We have always been open to side-projects leading to applications. One was CNT reinforced composites where we have written an influential patent. The other is the exploration of ion-sensitive field-effect transistors for biochemical sensing. Though there was a substantial literature, when we entered this field, we could contribute with several basic papers that are key to this field. In one paper we analyzed the requirement to obtain maximum transducer efficiency expressed by Nernst’s relation,1 another paper laid the basis for the detection limit (ultimate sensitivity) expressed by the background noise2 of the sensor and yet another important contribution discusses multi-ion sensing3 and how different reactions may influence each other due to charge coupling,4 and the requirements for biosensing.5  This research, in which more than 5 PhD students were involved, eventually led to the founding of a start-up by Oren Knopfmacher: Avails Medical.

  1. O. Knopfmacher, A. Tarasov, W. Y. Fu, M. Wipf, B. Niesen, M. Calame and CS, Nano Lett. 10 (6), 2268 (2010).
  2. A. Tarasov, W. Fu, O. Knopfmacher, J. Brunner, M. Calame and CS, Appl. Phys. Lett. 98 (1), 012114 (2011).
  3. M. Wipf, R. L. Stoop, A. Tarasov, K. Bedner, W. Y. Fu, I. A. Wright, C. J. Martin, E. C. Constable, M. Calame and CS, ACS Nano 7 (7), 5978-5983 (2013).
  4. R. L. Stoop, M. Wipf, S. Mueller, K. Bedner, I. A. Wright, C. J. Martin, E. C. Constable, W. Y. Fu, A. Tarasov, M. Calame and CS, Sens. Actuator B-Chem. 220, 500-507 (2015).
  5. A. Tarasov, M. Wipf, R. L. Stoop, K. Bedner, W. Y. Fu, V. A. Guzenko, O. Knopfmacher, M. Calame and CS, ACS Nano 6 (10), 9291-9298 (2012).

Funding: Nano-Tera

Relevant papers (keyword: ISFET):

  • [DOI] Charge Noise in Organic Electrochemical Transistors
    R. L. Stoop, K. Thodkar, M. Sessolo, H. J. Bolink, and Calame M. C. Schönenberger.
    Phys. Rev. Appl., 7(1):14009, jan 2017.

    Organic electrochemical transistors (OECTs) are increasingly studied as transducers in sensing applications. While much emphasis has been placed on analyzing and maximizing the OECT signal, noise has been mostly ignored, although it determines the resolution of the sensor. The major contribution to the noise in sensing devices is the 1/f noise, dominant at low frequency. In this work, we demonstrate that the 1/f noise in OECTs follows a charge-noise model, which reveals that the noise is due to charge fuctuations in proximity or within the bulk of the channel material. We present the noise scaling behavior with gate voltage, channel dimensions and polymer thickness. Our results suggest the use of large area channels in order to maximize the signal-to-noise-ratio (SNR) for biochemical and electrostatic sensing applications. Comparison with literature shows that the magnitude of the noise in OECTs is similar to that observed in graphene transistors, and only slightly higher compared to Carbon nanotubes and Silicon nanowire devices. In a model ion-sensing experiment with OECTs, we estimate crucial parameters such as the characteristic SNR and corresponding limit of detection.

  • [DOI] Competing surface reactions limiting the performance of ion-sensitive field-effect transistors
    R. L. Stoop, M. Wipf, S. Müller, K. Bedner, I. A. Wright, C. J. Martin, E. C. Constable, Wangyang Fu, A. Tarasova, M. Calame, and C. Schönenberger.
    Sensors and Actuators B, 220( ):500-507, Dec. 2015.
    [arXiv: ] [Abstract]

    Ion-sensitive field-effect transistors based on silicon nanowires are promising candidates for the detection of chemical and biochemical species. These devices have been established as pH sensors thanks to the large number of surface hydroxyl groups at the gate dielectrics which makes them intrinsically sensitive to protons. To specifically detect species other than protons, the sensor surface needs to be modified. However, the remaining hydroxyl groups after functionalization may still limit the sensor response to the targeted species. Here, we describe the influence of competing reactions on the measured response using a general site-binding model. We investigate the key features of the model with a real sensing example based on gold-coated nanoribbons functionalized with a self-assembled monolayer of calcium-sensitive molecules. We identify the residual pH response as the key parameter limiting the sensor response. The competing effect of pH or any other relevant reaction at the sensor surface has therefore to be included to quantitatively understand the sensor response and prevent misleading interpretations.

