Giovanni De Micheli

Eawag: Das Wasserforschungs-Institut des ETH-Bereichs, Duebendorf, Zurich, Switzerland

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Publications (361)149.9 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We report a novel electrochemical sensor based on nanographite grown on platinum microelectrodes for the determination of bilirubin in the presence of normal concentrations of albumin. The albumin is a protein with an intrinsic ability to bind the bilirubin therefore reducing the concentration of the free electroactive metabolite in human fluids. In addition, the proposed device permits the discrimination of free bilirubin from two interferents, uric acid and ascorbic acid, by the separation of their oxidation peaks in voltammetry. Preliminary measurements in human serum prove that the proposed nanostructured platform can be used to detect bilirubin.
    Talanta 12/2014; 130C:423-426. · 3.50 Impact Factor
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    ABSTRACT: In this work, we show the realization of a fully-implantable device for monitoring free-moving small animals. The device integrates a microfabricated sensing platform, a coil for power and data transmission and two custom designed integrated circuits. The device is intended to be implanted in mice, free to move in a cage, to monitor the concentration of metabolites. We show the system level design of each block of the device, and we present the fabrication of the passive sensing platform and its employment for the electrochemical detection of endogenous and exogenous metabolites. Moreover, we describe the assembly of the device to test the biocompatibility of the materials used for the microfabrication. To ensure biocompatibility, an epoxy enhanced polyurethane membrane was used to cover the device. We proved through an in-vitro characterization that the membrane was capable to retain enzyme activity up to 35 days. After 30 days of implant in mice, in-vivo experiments proved that the membrane promotes the integration of the sensor with the surrounding tissue, as demonstrated by the low inflammation level at the implant site.
    IEEE Transactions on Biomedical Circuits and Systems 10/2014; · 2.74 Impact Factor
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    ABSTRACT: With growing concern about process variation in deeply nano-scaled technologies, parameterized device and circuit modeling is becoming very important for design and verification. However, the high dimensionality of parameter space is a serious modeling challenge for emerging VLSI technologies, where the models are increasingly more complex. In this paper, we propose and validate a feature selection method to reduce the circuit modeling complexity associated with high parameter dimensionality. Despite the commonly used methods such as Principal Component Analysis (PCA) and Independent Component Analysis (ICA), this method is capable of dealing with mixed Gaussian and non-Gaussian parameters, and performs a parameter selection in the input space rather than creating a new space. By considering non-linear dependencies among input parameters and outputs, the method results in an effective parameter selection. The application of this method is demonstrated in digital circuit timing analysis to effectively reduce the number of simulations. The experimental results on Double-Gate Silicon NanoWire FET (DG-SiNWFET) technology indicate 2.5x speed up in timing variation analysis of the I5CA589-s27 benchmark with a controlled average error bound of 9.4%.
    2014 IEEE/ACM International Symposium on Nanoscale Architectures (NANOARCH); 07/2014
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    ABSTRACT: We describe an integrated biosensor capable of sensing multiple molecular targets using both cyclic voltammetry (CV) and chronoamperometry (CA). In particular, we present our custom IC to realize voltage control and current readout of the biosensors. A mixed-signal circuit block generates sub-Hertz triangular waveform for the biosensors by means of a direct-digital-synthesizer to control CV. A current to pulse-width converter is realized to output the data for CA measurement. The IC is fabricated in 0.18 μm technology. It consumes 220 μW from 1.8 V supply voltage, making it suitable for remotely-powered applications. Electrical measurements show excellent linearity in sub- μA current range. Electrochemical measurements including CA measurements of glucose and lactate and CV measurements of the anti-cancer drug Etoposide have been acquired with the fabricated IC and compared with a commercial equipment. The results obtained with the fabricated IC are in good agreement with those of the commercial equipment for both CV and CA measurements.
    IEEE Transactions on Biomedical Circuits and Systems 06/2014; · 2.74 Impact Factor
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    Luca Amarú, Pierre-Emmanuel Gaillardon, Giovanni De Micheli
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    ABSTRACT: In this paper, we present Majority-Inverter Graph (MIG), a novel logic representation structure for efficient optimization of Boolean functions. An MIG is a directed acyclic graph consisting of three-input majority nodes and regular/complemented edges. We show that MIGs include any AND/OR/Inverter Graphs (AOIGs), containing also the well-known AIGs. In order to support the natural manipulation of MIGs, we introduce a new Boolean algebra, based exclusively on majority and inverter operations, with a complete axiomatic system. Theoretical results show that it is possible to explore the entire MIG representation space by using only five primitive transformation rules. Such feature opens up a great opportunity for logic optimization and synthesis. We showcase the MIG potential by proposing a delay-oriented optimization technique. Experimental results over MCNC benchmarks show that MIG optimization reduces the number of logic levels by 18%, on average, with respect to AIG optimization performed by ABC academic tool. Employed in a traditional optimization-mapping circuit synthesis flow, MIG optimization enables an average reduction of {22%, 14%, 11%} in the estimated {delay, area, power} metrics, before physical design, as compared to academic/commercial synthesis flows.
