therapeutic efficacy of the peptide in a lethal Zika virus mouse model exhibiting systemic and brain infection. Therapeutic treatment protected against mortality and markedly reduced clinical symptoms, viral loads and neuroinflammation, as well as mitigated microgliosis, neurodegeneration and brain damage. In addition to controlling systemic infection, the peptide crossed the blood-brain barrier to reduce viral loads in the brain and protected against Zika-virus-induced blood-brain barrier injury. Our findings demonstrate how engineering strategies can be applied to develop peptide therapeutics and support the potential of a brain-penetrating peptide to treat neurotropic viral infections.

Molecular diffusion and nano-mechanical properties of multi-phase supported lipid bilayers.

Understanding the properties of cell membranes is important in the fields of fundamental and applied biology. While the characterization of simplified biological membrane mimics comprising liquid phase lipids has been routinely performed due to the ease of fabrication, the characterization of more realistic membrane mimics comprising multi-phase lipids remains challenging due to more complicated fabrication requirements. Herein, we report a convenient approach to fabricate and characterize multi-phase supported lipid bilayers (SLBs). We employed the solvent-assisted lipid bilayer (SALB) formation method to fabricate mixed lipid bilayers comprising liquid phase 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and gel phase 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipids at room temperature. The fabrication procedure was performed inside a newly designed microfluidic chamber, which facilitated the subsequent characterization of the SLBs without exposure to air. The SLBs were then characterized via fluorescence microscopy, fluorescence recovery after photobleaching (FRAP), atomic force microscopy (AFM) and AFM-based force-distance measurements. Interestingly, results from these characterization techniques revealed that regardless of the gel phase composition, the SALB formation method consistently yielded uniform SLBs at room temperature, even though the transition temperature of DPPC is considerably higher. Furthermore, the composition ratio of DOPC and DPPC in the precursor solution is well reproduced in the fabricated SLBs. We also identified from diffusivity measurements that a high ratio of gel phase lipid revitalizes lipid-lipid interactions, which led to reduced molecular fluidity and the suppression of thermal undulation within the SLBs. Taken together, our results highlight the robustness of the SALB formation method that allows the fabrication of complex lipid bilayers with a high degree of precision, which is suitable for functional studies of biological membranes.

Nanoplasmonic Ruler for Measuring Separation Distance between Supported Lipid Bilayers and Oxide Surfaces.

Unraveling the details of how supported lipid bilayers (SLBs) are coupled to oxide surfaces is experimentally challenging, and there is an outstanding need to develop highly surface-sensitive measurement strategies to determine SLB separation distances. Indeed, subtle variations in separation distance can be associated with significant differences in bilayer-substrate interaction energy. Herein, we report a nanoplasmonic ruler strategy to measure the absolute separation distance between SLBs and oxide surfaces. A localized surface plasmon resonance (LSPR) sensor was employed to track SLB formation onto titania- and silica-coated gold nanodisk arrays. To interpret measurement data, an analytical model relating the LSPR measurement response to bilayer-substrate separation distance was developed based on finite-difference time-domain (FDTD) simulations and theoretical calculations. The results indicate that there is a larger separation distance between SLBs and titania surfaces than silica surfaces, and the trend was consistent across three tested lipid compositions. We discuss these findings within the context of the interfacial forces underpinning bilayer-substrate interactions, and the nanoplasmonic ruler strategy provides the first direct experimental evidence comparing SLB separation distances on titania and silica surfaces.

Nanoplasmonic Sensing Architectures for Decoding Membrane Curvature-Dependent Biomacromolecular Interactions.

Nanoplasmonic sensors have emerged as a promising measurement approach to track biomacromolecular interactions involving lipid membrane interfaces. By taking advantage of nanoscale fabrication capabilities, it is possible to design sensing platforms with various architectural configurations. Such capabilities open the door to fabricating lipid membrane-coated nanoplasmonic sensors with varying degrees of membrane curvature in order to understand how biomacromolecular interaction processes are influenced by membrane curvature. Herein, we employed an indirect nanoplasmonic sensing approach to characterize the fabrication of supported lipid bilayers (SLBs) on silica-coated nanowell and nanodisk sensing platforms and to investigate how membrane curvature influences membrane-peptide interactions by evaluating the corresponding measurement responses from different spectral signatures that are sensitive to specific regions of the sensor geometries. SLBs were prepared by the vesicle fusion method, as monitored in real-time by nanoplasmonic sensing measurements and further characterized by fluorescence recovery after photobleaching (FRAP) experiments. By resolving different spectral signatures in the nanoplasmonic sensing measurements, it was determined that peptide binding induces membrane disruption at positively curved membrane regions, while peptide binding without subsequent disruption was observed at planar and negatively curved regions. These findings are consistent with the peptide's known preference to selectively form pores in positively curved membranes, providing validation to the nanoplasmonic sensing approach and highlighting how the integration of nanoplasmonic sensors with different nanoscale architectures can be utilized to study the influence of membrane curvature on biomacromolecular interaction processes.

