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Rapid, ultrasensitive, and selective quantification of circulating microRNA (miRNA) biomarkers in body fluids is increasingly deployed in early cancer diagnosis, prognosis, and therapy monitoring. While nanoparticle tags enable detection of nucleic acid or protein biomarkers with digital resolution and subfemtomolar detection limits without enzymatic amplification, the response time of these assays is typically dominated by diffusion-limited transport of the analytes or nanotags to the biosensor surface. Here, we present a magnetic activate capture and digital counting (mAC+DC) approach that utilizes magneto-plasmonic nanoparticles (MPNPs) to accelerate single-molecule sensing, demonstrated by miRNA detection

For decades, investigators have studied the interaction of Mycobacterium tuberculosis (Mtb) with macrophages, which serve as a major cellular niche for the bacilli. Because Mtb are prone to aggregation, investigators rely on varied methods to disaggregate the bacteria for these studies. Here, we examined the impact of routinely used preparation methods on bacterial cell envelope integrity, macrophage inflammatory responses, and intracellular Mtb survival. We found that both gentle sonication and filtering damaged the mycobacterial cell envelope and markedly impacted the outcome of infections in mouse bone marrow-derived macrophages. Unexpectedly, sonicated bacilli were hyperinflammatory, eliciting dramatically higher TLR2-dependent gene expression and elevated secretion of IL-1β and TNF-α. Despite evoking enhanced inflammatory responses, sonicated bacilli replicated normally in macrophages. In contrast, Mtb that had been passed through a filter induced little inflammatory response, and they were attenuated in macrophages. Previous work suggests that the mycobacterial cell envelope lipid, phthiocerol dimycocerosate (PDIM), dampens macrophage inflammatory responses to Mtb. However, we found that the impact of PDIM depended on the method used to prepare Mtb. In conclusion, widely used methodologies to disaggregate Mtb may introduce experimental artifacts in Mtb-host interaction studies, including alteration of host inflammatory signaling, intracellular bacterial survival, and interpretation of bacterial mutants.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread and resulted in the global pandemic of COVID-19. Although IgM/IgG serology assay has been widely used, with the entire spike or nucleocapsid antigens, they only indicate the presence or absence of antibodies against these proteins but are not specific to the neutralization antibodies, therefore providing only generic information about infection stage and possible future immune protection. Novel technologies enabling easy-to-use and sensitive detection of multiple specific antibodies simultaneously will facilitate precise diagnosis of infection stage, prediction of clinical outcomes, and evaluation of future immune protection upon viral exposure or vaccination. Here, we demonstrate a rapid and ultrasensitive quantification method for epitope-specific antibodies, including different isotypes and subclasses, in a multiplexed manner. Using an ultrabright fluorescent nanolabel, plasmonic-fluor, this novel assay can be completed in 20 min and more importantly, the limit of detection of the plasmon-enhanced immunoassay for SARS-CoV-2 antibodies is as much as 100-fold lower compared to the assays relying on enzymatic amplification of colorimetric signals. Using convalescent patient plasma, we demonstrate that this biodetection method reveals the patient-to-patient variability in immune response as evidenced by the variations in whole protein and epitope-specific antibodies. This cost-effective, rapid, and ultrasensitive plasmonically enhanced multiplexed epitope-specific serological assay has the potential to be broadly employed in the detection of specific antibodies, which may benefit the advanced epidemiology studies and enable improvement of the clinical outcomes and prediction of the future protection against the SARS-CoV-2.

Assays utilizing molecular fluorophores are common throughout life science research and diagnostic testing, although detection limits are generally limited by weak emission intensity, thus requiring many labeled target molecules to combine their output to achieve signal-to-noise greater than the background. Here, we describe how the synergistic coupling of plasmonic and photonic resonance modes can significantly boost the emission from fluorescent dye molecules without increasing the illumination intensity while utilizing a microscopy approach with a broad field of view. By optimally matching the resonant modes of a plasmonic fluor (PF) nanoparticle and a photonic crystal (PC) surface with the absorption and emission spectrum of the PF’s fluorescent dye, we observe a 52-fold improvement in signal intensity, enabling individual PFs to be observed and digitally counted, using an approach in which one PF tag represents detection of one target molecule. The photonic amplification from the PF can be attributed to the strong near-field enhancement due to the cavity-induced activation of the PF, PC band structure-mediated improvement in collection efficiency of emitted photons, and increased rate of spontaneous emission. We demonstrate the applicability of the method by dose-response characterization of a sandwich immunoassay for human interleukin-6, a biomarker commonly used to assist diagnosis of cancer, inflammation, sepsis, and autoimmune disease. We achieve a limit of detection of 10 fg/ml, representing a capability three orders of magnitude lower than standard immunoassays.

