23-06-2014, 02:17 PM
Microelectronic Pill
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INTRODUCTION
The invention of the transistor enabled the first radio telemetry capsules, which utilized simple circuits for in vivo telemetric studies of the gastro-intestinal tract. These units could only transmit from a single sensor channel, and were difficult to assemble due to the use of discrete components. The measurement parameters consisted of temperature, pH or pressure, and the first attempts of conducting real-time noninvasive physiological measurements suffered from poor reliability, low sensitivity, and short lifetimes of the devices. The first successful pH gut profiles were achieved in 1972, with subsequent improvements in sensitivity and lifetime. Single-channel radiotelemetrycapsules have since been applied for the detection of disease and abnormalities in the GI tract where restricted access prevents the use of traditional endoscopy.
Most radio telemetry capsules utilize laboratory type sensors such as glass pH electrodes, resistance thermometers, or moving inductive coils as pressure transducers. The relatively large size of these sensors limits the functional complexity of the pill for a given size of capsule. Adapting existing semiconductor fabrication technologies to sensor development has enabled the production of highly functional units for data collection, while the exploitation of integrated circuitry for sensor control, signal conditioning, and wireless transmission,and has extended the concept of single-channel radio telemetry to remote distributed sensing from microelectronic pills
MICROELECTRONICPILLDESIGN AND FABRICATION
ISFET
This new line of pH meters and probes, based on ISFET (Ion Sensitive Field Effect Transistor) sensor technology, includes four pH meters and 10 pH probes. The pH meters are designed for ease-of-use and feature an interactive graphics LCD display with on-board Help and Auto-Read functions. All meters constantly monitor and display probe status and an estimation of its remaining life. The advanced meters have real-time clocks for time/date stamping, calibration alerts and high/low pH alarms.Titan Bench top pH meters operate on AC or battery power and offer a host of sophisticated features, including programmable user alarms and data logging. Argus Portable meters are rugged, waterproof and operate on a long-life rechargeable battery. Each meter is available in simple or advanced versions and is supported by a variety of probes covering almost every application. The portable Argususes an inductive (contact-less) battery charging system and IR data transfer eliminating the need for battery replacement or open contact points. This design ensures a completely watertight (IP67) rating.
Three new series of ISFET probes include the Red-Line general purpose series for routine applications, the Hot-Line series for testing to 105°C and in aggressive samples, and the Stream-Line series that are temperature and chemically resistant, and employ a flow-type reference junction to maximize performance in difficult samples
pH value
pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at 25 °C (77 °F). Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline.pH measurements are in important in medicine, biology, chemistry, food science, environmental science, oceanography, civil engineering and many other applications
Sensors
The sensors were fabricated on two silicon chips located at the front end of the capsule. Chip 1 comprises the silicon diode temperature sensor, the pH ISFET sensor and a two electrode conductivity sensor. Chip 2 comprises the oxygen sensor and an optional nickel-chromium (NiCr) resistance thermometer. The silicon platform of Chip 1was based on a research product from EcoleSuperieureD’In-genieurs en Electro technique et Electroniquewith predefined n-channels in the p-type bulk silicon forming the basis for the diode and the ISFET. A total of 542 of such de-vices were batch fabricated onto a single 4-in wafer. In contrast, Chip 2was batch fabricated as a 9X9 array on a 380-m-thicksingle crystalline 3nSilicon wafer with <100>lattice orientation, precoated with 300 nm Si3N4, silicon nitride. One wafer yielded 80,5X5 mm2 sensors (the center of the wafer was used for alignment markers
Sensor Chip 1
An array of 4X2 combined temperature and pH sensor platforms were cut from the wafer and attached on to a 100-m-thick glass cover slip using S1818 photo resist cured on a hotplate. The cover slip acted as temporary carrier to assist handling of the device during the first level of lithography (Level 1) when the electric connection tracks, the electrodes and the bonding pads were defined. The pattern was defined in S1818 resist by photolithography prior to thermal evaporation of 200 nm gold (including an adhesion layer of 15 nm titanium and 15 nm palladium). An additional layer of gold (40 nm) was sputtered to improve the adhesion of the electroplated silver used in the reference electrode. Liftoff in acetone detached the chip array from the cover slip. Individual sensors were then diced prior to their re-attachment in pairs on a 100-m-thick cover slip by epoxy resin. The left-hand-side (LHS) unit comprised the diode, while the right-hand-side (RHS) unit comprised the ISFET. The15X600 m (LXW) floating gate of the ISFET was precovered with a 50-nm-thick proton sensitive layer of Si3N4 for pH detection. Photo curable polyimide de-fined the 10-nL electrolyte chamber for the pH sensor (above the gate) and the open reservoir above the conductivity sensor (Level 2).
