Modular Aptamer Switches for the Continuous Optical Detection of Small-Molecule Analytes in Complex Media.

Aptamers are a promising class of affinity reagents because signal transduction mechanisms can be built into the reagent, so that they can directly produce a physically measurable output signal upon target binding. However, endowing the signal transduction functionality into an aptamer remains a trial-and-error process that can compromise its affinity or specificity and typically requires knowledge of the ligand binding domain or its structure. In this work, a design architecture that can convert an existing aptamer into a "reversible aptamer switch" whose kinetic and thermodynamic properties can be tuned without a priori knowledge of the ligand binding domain or its structure is described. Finally, by combining these aptamer switches with evanescent-field-based optical detection hardware that minimizes sample autofluorescence, this study demonstrates the first optical biosensor system that can continuously measure multiple biomarkers (dopamine and cortisol) in complex samples (artificial cerebrospinal fluid and undiluted plasma) with second and subsecond-scale time responses at physiologically relevant concentration ranges.

Quantum Photonic Circuits Integrated with Color Centers in Designer Nanodiamonds.

Diamond has emerged as a leading host material for solid-state quantum emitters, quantum memories, and quantum sensors. However, the challenges in fabricating photonic devices in diamond have limited its potential for use in quantum technologies. While various hybrid integration approaches have been developed for coupling diamond color centers with photonic devices defined in a heterogeneous material, these methods suffer from either large insertion loss at the material interface or evanescent light-matter coupling. Here, we present a new technique that enables the deterministic assembly of diamond color centers in a silicon nitride photonic circuit. Using this technique, we observe Purcell enhancement of silicon vacancy centers coupled to a silicon nitride ring resonator. Our hybrid integration approach has the potential for achieving the maximum possible light-matter interaction strength while maintaining low insertion loss and paves the way toward scalable manufacturing of large-scale quantum photonic circuits integrated with high-quality quantum emitters and spins.

An antibody-based molecular switch for continuous small-molecule biosensing.

We present a generalizable approach for designing biosensors that can continuously detect small-molecule biomarkers in real time and without sample preparation. This is achieved by converting existing antibodies into target-responsive "antibody-switches" that enable continuous optical biosensing. To engineer these switches, antibodies are linked to a molecular competitor through a DNA scaffold, such that competitive target binding induces scaffold switching and fluorescent signaling of changing target concentrations. As a demonstration, we designed antibody-switches that achieve rapid, sample preparation-free sensing of digoxigenin and cortisol in undiluted plasma. We showed that, by substituting the molecular competitor, we can further modulate the sensitivity of our cortisol switch to achieve detection at concentrations spanning 3.3 nanomolar to 3.3 millimolar. Last, we integrated this switch with a fiber optic sensor to achieve continuous sensing of cortisol in a buffer and blood with <5-min time resolution. We believe that this modular sensor design can enable continuous biosensor development for many biomarkers.

An Inverse-Designed Nanophotonic Interface for Excitons in Atomically Thin Materials.

Efficient nanophotonic devices are essential for applications in quantum networking, optical information processing, sensing, and nonlinear optics. Extensive research efforts have focused on integrating two-dimensional (2D) materials into photonic structures, but this integration is often limited by size and material quality. Here, we use hexagonal boron nitride (hBN), a benchmark choice for encapsulating atomically thin materials, as a waveguiding layer while simultaneously improving the optical quality of the embedded films. When combined with a photonic inverse design, it becomes a complete nanophotonic platform to interface with optically active 2D materials. Grating couplers and low-loss waveguides provide optical interfacing and routing, tunable cavities provide a large exciton-photon coupling to transition metal dichalcogenide (TMD) monolayers through Purcell enhancement, and metasurfaces enable the efficient detection of TMD dark excitons. This work paves the way for advanced 2D-material nanophotonic structures for classical and quantum nonlinear optics.

Inverse-designed silicon carbide quantum and nonlinear photonics.

Inverse design has revolutionized the field of photonics, enabling automated development of complex structures and geometries with unique functionalities unmatched by classical design. However, the use of inverse design in nonlinear photonics has been limited. In this work, we demonstrate quantum and classical nonlinear light generation in silicon carbide nanophotonic inverse-designed Fabry-Pérot cavities. We achieve ultra-low reflector losses while targeting a pre-specified anomalous dispersion to reach optical parametric oscillation. By controlling dispersion through inverse design, we target a second-order phase-matching condition to realize second- and third-order nonlinear light generation in our devices, thereby extending stimulated parametric processes into the visible spectrum. This first realization of computational optimization for nonlinear light generation highlights the power of inverse design for nonlinear optics, in particular when combined with highly nonlinear materials such as silicon carbide.

