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performance. As we have seen there is rapid progress away from

bench-top instrumentation design to modern integrated circuit

implementations. As a consequence it is appropriate to use silicon

design methodologies. Such methodologies have emerged from

the microelectronics industry as more complex designs have been

required (45, 46). We present a methodology here that is relatively

simple by the standards of the industry, but encapsulates sufficient

detail to enable accurate design of a sensor system.

5.1. Analogue

Electronic Front-End

Signal Acquisition

Design

The steps involved in designing an analogue circuit are illustrated

in Fig. 10.11. The main difference from digital design is that both

the schematic and physical designs are created by hand. An analo-

gue circuit starts off as a high-level model or simply a list of

requirements that must be met. The first attempt at a circuit design

is made using a schematic editor to draw a diagram of the compo-

nents and their connections. The standard components available in

a CMOS process are MOSFETs, resistors and capacitors, but

others such as diodes, bipolar transistors and inductors can also

be created. Parameterised models for all available component

types, obtained by characterising fabricated devices, are provided

by the foundry. The circuit is simulated by an analogue circuit

simulator such as SPICE.

The circuit is unlikely to fulfil its requirements at the first

attempt, so either the topology of the circuit or the parameters

of its components are changed. Depending on the complexity of

the circuit, several iterations may be required until the simulated

response matches the desired response. When this is achieved,

work can begin on the physical design (layout) of the circuit. A

layout editor is used to draw areas of n-type and p-type silicon,

polysilicon and metal that will form the components and connec-

tions. The task is usually made easier by the foundry that provides

parameterised cell macros that generate the layout data for

MOSFETs, resistors and capacitors. However, for low-noise,

Fig. 10.11. Flow-chart for the computer-aided analogue circuit design process.

Wireless Endoscopy: Technology and Design 237

well-matched, or compact circuits it is often necessary to create

these devices by hand. The arrangement of devices and the con-

nections between them is also carried out by hand. Once complete,

design rule check (DRC), electrical rule check (ERC) and layout

versus schematic (LVS) checks are performed to ensure that the

final design is as intended. The design can be modified as required

until a satisfactory conclusion is reached.

5.2. Digital System

Design

A flow diagram of the steps involved in designing a digital circuit is

shown in Fig. 10.12. In contrast to the analogue design flow, the

physical design can be generated using software. The digital circuit

may start off as a high-level ‘‘behavioural’’ model written in a

programming language such as C or Matlab. It is then re-coded

in a hardware description language (HDL) that allows the designer

to describe digital circuits. The code is then compiled, simulated

and debugged. Once the errors have been removed, simulation is

required to ensure that the HDL code performs the functions

described by the original high-level model.

If the HDL code uses only certain constructs that are allowed at a

code may be synthesised. The synthesis process automatically gener-

ates the details of the gates and their interconnections to form a

Fig. 10.12. Flow-chart for the computer-aided digital circuit design process.

238 Cumming, Hammond, and Wang

structural netlist. It attempts to optimise the netlist based on timing,

area and power constraints that are set by the designer, and on the

information contained in the library models provided by the foundry.

After synthesis, the netlist is converted into a physical layout by

the automatic ‘‘place and route’’ tool. Delay information is extracted

from this tool and used to annotate the structural netlist. If the

simulation of this timing-accurate netlist fails to meet the specifica-

tions, then another iteration of the design loop is required. The next

step in the process is to export the design, using the GDSII file

format (the standard file format for transferring/archiving 2D gra-

phical design data.) to describe the layout. The GDSII data and the

HDL structural netlist are then imported into the layout editor (as

used for the analogue design) to create the layout and schematic

views respectively. As a final check DRC, ERC and LVS checks are

performed as for the analogue design process.

6. The Wireless

Environment

The transmission of radio signals in and around the human body is

of considerable importance to the success of a wireless capsule

device. The behaviour of an electromagnetic field in the presence

of a human body is influenced by the dielectric properties of human

tissue. In addition, the dielectric function is frequency-dependent

and the absorption of electromagnetic waves increases with increas-

ing frequency. As a consequence, reflection at boundaries, scatter-

ing, absorption and refraction of electromagnetic fields are

frequency dependent. However, the radiation from electrically

small sources in free space increases with frequency. In addition,

the effect of the capacitive loading of the surrounding tissue on the

source has a complicated frequency and spatial dependence.

