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ABSTRACT
A micro electronic pill is basically a multi channel sensor used for remote bio
medical measurements using microtechnology this has been developed for the internal study and
detection of diseases and abnormalities in the gastro intestinal GI tract where restricted access
prevents the use of traditional endoscopy the measurement parameters for detection include real
time remote recording of temperature, pH, conductivity and dissolved oxygen in the GI tract
This paper with the design of the micro electronic pill which mainly consists of an outer
biocompatible capsule encasing 4 channel micro sensors a control chip, a discrete component
radio transmitter and 2 silver oxide cells.
In this report, we present a novel analytical micro system which incorporates a four-channel
micro sensor array for real-time determination of temperature, pH, conductivity and oxygen. The
sensors were fabricated using electron beam and photolithographic pattern integration, and were
controlled by an application specific integrated circuit (ASIC), which sampled the data with 10-bit
resolution prior to communication off chip as a single interleaved data stream. An integrated radio
transmitter sends the signal to a local receiver (base station), prior to data acquisition on a computer.
Real-time wireless data transmission is presented from a model in vitro experimental setup, for the
first time.
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CONTENTS
i.
INTRODUCTION
ii.
BLOCK DIAGRAM
iii.
BASIC COMPONENTS
iv.
PERFORMANCE
v.
ADVANTAGES/DISADAVNATGES
vi.
OTHER APPLICATIONS
vii.
FUTURE DEVELOPMENTS
viii.
FUTURE CHALLENGES
ix.
CONCLUSION
x.
REFERENCES
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INTRODUCTION
The invention of transistor enabled the first use of radiometry capsules, which used
simple circuits for the internal study of the gastro-intestinal (GI) [1] tract. They couldnt be used
as they could transmit only from a single channel and also due to the size of the components.
They also suffered from poor reliability, low sensitivity and short lifetimes of the devices. This
led to the application of single-channel telemetry capsules for the detection of disease and
abnormalities in the GI tract where restricted area prevented the use of traditional endoscopy.
They were later modified as they had the disadvantage of using laboratory type
sensors such as the glass pH electrodes, resistance thermometers, etc. They were also of very
large size. The later modification is similar to the above instrument but is smaller in size due to
the application of existing semiconductor fabrication technologies. These technologies led to the
formation of MICROELECTRONIC CAPSULE.
Microelectronic pill is basically a multichannel sensor used for remote biomedical
measurements using micro technology. This is used for the real-time measurement parameters
such as temperature, pH, conductivity and dissolved oxygen. The sensors are fabricated using
electron beam and photolithographic pattern integration and were controlled by an application
specific integrated circuit (ASIC).
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BLOCK DIAGRAM
Fig 1.
Microelectronic pill consists of 4 sensors (2) which are mounted on two silicon chips (Chip 1
& 2), a control chip (5), a radio transmitter (STD- type 1-7, type2-crystal type-10) & silver
oxide batteries (8).
1-access channel, 3-capsule, 4- rubber ring, 6-PCB chip carrier
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BASIC COMPONENTS
A. SENSORS
Fig 2.
There are basically 4 sensors mounted on two chips- Chip 1 & chip 2. On chip 1(shown in fig 2
a), c), e)), temperature sensor silicon diode (4), pH ISFET sensor (1) and dual electrode
conductivity sensor (3) are fabricated. Chip 2 comprises of three electrode electrochemical cell
oxygen sensor (2) and optional NiCr resistance thermometer.
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1)
Sensor chip 1:
An array consisting of both temperature sensor & pH sensor platforms were cut
from the wafer & attached onto 100-m- thick glass cover slip cured on a hot plate. The plate acts
as a temporary carrier to assist handling of the device during level 1 of lithography when the
electric connections tracks, electrodes bonding pads are defined. Bonding pads provide electrical
contact to the external electronic circuit.
Lithography [2] was the first fundamentally new printing technology since the
invention of relief printing in the fifteenth century. It is a mechanical Plano graphic process in
which the printing and non-printing areas of the plate are all at the same level, as opposed to
intaglio and relief processes in which the design is cut into the printing block. Lithography is
based on the chemical repellence of oil and water. Designs are drawn or painted with greasy ink
or crayons on specially prepared limestone. The stone is moistened with water, which the stone
accepts in areas not covered by the crayon. Oily ink, applied with a roller, adheres only to the
drawing and is repelled by the wet parts of the stone. Pressing paper against the inked drawing
then makes the print.