Nanotechnology-enabled neuromodulation, a rapidly growing technique, is a promising minimally-invasive tool in neuroscience and engineering for both fundamental studies as well as clinical applications. However, the nano-neuro interactions at different stages of maturation of a neural network and its implications on the nano-neuromodulation remain unclear. Here, we report heterogeneous to homogenous transformation of neuromodulation in a progressively maturing neural network. Utilizing plasmonic fluors as ultrabright fluorescent nanolabels, we reveal that negative surface charge of the nanoparticles renders selective nano-neuro interaction with a strong correlation between the maturation stage of the individual neurons in the neural network and the density of the nanoparticles bound on the neurons. In stark contrast to homogeneous neuromodulation in a mature neural network reported so far, the maturation-dependent density of the nanoparticles bound to neurons in a developing neural network resulted in a heterogeneous optical neuromodulation (i.e., simultaneous excitation and inhibition of neural network activity). This study advances our understanding of nano-neuro interactions and nano-neuromodulation with potential applications in minimally-invasive technologies for treating neuronal disorders in parts of mammalian brain where neurogenesis persists throughout aging.

Secreted proteins mediate essential physiological processes. With conventional assays, it is challenging to map the spatial distribution of proteins secreted by single cells, to study cell-to-cell heterogeneity in secretion, or to detect proteins of low abundance or incipient secretion. Here, we introduce the "FluoroDOT assay," which uses an ultrabright nanoparticle plasmonic-fluor that enables high-resolution imaging of protein secretion. We find that plasmonic-fluors are 16,000-fold brighter, with nearly 30-fold higher signal-to-noise compared with conventional fluorescence labels. We demonstrate high-resolution imaging of different secreted cytokines in the single-plexed and spectrally multiplexed FluoroDOT assay that revealed cellular heterogeneity in secretion of multiple proteins simultaneously. Using diverse biochemical stimuli, including Mycobacterium tuberculosis infection, and a variety of immune cells such as macrophages, dendritic cells (DCs), and DC-T cell co-culture, we demonstrate that the assay is versatile, facile, and widely adaptable for enhancing biological understanding of spatial and temporal dynamics of single-cell secretome.

For decades, investigators have studied the interaction ofMycobacterium tuberculosis(Mtb) with macrophages, which serve as a major cellular niche for the bacilli. Because Mtb are prone to aggregation, investigators rely on varied methods to disaggregate the bacteria for these studies. Here, we examined the impact of routinely used preparation methods on bacterial cell envelop integrity, macrophage inflammatory responses, and intracellular Mtb survival. We found that both gentle sonication and filtering damaged the mycobacterial cell envelope and markedly impacted the outcome of macrophage infections. Unexpectedly, sonicated bacilli were hyperinflammatory, eliciting dramatically higher TLR2-dependent gene expression and elevated secretion of IL-1β and TNF-α. Despite evoking enhanced inflammatory responses, sonicated bacilli replicated normally in macrophages. In contrast, Mtb that had been passed through a filter induced little inflammatory response, and they were attenuated in macrophages. Previous work suggests that the mycobacterial cell envelope lipid, phthiocerol dimycocerosate (PDIM), dampens macrophage inflammatory responses to Mtb. However, we found that the impact of PDIM depended on the method used to prepare Mtb. In conclusion, widely used methodologies to disaggregate Mtb may introduce experimental artifacts in Mtb-host interaction studies, including alteration of host inflammatory signaling, intracellular bacterial survival, and interpretation of bacterial mutants.

Plasmon-enhanced fluorescence (PEF) is a simple and highly effective approach for improving the signal-to-noise ratio and sensitivity of various fluorescence-based bioanalytical techniques. Here, we show that the fluorescence enhancement efficacy of gold nanorods (AuNRs), which are widely employed for PEF, is highly dependent on their absolute dimensions (i.e., length and diameter). Notably, an increase in the dimensions (length × diameter) of the AuNRs from 46 × 14 to 120 × 38 nm2 while holding the aspect ratio constant leads to nearly 300% improvement in fluorescence enhancement efficiency. Further increase in the AuNR size leads to a decrease of the fluorescence enhancement efficiency. Through finite-difference time-domain (FDTD) simulation, we reveal that the size-dependent fluorescence enhancement efficiency of AuNR stems from the size-dependent electromagnetic field around the plasmonic nanostructures. AuNRs with optimal dimensions resulted in a nearly 120-fold enhancement in the ensemble fluorescence emission from molecular fluorophores bound to the surface. These plasmonic nanostructures with optimal dimensions also resulted in a nearly 30-fold improvement in the limit of detection of human interleukin-6 (IL-6) compared to AuNRs with smaller size, which are routinely employed in PEF.