    06/2014;
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    ABSTRACT: Nowadays medical software is tightly coupled with medical devices that perform patient state monitoring and lately even some basic treatment procedures. Medical guidelines (GLs) can be seen as specification of a medical system which requires their computer-interpretable representation of medical GLs. Until now most of the medical GLs are often represented in a textual format and therefore often suffer from such structural problems as incompleteness, inconsistencies, ambiguity and redundancy, which makes the translation process to the machine-interpretable language more complicated. Computer-based interpretation of GLs can improve the quality of protocols as well as the quality of medical service. Several GLs formal representation methods have been presented recently. Only some of them enable automatic formal verification by introducing an additional translation path to the existing model checking environments. However, if a verified property fails it is difficult to trace back the result needed to change the model. Moreover, these formalisms provide the notion of time mostly in terms of actions order. In this paper we preset the application of a well-know formal behaviour representation approach of embedded systems design domain to medical GLs interpretation. We use Timed Automata extended with Tasks (TAT) and TIMES toolbox to represent medical GLs as a system behaviour in a computer interpretable form. We discuss the verification issues with the help of the anticancer drug imatinib case study.
    International Journal of Artificial Intelligence Tools 05/2014; 23(03). · 0.25 Impact Factor
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    ABSTRACT: Conventional pharmaceutical processes involving cell culture growth are generally taken under control with expensive and long laboratory tests performed by direct sampling to evaluate quality. This traditional and well-established approach is just partially adequate in providing information about cell state. Electrochemical enzyme-based biosensors offer several advantages towards this application. In particular, they lend themselves to miniaturization and integration with cheap electronics. In the present work we go through the design, the development, and the validation of a self-contained device for the on-line measurement of metabolites in cell culture media. We microfabricated a sensing platform by using thin film technologies. We exploited electrodeposition to precisely immobilize carbon nanotubes and enzymes on miniaturized working electrodes. We designed and realized the electronics to perform the electrochemical measurements and an Android application to display the measurements on smartphones and tablets. In cell culture media glucose biosensor shows a sensitivity of 4.7±1.3nAmM(-1)mm(-2) and a detection limit of 1.4mM (S/N=3σ), while for lactate biosensor the sensitivity is 12.2±3.8nAmM(-1)mm(-2) and the detection limit is 0.3mM. The whole system was then validated by monitoring U937 cell line over 88h. Metabolic trends were fully congruent with cell density and viability. This self-contained device is a promising tool to provide more detailed information on cell metabolism that are unprecedented in cell biology.
    Biosensors & bioelectronics. 05/2014; 61C:251-259.
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    ABSTRACT: We report the first selective growth of nanographite petals and various carbon nanomaterials onto a multi-panel electrochemical platform. Different types of nanomaterials can be obtained by fine tuning the growth parameters of the CVD process. First absolute novelty is the catalytic CVD selective growth of different carbon nanomaterials only on the working electrodes of the platform. A second novelty is the growth obtained at CMOS compatible temperatures. These novel electrodes have been incorporated in sensors which performance characteristics improve with the content of nanostructures. Unprecedented sensing parameters with respect to both direct and enzyme-mediated electrochemical biodetection have been obtained.
    Nano Letters 05/2014; · 13.03 Impact Factor
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    ABSTRACT: We attempt to examine the potential of silicon nanowire memristors in the field of nanobiosensing. The memristive devices are crystalline Silicon (Si) Nanowires (NWs) with Nickel Silicide (NiSi) terminals. The nanowires are fabricated on a Silicon-on-Insulator (SOI) wafer by an Ebeam Lithography Technique (EBL) process that allows high resolution at the nanoscale. A Deep Reactive Ion Etching (DRIE) technique is used to define free-standing nanowires. The close alignment between Silicon (Si) and Nickel-Silicide (NiSi) terminals forms a Schottky-barrier at their junction. The memristive effect of the fabricated devices matches well with the memristor theory. An equivalent circuit reproducing the memristive effect in current-voltage (I-V) characteristics of our silicon nanowires is presented too. The memristive silicon nanowire devices are then functionalized with anti-human VEGF (Vascular Endothelial Growth Factor) antibody and I-V characteristics are examined for the nanowires prior to and after protein functionalization. The uptake of bio-molecules linked to the surface of the memristive NWs is confirmed by the increased voltage gap in the hysteresis curve. The effects of varying humidity conditions on the conductivity of bio-modified memristive silicon nanowires are deeply investigated.
