Optical Readout Research Articles

Biosensing with Fluorescent Carbon Nanotubes

AbstractBiosensors are powerful tools for modern basic research and biomedical diagnostics. Their development requires substantial input from the chemical sciences. Sensors or probes with an optical readout, such as fluorescence, offer rapid, minimally invasive sensing of analytes with high spatial and temporal resolution. The near‐infrared (NIR) region is beneficial because of the reduced background and scattering of biological samples (tissue transparency window) in this range. In this context, single‐walled carbon nanotubes (SWCNTs) have emerged as versatile NIR fluorescent building blocks for biosensors. Here, we provide an overview of advances in SWCNT‐based NIR fluorescent molecular sensors. We focus on chemical design strategies for diverse analytes and summarize insights into the photophysics and molecular recognition. Furthermore, different application areas are discussed—from chemical imaging of cellular systems and diagnostics to in vivo applications and perspectives for the future.

A monolithically sculpted van der Waals nano-opto-electro-mechanical coupler

The nano-opto-electro-mechanical systems (NOEMS) are a class of hybrid solid devices that hold promises in both classical and quantum manipulations of the interplay between one or more degrees of freedom in optical, electrical and mechanical modes. To date, studies of NOEMS using van der Waals (vdW) heterostructures are very limited, although vdW materials are known for emerging phenomena such as spin, valley, and topological physics. Here, we devise a universal method to easily and robustly fabricate vdW heterostructures into an architecture that hosts opto-electro-mechanical couplings in one single device. We demonstrated several functionalities, including nano-mechanical resonator, vacuum channel diodes, and ultrafast thermo-radiator, using monolithically sculpted graphene NOEMS as a platform. Optical readout of electric and magnetic field tuning of mechanical resonance in a CrOCl/graphene vdW NOEMS is further demonstrated. Our results suggest that the introduction of the vdW heterostructure into the NOEMS family will be of particular potential for the development of novel lab-on-a-chip systems.

Inverse-designed waveguide-based biosensor for high-sensitivity, single-frequency detection of biomolecules

Abstract Integrated silicon photonic waveguide biosensors have shown great potential for detecting bio-molecules because they enable efficient device functionalization via a well-developed surface chemistry, as well as simple scalable manufacturing, which makes them particularly suitable for low-cost point-of-care diagnostic. The on-chip integrated biosensors can be broadly classified into two types: (i) high-quality factor resonator sensors and (ii) interferometric sensors relying on non-resonant optical elements such as e.g. integrated waveguides. The former type usually requires a broadband or a tunable light source as well as complicated signal post-processing to measure a shift of the resonance frequency, while the latter exhibits a relatively low sensitivity due to the lack of efficient light recycling and phase accumulation mechanism in low quality factor elements. Additionally, high quality factor resonant photonic structures can be very sensitive to the presence of other non-target molecules in the water solution, causing sensor vulnerability to any noise. In this work, we combine a computational “inverse design” technique and a recently introduced high-contrast probe cleavage detection (HCCD) technique to design and optimize waveguide-based biosensors that demonstrate high sensitivity to the target molecule while being less sensitive to noise. The proposed biosensors only require a single frequency (or narrow-band) source and an intensity detector, which greatly simplifies the detection system, making it suitable for point-of-care applications. The optimal integrated sensor design that we demonstrate shows 98.3% transmission for the positive (target detected, probes cleaved) state and 4.9% transmission for the negative (probes are still attached) state at 1550 nm wavelength. The signal intensity contrast (20.06-fold transmission increase) shown in this work is much greater than the shift of the resonance frequency (less than 1% wavelength shift) observed in conventional ring-resonator-based biosensors. The new design may pave the way for realizing a single-frequency highly sensitive and selective optical biosensor system with a small physical footprint and a simple optical readout on a silicon chip.