Quantitative Comparison of Protein Adsorption and Conformational Changes on Dielectric-Coated Nanoplasmonic Sensing Arrays.

Nanoplasmonic sensors are a popular, surface-sensitive measurement tool to investigate biomacromolecular interactions at solid-liquid interfaces, opening the door to a wide range of applications. In addition to high surface sensitivity, nanoplasmonic sensors have versatile surface chemistry options as plasmonic metal nanoparticles can be coated with thin dielectric layers. Within this scope, nanoplasmonic sensors have demonstrated promise for tracking protein adsorption and substrate-induced conformational changes on oxide film-coated arrays, although existing studies have been limited to single substrates. Herein, we investigated human serum albumin (HSA) adsorption onto silica- and titania-coated arrays of plasmonic gold nanodisks by localized surface plasmon resonance (LSPR) measurements and established an analytical framework to compare responses across multiple substrates with different sensitivities. While similar responses were recorded on the two substrates for HSA adsorption under physiologically-relevant ionic strength conditions, distinct substrate-specific behavior was observed at lower ionic strength conditions. With decreasing ionic strength, larger measurement responses occurred for HSA adsorption onto silica surfaces, whereas HSA adsorption onto titania surfaces occurred independently of ionic strength condition. Complementary quartz crystal microbalance-dissipation (QCM-D) measurements were also performed, and the trend in adsorption behavior was similar. Of note, the magnitudes of the ionic strength-dependent LSPR and QCM-D measurement responses varied, and are discussed with respect to the measurement principle and surface sensitivity of each technique. Taken together, our findings demonstrate how the high surface sensitivity of nanoplasmonic sensors can be applied to quantitatively characterize protein adsorption across multiple surfaces, and outline broadly-applicable measurement strategies for biointerfacial science applications.

Probing Spatial Proximity of Supported Lipid Bilayers to Silica Surfaces by Localized Surface Plasmon Resonance Sensing.

On account of high surface sensitivity, localized surface plasmon resonance (LSPR) sensors have proven widely useful for studying lipid membrane configurations at solid-liquid interfaces. Key measurement capabilities include distinguishing adsorbed vesicles from supported lipid bilayers (SLBs) as well as profiling the extent of deformation among adsorbed vesicles. Such capabilities rely on detecting geometrical changes in lipid membrane configuration on a length scale that is comparable to the decay length of the LSPR-induced electromagnetic field enhancement (∼5-20 nm). Herein, we report that LSPR sensors are also capable of probing nanoscale (∼1 nm) variations in the distance between SLBs and underlying silica-coated surfaces. By tuning the electrostatic properties of lipid membranes, we could modulate the bilayer-substrate interaction and corresponding separation distance, as verified by simultaneous LSPR and quartz crystal microbalance-dissipation (QCM-D) measurements. Theoretical calculations of the expected variation in the LSPR measurement response agree well with experimental results and support that the LSPR measurement response is sensitive to subtle variations in the bilayer-substrate separation distance.

Indirect Nanoplasmonic Sensing Platform for Monitoring Temperature-Dependent Protein Adsorption.

The development of highly surface-sensitive measurement approaches to monitor protein adsorption across different temperatures would advance understanding of how thermally activated processes contribute to the denaturation of adsorbed proteins. Herein, we established an indirect nanoplasmonic sensing approach to monitor the temperature-dependent adsorption and denaturation of bovine serum albumin (BSA) protein onto a silica-coated array of plasmonic gold nanodisks. A theoretical model was developed to explain how the denaturation of an individual, adsorbed protein molecule influences the localized surface plasmon resonance (LSPR) measurement response and provided an analytical framework to estimate the effect of temperature-dependent protein denaturation on the corresponding adsorption kinetics. The sensing performance of this measurement platform was also characterized across the tested range of temperatures. With increasing temperature (up to 50 °C), it was observed that adsorbed proteins undergo greater denaturation. Circular dichroism spectroscopy and dynamic light scattering experiments verified that individual BSA monomers in bulk solution had increasingly lower conformational stability at higher temperatures within this range, which correlated with the extent of denaturation in the adsorbed state. At higher temperatures, distinct kinetic profiles arising from multilayer/aggregate formation on the sensor surface were also detected. Taken together, our findings identify that the high surface sensitivity and temperature stability of LSPR sensors make them broadly useful analytical tools for monitoring thermally activated biomacromolecular interaction processes.

