Federico Pittino

Real-time imaging of microparticles and living cells with CMOS nanocapacitor arrays

Platforms that offer massively parallel, label-free biosensing can, in principle, be created by combining all-electrical detection with low-cost integrated circuits. Examples include field-effect transistor arrays, which are used for mapping neuronal signals and sequencing DNA. Despite these successes, however, bioelectronics has so far failed to deliver a broadly applicable biosensing platform. This is due, in part, to the fact that d.c. or low-frequency signals cannot be used to probe beyond the electrical double layer formed by screening salt ions, which means that under physiological conditions the sensing of a target analyte located even a short distance from the sensor (∼1 nm) is severely hampered. Here, we show that high-frequency impedance spectroscopy can be used to detect and image microparticles and living cells under physiological salt conditions. Our assay employs a large-scale, high-density array of nanoelectrodes integrated with CMOS electronics on a single chip and the sensor response depends on the electrical properties of the analyte, allowing impedance-based fingerprinting. With our platform, we image the dynamic attachment and micromotion of BEAS, THP1 and MCF7 cancer cell lines in real time at submicrometre resolution in growth medium, demonstrating the potential of the platform for label/tracer-free high-throughput screening of anti-tumour drug candidates.

A TCAD-Based Methodology to Model the Site-Binding Charge at ISFET/Electrolyte Interfaces

We propose a new approach to describe in commercial TCAD the chemical reactions that occur at dielectric/electrolyte interface and make the ion sensitive FET (ISFET) sensitive to pH. The accuracy of the proposed method is successfully verified against the available experimental data. We demonstrate the usefulness of the method by performing, for the first time in a commercial TCAD environment, a full 2-D analysis of ISFET operation, and a comparison between threshold voltage and drain current differential sensitivities in the linear and saturation regimes. The method paves the way to accurate and efficient ISFET modeling with standard TCAD tools.

Numerical simulation of the position and orientation effects on the impedance response of nanoelectrode array biosensors to DNA and PNA strands

This paper investigates by simulation the response of a nanoelectrode capacitive biosensor to single and double strands of DNA/PNA and up to frequencies well above the electrolyte dielectric relaxation limit. The expected change in capacitance both for an idealized two electrodes system with 2D cylindrical symmetry and a complex nanoelectrode array, where the biomolecule is represented by a dielectric and charged rod, is calculated for different positions and orientations of the strand. DNA and PNA hybridization is also considered. The results provide indications on optimum detection conditions for admittance based DNA biosensors.

On the response of nanoelectrode capacitive biosensors to DNA and PNA strands

This paper investigates the response of a nanoelectrode based capacitive biosensor to the presence of single and double strands of DNA/PNA. The expected admittance spectrum for an idealized system with cylindrical symmetry, where the biomolecule is represented by a simple dielectric and charged rod, is calculated over a broad frequency range extending from below to above the electrolytes dielectric relaxation cut-off frequency. DNA and PNA hybridization is also considered. The results provide indications on optimum detection conditions for admittance based DNA biosensors.

Characterization and modelling of differential sensitivity of nanoribbon-based pH-sensors

We report accurate characterization, modelling and simulation of SOI nanoribbon-based pH sensors and we compare operation in air (dry) and electrolyte (wet) environments. We find remarkably different current density distributions and geometry scaling rules, but similar series resistances and active trap state densities in the two configurations. Calibrated TCAD based simulations implementing an original approach to model the site-binding charge, and in good agreement with experiments, provide the necessary insights to interpret the non trivial dependence of the threshold voltage and current sensitivity on pH.

Derivation and Numerical Verification of a Compact Analytical Model for the AC Admittance Response of Nanoelectrodes, Suitable for the Analysis and Optimization of Impedance Biosensors

This paper presents a compact analytical model for the AC response of nanoelectrode-based impedimetric biosensors to dielectric nanoparticles suspended in the electrolyte. The model highlights the functional dependence of the impedance change on the nanoparticle and the system geometrical and physical parameters. The model is carefully verified by means of 2-D simulations carried out with an ad hoc numerical solver of the Poisson-Nernst-Planck (Poisson-Drift-Diffusion) equations. The results can be useful to determine optimum detection conditions for impedimetric nanobiosensors, and to interpret experimental results.

Simulation of nano-biosensors based on conventional TCAD

We present a simple methodology to include the modeling of an electrolyte into a TCAD simulator exploiting the similarity between the transport equations for electrons and holes in semiconductors and the ones for charged ions in a solution. Applications to the simulation of pH-meters and biosensors are reported as examples.

Efficient DC and AC simulation of nanoelectrode-nanoparticle interactions in capacitive biosensors

This paper presents a case study of the interaction between nanoelectrodes and dielectric nanoparticles possibly representative of biomolecules in a simple cylindrical capacitive biosensor. The small signal admittance change due to the insertion of the biomolecule in the biosensor electrolyte is studied as a function of the position, aspect ratio and charge of the biomolecule and of the signal frequency. Results suggest clear advantages in operating the biosensor beyond the electrolyte cutoff frequency.

Improved sensitivity of nanowire Bio-FETs operated at high-frequency: A simulation study

Silicon Nanowire (SiNW) Bio-FETs emerged as promising candidates for DNA and proteins detection, but static screening severely limits the response to analytes located beyond approximately one Debye length from the surface. In this paper we investigate for the first time the potential advantages of the small signal response of SiNW Bio-FETs in wet environment and up to frequency above the electrolytes dielectric relaxation cut-off frequency by means of three-dimensional simulations calibrated on experiments. We find that the static Debye screening limit is overcome at high frequency, where the change in capacitance due to the analyte binding is weakly sensitive on distance from electrode, salt concentration and hardly controllable surface charges.

A technique to model the AC response of diffuse layers at electrode/electrolyte interfaces and to efficiently simulate impedimetric biosensor arrays for many analyte configurations

We describe a technique to overcome the numerical difficulties in the accurate description of the small signal AC response of the thin electrical double layers at the surface of impedimetric biosensor electrodes. The technique significantly reduces the computational burden of the calculation, thus enabling the fast simulation of many analyte configurations.