Creation of nitrogen-vacancy centers in chemical vapor deposition diamond for sensing applications

The nitrogen-vacancy (NV) center in diamond is a promising quantum system for magnetometry applications exhibiting optical readout of minute energy shifts in its spin sub-levels. Key material requirements for NV ensembles are a high NV− concentration, a long spin coherence time and a stable charge state. However, these are interdependent and can be difficult to optimize during diamond growth and subsequent NV creation. In this work, we systematically investigate the NV center formation and properties in bulk chemical vapor deposition (CVD) diamond. The nitrogen flow during growth is varied by over four orders of magnitude, resulting in a broad range of single substitutional nitrogen concentrations of 0.2–20 parts per million. For a fixed nitrogen concentration, we optimize electron-irradiation fluences with two different accelerated electron energies, and we study defect formation via optical characterizations. We discuss a general approach to determine the optimal irradiation conditions, for which an enhanced NV concentration and an optimum of NV charge states can both be satisfied. We achieve spin–spin coherence times T 2 ranging from 45.5 to 549 μs for CVD diamonds containing 168 to 1 parts per billion NV− centers, respectively. This study shows a pathway to engineer properties of NV-doped CVD diamonds for improved sensitivity.

Nanofabricating neural networks: Strategies, advances, and challenges

Nanofabrication can help us to emulate natural intelligence. Forward-engineering brain gained enormous momentum but still falls short in human neurodegenerative disease modeling. Here, organ-on-chip (OoC) implementation of tissue culture concepts in microfluidic formats already progressed with the identification of our knowledge gap in toxicology and drug metabolism studies. We believe that the self-organization of stem cells and chip technology is a key to advance such complex in vitro tissue models, including models of the human nervous system as envisaged in this review. However, current cultured networks of neurons show limited resemblance with the biological functions in the real nervous system or brain tissues. To take full advantage of scaling in the engineering domain of electron-, ion-, and photon beam technology and nanofabrication methods, more research is needed to meet the requirements of this specific field of chip technology applications. So far, surface topographies, microfluidics, and sensor and actuator integration concepts have all contributed to the patterning and control of neural network formation processes in vitro. However, when probing the state of the art for this type of miniaturized three-dimensional tissue models in PubMed, it was realized that there is very little systematic cross-disciplinary research with biomaterials originally formed for tissue engineering purposes translated to on-chip solutions for in vitro modeling. Therefore, this review contributes to the formulation of a sound design concept based on the understanding of the existing knowledge and the technical challenges toward finding better treatments and potential cures for devastating neurodegenerative diseases, like Parkinson's disease. Subsequently, an integration strategy based on a modular approach is proposed for nervous system-on-chip (NoC) models that can yield efficient and informative optical and electronic NoC readouts in validating and optimizing these conceptual choices in the innovative process of a fast growing and exciting new OoC industry.

Single Cell Imaging of Electrochemiluminescence‐Driven Photodynamic Therapy

AbstractWe report a photodynamic therapy driven by electrochemiluminescence (ECL). The luminescence generated by Ru(bpy)32+ and co‐reactant tripropylamine (TPA) pair acts as both optical readout for ECL imaging, and light source for the excitation of photosensitizer to produce reactive oxygen species (ROS) in photodynamic therapy (PDT) system. The ECL‐driven PDT (ECL‐PDT) relies on the effective energy transfer from ECL emission to photosensitizer chlorin e6 (Ce6), which sensitizes the surrounding O2 into ROS. The dynamic process of gradual morphological changes, the variation of cell‐matrix adhesions, as well as the increase of cell membrane permeability in the process of ECL‐PDT were monitored under ECL microscopy (ECLM) with good spatiotemporal resolution. Combining real‐time imaging with ECL‐PDT, this new strategy provides not only new insights into dynamic cellular processes, but also promising potential of ECL in clinical applications.

Single Cell Imaging of Electrochemiluminescence‐Driven Photodynamic Therapy

We report a photodynamic therapy driven by electrochemiluminescence (ECL). The luminescence generated by Ru(bpy)32+ and co-reactant tripropylamine (TPA) pair acts as both optical readout for ECL imaging, and light source for the excitation of photosensitizer to produce reactive oxygen species (ROS) in photodynamic therapy (PDT) system. The ECL-driven PDT (ECL-PDT) relies on the effective energy transfer from ECL emission to photosensitizer chlorin e6 (Ce6), which sensitizes the surrounding O2 into ROS. The dynamic process of gradual morphological changes, the variation of cell-matrix adhesions, as well as the increase of cell membrane permeability in the process of ECL-PDT were monitored under ECL microscopy (ECLM) with good spatiotemporal resolution. Combining real-time imaging with ECL-PDT, this new strategy provides not only new insights into dynamic cellular processes, but also promising potential of ECL in clinical applications.

