Real-Time Multi-Ion-Monitoring Front-End With Interference Compensation by Multi-Output Support Vector Regressor.

Ion-sensors play a major role in physiology and healthcare monitoring since they are capable of continuously collecting biological data from body fluids. Nevertheless, ion interference from background electrolytes present in the sample is a paramount challenge for a precise multi-ion-monitoring. In this work, we propose the first system combining a battery-powered portable multi-channel electronic front-end, and an embedded Multi-output Support Vector Regressor (M-SVR), that supplies an accurate, continuous, and real-time monitoring of sodium, potassium, ammonium, and calcium ions. These are typical analytes tracked during physical exercise. The front-end interface was characterized through a sensor array built with screen-printed electrodes. Nernstian sensitivity and limit of detection comparable to a bulky laboratory potentiometer were achieved in both water and artificial sweat. The multivariate calibration model was deployed on a Raspberry Pi where the activity of the target ions were locally computed. The M-SVR model was trained, optimized, and tested on an experimental dataset acquired following a design of experiments. We demonstrate that the proposed multivariate regressor is a compact, low-complexity, accurate, and unbiased estimator of sodium and potassium ions activity. A global normalized root mean-squared error improvement of 6.97%, and global mean relative error improvement of 10.26%, were achieved with respect to a standard Multiple Linear Regressor (MLR). Within a real-time multi-ion-monitoring task, the overall system enabled the continuous monitoring and accurate determination of the four target ions activity, with an average accuracy improvement of 27.73% compared to a simple MLR, and a prediction latency of [Formula: see text].

Continuous monitoring of propofol in human serum with fouling compensation by support vector classifier.

We present a new method for electrochemical sensing, which compensates the fouling effect of propofol through machine learning (ML) model. Direct and continuous monitoring of propofol is crucial in the development of automatic systems for control of drug infusion in anaesthesiology. The fouling effect on electrodes discourages the possibility of continuous online monitoring of propofol since polymerization of the surface produces sensor drift. Several approaches have been proposed to limit the phenomenon at the biochemical interface; instead, here, we present a novel ML-based calibration procedure. In this paper, we analyse a dataset of 600 samples acquired through staircase cyclic voltammetry (SCV), resembling the scenario of continuous monitoring of propofol, both in PBS and in undiluted human serum, to demonstrate that ML-based model solves electrode fouling of anaesthetics. The proposed calibration approach is based on Gaussian radial basis function support vector classifier (RBF-SVC) that achieves classification accuracy of 98.9% in PBS, and 100% in undiluted human serum. The results prove the ability of the ML-based model to correctly classify propofol concentration in the therapeutic range between 1µM and 60µM with levels of 10µM, continuously up to ten minutes, with one sample every 30s.

Boolean satisfiability in quantum compilation.

Quantum compilation is the task of translating a quantum algorithm implemented in a high-level quantum programming language into a technology-dependent instructions flow for a physical quantum computer. To tackle the large gap between the quantum program and the low-level instructions, quantum compilation is split into a multi-stage flow consisting of several layers of abstraction. Several different individual tasks have been proposed for the layers in the flow, many of them are NP-hard. In this article, we will describe the flow and we will propose algorithms based on Boolean satisfiability, which is a good match to tackle such computationally complex problems. This article is part of the theme issue 'Harmonizing energy-autonomous computing and intelligence'.

Fast Procedures for the Electrodeposition of Platinum Nanostructures on Miniaturized Electrodes for Improved Ion Sensing.

