Plasmonic silver and gold nanoparticles: shape- and structure-modulated plasmonic functionality for point-of-caring sensing, bio-imaging and medical therapy.

Silver and gold nanoparticles have found extensive biomedical applications due to their strong localized surface plasmon resonance (LSPR) and intriguing plasmonic properties. This review article focuses on the correlation among particle geometry, plasmon properties and biomedical applications. It discusses how particle shape and size are tailored via controllable synthetic approaches, and how plasmonic properties are tuned by particle shape and size, which are embodied by nanospheres, nanorods, nanocubes, nanocages, nanostars and core-shell composites. This article summarizes the design strategies for the use of silver and gold nanoparticles in plasmon-enhanced fluorescence, surface-enhanced Raman scattering (SERS), electroluminescence, and photoelectrochemistry. It especially discusses how to use plasmonic nanoparticles to construct optical probes including colorimetric, SERS and plasmonic fluorescence probes (labels/reporters). It also demonstrates the employment of Ag and Au nanoparticles in polymer- and paper-based microfluidic devices for point-of-care testing (POCT). In addition, this article highlights how to utilize plasmonic nanoparticles for in vitro and in vivo bio-imaging based on SERS, fluorescence, photoacoustic and dark-field models. Finally, this article shows perspectives in plasmon-enhanced photothermal and photodynamic therapy.

Phase-Tunable Molybdenum Boride Ceramics as an Emerging Sensitive and Reliable SERS Platform in Harsh Environments.

Traditional surface-enhanced Raman scattering (SERS) sensors rely heavily on the use of plasmonic noble metals, which have limitations due to their high cost and lack of physical and chemical stability. Hence, it is imperative to explore new materials as SERS platforms that can withstand high temperatures and harsh conditions. In this study, the SERS effect of molybdenum boride ceramic powders is presented with an enhancement factor of 5 orders, which is comparable to conventional noble metal substrates. The molybdenum boride powders synthesized through liquid-phase precursor and carbothermal reduction have ß-MoB, MoB2 , and Mo2 B5 phases. Among these phases, ß-MoB demonstrates the most significant SERS activity, with a detection limit for rhodamine 6G (R6G) molecules of 10-9  m. The impressive SERS enhancement can be attributed to strong molecule interactions and prominent charge interactions between R6G and the various phases of molybdenum boride, as supported by theoretical calculations. Additionally, Raman measurements show that the SERS activity remains intact after exposure to high temperature, strong acids, and alkalis. This research introduces a novel molybdenum boride all-ceramic SERS platform capable of functioning in harsh conditions, thereby showing the promising of boride ultrahigh-temperature ceramics for detection applications in extreme environments.

Visible-light and near-infrared fluorescence and surface-enhanced Raman scattering point-of-care sensing and bio-imaging: a review.

This review article deals with the concepts, principles and applications of visible-light and near-infrared (NIR) fluorescence and surface-enhanced Raman scattering (SERS) in in vitro point-of-care testing (POCT) and in vivo bio-imaging. It has discussed how to utilize the biological transparency windows to improve the penetration depth and signal-to-noise ratio, and how to use surface plasmon resonance (SPR) to amplify fluorescence and SERS signals. This article has highlighted some plasmonic fluorescence and SERS probes. It has also reviewed the design strategies of fluorescent and SERS sensors in the detection of metal ions, small molecules, proteins and nucleic acids. Particularly, it has provided perspectives on the integration of fluorescent and SERS sensors into microfluidic chips as lab-on-chips to realize point-of-care testing. It has also discussed the design of active microfluidic devices and non-paper- or paper-based lateral flow assays for in vitro diagnostics. In addition, this article has discussed the strategies to design in vivo NIR fluorescence and SERS bio-imaging platforms for monitoring physiological processes and disease progression in live cells and tissues. Moreover, it has highlighted the applications of POCT and bio-imaging in testing toxins, heavy metals, illicit drugs, cancers, traumatic brain injuries, and infectious diseases such as COVID-19, influenza, HIV and sepsis.

