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The reconfigurable chiroptical effect is highly desirable for spin photonics, chiral spectroscopy, and photocatalysis due to its merits for dynamic and broadband applications. The coupling of an epsilon-near-zero (ENZ) mode to a chiral plasmon is expected to enable active and effective manipulation of the chiroptical effect but remains unexplored. Here we, for the first time to our knowledge, propose and demonstrate the strong coupling of an ENZ mode to a chiral plasmon by using a hybrid system composed of two identical vertically placed gold nanorods and an in-between ENZ film. An analytical three-oscillator model combined with numerical simulations is established to study the coupling mechanism, which predicts a Rabi splitting up to 240â meV with an ENZ film thickness of 60â nm in circular dichroism.
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Diamond is a supreme material for mid-infrared (MIR) integrated photonics as it has a transparency window up to 20â µm that covers the entire fingerprint region. However, its relatively low refractive index poses a challenge in designing an MIR diamond functional device with both small footprint and high transmission efficiency. Here we propose and demonstrate the inverse design of an MIR diamond waveguide beam splitter operating at the wavelength of 15â µm with a small footprint of â¼15â µm × â¼15â µm and a total transmission efficiency above 95%. Our work paves a new avenue for the design of compact and high-efficiency MIR diamond photonic devices.
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Uncovering the mystery of efficient and directional energy transfer in photosynthetic organisms remains a critical challenge in quantum biology. Recent experimental evidence and quantum theory developments indicate the significance of quantum features of molecular vibrations in assisting photosynthetic energy transfer, which provides the possibility of manipulating the process by controlling molecular vibrations. Here, we propose and theoretically demonstrate efficient manipulation of photosynthetic energy transfer by using vibrational strong coupling between the vibrational state of a Fenna-Matthews-Olson (FMO) complex and the vacuum state of an optical cavity. Specifically, based on a full-quantum analytical model to describe the strong coupling effect between the optical cavity and molecular vibration, we realize efficient manipulation of energy transfer efficiency (from 58% to 92%) and energy transfer time (from 20 to 500 ps) in one branch of FMO complex by actively controlling the coupling strength and the quality factor of the optical cavity under both near-resonant and off-resonant conditions, respectively. Our work provides a practical scenario to manipulate photosynthetic energy transfer by externally interfering molecular vibrations via an optical cavity and a comprehensible conceptual framework for researching other similar systems.
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Surface-enhanced Raman spectroscopy (SERS) is a potent analytical tool, particularly for molecular identification and structural analysis. Conventional metallic SERS substrates, however, suffer from low reproducibility and compatibility with biological molecules. Recently, metal-free SERS substrates based on chemical enhancement have emerged as a promising alternative with carbon-based materials offering excellent reproducibility and compatibility. Nevertheless, our understanding of carbon materials in SERS remains limited, which hinders their rational design. Here we systematically explore multidimensional carbon materials, including zero-dimensional fullerenes (C60), one-dimensional carbon nanotubes, two-dimensional graphene, and their B-, N-, and O-doped derivatives, for SERS applications. Using density functional theory, we elucidate the nonresonant polarizability-enhanced and resonant charge-transfer-based chemical enhancement mechanisms of these materials by evaluating their static/dynamic polarizability and electron excitation properties. This work provides a critical reference for the future design of carbon-based SERS substrates, opening a new avenue in this field.
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In-silico clearing enables deep optical imaging of biological samples by correcting image blur caused by scattering and aberration. This breakthrough method offers researchers unprecedented insights into three-dimensional biological systems, with enormous potential for advancing biology and medicine to better understand living organisms and human health.
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Fiber-optic sensors are an indispensable element of modern sensing technologies by virtue of their low cost, excellent electromagnetic immunity, and remote sensing capability. Optical Vernier effect is widely used to enhance sensitivity of fiber-optic sensors but requires bulky and complex cascaded interferometers. Here we propose and experimentally demonstrate an ultracompact (â¼2 mm by â¼2 mm) Vernier-effect-improved sensor by only using a single microfiber-knot resonator. With the Vernier effect achieved by controlling the optical beating with the spectral ripple of a super light emitting diode (SLED), we show â¼20x sensitivity enhancement for quantitative temperature monitoring. Our sensor creates a new practical method to realize Vernier effect in fiber-optic sensors and beyond.