Nanostructured materials have attracted considerable interest over the last few decades to enhance sensing capabilities thanks to their unique properties and large surface area. In particular, noble metal nanostructures offer several advantages including high stability, non-toxicity and excellent electrochemical behaviour. However, in recent years the great expansion of point-of-care (POC) and wearable systems and the attempt to perform measurements in tiny spaces have also risen the need of increasing sensors miniaturization. Fast constant potential electrodeposition techniques have been proven to be an efficient way to obtain conformal platinum and gold nanostructured layers on macro-electrodes. However, this technique is not effective on micro-electrodes. In this paper, we investigate an alternative one-step deposition technique of platinum nanoflowers on micro-electrodes by linear sweep voltammetry (LSV). The effective deposition of platinum nanoflowers with similar properties to the ones deposited on macro-electrodes is confirmed by morphological analysis and by the similar roughness factor (~200) and capacitance (~18 µ F/mm 2 ). The electrochemical behaviour of the nanostructured layer is then tested in an solid-contact (SC) L i + -selective micro-electrode and compared to the case of macro-electrodes. The sensor offers Nernstian calibration with same response time (~15 s) and a one-order of magnitude smaller limit of detection (LOD) ( 2.6 × 10 - 6 ) with respect to the macro-ion-selective sensors (ISE). Finally, sensor reversibility and stability in both wet and dry conditions is proven.

An IoT Solution for Online Monitoring of Anesthetics in Human Serum Based on an Integrated Fluidic Bioelectronic System.

In this paper, we present the design, the implementation and the validation of a novel Internet of Things (IoT) drug monitoring system for the online continuous and simultaneous detection of two main anesthetics, e.g., propofol and paracetamol, in undiluted human serum. The described full system consists of a custom-built electronic Raspberry Pi (RPi) based Printed Circuit Board (PCB) that drives and reads out the signal from an electrochemical sensing platform integrated into a fluidic system. Thanks to the Polydimethylsiloxane (PDMS) fluidic device, the analyzed sample is automatically fluxed on the sensing site. The IoT network is supported by a Cloud system, which allows the doctor to control and share all the patient's data through a dedicated Android application and a smart watch. The validation closes with the first ever demonstration that our system successfully works for the simultaneous monitoring of propofol and paracetamol in undiluted human serum by measuring the concentration trends of these two drugs in fluxing conditions over time.

Towards Ultrasound Everywhere: A Portable 3D Digital Back-End Capable of Zone and Compound Imaging.

Ultrasound imaging is a ubiquitous diagnostic technique, but does not fit the requirements of the telemedicine approach, because it relies on the real-time manipulation and image recognition skills of a trained expert, called sonographer. Sonographers are only available in hospitals and clinics, negating or at least delaying access to ultrasound scans in many locales-rural areas, developing countries-as well as in medical rescue operations. Telesonography would require an advanced imager that supports three-dimensional (3-D) acquisition; this would allow untrained operators to acquire broad scans and upload them remotely for diagnosis. Such advanced imagers do exist, but do not meet several other requirements for telesonography, such as being portable, inexpensive, and sufficiently low power to enable battery operation. In this work, we present our prototype of the first portable 3-D digital ultrasound back-end system. The prototype is implemented in a single midrange Xilinx field programmable gate array (FPGA), for an estimated power consumption of 5 W. The device supports up to 1024 input channels, which is state of the art and could be scaled further, and supports multiple image reconstruction modes. We evaluate the resource utilization of the FPGA and provide various quality metrics to ascertain the output image quality.

Doping-Free Complementary Logic Gates Enabled by Two-Dimensional Polarity-Controllable Transistors.

Atomically thin two-dimensional (2D) materials belonging to transition metal dichalcogenides, due to their physical and electrical properties, are an exceptional vector for the exploration of next-generation semiconductor devices. Among them, due to the possibility of ambipolar conduction, tungsten diselenide (WSe2) provides a platform for the efficient implementation of polarity-controllable transistors. These transistors use an additional gate, named polarity gate, that, due to the electrostatic doping of the Schottky junctions, provides a device-level dynamic control of their polarity, that is, n- or p-type. Here, we experimentally demonstrate a complete doping-free standard cell library realized on WSe2 without the use of either chemical or physical doping. We show a functionally complete family of complementary logic gates (INV, NAND, NOR, 2-input XOR, 3-input XOR, and MAJ) and, due to the reconfigurable capabilities of the single devices, achieve the realization of highly expressive logic gates, such as exclusive-OR (XOR) and majority (MAJ), with fewer transistors than possible in conventional complementary metal-oxide-semiconductor logic. Our work shows a path to enable doping-free low-power electronics on 2D semiconductors, going beyond the concept of unipolar physically doped devices, while suggesting a road to achieve higher computational densities in two-dimensional electronics.