Quantitative Profiling of Nanoscale Liposome Deformation by a Localized Surface Plasmon Resonance Sensor.

Characterizing the shape of sub-100 nm, biological soft-matter particulates (e.g., liposomes and exosomes) adsorbed at a solid-liquid interface remains a challenging task. Here, we introduce a localized surface plasmon resonance (LSPR) sensing approach to quantitatively profile the deformation of nanoscale, fluid-phase 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes contacting a titanium dioxide substrate. Experimental and theoretical results validate that, due to its high sensitivity to the spatial proximity of phospholipid molecules near the sensor surface, the LSPR sensor can discriminate fine differences in the extent of ionic strength-modulated liposome deformation at both low and high surface coverages. By contrast, quartz crystal microbalance-dissipation (QCM-D) measurements performed with equivalent samples were qualitatively sensitive to liposome deformation only at saturation coverage. Control experiments with stiffer, gel-phase 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes verified that the LSPR measurement discrimination arises from the extent of liposome deformation, while the QCM-D measurements yield a more complex response that is also sensitive to the motion of adsorbed liposomes and coupled solvent along with lateral interactions between liposomes. Collectively, our findings demonstrate the unique measurement capabilities of LSPR sensors in the area of biological surface science, including competitive advantages for probing the shape properties of adsorbed, nanoscale biological particulates.

Investigating how vesicle size influences vesicle adsorption on titanium oxide: a competition between steric packing and shape deformation.

Understanding the adsorption behavior of lipid vesicles at solid-liquid interfaces is important for obtaining fundamental insights into soft matter adsorbates as well as for practical applications such as supported lipid bilayer (SLB) fabrication. While the process of SLB formation has been highly scrutinized, less understood are the details of vesicle adsorption without rupture, especially at high surface coverages. Herein, we tackle this problem by employing simultaneous quartz crystal microbalance-dissipation (QCM-D) and localized surface plasmon resonance (LSPR) measurements in order to investigate the effect of vesicle size (84-211 nm diameter) on vesicle adsorption onto a titanium oxide surface. Owing to fundamental differences in the measurement principles of the two techniques as well as a mismatch in probing volumes, it was possible to determine both the lipid mass adsorbed near the sensor surface as well as the total mass of adsorbed lipid and hydrodynamically coupled solvent in the adsorbed vesicle layer as a whole. With increasing vesicle size, the QCM-D frequency signal exhibited monotonic behavior reaching an asymptotic value, whereas the QCM-D energy dissipation signal continued to increase according to the vesicle size. In marked contrast, the LSPR-tracked lipid mass near the sensor surface followed a parabolic trend, with the greatest corresponding measurement response occurring for intermediate-size vesicles. The findings reveal that the maximum extent of adsorbed vesicles contacting a solid surface occurs at an intermediate vesicle size due to the competing influences of vesicle deformation and steric packing. Looking forward, such information can be applied to control the molecular self-assembly of phospholipid assemblies as well as provide the basis for investigating deformable, soft matter adsorbates.

Controlling adsorption and passivation properties of bovine serum albumin on silica surfaces by ionic strength modulation and cross-linking.