Solar-driven desalination, which involves the conversion of solar energy to heat for freshwater generation, has been recognized as an attractive and sustainable desalination technology to alleviate freshwater shortage. In particular, photothermally driven membrane distillation (PMD) is a highly promising solar-driven desalination technology, especially in remote regions and disaster-struck communities, where no power infrastructure or waste heat from industrial plants is available. MXene, more specifically Ti3C2Tx, with excellent photothermal properties, easy processability, and electrical conductivity offers a great opportunity for realizing highly efficient, stable and multifunctional PMD membranes. Herein, we realize a MXene composite aerogel comprised of hydroxyapatite nanowires and poly(vinyl alcohol) with high thermal efficiency (61%) and water flux (0.72 kg m−2 h−1) under 0.8 sun irradiation (0.8 kW m−2), representing the first validation of highly efficient MXene-based PMD systems in treating ambient saline water. Owing to the strong interfacial interaction (i.e., hydrogen bonding) between the building blocks, the MXene composite aerogel with high porosity (up to 91%) exhibited excellent mechanical stability. This highly interconnected porous network offers low resistance to vapor transport and low thermal conductivity, which minimizes conductive heat transfer across the aerogel, thus maximizing the thermal efficiency. Furthermore, the outstanding bactericidal activity induced by solar irradiation or electric potential makes the MXene composite aerogel a highly attractive candidate for PMD in the real world.

Protein materials are promising candidates as the building blocks for functional and high-performance bionanocomposites, owing to their unique and well-developed nanoscale structure, rich chemical functionality, excellent mechanical properties, biocompatibility, and biodegradability. Rational integration of protein materials with synthetic organic and inorganic nanomaterials through tailored interfacial interactions leads to synergistic enhancement in the properties compared to the individual components. In this article, we discuss the recent progress in protein-based nanocomposites, which aim to harness the unique structure and properties of proteins and synthetic nanomaterials for realizing advanced materials with greatly enhanced properties. Specifically, we highlight bionanocomposites based on two β-sheet rich proteins, silk fibroin and amyloid fibril, as representative examples as well as a few other protein materials such as keratin, elastin, and collagens. We describe the biotic–abiotic interfaces, processing methods, physical properties, and potential applications of these protein nanocomposites. Considering the additional value of renewability, abundancy, and ambient processability, such bionanocomposites are promising candidates for advanced and emerging applications, such as environmental remediation, biomedicine, biosensors, and photonics.

Cancer immunotherapy involves a cascade of events that ultimately leads to cytotoxic immune cells effectively identifying and destroying cancer cells. Responsive nanomaterials, which enable spatiotemporal orchestration of various immunological events for mounting a highly potent and long-lasting anti-tumor immune response, are an attractive platform to overcome challenges associated with existing cancer immunotherapies. Here, we report a multifunctional near infrared (NIR)-responsive core-shell nanoparticle, which enables (i) photothermal ablation of cancer cells for generating tumor associated antigen (TAA) and (ii) triggered release of an immunomodulatory drug (gardiquimod) for starting a series of immunological events. The core of these nanostructures is composed of polydopamine nanoparticle, which serves as a photothermal agent, and the shell is made of mesoporous silica, which serves as a drug carrier. We employed a phase-change material as gatekeeper to achieve concurrent release of both TAA and adjuvant, thus efficiently activating the antigen presenting cells (APCs). Photothermal-immunotherapy enabled by these nanostructures resulted in regression of primary tumor and significantly improved inhibition of secondary tumor in a mouse melanoma model. These biocompatible, biodegradable, and NIR-responsive core-shell nanostructures simultaneously deliver payload and cause photothermal ablation of the cancer cells. Our results demonstrate potential of responsive nanomaterials in generating highly synergistic photothermal-immunotherapeutic response.

Plasmonic nanoparticles (NPs) hold tremendous promise for catalyzing light-driven chemical reactions. The conventionally assumed detrimental absorption loss from plasmon damping can now be harveste...

Removal of organic pollutants from industrial wastewater is of significant importance in wastewater treatment. Here, we present a highly efficient composite membrane comprised of bacterial nanocell...

The detection and quantification of low-abundance molecular biomarkers in biological samples is challenging. Here, we show that a plasmonic nanoscale construct serving as an ‘add-on’ label for a broad range of bioassays improves their signal-to-noise ratio and dynamic range without altering their workflow and readout devices. The plasmonic construct consists of a bovine serum albumin scaffold with approximately 210 IRDye 800CW fluorophores (with a fluorescence intensity approximately 6,700-fold that of a single 800CW fluorophore), a polymer-coated gold nanorod acting as a plasmonic antenna and biotin as a high-affinity biorecognition element. Its emission wavelength can be tuned over the visible and near-infrared spectral regions by modifying its size, shape and composition. It improves the limit of detection in fluorescence-linked immunosorbent assays by up to 4,750-fold and is compatible with multiplexed bead-based immunoassays, immunomicroarrays, flow cytometry and immunocytochemistry methods, and it shortens overall assay times (to 20 min) and lowers sample volumes, as shown for the detection of a pro-inflammatory cytokine in mouse interstitial fluid and of urinary biomarkers in patient samples. A plasmonic nanoscale construct serving as a customizable ‘add-on’ fluorescent label improves the signal-to-noise ratio and dynamic range of a range of fluorescence-based bioassays.