Prognostic Value of Redox Status Biomarkers in Patients Presenting with STEMI or Non-STEMI: A Prospective Case-Control Clinical Study.

(1) Background: The aim of our study was to determine the role of oxidative stress (OS) during early evaluation of acute ST-elevated myocardial infarction (STEMI) and non-ST-elevated myocardial infarction (NSTEMI) patients in order to define the role of redox balance in profiling the development of myocardial infarction (MI). (2) Methods: This prospective observational case-control study included 40 consecutive STEMI and 39 NSTEMI patients hospitalized in the coronary care unit of the cardiology clinic at the Kragujevac Clinical Center, Serbia, between 1 January 2016 and 1 January 2017. Blood samples were collected from all patients for measuring cardio-specific enzymes at admission and 12 h after admission to evaluate systemic oxidative stress biomarkers and the activity of antioxidant enzymes. (3) Results: In this study, participants were predominately female (52%), with a mean age of 56.17 ± 1.22 years old in the STEMI group and 69.17 ± 3.65 in the non-STEMI group. According to the Killip classification, the majority of patients (>50%) were at the second and third level. We confirmed the elevation of superoxide anion radicals in the non-STEMI group 6 h after admission in comparison with the STEMI and CTRL groups, but levels had decreased 12 h after admission. Levels of hydrogen peroxide were statistically significantly increased in the NSTEMI group. A positive correlation of superoxide anion radicals and levels of troponin I at admission was observed (r = 0.955; p = 0.045), as well as an inverse correlation between reduced glutathione and levels of NT-pBNP measured 6 h after admission (r = -0.973; p = 0.027). (4) Conclusions: We confirmed that superoxide anion radicals and reduced glutathione observed together with hs-troponin I at admission and NT-pBNP during hospital treatment could be predictors of ST evolution.

DYMUS-Hr self-assessment questionnaire (Croatian version) for dysphagia in multiple sclerosis-validity, reliability, and cross-cultural adaptation.

BACKGROUND: The prevalence of dysphagia in the early phases of multiple sclerosis is 30-40%, with an estimated of 30% of cases going undiagnosed cases. Such complications can lead to malnutrition, dehydration, and aspiration pneumonia and have a great impact on the quality of life and psychosocial status of a person with MS. The aim of this study was the validation of dysphagia in multiple sclerosis self-assessment questionnaire (DYMUS) in the Croatian language. METHODS AND PATIENTS: The cross-cultural adaptation process included a back-forward translation technique of the English language version of DYMUS to the Croatian language, with pilot testing on 30 participants. The validity and reliability of the Croatian version of DYMUS (DYMUS-Hr) was applied to 106 MS patients, with comparison to the Eating Assessment Tool (EAT10), the Water Swallowing Test (WST), and a dichotomous self-assessment question. In the assessment of test-retest reliability, 99 MS patients were included. RESULTS: Internal consistency of DYMUS-Hr was very good (Cronbach's alpha-0.837); Cronbach's alpha was 0.819 for the "dysphagia for solids", and 0.562 for "dysphagia for liquids" subscale. A significant correlation (p < 0.001) was found between DYMUS-Hr and EAT10 (Spearman's rho-0.787), and WST (Spearman's rho-0.483). Construct validity was assessed with the self-assessment question and interpreted with the Mann-Whitney U test. Test-retest reliability showed moderate to substantial Cohen's Kappa reliability for each item. CONCLUSION: DYMUS-Hr is a valid and reliable screening assessment tool for patients with MS. There is a general lack of awareness about dysphagia symptoms among patients with MS; consequently, this disorder receives inadequate attention and often goes untreated.

Multi-dimensional data transmission using inverse-designed silicon photonics and microcombs.

