Paul P. Bey

Portable cell-based biosensor system for toxin detection

Abstract A portable cell-based biosensor has been developed and characterized. The prototype system relies on extracellular recording from excitable cells cultured over an array of platinized gold microelectrodes. Extracellular potentials were bandpass filtered between 80 Hz to 2.8 kHz and amplified with a selectable gain of either 1000 or 5000. The input-referred noise level of the system was only 8.7 μV RMS in the laboratory setting, reaching only 10.6 μV RMS in an outdoor environment, more than sufficient for measurement of extracellular potentials from excitable cells. The system also incorporates a feedback control system for temperature regulation and a 36-channel multiplexer for selection of up to four output channels for simultaneous display. Wherever possible, low-cost ‘off-the-shelf’ components were utilized in this prototype biosensor design. Using this system, extracellular recordings from chick myocardiocytes were performed under both laboratory and outdoor conditions.

Description and demonstration of a CMOS amplifier-based-system with measurement and stimulation capability for bioelectrical signal transduction

An extracellular recording system incorporating an electrode array and an amplifier/stimulator CMOS chip is described and characterized. Important features of this custom VLSI chip include 16 instrumentation amplifiers with a gain of 50 and the incorporation of a cross-point array allowing designation of an extracellular microelectrode as either a stimulator or sensor. The planar array consisted of 32 microelectrodes, 14 microns in diameter, and four larger reference electrodes. Microelectrodes, interconnecting traces, and bond pads were patterned with a 500-nm layer of gold. The interconnecting traces were passivated with a 1-micron thick layer of silicon nitride to provide chemical and electrical insulation and microelectrode impedance was lowered utilizing electrode position of platinum black. The amplifier exhibited a nearly flat frequency response with high pass and low pass corner frequencies of 0.7 Hz and 50 kHz, respectively. The input referred noise over the 50 kHz bandwidth was 12-16 microVRMS, well below the magnitude of previously reported extracellular potentials. Crosstalk between neighboring channels resulted in an output signal below the amplifier noise level, even for relatively large extracellular potentials. Using this system, extracellular recording were demonstrated yielding typical peak-to-peak biopotentials of magnitude 0.9-2.1 mV and 100-400 microV for chick cardiac myocytes and rat spinal cord neurons, respectively. The key components of this extracellular recording system can be manufactured using industry standard thin film photolithographic techniques.

Cell-based sensor microelectrode array characterized by imaging x-ray photoelectron spectroscopy, scanning electron microscopy, impedance measurements, and extracellular recordings

We are developing a cell-based biosensor consisting of a planar microelectrode array that allows detection of extracellular potentials and their modulation in the presence of toxins or other active agents. To improve cell–electrode coupling, the microelectrodes were electroplated with platinum black. We report on the use of imaging x-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), impedance measurements, and extracellular recordings to assess the effectiveness of this procedure. SEM provided highly detailed images of the shape and structure of well-formed deposits of thickness on the order of 1 μm or more. Because of its inherent high surface sensitivity, imaging XPS could reveal the presence of platinum deposits that were too thin to be detected by SEM. For typical, well-plated microelectrodes, impedance measurements showed reductions in the electrical resistance at 100 Hz from roughly 60 MΩ or more 1 MΩ. The overall electronic coupling of biopotentials to the microelectrodes wa...

A DC autonulling bridge for real-time resistance measurement

This paper describes a resistance measurement system based on a Wheatstone bridge topology that overcomes the limitations of a direct differential measurement and is suited for monolithic sensor applications. An analog feedback network provides a wide dynamic range and maximizes noise rejection by automatically driving the bridge to null via a voltage-controlled resistor. The circuit also provides transient monitoring of resistance changes in any sensor that produces a resistance change due to an environmental stimulus. The system stability is discussed and analyzed using Liapunov analysis, SPICE simulations, and a prototype circuit implemented using basic off-the-shelf components produces results similar to the theoretical analysis.

Autonulling ac bridge for accurate measurement of small impedance variations using MOS components

A self‐contained prototype of an autonulling ac bridge based on phase‐sensitive detection is discussed. The bridge nulling circuit uses an analog feedback network to establish a stable null for a wide range of resistive and capacitive values and requires minimal supporting hardware. Changes in resistance and capacitance in one arm of the bridge are compensated independently using a discrete voltage‐variable resistor and capacitor in the alternate arm for nulling. The feedback voltage to the discrete control elements can be used to transduce signals from pressure, temperature, or chemical sensors. This bridge is especially well suited for microfabrication and is readily compatible with silicon‐based sensors. It offers high noise rejection due to the phase‐sensitive measurement taken differentially across the bridge nodes. State‐space analysis is used to demonstrate the stability of this feedback network design.

Stability analysis of an autonulling AC bridge for use with silicon-based sensors

A novel circuit incorporating integral feedback to automatically null an AC bridge is analyzed and discussed. Stability of the feedback scheme is examined by linearizing the system near the critical point (null) of the bridge using a standard perturbation method. Solutions of the nonlinear coupled differential equations that describe the operation of the autonulling AC bridge were obtained by numerical integration. A prototype was constructed using integrated circuits and discrete components to measure the transient response; test results of the circuit from transient impedance changes are compared to the time-dependent numerical solutions. >

Optical Film Thickness Monitoring

Experiments and theoretical calculations are carried out to determine the accuracy attainable by intensity modulation and wavelength modulation optical monitoring techniques used to specify film thickness. Experimental results show that film thickness errors of 5% are typical in deposition thickness monitoring based on intensity modulation techniques. It is demonstrated by calculation that an appreciable improvement of film thickness accuracy can be obtained by wavelength modulation techniques, and that variable wavelength dielectric filters may conveniently be used as spectral filters for wavelength modulation devices to provide a film thickness accuracy between 0.5 and 1%. Results obtained may be used for the design of optical thickness monitoring systems.