Lithography was invented by Alois Senefelder in Germany in 1798 and, within
twenty years, appeared in England and the United States. Almost immediately, attempts were
made to print pictures in color. Multiple stones were used; one for each color, and the print went
through the press as many times as there were stones. The problem for the printers was keeping
the image in register, making sure that the print would be lined up exactly each time it went
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through the press so that each color would be in the correct position and the overlaying colors
would merge correctly.
Early colored lithographs used one or two colors to tint the entire plate and create a
watercolor-like tone to the image. This atmospheric effect was primarily used for landscape or
topographical illustrations. For more detailed coloration, artists continued to rely on hand
coloring over the lithograph. Once tinted lithographs were well established, it was only a small
step to extend the range of color by the use of multiple tint blocks printed in succession.
Generally, these early chromolithographs were simple prints with flat areas of color, printed sideby-side.
Increasingly ornate designs and dozens of bright, often gaudy, colors characterized
chromolithography in the second half of the nineteenth century. Overprinting and the use of
silver and gold inks widened the range of color and design. Still a relatively expensive process,
chromolithography was used for large-scale folio works and illuminated gift books that often
attempted to reproduce the handwork of manuscripts of the Middle Ages. The steam-driven
printing press and the wider availability of inexpensive paper stock lowered production costs and
made chromolithography more affordable. By the 1880s, the process was widely used for
magazines and advertising. At the same time, however, photographic processes were being
developed that would replace lithography by the beginning of the twentieth century.
Chip 1 is divided into two- LHS unit having the diode while RHS unit comprises the
ISFET.
Fig. 3.
DT-470-SD Features
ECE Department , SRMGPC , Lucknow
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The rugged, reliable Lake Shore SD package designed to withstand repeated thermal cycling
and minimize sensor self-heating Variety of packaging options
ISFET: [4]
Ion Selective Field Effect Transistor; this type of electrode contains a transistor
coated with a chemically sensitive material to measure pH in solution and moist surfaces. As the
potential at the chemically active surface changes with the pH, the current induced through the
transistor varies. A temperature diode simultaneously monitors the temperature at the sensing
surface. The pH meter to a temperature compensated pH reading correlates the change in current
and temperature.
This device [5] has an affinity for hydrogen ions, which is the basis for the
determination of the pH. The surface of the sensitive area of the sensor contains hydroxyl groups
that are bound to an oxide layer. At low pH values hydrogen ions in the sample will bind to these
hydroxyl groups resulting in a positively charged surface. In alkaline environments hydrogen
ions are abstracted from the hydroxyl groups, leading to a negatively charged surface.
Thus, each pH change has a certain influence on the surface charge. On its turn, this
attracts or repulses the electrons flowing between two electrodes in the semiconductor device.
The electronics compensates the voltage in order to keep the current between the two electrodes
at its set point. In this way this potential change is related to the pH.
Attachment of a polymer membrane on the ISFET introduces the possibility to go
beyond the measurement of pH toward other ions. In this plastic layer certain chemicals
(ionophores), which can recognize and bind the desired ion, are put in. Now, complex formations
of the ionophore and the ion introduce a charge. The potential change is a measure for the ion
concentration. Typically, these sensors can be used in a concentration range between app. 10-5
up to 1 mol/l.
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Level 1 pattern was defined in 0.9 m UV3 resist by electron beam lithography. It
contains three-electrode electrochemical oxygen sensor & NiCr resistance thermometer.
Oxygen sensor detection principle: [6]
Most portable or survey instruments used for workplace evaluation of oxygen
concentrations make use of "fuel cell" type oxygen sensors. "Fuel cell" oxygen sensors consist of
a diffusion barrier, a sensing electrode (cathode) made of a noble metal such as gold or platinum,
and a working electrode made of a base metal such as lead or zinc immersed in a basic
electrolyte (such as a solution of potassium hydroxide).
Oxygen diffusing into the sensor is reduced to hydroxyl ions at the cathode:
O2 + 2H2O + 4e-
OH
2PbO + 2H2O + 4e
2PbO
Fuel cell oxygen sensors are current generators. The amount of current generated is
proportional to the amount of oxygen consumed (Faraday's Law). Oxygen reading instruments
simply monitor the current output of the sensor.