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The ability to perform sensitive, real-time, in situ, multiplex chemical analysis is indispensable for diverse applications such as human health monitoring, food safety testing, forensic analysis, environmental sensing, and homeland security. Surface-enhanced Raman spectroscopy (SERS) is an effective tool to offer the ability by virtue of its high sensitivity and rapid label-free signal detection as well as the availability of portable Raman spectrometers. Unfortunately, the practical utility of SERS is limited because it generally requires sample collection and preparation, namely, collecting a sample from an object of interest and placing the sample on top of a SERS substrate to perform a SERS measurement. In fact, not all analytes can satisfy this requirement because the sample collection and preparation process may be undesirable, laborious, difficult, dangerous, costly, or time-consuming. Here we introduce "Place & Play SERS" based on an ultrathin, flexible, stretchable, adhesive, biointegratable gold-deposited polyvinyl alcohol (PVA) nanomesh substrate that enables placing the substrate on top of an object of interest and performing a SERS measurement of the object by epi-excitation without the need for touching, destroying, and sampling it. Specifically, we characterized the sensitivity of the gold/PVA nanomesh substrate in the Place & Play SERS measurement scheme and then used the scheme to conduct SERS measurements of both wet and dry objects under nearly real-world conditions. To show the practical utility of Place & Play SERS, we demonstrated two examples of its application: food safety testing and forensic analysis. Our results firmly verified the new measurement scheme of SERS and are expected to extend the potential of SERS by opening up untapped applications of sensitive, real-time, in situ multiplex chemical analysis.
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Microvascular thrombosis is a typical symptom of COVID-19 and shows similarities to thrombosis. Using a microfluidic imaging flow cytometer, we measured the blood of 181 COVID-19 samples and 101 non-COVID-19 thrombosis samples, resulting in a total of 6.3 million bright-field images. We trained a convolutional neural network to distinguish single platelets, platelet aggregates, and white blood cells and performed classical image analysis for each subpopulation individually. Based on derived single-cell features for each population, we trained machine learning models for classification between COVID-19 and non-COVID-19 thrombosis, resulting in a patient testing accuracy of 75%. This result indicates that platelet formation differs between COVID-19 and non-COVID-19 thrombosis. All analysis steps were optimized for efficiency and implemented in an easy-to-use plugin for the image viewer napari, allowing the entire analysis to be performed within seconds on mid-range computers, which could be used for real-time diagnosis.
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COVID-19 , Trombose , Humanos , Plaquetas , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de ComputaçãoRESUMO
Vascular stenosis caused by atherosclerosis instigates activation and aggregation of platelets, eventually resulting in thrombus formation. Although antiplatelet drugs are commonly used to inhibit platelet activation and aggregation, they unfortunately cannot prevent recurrent thrombotic events in patients with atherosclerosis. This is partially due to the limited understanding of the efficacy of antiplatelet drugs in the complex hemodynamic environment of vascular stenosis. Conventional methods for evaluating the efficacy of antiplatelet drugs under stenosis either fail to simulate the hemodynamic environment of vascular stenosis characterized by high shear stress and recirculatory flow or lack spatial resolution in their analytical techniques to statistically identify and characterize platelet aggregates. Here we propose and experimentally demonstrate a method comprising an in vitro 3D stenosis microfluidic chip and an optical time-stretch quantitative phase imaging system for studying the efficacy of antiplatelet drugs under stenosis. Our method simulates the atherogenic flow environment of vascular stenosis while enabling high-resolution and statistical analysis of platelet aggregates. Using our method, we distinguished the efficacy of three antiplatelet drugs, acetylsalicylic acid (ASA), cangrelor, and eptifibatide, for inhibiting platelet aggregation induced by stenosis. Specifically, ASA failed to inhibit stenosis-induced platelet aggregation, while eptifibatide and cangrelor showed high and moderate efficacy, respectively. Furthermore, we demonstrated that the drugs tested also differed in their efficacy for inhibiting platelet aggregation synergistically induced by stenosis and agonists (e.g., adenosine diphosphate, and collagen). Taken together, our method is an effective tool for investigating the efficacy of antiplatelet drugs under vascular stenosis, which could assist the development of optimal pharmacologic strategies for patients with atherosclerosis.