Implantable and wearable biosensors that enable monitoring of biophysical and biochemical parameters over long durations are highly attractive for early and presymptomatic diagnosis of pathological conditions and timely clinical intervention. Poor stability of antibodies used as biorecognition elements and the lack of effective methods to refresh the biosensors upon demand without severely compromising the functionality of the biosensor remain significant challenges in realizing protein biosensors for long-term monitoring. Here, we introduce a novel method involving organosilica encapsulation of antibodies for preserving their biorecognition capability under harsh conditions, typically encountered during the sensor refreshing process, and elevated temperature. Specifically, a simple aqueous rinsing step using sodium dodecyl sulfate (SDS) solution refreshes the biosensor by dissociating the antibody–antigen interactions. Encapsulation of the antibodies with an organosilica layer is shown to preserve the biorecognition capability of otherwise unstable antibodies during the SDS treatment, thus ultimately facilitating the refreshability of the biosensor over multiple cycles. Harnessing this method, we demonstrate the refreshability of plasmonic biosensors for anti-IgG (model bioanalyte) and neutrophil gelatinase-associated lipocalin (NGAL) (a biomarker for acute and chronic kidney injury). The novel encapsulation approach demonstrated can be easily extended to other transduction platforms to realize refreshable biosensors for monitoring of protein biomarkers over long durations.

In developing countries and resource-limited regions, where no power infrastructure or waste heat from industrial plants is available, photothermal-driven membrane distillation (PMD) has been recognized as an attractive and sustainable technology for freshwater generation. PMD enables easy water collection, inherent fouling resistance, low-pressure operation, and high-salinity water treatment. Hydroxyapatite (HA) nanowires with excellent mechanical flexibility owing to their high aspect ratio, low thermal conductivity, easy surface modification and scalable production offer great potential for highly efficient membrane distillation. Herein, we demonstrate that the environmentally benign HA nanowire-based bilayered film offers the highest photothermal efficiency (62%) and water flux (0.89 kg m−2 h−1) with 1 sun irradiation (1 kW m−2), among the existing PMD systems without auxiliary heating or multilayer heat recovery reported so far. The hierarchical porous structure formed by the remarkably flexible and intertwined HA nanowires allows low resistance to vapor transport, which is critical for high water flux. Simultaneously, the low thermal conductivity of the thermal insulator layer comprised of HA nanowires prevents conductive heat transfer across the membrane, which significantly enhances the thermal efficiency of the membrane. The completely biocompatible, scalable, and thermally engineered bilayered film demonstrated here achieves highly efficient PMD.

Lateral flow assays (LFAs) are the cornerstone of point-of-care diagnostics. Although rapid and inexpensive, they are 1000-fold less sensitive than laboratory-based tests and cannot be used for definitive negative diagnosis. Here, we overcome this fundamental limitation by employing plasmonically-enhanced nanoscale colorimetric and fluorescent labels. Plasmonic LFAs (p-LFAs) enabled ultrasensitive detection and quantification of low abundance analytes, without compromising the direct visual detection of conventional LFAs. Dynamic ranges and limits of detection were up to 100-fold superior to “gold standard” ELISA (enzyme-linked immunosorbent assay). p-LFAs had sample-to-answer time of 20 min, compared to 4 hours for ELISA, while achieving over 95% analytical sensitivity and 100% analytical specificity for antibodies and antigens of SARS-CoV-2 in human specimens. We also demonstrate that the p-LFAs enable quantitative detection of the target analytes in a standard-free manner. p-LFAs offer potential as a broadly adaptable point-of-care diagnostic platform that outperforms standard laboratory tests in sensitivity, speed, dynamic range, ease of use, and cost.

Chemiresistors based on metal-insulator-metal structures are attractive transducers for rapid tracing of a wide repertoire of (bio)chemical species in the vapor phase. However, current fabrication techniques suffer greatly from sensor-to-sensor variability, limiting their reproducible and reliable application in real-world settings. We demonstrate a novel, facile, and ubiquitously applicable strategy for fabricating highly reliable and reproducible organothiol-functionalized gold nanoisland-based chemiresistors. The novel fabrication technique involves iterative in situ seeding, growth, and surface functionalization of gold nanoislands on an interdigitated electrode, which in turn generates a multi-layered densely packed continuous gold nanoisland film. The chemiresistors fabricated using the proposed strategy exhibited high sensor-to-sensor reproducibility owing to the controlled iterative seeding and growth-based fabrication technique, long-term stability, and specificity for detection and identification of a wide variety of volatile organic compounds. Upon exposure to a specific odor, the chemiresistor ensemble comprised nine different chemical functionalities and produced a unique and discernable odor fingerprint that is reproducible for at least up to 90 days. Integrating these odor fingerprints with a simple linear classifier was found to be sufficient for discriminating between all six odors used in this study. We believe that the fabrication strategy presented here, which is agnostic to chemical functionality, enables fabrication of highly reliable and reproducible sensing elements, and thereby an adaptable electronic nose for a wide variety of real-world gas sensing applications.