    IEEE transactions on nanobioscience 03/2014; 13(1):19-30. · 1.71 Impact Factor
  • Pierre-Emmanuel Gaillardon, Luca Amarù, Giovanni De Micheli
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    ABSTRACT: Nowadays, Field Programmable Gate Arrays (FPGA) implement arithmetic functions using specific circuits at the logic block level, such as the carry paths, or at the structure level adopting Digital Signal Processing (DSP) blocks. Nevertheless, all these approaches, introduced to ease the realization of specific functions, are lacking of generality. In this paper, we introduce a new logic block that natively realizes arithmetic functions while preserving the versatility to implement general logic functions. It consists of a partially interconnected matrix of signal routers driven by comparators. We demonstrate that this structure can realize (i) any 2-output 2-input logic function or (ii) any single-output 3-input logic function or (iii) specific logic, such as arithmetic functions, with up to 4-output and 8-inputs. As compared to a standard 6-input Look Up Table (LUT), the proposed block requires roughly the same area but is 35.3% faster. Even though the proposed block has not the same exhaustive configurability of a 6-input LUT, there are arithmetic functions realizable in a single block that do not fit in one, or even more, 6-input LUT. For example, a single block inherently implements an entire 3-bit adder that requires 3× more resources with LUTs plus also custom circuitry. From a system level perspective, we show that a 256-bit adder is implemented with a gain on area×delay product of 31% as compared to its traditional LUT-based counterpart.
    Proceedings of the 2014 ACM/SIGDA international symposium on Field-programmable gate arrays; 02/2014
  • Jacopo Olivo, Sandro Carrara, Giovanni De Micheli
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    ABSTRACT: A micro-fabrication process is proposed to realize high-thickness spiral inductors for the remote powering of implantable biosensors through inductive link. The process is suitable for different substrates, such as silicon and Pyrex, and enables the fabrication of the receiving inductor directly on the implantable system. The use of Ordyl Alpha960 is explored to achieve high-thickness structures. Ordyl is a dry film, negative photoresist that enables high-thickness mold (starting from 60 μm) with a single-layer deposition. Copper spiral inductors with a trace thickness of 60 μm are fabricated on silicon and tested. These inductors can receive up to 8.7 mW, with a link efficiency of 25%, over a distance of 6 mm from the transmitter. Tested within a real setup, these inductors enable bidirectional data communication with the external transmitter. Downlink communication (ASK) is successfully tested at 100 kbps. Uplink communication (LSK) is successfully tested at 66.6 kbps.
    Microelectronic Engineering 01/2014; 113:130–135. · 1.22 Impact Factor
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    ABSTRACT: Conventional pharmaceutical processes involving cell culture growth are generally taken under control with expensive and long laboratory tests performed by direct sampling to evaluate quality. This traditional and well-established approach is just partially adequate in providing information about cell state. Electrochemical enzyme-based biosensors offer several advantages towards this application. In particular, they lend themselves to miniaturization and integration with cheap electronics. In the present work we go through the design, the development, and the validation of a self-contained device for the on-line measurement of metabolites in cell culture media. We microfabricated a sensing platform by using thin film technologies. We exploited electrodeposition to precisely immobilize carbon nanotubes and enzymes on miniaturized working electrodes. We designed and realized the electronics to perform the electrochemical measurements and an Android application to display the measurements on smartphones and tablets. In cell culture media glucose biosensor shows a sensitivity of 4.7±1.3 nA mM−1 mm−2 and a detection limit of 1.4 mM (S/N=3σ), while for lactate biosensor the sensitivity is 12.2±3.8 nA mM−1 mm−2 and the detection limit is 0.3 mM. The whole system was then validated by monitoring U937 cell line over 88 h. Metabolic trends were fully congruent with cell density and viability. This self-contained device is a promising tool to provide more detailed information on cell metabolism that are unprecedented in cell biology.
    Biosensors and Bioelectronics. 01/2014; 61:251–259.