Enabling Direct Protein Detection in a Drop of Whole Blood with an "On-Strip" Plasma Separation Unit in a Paper-Based Lateral Flow Strip.

Conventional paper lateral flow assays have low sensitivity and suffer from severe interference from complex human fluid sample matrices, which prevents their practical application in the testing of whole blood samples in the point-of-care settings. To solve this problem, gold nanostar@Raman reporter@silica-sandwiched nanoparticles have been developed as the surface-enhanced Raman scattering (SERS) probes for sensing transduction; and a functionalized filter membrane assembly has been designed and constructed in the paper-based lateral flow strip (PLFS) as a built-in plasma separation unit. In this "on-strip" plasma separation unit, three layers of filter membranes are stacked and surface-modified to maximize the separation efficiency and the plasma yield. As a result, the integrated PLFS has been successfully used for the detection of carcinoembryonic antigen (CEA) in 30 µL of whole blood with the assistance of a portable Raman reader, achieving a limit of detection of 1.0 ng mL-1. In short, this report presents an inexpensive, disposable, portable, and field-deployable paper-based device as a general point-of-care testing tool for protein biomarker detection in a drop of whole blood.

Plasmonic hot electrons for sensing, photodetection, and solar energy applications: A perspective.

In plasmonic metals, surface plasmon resonance decays and generates hot electrons and hot holes through non-radiative Landau damping. These hot carriers are highly energetic, which can be modulated by the plasmonic material, size, shape, and surrounding dielectric medium. A plasmonic metal nanostructure, which can absorb incident light in an extended spectral range and transfer the absorbed light energy to adjacent molecules or semiconductors, functions as a "plasmonic photosensitizer." This article deals with the generation, emission, transfer, and energetics of plasmonic hot carriers. It also describes the mechanisms of hot electron transfer from the plasmonic metal to the surface adsorbates or to the adjacent semiconductors. In addition, this article highlights the applications of plasmonic hot electrons in photodetectors, photocatalysts, photoelectrochemical cells, photovoltaics, biosensors, and chemical sensors. It discusses the applications and the design principles of plasmonic materials and devices.

Mouse pulmonary dose- and time course-responses induced by exposure to nitrogen-doped multi-walled carbon nanotubes.

Objective: In this study, we compared in vitro and in vivo bioactivity of nitrogen-doped multi-walled carbon nanotubes (NDMWCNT) to MWCNT to test the hypothesis that nitrogen doping would alter bioactivity.Materials and Methods: High-resolution transmission electron microscopy (TEM) confirmed the multilayer structure of MWCNT with an average layer distance of 0.36 nm, which was not altered by nitrogen doping: the nanomaterials had similar widths and lengths. In vitro studies with THP-1 cells and alveolar macrophages from C57BL/6 mice demonstrated that NDMWCNT were less cytotoxic and stimulated less IL-1ß release compared to MWCNT. For in vivo studies, male C57BL/6J mice received a single dose of dispersion medium (DM), 2.5, 10 or 40 µg/mouse of NDMWCNT, or 40 µg/mouse of MWCNT by oropharyngeal aspiration. Animals were euthanized between 1 and 7 days post-exposure for whole lung lavage (WLL) studies.Results and Discussion: NDMWCNT caused time- and dose-dependent pulmonary inflammation. However, it was less than that caused by MWCNT. Activation of the NLRP3 inflammasome was assessed in particle-exposed mice by determining cytokine production in WLL fluid at 1 day post-exposure. Compared to DM-exposed mice, IL-1ß and IL-18 were significantly increased in MWCNT- and NDMWCNT-exposed mice, but the increase caused by NDMWCNT was less than MWCNT. At 56 days post-exposure, histopathology determined lung fibrosis in MWCNT-exposed mice was greater than NDMWCNT-exposed mice.Conclusions: These data indicate nitrogen doping of MWCNT decreases their bioactivity, as reflected with lower in vitro and in vivo toxicity inflammation and lung disease. The lower activation of the NLRP3 inflammasome may be responsible. Abbreviations: NDMWCNT: nitrogen-doped multi-walled carbon nanotubes; MWCNT: multi-walled carbon nanotubes; TEM: transmission electron microscopy; HRTEM: high resolution transmission electron microscopy; IL-1ß: interleukin-1ß; DM: dispersion medium; WLL: whole lung lavage; IL-18: interleukin-18; GSD: geometric standard deviation; XPS: X-ray photoelectron spectroscopy; SEM: standard error of the mean; PMA: phorbol 12-myristate 13-acetate; LPS: lipopolysacharride; LDH: lactate dehydrogenase; AM: alveolar macrophage; PMN: polymorphonuclear leukocyte.