Demonstration of Gray Scale in Electroclinic Liquid Crystals

Liquid crystal (LC) materials possessing the chiral smectic A phase have been designed to yield high induced tilt angels and low response times. The primary objective of our work is to design materials that can provide the optimum tilt angle of 22.5 degrees for applied voltages less than 5V/micrometers , making them CMOS compatible Optical response measurement to illustrate the feasibility of obtaining 256 gray levels are presented. The gray scale capability of the material is visually demonstrated using a 1 X 64 array driven by a dc balanced circuit.

WAVE MEASUREMENTS IN OPEN OCEAN

A significant portion of the damage by hurricanes is the storm surges. The National Weather Service has developed a dynamical-numerical model to forecast hurricane storm surges. The model is used operationally for prediction, warning, and planning purposes. The model requires fixed oceanographic and real time meteorological input data. The oceanographic data were prepared for the Gulf and East coasts of the U.S. and are stored as an essential part of the program. Meteorological data for any tropical storm are supplied by the forecasters or planners using the model. The model was applied to hurricane Camille 1969. Comparison between the observed and computed surges for Camille was satisfactory for prediction purposes.The main consideration in harbor master planning is to maximize the amount of time that the harbor can be used. The potential level of harbor utilization can be evaluated by analyzing vessel performance during harbor operations in terms of the range of imposed environmental conditions. The harbor utilization level is expressed statistically as the probable amount of time that the harbor can be used as planned.The design and construction of a major ocean outfall and diffuser system for disposal of wastewater effluents is a complex process involving an interplay of requirements originating from various disciplines. These include, among others, considerations of physical oceanography, mixing and dispersion, treatment processes, regulatory requirements, marine geology, economics and construction. The recently completed Sand Island Outfall and the newly designed Barbers Point Outfall are both on the southern coast of the island of Oahu, Hawaii, and are designed for treated sewage effluents from the densely populated portion of the City and County of Honolulu. In this paper, some design considerations of these outfalls will be examined. The emphasis in this paper is on the hydrodynamics, although other design aspects are also discussed briefly.The height of dikes and other coastal structures can only be calculated after determination of the wave run-up. Several formulas for the calculation of wave run-up are developed after model tests as a rule. But the influences of scale effects and natural wind conditions are practically unknown. To clear these questions further investigations and especially field measurements should be carried out. By measuring the markerline of floating trash on the slope of the seadikes the maximum wave run-up could be found out after four storm surges in 1967 and 1973In two graphs it will be shown that on the tidal flats the run-up depends on the waterdepth. The run-up was higher than it could be expected after model tests of 1954. With a newly developed special echo sounder the run-up could be measured in January 1976. The waves and the run-up could be registrated synchronously during two severe storm surges. As shown in Fig. 9 it was found a logarithmic distribution of the wave height, wave period and the higher part of the wave run-up. The found wave run-up is considerably higher than estimated before. The measured 98 % run-up is found about twice the computed value. That is an interesting and important result of the first synchronous recording of wave run-up on sea dikes.In March 1972 the authors firm in association with two Portuguese firms of consulting engineers, Consulmar and Lusotecna, were appointed by the Portuguese Government agency Gabinete da Area de Sines to prepare designs for the construction of a new harbour at Sines on the west coast of Portugal. The location is shown in Figure 1. The main breakwater, which is the subject of this paper, is probably the largest breakwater yet built, being 2 km long and in depths of water of up to 50 m. It is exposed to the North Atlantic and has been designed for a significant wave height of 11 m. Dolos units invented by Merrifield (ref. 1) form the main armour. The project programme required that studies be first made of a wide range of alternative layouts for the harbour. After the client had decided on the layout to be adopted, documents were to be prepared to enable tenders for construction to be invited in January 1973. This allowed little time for the design to be developed and only one series of flume tests, using regular waves, was completed during this period. Further tests in the regular flume were completed during the tender period and a thorough programme of testing with irregular waves was commenced later in the year, continuing until August 1974 when the root of the breakwater was complete and the construction of the main cross-section was about to start. The model tests, which were carried out at the Laboratorio Nacional de Engenharia Civil in Lisbon, were reported by Morals in a paper presented to the 14th International Coastal Engineering Conference in 1974. (ref. 2)Estuaries may be sequentially classified into highly stratified, moderately mixed and vertically homogeneous. An important difference between moderately stratified or vertically homogeneous estuaries, and highly stratified estuaries (salt wedges) is that, in the former, tidal currents are sufficient to cause turbulent mixing of fresh water and sea water over the full depth of the estuary. In the latter, a distinct interface or interfacial layer exists which separates the two nearly homogeneous layers. The vertical advectlon of salt in this two-layer flow is the dominant process in maintaining the salt balance. This paper presents an analytical model describing this process. Experiments have been conducted in the laboratory to compare with the developed theory.