Chapter-1

Introduction
We are familiar with a wide range of sensors in the field of electronics. They areused
widely in the various experiments and research activities too. This microelectronicpill is
such a sensor with a number of channels and is called as a multichannel sensor.As the
name implies this sensor is a pill. That is it is meant to go inside the body and to study the
internal conditions.Earlier it was when transistor was invented, that radiometry capsules
were firstput into use. These capsules made use of simple circuits for studying the
gastrointestinaltract. Some of the reasons that prevented their use was their size and their
limitation of not to transmit through more than a single channel. They had poor reliability
andsensitivity. The lifespan of the sensors were also too short. This paved the way for
theimplementation of single channel telemetry capsules and they were later developed
toovercome the demerits of the large size of laboratory type sensors. The
semiconductortechnologies also helped in the formation and thus finally the presently
seenmicroelectronic pill was developed.These pills are now used for taking remote
biomedical measurements inresearches and diagnosis. A small miniaturized electronic pill
can reach areas such as small intestine and deliver real time video images wirelessly to an
external console The sensors make use of the micro technology to serve thepurpose. The
main intention of using the pill is to perform an internal study andrecognize or detect the
abnormalities and the diseases in the gastrointestinal tract. In thisGI(gastrointestinal) tract
we cannot use the old endoscope as the access is restricted. Anumber of parameters can
be possibly measured by these pills and they includeconductivity, pH temperature and the
amount of dissolved oxygen in the gastrointestinaltract.

Chapter-2

MICROELECTRONIC PILL
The design of the microelectronic pill is in the form of a capsule. The encasing ithas is
biocompatible. Inside this are multi- channel (four channel) sensors and a control chip. It
also comprises of a radio transmitter and two silver oxide cells. The four sensors are
mounted on the two silicon chips. In addition to it, there are a control chip, one access
channel and a radio transmitter.The four sensors commonly used are a temperature
sensor, pH ISFET sensor, adual electrode conductivity sensor and a three electrode
electrochemical oxygen sensor. Among these the temperature sensor, the pH ISFET
sensor and the dual electrode conductivity sensor are fabricated on the first chip. The
three electrode electrochemical cell oxygen sensor will be on chip 2. The second chip
also consists of a NiCr resistance thermometer which is optional.
Fig 1 block diagram

BASIC COMPONENTS
A. Sensors
There are basically 4 sensors mounted on two chips- Chip 1 & chip 2. On chip1(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 threeelectrode
electrochemical cell oxygen sensor (2) and optional NiCr resistancethermometer.

1) Sensorchip1:

An array consisting of both temperature sensor & pH sensor platforms were cutfrom the
wafer & attached onto 100-m- thick glass cover slip cured on a hot plate. Theplate 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 was the first
fundamentally new printing technology since theinvention of relief printing in the
fifteenth century. It is a mechanical Plano graphicprocess in which the printing and nonprinting areas of the plate are all at the samelevel, as opposed to intaglio and relief
processes in which the design is cut into theprinting block. Lithography is based on the
chemical repellence of oil and water.Designs are drawn or painted with greasy ink or
crayons on specially preparedlimestone. The stone is moistened with water, which the
stone accepts in areas notcovered by the crayon. Oily ink, applied with a roller, adheres
only to the drawing andis repelled by the wet parts of the stone. Pressing paper against
the inked drawing thenmakes the print.
Lithography was invented by Alois Senefelder in Germany in 1798 and, withintwenty
years, appeared in England and the United States. Almost immediately, attemptswere
made to print pictures in colour. Multiple stones were used; one for each color,and the
print went through the press as many times as there were stones. The problemfor the
printers was keeping the image in register, making sure that the print would belined up
exactly each time it went through the press so that each color would be in thecorrect
position and the overlaying colors would merge correctly.Early colored lithographs used
one or two colors to tint the entire plate and create awatercolour-like tone to the image.
This atmospheric effect was primarily used forlandscape or topographical illustrations.
For more detailed coloration, artists continuedto rely on hand colouring over the
lithograph. Once tinted lithographs were wellestablished, 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 simpleprints with flat areas of colour,
printed side-by-side.