An important consideration is that fuel cell oxygen sensors are used up over time.
In the cell reaction above, when all available surface area of the lead (Pb) anode has been
converted to lead oxide (PbO), electrochemical activity ceases, current output falls to zero, and the
sensor must be rebuilt or replaced. Fuel cell sensors are designed to last no more than one to two
years. Even when installed in an instrument which is never turned on, oxygen sensors which are
exposed to atmosphere which contains oxygen are generating current, and being used up.
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reaction. For this reason oxygen sensors usually include a temperature compensating load resistor
to hold current output steady in the face of fluctuating temperature. (Microprocessor based
instrument designs usually provide additional signal correction in software to further improve
accuracy.) Another limiting factor is cold. The freezing temperature of electrolyte mixtures
commonly used in oxygen sensors tends to be about 5 o F (- 20 o C). Once the electrolyte has frozen
solid, electrical output falls to zero, and readings may no longer be obtained. There are two basic
variations on the fuel cell oxygen sensor design. These variations have to do with the mechanism
by which oxygen is allowed to diffuse into the sensor. Dalton's Law states that the total pressure
exerted by a mixture of gases is equal to the sum of the partial pressures of the various gases. The
partial pressure for oxygen is that fraction of the total pressure due to oxygen. Partial atmospheric
pressure oxygen sensors rely on the partial pressure (or pO 2) of oxygen to drive molecules through
the diffusion barrier into the sensor. As long as the pO 2 remains constant, current output may be
used to indicate oxygen concentration. On the other hand, shifts in barometric pressure, altitude, or
other conditions which have an effect on atmospheric pressure will have a strong effect on pO
sensor readings. To illustrate the effects of pressure on pO 2 sensors, consider a sensor located at
sea level where atmospheric pressure equals 14.7 PSI (pounds per square inch). Now consider that
same sensor at an elevation of 10,000 feet. Although at both elevations the air contains 20.9
percent oxygen, at 10,000 feet the atmospheric pressure is only 10.2 PSI! Since there is less force
driving oxygen molecules through the diffusion barrier into the sensor, the current output is
significantly lower.
"Capillary pore" oxygen sensor designs include a narrow diameter tube through
which oxygen diffuses into the sensor. Oxygen is drawn into the sensor by capillary action in much
the same way that water or fluid is drawn up into the fibers of a paper towel. While capillary pore
sensors are not influenced by changes in pressure, care must be taken that the sensor design
includes a moisture barrier in order to prevent the pore from being plugged with water or other
fluids.
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is what is actually measured. Since the reference electrode is shielded from any reaction, it
maintains a constant potential which provides a true point of comparison. With this arrangement
the change in potential of the sensing electrode is due solely to the concentration of the reactant
gas.
CO2 + 2H+ + 2e -
The counter electrode acts to balance out the reaction at the sensing electrode by reducing
oxygen present in the air to water:
1/2 O2 + 2H+ + 2e-
H 2O
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designs allow for the detection of a number of less electrochemically active gases such as
hydrogen chloride and nitric oxide. Several other contaminants (such as ammonia) are detectable
by means of other less straight forward detection reactions.
Electrochemical sensors are stable, long lasting, require very little power and are
capable of resolution (depending on the sensor and contaminant being measured) in many cases
to 0.1 ppm. The chief limitation of electrochemical sensors is the effects of interfering
contaminants on toxic gas readings. Most substance-specific electrochemical sensors have been
carefully designed to minimize the effects of common interfering gases. Substance-specific
sensors are designed to respond only to the gases they are supposed to measure. The higher the
specificity of the sensor the less likely the sensor will be affected by exposure to other gases
which may be incidentally present. For instance, a substance-specific carbon monoxide sensor is
deliberately designed not to respond to other gases which may be present at the same time, such
as hydrogen sulfide or methane.
Even though care has been taken to reduce cross-sensitivity, some interfering gases
may still have an effect on toxic sensor readings. In some cases the interfering effect may be
"positive" and result in readings which are higher than actual. In some cases the interference may
be negative and produce readings which are lower than actual. Electrochemical sensor designs
may include a selective external filter designed to remove interfering gases which would
otherwise have an effect on the sensing electrode. The size and composition of the filter are
determined by the type and expected concentration of the interfering contaminants being
removed.
