Bioinspired Plasmo-virus for Point-of-Care SARS-CoV-2 Detection.

Directly identifying the presence of the virus in infected hosts with an appropriate speed and sensitivity permits early epidemic management even during the presymptomatic incubation period of infection. Here, we synthesize a bioinspired plasmo-virus (BPV) particle for rapid and sensitive point-of-care (POC) detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via a self-assembled plasmonic nanoprobe array on spike proteins. The BPV enables strong near-infrared (NIR) extinction peaks caused by plasmonic nanogaps. We quantify SARS-CoV-2 in viral transport medium (VTM) at low titers within 10 min with a limit of detection (LOD) of 1.4 × 101 pfu/mL, which is 103 times more sensitive than the current gold-standard method. The high-sensitivity and high-speed POC detection may be widely used for the timely, individualized diagnosis of infectious agents in low-resource settings.

Extreme-Pressure Imprint Lithography for Heat and Ultraviolet-Free Direct Patterning of Rigid Nanoscale Features.

Nanoimprint lithography (NIL) is typically performed by filling up of molds by heated polymers or UV-curable liquid resists, inevitably requiring subsequent pattern-transfer processes. Although direct NIL techniques have been suggested alternatively, they usually require precursors or ink-type resists containing undesired organic components. Here, we demonstrate extreme-pressure imprint lithography (EPIL) that effectively produces well-defined multiscale structures with a wide range from 10 nm to 10 mm on diverse surfaces even including pure or alloy metals without using any precursors, heating, UV exposure, or pattern transfer. In particular, EPIL is accomplished through precise control of room-temperature plastic deformation in nanoscale volumes, which is elucidated by finite element analyses and molecular dynamics simulations. In addition to scalability to macroscopic areas, we confirm the outstanding versatility of EPIL via its successful applications to Ni, Cu, steel, and organics. We expect that the state-of-the-art EPIL process combined with other emerging nanopatterning technologies will be extendable to the future large-area nanofabrication of various devices.

Few-Layer MoS2 Photodetector Arrays for Ultrasensitive On-Chip Enzymatic Colorimetric Analysis.

Enzymatic colorimetric analysis of metabolites provides signatures of energy conversion and biosynthesis associated with disease onsets and progressions. Miniaturized photodetectors based on emerging two-dimensional transition metal dichalcogenides (TMDCs) promise to advance point-of-care diagnosis employing highly sensitive enzymatic colorimetric detection. Reducing diagnosis costs requires a batched multisample assay. The construction of few-layer TMDC photodetector arrays with consistent performance is imperative to realize optical signal detection for a miniature batched multisample enzymatic colorimetric assay. However, few studies have promoted an optical reader with TMDC photodetector arrays for on-chip operation. Here, we constructed 4 × 4 pixel arrays of miniaturized molybdenum disulfide (MoS2) photodetectors and integrated them with microfluidic enzyme reaction chambers to create an optoelectronic biosensor chip device. The fabricated device allowed us to achieve arrayed on-chip enzymatic colorimetric detection of d-lactate, a blood biomarker signifying the bacterial translocation from the intestine, with a limit of detection that is 1000-fold smaller than the clinical baseline, a 10 min assay time, high selectivity, and reasonably small variability across the entire arrays. The enzyme (Ez)/MoS2 optoelectronic biosensor unit consistently detected d-lactate in clinically important biofluids, such as saliva, urine, plasma, and serum of swine and humans with a wide detection range (10-3-103 µg/mL). Furthermore, the biosensor enabled us to show that high serum d-lactate levels are associated with the symptoms of systemic infection and inflammation. The lensless, optical waveguide-free device architecture should readily facilitate development of a monolithically integrated hand-held module for timely, cost-effective diagnosis of metabolic disorders in near-patient settings.

Integrated on-site collection and detection of airborne microparticles for smartphone-based micro-climate quality control.