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Aterosclerose , Trombose , Humanos , Inibidores da Agregação Plaquetária/farmacologia , Eptifibatida/farmacologia , Constrição Patológica , Plaquetas , Aspirina/farmacologia , Aterosclerose/diagnóstico por imagem , Aterosclerose/tratamento farmacológico , Dispositivos Lab-On-A-ChipRESUMO
There is a global concern about the safety of COVID-19 vaccines associated with platelet function. However, their long-term effects on overall platelet activity remain poorly understood. Here we address this problem by image-based single-cell profiling and temporal monitoring of circulating platelet aggregates in the blood of healthy human subjects, before and after they received multiple Pfizer-BioNTech (BNT162b2) vaccine doses over a time span of nearly 1 year. Results show no significant or persisting platelet aggregation trends following the vaccine doses, indicating that any effects of vaccinations on platelet turnover, platelet activation, platelet aggregation, and platelet-leukocyte interaction was insignificant.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Vacinas contra COVID-19/efeitos adversos , Vacina BNT162 , COVID-19/prevenção & controle , Plaquetas , Vacinação/efeitos adversosRESUMO
Graphene oxide (GO) and reduced GO possess robust mechanical, electrical and chemical properties. Their nanocomposites have been extensively explored for applications in diverse fields. However, due to the high flexibility and weak interlayer interactions of GO nanosheets, the flexural mechanical properties of GO-based composites, especially in bulk materials, are largely constrained, which hinders their performance in practical applications. Here, inspired by the amorphous/crystalline feature of the heterophase within nacreous platelets, we present a centimetre-sized, GO-based bulk material consisting of building blocks of GO and amorphous/crystalline leaf-like MnO2 hexagon nanosheets adhered together with polymer-based crosslinkers. These building blocks are stacked and hot-pressed with further crosslinking between the layers to form a GO/MnO2-based layered (GML) bulk material. The resultant GML bulk material exhibits a flexural strength of 231.2 MPa. Moreover, the material exhibits sufficient fracture toughness and strong impact resistance while being light in weight. Experimental and numerical analyses indicate that the ordered heterophase structure and synergetic crosslinking interactions across multiscale interfaces lead to the superior mechanical properties of the material. These results are expected to provide insights into the design of structural materials and potential applications of high-performance GO-based bulk materials in aerospace, biomedicine and electronics.
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Grafite , Óxidos , Grafite/química , Compostos de Manganês , Óxidos/química , Polímeros/químicaRESUMO
A characteristic clinical feature of COVID-19 is the frequent incidence of microvascular thrombosis. In fact, COVID-19 autopsy reports have shown widespread thrombotic microangiopathy characterized by extensive diffuse microthrombi within peripheral capillaries and arterioles in lungs, hearts, and other organs, resulting in multiorgan failure. However, the underlying process of COVID-19-associated microvascular thrombosis remains elusive due to the lack of tools to statistically examine platelet aggregation (i.e., the initiation of microthrombus formation) in detail. Here we report the landscape of circulating platelet aggregates in COVID-19 obtained by massive single-cell image-based profiling and temporal monitoring of the blood of COVID-19 patients (n = 110). Surprisingly, our analysis of the big image data shows the anomalous presence of excessive platelet aggregates in nearly 90% of all COVID-19 patients. Furthermore, results indicate strong links between the concentration of platelet aggregates and the severity, mortality, respiratory condition, and vascular endothelial dysfunction level of COVID-19 patients.
