A compact microelectrode array chip with multiple measuring sites for electrochemical applications

In this paper we demonstrate the fabrication and electrochemical characterization of a microchip with 12 identical but individually addressable electrochemical measuring sites, each consisting of a set of interdigitated electrodes acting as a working electrode as well as two circular electrodes functioning as a counter and reference electrode in close proximity. The electrodes are made of gold on a silicon oxide substrate and are passivated by a silicon nitride membrane. A method for avoiding the creation of high edges at the electrodes (known as lift-off ears) is presented. The microchip design is highly symmetric to accommodate easy electronic integration and provides space for microfluidic inlets and outlets for integrated custom-made microfluidic systems on top

Design and Implementation of an Integrated Biosensor Platform for Lab-on-a-Chip Diabetic Care Systems

Recent advances in semiconductor processing and microfabrication techniques allow the implementation of complex microstructures in a single platform or lab on chip. These devices require fewer samples, allow lightweight implementation, and offer high sensitivities. However, the use of these microstructures place stringent performance constraints on sensor readout architecture. In glucose sensing for diabetic patients, portable handheld devices are common, and have demonstrated significant performance improvement over the last decade. Fluctuations in glucose levels with patient physiological conditions are highly unpredictable and glucose monitors often require complex control algorithms along with dynamic physiological data. Recent research has focused on long term implantation of the sensor system. Glucose sensors combined with sensor readout, insulin bolus control algorithm, and insulin infusion devices can function as an artificial pancreas. However, challenges remain in integrated glucose sensing which include degradation of electrode sensitivity at the microscale, integration of the electrodes with low power low noise readout electronics, and correlation of fluctuations in glucose levels with other physiological data. This work develops 1) a low power and compact glucose monitoring system and 2) a low power single chip solution for real time physiological feedback in an artificial pancreas system. First, glucose sensor sensitivity and robustness is improved using robust vertically aligned carbon nanofiber (VACNF) microelectrodes. Electrode architectures have been optimized, modeled and verified with physiologically relevant glucose levels. Second, novel potentiostat topologies based on a difference-differential common gate input pair transimpedance amplifier and low-power voltage controlled oscillators have been proposed, mathematically modeled and implemented in a 0.18μm [micrometer] complementary metal oxide semiconductor (CMOS) process. Potentiostat circuits are widely used as the readout electronics in enzymatic electrochemical sensors. The integrated potentiostat with VACNF microelectrodes achieves competitive performance at low power and requires reduced chip space. Third, a low power instrumentation solution consisting of a programmable charge amplifier, an analog feature extractor and a control algorithm has been proposed and implemented to enable continuous physiological data extraction of bowel sounds using a single chip. Abdominal sounds can aid correlation of meal events to glucose levels. The developed integrated sensing systems represent a significant advancement in artificial pancreas systems

Distributed environmental monitoring

With increasingly ubiquitous use of web-based technologies in society today, autonomous sensor networks represent the future in large-scale information acquisition for applications ranging from environmental monitoring to in vivo sensing. This chapter presents a range of on-going projects with an emphasis on environmental sensing; relevant literature pertaining to sensor networks is reviewed, validated sensing applications are described and the contribution of high-resolution temporal data to better decision-making is discussed

Spatiotemporal Electrochemical Sensing in a Smart Contact Lens

An electrochemical smart contact lens (ESCL) capable of real-speed spatiotemporal electrochemical sensing across the surface of the eye is demonstrated. Four microelectrode arrays, each comprising 33 gold microdiscs of 30 μm diameter, and a distributed common gold counter electrode, are integrated into a soft smart contact lens platform based on polyimide and thermoplastic polyurethane. Using a novel fast-switching chronoamperometric method, an electrochemical ‘video’ of concentration variation in a model eye under flow conditions is produced, in which the introduction, progress, mixing and drainage of fluid of varying concentration can be observed. The device builds on previous work towards a platform suitable for clinical use and has proven to be robust under expected use conditions, with sensing performance remaining unchanged after thermoforming and repeated mechanical deformation. This work represents a significant step forward in ESCL design, and constitutes sig- nificant progress towards a technology with real clinical utility