Fig 2 Pill
Increasingly ornate designs and dozens of bright, often gaudy, colours characterized
chromolithography in the second half of the nineteenth century. Overprinting and the use
of silver and gold inks widened the range of colour 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.
2) Sensor Chip 2:
The level 1 pattern (electric tracks, bonding pads, and electrodes) was defined in0.9m
UV3 resist (Shipley, U.K.) by electron beam lithography. A layer of 200 nm gold
(including an adhesion layer of 15 nm titanium and 15 nm palladium) was deposited by

thermal evaporation. The fabrication process was repeated (Level 2) to define the5- mwide and 11-mm-long NiCr resistance thermometer made from a 100-nm-thick layer
of NiCr (30- resistance). Level 3 defined the 500-nm-thick layer of thermal evaporated
silver used to fabricate the reference electrode. An additional sacrificial layer of titanium
(20 nm) protected the silver from oxidation in subsequent fabrication levels.
The surface area Fig. 2. Photograph of the 4:75 2 4:75 mm application specific integrated
circuit control chip (a), the associated explanatory diagram (b), and aschematic of
the reference electrode was 1.5*10^-2 mm , whereas the of the architecture (c) illustrating
the interface to external components. MUX counter electrode made of gold had an area of
mm .(four-channel multiplexer), ADC, DAC , and OSC (32-kHz oscillator).
Level 4 defined the microelectrode array of the working electrode, comprising 57
circular gold electrodes, each 10m in diameter, with an inter electrode spacing of 25 m
and a combined area of 4.5*10^-3 mm .Such an array promotes electrode polarization
and reduces response time by enhancing transport to the electrode surface [26]. The
whole wafer was covered with500 nm plasma-enhanced chemical vapour deposited
(PECVD) Si3Ni4The pads, counter, reference, and the microelectrode array of the
working electrode was exposed using an
etching mask of S1818 photo resist prior to dry etching with C2F6. The chips were then
diced from the wafer and attached to separate100- m-thick cover slips by epoxy resin to
assist handling. The electrolyte chamber was defined in 50- m-thick polyimide at Level
5.Residual polyimide was removed in an barrel a shear(2 min), prior to removal of the
sacrificial titanium layer at Level6 in a diluted HF solution (HF to RO water, 1:26)for 15
s. The short exposure to HF prevented damage to the PECVD layer. Thermally
evaporated silver was oxidized to Ag AgCl (50%of film thickness) by
chronopotentiometry (120 nA, 300 s) at Level 7 in the presence of KCl, prior to injection
of the internal reference electrolyte at Level 8
A .sheet of oxygen
5*5mm sheet of oxygen permeable Teflon was cut out from a 12.5- m-thick film and
attached to the chip at Level 9 with epoxy resin prior to immobilization by the aid of a
stainless steel clamp

B. 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 mm silicon die using a 3-V, 2-poly, 3-metal
0.6M

Fig.3 , the associated explanatory diagram of4:75 2 4:75 mm application specific

integrated circuit control chip

Fig 4 a schematic of the architecture

is particularly effective when the measuring environment is acquiescent, a condition
encountered in many applications The entire design was constructed with a focus on low
power consumption and immunity from noise interference. The digital module was
deliberately clocked at 32 kHz and employed a sleep mode to conserve power from the
analogue module. Separate on-chip power supply trees and pad-ring segments were used
for the analogue and digital electronics sections in order to discourage noise propagation
and interference.

C. Radio Transmitter
The radio transmitter was assembled prior to integration in the capsule using discrete
surface mount components on a single-sided printed circuit board (PCB). The footprint of
the standard transmitter measured 8*5*3mm including the integrated coil(magnetic)
antenna. It was designed to operate at a trans-mission frequency of 40.01MHz at 20 C
generating a signal of 10 kHz bandwidth. A second crystal stabilized transmitter was also
used. This second unit was similar to the free running standard transmitter, apart from
having a larger footprint of 10*5*3mm, and a transmission frequency limited to
20.08MHz at 20 C, due to the crystal used. Pills incorporating the standard transmitter
were denoted
Type I
, whereas the pills in-cooperating the crystal stabilized unit were denoted
Type II

