A Bi-CMOS electronic photonic integrated circuit quantum light detector.

Complimentary metal-oxide semiconductor (CMOS) integration of quantum technology provides a route to manufacture at volume, simplify assembly, reduce footprint, and increase performance. Quantum noise-limited homodyne detectors have applications across quantum technologies, and they comprise photonics and electronics. Here, we report a quantum noise-limited monolithic electronic-photonic integrated homodyne detector, with a footprint of 80 micrometers by 220 micrometers, fabricated in a 250-nanometer lithography bipolar CMOS process. We measure a 15.3-gigahertz 3-decibel bandwidth with a maximum shot noise clearance of 12 decibels and shot noise clearance out to 26.5 gigahertz, when measured with a 9-decibel-milliwatt power local oscillator. This performance is enabled by monolithic electronic-photonic integration, which goes below the capacitance limits of devices made up of separate integrated chips or discrete components. It exceeds the bandwidth of quantum detectors with macroscopic electronic interconnects, including wire and flip chip bonding. This demonstrates electronic-photonic integration enhancing quantum photonic device performance.

Heterogeneous Integration of Solid-State Quantum Systems with a Foundry Photonics Platform.

Diamond color centers are promising optically addressable solid-state spins that can be matter-qubits, mediate deterministic interaction between photons, and act as single photon emitters. Useful quantum computers will comprise millions of logical qubits. To become useful in constructing quantum computers, spin-photon interfaces must, therefore, become scalable and be compatible with mass-manufacturable photonics and electronics. Here, we demonstrate the heterogeneous integration of NV centers in nanodiamond with low-fluorescence silicon nitride photonics from a standard 180 nm CMOS foundry process. Nanodiamonds are positioned over predefined sites in a regular array on a waveguide in a single postprocessing step. Using an array of optical fibers, we excite NV centers selectively from an array of six integrated nanodiamond sites and collect the photoluminescence (PL) in each case into waveguide circuitry on-chip. We verify single photon emission by an on-chip Hanbury Brown and Twiss cross-correlation measurement, which is a key characterization experiment otherwise typically performed routinely with discrete optics. Our work opens up a simple and effective route to simultaneously address large arrays of individual optically active spins at scale, without requiring discrete bulk optical setups. This is enabled by the heterogeneous integration of NV center nanodiamonds with CMOS photonics.

OrganoID: A versatile deep learning platform for tracking and analysis of single-organoid dynamics.

Organoids have immense potential as ex vivo disease models for drug discovery and personalized drug screening. Dynamic changes in individual organoid morphology, number, and size can indicate important drug responses. However, these metrics are difficult and labor-intensive to obtain for high-throughput image datasets. Here, we present OrganoID, a robust image analysis platform that automatically recognizes, labels, and tracks single organoids, pixel-by-pixel, in brightfield and phase-contrast microscopy experiments. The platform was trained on images of pancreatic cancer organoids and validated on separate images of pancreatic, lung, colon, and adenoid cystic carcinoma organoids, which showed excellent agreement with manual measurements of organoid count (95%) and size (97%) without any parameter adjustments. Single-organoid tracking accuracy remained above 89% over a four-day time-lapse microscopy study. Automated single-organoid morphology analysis of a chemotherapy dose-response experiment identified strong dose effect sizes on organoid circularity, solidity, and eccentricity. OrganoID enables straightforward, detailed, and accurate image analysis to accelerate the use of organoids in high-throughput, data-intensive biomedical applications.

Advantage of Coherent States in Ring Resonators over Any Quantum Probe Single-Pass Absorption Estimation Strategy.

Quantum states of light have been shown to enhance precision in absorption estimation over classical strategies. By exploiting interference and resonant enhancement effects, we show that coherent-state probes in all-pass ring resonators can outperform any quantum probe single-pass strategy even when normalized by the mean input photon number. We also find that under optimal conditions coherent-state probes equal the performance of arbitrarily bright pure single-mode squeezed probes in all-pass ring resonators.

Shot-noise limited homodyne detection for MHz quantum light characterisation in the 2 µm band.