Understanding the physicochemical factors that influence protein adsorption onto solid supports holds wide relevance for fundamental insights into protein structure and function as well as for applications such as surface passivation. Ionic strength is a key parameter that influences protein adsorption, although how its modulation might be utilized to prepare well-coated protein adlayers remains to be explored. Herein, we investigated how ionic strength can be utilized to control the adsorption and passivation properties of bovine serum albumin (BSA) on silica surfaces. As protein stability in solution can influence adsorption kinetics, the size distribution and secondary structure of proteins in solution were first characterized by dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), and circular dichroism (CD) spectroscopy. A non-monotonic correlation between ionic strength and protein aggregation was observed and attributed to colloidal agglomeration, while the primarily α-helical character of the protein in solution was maintained in all cases. Quartz crystal microbalance-dissipation (QCM-D) experiments were then conducted in order to track protein adsorption onto silica surfaces as a function of ionic strength, and the measurement responses indicated that total protein uptake at saturation coverage is lower with increasing ionic strength. In turn, the QCM-D data and the corresponding Voigt-Voinova model analysis support that the surface area per bound protein molecule is greater with increasing ionic strength. While higher protein uptake under lower ionic strengths by itself did not result in greater surface passivation under subsequent physiologically relevant conditions, the treatment of adsorbed protein layers with a gluteraldehyde cross-linking agent stabilized the bound protein in this case and significantly improved surface passivation. Collectively, our findings demonstrate that ionic strength modulation influences BSA adsorption uptake on account of protein spreading and can be utilized in conjunction with covalent cross-linking strategies to prepare well-coated protein adlayers for improved surface passivation.

Probing the Interaction of Dielectric Nanoparticles with Supported Lipid Membrane Coatings on Nanoplasmonic Arrays.

The integration of supported lipid membranes with surface-based nanoplasmonic arrays provides a powerful sensing approach to investigate biointerfacial phenomena at membrane interfaces. While a growing number of lipid vesicles, protein, and nucleic acid systems have been explored with nanoplasmonic sensors, there has been only very limited investigation of the interactions between solution-phase nanomaterials and supported lipid membranes. Herein, we established a surface-based localized surface plasmon resonance (LSPR) sensing platform for probing the interaction of dielectric nanoparticles with supported lipid bilayer (SLB)-coated, plasmonic nanodisk arrays. A key emphasis was placed on controlling membrane functionality by tuning the membrane surface charge vis-à-vis lipid composition. The optical sensing properties of the bare and SLB-coated sensor surfaces were quantitatively compared, and provided an experimental approach to evaluate nanoparticle-membrane interactions across different SLB platforms. While the interaction of negatively-charged silica nanoparticles (SiNPs) with a zwitterionic SLB resulted in monotonic adsorption, a stronger interaction with a positively-charged SLB resulted in adsorption and lipid transfer from the SLB to the SiNP surface, in turn influencing the LSPR measurement responses based on the changing spatial proximity of transferred lipids relative to the sensor surface. Precoating SiNPs with bovine serum albumin (BSA) suppressed lipid transfer, resulting in monotonic adsorption onto both zwitterionic and positively-charged SLBs. Collectively, our findings contribute a quantitative understanding of how supported lipid membrane coatings influence the sensing performance of nanoplasmonic arrays, and demonstrate how the high surface sensitivity of nanoplasmonic sensors is well-suited for detecting the complex interactions between nanoparticles and lipid membranes.

Integration of Quartz Crystal Microbalance-Dissipation and Reflection-Mode Localized Surface Plasmon Resonance Sensors for Biomacromolecular Interaction Analysis.

The combination of label-free, surface-sensitive measurement techniques based on different physical principles enables detailed characterization of biomacromolecular interactions at solid-liquid interfaces. To date, most combined measurement systems have involved experimental techniques with similar probing volumes, whereas the potential of utilizing techniques with different surface sensitivities remains largely unexplored, especially for data interpretation. Herein, we report a combined measurement approach that integrates a conventional quartz crystal microbalance-dissipation (QCM-D) setup with a reflection-mode localized surface plasmon (LSPR) sensor. Using this platform, we investigate vesicle adsorption on a titanium oxide-coated sensing substrate along with the amphipathic, α-helical (AH) peptide-induced structural transformation of surface-adsorbed lipid vesicles into a supported lipid bilayer (SLB) as a model biomacromolecular interaction. While the QCM-D and LSPR signals both detected mass uptake arising from vesicle adsorption, tracking the AH peptide-induced structural transformation revealed more complex measurement responses based on the different surface sensitivities of the two techniques. In particular, the LSPR signal recorded an increase in optical mass near the sensor surface which indicated SLB formation, whereas the QCM-D signals detected a significant loss in net acoustic mass due to excess lipid and coupled solvent leaving the probing volume. Importantly, these measurement capabilities allowed us to temporally distinguish the process of SLB formation at the sensor surface from the overall structural transformation process. Looking forward, these label-free measurement capabilities to simultaneously probe adsorbates at multiple length scales will provide new insights into complex biomacromolecular interactions.