Unsurprisingly, given the prevalence of mobile telephony, the

majority of work that has been done to obtain a detailed under-

standing of radio transmission near the human body has focussed

on the head and neck. Early work used relatively simple body

models that assumed that human tissue was homogenous (48).

As work progressed, research moved to more sophisticated models

(49). More recently, there have been a number of studies looking

at the abdominal region using detailed models for both female

(50) and male bodies (51). The main results of these latter simula-

tions are shown in Fig. 10.13. The simulations were carried out

for an ingested transmitter at a number of possible locations and

orientations and the data shown is therefore only representative.

Despite the fact that absorption of electromagnetic radiation

increases with frequency it is found that, up to a point, increasing

the frequency can improve the far-field signal strength from an

Wireless Endoscopy: Technology and Design 239

ingested source (Fig. 10.13a). The reason for this is that the size of

the capsule device demands that an electrically small antenna be

used and that typically the antenna be very much smaller than /2

(the preferred size for the simplest radiating device), where  is the

wavelength. As a consequence, when the frequency is increased, the

wavelength decreases towards the antenna dimensions, increasing

the antenna’s efficiency. It has been found that there is a competing

effect between the increased efficiency of the antenna and the

increasing absorption of the body tissue, and ultimately there is a

trade-off in which an optimum frequency is found. Simulations have

shown this to be in the region of 650 MHz which does not corre-

spond exactly with any of the available ISM bands around the world.

Since it is comfortably between European and USA frequencies,

most major markets can be supplied.

The near-field pattern data is of interest since in many applica-

tions it is anticipated that the receiver antennae will be in close

proximity to the body, which is for the most part located in the

near-field for the wavelengths concerned. From Fig. 10.13b it can

be seen that there is greater field strength to the left-hand anterior

position of the abdomen due to the strongly absorbent nature of the

liver on the right-hand side. The results of simulations of this kind

can be used directly to assist in the design of the antenna system.

An alternative to conventional propagating wireless systems is to

communicate wirelessly using the inductive near-field (52). Without

dealing in detail with the electromagnetic problem here, it is possible

to transmit wirelessly at low frequencies over distances that are very

small compared to the propagating wavelength. In this evanescent

regime, designers can take advantage of the lower absorption of RF

power at lower frequencies and replace the antenna with two coils

Fig. 10.13. (a) Far-field radiation patterns from an ingested source at 150 MHZ (lower)

and 434 MHz (upper). The solid line is for E-field polarisation horizontal to the body and

the dashed line is for the vertical polarisation. (b) the near-field pattern showing the field

strength around the body.

240 Cumming, Hammond, and Wang

(one internally and one externally) that effectively behave as the

primary and secondary coils of a transformer respectively. Detailed

design and experimentation have shown that such a system can

communicate effectively over the required range consuming less

electrical power than a more conventional radio system.

6.1. Power Sources Powering capsule devices is perhaps one of the greatest challenges.

There are many possible micro-power sources currently being

researched, a review of which has been written by Roundy (53).

Not all the available techniques are useful in the context of an

ingested device, e.g. solar power. More practical techniques include:

a battery; electromagnetic induction; and electro-mechanical con-

version. Other schemes, such as making direct use of gut mucosa as

an electrolyte in an electrochemical cell arrangement, have been

proposed but have not been explored in any serious way.

Although the use of batteries is by far the simplest power

source, it comes with severe restrictions. Not all types of cell are

favourable to use in implants (e.g. ZnO

), and achieving adequate

power density from the safer choices available is difficult (e.g.

AgO). However a potentially greater problem than integrated

energy storage is peak current delivery, since even short periods

of high demand, for example during signal transmission, can very

rapidly deplete a battery. As a consequence, when designing a

microtelemetry system it is important to complete a detailed

power budget and make design decisions that will ultimately com-

promise the devices performance in order to ensure correct func-

tionality during a complete gut transit.