Characterising quantum states of light in the 2 µm band requires high-performance shot-noise limited detectors. Here, we present the characterisation of a homodyne detector that we use to observe vacuum shot-noise via homodyne measurement with a 2.07 µm pulsed mode-locked laser. The device is designed primarily for pulsed illumination. It has a 3-dB bandwidth of 13.2 MHz, total conversion efficiency of 57% at 2.07 µm, and a common-mode rejection ratio of 48 dB at 39.5 MHz. The detector begins to saturate at 1.8 mW with 9 dB of shot-noise clearance at 5 MHz. This demonstration enables the characterisation of megahertz-quantum optical behaviour in the 2 µm band and provides a guide of how to design a 2 µm homodyne detector for quantum applications.

Implementing graph-theoretic quantum algorithms on a silicon photonic quantum walk processor.

Applications of quantum walks can depend on the number, exchange symmetry and indistinguishability of the particles involved, and the underlying graph structures where they move. Here, we show that silicon photonics, by exploiting an entanglement-driven scheme, can realize quantum walks with full control over all these properties in one device. The device we realize implements entangled two-photon quantum walks on any five-vertex graph, with continuously tunable particle exchange symmetry and indistinguishability. We show how this simulates single-particle walks on larger graphs, with size and geometry controlled by tuning the properties of the composite quantum walkers. We apply the device to quantum walk algorithms for searching vertices in graphs and testing for graph isomorphisms. In doing so, we implement up to 100 sampled time steps of quantum walk evolution on each of 292 different graphs. This opens the way to large-scale, programmable quantum walk processors for classically intractable applications.

Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids.

Three-dimensional (3D) cell culture technologies, such as organoids, are physiologically relevant models for basic and clinical applications. Automated microfluidics offers advantages in high-throughput and precision analysis of cells but is not yet compatible with organoids. Here, we present an automated, high-throughput, microfluidic 3D organoid culture and analysis system to facilitate preclinical research and personalized therapies. Our system provides combinatorial and dynamic drug treatments to hundreds of cultures and enables real-time analysis of organoids. We validate our system by performing individual, combinatorial, and sequential drug screens on human-derived pancreatic tumor organoids. We observe significant differences in the response of individual patient-based organoids to drug treatments and find that temporally-modified drug treatments can be more effective than constant-dose monotherapy or combination therapy in vitro. This integrated platform advances organoids models to screen and mirror real patient treatment courses with potential to facilitate treatment decisions for personalized therapy.

Quantum Optical Metrology of Correlated Phase and Loss.

Optical absorption measurements characterize a wide variety of systems from atomic gases to in vivo diagnostics of living organisms. Here we study the potential of nonclassical techniques to reduce statistical noise below the shot-noise limit in absorption measurements with concomitant phase shifts imparted by a sample. We consider both cases where there is a known relationship between absorption and a phase shift, and where this relationship is unknown. For each case we derive the fundamental limit and provide a practical strategy to reduce statistical noise. Furthermore, we find an intuitive correspondence between measurements of absorption and of lossy phase shifts, which both show the same analytical form for precision enhancement for bright states. Our results demonstrate that nonclassical techniques can aid real-world tasks with present-day laboratory techniques.

Widely-tunable mid-infrared ring cavity pump-enhanced OPO and application in photo-thermal interferometric trace ethane detection.

The development of a broadly and accurately tunable single-frequency mid-infrared laser source and its application to a sensitive laser absorption detection method are described. Photo-thermal interferometric spectroscopy is employed as a phase-sensitive method to detect the minute refractive index change caused by the heating of a gas under laser radiation. A separate probe beam allows for the spectrally-interesting mid-infrared region to be examined whilst utilizing low cost, high detectivity photodetectors in the visible/near-infrared region. We also describe the implementation of a Sagnac interferometer to minimize the effects of environmental perturbation and provide inherent passive stability. A continuous-wave ring-cavity pump-enhanced OPO has been developed to provide excitation light from 3-4 µm at 140 mW with the ability to mode-hop tune continuously over 90 cm-1 in 0.07 cm-1 steps. Complementary use of both detection apparatus and excitation source has allowed for presence of ethane to be detected down to 200 parts per billion.