Trends in Nanophotonics‐Enabled Optofluidic Biosensors

AbstractOptofluidic sensors integrate photonics with micro/nanofluidics to realize compact devices for the label‐free detection of molecules and the real‐time monitoring of dynamic surface binding events with high specificity, ultrahigh sensitivity, low detection limit, and multiplexing capability. Nanophotonic structures composed of metallic and/or dielectric building blocks excel at focusing light into ultrasmall volumes, creating enhanced electromagnetic near‐fields ideal for amplifying the molecular signal readout. Furthermore, fluidic control on small length scales enables precise tailoring of the spatial overlap between the electromagnetic hotspots and the analytes, boosting light‐matter interaction, and can be utilized to integrate advanced functionalities for the pre‐treatment of samples in real‐world‐use cases, such as purification, separation, or dilution. In this review, the authors highlight current trends in nanophotonics‐enabled optofluidic biosensors for applications in the life sciences while providing a detailed perspective on how these approaches can synergistically amplify the optical signal readout and achieve real‐time dynamic monitoring, which is crucial in biomedical assays and clinical diagnostics.

Self‐Propelled Multifunctional Microrobots Harboring Chiral Supramolecular Selectors for “Enantiorecogniton‐on‐the‐Fly”

AbstractHerein, a general procedure for the synthesis of multifunctional MRs, which simultaneously exhibit i) chiral, ii) magnetic, and iii) fluorescent properties in combination with iv) self‐propulsion, is reported. Self‐propelled Ni@Pt superparamagnetic microrockets have been functionalized with fluorescent CdS quantum dots carrying a chiral host biomolecule as β‐cyclodextrin (β‐CD). The “on‐the‐fly” chiral recognition potential of MRs has been interrogated by taking advantage of the β‐CD affinity to supramolecularly accommodate different chiral biomolecules (i.e., amino acids). As a proof‐of‐concept, tryptophan enantiomers have been discriminated with a dual‐mode (optical and electrochemical) readout. This approach paves the way to devise intelligent cargo micromachines with “built‐in” chiral supramolecular recognition capabilities to elucidate the concept of “enantiorecognition‐on‐the‐fly”, which might be facilely customized by tailoring the supramolecular host–guest encapsulation.

Self-Propelled Multifunctional Microrobots Harboring Chiral Supramolecular Selectors for "Enantiorecognition-on-the-Fly".

Herein, a general procedure for the synthesis of multifunctional MRs, which simultaneously exhibit i) chiral, ii) magnetic, and iii) fluorescent properties in combination with iv) self‐propulsion, is reported. Self‐propelled Ni@Pt superparamagnetic microrockets have been functionalized with fluorescent CdS quantum dots carrying a chiral host biomolecule as β‐cyclodextrin (β‐CD). The “on‐the‐fly” chiral recognition potential of MRs has been interrogated by taking advantage of the β‐CD affinity to supramolecularly accommodate different chiral biomolecules (i.e., amino acids). As a proof‐of‐concept, tryptophan enantiomers have been discriminated with a dual‐mode (optical and electrochemical) readout. This approach paves the way to devise intelligent cargo micromachines with “built‐in” chiral supramolecular recognition capabilities to elucidate the concept of “enantiorecognition‐on‐the‐fly”, which might be facilely customized by tailoring the supramolecular host–guest encapsulation.