Length, but Not Reactive Edges, of Cup-stack MWCNT Is Responsible for Toxicity and Acute Lung Inflammation.

Multiwalled carbon nanotube (MWCNT) toxicity after inhalation has been associated with size, aspect ratio, rigidity, surface modification, and reactive oxygen species production. In this study, we investigated a series of cup-stacked MWCNT prepared as variants of the Creos 24PS. Mechanical chopping produced a short version (AR10) and graphitization to remove active reaction sites by extreme heat (2,800°C; Creos 24HT) to test the contribution of length and alteration of potential reaction sites to toxicity. The 3 MWCNT variants were tested in vitro in a human macrophage-like cell model and with C57BL/6 alveolar macrophages for dose-dependent toxicity and NLRP3 inflammasome activation. The 24PS and 24HT variants showed significant dose-dependent toxicity and inflammasome activation. In contrast, the AR10 variant showed no toxicity or bioactivity at any concentration tested. The in vivo results reflected those observed in vitro, with the 24PS and 24HT variants resulting in acute inflammation, including elevated polymorphonuclear counts, Interleukin (IL)-18, cathepsin B, and lactate dehydrogenase in isolated lung lavage fluid from mice exposed to 40 µg MWCNT. Taken together, these data indicate that length, but not the absence of proposed reaction sites, on the MWCNT influences particle bioactivity.

Paper-Based Surface-Enhanced Raman Scattering Lateral Flow Strip for Detection of Neuron-Specific Enolase in Blood Plasma.

An inexpensive and disposable paper-based lateral flow strip (PLFS) has been developed as an immunoassay, in which surface-enhanced Raman scattering (SERS) is utilized for sensing signal transduction. The Au nanostar@Raman Reporter@silica sandwich nanoparticles are developed as the SERS probes, which is the key to the high sensitivity of the device. Compared with a colorimetric PLFS, the SERS-PLFS exhibits superior performance in terms of sensitivity and limit of detection (LOD) in a blood plasma-containing sample matrix. In addition, the SERS-PLFS has been successfully used for detection of neuron-specific enolase (NSE), a traumatic brain injury (TBI) protein biomarker, in diluted blood plasma samples, achieving a LOD of 0.86 ng/mL. Moreover, the SERS-PLFS was successfully employed to measure the NSE level in clinical blood plasma samples taken from deidentified TBI patients. This work demonstrates that the SERS-PLFS has great potential in assisting screening of TBI patients in the point-of-care setting.

Effects of titanium dioxide nanoparticles on human keratinocytes.

Titanium dioxide (TiO2) is a ubiquitous whitening compound widely used in topical products such as sunscreens, lotions and facial creams. The damaging health effects of TiO2 inhalation has been widely studied in rats, mice and humans showing oxidative stress increase, DNA damage, cell death and inflammatory gene upregulation in lung and throat cells; however, the effects on skin cells from long-term topical use of various products remain largely unknown. In this study, we assessed the effect of specific TiO2 nanoparticles (H2TiO7) on a human keratinocyte cell line (HaCaT). We performed a comparative analysis using three TiO2 particles varying in size (Fine, Ultrafine and H2TiO7) and analyzed their effects on HaCaTs. There is a clear dose-dependent increase in superoxide production, caspase 8 and 9 activity, and apoptosis in HaCaTs after treatment with all three forms of TiO2; however, there is no consistent effect on cell viability and proliferation with either of these TiO2 particles. While there is data suggesting UV exposure can enhance the carcinogenic effects of TiO2, we did not observe any significant effect of UV-C exposure combined with TiO2 treatment on HaCaTs. Furthermore, TiO2-treated cells showed minimal effects on VEGF upregulation and Wnt signaling pathway thereby showing no potential effect on angiogenesis and malignant transformation. Overall, we report here an increase in apoptosis, which may be caspase 8/Fas-dependent, and that the H2TiO7 nanoparticles, despite their smaller particle size, had no significant enhanced effect on HaCaT cells as compared to Fine and Ultrafine forms of TiO2.

