A Scalable CMOS Molecular Electronics Chip for Single-Molecule Biosensing.

This work reports the first CMOS molecular electronics chip. It is configured as a biosensor, where the primary sensing element is a single molecule "molecular wire" consisting of a ∼100 GΩ, 25 nm long alpha-helical peptide integrated into a current monitoring circuit. The engineered peptide contains a central conjugation site for attachment of various probe molecules, such as DNA, proteins, enzymes, or antibodies, which program the biosensor to detect interactions with a specific target molecule. The current through the molecular wire under a dc applied voltage is monitored with millisecond temporal resolution. The detected signals are millisecond-scale, picoampere current pulses generated by each transient probe-target molecular interaction. Implemented in a 0.18 µm CMOS technology, 16k sensors are arrayed with a 20 µm pitch and read out at a 1 kHz frame rate. The resulting biosensor chip provides direct, real-time observation of the single-molecule interaction kinetics, unlike classical biosensors that measure ensemble averages of such events. This molecular electronics chip provides a platform for putting molecular biosensing "on-chip" to bring the power of semiconductor chips to diverse applications in biological research, diagnostics, sequencing, proteomics, drug discovery, and environmental monitoring.

A Neural Probe With Up to 966 Electrodes and Up to 384 Configurable Channels in 0.13 $\mu$m SOI CMOS.

In vivo recording of neural action-potential and local-field-potential signals requires the use of high-resolution penetrating probes. Several international initiatives to better understand the brain are driving technology efforts towards maximizing the number of recording sites while minimizing the neural probe dimensions. We designed and fabricated (0.13- µm SOI Al CMOS) a 384-channel configurable neural probe for large-scale in vivo recording of neural signals. Up to 966 selectable active electrodes were integrated along an implantable shank (70 µm wide, 10 mm long, 20  µm thick), achieving a crosstalk of [Formula: see text] dB. The probe base (5 × 9 mm 2 ) implements dual-band recording and a 171.6 Mbps digital interface. Measurement results show a total input-referred noise of 6.4 µ V rms and a total power consumption of 49.1  µW/channel.

Visible-to-near-infrared octave spanning supercontinuum generation in a silicon nitride waveguide.

The generation of an octave spanning supercontinuum covering 488-978 nm (at -30 dB) is demonstrated for the first time on-chip. This result is achieved by dispersion engineering a 1-cm-long Si3N4 waveguide and pumping it with an 100-fs Ti:Sapphire laser emitting at 795 nm. This work offers a bright broadband source for biophotonic applications and frequency metrology.

Single-cell recording and stimulation with a 16k micro-nail electrode array integrated on a 0.18 µm CMOS chip.

To cope with the growing needs in research towards the understanding of cellular function and network dynamics, advanced micro-electrode arrays (MEAs) based on integrated complementary metal oxide semiconductor (CMOS) circuits have been increasingly reported. Although such arrays contain a large number of sensors for recording and/or stimulation, the size of the electrodes on these chips are often larger than a typical mammalian cell. Therefore, true single-cell recording and stimulation remains challenging. Single-cell resolution can be obtained by decreasing the size of the electrodes, which inherently increases the characteristic impedance and noise. Here, we present an array of 16,384 active sensors monolithically integrated on chip, realized in 0.18 µm CMOS technology for recording and stimulation of individual cells. Successful recording of electrical activity of cardiac cells with the chip, validated with intracellular whole-cell patch clamp recordings are presented, illustrating single-cell readout capability. Further, by applying a single-electrode stimulation protocol, we could pace individual cardiac cells, demonstrating single-cell addressability. This novel electrode array could help pave the way towards solving complex interactions of mammalian cellular networks.

A novel 16k micro-nail CMOS-chip for in-vitro single-cell recording, stimulation and impedance measurements.

In neurophysiological and pharmaceutical research, parallel and individual access to a dense population of in-vitro cultured neurons is a key feature for analyzing networks of neurons. This paper presents a 0.18µm CMOS chip containing a dense array of micro-nail electrodes, a 128×128 sensor/actuator matrix with in-situ differential amplification circuits, pico-Ampere current stimulation, and impedance measurement circuits. Measurements on packaged chips show successful impedance measurements matching the simulation model and electrical recordings of in-vitro cultured cardiomyocytes, correlated with recorded changes in intra-cellular calcium concentrations. This system is a first step towards a high-throughput neuron/chip interface.

Local electrical stimulation of single adherent cells using three-dimensional electrode arrays with small interelectrode distances.

In this paper, we describe the localized and selective electrical stimulation of single cells using a three-dimensional electrode array. The chip consisted of 84 nail-like electrodes with a stimulation surface of 0.8 microm(2) and interelectrode distances as small as 3 microm. N2A cells were used to compare bipolar stimulation between one electrode in- and one outside the cell on the one hand, and two electrodes in the same cell on the other hand. Selective and localized stimulation of primary embryonic cardiomyocytes showed the possibility to use this chip with excitable cells. The response of the cells to applied electrical fields was monitored using calcium imaging whereas assessment of electroporation was determined following influx of propidium iodide. Arrays of these three-dimensional electrodes could eventually be used as a tool to selectively electroporate the membrane of single cells for genetic manipulation or to obtain electrical access to the inner compartment of the cell.