Magnetic bead mixing in a microfluidic chamber induced by an in-plane rotating magnetic field

Magnetic microbeads have been widely used for the capturing of biomarkers, as well as for microfluidic mixing for point-of-care diagnostics. In magnetic micromixing, microbead motion is generated by external electromagnets, inducing fluid kinetics, and consequently mixing. Here, we utilize an in-plane rotating magnetic field to induce magnetic bead mixing in a circular microfluidic chamber that allows better access with (optical) readout than for existing micromixing approaches. We analyze the magnetic bead dynamics, the induced fluid profiles and we quantify the mixing performance of the system. The rotating field causes the combination of (1) a global rotating flow counter to the external field rotation induced by magnetic particles moving along the chamber side wall, with (2) local flow perturbations induced by rotating magnetic bead clusters in the central area of the chamber, rotating in the same direction as the external field. This combination leads to efficient mixing performance within 2 min of actuated magnetic field. We integrate magnetic mushroom-shaped features around the circumference of the chamber to generate significantly higher global fluid velocities compared with the no-mushroom configuration, but this results in less efficient mixing due to the absence of the central rotating bead clusters. To validate and understand the experimental results and to predict further enhancement of mixing, we carry out numerical simulations of induced fluid profiles and their corresponding mixing indices, and we explore the additional effect of integrating geometrical structures. The micromixing method we introduce here is particularly suitable for microfluidic devices in which the biochemical assay happens in a microfluidic chamber under no-flow conditions, i.e., with initially stagnant fluids, and for which the time-to-result is critical, such as in point-of-care diagnostics.

Optical Nanopore Sensors for Quantitative Analysis.

Nanopore sensors have received significant interest for the detection of clinically important biomarkers with single-molecule resolution. These sensors typically operate by detecting changes in the ionic current through a nanopore due to the translocation of an analyte. Recently, there has been interest in developing optical readout strategies for nanopore sensors for quantitative analysis. This is because they can utilize wide-field microscopy to independently monitor many nanopores within a high-density array. This significantly increases the amount of statistics that can be obtained, thus enabling the analysis of analytes present at ultralow concentrations. Here, we review the use of optical nanopore sensing strategies for quantitative analysis. We discuss optical nanopore sensing assays that have been developed to detect clinically relevant biomarkers, the potential for multiplexing such measurements, and techniques to fabricate high density arrays of nanopores with a view toward the use of these devices for clinical applications.

The CYGNO Experiment

The search for a novel technology able to detect and reconstruct nuclear and electron recoil events with the energy of a few keV has become more and more important now that large regions of high-mass dark matter (DM) candidates have been excluded. Moreover, a detector sensitive to incoming particle direction will be crucial in the case of DM discovery to open the possibility of studying its properties. Gaseous time projection chambers (TPC) with optical readout are very promising detectors combining the detailed event information provided by the TPC technique with the high sensitivity and granularity of latest-generation scientific light sensors. The CYGNO experiment (a CYGNus module with Optical readout) aims to exploit the optical readout approach of multiple-GEM structures in large volume TPCs for the study of rare events as interactions of low-mass DM or solar neutrinos. The combined use of high-granularity sCMOS cameras and fast light sensors allows the reconstruction of the 3D direction of the tracks, offering good energy resolution and very high sensitivity in the few keV energy range, together with a very good particle identification useful for distinguishing nuclear recoils from electronic recoils. This experiment is part of the CYGNUS proto-collaboration, which aims at constructing a network of underground observatories for directional DM search. A one cubic meter demonstrator is expected to be built in 2022/23 aiming at a larger scale apparatus (30 m3–100 m3) at a later stage.

Multi-mode readout via opto-mechano-photothermo-responsive luminescence from electron trapping material for optical information storage application

Optical storage material is one of the promising candidates for next generation of information memory medium owing to large capacity, reusable rewritable, and rapid response performance. However, as the typical optical storage medium, electron trapping materials (ETMs) are limited in applications of information preservation or optical display technology due to their single readout route relying on photostimulated luminescence (PSL). A crucial limitation to the feasibility of multi-mode optical information readout is the inevitable mismatch between trap depth and the energy of external stimuli. In this study, by introducing Bi3+ ions as intermediate levels between deep traps and emitters, we developed a LiTaO3:Tb3+/Bi3+ (LTO) material that can simultaneously response to optical, mechanical, and thermal stimuli efficiently, showing as multiple trap-controlling luminescence. The tantalate material was endowed with opto-mechano-responsive readout capacity when assembled with polymer matrix. Moreover, by utilizing LiCaYb0.5Nd0.5(WO4)3 microcrystals (LCYW) with near-infrared-induced photothermy property, we designed a LTO-LCYW bilayer composite film then achieved non-contact thermo-responsive readout of optical information via photothermo-stimulated luminescence. These findings provide a unique perspective for designing multi-mode responsive luminophors and photonic devices towards widespread applications, especially optical display, optical memory technology, and anticounterfeiting.