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    ABSTRACT: A large progress in pH sensing with nanowire based ion-sensitive field-effect transistors (ISFETs) has been demonstrated over the years. The electrochemical reactions occurring at the wire surface-to-electrolyte interface play a key role in the detection of ions. In this letter, we show that pH sensing can also be performed on dried samples, through electrical measurements in air with a new kind of memristive sensor. The detection of different concentrations of [H+] is confirmed by both the increased conductance and hysteretic voltage gap of the wires. The observed change in the electrical properties with pH in dry conditions is related to the formation of a wet film at the nanowire surface. Ions from the initial solution are free to move in the final water thin film at the sensing interface with consequent polarization of the NW surface.
    Surface Science. 01/2014; 624:76–79.
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    ABSTRACT: Nanosystems are large-scale integrated systems exploiting nanoelectronic devices. In this study, we consider double independent gate, vertically stacked nanowire field effect transistors (FETs) with gate-all-around structures and typical diameter of 20 nm. These devices, which we have successfully fabricated and evaluated, control the ambipolar behaviour of the nanostructure by selectively enabling one type of carriers. These transistors work as switches with electrically programmable polarity and thus realize an exclusive or operation. The intrinsic higher expressive power of these FETs, when compared with standard complementary metal oxide semiconductor technology, enables us to realize more efficient logic gates, which we organize as tiles to realize nanowire systems by regular arrays. This article surveys both the technology for double independent gate FETs as well as physical and logic design tools to realize digital systems with this fabrication technology.
    Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences 01/2014; 372(2012):20130102. · 2.89 Impact Factor
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    ABSTRACT: Inexact hardware design, which advocates trading the accuracy of computations in exchange for significant savings in area, power and/or performance of computing hardware, has received increasing prominence in several error-tolerant application domains, particularly those involving perceptual or statistical end-users. In this paper, we evaluate inexact hardware for its applicability in weather and climate modelling. We expand previous studies on inexact techniques, in particular probabilistic pruning, to floating point arithmetic units and derive several simulated set-ups of pruned hardware with reasonable levels of error for applications in atmospheric modelling. The set-up is tested on the Lorenz ‘96 model, a toy model for atmospheric dynamics, using software emulation for the proposed hardware. The results show that large parts of the computation tolerate the use of pruned hardware blocks without major changes in the quality of short- and long-time diagnostics, such as forecast errors and probability density functions. This could open the door to significant savings in computational cost and to higher resolution simulations with weather and climate models.
    Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences 01/2014; 372(2018). · 2.89 Impact Factor
  • Thin Solid Films 12/2013; · 1.87 Impact Factor
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    ABSTRACT: Multi-walled carbon nanotubes and graphene nanoflowers were grown by a catalytic chemical vapor deposition process on metal surfaces. Electrodeposition was used as a versatile technique to obtain three different iron catalyst coatings on platinum microelectrodes. The influence of growth parameters on carbon deposits was investigated. Characterization was carried out by scanning electron microscopy and Raman spectroscopy. A chemical treatment in sulphuric acid produced an increased voltammetric background current. In Raman spectra, the effect of the chemical treatment is seen as a more pronounced sp(3) hybridisation mode of C resulting from surface functionalization of the C nanomaterials. Overall, the hybrid electrodes we produced exhibit a promising performance for oxidase-based array biosensors. Therefore, our study opens the possibility of integrating the hybrid electrodes in biochip applications.
    Nanoscale 10/2013; · 6.73 Impact Factor
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    ABSTRACT: Despite the huge research effort to improve the performance of the complementary metal oxide semiconductor (CMOS) image sensors, charge-coupled devices (CCDs) still dominate the cell biology-related conventional fluorescence microscopic imaging market where low or ultra-low noise imaging is required. A detailed comparison of the sensor specifications and performance is usually not provided by the manufacturers which leads the end users not to go out of the habitude and choose a CCD camera instead of a CMOS one. However, depending on the application, CMOS cameras, when empowered by image processing algorithms, can become cost-efficient solutions for conventional fluorescence microscopy. In this paper, we introduce an application-based comparative study between the default CCD camera of an inverted microscope (Nikon Ti-S Eclipse) and a custom-designed CMOS camera and apply efficient image processing algorithms to improve the performance of CMOS cameras. Quantum micro-bead samples (emitting fluorescence light at different intensity levels), breast cancer diagnostic tissue cell samples, and Caco-2 cell samples are imaged by both CMOS and CCD cameras. The results are provided to show the reliability of CMOS camera processed images and finally to be of assistance when scientists select their cameras for desired applications.