Oriented gold nanoparticle aggregation for colorimetric sensors with surprisingly high analytical figures of merit.

The common drawbacks of current colorimetric sensors using gold nanoparticle aggregation is its relatively low sensitivity and narrow dynamic range, which restrict their application in real sample analysis when competing with other analytical techniques such as fluorescence and chemiluminescence. In this article, we demonstrate a novel strategy to construct colorimetric sensors based on gold nanoparticle aggregation. Unlike the conventional colorimetric sensors which cause the formation of large nanoparticle aggregates, in our strategy, dimers are selectively formed upon target binding, which results in significantly improved long-term stability and a more than 2 orders of magnitude wider dynamic range of detection than that of the conventional colorimetric sensors. In addition, a strategy to minimize the interparticle gap through the formation of a Y-shaped DNA duplex enables to increase the limit of detection by 10,000 times. The analytical figures of merit of the proposed sensor are comparable to those of the fluorescence-based sensors.

Solid-phase colorimetric sensor based on gold nanoparticle-loaded polymer brushes: lead detection as a case study.

We introduce a novel solid-phase colorimetric sensor facilely fabricated by loading unmodified gold nanoparticles into poly(oligo(ethylene glycol)methacrylate) (POEGMA) brushes grown on glass. Our work reports the first synergistic combination of metallic nanoparticles acting as a colorimetric sensing module with a nonfouling polymer matrix acting both as a nonrigid scaffold and a screen to reduce interference from nontarget molecules. In addition, as the nanocomposite is formed on a transparent substrate, solid-phase detection can be performed in the same manner as in the solution-phase. We demonstrate the use of this unique platform for label-free lead detection based on the release of gold nanoparticles from the polymer brush upon exposure to lead ions. An ultralow limit-of-detection of 25 pM (S/N = 3) and a dynamic range of 100 pM to 100 nM (R(2) = 0.987) are achieved. Furthermore, the detection is up to 1000-fold more selective to lead over other common heavy metal ions.

Distance-mediated plasmonic dimers for reusable colorimetric switches: a measurable peak shift of more than 60 nm.

The first reconfigurable colorimetric DNA switches based on target DNA binding are reported. This DNA binding actuates a change in the interparticle distance between gold nanoparticle dimers. A significant spectral shift of 68 nm is achievable from on-off switching. The reconfigurability is possible owing to thiol and EDC-imidazole coupling which anchors the DNA linkers to the nanoparticles. The huge spectral shift allows the unaided eye to observe single target biomolecular binding event in real time under a darkfield microscope. The limit-of-detection for target molecules in PBS and human serum are 10(-13) M and 10(-11) M respectively. An improved fabrication strategy via asymmetric functionalization is also described, assisted by solid phase synthesis which minimizes the formation of trimers and multimers.

Optimizing Plasmonic Gold Nanorod Deposition on Glass Surfaces for High-Sensitivity Refractometric Biosensing.

Owing to high surface sensitivity, gold nanorods (AuNRs) are widely used to construct surface-based nanoplasmonic biosensing platforms for label-free molecular diagnostic applications. A key fabrication step involves controlling AuNR deposition onto the target surface, which requires maximizing surface density while minimizing inter-particle aggregation, and is often achieved by surface functionalization with a self-assembled monolayer (SAM) prior to AuNR deposition. To date, existing studies have typically used a fixed concentration of SAM-forming organic molecules (0.2-10% v/v) while understanding how SAM density affects AuNR deposition and resulting sensing performance would be advantageous. Herein, we systematically investigated how controlling the (3-aminopropyl)triethoxysilane (APTES) concentration (1-30% v/v) during SAM preparation affects the fabrication of AuNR-coated glass surfaces for nanoplasmonic biosensing applications. Using scanning electron microscopy (SEM) and UV-visible spectroscopy, we identified an intermediate APTES concentration range that yielded the highest density of individually deposited AuNRs with minimal aggregation and also the highest peak wavelength in aqueous solution. Bulk refractive index sensitivity measurements indicated that the AuNR configuration had a strong effect on the sensing performance, and the corresponding wavelength-shift responses ranged from 125 to 290 nm per refractive index unit (RIU) depending on the APTES concentration used. Biosensing experiments involving protein detection and antigen-antibody interactions further demonstrated the high surface sensitivity of the optimized AuNR platform, especially in the low protein concentration range where the measurement shift was ~8-fold higher than that obtained with previously used sensing platforms.