Plasmonic photonic biosensor: in situ detection and quantification of SARS-CoV-2 particles.

We conceptualized and numerically investigated a photonic crystal fiber (PCF)-based surface plasmon resonance (SPR) sensor for rapid detection and quantification of novel coronavirus. The plasmonic gold-based optical sensor permits three different ways to quantify the virus concentrations inside patient's body based on different ligand-analyte conjugate pairs. This photonic biosensor demonstrates viable detections of SARS-CoV-2 spike receptor-binding-domain (RBD), mutated viral single-stranded ribonucleic acid (RNA) and human monoclonal antibody immunoglobulin G (IgG). A marquise-shaped core is introduced to facilitate efficient light-tailoring. Analytes are dissolved in sterile phosphate buffered saline (PBS) and surfaced on the plasmonic metal layer for realizing detection. The 1-pyrene butyric acid n-hydroxy-succinimide ester is numerically used to immobilize the analytes on the sensing interface. Using the finite element method (FEM), the proposed sensor is studied critically and optimized for the refractive index (RI) range from 1.3348-1.3576, since the target analytes RIs fluctuate within this range depending on the severity of the viral infection. The polarization-dependent sensor exhibits dominant sensing attributes for x-polarized mode, where it shows the average wavelength sensitivities of 2,009 nm/RIU, 2,745 nm/RIU and 1,984 nm/RIU for analytes: spike RBD, extracted coronavirus RNA and antibody IgG, respectively. The corresponding median amplitude sensitivities are 135 RIU-1, 196 RIU-1 and 140 RIU-1, respectively. The maximum sensor resolution and figure of merit are found 2.53 × 10-5 RIU and 101 RIU-1, respectively for viral RNA detection. Also, a significant limit of detection (LOD) of 6.42 × 10-9 RIU2/nm is obtained. Considering modern bioassays, the proposed compact photonic sensor will be well-suited for rapid point-of-care COVID testing.

Large-Scale Functionalized Metasurface-Based SARS-CoV-2 Detection and Quantification.

Plasmonic metasurfaces consist of metal-dielectric interfaces that are excitable at background and leakage resonant modes. The sharp and plasmonic excitation profile of metal-free electrons on metasurfaces at the nanoscale can be used for practical applications in diverse fields, including optoelectronics, energy harvesting, and biosensing. Currently, Fano resonant metasurface fabrication processes for biosensor applications are costly, need clean room access, and involve limited small-scale surface areas that are not easy for accurate sample placement. Here, we leverage the large-scale active area with uniform surface patterns present on optical disc-based metasurfaces as a cost-effective method to excite asymmetric plasmonic modes, enabling tunable optical Fano resonance interfacing with a microfluidic channel for multiple target detection in the visible wavelength range. We engineered plasmonic metasurfaces for biosensing through efficient layer-by-layer surface functionalization toward real-time measurement of target binding at the molecular scale. Further, we demonstrated the quantitative detection of antibodies, proteins, and the whole viral particles of SARS-CoV-2 with a high sensitivity and specificity, even distinguishing it from similar RNA viruses such as influenza and MERS. This cost-effective plasmonic metasurface platform offers a small-scale light-manipulation system, presenting considerable potential for fast, real-time detection of SARS-CoV-2 and pathogens in resource-limited settings.

Acoustic Fabrication of Living Cardiomyocyte-based Hybrid Biorobots.

Organized assemblies of cells have demonstrated promise as bioinspired actuators and devices; still, the fabrication of such "biorobots" has predominantly relied on passive assembly methods that reduce design capabilities. To address this, we have developed a strategy for the rapid formation of functional biorobots composed of live cardiomyocytes. We employ tunable acoustic fields to facilitate the efficient aggregation of millions of cells into high-density macroscopic architectures with directed cell orientation and enhanced cell-cell interaction. These biorobots can perform actuation functions both through naturally occurring contraction-relaxation cycles and through external control with chemical and electrical stimuli. We demonstrate that these biorobots can be used to achieve controlled actuation of a soft skeleton and pumping of microparticles. The biocompatible acoustic assembly strategy described here should prove generally useful for cellular manipulation in the context of tissue engineering, soft robotics, and other applications.