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B. CONTROL CHIP:
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The analog module is based on the AMS OP05B opamp, which offer a lot of power
saving scheme (sleep mode) & a compact IC design. The temperature circuitry biased the diode
at constant current, so that a change in temperature would result in corresponding change in
diode voltage. The pH ISFET sensor was biased as a simple source & drain follower at constant
current with D-S voltage changing with threshold voltage & pH. Conductivity circuit operated at
direct current measuring the resistance across the electrode pair as an inverse function of
solution conductivity. An incorporated potentiostat operated the amperometric oxygen sensor
with a 10-bit DAC controlling the working electrode potential w.r.t. reference. The analog
signals were sequenced through a MUX prior to being digitized by the ADC. The BW for each
channel was limited by the sampling interval of 0.2 ms.
The digital data processing module conditioned the digitized signals through the
use of a serial bit stream data compression algorithm, which decided when transmission was
required by comparing the most recent sample with the previous one. This minimizes the
transmission length & particularly effective when the measuring environment is at quiescent, a
condition encountered in many applications. The entire design is based on low power
consumption & immunity from noise interference. The digital module is clocked at 32 kHz &
employed in sleep mode to conserve power from analog module.
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C. RADIO TRANSMITTER
Its assembled prior to integration in the capsule using discrete surface mount
components on a single-sided PCB. Its designed to operate at a transmission freq. of 40.01 MHz
at 20C generating a signal of 10 kHz. BW. A second crystal stabilized transmitter was also used.
This unit is similar to the free running STD transmitter, having a transmission freq. limited to
20.08 MHz at 20C, due to crystal used. Pills incorporating the STD transmitter are Type 1, where
as the pills having crystal stabilized unit is Type 2. The transmission range was measured as being
1 m & the modulation scheme FSK, with a data rate of 1 kb/s.
Fig 7.
Capsule
The microelectronic pill consists of a machined biocompatible (non-cytotoxic),
chemically resistant polyether-terketone (PEEK) capsule and a PCB chip carrier acting as a
common platform for attachment of sensors, ASIC, transmitter & batteries (fig 1.). The fabricated
sensors were each attached by wire bonding to a custom made chip carrier made from a 10-pin,
0.5-pitch polymide ribbon connector. The connector in turn was connected to an industrial STD.
flat cable plug (FCP) socket attached to the PCB carrier chip of the microelectronic pill, to
facilitate the rapid replacement off the sensors when required. The PCB chip carrier was made
from 2 STD. 1.6 mm-thick fiber glass boards attached back to back epoxy resin which maximized
the distance between the 2 sensor chips. The sensor chips are connected to both sides of the PCB
by separate FCP sockets, with sensor chip 1 facing the top face, with the sensor chip 2 facing
down. Thus, the oxygen sensor on chip 2 had to be connected to the top face by 3 200 nm copper
ECE Department , SRMGPC , Lucknow
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leads soldered onto the board. The transmitter was integrated in the PCB which also incorporated
the power supply rails, the connection points to the sensors, as well as the transmitter & the ASIC
& the supporting slots for the capsule in which the carrier is located.
The ASIC was attached with double-sided Cu conducting tape prior to wire bonding
to the power supply rails, the sensor inputs & the transmitter (a process which entailed the
connection of 64 bonding pads). The unit was powered by 2 STD. 1.55V SR44 Silver oxide
(Ag2O) cells with a capacity of 175mAh. The batteries were connected & attached to a custom
made 3-pin, 1.27 mm pitch plug by electrical epoxy. The connection on the matching socket on the
PCB carrier provided a three point power supply to the circuit comprising a negative supply rail
(1.55V).
Fig 8.
The capsule was machined as two separate screw-fitting compartments. The PCB
chip carrier was attached to the front section of the capsule (fig 1.). The sensor chips were exposed
to the ambient environment through access ports & were sealed by 2 stainless steel clamps
incorporating a 0.8 m thick sheet of Viton fluoroelastometer seal. A 3 mm dia access channel in
center of each of the steel clamps (incl. the seal), exposed in sensing regions of the chips. The rear
section of the capsule is attached to the front section by a 13 mm screw connection incorporating a
Viton rubber O-ring. The seals rendered the capsule water proof, as well as making it easy to
maintain (e.g. during sensor & battery replacement).The complete prototype was 16*55 mm &
weighs 13.5 g including the batteries.