Highly-stable Li+ ion-selective electrodes based on noble metal nanostructured layers as solid-contacts.

Nowadays the development of stable and highly efficient Solid-Contact Ion-Selective Electrodes (SC-ISEs) attracts much attention in the research community because of the great expansion of portable analytical devices. In this work, we present highly stable Li+ all-solid-state ISEs exploiting noble metals nanostructures as ion-to-electron transducers. The detection of lithium is essential for therapeutic drug monitoring of bipolar patients. In addition, greater environmental exposure to this ion is occurring due to the large diffusion of lithium-ion batteries. However, only a limited number of SC Li+ ISEs already exists in literature based on Conductive Polymers (CPs) and carbon nanotubes. The use of noble metals for ion-to-electron transduction offers considerable advantages over CPs and carbon materials, including fast and conformal one-step deposition by electrochemical means, non-toxicity and high stability. We investigate for the first time the use of gold nanocorals obtained by means of a one-step electrodeposition process to improve sensor performance and we compare it to all-solid-state ISEs based on electrodeposited platinum nanoflowers. In addition, the effect of substrate electrode material, membrane thickness and conditioning concentration on the potentiometric response is carefully analysed. Scanning Electron Microscopy (SEM) and Current Reversal Chronopotentiometry (CRC) techniques are used to characterize the morphology and the electrochemical behaviour of the different ISEs. The use of nanostructured gold and platinum contacts allows the increase of the SC capacitance by one or two orders of magnitude, respectively, with respect to the flat metal, while the SC resistance is significantly reduced. We show that the microfabricated sensors offer Nernstian behaviour (58.7±0.8 mV/decade) in the activity range from 10-5 to 0.1 M, with short response time (∼15 s) and small potential drift during CRC measurements (dEdt=3×10-5±2×10-5 V/s). The exceptional response stability is verified also when no potential is applied. The sensor shows high selectivity towards all clinically important ions, with values very similar to conventional ISEs. Furthermore, to our knowledge, the selectivity towards Ca+2 is the best ever reported for SC-ISEs. In conclusion, the present study opens up new interesting perspectives towards the development of simple and reproducible fabrication protocols to obtain high-quality and high-stability all-solid-state ISEs.

A Differential Electrochemical Readout ASIC With Heterogeneous Integration of Bio-Nano Sensors for Amperometric Sensing.

A monolithic biosensing platform is presented for miniaturized amperometric electrochemical sensing in CMOS. The system consists of a fully integrated current readout circuit for differential current measurement as well as on-die sensors developed by growing platinum nanostructures (Pt-nanoS) on top of electrodes implemented with the top metal layer. The circuit is based on the switch-capacitor technique and includes pseudodifferential integrators for concurrent sampling of the differential sensor currents. The circuit further includes a differential to single converter and a programmable gain amplifier prior to an ADC. The system is fabricated in [Formula: see text] technology and measures current within [Formula: see text] with minimum input-referred noise of [Formula: see text] and consumes [Formula: see text] from a [Formula: see text] supply. Differential sensing for nanostructured sensors is proposed to build highly sensitive and offset-free sensors for metabolite detection. This is successfully tested for bio-nano-sensors for the measurement of glucose in submilli molar concentrations with the proposed readout IC. The on-die electrodes are nanostructured and cyclic voltammetry run successfully through the readout IC to demonstrate detection of [Formula: see text].

The memristive effect as a novelty in drug monitoring.