Plasmonic Micro-Channel Assisted Photonic Crystal Fiber Based Highly Sensitive Sensor for Multi-Analyte Detection.

A dual-channel propagation controlled photonic crystal fiber (PCF)-based plasmonic sensor was presented to detect multiple analytes simultaneously. Plasmonic micro-channels were placed on the outer surface of the PCF, which facilitates an easy sensing mechanism. The sensor was numerically investigated by the finite element method (FEM) with the perfectly matched layer (PML) boundary conditions. The proposed sensor performances were analyzed based on optimized sensor parameters, such as confinement loss, resonance coupling, resolution, sensitivity, and figure of merit (FOM). The proposed sensor showed a maximum wavelength sensitivity (WS) of 25,000 nm/refractive index unit (RIU) with a maximum sensor resolution (SR) of 4.0 × 10-6 RIU for channel 2 (Ch-2), and WS of 3000 nm/RIU with SR of 3.33 × 10-5 RIU for channel 1 (Ch-1). To the best of our knowledge, the proposed sensor exhibits the highest WS compared with the previously reported multi-analyte based PCF surface plasmon resonance (SPR) sensors. The proposed sensor could detect the unknown analytes within the refractive index (RI) range of 1.32 to 1.39 in the visible to near infrared region (550 to 1300 nm). In addition, the proposed sensor offers the maximum Figure of Merit (FOM) of 150 and 500 RIU-1 with the limit of detection (LOD) of 1.11 × 10-8 RIU2/nm and 1.6 × 10-10 RIU2/nm for Ch-1 and Ch-2, respectively. Due to its highly sensitive nature, the proposed multi-analyte PCF SPR sensor could be a prominent candidate in the field of biosensing to detect biomolecule interactions and chemical sensing.

Advanced Point-of-Care Testing Technologies for Human Acute Respiratory Virus Detection.

The ever-growing global threats to human life caused by the human acute respiratory virus (RV) infections have cost billions of lives, created a significant economic burden, and shaped society for centuries. The timely response to emerging RVs could save human lives and reduce the medical care burden. The development of RV detection technologies is essential for potentially preventing RV pandemic and epidemics. However, commonly used detection technologies lack sensitivity, specificity, and speed, thus often failing to provide the rapid turnaround times. To address this problem, new technologies are devised to address the performance inadequacies of the traditional methods. These emerging technologies offer improvements in convenience, speed, flexibility, and portability of point-of-care test (POCT). Herein, recent developments in POCT are comprehensively reviewed for eight typical acute respiratory viruses. This review discusses the challenges and opportunities of various recognition and detection strategies and discusses these according to their detection principles, including nucleic acid amplification, optical POCT, electrochemistry, lateral flow assays, microfluidics, enzyme-linked immunosorbent assays, and microarrays. The importance of limits of detection, throughput, portability, and specificity when testing clinical samples in resource-limited settings is emphasized. Finally, the evaluation of commercial POCT kits for both essential RV diagnosis and clinical-oriented practices is included.

Multi-Analyte Detection Based on Integrated Internal and External Sensing Approach.