Monitoring single heart cell biology using lab-on-a- chip technologies

Abstract There has been considerable interest in developing microsensors integrated within lab-on-a-chip structures for the analysis of single cells; however, substantially less work has focused on developing "active" assays, where the cell‘s metabolic and physiological function is itself controlled on-chip. The heart attack is considered the largest cause of mortality and morbidity in the western world. Dynamic information during metabolism from a single heart cell is difficult to obtain. There is a demand for the development of a robust and sensitive analytical system that will enable us to study dynamic metabolism at single-cell level to provide intracellular information on a single-cell scale in different metabolic conditions (such as healthy or simulated unhealthy conditions). The system would also provide medics and clinicians with a better understanding of heart disease, and even help to find new therapeutic compounds. Towards this objective, we have developed a novel platform based on five individually addressable microelectrodes, fully integrated within a microfluidic system, where the cell is electrically stimulated at pre-determined rates and real-time ionic and metabolic fluxes from active, beating single heart cells are measured. The device is comprised of one pair of pacing microelectrodes, used for field-stimulation of the cell, and three other microelectrodes, configured as an enzyme-modified lactate microbiosensor, used to measure the amounts of lactate produced by the heart cell. The device also enables simultaneous in-situ microscopy, allowing optical measurements of single-cell contractility and fluorescence measurements of extracellular pH and cellular Ca2+ from the single beating heart cell at the same time, providing details of its electrical and metabolic state. Further, we have developed a robust microfluidic array, wherein a sensor array is integrated within an array of polydimethylsiloxane (PDMS) chambers, enabling the efficient manipulation of single heart cells and real-time analysis without the need to regenerate either working electrodes or reference electrodes fouled by any extracellular constituents. This sensor array also enables simultaneous electrochemical and optical measurements of single heart cells by integrating an enzyme-immobilized microsensor. Using this device, the fluorescence measurements of intracellular pH were obtained from a single beating heart cell whose electrical and metabolic states were controlled. The mechanism of released intracellular [H+] was investigated to examine extracellular pH change during contraction. In an attempt to measure lactate released from the electrically stimulated contracting cell, the cause of intracellular pH change is discussed. The preliminary investigation was made on the underlying relationship between intracellular pH and lactate from single heart cells in controlled metabolic states

Modified-Electrodes for Redox-Magnetohydrodynamic (MHD) Pumping for Microfluidic Applications

A new microfluidic pumping and stirring technique was demonstrated for lab-on-a-chip applications. Microfluidics was accomplished via redox-MHD, which takes advantage of a body force (FB) that is generated when there is a net movement of ions in solution (j) in the presence of a perpendicular magnetic field (B), according to the equation FB = j×B. In this work the movement of ions in solution was generated using electrodes modified with the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) rather than a redox species in solution, which can interfere with analyte detection and with biological species. The monomer solution and electrochemical method used for electrodeposition has a profound effect on the morphology and the electrochemical behavior of the film. These conditions were investigated to improve the properties of the PEDOT film for redox-MHD applications, such as coulombic capacity, current response, and electrochemical stability. PEDOT-modified microband electrodes were shown to be effective for microfluidic pumping applications, exhibiting a fairly flat flow across a 5600 μm gap. PEDOT-modified concentric ring-disk electrodes demonstrated a rotational fluid flow with nonuniform velocity between the disk and ring electrodes. This created a spiraling fluid flow that could be useful for stirring applications. PEDOT-modified electrodes were shown to be capable of initially high currents, and therefore velocities (up to 980 μm s-1 at microband electrodes during an applied potential experiment), until the film was exhausted, limiting the time scale of pumping. This limitation was solved by taking advantage of the reversible nature of PEDOT. The bias of the PEDOT-modified electrodes was switched by applying a sinusoidal potential waveform while a synchronized potential waveform was driving an electromagnet under the chip, creating an AC magnetic field. This generated continuous fluid flow in a single direction. AC redox-MHD pumping was demonstrated at PEDOT-modified microband electrodes (115 μm s-1) and at concentric ring-disk electrodes (\u3c268 μm s-1) for pumping and stirring applications respectively

Development and modelling of a versatile active micro-electrode array for high density in-vivo and in-vitro neural signal investigation