Nanoscale devices exhibiting memristive properties show great potential in a plethora of applications. In this work, memristive nanowires are presented for the first time as ideal candidates for absolutely novel, ultrasensitive, highly specific and selective drug-biosensors, also paving the way for real-time monitoring applications, in coupling with the restoration properties of DNA-aptamers. The hysteretic properties exhibited by the hereby-presented special nanodevices, modified via surface treatments, are leveraged along the complete cycle consisting of DNA-aptamer immobilization, target binding, and DNA-aptamer regeneration for successful and effective detection of Tenofovir, an antiviral drug for HIV treatment, in buffer as well as in non-diluted human serum. This results in ultrasensitive, label-free monitoring of the therapeutic compound with a limit of detection of 3.09 pM in buffer and 1.38 nM in full serum. These LODs demonstrate 10 times higher sensitivity for the in-buffer drug detection, and twice better performance for drug sensing in full human serum, ever obtained. The selectivity of the memristive biosensor for Tenofovir detection was verified through both positive and negative controls in full human serum. In addition, the DNA-aptamer regeneration character is portrayed for the first time through a memristive effect, and scanning electron microscopy throws more light on the binding mechanism efficiency through the variation of the nanodevice surface properties at the nanoscale.The results presented in this work demonstrate that the coupling of the memristive effect and aptamer regeneration provides the best ever realized nano-biosensor for drug detection also in full human serum.

Efficient Sample Delay Calculation for 2-D and 3-D Ultrasound Imaging.

Ultrasound imaging is a reference medical diagnostic technique, thanks to its blend of versatility, effectiveness, and moderate cost. The core computation of all ultrasound imaging methods is based on simple formulae, except for those required to calculate acoustic propagation delays with high precision and throughput. Unfortunately, advanced three-dimensional (3-D) systems require the calculation or storage of billions of such delay values per frame, which is a challenge. In 2-D systems, this requirement can be four orders of magnitude lower, but efficient computation is still crucial in view of low-power implementations that can be battery-operated, enabling usage in numerous additional scenarios. In this paper, we explore two smart designs of the delay generation function. To quantify their hardware cost, we implement them on FPGA and study their footprint and performance. We evaluate how these architectures scale to different ultrasound applications, from a low-power 2-D system to a next-generation 3-D machine. When using numerical approximations, we demonstrate the ability to generate delay values with sufficient throughput to support 10 000-channel 3-D imaging at up to 30 fps while using 63% of a Virtex 7 FPGA, requiring 24 MB of external memory accessed at about 32 GB/s bandwidth. Alternatively, with similar FPGA occupation, we show an exact calculation method that reaches 24 fps on 1225-channel 3-D imaging and does not require external memory at all. Both designs can be scaled to use a negligible amount of resources for 2-D imaging in low-power applications and for ultrafast 2-D imaging at hundreds of frames per second.

A bimetallic nanocoral Au decorated with Pt nanoflowers (bio)sensor for H2O2 detection at low potential.

In this work, we have developed for the first time a method to make novel gold and platinum hybrid bimetallic nanostructures differing in shape and size. Au-Pt nanostructures were prepared by electrodeposition in two simple steps. The first step consists of the electrodeposition of nanocoral Au onto a gold substrate using hydrogen as a dynamic template in an ammonium chloride solution. After that, the Pt nanostructures were deposited onto the nanocoral Au organized in pores. Using Pt (II) and Pt (IV), we realized nanocoral Au decorated with Pt nanospheres and nanocoral Au decorated with Pt nanoflowers, respectively. The bimetallic nanostructures showed better capability to electrochemically oxidize hydrogen peroxide compared with nanocoral Au. Moreover, Au-Pt nanostructures were able to lower the potential of detection and a higher performance was obtained at a low applied potential. Then, glucose oxidase was immobilized onto the bimetallic Au-Pt nanostructure using cross-linking with glutaraldehyde. The biosensor was characterized by chronoamperometry at +0.15V vs. Ag pseudo-reference electrode (PRE) and showed good analytical performances with a linear range from 0.01 to 2.00mM and a sensitivity of 33.66µA/mMcm2. The good value of Kmapp (2.28mM) demonstrates that the hybrid nanostructure is a favorable environment for the enzyme. Moreover, the low working potential can minimize the interference from ascorbic acid and uric acid as well as reducing power consumption to effect sensing. The simple procedure to realize this nanostructure and to immobilize enzymes, as well as the analytical performances of the resulting devices, encourage the use of this technology for the development of biosensors for clinical analysis.

Scaling trends and performance evaluation of 2-dimensional polarity-controllable FETs.