The rapid emergence of air-mediated diseases in a micro-climate demands on-site monitoring of airborne microparticles. The on-site detection of airborne microparticles becomes more challenging as the particles are highly localized and change dynamically over time. However, most existing monitoring systems rely on time-consuming sample collection and centralized off-site analysis. Here, we report a smartphone-based integrated microsystem for on-site collection and detection that enables real-time detection of indoor airborne microparticles with high sensitivity. The collection device, inspired by the Venturi effect, was designed to collect airborne microparticles without requiring an additional power supply. Our systematic analysis showed that the collection device was able to collect microparticles with consistent negative pressure, regardless of the particle concentration in the air sample. By incorporating a microfluidic-biochip based on inertial force to trap particles and an optoelectronic photodetector into a miniaturized device with a smartphone, we demonstrate real-time and sensitive detection of the collected airborne microparticles, such as Escherichia coli, Bacillus subtilis, Micrococcus luteus, and Staphylococcus with a particle-density dynamic range of 103-108 CFU mL-1. Because of its capabilities of minimal-power sample collection, high sensitivity, and rapid detection of airborne microparticles, this integrated platform can be readily adopted by the government and industrial sectors to monitor indoor air contamination and improve human healthcare.

Inkjet-defined site-selective (IDSS) growth for controllable production of in-plane and out-of-plane MoS2 device arrays.

Along with the increasing interest in MoS2 as a promising electronic material, there is also an increasing demand for nanofabrication technologies that are compatible with this material and other relevant layered materials. In addition, the development of scalable nanofabrication approaches capable of directly producing MoS2 device arrays is an imperative task to speed up the design and commercialize various functional MoS2-based devices. The desired fabrication methods need to meet two critical requirements. First, they should minimize the involvement of resist-based lithography and plasma etching processes, which introduce unremovable contaminations to MoS2 structures. Second, they should be able to produce MoS2 structures with in-plane or out-of-plane edges in a controlled way, which is key to increase the usability of MoS2 for various device applications. Here, we introduce an inkjet-defined site-selective (IDSS) method that meets these requirements. IDSS includes two main steps: (i) inkjet printing of microscale liquid droplets that define the designated sites for MoS2 growth, and (ii) site-selective growth of MoS2 at droplet-defined sites. Moreover, IDSS is capable of generating MoS2 with different structures. Specifically, an IDSS process using deionized (DI) water droplets mainly produces in-plane MoS2 features, whereas the processes using graphene ink droplets mainly produce out-of-plane MoS2 features rich in exposed edges. Using out-of-plane MoS2 structures, we have demonstrated the fabrication of miniaturized on-chip lithium ion batteries, which exhibit reversible lithiation/delithiation capacity. This IDSS method could be further expanded as a scalable and reliable nanomanufacturing method for generating miniaturized on-chip energy storage devices.

An Integrated Plasmo-Photoelectronic Nanostructure Biosensor Detects an Infection Biomarker Accompanying Cell Death in Neutrophils.

Bacterial infections leading to sepsis are a major cause of deaths in the intensive care unit. Unfortunately, no effective methods are available to capture the early onset of infectious sepsis near the patient with both speed and sensitivity required for timely clinical treatment. To fill the gap, the authors develop a highly miniaturized (2.5 × 2.5 µm2 ) plasmo-photoelectronic nanostructure device that detected citrullinated histone H3 (CitH3), a biomarker released to the blood circulatory system by neutrophils. Rapidly detecting CitH3 with high sensitivity has the great potential to prevent infections from developing life-threatening septic shock. To this end, the author's device incorporates structurally engineered arrayed hemispherical gold nanoparticles that are functionalized with high-affinity antibodies. A nanoplasmonic resonance shift induces a photoconduction increase in a few-layer molybdenum disulfide (MoS2 ) channel, and it provides the sensor signal. The device achieves label-free detection of serum CitH3 with a 5-log dynamic range from 10-4 to 101 ng mL and a sample-to-answer time <20 min. Using this biosensor, the authors longitudinally measure the dynamic CitH3 profiles of individual living mice in a sepsis model at high resolution over 12 hours. The developed biosensor may be poised for future translation to personalized management of systemic bacterial infections.