Novel methods that enable facile, ultrasensitive and multiplexed detection of low molecular weight organic compounds such as metabolites, drugs, additives, and organic pollutants are valuable in biomedical research, clinical diagnosis, food safety and environmental monitoring. Here, we demonstrate a simple, rapid, and ultrasensitive method for detection and quantification of small molecules by implementing a competitive immunoassay with an ultrabright fluorescent nanolabel, plasmonic fluor. Plasmonic-fluor is comprised of a polymer-coated gold nanorod and bovine serum albumin conjugated with molecular fluorophores and biotin. The synthesis steps and fluorescence emission of plasmonic-fluor was characterized by UV-vis spectroscopy, transmission electron microscopy, and fluorescence microscopy. Plasmon-enhanced competitive assay can be completed within 20 minutes and exhibited more than 30-fold lower limit-of-detection for cortisol compared to conventional competitive ELISA. The plasmon-enhanced competitive immunoassay when implemented as partition-free digital assay enabled further improvement in sensitivity. Further, spatially multiplexed plasmon-enhanced competitive assay enabled the simultaneous detection of two analytes (cortisol and fluorescein). This simple, rapid, and ultrasensitive method can be broadly employed for multiplexed detection of various small molecules in research, in-field and clinical settings.

Lithium-ion batteries consisting of the particulate porous electrodes, are the dominant energy storage devices, however, they suffer from random failures and safety-related accidents. Such arbitrary incidents arise from the spatiotemporal heterogeneities occurring due to the material thermodynamics[1] which results to local hot and cold spots and early battery failures. The past investigations of the heterogeneities in the battery materials rely on the sophisticated synchrotron X-ray methods[2]–[4], which are not easily accessible. Instead, in this study, we employ Raman spectroscopy on an in situ benchtop setup which provides several advantages while investigating the true electrochemical kinetics in graphite electrodes, such as: (i) the setup houses practical porous NMC532 cathodes under realistic electrochemical surroundings; (ii) the high resolution of 1-2 µm provides sufficient information on the larger cathode particles; (iii) the method can analyze hundreds of particles, statistically representing the entire composite electrode; and (iv) the spectra can be quantified to reveal the actual reaction area, thus revealing high-fidelity real-time electrochemical performance. We use this simple but precision method to track and analyze the active reaction regions at the mesoscale in the NMC532 electrode to obtain the true local current density, which was found to be an order of magnitude higher than the globally-averaged current density adopted by the existing studies. Raman spectroscopy can distinguish the vibrational modes of NMC532 with varying Li ion concentration. Since NMC532 is a solid-solution material, the Raman spectrum at each selected location can be deconvoluted into three distinct phases: empty, completely lithiated and partially lithiated. The partially lithiated regions participate in the surface reaction and can be identified to reveal the active reaction area. Thus, we quantified the active area fraction under slow galvanostatic conditions and generated a map of active regions with varying global Li ion fractions. Our results show that only 18% – 50% of the total particle area is active at any instant leading to higher local current densities than the globally-averaged electrode responses. The methods developed in this study are critical to estimate the kinetic parameters using true electrochemical responses and further aid in the design of the particulate porous electrodes. References [1] S. Agrawal, P. Bai, Cell Reports Phys. Sci. 2022, 3, 1. [2] S.J. Harris, A. Timmons, D.R. Baker, C. Monroe, Chem. Phys. Lett. 2010, 485, 265. [3] C. Tian, Y. Xu, D. Nordlund, F. Lin, J. Liu, Z. Sun, Y. Liu, M. Doeff, Joule 2018, 2, 464. [4] S. Fang, M. Yan, R.J. Hamers, J. Power Sources 2017, 352, 18.

Novel methods that enable sensitive, accurate and rapid detection of RNA would not only benefit fundamental biological studies but also serve as diagnostic tools for various pathological conditions, including bacterial and viral infections and cancer. Although highly sensitive, existing methods for RNA detection involve long turn-around time and extensive capital equipment. Here, an ultrasensitive and amplification-free RNA quantification method is demonstrated by integrating CRISPR-Cas13a system with an ultrabright fluorescent nanolabel, plasmonic fluor. This plasmonically enhanced CRISPR-powered assay exhibits nearly 1000-fold lower limit-of-detection compared to conventional assay relying on enzymatic reporters. Using a xenograft tumor mouse model, it is demonstrated that this novel bioassay can be used for ultrasensitive and quantitative monitoring of cancer biomarker (lncRNA H19). The novel biodetection approach described here provides a rapid, ultrasensitive, and amplification-free strategy that can be broadly employed for detection of various RNA biomarkers, even in resource-limited settings.