    BioNanoScience. 09/2013;
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    ABSTRACT: In this article, we explore adaptive global and local segmentation techniques for a lab-on-chip nutrition monitoring system (NutriChip). The experimental setup consists of Caco-2 intestinal cells that can be artificially stimulated to trigger an immune response. The eventual response is optically monitored using immunofluoresence techniques targeting toll-like receptor 2 (TLR2). Two problems of interest need to be addressed by means of image processing. First, a new cell sample must be properly classified as stimulated or not. Second, the location of the stained TLR2 must be recovered in case the sample has been stimulated. The algorithmic approach to solving these problems is based on the ability of a segmentation technique to properly segment fluorescent spots. The sample classification is based on the amount and intensity of the segmented pixels, while the various segmenting blobs provide an approximate localization of TLR2. A novel local thresholding algorithm and three well-known spot segmentation techniques are compared in this study. Quantitative assessment of these techniques based on real and synthesized data demonstrates the improved segmentation capabilities of the proposed algorithm. © 2013 International Society for Advancement of Cytometry.
    Cytometry Part A 09/2013; · 3.71 Impact Factor
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    ABSTRACT: 3D Monolithic Integration (3DMI), also termed as sequential integration, is a potential technology for future gigascale circuits. In 3DMI technology the 3D contacts, connecting different active layers, are in the order of few 100nm. Given the advantage of such small contacts, 3DMI enables fine-grain (gate-level) partitioning of circuits. In this work we present three cell transformation techniques for standard cell-based ICs with 3DMI technology. As a major contribution of this work, we propose a design flow comprising of a cell transformation technique, cell-on-cell stacking, and a physical design technique (CELONCELPD) aimed at placing cells transformed with cell-on-cell stacking. We analyze and compare various cell transformation techniques for 3DMI technology without disrupting the regularity of the IC design flow. Our experiments demonstrate the effectiveness of CELONCEL design technique, yielding us an area reduction of 37.5%, 16.2% average reduction in wirelength, and 6.2% average improvement in overall delay, compared with a 2D case when benchmarked across various designs in 45nm technology node.
    ACM Journal on Emerging Technologies in Computing Systems (JETC). 09/2013; 9(3).

Publication Stats

6k Citations
149.90 Total Impact Points

Institutions

  • 2009–2014
    • Eawag: Das Wasserforschungs-Institut des ETH-Bereichs
      Duebendorf, Zurich, Switzerland
  • 1970–2014
    • École Polytechnique Fédérale de Lausanne
      • • Integrated Systems Laboratory
      • • Laboratoire de systèmes microélectroniques
      Lausanne, Vaud, Switzerland
  • 2013
    • Integrated Laboratory Systems
      North Carolina, United States
  • 2012
    • École Polytechnique
      Paliseau, Île-de-France, France
    • Italian Institute of Technology (IIT)
      Genova, Liguria, Italy
  • 2010
    • University of Cyprus
      • Department of Electrical and Computer Engineering
      Nicosia, Nicosia District, Cyprus
    • Delft University of Technology
      Delft, South Holland, Netherlands
  • 2006–2010
    • Università degli studi di Cagliari
      • Department of Electrical and Electronic Engineering
      Cagliari, Sardinia, Italy
    • Complutense University of Madrid
      • Department of Computer Architecture and Automation
      Madrid, Madrid, Spain
  • 2008
    • LSI Corporation
      San Jose, California, United States
  • 1999–2008
    • University of Bologna
      • "Guglielmo Marconi" Department of Electrical, Electronic and Information Engineering DEI
      Bologna, Emilia-Romagna, Italy
  • 2007
    • Università degli Studi di Urbino "Carlo Bo"
      Urbino, The Marches, Italy
  • 1988–2007
    • Stanford University
      • • Computer Systems Laboratory
      • • Center for Integrated Systems
      Stanford, CA, United States
  • 1983–2006
    • University of California, Berkeley
      • Department of Electrical Engineering and Computer Sciences
      Berkeley, MO, United States
  • 2005
    • CSL Behring
      King of Prussia, Pennsylvania, United States
  • 2004
    • Cea Leti
      Grenoble, Rhône-Alpes, France
  • 2001
    • Synopsys
      Mountain View, California, United States
  • 1998
    • Georgia Institute of Technology
      • School of Electrical & Computer Engineering
      Atlanta, GA, United States
    • Politecnico di Torino
      • DAUIN - Department of Control and Computer Engineering
      Torino, Piedmont, Italy
  • 1996
    • Federal University of Minas Gerais
      Cidade de Minas, Minas Gerais, Brazil