All-optical tunable plasmonic nano-aggregations for surface-enhanced Raman scattering.

Interparticle forces play a crucial role in nanoparticle-based nanoscience and nanoengineering for synthesizing new materials, manipulating nanoscale structures, understanding biological processes and ultrasensitive sensing. Complicated by the fluid-dynamical and chemical nature of the liquid environment of nanoparticles, previous attempts are limited to electromagnetic and chemical methods. Alternatively, optically induced forces provide a convenient and fabrication-free route to manipulate nanoparticles at the nanoscale. Here we demonstrate a new double laser trapping scheme for metallic nano-aggregation by inducing strong near-field optical interparticle forces without any chemical agents or complicated fabrication processes. These induced optical forces arising from strong localized plasmon resonance strongly depend on the interparticle separation well beyond the diffraction limit and the polarization of the incident laser field. We examine such sub-resolved interparticle separation in trapped nanoaggregates by measuring surface-enhanced Raman scattering, and further demonstrate the single-molecule sensitivity by implementing such nanostructures. This new technique opens a new avenue for all-optical manipulation of nanomaterials as well as ultra-sensitive bio-chemical sensing applications.

Resolution-enhanced imaging through scattering media by high-order correlation.

Super-resolution optical imaging is a rapidly emerging technology enabling many applications. Recently, correlation imaging has shown its capability in imaging beyond the diffraction limit, relying on quantum and statistical properties of light. High-order correlation imaging can further enhance resolution, however, at the expense of complicated algorithms. Here, we experimentally demonstrate a resolution-enhanced method of imaging through scattering media by exploiting high-order correlation of fluorescence light. Based on this method, individual fluorophores' temporal fluctuations are recorded and computed for their distinguished high-order correlations that enable super-resolution. Special designed time sequences are chosen to reduce computation time and memory. Such high-order correlation imaging exhibits reliable performance through scattering media with significant resolution enhancement and background noise reduction. This efficient imaging method paves the way for new biomedical applications.

Ionic modulation and ionic coupling effects in MoS2 devices for neuromorphic computing.

Coupled ionic-electronic effects present intriguing opportunities for device and circuit development. In particular, layered two-dimensional materials such as MoS2 offer highly anisotropic ionic transport properties, facilitating controlled ion migration and efficient ionic coupling among devices. Here, we report reversible modulation of MoS2 films that is consistent with local 2H-1T' phase transitions by controlling the migration of Li+ ions with an electric field, where an increase/decrease in the local Li+ ion concentration leads to the transition between the 2H (semiconductor) and 1T' (metal) phases. The resulting devices show excellent memristive behaviour and can be directly coupled with each other through local ionic exchange, naturally leading to synaptic competition and synaptic cooperation effects observed in biology. These results demonstrate the potential of direct modulation of two-dimensional materials through field-driven ionic processes, and can lead to future electronic and energy devices based on coupled ionic-electronic effects and biorealistic implementation of artificial neural networks.

Rubbing-Induced Site-Selective Growth of MoS2 Device Patterns.