Observation of nonlinear interference on a silicon photonic chip.

Photonic integrated circuits represent a promising platform for applying quantum information science to areas such as quantum computation, quantum communication, and quantum metrology. While the linear optical approach has greatly contributed to this field, it is often possible to improve the functionality and scalability by making use of nonlinear processes. One interesting phenomenon is the interference between two nonlinear optical processes, where the interference occurs by removing the information as to which of two processes have occurred. In this Letter, we demonstrate a nonlinear interferometer in the pair-photon generation regime by using spontaneous four-wave mixing in an integrated silicon photonic chip. We observe a nonlinear interference in the production rate of photon pairs generated from two different four-wave mixing waveguides. We obtain an interference visibility of 96.8%. This work shows the possibility of integrating and controlling nonlinear-optical-interference components for silicon quantum photonics.

Generation of random numbers by measuring phase fluctuations from a laser diode with a silicon-on-insulator chip.

Random numbers are a fundamental resource in science and technology. Among the different approaches to generating them, random numbers created by exploiting the laws of quantum mechanics have proven to be reliable and can be produced at enough rates for their practical use. While these demonstrations have shown very good performance, most of the implementations using free-space and fibre optics suffer from limitations due to their size, which strongly limits their practical use. Here we report a quantum random number generator based on phase fluctuations from a diode laser, where the other required optical components are integrated on a mm-scale monolithic silicon-on-insulator chip. The post-processing reported in this experiment is performed via software. However, our physical device shows the potential of operation at generation rates in the Gbps regime. Considering the device's size, its simple, robust and low power operation, and the rapid industrial uptake of silicon photonics, we foresee the widespread integration of the reported design in more complex systems.

An Embedded Device for Real-Time Noninvasive Intracranial Pressure Estimation.

OBJECTIVE: The monitoring of intracranial pressure (ICP) is indicated for diagnosing and guiding therapy in many neurological conditions. Current monitoring methods, however, are highly invasive, limiting their use to the most critically ill patients only. Our goal is to develop and test an embedded device that performs all necessary mathematical operations in real-time for noninvasive ICP (nICP) estimation based on a previously developed model-based approach that uses cerebral blood flow velocity (CBFV) and arterial blood pressure (ABP) waveforms. MATERIALS AND METHODS: The nICP estimation algorithm along with the required preprocessing steps were implemented on an NXP LPC4337 microcontroller unit (MCU). A prototype device using the MCU was also developed, complete with display, recording functionality, and peripheral interfaces for ABP and CBFV monitoring hardware. RESULTS: The device produces an estimate of mean ICP once per minute and performs the necessary computations in 410 ms, on average. Real-time nICP estimates differed from the original batch-mode MATLAB implementation of theestimation algorithm by 0.63 mmHg (root-mean-square error). CONCLUSIONS: We have demonstrated that real-time nICP estimation is possible on a microprocessor platform, which offers the advantages of low cost, small size, and product modularity over a general-purpose computer. These attributes take a step toward the goal of real-time nICP estimation at the patient's bedside in a variety of clinical settings.

Demonstrating an absolute quantum advantage in direct absorption measurement.

Engineering apparatus that harness quantum theory promises to offer practical advantages over current technology. A fundamentally more powerful prospect is that such quantum technologies could out-perform any future iteration of their classical counterparts, no matter how well the attributes of those classical strategies can be improved. Here, for optical direct absorption measurement, we experimentally demonstrate such an instance of an absolute advantage per photon probe that is exposed to the absorbative sample. We use correlated intensity measurements of spontaneous parametric downconversion using a commercially available air-cooled CCD, a new estimator for data analysis and a high heralding efficiency photon-pair source. We show this enables improvement in the precision of measurement, per photon probe, beyond what is achievable with an ideal coherent state (a perfect laser) detected with 100% efficient and noiseless detection. We see this absolute improvement for up to 50% absorption, with a maximum observed factor of improvement of 1.46. This equates to around 32% reduction in the total number of photons traversing an optical sample, compared to any future direct optical absorption measurement using classical light.

