Towards A Wireless Image Sensor for Real-Time Fluorescence Microscopy in Cancer Therapy.

We present a mm-sized, ultrasonically powered lensless CMOS image sensor as a progress towards wireless fluorescence microscopy. Access to biological information within the tissue has the potential to provide insights guiding diagnosis and treatment across numerous medical conditions including cancer therapy. This information, in conjunction with current clinical imaging techniques that have limitations in obtaining images continuously and lack wireless compatibility, can improve continual detection of multicell clusters deep within tissue. The proposed platform incorporates a 2.4×4.7 mm2 integrated circuit (IC) fabricated in TSMC 0.18 µm, a micro laser diode (µLD), a single piezoceramic and off-chip storage capacitors. The IC consists of a 36×40 array of capacitive trans-impedance amplifier-based pixels, wireless power management and communication via ultrasound and a laser driver all controlled by a Finite State Machine. The piezoceramic harvests energy from the acoustic waves at a depth of 2 cm to power up the IC and transfer 11.5 kbits/frame via backscattering. During Charge-Up, the off-chip capacitor stores charge to later supply a high-power 78 mW µLD during Imaging. Proof of concept of the imaging front end is shown by imaging distributions of CD8 T-cells, an indicator of the immune response to cancer, ex vivo, in the lymph nodes of a functional immune system (BL6 mice) against colorectal cancer consistent with the results of a fluorescence microscope. The overall system performance is verified by detecting 140 µm features on a USAF resolution target with 32 ms exposure time and 389 ms ultrasound backscattering.

Towards A Wireless Image Sensor for Real-Time Fluorescence Microscopy in Cancer Therapy.

We present a mm-sized, ultrasonically powered lensless CMOS image sensor as a progress towards wireless fluorescence microscopy. Access to biological information within the tissue has the potential to provide insights guiding diagnosis and treatment across numerous medical conditions including cancer therapy. This information, in conjunction with current clinical imaging techniques that have limitations in obtaining images continuously and lack wireless compatibility, can improve continual detection of multicell clusters deep within tissue. The proposed platform incorporates a 2.4×4.7 mm2 integrated circuit (IC) fabricated in TSMC 0.18 µm, a micro laser diode (µLD), a single piezoceramic and off-chip storage capacitors. The IC consists of a 36×40 array of capacitive trans-impedance amplifier-based pixels, wireless power management and communication via ultrasound and a laser driver all controlled by a Finite State Machine. The piezoceramic harvests energy from the acoustic waves at a depth of 2 cm to power up the IC and transfer 11.5 kbits/frame via backscattering. During Charge-Up, the off-chip capacitor stores charge to later supply a high-power 78 mW µLD during Imaging. Proof of concept of the imaging front end is shown by imaging distributions of CD8 T-cells, an indicator of the immune response to cancer, ex vivo, in the lymph nodes of a functional immune system (BL6 mice) against colorectal cancer consistent with the results of a fluorescence microscope. The overall system performance is verified by detecting 140 µm features on a USAF resolution target with 32 ms exposure time and 389 ms ultrasound backscattering.

Q-learning based fault estimation and fault tolerant iterative learning control for MIMO systems.

This paper proposes a Q-learning based fault estimation (FE) and fault tolerant control (FTC) scheme under iterative learning control (ILC) framework. Due to the repetitive demands on control actuators for repetitive tasks, ILC is sensitive to actuator faults. Moreover, unknown faults varying with both time and trial axes pose a challenge to the control performance of ILC. This paper introduces Q-learning algorithm for FE to continuously adjust the estimator and adapt the changing faults. Then, FTC is designed by adopting the norm-optimal iterative learning control (NOILC) framework, where the controller is adjusted based on the FE results from Q-learning to counteract the influence of faults. Finally, the simulation on the plant of a mobile robot verifies the effectiveness of the proposed algorithm.

Data-driven control of hydraulic servo actuator: An event-triggered adaptive dynamic programming approach.

