W. Franks

Impedance characterization and modeling of electrodes for biomedical applications

A low electrode-electrolyte impedance interface is critical in the design of electrodes for biomedical applications. To design low-impedance interfaces a complete understanding of the physical processes contributing to the impedance is required. In this work a model describing these physical processes is validated and extended to quantify the effect of organic coatings and incubation time. Electrochemical impedance spectroscopy has been used to electrically characterize the interface for various electrode materials: platinum, platinum black, and titanium nitride; and varying electrode sizes: 1 cm/sup 2/, and 900 /spl mu/m/sup 2/. An equivalent circuit model comprising an interface capacitance, shunted by a charge transfer resistance, in series with the solution resistance has been fitted to the experimental results. Theoretical equations have been used to calculate the interface capacitance impedance and the solution resistance, yielding results that correspond well with the fitted parameter values, thereby confirming the validity of the equations. The effect of incubation time, and two organic cell-adhesion promoting coatings, poly-L-lysine and laminin, on the interface impedance has been quantified using the model. This demonstrates the benefits of using this model in developing a better understanding of the physical processes occurring at the interface in more complex, biomedically relevant situations.

CMOS microelectrode array for bidirectional interaction with neuronal networks

A CMOS metal-electrode-based micro system for bidirectional communication (stimulation and recording) with neuronal cells in vitro is presented. The chip overcomes the interconnect challenge that limits todays bidirectional microelectrode arrays. The microsystem has been fabricated in an industrial CMOS technology with several post-CMOS processing steps to realize 128 biocompatible electrodes and to ensure chip stability in physiological saline. The system comprises all necessary control circuitry and on-chip A/D and D/A conversion. A modular design has been implemented, where individual stimulation- and signal-conditioning circuitry units are associated with each electrode. Stimulation signals with a resolution of 8 bits can be sent to any subset of electrodes at a rate of 60 kHz, while all electrodes of the chip are continuously sampled at a rate of 20 kHz. The circuitry at each electrode can be individually reset to its operating point in order to suppress artifacts evoked by the stimulation pulses. Biological measurements from cultured neuronal networks originating from dissociated cortical tissue of fertilized chicken eggs with amplitudes of up to 500 muVpp are presented

CMOS monolithic microelectrode array for stimulation and recording of natural neural networks

An array of platinum electrodes has been integrated with analog and digital circuitry in standard CMOS technology for stimulation and recording of natural neural networks. The array utilizes a shifted electrode design that has been electrically characterized and modeled. The electrode and its circuitry form a repeatable unit, which can be multiplied to achieve a larger array. Each circuitry unit contains a buffer for stimulation and a bandpass filter for readout. In contrast to traditional electrode arrays used for measuring action potentials, this device is capable of on-chip signal filtering, improving the signal to noise ratio (SNR), on-chip analog to digital conversation (preventing further signal degradation), and simultaneous recording and stimulation.

Nanochemical surface analyzer in CMOS technology.

We have developed an atomic force microscopy (AFM) cantilever system, fabricated using a standard CMOS process and a few post-processing steps, capable of detecting the difference between hydrophilic and hydrophobic samples for the purpose of nanochemical surface analysis. The fully integrated cantilever comprises a thermal actuator for cantilever deflection and a Wheatstone bridge to sense cantilever bending, thus obviating the need for cumbersome laser detection and external piezoelectric drives. Glass microspheres have been affixed to the cantilevers and, were either modified with a self-assembled monolayer to form hydrophobic tips, or left unmodified for hydrophilic tips. Force-distance curves have been used to measure the force between the functionalized/unfunctionalized tips and hydrophobic/hydrophilic sample surfaces. In an optimization step three different Wheatstone bridge sensors have been designed and characterized; best Wheatstone bridge sensitivity is 8.0 microV/nm with a 713 nm/mW actuator efficiency.

CMOS Bidirectional Electrode Array for Electrogenic Cells

We report on a CMOS-based microelectrode-array chip (6.5 by 6.5 mm2) for bidirectional communication (stimulation and recording) with electrogenic cells such as cardiomyocytes or neurons targeted at investigating electrical signal propagation within cellular networks in vitro. The integration of on-chip circuitry, which includes analog signal amplification and filtering stages, analog-to-digital converters, a digital-to-analog converter, stimulation buffers, temperature sensors, and a digital interface for data transmission notably improves the overall system performance. Additionally, the interconnect challenge that limits the size of currently used microelectrode arrays is overcome. Measurements with cardiomyocytes and neuronal cells were successfully carried out, and the circuitry characterization evidenced a total equivalent input noise of 11.7 µ VRMS(0.1 Hz -100 kHz) at a gain of 1,000.

CMOS microelectrode array for extracellular stimulation and recording of electrogenic cells

An extra cellular monolithic recording system fabricated in an industrial CMOS-technology combined with post-CMOS processing is presented. The chip comprises 16 platinum electrodes each equipped with stimulation and signal-conditioning circuitry. The micro-electrode array (MEA) is realized in a shifted-electrode design where the passivation is a 1.6 /spl mu/m stack of alternating Si/sub 3/N/sub 4/ and SiO/sub 2/ required for effective chip protection. The electrode and its adjacent circuitry (which includes a stimulation buffer and a readout band-pass filter) form a modular unit that is repeated in a 4 by 4 structure. Simultaneous recording and stimulation is possible at all electrodes at any time throughout the measurement. The system architecture includes multiplexers and A/D converters for each row and a digital control unit that scans the array and provides a digital interface with the outside world.

CMOS biosensor with guided cell growth

Bioelectronic devices for the investigation of electrogenic cells either comprise advanced system architectures (K. Gilchrist et al., Biosens. & Bioelects., vol. 16, pp. 557-564, 2001) or patterned structures for guided cell growth (S. Rohr et al., Pflugers Arch., vol. 446, pp. 125-32, 2003). Here we present an approach to combine a CMOS biosensor with sophisticated surface patterning for guided cell growth. The CMOS biosensor comprises a 128-electrode array, with on-chip stimulation and recording capabilities. An engineered surface for high-contrast protein adsorption and cell attachment has been developed. Surface functionalization is based on selective molecular assembly patterning (SMAP) (R. Michel et al., Langmuir, vol. 18, pp. 3281-3287, 2002) thus obviating the need for additional lithographic steps. An amine-terminated self-assembled monolayer is used for cell adhesion at each electrode site. A protein-repellent grafted copolymer, poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG), is used to render the surrounding silicon oxide resistant to protein adsorption.