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COVID-19/diagnóstico , Agregação Plaquetária , Análise de Célula Única , Trombose/virologia , COVID-19/sangue , Feminino , Humanos , Masculino , Microscopia , Fatores SexuaisRESUMO
Sepsis is a life-threatening condition caused by the extreme release of inflammatory mediators into the blood in response to infection (e.g., bacterial infection, COVID-19), resulting in the dysfunction of multiple organs. Currently, there is no direct treatment for sepsis. Here we report an abiotic hydrogel nanoparticle (HNP) as a potential therapeutic agent for late-stage sepsis. The HNP captures and neutralizes all variants of histones, a major inflammatory mediator released during sepsis. The highly optimized HNP has high capacity and long-term circulation capability for the selective sequestration and neutralization of histones. Intravenous injection of the HNP protects mice against a lethal dose of histones through the inhibition of platelet aggregation and migration into the lungs. In vivo administration in murine sepsis model mice results in near complete survival. These results establish the potential for synthetic, nonbiological polymer hydrogel sequestrants as a new intervention strategy for sepsis therapy and adds to our understanding of the importance of histones to this condition.
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Hidrogéis/uso terapêutico , Nanopartículas/uso terapêutico , Sepse/tratamento farmacológico , Animais , Plaquetas/efeitos dos fármacos , Adesão Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Histonas/antagonistas & inibidores , Histonas/metabolismo , Histonas/toxicidade , Hidrogéis/química , Hidrogéis/metabolismo , Hidrogéis/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Nanopartículas/química , Nanopartículas/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Polietilenoglicóis/química , Polietilenoglicóis/metabolismo , Polietilenoglicóis/farmacologia , Polietilenoglicóis/uso terapêutico , Ligação Proteica , Sepse/mortalidade , Taxa de SobrevidaRESUMO
Raman optical activity (ROA) is effective for studying the conformational structure and behavior of chiral molecules in aqueous solutions and is advantageous over X-ray crystallography and nuclear magnetic resonance spectroscopy in sample preparation and cost performance. However, ROA signals are inherently minuscule; 3-5 orders of magnitude weaker than spontaneous Raman scattering due to the weak chiral light-matter interaction. Localized surface plasmon resonance on metallic nanoparticles has been employed to enhance ROA signals, but suffers from detrimental spectral artifacts due to its photothermal heat generation and inability to efficiently transfer and enhance optical chirality from the far field to the near field. Here we demonstrate all-dielectric chiral-field-enhanced ROA by devising a silicon nanodisk array and exploiting its dark mode to overcome these limitations. Specifically, we use it with pairs of chemical and biological enantiomers to show >100x enhanced chiral light-molecule interaction with negligible artifacts for ROA measurements.
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Technological advances in image-based platelet analysis or platelet morphometry are critical for a better understanding of the structure and function of platelets in biological research as well as for the development of better clinical strategies in medical practice. Recently, the advent of high-throughput optical imaging and deep learning has boosted platelet morphometry to the next level by providing a new set of capabilities beyond what is achievable with traditional platelet morphometry, shedding light on the unexplored domain of platelet analysis. This Opinion article introduces emerging opportunities in 'intelligent' platelet morphometry, which are expected to pave the way for a new class of diagnostics, pharmacometrics, and therapeutics.
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PlaquetasRESUMO
Surface-enhanced Raman spectroscopy (SERS) is a powerful tool for vibrational spectroscopy as it provides several orders of magnitude higher sensitivity than inherently weak spontaneous Raman scattering by exciting localized surface plasmon resonance (LSPR) on metal substrates. However, SERS can be unreliable for biomedical use since it sacrifices reproducibility, uniformity, biocompatibility, and durability due to its strong dependence on "hot spots", large photothermal heat generation, and easy oxidization. Here, we demonstrate the design, fabrication, and use of a metal-free (i.e., LSPR-free), topologically tailored nanostructure composed of porous carbon nanowires in an array as a SERS substrate to overcome all these problems. Specifically, it offers not only high signal enhancement (~106) due to its strong broadband charge-transfer resonance, but also extraordinarily high reproducibility due to the absence of hot spots, high durability due to no oxidization, and high compatibility to biomolecules due to its fluorescence quenching capability.