Paper-based electrochromic glucose sensor with polyaniline on indium tin oxide nanoparticle layer as the optical readout

Surging interests in point-of-care diagnostics have led to the development of many lightweight and cost-effective paper-based sensors. Particularly, sensors using colorimetric readouts are considered highly advantageous because no additional detector or device is required for signal display. Herein, we introduce an electrochemically operated colorimetric sensor that can compensate for the disadvantages of traditional colorimetry, hence enhancing response time, reusability and color uniformity. On a single paper substrate, carbon/graphite paste was screen printed to form the working and counter electrodes, and Ag/AgCl ink was applied for the reference electrode. Prussian blue and Glucose oxidase were employed on the one of the carbon electrodes for the detection of analytes, hydrogen peroxide and glucose. For the colorimetric readout, indium tin oxide nanoparticles and polyaniline were consecutively introduced on the other carbon electrode, which is used as the counter electrode. The color change of electrochromic polyaniline could be clearly observed, and its application as a colorimetric sensor was demonstrated by the quantitative analyses of hydrogen peroxide and glucose. This paper-based electrochromic glucose sensor showed a short response time of 30 s and exhibited a detection limit of 126 μM for glucose. Along with its rapid and easy detection by incorporating the merits of electrochemical sensing and colorimetry, the paper-based electrochromic sensor could potentially contribute to the development of point-of-care devices by combination with portable power sources.

Quantum emitters in 2D materials: Emitter engineering, photophysics, and integration in photonic nanostructures

Quantum emitters have become a vital tool for both fundamental science and emerging technologies. In recent years, the focus in the field has shifted to exploration and identification of new quantum systems enabled by the emerging library of atomically thin, two dimensional materials. In this review, we highlight the current state of the art in engineering of quantum emitters in 2D systems, with an emphasis on transition metal di-chalcogenides (TMDCs) and hexagonal boron nitride. We start by reviewing progress in TMDCs, with focus on emitter engineering, ability to tune their spectral properties, and observation of interlayer excitons. We then discuss emitters in hBN and focus on emitters' origin, engineering, and emerging phenomena—spanning super-resolution imaging and optical spin readout. We summarize by discussing practical advances of integration of emitters in 2D hosts with plasmonic and dielectric photonic cavities, underpinned by quantum light–matter interactions. We conclude by outlining pathways for practical on-chip quantum photonics applications and highlight challenges and opportunities within this field of research.

Engineering a Fluorescent Protein Color Switch Using Entropy-Driven β-Strand Exchange.

Protein conformational switches are widely used in biosensing. They are often composed of an input domain (which binds a target ligand) fused to an output domain (which generates an optical readout). A central challenge in designing such switches is to develop mechanisms for coupling the input and output signals via conformational changes. Here, we create a biosensor in which binding-induced folding of the input domain drives a conformational shift in the output domain that results in a sixfold green-to-yellow ratiometric fluorescence change in vitro and a 35-fold intensiometric fluorescence increase in cultured cells. The input domain consists of circularly permuted FK506 binding protein (cpFKBP) that folds upon binding its target ligand (FK506 or rapamycin). cpFKBP folding induces the output domain, an engineered green fluorescent protein (GFP) variant, to replace one of its β-strands (containing T203 and specifying green fluorescence) with a duplicate β-strand (containing Y203 and specifying yellow fluorescence) in an intramolecular exchange reaction. This mechanism employs the loop-closure entropy principle, embodied by the folding of the partially disordered cpFKBP domain, to couple ligand binding to the GFP color shift. This study highlights the high-energy barriers present in GFP folding which cause β-strand exchange to be slow and are also likely responsible for the shift from the β-strand exchange mechanism in vitro to ligand-induced chromophore maturation in cells. The proof-of-concept design has the advantages of full genetic encodability and potential for modularity. The latter attribute is enabled by the natural coupling of binding and folding and circular permutation of the input domain, which theoretically allows different binding domains to be compatible for insertion into the GFP surface loop.