The use of optical interconnects has burgeoned as a promising technology that can address the limits of data transfer for future high-performance silicon chips. Recent pushes to enhance optical communication have focused on developing wavelength-division multiplexing technology, and new dimensions of data transfer will be paramount to fulfill the ever-growing need for speed. Here we demonstrate an integrated multi-dimensional communication scheme that combines wavelength- and mode- multiplexing on a silicon photonic circuit. Using foundry-compatible photonic inverse design and spectrally flattened microcombs, we demonstrate a 1.12-Tb/s natively error-free data transmission throughout a silicon nanophotonic waveguide. Furthermore, we implement inverse-designed surface-normal couplers to enable multimode optical transmission between separate silicon chips throughout a multimode-matched fibre. All the inverse-designed devices comply with the process design rules for standard silicon photonic foundries. Our approach is inherently scalable to a multiplicative enhancement over the state of the art silicon photonic transmitters.

Creating boundaries along a synthetic frequency dimension.

Synthetic dimensions have garnered widespread interest for implementing high dimensional classical and quantum dynamics on low-dimensional geometries. Synthetic frequency dimensions, in particular, have been used to experimentally realize a plethora of bulk physics effects. However, in synthetic frequency dimension there has not been a demonstration of a boundary which is of paramount importance in topological physics due to the bulk-edge correspondence. Here we construct boundaries in the frequency dimension of dynamically modulated ring resonators by strongly coupling an auxiliary ring. We explore various effects associated with such boundaries, including confinement of the spectrum of light, discretization of the band structure, and the interaction of boundaries with one-way chiral modes in a quantum Hall ladder, which exhibits topologically robust spectral transport. Our demonstration of sharp boundaries fundamentally expands the capability of exploring topological physics, and has applications in classical and quantum information processing in synthetic frequency dimensions.

Convex restrictions in physical design.

In a physical design problem, the designer chooses values of some physical parameters, within limits, to optimize the resulting field. We focus on the specific case in which each physical design parameter is the ratio of two field variables. This form occurs for photonic design with real scalar fields, diffusion-type systems, and others. We show that such problems can be reduced to a convex optimization problem, and therefore efficiently solved globally, given the sign of an optimal field at every point. This observation suggests a heuristic, in which the signs of the field are iteratively updated. This heuristic appears to have good practical performance on diffusion-type problems (including thermal design and resistive circuit design) and some control problems, while exhibiting moderate performance on photonic design problems. We also show in many practical cases there exist globally optimal designs whose design parameters are maximized or minimized at each point in the domain, i.e., that there is a discrete globally optimal structure.

Generating arbitrary topological windings of a non-Hermitian band.

The nontrivial topological features in the energy band of non-Hermitian systems provide promising pathways to achieve robust physical behaviors in classical or quantum open systems. A key topological feature of non-Hermitian systems is the nontrivial winding of the energy band in the complex energy plane. We provide experimental demonstrations of such nontrivial winding by implementing non-Hermitian lattice Hamiltonians along a frequency synthetic dimension formed in a ring resonator undergoing simultaneous phase and amplitude modulations, and by directly characterizing the complex band structures. Moreover, we show that the topological winding can be controlled by changing the modulation waveform. Our results allow for the synthesis and characterization of topologically nontrivial phases in nonconservative systems.

Site-Controlled Quantum Emitters in Monolayer MoSe2.

Atomically thin semiconductors provide a highly attractive platform for quantum emitters (QEs): They can be combined with arbitrary substrates, can be spatially aligned with photonic structures, and can be electrically driven. All QEs reported to date in these materials have, however, relied on nominally spin-forbidden transitions, with radiative rates falling substantially below those of other solid-state QE systems. Here we employ strain confinement in monolayer MoSe2 to produce engineered QEs, as confirmed in photon antibunching measurements. We discuss spin-allowed versus spin-forbidden transitions based on magneto- and time-resolved photoluminescence measurements. We calculate a radiative rate for spin-allowed quantum emission greater than 1 ns-1, which exceeds reported radiative rates of WSe2 QEs by 2 orders of magnitude.

Heuristic methods and performance bounds for photonic design.