Hydraulic servo actuators (HSAs) are often used in the industry in tasks that request great power, high accuracy and dynamic motion. It is well known that an HSA is a highly complex nonlinear system, and that the system parameters cannot be accurately determined due to various uncertainties, an inability to measure some parameters and disturbances. This paper considers an event-triggered learning control problem of the HSA with unknown dynamics based on adaptive dynamic programming (ADP) via output feedback. Due to increasing practical application of the control algorithm, a linear discrete model of HSA is considered and an online learning data driven controller is used, which is based on measured input and output data instead of unmeasurable states and unknown system parameters. Hence, the ADP-based data driven controller in this paper requires neither the knowledge of the HSA dynamics nor exosystem dynamics. Then, an event-based feedback strategy is introduced to the closed-loop system to save the communication resources and reduce the number of control updates. The convergence of the ADP-based control algorithm is also theoretically shown. Simulation results verify the feasibility and effectiveness of the proposed approach in solving the optimal control problem of HSAs.

Blood pressure cut-offs to diagnose impending hypertensive emergency depend on previous hypertension-mediated organ damage and comorbid conditions.

Background Hypertensive emergencies (HTN-E) are important due to a high risk of mortality. However, a sudden increase in blood pressure (BP) can damage target organs before the BP reaches cut-offs to diagnose HTN-E. We (i) analyse HTN guidelines for recommendations of treatment individualization, such as adjusting BP cut-offs for hypertensive urgency or impending HTN-E according to patient's susceptibility to complications (because of previous hypertension-mediated organ damage [HMOD], cardiovascular events and comorbid conditions), and (ii) provide a rationale for the inclusion of patient's susceptibility in protocols for treatment of acute HTN-E. Methods We searched PubMed, SCOPUS, Science Direct, Springer, Oxford Press, Wiley, SAGE and Google Scholar for the following terms: arterial hypertension, impending, emergency, target organ damage, hypertension-mediated organ damage, and comorbidity. Results The available guidelines do not recommend that when we estimate the probability of HTN-E in a patient with very high BP, we take into account not only the 'aggressive factor' (i.e. history of HTN, absolute BP values and rate of its increase), but also the 'vulnerability of the patient' due to previous major adverse cardio-vascular events, HMOD and comorbid conditions. Conclusion The risk does not depend only on the aggressiveness of the health threat but also on the strength of the host's defence. It is, therefore, surprising that one side of the natural interaction (i.e. susceptibility of a patient) is overlooked in almost all available guidelines on HTN.

Asynchronous Fault Detection Observer for 2-D Markov Jump Systems.

In this article, the problem of the asynchronous fault detection (FD) observer design is discussed for 2-D Markov jump systems (MJSs) expressed by a Roesser model. In general, the FD observer cannot work synchronously with the system, that is, the mode of the observer varies with the mode of the system in line with some conditional transitional probabilities. For dealing with this difficult point, a hidden Markov model (HMM) is employed. Then, combining the H∞ attenuation index and H_ increscent index, a multiobjective solution to the FD problem is formed. In terms of linear matrix inequality technology, sufficient conditions are gained to guarantee the existence of the asynchronous FD. Simultaneously, an asynchronous FD algorithm is generated to acquire the optimal performance indices. Finally, a numerical example concerned with the Darboux equation is demonstrated to exhibit the soundness of the developed approach.

Fuzzy Fault Detection for Markov Jump Systems With Partly Accessible Hidden Information: An Event-Triggered Approach.

This article addresses the design issue of fuzzy asynchronous fault detection filter (FAFDF) for a class of nonlinear Markov jump systems by an event-triggered (ET) scheme. The ET scheme can be applied to cut down the transmission times from the system to FAFDF. It is assumed that the system modes cannot be obtained synchronously by the filter, and instead, there is a detector that can measure the estimated modes of the system. The asynchronous phenomenon between the system and the filter is characterized via a hidden Markov model with partly accessible mode detection probabilities. Applying the Lyapunov function methods, sufficient conditions for the presence of FAFDF are obtained. Finally, an application of a wheeled mobile manipulator with hybrid joints is employed to clarify that the devised FAFDF can detect the faults without any incorrect alarm.

Towards an Implantable Fluorescence Image Sensor for Real-Time Monitoring of Immune Response in Cancer Therapy.

Real-time monitoring of cellular-level changes inside the body provides key information regarding disease progression and therapy assessment for critical care including cancer therapy. Current state-of-the-art oncological imaging methods impose unnecessary latencies to detect small cell foci. Invasive methods such as biopsies, on the other hand, cause disruption if deployed on a repeated basis. Therefore, they are not practical for real-time assessments of the tumor tissue. This work presents a proof-of-concept design for an implantable fluorescence lensless image sensor to address the pervasive challenge of real-time tracking of the immune response in immunotherapy. The 2.4x4.7 mm2 integrated circuit (IC) prototype consists of a 36 by 40 pixel array, a laser driver and a power management unit harvesting power and transferring 11.5 kbits/frame through a wireless ultrasound link while implanted 2 cm deep inside the body. Compared to prior art, this is the first full-fledged wireless system implementing chip-scale fluorescence microscopy to the best of our knowledge.Clinical relevance- This prototype can be used to personalize immunotherapy for the 50% of cancer patients who do not initially respond to the therapy.