The superior electronic and mechanical properties of two-dimensional layered transition-metal dichalcogenides could be exploited to make a broad range of devices with attractive functionalities. However, the nanofabrication of such layered material-based devices still needs resist-based lithography and plasma etching processes for patterning layered materials into functional device features. Such patterning processes lead to unavoidable contaminations, to which the transport characteristics of atomically thin-layered materials are very sensitive. More seriously, such lithography-introduced contaminants cannot be safely eliminated by conventional semiconductor cleaning approaches. This challenge seriously retards the manufacturing of large arrays of layered material-based devices with consistent characteristics. Toward addressing this challenge, we introduce a rubbing-induced site-selective growth method capable of directly generating few-layer MoS2 device patterns without the need of any additional patterning processes. This method consists of two critical steps: (i) a damage-free mechanical rubbing process for generating microscale triboelectric charge patterns on a dielectric surface and (ii) site-selective deposition of MoS2 within rubbing-induced charge patterns. Our microscopy characterizations in combination with finite element analysis indicate that the field magnitude distribution within triboelectric charge patterns determines the morphologies of grown MoS2 patterns. In addition, the MoS2 line patterns produced by the presented method have been implemented for making arrays of working transistors and memristors. These devices exhibit a high yield and good uniformity in their electronic properties over large areas. The presented method could be further developed into a cost-efficient nanomanufacturing approach for producing functional device patterns based on various layered materials.

MoS2 Memristors Exhibiting Variable Switching Characteristics toward Biorealistic Synaptic Emulation.

Memristors based on 2D layered materials could provide biorealistic ionic interactions and potentially enable construction of energy-efficient artificial neural networks capable of faithfully emulating neuronal interconnections in human brains. To build reliable 2D-material-based memristors suitable for constructing working neural networks, the memristive switching mechanisms in such memristors need to be systematically analyzed. Here, we present a study on the switching characteristics of the few-layer MoS2 memristors made by mechanical printing. First, two types of dc-programmed switching characteristics, termed rectification-mediated and conductance-mediated behaviors, are observed among different MoS2 memristors, which are attributed to the modulation of MoS2/metal Schottky barriers and redistribution of vacancies, respectively. We also found that an as-fabricated MoS2 memristor initially exhibits an analog pulse-programmed switching behavior, but it can be converted to a quasi-binary memristor with an abrupt switching behavior through an electrical stress process. Such a transition of switching characteristics is attributed to field-induced agglomeration of vacancies at MoS2/metal interfaces. The additional Kelvin probe force microscopy, Auger electron spectroscopy analysis, and electronic characterization results support this hypothesis. Finally, we fabricated a testing device consisting of two adjacent MoS2 memristors and demonstrated that these two memristors can be ionically coupled to each other. This device interconnection scheme could be exploited to build neural networks for emulating ionic interactions among neurons. This work advances the device physics for understanding the memristive properties of 2D-material-based memristors and serves as a critical foundation for building biorealistic neuromorphic computing systems based on such memristors.

Cyclewise Operation of Printed MoS2 Transistor Biosensors for Rapid Biomolecule Quantification at Femtomolar Levels.

Field-effect transistors made from MoS2 and other emerging layered semiconductors have been demonstrated to be able to serve as ultrasensitive biosensors. However, such nanoelectronic sensors still suffer seriously from a series of challenges associated with the poor compatibility between electronic structures and liquid analytes. These challenges hinder the practical biosensing applications that demand rapid, low-noise, highly specific biomolecule quantification at femtomolar levels. To address such challenges, we study a cyclewise process for operating MoS2 transistor biosensors, in which a series of reagent fluids are delivered to the sensor in a time-sequenced manner and periodically set the sensor into four assay-cycle stages, including incubation, flushing, drying, and electrical measurement. Running multiple cycles of such an assay can acquire a time-dependent sensor response signal quantifying the reaction kinetics of analyte-receptor binding. This cyclewise detection approach can avoid the liquid-solution-induced electrochemical damage, screening, and nonspecific adsorption to the sensor and therefore improves the transistor sensor's durability, sensitivity, specificity, and signal-to-noise ratio. These advantages in combination with the inherent high sensitivity of MoS2 biosensors allow for rapid biomolecule quantification at femtomolar levels. We have demonstrated the cyclewise quantification of Interleukin-1ß in pure and complex solutions (e.g., serum and saliva) with a detection limit of ∼1 fM and a total detection time ∼23 min. This work leverages the superior properties of layered semiconductors for biosensing applications and advances the techniques toward realizing fast real-time immunoassay for low-abundance biomolecule detection.