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Carbono/química , Nanofios/química , Análise Espectral Raman/métodos , Fluorescência , Porosidade , Reprodutibilidade dos Testes , Ressonância de Plasmônio de Superfície/métodos , Propriedades de SuperfícieRESUMO
Optical assembly as a multiple optical trapping technique enables patterned arrangements of matter ranging from atoms to microparticles for diverse applications in biophysics, quantum physics, surface chemistry, and cell biology. Optical potential energy landscapes based on evanescent fields are conventionally employed for optical assembly of subwavelength particles, but are typically limited to predefined patterns and lacking in tunability. Here we present a microfiber photonic crystal cavity applicable for tunable optical assembly of subwavelength particles along a flexible path. This is enabled by excellent mechanical flexibility of the microfiber cavity as well as its broadband photonic crystal reflectors. By virtue of the broadband reflectors, the lattice constant of the assembled particles is precisely tunable via altering the wavelength of input light. Three-dimensional optical assembly is also realized by making use of the high-order transverse mode of the microfiber cavity. Moreover, the optical assembly process is detectable by simply monitoring the reflection/transmission spectrum of the microfiber cavity. The design of the microfiber cavity heralds a new way for tunable optical assembly of subwavelength particles, potentially applicable for development of tunable photonic crystals, metamaterials, and sensors.
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Optical activity is an effect of prominent importance in stereochemistry, analytical chemistry, metamaterials, spin photonics, and astrobiology, but is naturally minuscule. Metallic nanostructures are commonly exploited as basic elements for artificially producing large optical activity by virtue of surface plasmon resonance (SPR) on the nanostructures. However, their intrinsic high ohmic loss amplified by the SPR results in low energy efficiency and large photothermal heat generation, severely limiting their performance and practical utility. Giant optical activity by inducing magnetic resonance in an all-dielectric spiral nanoflower (spiral-flower-shaped nanostructure) is demonstrated here. Specifically, a large circular-intensity difference of ≈35% is theoretically predicted and experimentally demonstrated by optimizing the magnetic quadrupole contribution of the nanoflower to scattered light. The nanoflower overcomes the bottleneck of the traditional metallic platforms and enables the development of diverse chiroptical devices and applications.
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Germanium is a promising material for mid-infrared (MIR) integrated photonics due to its CMOS compatibility and wide transparency window covering the fingerprint spectral region (2-15 µm). However, due to the limited quality and structural configurations of conventional germanium-based integration platforms, the realization of high-Q on-chip germanium resonators in the MIR spectral range remains challenging to date. Here we experimentally demonstrate an air-cladding MIR germanium microring resonator with, to the best of our knowledge, the highest loaded Q-factor of â¼57,000 across all germanium-based integration platforms to date. A propagation loss of 5.4 dB/cm and a high extinction ratio of 22 dB approaching the critical coupling condition are experimentally realized. These are enabled by our smart-cut methods for developing high-quality germanium-on-insulator wafers and by implementing our suspended-membrane structure. Our high-Q germanium microring resonator is a promising step towards a number of on-chip applications in the MIR spectral range.
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The mid-infrared (MIR) spectral range holds significant potential for spectroscopic and sensing applications because it encompasses the fingerprint region that unveils the vibrational and rotational signatures of molecules. CMOS-compatible on-chip devices that can achieve strong light-matter interaction in the entire fingerprint region are considered a promising way for such applications, but remain unprecedented. Here we present an on-chip MIR germanium photonic crystal cavity that covers the entire fingerprint region. This is made possible by harnessing a homemade air-cladding germanium platform. Our MIR device creates a new avenue toward integrated nonlinear optics and on-chip biochemical sensing in the fingerprint region.