Microfluidic Packaging Integration with Electronic-Photonic Biosensors Using 3D Printed Transfer Molding.

Multiplexed sensing in integrated silicon electronic-photonic platforms requires microfluidics with both high density micro-scale channels and meso-scale features to accommodate for optical, electrical, and fluidic coupling in small, millimeter-scale areas. Three-dimensional (3D) printed transfer molding offers a facile and rapid method to create both micro and meso-scale features in complex multilayer microfluidics in order to integrate with monolithic electronic-photonic system-on-chips with multiplexed rows of 5 µm radius micro-ring resonators (MRRs), allowing for simultaneous optical, electrical, and microfluidic coupling on chip. Here, we demonstrate this microfluidic packaging strategy on an integrated silicon photonic biosensor, setting the basis for highly multiplexed molecular sensing on-chip.

Bare-Excitation Ground State of a Spinless-Fermion-Boson Model and W-State Engineering in an Array of Superconducting Qubits and Resonators.

This Letter unravels an interesting property of a one-dimensional lattice model that describes a single itinerant spinless fermion (excitation) coupled to zero-dimensional (dispersionless) bosons through two different nonlocal coupling mechanisms. Namely, below a critical value of the effective excitation-boson coupling strength, the exact ground state of this model is the zero-quasimomentum Bloch state of a bare (i.e., completely undressed) excitation. It is demonstrated here how this last property of the lattice model under consideration can be exploited for a fast, deterministic preparation of multipartite W states in a readily realizable system of inductively coupled superconducting qubits and microwave resonators.

Publisher Correction: Integrating photonics with silicon nanoelectronics for the next generation of systems on a chip.

In this Letter, owing to an error during the production process, the author affiliations were listed incorrectly. Affiliation number 5 (Colleges of Nanoscale Science and Engineering, State University of New York (SUNY)) was repeated, and affiliation numbers 6-8 were incorrect. In addition, the phrase "two oxide thickness variants" should have been "two gate oxide thickness variants". These errors have all been corrected online.

Monolithic silicon-photonic platforms in state-of-the-art CMOS SOI processes [Invited].

Integrating photonics with advanced electronics leverages transistor performance, process fidelity and package integration, to enable a new class of systems-on-a-chip for a variety of applications ranging from computing and communications to sensing and imaging. Monolithic silicon photonics is a promising solution to meet the energy efficiency, sensitivity, and cost requirements of these applications. In this review paper, we take a comprehensive view of the performance of the silicon-photonic technologies developed to date for photonic interconnect applications. We also present the latest performance and results of our "zero-change" silicon photonics platforms in 45 nm and 32 nm SOI CMOS. The results indicate that the 45 nm and 32 nm processes provide a "sweet-spot" for adding photonic capability and enhancing integrated system applications beyond the Moore-scaling, while being able to offload major communication tasks from more deeply-scaled compute and memory chips without complicated 3D integration approaches.

Integrating photonics with silicon nanoelectronics for the next generation of systems on a chip.

Electronic and photonic technologies have transformed our lives-from computing and mobile devices, to information technology and the internet. Our future demands in these fields require innovation in each technology separately, but also depend on our ability to harness their complementary physics through integrated solutions1,2. This goal is hindered by the fact that most silicon nanotechnologies-which enable our processors, computer memory, communications chips and image sensors-rely on bulk silicon substrates, a cost-effective solution with an abundant supply chain, but with substantial limitations for the integration of photonic functions. Here we introduce photonics into bulk silicon complementary metal-oxide-semiconductor (CMOS) chips using a layer of polycrystalline silicon deposited on silicon oxide (glass) islands fabricated alongside transistors. We use this single deposited layer to realize optical waveguides and resonators, high-speed optical modulators and sensitive avalanche photodetectors. We integrated this photonic platform with a 65-nanometre-transistor bulk CMOS process technology inside a 300-millimetre-diameter-wafer microelectronics foundry. We then implemented integrated high-speed optical transceivers in this platform that operate at ten gigabits per second, composed of millions of transistors, and arrayed on a single optical bus for wavelength division multiplexing, to address the demand for high-bandwidth optical interconnects in data centres and high-performance computing3,4. By decoupling the formation of photonic devices from that of transistors, this integration approach can achieve many of the goals of multi-chip solutions 5 , but with the performance, complexity and scalability of 'systems on a chip'1,6-8. As transistors smaller than ten nanometres across become commercially available 9 , and as new nanotechnologies emerge10,11, this approach could provide a way to integrate photonics with state-of-the-art nanoelectronics.