Autosomal dominant tubulointerstitial kidney disease (ADTKD)-uromodulin (UMOD) is the most common nonpolycystic genetic kidney disease, but it remains unrecognized due to its clinical heterogeneity and lack of screening test. Moreover, the fact that the clinical feature is a poor predictor of disease outcome further highlights the need for the development of mechanistic biomarkers in ADTKD. However, low abundant urinary proteins secreted by thick ascending limb cells, where UMOD is synthesized, have posed a challenge for the detection of biomarkers in ADTKD-UMOD. In the CRISPR/Cas9-generated murine model and patients with ADTKD-UMOD, we found that immunoglobulin heavy chain-binding protein (BiP), an endoplasmic reticulum chaperone, was exclusively upregulated by mutant UMOD in the thick ascending limb and easily detected by Western blot analysis in the urine at an early stage of disease. However, even the most sensitive ELISA failed to detect urinary BiP in affected individuals. We therefore developed an ultrasensitive, plasmon-enhanced fluorescence-linked immunosorbent assay (p-FLISA) to quantify urinary BiP concentration by harnessing the newly invented ultrabright fluorescent nanoconstruct, termed “plasmonic Fluor.” p-FLISA demonstrated that urinary BiP excretion was significantly elevated in patients with ADTKD-UMOD compared with unaffected controls, which may have potential utility in risk stratification, disease activity monitoring, disease progression prediction, and guidance of endoplasmic reticulum-targeted therapies in ADTKD. NEW & NOTEWORTHY Autosomal dominant tubulointerstitial kidney disease (ADTKD)-uromodulin (UMOD) is an underdiagnosed cause of chronic kidney disease (CKD). Lack of ultrasensitive bioanalytical tools has hindered the discovery of low abundant urinary biomarkers in ADTKD. Here, we developed an ultrasensitive plasmon-enhanced fluorescence-linked immunosorbent assay (p-FLISA). p-FLISA demonstrated that secreted immunoglobulin heavy chain-binding protein is an early urinary endoplasmic reticulum stress biomarker in ADTKD-UMOD, which will be valuable in monitoring disease progression and the treatment response in ADTKD.

Electromagnetic hotspots at the interstices of plasmonic assemblies are recognized to be the most potent sites for surface-enhanced Raman scattering (SERS). We demonstrate a novel "add-on" electromagnetic hotspot formation technique, which significantly improves the sensitivity of conventional SERS substrates composed of individual plasmonic nanostructures. The novel approach demonstrated here involves the transfer of "plasmonic patch", a transparent, flexible, and conformal elastomeric film adsorbed with plasmonic nanostructures, onto a conventional SERS substrate. The addition of the plasmonic patch onto a conventional SERS substrate following the analyte capture results in the formation of electromagnetic hotspots and hence a large SERS enhancement. The application of the plasmonic patch improves the sensitivity and limit of detection of conventional SERS substrates by up to ∼100-fold. The transfer of the plasmonic patch also effectively transforms the SERS-inactive gold mirror to a highly SERS-active "particle-on-mirror" system. Furthermore, we demonstrate that the "add-on" technique can be effectively utilized for the vapor-phase detection of explosives such as trinitrotoluene (TNT) using peptide recognition elements. We believe that the on-demand hotspot formation approach presented here represents a highly versatile and ubiquitously applicable technology readily expandable to any existing SERS substrate without employing complicated modification.

Here, we report that a marine sandworm Nereis virens jaw protein, Nvjp1, nucleates hemozoin with similar activity as the native parasite hemozoin protein, HisRPII. X-ray diffraction and scanning electron microscopy confirm the identity of the hemozoin produced from Nvjp1-containing reactions. Finally, we observed that nAl assembled with hemozoin from Nvjp1 reactions has a substantially higher energetic output when compared to analogous thermite from the synthetic standard or HisRPII-nucleated hemozoin. Our results demonstrate that a marine sandworm protein can nucleate malaria pigment and set the stage for engineering recombinant hemozoin production for nanoenergetic applications.

We introduce the “plasmonic nose” as a novel approach for detection, recognition, and quantification of mixtures of chemical species. Using a paper substrate and a calligraphy-based fabrication app...

Minimally invasive devices to detect molecules in dermal interstitial fluid (ISF) are desirable for point-of-care diagnostic and monitoring applications. In this study, we developed a microneedle (MN) patch that collects ISF for on-patch biomarker analysis by surface-enhanced Raman scattering (SERS). The micrometer-scale MNs create micropores in the skin surface, through which microliter quantities of ISF are collected onto plasmonic paper on the patch backing. The plasmonic paper was prepared by immobilizing poly(styrenesulfonate) (PSS) coated gold nanorods (AuNRs) on a thin strip of filter paper using plasmonic calligraphy. Negatively charged PSS was used to bind positively charged rhodamine 6G (R6G), which served as a model compound, and thereby localize R6G on AuNR surface. R6G bound on the AuNR surface was detected and quantified by acquiring SERS spectra from the plasmonic paper MN patch. This approach was used to measure pharmacokinetic profiles of R6G in ISF and serum from rats in vivo. This proof-of-concept study indicates that a plasmonic paper MN patch has the potential to enable on-patch measurement of molecules in ISF for research and future medical applications.