Fabrication of hexagonally patterned flower-like silver particle arrays as surface-enhanced Raman scattering substrates.

Hierarchical assembly of plasmonic nanostructures can induce high surface-enhanced Raman scattering (SERS) activity. However, it is a challenge to uniformly disperse the hierarchical nanostructures onto a planar substrate to achieve SERS signal reproducibility. This report presents a facile route to fabricate a hexagonally patterned flower-like silver particle array as the SERS substrate. First, hexagonally ordered silver hemisphere arrays with smooth surface are molded in the pores of an anodic aluminum oxide template. Ag-nanosheets are then electrodeposited onto the surface of individual silver hemispheres. The numerous nano-edges and nano-gaps between adjacent nanosheets render a large number of hot spots, leading to high SERS activity over a larger area of chip. The silver flower-like array is employed as the SERS substrate, which is able to detect 0.1 nM rhodamine 6 G and 1 µM 3,3',4,4'-tetrachlorobiphenyl (PCB-77, a persistent organic pollutant).

An ordered array of hierarchical spheres for surface-enhanced Raman scattering detection of traces of pesticide.

An ordered array of hierarchically-structured core-nanosphere@space-layer@shell-nanoparticles has been fabricated for surface-enhanced Raman scattering (SERS) detection. To fabricate this hierarchically-structured chip, a long-range ordered array of Au/Ag-nanospheres is first patterned in the nano-bowls on the planar surface of ordered nanoporous anodic titanium oxide template. A ultra-thin alumina middle space-layer is then conformally coated on the Au/Ag-nanospheres, and Ag-nanoparticles are finally deposited on the surface of the alumina space-layer to form an ordered array of Au/Ag-nanosphere@Al2O3-layer@Ag-nanoparticles. Finite-difference time-domain simulation shows that SERS hot spots are created between the neighboring Ag-nanoparticles. The ordered array of hierarchical nanostructures is used as the SERS-substrate for a trial detection of methyl parathion (a pesticide) in water and a limit of detection of 1 nM is reached, indicating its promising potential in rapid monitoring of organic pollutants in aquatic environment.

Study of the inorganic substitution in a functionalized UiO-66 metal-organic framework.

In this study the band gap modulation was studied in response to inorganic ion substitution within a thermally stable UiO-66 metal-organic framework (MOF). A combination of density functional theory prediction in conjunction with experimental predictions were used to map out the complete composition space for three inorganic ions (Zr, Ti, Hf) and three functional groups. The three functional groups include an amino group (NH2), a nitro group (NO2), and a hydrogenated case (H). The smallest band gap that experimentally determined was for a partially substituted UiO-66(Ti5Zr1)-NH2 resulting in 2.60 eV. Theoretical results indicated that Ti can be fully substituted within the lattice resulting in a predicted band gap as low as 1.62 eV. Modulation was a result of a mid-gap state introduced through the amino functionalization and HOMO shifting as a result of increased binding of the Ti-O-C bonds.

Plasmon-enhanced optical sensors: a review.

Surface plasmon resonance (SPR) has found extensive applications in chemi-sensors and biosensors. Plasmons play different roles in different types of optical sensors. SPR transduces a signal in a colorimetric sensor through shifts in the spectral position and intensity in response to external stimuli. SPR can also concentrate the incident electromagnetic field in a nanostructure, modulating fluorescence emission and enabling plasmon-enhanced fluorescence to be used for ultrasensitive detection. Furthermore, plasmons have been extensively used for amplifying a Raman signal in a surface-enhanced Raman scattering sensor. This paper presents a review of recent research progress in plasmon-enhanced optical sensing, giving emphasis on the physical basis of plasmon-enhanced sensors and how these principles guide the design of sensors. In particular, this paper discusses the design strategies for nanomaterials and nanostructures to plasmonically enhance optical sensing signals, also highlighting the applications of plasmon-enhanced optical sensors in healthcare, homeland security, food safety and environmental monitoring.