Nanofriction in Cavity Quantum Electrodynamics.

The dynamics of cold trapped ions in a high-finesse resonator results from the interplay between the long-range Coulomb repulsion and the cavity-induced interactions. The latter are due to multiple scatterings of laser photons inside the cavity and become relevant when the laser pump is sufficiently strong to overcome photon decay. We study the stationary states of ions coupled with a mode of a standing-wave cavity as a function of the cavity and laser parameters, when the typical length scales of the two self-organizing processes, Coulomb crystallization and photon-mediated interactions, are incommensurate. The dynamics are frustrated and in specific limiting cases can be cast in terms of the Frenkel-Kontorova model, which reproduces features of friction in one dimension. We numerically recover the sliding and pinned phases. For strong cavity nonlinearities, they are in general separated by bistable regions where superlubric and stick-slip dynamics coexist. The cavity, moreover, acts as a thermal reservoir and can cool the chain vibrations to temperatures controlled by the cavity parameters and by the ions' phase. These features are imprinted in the radiation emitted by the cavity, which is readily measurable in state-of-the-art setups of cavity quantum electrodynamics.

Single-chip microprocessor that communicates directly using light.

Data transport across short electrical wires is limited by both bandwidth and power density, which creates a performance bottleneck for semiconductor microchips in modern computer systems--from mobile phones to large-scale data centres. These limitations can be overcome by using optical communications based on chip-scale electronic-photonic systems enabled by silicon-based nanophotonic devices. However, combining electronics and photonics on the same chip has proved challenging, owing to microchip manufacturing conflicts between electronics and photonics. Consequently, current electronic-photonic chips are limited to niche manufacturing processes and include only a few optical devices alongside simple circuits. Here we report an electronic-photonic system on a single chip integrating over 70 million transistors and 850 photonic components that work together to provide logic, memory, and interconnect functions. This system is a realization of a microprocessor that uses on-chip photonic devices to directly communicate with other chips using light. To integrate electronics and photonics at the scale of a microprocessor chip, we adopt a 'zero-change' approach to the integration of photonics. Instead of developing a custom process to enable the fabrication of photonics, which would complicate or eliminate the possibility of integration with state-of-the-art transistors at large scale and at high yield, we design optical devices using a standard microelectronics foundry process that is used for modern microprocessors. This demonstration could represent the beginning of an era of chip-scale electronic-photonic systems with the potential to transform computing system architectures, enabling more powerful computers, from network infrastructure to data centres and supercomputers.

Electro-optical co-simulation for integrated CMOS photonic circuits with VerilogA.

We present a Cadence toolkit library written in VerilogA for simulation of electro-optical systems. We have identified and described a set of fundamental photonic components at the physical level such that characteristics of composite devices (e.g. ring modulators) are created organically - by simple instantiation of fundamental primitives. Both the amplitude and phase of optical signals as well as optical-electrical interactions are simulated. We show that the results match other simulations and analytic solutions that have previously been compared to theory for both simple devices, such as ring resonators, and more complicated devices and systems such as single-sideband modulators, WDM links and Pound Drever Hall Locking loops. We also illustrate the capability of such toolkit for co-simulation with electronic circuits, which is a key enabler of the electro-optic system development and verification.

Protein-losing nephropathy associated with Borrelia burgdorferi seropositivity in a soft-coated wheaten terrier: response to therapy.

A soft-coated wheaten terrier was examined for lameness with subsequent identification of protein-losing nephropathy, hypoalbuminemia, hyperglobulinemia, and seroconversion to Borrelia burgdorferi. Following doxycycline therapy, the urine protein loss decreased significantly and serum albumin concentration remained close to or within the reference interval for over 3 years, contrary to the reported poor prognosis for renal disease associated with B. burgdorferi or protein-losing nephropathy of soft-coated wheaten terriers.