Spectrophotometric comparison of 4-Nitrophenyl carbonates & carbamates as base-labile protecting groups

In organic synthesis, protecting groups are derivatives of reactive functionalities that play a key role in ensuring chemoselectivity of chemical transformations. To protect alcohols and amines, acid-labile tert-butyloxycarbonyl protecting groups are often employed but are avoided when the substrate is acid-sensitive. Thus, orthogonal base-labile protecting groups have been in demand to enable selective deprotection and to preserve the reactivity of acid-sensitive substrates. To meet this demand, we present 4-nitrophenyl carbonates and carbamates as orthogonal base-labile protecting group strategies. These protecting groups are relatively stable in aqueous and acidic solution yet cleaved and irreversibly decarboxylated in mild basic conditions. We showed that deprotection can be monitored spectroscopically, as hydrolysis yields 4-nitrophenol, a bright yellow compound with an optical readout at 413 nm. Finally, we demonstrated that the use of 4-nitrophenol as an effective leaving group allows for deprotection to be carried out in mild conditions. We protected benzyl alcohol and benzylamine via acylation by 4-nitrophenyl chloroformate, yielding substrates that were subsequently subjected to hydrolysis in various pH conditions. The release of 4-nitrophenol was monitored spectroscopically and the reaction kinetics were derived from absorbance data, yielding that hydrolysis was accelerated only in basic conditions and was most effective in pH 12 and above. These results inform the feasibility of our protecting group in organic synthesis and open avenues toward new synthetic routes by broadening the spectrum of effective protecting group strategies.

Taft linear free-energy relationships in the biocatalytic hydrolysis of sterically hindered nitrophenyl ester substrates

Linear free-energy relationships (LFERs) have been commonly used to uncover reaction mechanisms in organic chemistry by correlating trends in reactivity to reactant properties. However, the applications of LFERs have largely been limited to traditional organic synthesis and have much less frequently been applied toward enzyme-catalyzed reactions. In this study, we used the Taft LFER, which correlates reaction rates with steric properties of reactants, to study kinetic trends in the enzymatic hydrolysis of sterically hindered substrates. We synthesized 4-nitrophenyl ester compounds with substituents of varying degrees of steric hindrance, and then subjected these compounds to hydrolysis by the enzymes lipase, trypsin, and nattokinase. Kinetic data was obtained by using a spectrophotometer to monitor the formation of 4-nitrophenol, a bright yellow product of the ester hydrolysis with an optical readout at 413 nm. Contrary to initial hypotheses, Taft plots did not exhibit linear relationships and further analysis yielded mechanistic insight into the nature of the Taft steric parameter, the relative sensitivity of each enzyme to steric effects, and potential enzyme-substrate binding interactions. This analysis was paralleled with computational calculations to determine local charge density of the reaction center, which supported that the unexpected trends were largely a function of the aforementioned factors rather than electronic effects. Ultimately, we demonstrate the unconventional application of the Taft LFER toward biocatalytic transformations and open avenues toward the broader use of biocatalysts in synthetic organic chemistry.

Optical fiber hydrogen sensor using metasurfaces composed of palladium

Palladium-based hydrogen sensors have been typically studied due to the dielectric function that changes with the hydrogen concentration. However, the development of a reliable, integral, and widely applicable hydrogen sensor requires a simple readout mechanism and an optimization of the fast detection of hydrogen. In this work, optical fiber hydrogen sensing platforms are developed using an optimized metasurface, which consists of a layer of palladium nanoantennas array suspended above a gold mirror layer. Since the optical properties of these palladium nanoantennas differ from the traditional palladium films, a high reflectance difference can be achieved when the sensor based on the metasurface is exposed to the hydrogen atmosphere. Finally, the optimized reflectance difference ΔR of ∼0.28 can be obtained when the sensor is exposed in the presence of hydrogen. It is demonstrated that this integrated system architecture with an optimized palladium-based metasurface and a simple optical fiber readout system provides a compact and light platform for hydrogen detection in various working environments.