Plasma-enhanced chemical vapor deposition (PECVD)
It is a process used to deposit thin films from a gas state (vapor) to a solid state on a substrate. Chemical reactions are involved in the process, which occur after creation of a plasma of the reacting gases. The plasma is generally created by RF (AC) frequency or DC discharge between two electrodes, the space between which is filled with the reacting gases.
Control Chip
The ASIC was a control unit that connected together the external components of the micro system. It was fabricated as a 22.5 mm2 silicon die using a 3-V, 2-poly, 3-metal 0.6-m CMOS process by Austria Microsystems (AMS) via the Euro-practice initiative. It is a novel mixed signal design that contains an analog signal conditioning module operating the sensors, an 10-bit analog-to-digital (ADC) and digital-to-analog(DAC) converters, and a digital data processing module. AnRCrelaxation oscillator (OSC) provides the clock signal.
The analog module was based on the AMS OP05B operational amplifier, which offered a combination of both a power-saving scheme (sleep mode) and a compact integrated circuitdesign. The temperature circuitry biased the diode at constantcurrent, so that a change in temperature would reflect a corresponding change in the diode voltage. The pH ISFET sensor was biased as a simple source and drain follower at constant current with the drainsource voltage changing with the threshold voltage and pH. The conductivity circuit operated at direct current measuring the resistance across the electrode pair as an inverse function of solution conductivity. An incorporated potentiostat circuit operated the amperometric oxygen sensor with a10-bit DAC controlling the working electrode potential with respect to the
MATERIAL ANDMETHODS
1 Fabrication
Thermal evaporation of silver generates a dense metal layer, with characteristics closer to bulk metal compared to porouselectroplated silver. Although electroplating allow for a thickerlayer of silver to be deposited, the lifetime of a Ag|AgClreference electrode made from 500-nm-thick thermally evaporated silver was compared to a Ag|AgCl electrode made froma 5-m-thick electroplated layer. The results clearly demonstrated the potential of utilizing thermally evaporated silver inAg|AgCl electrodes to extend lifetime by more than 100%.However, a protective layer of 20 nm titanium was required toprevent oxidation of the silver in subsequent fabrication levels,and which had to be removed by immersion in a HF solution. Since HF also attacks, this procedure could not be used inChip 1 to avoid damage to the thin 50–nm layer ofdefining the pH sensitive membrane of the ISFET. In contrast,the 500-nm-thick PECVDdefining the microelectrodearray of the oxygen sensor, was tolerant to HF exposure.
General Experimental Setup
All the devices were powered by batteries in order to demonstrate the concept of utilizing the microelectronic pill in re-mote locations (extending the range of applications fromin vivosensing to environmental or industrial monitoring). The pill wassubmerged in a 250-mL glass bottle located within a 2000-Mlbeaker to allow for a rapid change of pH and temperature of thesolution. A scanning receiver captured the wireless radio transmitted signal from themicroelectronic pill by using a coil antenna wrapped around the2000-mL polypropylene beaker in which the pill was located. A portable Pentium III computer controlled the data acquisition unit (National Instruments, Austin, TX) which digitally acquired analog data from the scanning receiver prior to recording it on the computer.
SensorCharacterization
The lifetime of the incorporated Ag|AgCl reference electrodes used in the pH and oxygen sensors was measured withan applied current of 1 pA immersed in a 1.0 M KCl electrolytesolution. The current reflects the bias input current of the operational amplifier in the analog sensor control circuitry to whichthe electrodes were connected.