Néphropathie avec perte de protéines associée à une séropositivité pourBorrelia burgdorferichez un Soft-Coated Wheaten Terrier : réponse au traitement. Un Soft-Coated Wheaten Terrier (Terrier irlandais à poil doux) a été examiné pour boiterie avec l'identification subséquente d'une néphropathie avec perte de protéines, d'hypoalbuminémie, d'hyperglobulinémie et de séroconversion à Borrelia burgdorferi. Après un traitement à la doxycycline, la perte de protéines dans l'urine a affiché une baisse significative et la concentration sérique de protéines est demeurée conforme aux intervalles de référence pendant plus de 3 ans, contrairement au pronostic sombre signalé pour la maladie rénale associée à B. burgdorferi ou à la néphropathie avec perte de protéines des Soft-Coated Wheaten Terriers.(Traduit par Isabelle Vallières).

Depletion-mode carrier-plasma optical modulator in zero-change advanced CMOS.

We demonstrate the first (to the best of our knowledge) depletion-mode carrier-plasma optical modulator fabricated in a standard advanced complementary metal-oxide-semiconductor (CMOS) logic process (45 nm node SOI CMOS) with no process modifications. The zero-change CMOS photonics approach enables this device to be monolithically integrated into state-of-the-art microprocessors and advanced electronics. Because these processes support lateral p-n junctions but not efficient ridge waveguides, we accommodate these constraints with a new type of resonant modulator. It is based on a hybrid microring/disk cavity formed entirely in the sub-90 nm thick monocrystalline silicon transistor body layer. Electrical contact of both polarities is made along the inner radius of the multimode ring cavity via an array of silicon spokes. The spokes connect to p and n regions formed using transistor well implants, which form radially extending lateral junctions that provide index modulation. We show 5 Gbps data modulation at 1265 nm wavelength with 5.2 dB extinction ratio and an estimated 40 fJ/bit energy consumption. Broad thermal tuning is demonstrated across 3.2 THz (18 nm) with an efficiency of 291 GHz/mW. A single postprocessing step to remove the silicon handle wafer was necessary to support low-loss optical confinement in the device layer. This modulator is an important step toward monolithically integrated CMOS photonic interconnects.

Depletion-mode polysilicon optical modulators in a bulk complementary metal-oxide semiconductor process.

We demonstrate depletion-mode carrier-plasma optical modulators fabricated in a bulk complementary metal-oxide semiconductor (CMOS), DRAM-emulation process. To the best of our knowledge, these are the first depletion-mode modulators demonstrated in polycrystalline silicon and in bulk CMOS. The modulators are based on novel optical microcavities that utilize periodic spatial interference of two guided modes to create field nulls along waveguide sidewalls. At these nulls, electrical contacts can be placed while preserving a high optical Q. These cavities enable active devices in a process with no partial silicon etch and with lateral p-n junctions. We demonstrate two device variants at 5 Gbps data modulation rate near 1610 nm wavelength. One design shows 3.1 dB modulation depth with 1.5 dB insertion loss and an estimated 160 fJ/bit energy consumption, while a more compact device achieves 4.2 dB modulation depth with 4.0 dB insertion loss and 60 fJ/bit energy consumption. These modulators represent a significant breakthrough in enabling active photonics in bulk silicon CMOS--the platform of the majority of microelectronic logic and DRAM processes--and lay the groundwork for monolithically integrated CMOS-to-DRAM photonic links.

Electron-phonon coupling in crystalline organic semiconductors: microscopic evidence for nonpolaronic charge carriers.

We consider electron-phonon coupling in crystalline organic semiconductors, using naphthalene for our case study. Employing a first-principles approach, we compute the changes in the selfconsistent Kohn-Sham potential corresponding to different phonon modes and go on to obtain the carrier-phonon coupling matrix elements (vertex functions). We then evaluate perturbatively the quasiparticle spectral residues for electrons at the bottom of the lowest unoccupied (LUMO), and holes at the top of the highest occupied (HOMO), band, obtaining Z(e) ≈ 0.74 and Z(h) ≈ 0.78, respectively. Along with the widely accepted notion that the carrier-phonon coupling strengths in polyacenes decrease with increasing molecular size, our results provide strong microscopic evidence for the previously conjectured nonpolaronic nature of bandlike carriers in these systems.