Highly sensitive, simple and multiplex detection capabilities are key criteria of point-of-care (POC) diagnosis in clinical samples. Here, a simple and highly sensitive multi-analyte detection technique is proposed by using photonic crystal fiber (PCF) based surface plasmon resonance (SPR) sensor that employs both internal and external sensing approaches. The proposed sensor can detect two different analytes simultaneously by the internal and external plasmonic micro-channels. The light propagation through the sensor is controlled by the scaled-down air-holes to excite the free electrons of the plasmonic metal layers. The light- guiding and sensing properties of the sensor is numerically analyzed by using the Finite Element Method (FEM). The proposed sensor shows the maximum wavelength sensitivities (WS) of 12,000 nm/refractive index unit (RIU), and 10,000 nm/RIU, for the internal and external sensing approaches, respectively, and corresponding resolution of 8.33×10 -6 RIU and 1.0×10-5 RIU. Moreover, the hybrid sensor is applicable to detect unknown analyte refractive index (RI) in the range of 1.33 to 1.40 which covers extensively investigating analytes such as viruses, different cancer cells, glucose, proteins and DNA/RNA. Due to high sensing performance with multi-analyte detection capability, the proposed sensor can play a significant role to detect bio targets at the POC platform.

Engineering Polysaccharide-Based Hydrogel Photonic Constructs: From Multiscale Detection to the Biofabrication of Living Optical Fibers.

Solid-state optics has been the pillar of modern digital age. Integrating soft hydrogel materials with micro/nanooptics could expand the horizons of photonics for bioengineering. Here, wet-spun multilayer hydrogel fibers are engineered through ionic-crosslinked natural polysaccharides that serve as multifunctional platforms. The resulting flexible hydrogel structure and reversible crosslinking provide tunable design properties such as adjustable refractive index and fusion splicing. Modulation of the optical readout via physical stimuli, including shape, compression, and multiple optical inputs/outputs is demonstrated. The unique permeability of the hydrogels is also combined with plasmonic nanoparticles for molecular detection of SARS-CoV-2 in fiber-coupled biomedical swabs. A tricoaxial 3D printing nozzle is then employed for the continuous fabrication of living optical fibers. Light interaction with living cells enables the quantification and digitalization of complex biological phenomena such as 3D cancer progression and drug susceptibility. These fibers pave the way for advances in biomaterial-based photonics and biosensing platforms.

Wearable Collector for Noninvasive Sampling of SARS-CoV-2 from Exhaled Breath for Rapid Detection.

Airborne transmission of exhaled virus can rapidly spread, thereby increasing disease progression from local incidents to pandemics. Due to the COVID-19 pandemic, states and local governments have enforced the use of protective masks in public and work areas to minimize the disease spread. Here, we have leveraged the function of protective face coverings toward COVID-19 diagnosis. We developed a user-friendly, affordable, and wearable collector. This noninvasive platform is integrated into protective masks toward collecting airborne virus in the exhaled breath over the wearing period. A viral sample was sprayed into the collector to model airborne dispersion, and then the enriched pathogen was extracted from the collector for further analytical evaluation. To validate this design, qualitative colorimetric loop-mediated isothermal amplification, quantitative reverse transcription polymerase chain reaction, and antibody-based dot blot assays were performed to detect the presence of SARS-CoV-2. We envision that this platform will facilitate sampling of current SARS-CoV-2 and is potentially broadly applicable to other airborne diseases for future emerging pandemics.

Strain -multiplexing optical-tuning based on single-pulsed holographic nanostructures.

Holographic flexible and rigid nanostructures in the visible to near infrared range play vital roles in various applications, including displays, data storage, imaging, and security. However, personalized use of holography is limited due to the time-consuming, costly and complex nanofabrication procedures. Personalized holography can be improved/extended through rapid, efficient and low-cost techniques on rigid, flexible and edible materials. Here, we utilize a single-pulsed nanosecond (ns) laser ablation in Denisyuk reflection mode to record one/two-dimension (1/2D) nanostructures on various substrates, including rigid glass coated with soft polymers, gelatin, and conductive (gold) and non-conductive materials (ink) as holographic multilayer metastructures (HMMs). The tunability of optical properties was investigated by illuminating monochromatic and broadband light sources on flexible-template nanostructures. The surface morphologies of the nano-structures were changed by applying mechanical force, which in turn tuned the far-field optical response depending upon the amount of applied force, acting as an optical shape and force sensor. Nanostructures engineered on an edible material (gelatin) as well as on soft polymers (polymeric diffusers) were also demonstrated for suitable application in food industries and optoelectronics.