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D. AG2O Batteries
Fig 9.
The unit was powered by two standard 1.55-V SR44 silver oxide (Ag 2O) cells with a capacity of
175 mAh. The batteries were serial connected and attached to a custom made 3-pin, 1.27-mm pitch
plug by electrical conducting epoxy. The connection to the matching socket on the PCB carrier
pro-vided a three point power supply to the circuit comprising a negative supply rail (-1.55 V),
virtual ground (0 V), and a positive supply rail (1.55 V). The battery pack was easily replaced
during the experimental procedures.
1.
2.
3.
4.
5.
PERFORMANCE
ECE Department , SRMGPC , Lucknow
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B. pH Channel Performance:
The linear performance from pH 1 to 13 corresponded to sensitivity of 41.7mV/pH
unit at 23C. The pH ISFET sensor operated in a constant current mode (15 A), with drain
voltage clamped to positive supply rail & the source voltage floating with the gate potential. The
Ag/AgCl reference electrode, representing the potential in which the floating gate was referred to,
was connected to ground. The sensor performance, once integrated in the pill (Fig 10 b)a)),
corresponded to 14.85 bits/pH which give a resolution of 0.07 pH/ data point. The sensor exhibits
a larger responsivity in alkaline solutions.
The sensor life time of 20h was limited by Ag\Agcl reference electrode made from electroplated
silver. The ph sensor exhibited a signal drift of 6 mV /h (0.14ph), o f which 2.5mV/h was
estimated to be due to the dissolution of Agcl from the reference electrode. The temperature
sensitivity of the ph sensor was measured as 16.8mV/c. The changing of the ph of the solution at
40c from ph 6.8 to 2.3 and 11.6 demonstrated that the two channels were completely independent
of each other and there was no signal interference from the temperature channel (Fig 10. b (b))
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was subsequently measured at -800 mV (versus the integrated Ag|AgCl) by recording the steadystate current in oxygen-depleted PBS, t hereby excluding any interfering species.
In order to calibrate the sensor, a three point calibration was performed (at saturated oxygen,
and with oxygen removed by the injection of Na 2SO3 to a final concentration of 1 M). the steady
state signal from the oxygen saturated solution was recorded at a constant working electrode
potential of -700 mV(versus Ag|AgCl).which was below the reduction potential for water. This
generated a full-scale signal of 65 nA corresponding 8.2 mg O 2L-1. The injection of Na2S03 into the
PBS after 90 s provided the zero point calibration. This fall in the reduction current provided
corroborative evidence that dissolve oxygen was being recorded, by returning the signal back to the
base line level once all available oxygen was consumed. A third, intermediate point was generated
through the addition of 0.01 M Na 2SO3. The resulting calibration graph form a linear regression
expressed in nanoamperes. The sensitivity of the sensor was 7.9 nA mg -1 O2,with the resolution of
0.4mg L-1 limited by noise or background drift. The lifetime of the integrated Ag|AgCl reference
electrode, made from thermal evaporated silver, was found to be to 45 h, with an average voltage
drift of -1.3 mVh-1 due to he dissolution of the AgCl during operation. Both measurements of FMCA
and oxygen redox behavior indicated a stable Ag|AgCl reference.
Fig. 11. Recording of pH and temperature in vitro using the electronic pill
E. Control Chip
The background noise from the ASIC corresponded to a constant level of 3-Mv peak-to-peak, which
is equivalent to one least significant bit (LSB) of the ADC. Since the second LSB were required to
ECE Department , SRMGPC , Lucknow
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provide an adequate noise margin, the 10-bit ADC was anticipated to have an effective resolution of
8 bits.
Fig. 12 .Long term in vitro pH measurements in response to a changing pH from the initial pH
4 to pH 7 (2 h) and pH 10.5 (4 h) at 36.50C
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Range
1. Temperature from 0 to 70 C
2. pH from 1 to 13
3. Dissolved Oxygen up to 8.2 mg per liter
4. Conductivity above 0.05 mScm-1
5. Full scale dynamic Range analogue signal = 2.8 V
Accuracy
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1. It is being beneficially used for disease detection & abnormalities in human body. Therefore
it is also called as MAGIC PILL FOR HEALTH CARE.