. The transmission range was measured as being 1meter and the modulation scheme
frequency shift keying (FSK), with a data rateof1Kbs^-1
D. Capsule
The microelectronic pill consisted of a machined biocompatible (noncytotoxic),
chemically resistant polyetherterket one (PEEK) capsule (Victrex, U.K.) and a PCBchip
carrier acting as a common platform for attachment of the sensors, ASIC, transmitter and
the batteries (Fig. 3). The fabricated sensors were each attached by wirebonding to a
custom made chip carrier made from a 10-pin, 0.5-mm pitch polyimide ribbon connector.
The ribbon connector was, in turn, connected to an industrial standard10-pin flat cable
plug (FCP) socket (Radio Spares, U.K.) attached to the PCB chip carrier of the
microelectronic pill, to facilitate rapid replacement of the sensors when required. The
PCB chip carrier was made from two standard1.6-mm-thick fiber glassboards attached
back to back by epoxy resin which maximized the distance between the two sensor chips.
The sensor chips were connected to both sides of the PCB by separate FCP sockets, with
sensor Chip 1 facing the top face, with Chip 2
facing down. Thus, the oxygen sensor on Chip 2 had to be connected to the top face by
three 200- m copper leads soldered on to 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 and the ASIC and the supporting slots for the capsule in which
the chip carrier was located. The ASIC was attached withdouble-sided copper conducting
tape (Agar Scientific, U.K.) prior to wire bonding to the power supply rails, the sensor
inputs, and the transmitter (a process which entailed the connection of 64 bonding pads).
The unit was powered by two standard 1.55-VSR44 silver oxide cells with a capacity of
175 mAh. The batteries were serial connected and attached to a custom made 3-pin, 1.27mm pitch plug well as making it easy to maintain (e.g., during sensor and battery
replacement). The complete prototype was16.55 mm and weighted 13.5 g including the
batteries.
A smaller pill suitable for physiological in vivo
trials (10 30 mm) is currently being developed from the prototype.

Fig.An ingested capsule transmits data wirelessly to an external base station.

10

3.MATERIAL AND METHODS

A.General Experimental Setup
All the devices were powered by batteries in order to demonstrate the concept of utilizing
the microelectronic pill in remote locations (extending the range of applications from
in vivo
sensing to environmental or industrial monitoring). The pill was submerged in a 250-mL
glass bottle located within a 2000-mLbeaker to allow for a rapid change of pH and
temperature of the solution. A scanning receiver (Win radio Communications, Australia)
captured the wireless radio transmitted signal from the microelectronic pill by using a
coil antenna wrapped around the 2000-polypropylenebeaker in which the pill was
located. A portable Pentium III computer controlled the data acquisition unit (National
Instruments, Austin, TX) which digitally acquired analogue data from the scanning
receiver prior to recording it on the computer. The solution volume used in all
experiments was 250 mL The beaker, pill, glass bottle, and antenna were located within
25*25 cm container of polystyrene, reducing temperature fluctuations from the ambient
environment (as might be expected within the GI tract)and as required to maintain a
stable transmission frequency. The data was acquired using Lab View (National
Instruments, Austin, TX) and processed using a MATLAB(Math works, Natick, MA)
routine.
B.Sensor Characterization
The lifetime of the incorporated AgCl reference electrodes used in the pH and oxygen
sensors was measured with an applied current of 1 pA immersed in a 1.0 M KCl
electrolyte solution. The current reflects the bias input current of the operational amplifier
in the analogue sensor control circuitry to which the electrodes were connected The
temperature sensor was calibrated with the pill submerged in reverse osmosis (RO) water
at different temperatures. The average temperature distribution over10 min was recorded
for each measurement, represented as 9.1 C, 21.2 C, 33.5C, and 47.9 C.
The system was allowed to temperature equilibrate for 5 min prior to data acquisition.
The control readings were performed with a thin wire K-type thermocouple(Radio
Spares, U.K.). The signal from the temperature sensor as investigated with respect to

11

supply voltage potential, due to the temperature circuitry being referenced to the negative
supply rail. Temperature compensated readings(normalized to23 C) were recorded at a
supply voltage potential of 3.123,3.094, 3.071,and 2.983 mV using a direct
communication link. Bench testing of the temperature sensor from 0 C to 70 C was also
performed to investigate the linear response characteristics of the temperature sensor. The
pH sensor of the microelectronic pill was calibrated in standard pH buffers [28] of pH 2,
4, 7, 9, and 13, which reflected the dynamic range of the sensor. The calibration
was performed at room temperature (23 C)over a period of 10 min, with the CMOS
process by Austria Microsystems (AMS) via the Euro practice initiative It is a novel
mixed signal design that contains an analogue signal conditioning module operating the
sensors, an 10-bit analogue-to-digital (ADC)and digital-to-analogue(DAC) converters,
and a digital data processing module. An RC relaxation oscillator (OSC) provides the
clock signal. The analogue module was based on the AMS OP05B operational amplifier,
which offered a combination of both a power having scheme (sleep mode) and a compact
integrated circuit design. The temperature circuitry biased the diode at constant current,
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 drain-source 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 potentios
at circuit operated the amperometric oxygen sensor with a10-bit DAC controlling the
working electrode potential with respect to the reference. The analogue signals had a fullscale dynamic range of 2.8 V(with respect to a 3.1-V supply rail) with the resolution
determined by the ADC. The analogue signals were sequenced through a multiplexer
prior to being digitized by the ADC. The bandwidth 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 sampled data. This