Engineering Hydrogel-Based Biomedical Photonics: Design, Fabrication, and Applications.

Light guiding and manipulation in photonics have become ubiquitous in events ranging from everyday communications to complex robotics and nanomedicine. The speed and sensitivity of light-matter interactions offer unprecedented advantages in biomedical optics, data transmission, photomedicine, and detection of multi-scale phenomena. Recently, hydrogels have emerged as a promising candidate for interfacing photonics and bioengineering by combining their light-guiding properties with live tissue compatibility in optical, chemical, physiological, and mechanical dimensions. Herein, the latest progress over hydrogel photonics and its applications in guidance and manipulation of light is reviewed. Physics of guiding light through hydrogels and living tissues, and existing technical challenges in translating these tools into biomedical settings are discussed. A comprehensive and thorough overview of materials, fabrication protocols, and design architectures used in hydrogel photonics is provided. Finally, recent examples of applying structures such as hydrogel optical fibers, living photonic constructs, and their use as light-driven hydrogel robots, photomedicine tools, and organ-on-a-chip models are described. By providing a critical and selective evaluation of the field's status, this work sets a foundation for the next generation of hydrogel photonic research.

Management of COVID-19: current status and future prospects.

COVID-19, a highly transmissible pandemic disease, is affecting millions of lives around the world. Severely infected patients show acute respiratory distress symptoms. Sustainable management strategies are required to save lives of the infected people and further preventing spread of the virus. Diagnosis, treatment, and vaccination development initiatives are already exhibited from the scientific community to fight against this virus. In this review, we primarily discuss the management strategies including prevention of spread, prophylaxis, vaccinations, and treatment for COVID-19. Further, analysis of vaccine development status and performance are also briefly discussed. Global socioeconomic impact of COVID-19 is also analyzed as part of this review.

Strain-Multiplex Metalens Array for Tunable Focusing and Imaging.

Metalenses on a flexible template are engineered metal-dielectric interfaces that improve conventional imaging system and offer dynamic focusing and zooming capabilities by controlling the focal length and bandwidth through a mechanical or external stretch. However, realizing large-scale and cost-effective flexible metalenses with high yields in a strain-multiplex fashion remains as a great challenge. Here, single-pulsed, maskless light interference and imprinting technique is utilized to fabricate reconfigurable, flexible metalenses on a large-scale and demonstrate its strain-multiplex tunable focusing. Experiments, in accordance with the theory, show that applied stretch on the flexible-template reconfigurable diffractive metalenses (FDMLs) accurately mapped focused wavefront, bandwidth, and focal length. The surface relief metastructures consisted of metal-coated hemispherical cavities in a hexagonal close-packed arrangement to enhance tunable focal length, numerical aperture, and fill factor, FF ≈ 100% through normal and angular light illumination with external stretch. The strain-multiplex of FDMLs approach lays the foundation of a new class of large-scale, cost-effective metalens offering tunable light focusing and imaging.

Diagnosis for COVID-19: current status and future prospects.

Introduction: Coronavirus disease 2019 (COVID-19), a respiratory illness caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had its first detection in December 2019 in Wuhan (China) and spread across the world. In March 2020, the World Health Organization (WHO) declared COVID-19 a pandemic disease. The utilization of prompt and accurate molecular diagnosis of SARS-CoV-2 virus, isolating the infected patients, and treating them are the keys to managing this unprecedented pandemic. International travel acted as a catalyst for the widespread transmission of the virus.Areas covered: This review discusses phenotype, structural, and molecular evolution of recognition elements and primers, its detection in the laboratory, and at point of care. Further, market analysis of commercial products and their performance are also evaluated, providing new ways to confront the ongoing global public health emergency.Expert commentary: The outbreak for COVID-19 created mammoth chaos in the healthcare sector, and still, day by day, new epicenters for the outbreak are being reported. Emphasis should be placed on developing more effective, rapid, and early diagnostic devices. The testing laboratories should invest more in clinically relevant multiplexed and scalable detection tools to fight against a pandemic like this where massive demand for testing exists.