Two-dimensional semiconducting materials of the transition-metal-dichalcogenide family, such as MoS2 and WSe2, have been intensively investigated in the past few years, and are considered as viable candidates for next-generation electronic devices. In this paper, for the first time, we study scaling trends and evaluate the performances of polarity-controllable devices realized with undoped mono- and bi-layer 2D materials. Using ballistic self-consistent quantum simulations, it is shown that, with the suitable channel material, such polarity-controllable technology can scale down to 5 nm gate lengths, while showing performances comparable to the ones of unipolar, physically-doped 2D electronic devices.

Low-Temperature Wet Conformal Nickel Silicide Deposition for Transistor Technology through an Organometallic Approach.

The race for performance of integrated circuits is nowadays facing a downscale limitation. To overpass this nanoscale limit, modern transistors with complex geometries have flourished, allowing higher performance and energy efficiency. Accompanying this breakthrough, challenges toward high-performance devices have emerged on each significant step, such as the inhomogeneous coverage issue and thermal-induced short circuit issue of metal silicide formation. In this respect, we developed a two-step organometallic approach for nickel silicide formation under near-ambient temperature. Transmission electron and atomic force microscopy show the formation of a homogeneous and conformal layer of NiSix on pristine silicon surface. Post-treatment decreases the carbon content to a level similar to what is found for the original wafer (∼6%). X-ray photoelectron spectroscopy also reveals an increasing ratio of Si content in the layer after annealing, which is shown to be NiSi2 according to X-ray absorption spectroscopy investigation on a Si nanoparticle model. I-V characteristic fitting reveals that this NiSi2 layer exhibits a competitive Schottky barrier height of 0.41 eV and series resistance of 8.5 Ω, thus opening an alternative low-temperature route for metal silicide formation on advanced devices.

Enzymatic and Nonenzymatic Electrochemical Interaction of Abiraterone (Antiprostate Cancer Drug) with Multiwalled Carbon Nanotube Bioelectrodes.

Unexplored electrochemical behavior of abiraterone, a recent and widely used prostate cancer drug, in interaction with cytochrome P450 3A4 (CYP3A4) enzyme and multiwalled carbon nanotubes (MWCNTs) is investigated in this work. The results reported in this work are significant for personalized medicine and point-of-care chemical treatment, especially to improve the life expectancy and quality of life of patients with prostate-cancer. To this purpose, enzymatic and nonenzymatic electrochemical biosensors were developed and characterized with different concentrations of abiraterone. Nonenzymatic biosensors were functionalized with MWCNTs as a catalyst for signal enhancement, while enzymatic biosensors have been obtained with CYP3A4 protein immobilized on MWCNTs as recognition biomolecule. Enzymatic electrochemical experiments demonstrated an inhibition effect on the CYP3A4, clearly observed as a diminished electrocatalytic activity of the enzyme. Electrochemical responses of nonenzymatic biosensors clearly demonstrated the direct electroactivity of abiraterone when reacting with MWCNT as well as an electrode-fouling effect.

Polarity control in WSe2 double-gate transistors.

As scaling of conventional silicon-based electronics is reaching its ultimate limit, considerable effort has been devoted to find new materials and new device concepts that could ultimately outperform standard silicon transistors. In this perspective two-dimensional transition metal dichalcogenides, such as MoS2 and WSe2, have recently attracted considerable interest thanks to their electrical properties. Here, we report the first experimental demonstration of a doping-free, polarity-controllable device fabricated on few-layer WSe2. We show how modulation of the Schottky barriers at drain and source by a separate gate, named program gate, can enable the selection of the carriers injected in the channel, and achieved controllable polarity behaviour with ON/OFF current ratios >10(6) for both electrons and holes conduction. Polarity-controlled WSe2 transistors enable the design of compact logic gates, leading to higher computational densities in 2D-flatronics.

Label-Free Ultrasensitive Memristive Aptasensor.