12

technique minimizes the transmission length, and comprising the electronic pill. The
prototype is 16 2 55 mm, weights 13.5 g. The
Type I
unit consist of the microelectronic sensors at the front enclosed by the metal clamp and
rubber seal (1) which provide a 3-mm-diameter access channel to the sensors (2). The
front section of the capsule, physically machined from solid PEEK, is illustrated (3) with
the rear section removed to illustrate the internal design. The front and rear section of the
capsule is joined by as crew connection sealed of by a Viton-rubber o-ring (4). The ASIC
control chip(5) is integrated on the common PCB chip carrier (6) which incorporate the
discrete component radio transmitter (7), and the silver oxide battery cells (8).The battery
is connected on the reverse side of the PCB (9). The Type II unit is identical to the
Type I with exception of an incorporated crystal stabilized radio transmitter (10) for
improved temperature stability. by electrical conducting epoxy (Chemtronics,
Kennesaw,GA).The connection to the matching socket on the PCB carrier provided 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. The capsule was machined as two separate screwfitting compartments. The PCB chip carrier was attached to the front section of the
capsule(Fig. 3). The sensor chips were exposed to the ambient environment through
accessports and were sealed by two sets of stainless steel clamps incorporating a 0.8mthick sheet of Viton fluoroelastomer seal. A 3-mm-diameter access channel in the centre
of each of the steel clamps (incl. the seal), exposed the sensing regions of the chips. There
section of the capsule was attached to the front section by a 13-mmscrewconnection
incorporating a Viton rubber O-ring (James Walker, U.K.). The seals rendered the capsule
water proof, as pill being washed in RO water between each step. A standard lab pH
electrode was used as a reference to monitor the pH of the solutions(Consort n.v.,
Belgium).
The pH channel of the pill was allowed to equilibrate for 5 min prior to starting
the data acquisition. Each measurement was performed twice. Bench test measurements
from pH 1 to 13 were also performed using an identical control circuit to the ASIC. The
oxygen sensor was bench tested with a standard laboratory potentiostat (Bio analytical

13

Systems, West Lafayette, IN),over its dynamic range in phosphate buffered saline(PBS)
using a direct communication link at 23 C. Cyclic voltammetry within sweep potential
from 0.1 to 0.45 V (versus Ag AgCl) was performed in 1-mM ferroscene-monocarboxylic
acid (FMCA) as model redox compound, to test the performance of themicro-electrode
array. A three-point calibration routine was performed at oxygen
concentrations of 0 mg L (PBS saturated with 2 MNa2So2), 4 mg L (PBS titration with 2
M) and 8.2mg L(oxygen saturated PBS solution). The solution saturated with dissolved
oxygen was equilibrated overnight prior to use. The dissolved oxygen was monitored
using a standard Clark electrode (Orion Research Inc., Beverly, MA).The reduction
potential of water was assessed in oxygen depleted PBS, to avoid interference from
oxygen, at the same time assessing the lower potential limit that couldbe used for
maximizing the efficiency of the sensor. The voltage was then fixed above this reduction
potential to assess the dynamic behaviour of the sensor upon injection
of saturated in oxygen saturated PBS.
C. Transmission
The pills transmission frequency was measured with respect to changes in
temperature. The Type I
pill (without crystal) was submerged in RO water at temperatures of 1 C, 11 C, 23 C, and
49 C, whereas the Type II pill (with crystal) was submerged in temperatures of 2 C, 25 C,
and 45 C. The change in frequency was measured with the scanning receiver, and the
results used to assess the advantage of crystals stabilized units at the cost of a larger
physical size of the transmitter.

D. Dynamic Measurements
Dynamic pH measurements were performed with the pill submerged in a PBSsolution at
23 C. The pH was changed from the initial value of 7.3 by the titration of 0.1M Hand0.1
MNaOH, respectively. Subsequently, the pH was changed from pH 7.3 topH 5.5 (after 5
min), pH 3.4 (after 8 min) top 9.9 (after 14 min) and back to pH 7.7(after 21 min). A
standard (bench-top) pH electrode monitored the pH of the solution.The solutions were
sampled after the pH change, and measured outside the experimentalsystem to prevent

14

electronic noise injection from the pH electrode. The temperature channel was recorded
simultaneously.
E. Sensor and Signal Drift
Long term static pH and temperature measurements were performed to assess signal drift
and sensor lifetime in physiological electrolyte (0.9% saline) solutions.A temperature of
36.5 Cwas achieved using a water bath, with the assay solutions continuously stirred and
re-circulated using a peristaltic pump. The sensors were transferred from solutions of pH
4 to pH 7, within2 h of commencing the experiment, and from pH 7 to pH 10.5