Graphene based hyperbolic metamaterial for tunable mid-infrared biosensing.

Plasmonic biosensors, operating in the mid-infrared (mid-IR) region, are well-suited for highly specific and label-free optical biosensing. The principle of operation is based on detecting the shift in resonance wavelength caused by the interaction of biomolecules with the surrounding medium. However, metallic plasmonic biosensors suffer from poor signal transduction and high optical losses in the mid-IR range, leading to low sensitivity. Here, we introduce a hyperbolic metamaterial (HMM) biosensor, that exploits the strong, tunable, mid-IR localization of graphene plasmons, for detecting nanometric biomolecules with high sensitivity. The HMM stack consists of alternating graphene/Al2O3 multilayers, on top of a gold grating structure with rounded corners, to produce plasmonic hotspots and enhance sensing performance. Sensitivity and figure-of-merit (FOM) can be systematically tuned, by varying the structural parameters of the HMM stack and the doping levels (Fermi energy) in graphene. Finite-difference time-domain (FDTD) analysis demonstrates that the proposed biosensor can achieve sensitivities as high as 4052 nm RIU-1 (refractive index unit) with a FOM of 11.44 RIU-1. We anticipate that the reported graphene/Al2O3 HMM device will find potential application as a mid-IR, highly sensitive plasmonic biosensor, for tunable and label-free detection.

Engineering the Interaction Dynamics between Nano-Topographical Immunocyte-Templated Micromotors across Scales from Ions to Cells.

Manufacturing mobile artificial micromotors with structural design factors, such as morphology nanoroughness and surface chemistry, can improve the capture efficiency through enhancing contact interactions with their surrounding targets. Understanding the interplay of such parameters targeting high locomotion performance and high capture efficiency at the same time is of paramount importance, yet, has so far been overlooked. Here, an immunocyte-templated nano-topographical micromotor is engineered and their interactions with various targets across multiple scales, from ions to cells are investigated. The macrophage templated nanorough micromotor demonstrates significantly increased surface interactions and significantly improved and highly efficient removal of targets from complex aqueous solutions, including in plasma and diluted blood, when compared to smooth synthetic material templated micromotors with the same size and surface chemistry. These results suggest that the surface nanoroughness of the micromotors for the locomotion performance and interactions with the multiscale targets should be considered simultaneously, for they are highly interconnected in design considerations impacting applications across scales.

Medical Micro/Nanorobots in Precision Medicine.

Advances in medical robots promise to improve modern medicine and the quality of life. Miniaturization of these robotic platforms has led to numerous applications that leverages precision medicine. In this review, the current trends of medical micro and nanorobotics for therapy, surgery, diagnosis, and medical imaging are discussed. The use of micro and nanorobots in precision medicine still faces technical, regulatory, and market challenges for their widespread use in clinical settings. Nevertheless, recent translations from proof of concept to in vivo studies demonstrate their potential toward precision medicine.

Asymmetric core-guided polarization-dependent plasmonic biosensor.

A modified solid-core photonic crystal fiber (PCF)-based plasmonic sensor is proposed where light propagation through the PCF is controlled by scaling down of air holes. The modified core facilitates the easy excitation of the plasmonic surface, resulting in improved sensor performance. The chemically stable gold is externally coated on the PCF surface, which helps to establish surface plasmon resonance phenomena. The response of the sensor is analyzed based on the numerical method, and the design parameters are optimized to enhance the sensing performance. The asymmetric fiber-core structure provides the polarization controllability and significantly suppresses the y-polarized response to achieve a dominant x-polarized response and additional functionalities. The sensor exhibits a maximum wavelength sensitivity of 11,000 nm/RIU (refractive index unit) and sensing resolution of 9.09×10-6 RIU in the x-polarized mode. Also, the sensor exhibits maximum amplitude sensitivity of 631RIU-1, and a good figure of merit is 157RIU-1. Furthermore, the sensor can detect the unknown analytes' refractive index (RI) in the sensing analyte RI range of 1.33 to 1.40, which will lead to finding the potential applications in biomolecules, organic chemicals, and environment monitoring.