Quality of Life in Long-term Survivors of Muscle-Invasive Bladder Cancer.

PURPOSE: Health-related quality of life (QOL) has not been well-studied in survivors of muscle-invasive bladder cancer (MIBC). The present study compared long-term QOL in MIBC patients treated with radical cystectomy (RC) versus bladder-sparing trimodality therapy (TMT). METHODS AND MATERIALS: This cross-sectional bi-institutional study identified 226 patients with nonmetastatic cT2-cT4 MIBC, diagnosed in 1990 to 2011, who were eligible for RC and were disease free for ≥2 years. Six validated QOL instruments were administered: EuroQOL EQ-5D, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire and EORTC MIBC module, Expanded Prostate Cancer Index Composite bowel scale, Cancer Treatment and Perception Scale, and Impact of Cancer, version 2. Multivariable analyses of the mean QOL scores were conducted using propensity score matching. RESULTS: The response rate was 77% (n=173). The median follow-up period was 5.6 years. Of the 173 patients, 64 received TMT and 109, RC. The median interval from diagnosis to questionnaire completion was 9 years after TMT and 7 years after RC (P=.009). No significant differences were found in age, gender, comorbidities, tobacco history, performance status, or tumor stage. On multivariable analysis, patients who received TMT had better general QOL by 9.7 points of 100 compared with those who had received RC (P=.001) and higher physical, role, social, emotional, and cognitive functioning by 6.6 to 9.9 points (P≤.04). TMT was associated with better bowel function by 4.5 points (P=.02) and fewer bowel symptoms by 2.7 to 7.1 points (P≤.05). The urinary symptom scores were similar. TMT was associated with better sexual function by 8.7 to 32.1 points (P≤.02) and body image by 14.8 points (P<.001). The patients who underwent TMT reported greater informed decision-making scores by 13.6 points (P=.01) and less concern about the negative effect of cancer by 6.8 points (P=.006). The study limitations included missing baseline QOL data and different follow-up times. CONCLUSIONS: Both TMT and RC result in good long-term QOL outcomes in MIBC survivors, supporting TMT as a good alternative to RC for selected patients. Whether TMT leads to superior QOL requires prospective validation.

Quantum Logic with Cavity Photons From Single Atoms.

We demonstrate quantum logic using narrow linewidth photons that are produced with an a priori nonprobabilistic scheme from a single ^{87}Rb atom strongly coupled to a high-finesse cavity. We use a controlled-not gate integrated into a photonic chip to entangle these photons, and we observe nonclassical correlations between photon detection events separated by periods exceeding the travel time across the chip by 3 orders of magnitude. This enables quantum technology that will use the properties of both narrow-band single photon sources and integrated quantum photonics.

Efficient quantum walk on a quantum processor.

The random walk formalism is used across a wide range of applications, from modelling share prices to predicting population genetics. Likewise, quantum walks have shown much potential as a framework for developing new quantum algorithms. Here we present explicit efficient quantum circuits for implementing continuous-time quantum walks on the circulant class of graphs. These circuits allow us to sample from the output probability distributions of quantum walks on circulant graphs efficiently. We also show that solving the same sampling problem for arbitrary circulant quantum circuits is intractable for a classical computer, assuming conjectures from computational complexity theory. This is a new link between continuous-time quantum walks and computational complexity theory and it indicates a family of tasks that could ultimately demonstrate quantum supremacy over classical computers. As a proof of principle, we experimentally implement the proposed quantum circuit on an example circulant graph using a two-qubit photonics quantum processor.

Noninvasive and continuous blood pressure measurement via superficial temporal artery tonometry.

The measurement of blood pressure is an important cardiovascular health assessment, yet the current set of methodologies is limited in resolution, repeatability, accuracy, simplicity, and safety. This paper presents the design and prototype implementation of a novel and easy-to-use medical device for noninvasive and continuous blood pressure monitoring through tonometry at the superficial temporal artery (STA). The device features a stable form factor inspired by over-ear headphones that adjusts easily from person to person using a combination prismatic and rotational joint. A stepper motor and pressure sensor, built into the device, apply a controlled force to flatten the artery and measure the wearer's blood pressure. The design is fully wireless, using Bluetooth communication to connect to a custom control and monitoring interface on the user's laptop that allows for easy calibration and real-time measurement. Preliminary testing of the device showed a percentage error from a blood pressure cuff mean arterial pressure measurement of 7.7% (7.0 mmHg). This was also compared to a Nexfin vascular unloading device, which showed a percentage error from the blood pressure cuff of 7.3% (6.6 mmHg).

