Daniel Rairigh

On-Chip Electrochemical Impedance Spectroscopy for Biosensor Arrays

Electrochemical impedance spectroscopy (EIS) is a powerful tool for characterizing biological materials, including lipid bilayers and many membrane proteins. However, traditional EIS methods are very slow at low frequencies, where these materials respond in biosensor applications. To enable dense arrays of biosensors based on tethered bilayer lipid membranes (tBLM), a new approach for EIS has been developed. This paper introduces a methodology and circuit that can rapidly perform EIS in the 1 mHz to 100 kHz frequency range. A circuit implementing this new approach has been realized in 0.5 mum CMOS technology with 3.3 voltage power supply. In the sub-hertz range where membrane protein biosensor response is most critical, the circuit can measure impedance with 8 bit resolution in 20 ms, three orders of magnitude faster than traditional integrator-based circuits. Though tailored for the low frequency spectrum in biosensor applications, the EIS circuit can be used to measure impedance in a wide range of sensory materials.

Sinusoid signal generator for on-chip impedance spectroscopy

Compact signal generators are a necessary component for many biomedical and chemical sensor microsystems. This paper presents a signal generator with precise digital frequency control that is 62% smaller the previous designs. The signal generator can produce analog sine waves and digital cosine waves from 4.8 Hz to 39 kHz with a SFDR greater than 99 dB. In a 0.5 µm CMOS process the total signal generator area is 361µm × 1048µm.

Fully Integrated Impedance Spectroscopy Systems for Biochemical Sensor Array

With rapid progress in the miniaturization of biosensors, array microsystems utilizing impedance spectroscopy (IS) are of emerging interest. Focused on the electronics portion of such IS microsystems, this paper analyzes FFT-based and frequency response analyzer (FRA)-based approaches and compares them for hardware efficiency in array applications. For the chosen FRA-based approach, two possible systems are described and their circuit-level realizations are presented, one targeting high accuracy applications and the other prioritizing rapid interrogation.

CMOS Baseline Tracking and Cancellation Instrumentation for Nanoparticle-Coated Chemiresistors

Chemiresistor (CR) sensors and sensor arrays coated with thiolate-monolayer-protected gold nanoparticle (MPN) interfaces show great promise as detectors in gas-chromatographic microsystems with applications in biomedical and environmental analysis including breath biomarkers of disease. This paper describes a new readout circuit that overcomes the wide range of baseline resistances and drift in baseline values inherent to MPN-coated CRs to achieve a 57 ppm readout resolution. The 0.5-mum CMOS circuit operates at 5 V and provides a response resolution of 74 muV. It can cancel baseline voltages from 0.3 to 4.3 V with an accuracy of 4.2 mV and can track and compensate for drifts up to 30 mV/min. Performance was verified with MPN-coated CRs, where drift was measured and effectively cancelled. The circuit topology and size support an on-chip MPN-coated CR sensor array.

CMOS Monolithic Nanoparticle-Coated Chemiresistor Array for Micro-Scale Gas Chromatography

Miniaturized detector arrays are critical to reducing size and maintaining measurement quality of integrated micro-gas chromatographs (μGC) used for the analysis of complex vapor mixtures. This paper presents an array of chemiresistors (CRs) with monolayer-protected gold nanoparticle films formed on the surface of a complementary-metal-oxide semiconductor (CMOS) readout chip, featuring high-resolution resistance measurement with adaptive cancellation of baseline resistance. The 8-channel readout circuit occupies 2.2 × 2.2 mm2 in 0.5 μm CMOS and consumes 66 μW per channel from a 3.3-V power supply. It achieves a worst-case resolution of 125 ppm over a broad baseline resistance range of 60 kΩ to 10 MΩ, equivalent to 122 dB dynamic range. Implementation of the CMOS monolithic detector array is discussed, and preliminary measurement results using chamber exposures to several vapors are presented. Eventual integration into a μGC is discussed.