The temperature sensor was calibrated with the pill sub-merged in reverse osmosis (RO) water at different temperatures. The average temperature distribution over 10 min was
IMPORTANT OBSERVATIONS
The power consumption of the microelectronic pill with the transmitter, ASIC and the sensors connected was calculated to12.1 mW, corresponding to the measured current consumptionof 3.9 mA at 3.1-V supply voltage. The ASIC and sensors consumed 5.3 mW, corresponding to 1.7 mA of current, whereasthe free running radio transmitter (Type I) consumed 6.8 mW(corresponding to 2.2 mA of current) with the crystal stabilized unit (Type II) consuming 2.1 mA. Two SR44 Ag2O batteries used provided an operating time of more than 40 h for themicro system
Temperature Channel Performance
The linear sensitivity was measured over a temperature range from 00C to 700C and found to be 15.4 mV0C-1. This amplified signal response was from the analog circuit, which waslater implemented in the ASIC. The sensor, once integrated in the pill, gave a linear regression of 11.9 bits-C with a resolution limited by the noise band of 0.40C. The diodewas forward biased with a constant current () with then-channel clamped to ground, while the p-channel was floating.Since the bias current supply circuit was clamped to the negative voltage rail, any change in the supply voltage potential would cause the temperature channel to drift. Thus, bench test measurements conducted on the temperature sensor revealed thatthe output signal changed by 1.45 mV per mV change in supply voltage expressed in millivolts, corresponding to a drift of-21mV h-1in the pill from a supply voltage change of-14.5mV
Transmission frequency
Frequency stabilized units were essential to prevent the transmission drifting out of range, particularly if the pill was subject to a temperature change during operation. The standard type 1 transmitter exhibited a negative linear frequency change from 39.17 MHz at 100C to 38.98 MHz at 490C, corresponding to -4 kHz0C-1 expressed in hertz. The narrow signal bandwidth of 10 kHz gave a temperature tolerance of only -+1.30C before the signal is lost. In contrast, the type 2 transmitter exhibited a positive linear frequency change from 20.07 MHz at 20C to 20.11 MHz at 400C, corresponding to 0.9 Khz0C-1. Considering the identical signal bandwidth of 10 KHz, the temperature tolerance was increased to -+5.50C. The transmitter’s signal magnitude was not affected with the pill immersed in the different electrolyte solutions or RO water, compared to the pill surrounded by air only. Tests were also conducted with the pill immersed in the large polypropylene beaker filled with 2000 mL of PBS without the signal quality being compromised. The electromagnetic noise baseline was measured to 78 dB of S/N in the 20 MHz band of the crystal stabilized transmitter.
CONCLUSION
We have developed an integrated sensor array system whichhas been incorporated in a mobile remote analytical microelectronic pill, designed to perform real-timein situ measurements of the GI tract, providing the firstin vitro wireless transmitted multichannel recordings of analytical parameters. Further work will focus on developing photopatternable gel electrolytes andoxygen and cationselective membranes. The microelectronic pill will be miniaturized for medical and veterinary applications by incorporating the transmitter on silicon and reducing powerconsumption by improving the data compression algorithm andutilizing a programmable standby power mode.
The generic nature of the microelectronic pill makes itadaptable for use in corrosive environments related to environ-mental and industrial applications, such as the evaluation ofwater quality, pollution detection, fermentation process controland the inspection of pipelines. The integration of radiationsensors and the application of indirect imaging technologiessuch as ultrasound and impedance tomography, will improvethe detection of tissue abnormalities and radiation treatmentassociated with cancer and chronic inflammation.
In the future, one objective will be to produce a device, analogous to a micro total analysis system (TAS) or lab on a chip sensorwhich is not only capable of collecting and processing data, but which can transmit it from a remote location. The overall concept will be to produce an array of sensor devicesdistributed throughout the body or the environment, capable oftransmitting high-quality information in real-time.