Microcapsules are emerging as promising microsize drug carriers due to their remarkable deformability. Shape plays a dominant role in determining their vascular transportation. Herein, we explored the effect of the shape of the microcapsules on the in vivo biodistribution for rational design of microcapsules to achieve optimized targeting efficiency. Silk fibroin, a biocompatible, biodegradable, and abundant material, was utilized as a building block to construct biconcave discoidal and spherical microcapsules with diameter of 1.8 μm and wall thickness of 20 nm. We have compared the cytocompatibility, cellular uptake, and biodistribution of both microcapsules. Both biconcave and spherical microcapsules exhibited excellent cytocompatibility and internalization into cancer cells. During blood circulation in mice, both microcapsules showed retention in liver and kidney and most underwent renal clearance. However, we observed significantly higher accumulation of biconcave silk microcapsules in lung compared with spherical microcapsules, and the accumulation was found to be stable in lung even after 3 days. The higher concentration of biconcave discoidal microcapsules found in lung arises from pulmonary environment, margination dynamics, and enhanced deformation in bloodstream. Red blood cell (RBC)-mimicking silk microcapsules demonstrated here can potentially serve as a promising platform for delivering drugs for lung diseases.

Toxic heavy metal ions and organic pollutants are significant concerns in wastewater treatment. Here, we demonstrate a novel membrane composed of polydopamine (PDA) particles and bacterial nanocellulose (BNC), which can efficiently remove a variety of metal ions and organic dyes from contaminated water. The biocompatible and biodegradable PDA/BNC membrane is synthesized by in situ incorporation of PDA particles into BNC matrix during its bacteria-mediated growth. We show that the PDA/BNC membrane can effectively remove heavy metal ions such as lead and cadmium, and organic dyes as surrogate markers of organic pollutants such as rhodamine 6G (R6G), methylene blue (MB), and methyl orange (MO). The removal efficiencies of contaminants were tested separately or simultaneously via simple filtration at pH values ranging from 4 to 7. Furthermore, after simple washing with regeneration agents, the membrane can be reused multiple times without compromising its contaminant sorption ability and mechanical integrity....

To alleviate the scarcity of clean water, solar steam generation, which utilizes the green and abundant resources of Earth, has attracted considerable attention and been recognized as a sustainable technology to purify seawater and wastewater. Within the past five to seven years, building on remarkable advances in the synthesis of nanoscale photothermal materials, significant progress has been made in the design and fabrication of solar evaporators. Here, we comprehensively review the materials and structures of the three key components of solar evaporators: solar absorbers, substrates (i.e., support layers), and water collectors towards efficient harvesting of sunlight, thermal management, water transportation, interfacial evaporation, and collection. In particular, we discuss the design principles of water collectors for solar-driven evaporation, which are in the early stages of development at present. Furthermore, bio-inspired water collectors provide exciting opportunities for the design and realization of efficient water harvesting from solar steam. Finally, we introduce photothermal-enhanced membrane distillation (PMD), a promising alternative technique involving solar-driven interfacial evaporation for producing clean water. PMD combines solar energy and membrane distillation, which facilitates efficient water purification and collection. In this review, we discuss the design guidelines and recent development of this photothermal-enhanced water purification. This review provides useful insights into the material choice and structure optimization to realize enhanced solar evaporators towards freshwater generation.

Advances in the design and synthesis of nanomaterials with desired biophysicochemical properties can be harnessed to develop non-invasive neuromodulation technologies. Here, we demonstrate the reversible modulation of the electrical activity of neurons and cardiomyocytes using polydopamine (PDA) nanoparticles as photothermal nanotransducers. In addition to their broad light absorption and excellent photothermal activity, PDA nanoparticles are highly biocompatible and biodegradable, making them excellent candidates for both in vitro and in vivo applications. The modulation of the activity (i.e. spike rate of the neurons and beating rate of cardiomyocytes) of excitable cells could be finely controlled by varying the excitation power density and irradiation duration. Under optimal conditions, we demonstrate reversible suppression (~100%) of neural activity and reversible enhancement (two-fold) in the beating rate of cardiomyocytes. To improve the ease of interfacing of photothermal transducers with these excitable cells and enable spatial localization of the photothermal stimulus, we have realized a collagen/PDA nanoparticle foam, which can be used as an “add-on patch” for photothermal stimulation. The non-genetic optical neuromodulation approach using biocompatible and biodegradable nanoparticles represents a minimally-invasive method for controlling the activity of excitable cells with potential applications in nano-neuroscience and engineering.