QUANTUM OPTICS. Universal linear optics.

Linear optics underpins fundamental tests of quantum mechanics and quantum technologies. We demonstrate a single reprogrammable optical circuit that is sufficient to implement all possible linear optical protocols up to the size of that circuit. Our six-mode universal system consists of a cascade of 15 Mach-Zehnder interferometers with 30 thermo-optic phase shifters integrated into a single photonic chip that is electrically and optically interfaced for arbitrary setting of all phase shifters, input of up to six photons, and their measurement with a 12-single-photon detector system. We programmed this system to implement heralded quantum logic and entangling gates, boson sampling with verification tests, and six-dimensional complex Hadamards. We implemented 100 Haar random unitaries with an average fidelity of 0.999 ± 0.001. Our system can be rapidly reprogrammed to implement these and any other linear optical protocol, pointing the way to applications across fundamental science and quantum technologies.

A dominance shift from the zebra mussel to the invasive quagga mussel may alter the trophic transfer of metals.

Bioinvasions are a major cause of biodiversity and ecosystem changes. The rapid range expansion of the invasive quagga mussel (Dreissena rostriformis bugensis) causing a dominance shift from zebra mussels (Dreissena polymorpha) to quagga mussels, may alter the risk of secondary poisoning to predators. Mussel samples were collected from various water bodies in the Netherlands, divided into size classes, and analysed for metal concentrations. Concentrations of nickel and copper in quagga mussels were significantly lower than in zebra mussels overall. In lakes, quagga mussels contained significantly higher concentrations of aluminium, iron and lead yet significantly lower concentrations of zinc66, cadmium111, copper, nickel, cobalt and molybdenum than zebra mussels. In the river water type quagga mussel soft tissues contained significantly lower concentrations of zinc66. Our results suggest that a dominance shift from zebra to quagga mussels may reduce metal exposure of predator species.

Low testosterone has a similar prevalence among men with sexual dysfunction due to either Peyronie's disease or erectile dysfunction and does not correlate with Peyronie's disease severity.

INTRODUCTION: Low testosterone (T) has been suggested as a risk factor for Peyronie's disease (PD) that may correlate with disease severity. Low T is common in men with sexual dysfunction but its role in the pathogenesis of PD remains unclear. AIM: The aim of this study was to compare the prevalence of low T (<300 ng/dL) in patients presenting with PD or erectile dysfunction (ED), as well as disease severity between men with PD and either low T or normal T (≥300 ng/dL). METHODS: Retrospective review of 300 men with either PD or ED was conducted. Men were excluded for combined PD and ED, psychogenic ED, or prior T use. For men with PD, plaque size, degree of curvature, and surgical correction rate were compared. MAIN OUTCOME MEASURES: The main outcome measures were (i) mean T levels in men with PD or ED and (ii) plaque size, degree of curvature, and surgical correction rates among men with PD and either low T or normal T. RESULTS: Eighty-seven men with PD and 98 men with ED were identified. Men with PD had mean total T and free T of 328 ng/dL and 11.5 ng/dL, while men with ED had mean levels of 332 ng/dL and 12.1 ng/dL, respectively (P > 0.05). Of PD men, 52.9% had low T, compared with 45.9% of men with ED (P = 0.35). T levels did not correlate with plaque size or degree of curvature in the PD group (P > 0.05). CONCLUSIONS: Men with sexual dysfunction characterized by either PD or ED had similarly low T levels, and low T did not correlate with PD severity or surgical correction rate. The comparable prevalence of low T in men with PD or ED suggests the high rate of low T in PD men may be related to a common process among men with abnormal erectile physiology and not specifically causative in plaque formation.