  • [DOI] Sensing with Advanced Computing Technology: Fin Field Effect Transistors with High-K Gate Stack on Bulk Silicon
    S. Rigante, P. Scarbolo, M. Wipf, R. L. Stoop, K. Bedner, E. Buitrago, A. Bazigos, D. Bouvet, M. Calame, C. Schönenberger, and A. M. Ionescu..
    ACS Nano, 9(5):4972, March 2015.

    Field-effect transistors (FETs) form an established technology for sensing applications. However, recent advancements and use of high-performance multigate metal–oxide semiconductor FETs (double-gate, FinFET, trigate, gate-all-around) in computing technology, instead of bulk MOSFETs, raise new opportunities and questions about the most suitable device architectures for sensing integrated circuits. In this work, we propose pH and ion sensors exploiting FinFETs fabricated on bulk silicon by a fully CMOS compatible approach, as an alternative to the widely investigated silicon nanowires on silicon-on-insulator substrates. We also provide an analytical insight of the concept of sensitivity for the electronic integration of sensors. N-channel fully depleted FinFETs with critical dimensions on the order of 20 nm and HfO2 as a high-k gate insulator have been developed and characterized, showing excellent electrical properties, subthreshold swing, SS ~ 70 mV/dec, and on-to-off current ratio, Ion/Ioff ~ 10^6, at room temperature. The same FinFET architecture is validated as a highly sensitive, stable, and reproducible pH sensor. An intrinsic sensitivity close to the Nernst limit, S = 57 mV/pH, is achieved. The pH response in terms of output current reaches S_out = 60\%. Long-term measurements have been performed over 4.5 days with a resulting drift in time δVth/δt = 0.10 mV/h. Finally, we show the capability to reproduce experimental data with an extended three-dimensional commercial finite element analysis simulator, in both dry and wet environments, which is useful for future advanced sensor design and optimization.

  • [DOI] Sensor system including silicon nanowire ion sensitive FET arrays and CMOS readout
    P. Livi, A. Shadmani, M. Wipf, R. L. Stoop, J. Rothe, Y. Chen, M. Calame, and C. Schönenberger.
    Sensors and Actuators B, 204( ):568577, Aug 2014.
    [arXiv: ] [Abstract]

    We present a highly sensitive chemical sensor system including a chip with an array of silicon nanowire ISFETs and a CMOS chip with custom-designed signal-conditioning circuitry. The CMOS circuitry, comprising 8 sigma–delta (Σ–Δ) modulators and 8 current-to-frequency converters, has been interfaced to each of the nanowires to apply a constant voltage for measuring the respective current through the nanowire. Each nanowire has a dedicated readout channel, so that no multiplexing is required, which helps to avoid leakage current issues. The analog signal has been digitized on chip and transmitted to a host PC via a FPGA. The system has been successfully fabricated and tested and features, depending on the settings, noise values as low as 8.2 pARMS and a resolution of 13.3 bits while covering an input current range from 200 pA to 3 μA. The two readout architectures (Σ–Δ and current to frequency) have been compared, and measurements showing the advantages of combining a CMOS readout with silicon nanowire sensors are presented: (1) simultaneous readout of different silicon nanowires for high-temporal-resolution experiments and parallel sensor experiments (results from pH and KCl concentration sweeps are presented); (2) high speed measurements showing how the CMOS chip can enhance the performance of the nanowire sensors by compensating its non-idealities as a consequence of hysteresis.

  • [DOI] Investigation of the dominant 1/f Noise Source in Silicon Nanowire Sensors
    K. Bedner, V. A. Guzenko, A. Tarasov, M. Wipf, L. Stoop, S. Rigante, J. Brunner, W. Fu, C. David, M. Calame, J. Gobrecht, and C. Schönenberger.
    Sensor & Actuators B, 191( ):270-275, 2014.
    [arXiv: ] [Abstract]

    We analyzed 1/f noise in silicon nanowire ion-sensitive field-effect transistors (SiNW-ISFETs) having different wire widths ranging from 100 nm to 1 μm and operated under different gating conditions in order to determine the noise source and the sensor accuracy. We find that the gate-referred voltage noise SVG (power spectral density) is constant over a large range of SiNWs resistances tuned by a DC gate voltage. The measurements of SVG for SiNWs with two different gate-oxide thicknesses, but otherwise similar device parameters, are only compatible with the so-called trap state noise model in which the source of 1/f noise is due to trap states residing in the gate oxide (most likely in the interface between the semiconductor and the oxide). SVG is found to be inversely proportional to the wire width for constant wire length. From the noise data we determine a sensor accuracy of 0.017\% of a full Nernstian shift of 60 mV/pH for a SiNW wire with a width of 1 μm. No influence of the ions in the buffer solution was found.