Ab initio calculation of electronic charge mobility in metal-organic frameworks.

A density functional theory approach coupled with the Boltzmann transport equation within the relaxation time approximation was used to investigate the charge mobility for three MOF functionalization designs. The specific MOF investigated was a Zr-UiO-66 MOF with three functionalizations that included benzenedicarboxylate (BDC), BDC functionalized with an amino group (BDC + NH2), and BDC functionalized with a nitro group (BDC + NO2). Previous experimental studies have confirmed a 40% decrease in the optical band-gap with functionization; this study predicted an accompanying decrease in mobility by 14%. On the contrary, the charge density was found to increase with functionalization. The culmination of these two findings resulted in a predicted conductivity of approximately 3.8 × 10(-8) S cm(-1) for BDC design and decreasing less than 2% for other cases. Furthermore, band conduction was confirmed for this MOF design as a result of the de-localized π electron of the carbon atoms along the organic linker. Overall, the functionalization proved to decrease mobility; however, it was evident that the functionalization has potential for tailoring the spectral layout of low lying unoccupied orbitals and ultimately the charge concentration, which could prove to be important for increasing the overall conductivity of MOFs.

Theoretical maximum efficiency of solar energy conversion in plasmonic metal-semiconductor heterojunctions.

Plasmonics can enhance solar energy conversion in semiconductors by light trapping, hot electron transfer, and plasmon-induced resonance energy transfer (PIRET). The multifaceted response of the plasmon and multiple interaction pathways with the semiconductor makes optimization challenging, hindering design of efficient plasmonic architectures. Therefore, in this paper we use a density matrix model to capture the interplay between scattering, hot electrons, and dipole-dipole coupling through the plasmon's dephasing, including both the coherent and incoherent dynamics necessary for interactions on the plasmon's timescale. The model is extended to Shockley-Queisser limit calculations for both photovoltaics and solar-to-chemical conversion, revealing the optimal application of each enhancement mechanism based on plasmon energy, semiconductor energy, and plasmon dephasing. The results guide application of plasmonic solar-energy harvesting, showing which enhancement mechanism is most appropriate for a given semiconductor's weakness, and what nanostructures can achieve the maximum enhancement.

Tailoring plasmonic properties of gold nanohole arrays for surface-enhanced Raman scattering.

The wide plasmonic tuning range of nanotriangle and nanohole array patterns fabricated by nanosphere lithography makes them promising in surface-enhanced Raman scattering (SERS) sensors. Unfortunately, it is challenging to optimize these patterns for SERS sensing because their optical response is a complex mixture of localized surface plasmon resonance (SPR) and propagating surface plasmon polariton (SPP). In this paper, transmission and reflection measurements are combined with finite difference time domain simulations to identify and separate each plasmonic mode, discerning which resonance leads to the electromagnetic field enhancement. The SERS enhancement is found to be dominated by the absorption, which is shifted from the transmission and reflection dips usually used as tuning points, and by the 'gap' defects formed within the pattern. These effects have different spectral and geometric dependences, forming two optimization curves which can be used to predict the best performance for a given excitation wavelength. The developed model is verified with experimental SERS measurements for several nanohole sizes and periodicities, and then used to give optimal fabrication parameters for a range of measurement conditions. The results will promote the application of two-dimensional plasmonic nanoarrays in SERS sensors.

Band gap narrowing in nitrogen-doped La2Ti2O7 predicted by density-functional theory calculations.