2. Adaptable for use in corrosive & quiescent environment.
3. It can be used in industries in evaluation of water quality, Pollution Detection, fermentation
process control & inspection of pipelines.
4. Micro Electronic Pill utilizes a PROGRAMMABLE STANDBY MODE, So Power
consumption is very less.
5. It has very small size, hence it is very easy for practical usage
6. High sensitivity, Good reliability & Life times.
7. Very long life of the cells(40 hours), Less Power, Current & Voltage requirement (12.1 mW,
3.9 mA, 3.1 V)
8. Less transmission length & hence has zero noise interference
Disadvantages
OTHER APPLICATIONS
Apart from the detection of real time remote recording of temperature, pH, conductivity and
dissolved oxygen in the GI tract the Micro electronic Capsule can also be used for many other uses
in the real world.
The generic nature of microelectronic pill makes it adaptable for use in corrosive
environments related to environmental & industrial applications, such as
ECE Department , SRMGPC , Lucknow
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A. Evaluation of Water Quality Just like the pill is used for detection of amount of
dissolved oxygen in the stomach or GI tract similarly it can be used to detect if the water
is suitable for drinking and suitable for survival of the plants and animals.
B. Pollution Detection
C. Fermentation Process Control
D. Inspection of the pipelines.
E. The Integration of Radiation Sensors
F. The application of indirect imaging technologies such as ultrasound & impedance
tomography will improve the detection of tissue abnormalities & radiation treatment
associated with cancer & chronic inflammation.
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FUTURE DEVELOPMENTS
Further developments focus on the photo pattern able gel electrolyte and oxygen
and cat ion selective membranes. Also in the future, these measurements will be used to perform
physiological analysis of the GI tract. For e.g., Temperature sensors can be used to measure the
body core temperature, also locate any changes corresponding to ulcers or tissue inflammation; pH
sensors may be used for determination of presence of pathological conditions associated with
abnormal ph levels etc.
In the future, one objective will be to produce a device, analogous to a micro total analysis
system (TAS) or lab on a chip sensor which 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 devices distributed throughout the body or the environment, capable of transmitting highquality information in real-time.
In future another objective will be to develop a micro electronic pill with a camera to study
the internal structure of GI tract visually , with the imaging technology added it will help the doctors
to view the internal abnormalities or tumors without any operation so it will benefit both the patients
and as well as the doctors.
After recent significant technology improvements, design of small size camera and battery
could have been possible. Thus in the last ten years some research projects looking at developing
electronic pills have concentrated mostly on the visual sensor system. Thus a high frequency link is
required for better resolution and a miniaturized system.
Another category of electronic pill technology is to use fluorescence spectroscopy and
imaging, similar to those that are commercially available. Kfouri, et al., studied a Fluorescence based
electronic pill system that uses UV light with illumination LEDs to obtain clearer images . This is
like flash based digital camera widely used by people.
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FUTURE CHALLENGES
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CONCLUSION
We have therefore described about the multichannel sensor, which has been
implemented in remote biomedical using micro technology, the micro electronic pills, which is
designed to perform real time measurements in the GI tract providing the best in vitro wireless
transmitter, multi channel recordings of analytical parameters.
We have developed an integrated sensor array system which has been incorporated in
a mobile remote analytical microelectronic pill, designed to perform real-time in situ measurements
of the GI tract, providing the first in vitro wireless transmitted multichannel recordings of analytical
parameters. Further work will focus on developing photopatternable gel electrolytes and oxygen and
cation selective membranes. The microelectronic pill will be miniaturized for medical and veterinary
applications by incorporating the transmitter on silicon and reducing power consumption by
improving the data compression algorithm and utilizing a programmable standby power mode.
The generic nature of the microelectronic pill makes it adaptable for use in corrosive
environments related to environ-mental and industrial applications, such as the evaluation of water
quality, pollution detection, fermentation process control and the inspection of pipelines. The
integration of radiation sensors and the application of indirect imaging technologies such as
ultrasound and impedance tomography, will improve the detection of tissue abnormalities and
radiation treatment associated with cancer and chronic inflammation.
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