Biotunable Nanoplasmonic Filter on Few-Layer MoS2 for Rapid and Highly Sensitive Cytokine Optoelectronic Immunosensing.

Monitoring of the time-varying immune status of a diseased host often requires rapid and sensitive detection of cytokines. Metallic nanoparticle-based localized surface plasmon resonance (LSPR) biosensors hold promise to meet this clinical need by permitting label-free detection of target biomolecules. These biosensors, however, continue to suffer from relatively low sensitivity as compared to conventional immunoassay methods that involve labeling processes. Their response speeds also need to be further improved to enable rapid cytokine quantification for critical care in a timely manner. In this paper, we report an immunobiosensing device integrating a biotunable nanoplasmonic optical filter and a highly sensitive few-layer molybdenum disulfide (MoS2) photoconductive component, which can serve as a generic device platform to meet the need of rapid cytokine detection with high sensitivity. The nanoplasmonic filter consists of anticytokine antibody-conjugated gold nanoparticles on a SiO2 thin layer that is placed 170 µm above a few-layer MoS2 photoconductive flake device. The principle of the biosensor operation is based on tuning the delivery of incident light to the few-layer MoS2 photoconductive flake thorough the nanoplasmonic filter by means of biomolecular surface binding-induced LSPR shifts. The tuning is dependent on cytokine concentration on the nanoplasmonic filter and optoelectronically detected by the few-layer MoS2 device. Using the developed optoelectronic biosensor, we have demonstrated label-free detection of IL-1ß, a pro-inflammatory cytokine, with a detection limit as low as 250 fg/mL (14 fM), a large dynamic range of 106, and a short assay time of 10 min. The presented biosensing approach could be further developed and generalized for point-of-care diagnosis, wearable bio/chemical sensing, and environmental monitoring.

Abnormal Multiple Charge Memory States in Exfoliated Few-Layer WSe2 Transistors.

To construct reliable nanoelectronic devices based on emerging 2D layered semiconductors, we need to understand the charge-trapping processes in such devices. Additionally, the identified charge-trapping schemes in such layered materials could be further exploited to make multibit (or highly desirable analog-tunable) memory devices. Here, we present a study on the abnormal charge-trapping or memory characteristics of few-layer WSe2 transistors. This work shows that multiple charge-trapping states with large extrema spacing, long retention time, and analog tunability can be excited in the transistors made from mechanically exfoliated few-layer WSe2 flakes, whereas they cannot be generated in widely studied few-layer MoS2 transistors. Such charge-trapping characteristics of WSe2 transistors are attributed to the exfoliation-induced interlayer deformation on the cleaved surfaces of few-layer WSe2 flakes, which can spontaneously form ambipolar charge-trapping sites. Our additional results from surface characterization, charge-retention characterization at different temperatures, and density functional theory computation strongly support this explanation. Furthermore, our research also demonstrates that the charge-trapping states excited in multiple transistors can be calibrated into consistent multibit data storage levels. This work advances the understanding of the charge memory mechanisms in layered semiconductors, and the observed charge-trapping states could be further studied for enabling ultralow-cost multibit analog memory devices.

Scaling behavior of nanoimprint and nanoprinting lithography for producing nanostructures of molybdenum disulfide.