In order to reveal the origin of enhanced photocatalytic activity of N-doped La2Ti2O7 in both the visible light and ultraviolet light regions, its electronic structure has been studied using spin-polarized conventional density functional theory (DFT) and the Heyd-Scuseria-Ernzerhof (HSE06) hybrid approach. The results show that the deep localized states are formed in the forbidden band when nitrogen solely substitutes for oxygen. Introducing the interstitial Ti atom into the N-doped La2Ti2O7 photocatalyst still causes the formation of a localized energy state. Two nitrogen substitutions co-exist stably with one oxygen vacancy, creating a continuum energy band just above the valence band maximum. The formation of a continuum band instead of mid-gap states can extend the light absorption to the visible light region without increasing the charge recombination, explaining the enhanced visible light performance without deteriorating the ultraviolet light photocatalytic activity.

Investigation of band gap narrowing in nitrogen-doped La2Ti2O7 with transient absorption spectroscopy.

Doping a semiconductor can extend the light absorption range, however, it usually introduces mid-gap states, reducing the charge carrier lifetime. This report shows that doping lanthanum dititinate (La2Ti2O7) with nitrogen extends the valence band edge by creating a continuum of dopant states, increasing the light absorption edge from 380 nm to 550 nm without adding mid-gap states. The dopant states are experimentally resolved in the excited state by correlating transient absorption spectroscopy with a supercontinuum probe and DFT prediction. The lack of mid-gap states is further confirmed by measuring the excited state lifetimes, which reveal the shifted band edge only increased carrier thermalization rates to the band edge and not interband charge recombination under both ultraviolet and visible excitation. Terahertz (time-domain) spectroscopy also reveals that the conduction mechanism remains unchanged after doping, suggesting the states are delocalized.

Microfluidic gradient device for studying mesothelial cell migration and the effect of chronic carbon nanotube exposure.

Cell migration is one of the crucial steps in many physiological and pathological processes, including cancer development. Our recent studies have shown that carbon nanotubes (CNTs), similarly to asbestos, can induce accelerated cell growth and invasiveness that contribute to their mesothelioma pathogenicity. Malignant mesothelioma is a very aggressive tumor that develops from cells of the mesothelium, and is most commonly caused by exposure to asbestos. CNTs have a similar structure and mode of exposure to asbestos. This has raised a concern regarding the potential carcinogenicity of CNTs, especially in the pleural area which is a key target for asbestos-related diseases. In this paper, a static microfluidic gradient device was applied to study the migration of human pleural mesothelial cells which had been through a long-term exposure (4 months) to subcytotoxic concentration (0.02 µg cm-2) of single-walled CNTs (SWCNTs). Multiple migration signatures of these cells were investigated using the microfluidic gradient device for the first time. During the migration study, we observed that cell morphologies changed from flattened shapes to spindle shapes prior to their migration after their sensing of the chemical gradient. The migration of chronically SWCNT-exposed mesothelial cells was evaluated under different fetal bovine serum (FBS) concentration gradients, and the migration speeds and number of migrating cells were extracted and compared. The results showed that chronically SWCNT-exposed mesothelial cells are more sensitive to the gradient compared to non-SWCNT-exposed cells. The method described here allows simultaneous detection of cell morphology and migration under chemical gradient conditions, and also allows for real-time monitoring of cell motility that resembles in vivo cell migration. This platform would be much needed for supporting the development of more physiologically relevant cell models for better assessment and characterization of the mesothelioma hazard posed by nanomaterials.

Gaussian process based modeling and experimental design for sensor calibration in drifting environments.

It remains a challenge to accurately calibrate a sensor subject to environmental drift. The calibration task for such a sensor is to quantify the relationship between the sensor's response and its exposure condition, which is specified by not only the analyte concentration but also the environmental factors such as temperature and humidity. This work developed a Gaussian Process (GP)-based procedure for the efficient calibration of sensors in drifting environments. Adopted as the calibration model, GP is not only able to capture the possibly nonlinear relationship between the sensor responses and the various exposure-condition factors, but also able to provide valid statistical inference for uncertainty quantification of the target estimates (e.g., the estimated analyte concentration of an unknown environment). Built on GP's inference ability, an experimental design method was developed to achieve efficient sampling of calibration data in a batch sequential manner. The resulting calibration procedure, which integrates the GP-based modeling and experimental design, was applied on a simulated chemiresistor sensor to demonstrate its effectiveness and its efficiency over the traditional method.