Fast nucleic acid (NA) amplification has found widespread biomedical applications, where high thermocycling rate is the key. The plasmon-driven nano-localized thermocycling around the gold nanorods (AuNRs) is a promising alternative, as the significantly reduced reaction volume enables a rapid temperature response. However, quantifying and adjusting the nano-localized temperature field remains challenging for now. Herein, a simple method is developed to quantify and adjust the nano-localized temperature field around AuNRs by combining experimental measurement and numerical simulation. An indirect method to measure the surface temperature of AuNRs is first developed by utilizing the temperature-dependent stability of Authiol bond. Meanwhile, the relationship of AuNRs' surface temperature with the AuNRs concentration and laser intensity, is also studied. In combination with thermal diffusion simulation, the nano-localized temperature field under the laser irradiation is obtained. The results show that the restricted reaction volume (≈aL level) enables ultrafast thermocycling rate (10

Macrophage adhesion and stretching have been shown to induce interleukin (IL)-1β production, but the mechanism of this mechanotransduction remains unclear. Here we specify the molecular link between mechanical tension on tissue-resident macrophages and activation of the NLRP3 inflammasome, which governs IL-1β production. NLRP3 activation enhances antimicrobial defense, but excessive NLRP3 activity causes inflammatory tissue damage in conditions such as pulmonary fibrosis and acute respiratory distress syndrome. We find that the actin-bundling protein L-plastin (LPL) significantly enhances NLRP3 assembly. Specifically, LPL enables apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) oligomerization during NLRP3 assembly by stabilizing ASC interactions with the kinase Pyk2, a component of cell-surface adhesive structures called podosomes. Upon treatment with exogenous NLRP3 activators, lung-resident alveolar macrophages (AMs) lacking LPL exhibit reduced caspase-1 activity, IL-1β cleavage, and gasdermin-D processing. LPL

The detection and quantification of protein biomarkers in interstitial fluid is hampered by challenges in its sampling and analysis. Here we report the use of a microneedle patch for fast in vivo sampling and on-needle quantification of target protein biomarkers in interstitial fluid. We used plasmonic fluor-an ultrabright fluorescent label-to improve the limit of detection of various interstitial fluid protein biomarkers by nearly 800-fold compared with conventional fluorophores, and a magnetic backing layer to implement conventional immunoassay procedures on the patch and thus improve measurement consistency. We used the microneedle patch in mice for minimally invasive evaluation of the efficiency of a cocaine vaccine, for longitudinal monitoring of the levels of inflammatory biomarkers, and for efficient sampling of the calvarial periosteum-a challenging site for biomarker detection-and the quantification of its levels of the matricellular protein periostin, which cannot be accurately inferred from blood or other systemic biofluids. Microneedle patches for the minimally invasive collection and analysis of biomarkers in interstitial fluid might facilitate point-of-care diagnostics and longitudinal monitoring.

We demonstrate that gold nanocages (AuNCs) with built-in artificial antibodies enable the detection of kidney injury biomarker from synthetic urine down to a concentration of 25 ng ml−1. Molecularly imprinted AuNCs exhibit excellent selectivity against numerous interfering urinary proteins and remarkable stability over a wide range of pH and specific gravity.

Developing insect cyborgs by integrating external components (optical, electrical or mechanical) with biological counterparts has a potential to offer elegant solutions for complex engineering problems.1 A key limiting step in the development of such biorobots arises at the nano-bio interface, i.e. between the organism and the nano implant that offers remote controllability.1,2 Often, invasive procedures are necessary that tend to severely compromise the navigation capabilities as well as the longevity of such biorobots. Therefore, we sought to develop a non-invasive solution using plasmonic nanostructures that can be photoexcited to generate heat with spatial and temporal control. We designed a ‘nanotattoo’ using silk that can interface the plasmonic nanostructures with a biological tissue. Our results reveal that both structural and functional integrity of the biological tissues such as insect antenna, compound eyes and wings were preserved after the attachment of the nanotattoo. Finally, we demonstrate that insects with the plasmonic nanotattoos can be remote controlled using light and integrated with functional recognition elements to detect the chemical environment in the region of interest. In sum, we believe that the proposed technology will play a crucial role in the emerging fields of biorobotics and other nano-bio applications.

Biological photonic structures can precisely control light propagation, scattering, and emission via hierarchical structures and diverse chemistry, enabling biophotonic applications for transparency, camouflaging, protection, mimicking and signaling. Corresponding natural polymers are promising building blocks for constructing synthetic multifunctional photonic structures owing to their renewability, biocompatibility, mechanical robustness, ambient processing conditions, and diverse surface chemistry. In this review, we provide a summary of the light phenomena in biophotonic structures found in nature, the selection of corresponding biopolymers for synthetic photonic structures, the fabrication strategies for flexible photonics, and corresponding emerging photonic-related applications. We introduce various photonic structures, including multi-layered, opal, and chiral structures, as well as photonic networks in contrast to traditionally considered light absorption and structural photonics. Next, we summarize the bottom-up and top-down fabrication approaches and physical properties of organized biopolymers and highlight the advantages of biopolymers as building blocks for realizing unique bioenabled photonic structures. Furthermore, we consider the integration of synthetic optically active nanocomponents into organized hierarchical biopolymer frameworks for added optical functionalities, such as enhanced iridescence and chiral photoluminescence. Finally, we present an outlook on current trends in biophotonic materials design and fabrication, including current issues, critical needs, as well as promising emerging photonic applications.