The electrophysiological observation of neurological cells has allowed much knowledge to be gathered regarding how living organisms are believed to acquire and process sensation. Although much has been learned about neurons in isolation, there is much more to be discovered in how these neurons communicate within large networks. The challenges of measuring neurological networks at the scale, density and chronic level of non invasiveness required to observe neurological processing and decision making are manifold, however methods have been suggested that have allowed small scale networks to be observed using arrays of micro-fabricated electrodes. These arrays transduce ionic perturbations local to the cell membrane in the extracellular fluid into small electrical signals within the metal that may be measured. A device was designed for optimal electrical matching to the electrode interface and maximal signal preservation of the received extracellular neural signals. Design parameters were developed from electrophysiological computer simulations and experimentally obtained empirical models of the electrode-electrolyte interface. From this information, a novel interface based signal filtering method was developed that enabled high density amplifier interface circuitry to be realised. A novel prototype monolithic active electrode was developed using CMOS microfabrication technology. The device uses the top metallization of a selected process to form the electrode substrate and compact amplification circuitry fabricated directly beneath the electrode to amplify and separate the neural signal from the baseline offsets and noise of the electrode interface. The signal is then buffered for high speed sampling and switched signal routing. Prototype 16 and 256 active electrode array with custom support circuitry is presented at the layout stage for a 20 μm diameter 100 μm pitch electrode array. Each device consumes 26.4 μW of power and contributes 4.509 μV (rms) of noise to the received signal over a controlled bandwidth of 10 Hz - 5 kHz. The research has provided a fundamental insight into the challenges of high density neural network observation, both in the passive and the active manner. The thesis concludes that power consumption is the fundamental limiting factor of high density integrated MEA circuitry; low power dissipation being crucial for the existence of the surface adhered cells under measurement. With transistor sizing, noise and signal slewing each being inversely proportional to the dc supply current and the large power requirements of desirable ancillary circuitry such as analogue-to-digital converters, a situation of compromise is approached that must be carefully considered for specific application design

Design, characterization and testing of a thin-film microelectrode array and signal conditioning microchip for high spatial resolution surface laplacian measurement.

Cardiac mapping has become an important area of research for understanding the mechanisms responsible for cardiac arrhythmias and the associated diseases. Current technologies for measuring electrical potentials on the surface of the heart are limited due to poor spatial resolution, localization issues, signal distortion due to noise, tissue damage, etc. Therefore, the purpose of this study is to design, develop, characterize and investigate a custom-made microfabricated, polyimide-based, flexible Thin-Film MicroElectrode Array (TFMEA) that is directly interfaced to an integrated Signal Conditioning Microchip (SCM) to record cardiac surface potentials on the cellular level to obtain high spatial resolution Surface Laplacian (SL) measurement. TFMEAs consisting of five fingers (Cover area = 4 mm2 and 16 mm2), which contained five individual microelectrodes placed in orthogonal directions (25-µm in diameter, 75-µm interelectrode spacing) to one another, were fabricated within a flexible polyimide substrate and capable of recording electrical activities of the heart on the order of individual cardiomyocytes. A custom designed SCM consisting of 25 channels of preamplification stages and second order band-pass filters was interfaced directly with the TFMEA in order to improve the signal-to-noise ratio (SNR) characteristics of the high spatial resolution recording data. Metrology characterization using surface profilometry and high resolution Scanning Electron Microscope (SEM) indicated the geometry of fabricated TFMEAs closely matched the design parameters \u3c 0.4%). The DC resistances of the 25 individual micro electrodes were consistent (1.050 ± 0.026 kO). The simulation and testing results of the SCM verified the pre-amplification and filter stages met the designed gain and frequency parameters within 2.96%. The functionality of the TFMEA-SCM system was further characterized on a TX 151 conductive gel. The characterization results revealed that the system functionality was sufficient for high spatial cardiac mapping. In vivo testing results clearly demonstrated feasibility of using the TFMEA-SCM system to obtain cellular level SL measurements with significantly improved the SNRs during normal sinus rhythm and Ventricular Fibrillation (VF). Local activation times were detected via evaluating the zero crossing of the SL electro grams, which coincided with the gold standard (dV/dt)min of unipolar electro grams within ± 1%. The in vivo transmembrane current densities calculated from the high spatial resolution SLs were found to be significantly higher than the transmembrane current densities computed using electrodes with higher interelectrode spacings. In conclusion, the custom-made TFMEASCM systems demonstrated feasibility as a tool for measuring cardiac potentials and to perform high resolution cardiac mapping experiments

Developing Next-generation Brain Sensing Technologies - A Review.

Advances in sensing technology raise the possibility of creating neural interfaces that can more effectively restore or repair neural function and reveal fundamental properties of neural information processing. To realize the potential of these bioelectronic devices, it is necessary to understand the capabilities of emerging technologies and identify the best strategies to translate these technologies into products and therapies that will improve the lives of patients with neurological and other disorders. Here we discuss emerging technologies for sensing brain activity, anticipated challenges for translation, and perspectives for how to best transition these technologies from academic research labs to useful products for neuroscience researchers and human patients