We present the very first worldwide ever-reported electrochemical biosensor based on a memristive effect and DNA aptamers. This novel device is developed to propose a completely new approach in cancer diagnostics. In this study, an affinity-based technique is presented for the detection of the prostate specific antigen (PSA) using DNA aptamers. The hysteretic properties of memristive silicon nanowires functionalized with these DNA aptamers provide a label-free and ultrasensitive biodetection technique. The ultrasensitive detection is hereby demonstrated for PSA with a limit of detection down to 23 aM, best ever published value for electrochemical biosensors in PSA detection. The effect of polyelectrolytes on our memristive devices is also reported to further show how positive or negative charges affect the memristive hysteresis. With such an approach, combining memristive nanowires and aptamers, memristive aptamer-based biosensors can be proposed to detect a wide range of cancer markers with unprecedent ultrasensitivities to also address the issue of an early detection of cancer.

Bubble electrodeposition of gold porous nanocorals for the enzymatic and non-enzymatic detection of glucose.

Au nanocorals are grown on gold screen-printed electrodes (SPEs) by using a novel and simple one-step electrodeposition process. Scanning electron microscopy was used for the morphological characterization. The devices were assembled on a three-electrode SPE system, which is flexible and mass producible. The electroactive surface area, determined by cyclic voltammetry in sulphuric acid, was found to be 0.07±0.01cm(2) and 35.3±2.7cm(2) for bare Au and nanocoral Au, respectively. The nanocoral modified SPEs were used to develop an enzymatic glucose biosensor based on H2O2 detection. Au nanocoral electrodes showed a higher sensitivity of 48.3±0.9µA/(mMcm(2)) at +0.45V vs Ag|AgCl compared to a value of 24.6±1.3µA/(mMcm(2)) at +0.70V vs Ag|AgCl obtained with bare Au electrodes. However, the modified electrodes have indeed proven to be extremely powerful for the direct detection of glucose with a non-enzymatic approach. The results confirmed a clear peak observed by using nanocoral Au electrode even in the presence of chloride ions at physiological concentration. Amperometric study carried out at +0.15V vs Ag|AgCl in the presence of 0.12M NaCl showed a linear range for glucose between 0.1 and 13mM.

In-Vivo Validation of Fully Implantable Multi-Panel Devices for Remote Monitoring of Metabolism.

This paper presents the in-vivo tests on a Fully Implantable Multi-Panel Devices for Remote Monitoring of endogenous and exogenous analytes. To investigate issues on biocompatibility, three different covers have been designed, realized and tested in mice for 30 days. ATP and neutrophil concentrations have been measured, at the implant site after the device was explanted, to assess the level of biocompatibility of the device. Finally, fully working prototypes of the device were implanted in mice and tested. The implanted devices were used to detect variations in the physiological concentrations of glucose and paracetamol. Data trends on these analytes have been successfully acquired and transmitted to the external base station. Glucose and paracetamol (also named acetaminophen) have been proposed in this research as model molecules for applications to personalized and translational medicine.

Fast synthesis of platinum nanopetals and nanospheres for highly-sensitive non-enzymatic detection of glucose and selective sensing of ions.

Novel methods to obtain Pt nanostructured electrodes have raised particular interest due to their high performance in electrochemistry. Several nanostructuration methods proposed in the literature use costly and bulky equipment or are time-consuming due to the numerous steps they involve. Here, Pt nanostructures were produced for the first time by one-step template-free electrodeposition on Pt bare electrodes. The change in size and shape of the nanostructures is proven to be dependent on the deposition parameters and on the ratio between sulphuric acid and chloride-complexes (i.e., hexachloroplatinate or tetrachloroplatinate). To further improve the electrochemical properties of electrodes, depositions of Pt nanostructures on previously synthesised Pt nanostructures are also performed. The electroactive surface areas exhibit a two order of magnitude improvement when Pt nanostructures with the smallest size are used. All the biosensors based on Pt nanostructures and immobilised glucose oxidase display higher sensitivity as compared to bare Pt electrodes. Pt nanostructures retained an excellent electrocatalytic activity towards the direct oxidation of glucose. Finally, the nanodeposits were proven to be an excellent solid contact for ion measurements, significantly improving the time-stability of the potential. The use of these new nanostructured coatings in electrochemical sensors opens new perspectives for multipanel monitoring of human metabolism.