We describe the realization of a fully-electronic label-free temperature-controlled biosensing platform aimed to overcome the Debye screening limit over a wide range of electrolyte salt concentrations. It is based on an improved version of a 90 nm CMOS integrated circuit featuring a nanocapacitor array, readout and A/D conversion circuitry, and an FPGA-based interface board with NIOS II soft processor. We describe the chip's processing, the mounting, the microfluidics, the temperature control system, as well as the calibration and compensation procedures to reduce systematic errors, which altogether make up a complete quantitative sensor platform. Capacitance spectra recorded up to 50-70 MHz are shown and successfully compared to predictions by FEM numerical simulations in the Poisson-Drift-Diffusion formalism. They demonstrate the ability of the chip to reach high upper frequency of operation, thus overcoming the low-frequency Debye screening limit at nearly physiological salt concentrations in the electrolyte, and allowing for detection of events occurring beyond the extent of the electrical double layer. Furthermore, calibrated multi-frequency measurements enable quantitative recording of capacitance spectra, whose features can reveal new properties of the analytes. The scalability of the electrode dimensions, inter-electrode pitch and size of the array make this sensing approach of quite general applicability, even in a non-bio context (e.g. gas sensing).

We have developed a measurement platform for performing high-frequency AC detection at nanoelectrodes. The system consists of 65 536 electrodes (diameter 180 nm) arranged in a sub-micrometer rectangular array. The electrodes are actuated at frequencies up to 50 MHz, and the resulting AC current response at each separately addressable electrode is measured in real time. These capabilities are made possible by fabricating the electrodes on a complementary metal-oxide-semiconductor (CMOS) chip together with the associated control and readout electronics, thus minimizing parasitic capacitance and maximizing the signal-to-noise ratio. This combination of features offers several advantages for a broad range of experiments. First, in contrast to alternative CMOS-based electrical systems based on field-effect detection, high-frequency operation is sensitive beyond the electrical double layer and can probe entities at a range of micrometers in electrolytes with high ionic strength such as water at physiological salt concentrations. Far from being limited to single- or few-channel recordings like conventional electrochemical impedance spectroscopy, the massively parallel design of the array permits electrically imaging micrometer-scale entities with each electrode serving as a separate pixel. This allows observation of complex kinetics in heterogeneous environments, for example, the motion of living cells on the surface of the array. This imaging aspect is further strengthened by the ability to distinguish between analyte species based on the sign and magnitude of their AC response. Finally, we show here that sensitivity down to the attofarad level combined with the small electrode size permits detection of individual 28 nm diameter particles as they land on the sensor surface. Interestingly, using finite-element methods, it is also possible to calculate accurately the full three-dimensional electric field and current distributions during operation at the level of the Poisson-Nernst-Planck formalism. This makes it possible to validate the interpretation of measurements and to optimize the design of future experiments. Indeed, the complex frequency and spatial dependence of the data suggests that experiments to date have only scratched the surface of the method's capabilities. Future iterations of the hardware will take advantage of the higher frequencies, higher electrode packing densities and smaller electrode sizes made available by continuing advances in CMOS manufacturing. Combined with targeted immobilization of targets at the electrodes, we anticipate that it will soon be possible to realize complex biosensors based on spatial- and time-resolved nanoscale impedance detection.

We present the implementation of seizure detection algorithms based on a minimal number of EEG channels on a parallel ultra-low-power embedded platform. The analyses are based on the CHB-MIT dataset, and include explorations of different classification approaches (Support Vector Machines, Random Forest, Extra Trees, AdaBoost) and different pre/postprocessing techniques to maximize sensitivity while guaranteeing no false alarms. We analyze global and subject-specific approaches, considering all 23-electrodes or only 4 temporal channels. For 8 s window size and subject-specific approach, we report zero false positives and 100% sensitivity. These algorithms are parallelized and optimized for a parallel ultra-low power (PULP) platform, enabling 300h of continuous monitoring on a 300 mAh battery, in a wearable form factor and power budget. These results pave the way for the implementation of affordable, wearable, long-term epilepsy monitoring solutions with low falsepositive rates and high sensitivity, meeting both patient and caregiver requirements.

Wide-scale adoption of optoacoustic imaging in biology and medicine critically depends on availability of affordable scanners combining ease of operation with optimal imaging performance. Here we introduce LightSpeed: a low-cost real-time volumetric handheld optoacoustic imager based on a new compact software-defined ultrasound digital acquisition platform and a pulsed laser diode. It supports the simultaneous signal acquisition from up to 192 ultrasound channels and provides a hig-bandwidth direct optical link (2x 100G Ethernet) to the host-PC for ultra-high frame rate image acquisitions. We demonstrate use of the system for ultrafast (500Hz) 3D human angiography with a rapidly moving handheld probe. LightSpeed attained image quality comparable with a conventional optoacoustic imaging systems employing bulky acquisition electronics and a Q-switched pulsed laser. Our results thus pave the way towards a new generation of compact, affordable and high-performance optoacoustic scanners.

A simplified lumped geometrical and electrical model for the high-frequency impedance spectroscopy (HFIS) response of nanoelectrodes to capsids and full viruses is developed starting from atomistic descriptions, in order to test the theoretical response of a realistic HFIS CMOS biosensor platform to different viruses. Capacitance spectra are computed for plant (cowpea chlorotic mottle virus), animal (rabbit haemorrhagic disease virus), and human (hepatitis A virus) viruses. A few common features of the spectra are highlighted, and the role of virus charge, pH, and ionic strength on the expected signal is discussed. They suggest that the frequency of highest sensitivity at nearly physiological concentrations (100 mM) is within reach of existing HFIS platform designs.