In the photonic design problem, a scientist or engineer chooses the physical parameters of a device to best match some desired device behavior. Many instances of the photonic design problem can be naturally stated as a mathematical optimization problem that is computationally difficult to solve globally. Because of this, several heuristic methods have been developed to approximately solve such problems. These methods often produce very good designs, and, in many practical applications, easily outperform 'traditional' designs that rely on human intuition. Yet, because these heuristic methods do not guarantee that the approximate solution found is globally optimal, the question remains of just how much better a designer might hope to do. This question is addressed by performance bounds or impossibility results, which determine a performance level that no design can achieve. We focus on algorithmic performance bounds, which involve substantial computation to determine. We illustrate a variety of both heuristic methods and performance bounds on two examples. In these examples (and many others not reported here) the performance bounds show that the heuristic designs are nearly optimal, and can be considered globally optimal in practice. This review serves to clearly set up the photonic design problem and unify existing approaches for calculating performance bounds, while also providing some natural generalizations and properties.

A fluorescence sandwich immunoassay for the real-time continuous detection of glucose and insulin in live animals.

Biosensors that continuously measure circulating biomolecules in real time could provide insights into the health status of patients and their response to therapeutics. But biosensors for the continuous real-time monitoring of analytes in vivo have only reached nanomolar sensitivity and can measure only a handful of molecules, such as glucose and blood oxygen. Here we show that multiple analytes can be continuously and simultaneously measured with picomolar sensitivity and sub-second resolution via the integration of aptamers and antibodies into a bead-based fluorescence sandwich immunoassay implemented in a custom microfluidic chip. After an incubation time of 30 s, bead fluorescence is measured using a high-speed camera under spatially multiplexed two-colour laser illumination. We used the assay for continuous quantification of glucose and insulin concentrations in the blood of live diabetic rats to resolve inter-animal differences in the pharmacokinetic response to insulin as well as discriminate pharmacokinetic profiles from different insulin formulations. The assay can be readily modified to continuously and simultaneously measure other blood analytes in vivo.

Crux of Using the Cascaded Emission of a Three-Level Quantum Ladder System to Generate Indistinguishable Photons.

We investigate the degree of indistinguishability of cascaded photons emitted from a three-level quantum ladder system; in our case the biexciton-exciton cascade of semiconductor quantum dots. For the three-level quantum ladder system we theoretically demonstrate that the indistinguishability is inherently limited for both emitted photons and determined by the ratio of the lifetimes of the excited and intermediate states. We experimentally confirm this finding by comparing the quantum interference visibility of noncascaded emission and cascaded emission from the same semiconductor quantum dot. Quantum optical simulations produce very good agreement with the measurements and allow us to explore a large parameter space. Based on our model, we propose photonic structures to optimize the lifetime ratio and overcome the limited indistinguishability of cascaded photon emission from a three-level quantum ladder system.

Publisher Correction: Data-driven acceleration of photonic simulations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Revealing multiple classes of stable quantum emitters in hexagonal boron nitride with correlated optical and electron microscopy.

Defects in hexagonal boron nitride (hBN) exhibit high-brightness, room-temperature quantum emission, but their large spectral variability and unknown local structure challenge their technological utility. Here, we directly correlate hBN quantum emission with local strain using a combination of photoluminescence (PL), cathodoluminescence (CL) and nanobeam electron diffraction. Across 40 emitters, we observe zero phonon lines (ZPLs) in PL and CL ranging from 540 to 720 nm. CL mapping reveals that multiple defects and distinct defect species located within an optically diffraction-limited region can each contribute to the observed PL spectra. Local strain maps indicate that strain is not required to activate the emitters and is not solely responsible for the observed ZPL spectral range. Instead, at least four distinct defect classes are responsible for the observed emission range, and all four classes are stable upon both optical and electron illumination. Our results provide a foundation for future atomic-scale optical characterization of colour centres.

Generation of Tin-Vacancy Centers in Diamond via Shallow Ion Implantation and Subsequent Diamond Overgrowth.

Group IV color centers in diamond have garnered great interest for their potential as optically active solid-state spin qubits. The future utilization of such emitters requires the development of precise site-controlled emitter generation techniques that are compatible with high-quality nanophotonic devices. This task is more challenging for color centers with large group IV impurity atoms, which are otherwise promising because of their predicted long spin coherence times without a dilution refrigerator. For example, when applied to the negatively charged tin-vacancy (SnV-) center, conventional site-controlled color center generation methods either damage the diamond surface or yield bulk spectra with unexplained features. Here we demonstrate a novel method to generate site-controlled SnV- centers with clean bulk spectra. We shallowly implant Sn ions through a thin implantation mask and subsequently grow a layer of diamond via chemical vapor deposition. This method can be extended to other color centers and integrated with quantum nanophotonic device fabrication.