  • pH Response of Silicon Nanowire Sensors: Impact of Nanowire Width and Gate Oxide
    K. Bedner, V. A. Guzenko, A. Tarasov, M. Wipf, L. Stoop, D. Just, S. Rigante, W. Fu, R. A. Minamisawa, C. David, M. Calame, J. Gobrecht, and C. Schönenberger.
    Sensors and Materials, 25(8):567, 2013.

  • [DOI] High mobility graphene ion-sensitive field-effect transistors by noncovalent functionalization
    W. Fu, C. Nef, A. Tarasov, M. Wipf, R. Stoop, O. Knopfmacher, M. Weiss, M. Calame, and C. Schönenberger.
    Nanoscale, 5( ):12104, 2013.
    [arXiv: ] [Abstract]

    Noncovalent functionalization is a well-known nondestructive process for property engineering of carbon nanostructures, including carbon nanotubes and graphene. However, it is not clear to what extend the extraordinary electrical properties of these carbon materials can be preserved during the process. Here, we demonstrated that noncovalent functionalization can indeed delivery graphene field-effect transistors (FET) with fully preserved mobility. In addition, these high-mobility graphene transistors can serve as a promising platform for biochemical sensing applications.

  • Silicon Nanowire Ion-Sensitive Field-Effect Transistor Array Integrated with a CMOS-based Readout Chip
    P. Livi, M. Wipf, A. Tarasov, R. Stoop, K. Bedner, J. Rothe, Y. Chen, A. Stettler, C. Schönenberger, and A. Hierlemann.
    Proc. Of IEEE Transducers, Barcelona, SPAIN, 16-20 June 2013, ( ):1751-1754, 2013.

  • Selective Sodium Sensing with Gold-Coated Silicon Nanowire Field-Effect Transistors in a Differential Setup
    M. Wipf, R. L. Stoop, A. Tarasov, K. Bedner, W. Fu, I. A. Wright, C. J. Martin, E. C. Constable, M. Calame, and C. Schönenberger.
    ACS Nano, 7(7):5978-5983, 2013.

  • pH Response of Silicon Nano\-wire Sensors: Impact of Nano\-wire Width and Gate Oxide
    K. Bedner, V. A. Guzenko, A. Tarasov, M. Wipf, R. L. Stoop, D. Just, S. Rigante, W. Fu, R. A. Minamisawa, C. David, M. Calame, J. Gobrecht, and C. Schönenberger.
    Sensors and Materials, 25(8):567-576, 05 2013.

    We present a systematic study of the performance of silicon nanowires (SiNWs) with different widths when they are used as ion-sensitive field-effect transistors (ISFETs) in pH-sensing experiments. The SiNW widths ranged from 100 nm to 1 micrometer. The SiNW-ISFETs were successfully fabricated from silicon-on-insulator (SOI) wafers with Al2O3 or HfO2 as gate dielectric. All the SiNWs showed a pH Response close to the Nernstian limit of 59.5 mV/pH at 300 K, independent of their width, or the investigated gate dielectric or operating mode. Even nanowires (NWs) in the 100 nm range operated reliably without degradation of their functionality. This result is of importance for a broad research field using SiNW sensors as a candidate for future applications.

  • A Verilog-A Model for Silicon Nanowire Biosensors: From Theory to Verification
    P. Livi, K. Bedner, A. Tarasov, Mathias Wipf, Y. Chen, C. Schönenberger, and A. Hierlemann.
    Sensors and Actuators B, 186(doi:10.1016/j.snb.2012.09.026):789-795, Dec. 2012.

    Silicon nanowires offer great potential as highly sensitive biosensors. Since the signals they produce are quite weak and noisy, the use of integrated circuits is preferable to read out and digitize these signals as quickly as possible following the sensing event to take full advantage of the properties of the nanowires. In order to design optimized and tailored circuits, simulations involving the sensor itself in the design phase are needed. We propose here a Verilog-A model for silicon nanowire-based biosensors. The model can easily be applied using commercially available Electronic Design Automation (EDA) tools that are commonly used for integrated circuit design and simulations. The model is quite general and comprehensive; it can be used to simulate different types of sensing events, while still being quite simple and undemanding in terms of computational power. The model is described in detail and verified with measurements from two different nanowire sensors featuring aluminum-oxide and hafnium-oxide coatings. Good agreement has been achieved in all cases, with errors never exceeding 21 percent. The complete Verilog-A code is made available in the Appendix.