15

16

Fig. 6.pH sensor: (a) pH recording in the range of pH 2 to 13, representedby digital
data points; (b) dynamic recording of temperature (1) and pH (2) using adirect
communication link illustrates the temperature sensitivity of the pHchannel

17

18

Fig. 7 Temperature sensor: (a) temperature recording over a range from9.1 C to

47.9 C, represented by digital data points; (b) high-resolution plot ofatemperature
change from 49.8 C to 48.7 C
The control measurement from the thermocouples is presented as solid pointswith error
bars representing the resolution of the thermometer. The resolution of thetemperature
channel was noise limited to 0.4 C(16:8 mV C ),whereas the temperature channel is
insensitive to any pH ischanced use the temperature channel to drift. Thus, bench test
measurements conductedon the temperature sensor revealed that the output signal
changed by 1.45 mV per mVchange in supply voltage ( (mV)-1.4Mv expressed in mill
volts, corresponding to a driftof -21mVin the pill from a supply voltage change of
14.5Mv.

Applications:
Capsules as Actuators
Drug delivery system is an issue of optimization for many
interests,immediate release drug will be absorbed in the upper part of the small
intestine afterstomach, extended release drug is desired to be absorbed in the lower level
of the intestine. Achievement of the second by normal coating
tablets is difficult dueto the complexity of the GI tract of human being, intubations is an a
lternativesolution, but it is uncomfortable for patients. Alternative solution will be of mor
einterest, and the idea of developing swallowed capsules
devices was , over twodecades engineers are trying to develop different capsules with the
capability tocontrol the time and the location of the drug release. The earlier capsules in
this domainwere HF, Indelicate, and Telemetric Capsules. They are triggered by a radiofrequency

19

(RF) pulse from a generator outside body, the heat generated

in thecircuit will melt a thread releasing a needle that pierces the container and spellsout
the drug. State-of-the-art in this domain are the Enterion capsule and ChipRxThe
patient must undergo several gamma scans to identify the location. Telemetriccapsule
uses a cogwheel means for localization. Enhancement in localization is of more interest
and more work can be done in this domain to achieve a practical solutionfor position
determination
Capsules as Sensors
Monitoring the variation of temperature, pH, motility and other functions aregetting easie
r and comfortable for patients. The need to collect biomedicalinformation within a specifi
c location is of high interest, most of the existing sensor
capsules dont provide location determination. Earlier products in this field are the
Radio Pill, BRAVO, Heidelberg and Temperature capsules. Almost all of themuse
internal battery for power consumption. New
capsules in this field are Anewplatform of an electronic pill with bidirectional communic
ation system forminiaturized and low power biomedical applications

20

Chapter -4
6.ADVANTAGES

It is being beneficially used for disease detection & abnormalities in human body.There
fore it is also called as MAGIC PILL FOR HEALTH CARE

Adaptable for use in corrosive & quiescent environment

It can be used in industries in evaluation of water quality, Pollution

Detection,fermentation process control & inspection of pipelines.

Micro Electronic Pill utilizes a PROGRAMMABLE STANDBY MODE, SoPower

consumption is very less.

It has very small size, hence it is very easy for practical usage

High sensitivity, Good reliability & Life times.

Very long life of the cells(40 hours), Less Power, Current & Voltage requirement(12.1
mW, 3.9 mA, 3.1 V)

21

Less transmission length & hence has zero noise interference.

7.CONCLUSION
We have developed an integrated sensor array system which has beenincorporated in a
mobile remote analytical microelectronic pill, designed to performreal-time
in situ
measurements of the GI tract, providing the first
in vitro
wirelesstransmitted multichannel records of analytical parameters. Further work will
focus ondeveloping photo pattern able gel electrolytes and oxygen and
cationselectivemembranes. The microelectronic pill will be miniaturized for medical and
veterinaryapplications by incorporating the transmitter on silicon and reducing
powerconsumption by improving the data compression algorithm and utilizing
aprogrammable standby power mode. The generic nature of the microelectronic
pillmakes it adaptable for use in corrosive environments related to environmental
andindustrial 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
asultrasound and impedance tomography, will improve the detection of
tissueabnormalities and radiation treatment associated with cancer and chronic
inflammation.In the future, one objective will be to produce a device, analogous to a
micro totalanalysis system ( TAS) or lab on a chip sensor [35] which is not only capable
of collecting and processing data, but which can transmit it from a remote location.
Theoverall concept will be to produce an array of sensor devices distributed throughout
thebody or the environment, capable of transmitting high-quality information in realtime.

22

23