Mode-multiplex plasmonic sensor for multi-analyte detection.

Highly sensitive mode-multiplex miniaturized sensors enable the detection and quantification of multiple biomolecules simultaneously through their real-time interactions. Here, we demonstrate a grapefruit photonic crystal fiber (PCF)-based mode-multiplex surface plasmon resonance (SPR) sensor that detects multiple analytes simultaneously. Three grapefruit-shaped air-holes are internally coated with plasmonic gold (Au) material, which allows them to act as mode-multiplex channels that detect three unknown analytes. The sensor performance was investigated using the finite element method (FEM), and the optimized fiber structure was fabricated with the standard stack-and-draw method. For the y-polarized mode, channels one and three showed the maximum wavelength sensitivities of 2000 and 18,000 nm/RIU (refractive index unit) at the analyte refractive indices of 1.34 and 1.41, respectively. On the other hand, channel two showed the maximum wavelength sensitivity of 3000 nm/RIU at the analyte refractive index (RI) of 1.36 for the x-polarized mode. To the best of our knowledge, this is the first demonstration of a mode-multiplex grapefruit PCF-based SPR sensor to simultaneously detect and quantify three different analytes. We anticipate that the proposed sensor will find potential applications in the detection of real-time biomolecular interactions and binding affinity.

Tunable Fano-Resonant Metasurfaces on a Disposable Plastic-Template for Multimodal and Multiplex Biosensing.

Metasurfaces are engineered nanostructured interfaces that extend the photonic behavior of natural materials, and they spur many breakthroughs in multiple fields, including quantum optics, optoelectronics, and biosensing. Recent advances in metasurface nanofabrication enable precise manipulation of light-matter interactions at subwavelength scales. However, current fabrication methods are costly and time-consuming and have a small active area with low reproducibility due to limitations in lithography, where sensing nanosized rare biotargets requires a wide active surface area for efficient binding and detection. Here, a plastic-templated tunable metasurface with a large active area and periodic metal-dielectric layers to excite plasmonic Fano resonance transitions providing multimodal and multiplex sensing of small biotargets, such as proteins and viruses, is introduced. The tunable Fano resonance feature of the metasurface is enabled via chemical etching steps to manage nanoperiodicity of the plastic template decorated with plasmonic layers and surrounding dielectric medium. This metasurface integrated with microfluidics further enhances the light-matter interactions over a wide sensing area, extending data collection from 3D to 4D by tracking real-time biomolecular binding events. Overall, this work resolves cost- and complexity-related large-scale fabrication challenges and improves multilayer sensitivity of detection in biosensing applications.

Lateral and Vertical Flow Assays for Point-of-Care Diagnostics.

Lateral flow assays (LFAs) have been the pillar of rapid point-of-care (POC) diagnostics due to their simplicity, rapid process, and low cost. Recent advances in sensitivity, selectivity, and chemical stability enhancement have ensured the foothold of LFAs in commercial POC diagnostics. This paper reviews recent developments in labeling strategies and detection methods of LFAs. Moreover, vertical flow assays (VFAs) have emerged as an alternate paper-based assay due to faster detection time and unique multiplexing capabilities. Smartphones as LFA readers have been transformed into a universal integrated platform for imaging, data processing, and storage, providing quantitative results in low-resource settings. Commercial LFAs and VFAs products are evaluated with regards to their performance, market trends, and regulatory issues. The future outlook of the flow-based assays for POC diagnostics is also discussed.