Top-down lithography techniques are needed for manufacturing uniform device structures based on emerging 2D-layered materials. Mechanical exfoliation approaches based on nanoimprint and nanoprint principles are capable of producing ordered arrays of multilayer transition metal dichalcogenide microstructures with a high uniformity of feature dimensions. In this study, we present a study on the applicability of nanoimprint-assisted shear exfoliation for generating ultrathin monolayer and few-layer MoS2 structures as well as the critical limits of feature dimensions produced via such nanoimprint and nanoprint-based processes. In particular, this work shows that give a lateral feature size of MoS2 structures that are pre-patterned on a bulk stamp, there exists a critical thickness or aspect ratio value, below which the exfoliated layered structures exhibit major defects. To exfoliate a high-quality, uniform monolayer or few-layer structures, the characteristic lateral feature sizes of such structures need to be in the sub-100 nm regimes. In addition, the exfoliated MoS2 flakes of critical thicknesses exhibit prominent interlayer twisting features on their cleaved surfaces. Field-effect transistors made from these MoS2 flakes exhibit multiple (or quasi-analog-tunable) charge memory states. This work advances the knowledge regarding the limitations and application scope of nanoimprint and nanoprint processes in manufacturing nano/microstructures based on layered materials and provides a method for producing multi-bit charge memory devices.

Optically induced transparency in a micro-cavity.

Electromagnetically induced transparency has the unique ability to optically control transparency windows with low light in atomic systems. However, its practical applications in quantum physics and information science are limited due to rigid experimental requirements. Here we demonstrate a new mechanism of optically induced transparency in a micro-cavity by introducing a four-wave mixing gain to nonlinearly couple two separated resonances of the micro-cavity in an ambient environment. A signature Fano-like resonance was observed owing to the nonlinear interference of the two coupled resonances. Moreover, we show that the unidirectional gain of the four-wave mixing can lead to the remarkable effect of non-reciprocal transmission at the transparency windows. Optically induced transparency may offer a unique platform for a compact, integrated solution to all-optical and quantum information.

Nanoimprint-Assisted Shear Exfoliation (NASE) for Producing Multilayer MoS2 Structures as Field-Effect Transistor Channel Arrays.

MoS2 and other semiconducting transition metal dichalcogenides (TMDCs) are of great interest due to their excellent physical properties and versatile chemistry. Although many recent research efforts have been directed to explore attractive properties associated with MoS2 monolayers, multilayer/few-layer MoS2 structures are indeed demanded by many practical scale-up device applications, because multilayer structures can provide sizable electronic/photonic state densities for driving upscalable electrical/optical signals. Currently there is a lack of processes capable of producing ordered, pristine multilayer structures of MoS2 (or other relevant TMDCs) with manufacturing-grade uniformity of thicknesses and electronic/photonic properties. In this article, we present a nanoimprint-based approach toward addressing this challenge. In this approach, termed as nanoimprint-assisted shear exfoliation (NASE), a prepatterned bulk MoS2 stamp is pressed into a polymeric fixing layer, and the imprinted MoS2 features are exfoliated along a shear direction. This shear exfoliation can significantly enhance the exfoliation efficiency and thickness uniformity of exfoliated flakes in comparison with previously reported exfoliation processes. Furthermore, we have preliminarily demonstrated the fabrication of multiple transistors and biosensors exhibiting excellent device-to-device performance consistency. Finally, we present a molecular dynamics modeling analysis of the scaling behavior of NASE. This work holds significant potential to leverage the superior properties of MoS2 and other emerging TMDCs for practical scale-up device applications.

Dielectric Optical-Controllable Magnifying Lens by Nonlinear Negative Refraction.

A simple optical lens plays an important role for exploring the microscopic world in science and technology by refracting light with tailored spatially varying refractive indices. Recent advancements in nanotechnology enable novel lenses, such as, superlens and hyperlens, with sub-wavelength resolution capabilities by specially designed materials' refractive indices with meta-materials and transformation optics. However, these artificially nano- or micro-engineered lenses usually suffer high losses from metals and are highly demanding in fabrication. Here, we experimentally demonstrate, for the first time, a nonlinear dielectric magnifying lens using negative refraction by degenerate four-wave mixing in a plano-concave glass slide, obtaining magnified images. Moreover, we transform a nonlinear flat lens into a magnifying lens by introducing transformation optics into the nonlinear regime, achieving an all-optical controllable lensing effect through nonlinear wave mixing, which may have many potential applications in microscopy and imaging science.