A fully integrated multi-channel impedance extraction circuit for biosensor arrays

Impedance spectroscopy (IS) is a powerful tool for characterizing materials that exhibit a frequency dependent behavior to an applied electric field. This paper introduces a fully integrated multi-channel impedance extraction circuit that can both generate AC stimulus signals over a broad frequency range and also measure and digitize the real and imaginary components of the impedance response. The circuit was fabricated in 0.5μm CMOS and consumes 355μW at 3.3V. Tailored for protein and lipid bilayer characterization, the signal generator produces sinusoidal waves from 1Hz to 10kHz. To suit a variety of applications, the impedance extraction circuit provides a programmable current measurement range from~100pA to 100nA with a measured resolution of ~100fA. Occupying only 0.045mm2 per measurement channel, the circuit is compact enough to include nearly 100 channels and the signal generator on 3 × 3mm die.

Baseline resistance cancellation circuit for high resolution thiolate-monolayer-protected gold nanoparticle vapor sensor arrays

Chemiresistive (CR) sensors and sensor arrays coated with thiolate-monolayer-protected gold nanoparticle (MPN) interfaces show great promise for high-sensitivity multi-vapor analysis but suffer from process variation and drift in baseline values. This paper describes a new readout circuit that cancels baseline resistance and compensates for baseline drift to achieve ppm resolution. Requiring only 5100 mum in a 0.5 mum CMOS process, the circuit is well suited for high density on-chip CR sensor arrays. The resulting CR array microsystem introduces a valuable tool for monitoring environmental hazards including explosive compounds.

Impedance-to-digital converter for sensor array microsystems

Many emerging micro/nano sensor interfaces suitable for microsystem integration produce a change of impedance that must be monitored over a broad frequency range. This paper introduces a mixed-signal integrated circuit that can extract and digitize the real and imaginary components of a sensors impedance response. The ultra compact size of this circuit enables each element in a multi-channel sensor array microsystem to have its own individual readout channel, permitting simultaneous readout and digitization of a high density sensor array. The circuit was fabricated in 0.5µm CMOS and occupies only 0.045mm2 per cell. With a 3.3V supply, each cell consumes only 5.2µW at a typical 200kHZ sampling frequency. For a 3mm by 3mm die, this circuit can be instantiated well over 100 times, which is sufficient for the needs of many anticipated sensor array microsystems.

125ppm resolution and 120dB dynamic range nanoparticle chemiresistor array readout circuit

Nanoparticle coated chemiresistor (CR) arrays enable highly sensitive vapor detection in systems such as a micro gas chromatograph or an electronic nose. However, they suffer shortcomings such as a small response compared to a large baseline value, large baseline variation across devices, and significant baseline drift over time. This paper describes a new high-resolution CR array readout circuit with adaptive baseline control. The 8-channel readout circuit occupies 2.2mm × 2.2mm in 0.5µm CMOS technology, consuming 66µW per channel from a 3.3V power supply. It achieves a worst-case resolution of 125ppm over a baseline resistance of 60kΩ to 10MΩ, equivalent to 120dB dynamic range.

Rapid impedance measurement of tethered bilayer lipid membrane biosensors

Tethered bilayer lipid membranes (tBLM) offer a promising means to immobilize membrane proteins for sensor applications and study biological phenomena including membrane-nanoparticle interactions. tBLM biointerfaces are typically characterized using electrochemical impedance spectroscopy (EIS) in the 1mHz to 1Hz range due to interface parasitics. To enable rapid characterization of biointerfaces for high throughput applications, this paper introduces a method for high resolution EIS characterization of tBLMs at higher frequencies. The tBLM equivalent electrical model is analyzed, and the benefit of extracting the real portion of interface admittance is described. Mathematical analysis shows that the maximum frequency for measuring membrane resistance is a function of membrane characteristics and that small area membranes could enable measurement well into the kHz range, permitting observation of millisecond membrane protein activity in biosensor arrays.