  • Silicon-Based Ion-Sensitive Field-Effect Transistor Shows Negligible Dependence on Salt Concentration at Constant pH
    O. Knopfmacher, A. Tarasov, M. Wipf, W. Fu, M. Calame, and C. Schönenberger.
    ChemPhysChem, 6( ):9291-9298, Sept. 2012.

  • Understanding the Electrolyte Background for Biochemical Sensing with Ion-Sensitive Field-Effect Transistors
    A. Tarasov, M. Wipf, R. L. Stoop, K. Bedner, W. Fu, V. A. Guzenko, O. Knopfmacher, M. Calame, and C. Schönenberger.
    ACS Nano, 6( ):9291-9298, Sept. 2012.

    Silicon nanowire field-effect transistors have attracted substantial interest for various biochemical sensing applications, yet there remains uncertainty concerning their response to changes in the supporting electrolyte concentration. In this study, we use silicon nanowires coated with highly pH-sensitive hafnium oxide (HfO2) and aluminum oxide (Al2O3) to determine their response to variations in KCl concentration at several constant pH values. We observe a nonlinear sensor response as a function of ionic strength, which is independent of the pH value. Our results suggest that the signal is caused by the adsorption of anions (Cl-) rather than cations (K+) on both oxide surfaces. By comparing the data to three well established models, we have found that none of those can explain the present data set. Finally, we propose a new model which gives excellent quantitative agreement with the data.

  • Sensing with liquid-gated graphene field-effect transistors
    W. Fu, C. Nef, A. Tarasov, M. Wipf, R. Stoop, O. Knopfmacher, M. Weiss, M. Calame, and C. Schönenberger.
    Proceedings of the IEEE conference on nanotechnology (IEEE-NANO), ( ): , Aug. 2012.

    Liquid-gated graphene field-effect transistors (GFETs) with reliable performance are developed. It is revealed that ideal defect-free graphene should be inert to electrolyte composition changes in solution, whereas a defective one responses to electrolyte composition. This finding sheds light on the large variety of pH or ion-induced gate shifts that have been published for GFETs in the recent literature. As a next step to target graphene-based (bio-) chemical sensing platform, non-covalent functionalization of graphene has to be introduced.

  • True Reference Nanosensor Realized with Silicon Nanowires
    A. Tarasov, M. Wipf, K. Bedner, J. Kurz, W. Fu, V. A. Guzenko, O. Knopfmacher, L. Stoop, M. Calame, and C. Schönenberger.
    Langmuir, 28( ):9899-9905, May 2012.

    Conventional gate oxide layers (e.g., SiO2, Al2O3, or HfO2) in silicon field-effect transistors (FETs) provide highly active surfaces, which can be exploited for electronic pH sensing. Recently, great progress has been achieved in pH sensing using compact integrateable nanowire FETs. However, it has turned out to be much harder to realize a true reference electrode, which — while sensing the electrostatic potential — does not respond to the proton concentration. In this work, we demonstrate a highly effective reference sensor, a so-called reference FET, whose proton sensitivity is suppressed by as much as 2 orders of magnitude. To do so, the Al2O3 surface of a nanowire FET was passivated with a self-assembled monolayer of silanes with a long alkyl chain. We have found that a full passivation can be achieved only after an extended period of self-assembling lasting several days at 80 degC. We use this slow process to measure the number of active proton binding sites as a function of time by a quantitative comparison of the measured nonlinear pH-sensitivities to a theoretical model (site-binding model). Furthermore, we have found that a partially passivated surface can sense small changes in the number of active binding sites reaching a detection limit of delta Ns approx 170 1/micron^2 Hz^1/2 at 10 Hz and pH 3.

  • Graphene Transistors Are Insensitive to pH Changes in Solution
    W. Fu, C. Nef, O. Knopfmacher, A. Tarasov, M. Weiss, M. Calame, and C. Schönenberger.
    Nano Letters, 11( ):3597, 2011.

  • Signal-to-noise ratio in dual-gated silicon nanotibbon field-effect sensors
    A. Tarasov, W. Fu, O. Knopfmacher, J. Brunner, M. Calame, and C. Schönenberger.
    Appl. Phys. Lett., 98( ):12114, 2011.

  • Sensitivity considerations in dual-gated Si-nanowire FET sensors
    O. Knopfmacher, A. Tarasov, W. Fu, M. Calame, and C. Schönenberger.
    European Cells and Materials, 20, Suppl. 3( ):140, November 2010.

  • The Nernst limit in dual-gated Si nanowire FET sensors
    O. Knopfmacher, A. Tarasov, Wangyang Fu, M. Wipf, B. Niesen, M. Calame, and C. Schönenberger.
    Nano Letters, 10(6):2268-2274, 2010.