Electromagnetic induction is an attractive option not only

because it reduces the power constraint on the device but also

because removing the need for batteries would make the device

smaller. The maximum power density permitted near the human

body is in the region of 1 mW/cm

but varies from country to

country (54). This is a severe limitation given the power require-

ment and distance over which power must be transmitted to reach

a device deeply embedded in the human abdomen. With the

exception of the relatively simple RFID temperature sensing

devices developed for animal use that we have already discussed

there has not yet been any significant demonstration of this tech-

nology for the more sophisticated human medical devices.

7. Packaging

Having decided upon the internal apparatus of a laboratory-in-a-

pill it must all be packaged into a capsule. The package must be

mechanically strong, chemically inert and allow access between the

Wireless Endoscopy: Technology and Design 241

sensors and their environment. For optical devices there is always

the prospect of an obstruction blocking the lens, but the clear

plastic dome structures that are used in current products, such as

the M2A from Given Imaging, are relatively easy to manufacture

and strong. It is significantly more complicated to construct

packages that will permit fluid access onto sensor devices, espe-

cially if these devices are integrated circuits or chips that will be

adversely affected by current leakage due to liquids seeping into

the encapsulating materials.

One of the main obstacles that has prevented the commercia-

lisation of ISFET-based devices is the repeatability and reliability of

the encapsulation procedure. It is normal for the encapsulant to be

applied by hand, covering the chip and bond-wires but leaving a

small opening above the sensing area. Epoxy is the most exten-

sively used material although it is important to select a composi-

tion that is stable, is a good electrical insulator and does not flow

during encapsulation. Many commercially available epoxies have

been assessed for their suitability by making measurements of their

electrical impedance over time (55–58).

By using UV-curable polymers, it is possible to increase the

automation of the packaging process using a standard mask-aligner.

A lift-off technique was developed using a sacrificial layer of photo-

sensitive polyimide to protect the ISFET gates. Alumina-filled epoxy

was applied by screen printing and partially cured, before the poly-

imide was etched away leaving a well in the epoxy (59). After ten days

in solution, leakage currents as high as 200 nA were observed. Better

results were achieved by direct photo-polymerisation of an epoxy-

based encapsulant. ISFETs packaged using this method showed

leakage currents of 35 nA after three months in solution. To avoid

polarising the reference electrode, common to such devices, a leakage

current of less than 1 nA is desirable (60).

This photolithographic patterning of the encapsulant was

done at the wafer level to all the devices simultaneously. Subse-

quently the wafer was diced up and the individual chips were wire-

bonded and coated with more encapsulant by hand. At the chip

level, wire-bonded ISFET chips have been covered (again by hand)

with a 0.5–1 mm thick photo-sensitive, epoxy-based film, then

exposed and developed (61). After 20 days in solution, the devices

retained low leakage currents. Some degree of automation was

introduced by Sibbald (56) who used a dip-coating method to

apply the polymers. They first recessed the chip into a PCB and

wire-bonded the connections, before coating it with a layer of

polyimide. Two layers of photoresist followed, before the under-

lying polyimide was etched away (Fig. 10.14). The slight under-

cutting of the polyimide was reported to be useful in anchoring the

CHEMFET membrane in place. The packaged devices showed less

than 10 pA leakage current after 10 days in solution. However, the

encapsulation did exhibit electrical breakdown for applied bias

242 Cumming, Hammond, and Wang

voltages in excess of 1.5–2 V. This was attributed to the high

electric field in the thin layer of resist covering the bond-wires.

More recently, a single layer of an epoxy-based photoresist (SU-8)

has been used to package a pH-sensing microchip (62). In a

separate study, photo-sensitive polyimide has also been used to

create the wells that separate the ion-selective membranes on a

multiple ISFET chip (63).

It is interesting to note that although flip-chip bonding is a

well-established and robust packaging technique, it has not been

applied to liquid-sensing ISFETs. In flip-chip bonding, solder

bumps are patterned onto the bond-pads, allowing the chip to

be directly connected to a PCB without the need for bond-wires. A

gas sensor has been fabricated in this way, by bonding an ISFET to

a ceramic substrate that had been coated with a suitable polymer

(64). It may be that the high cost of solder bumping, which is

normally applied to a whole wafer of devices, has prevented wider

use of flip-chip bonding in capsule packaging.

8. Conclusion

Diagnostic pill devices have been in use for almost half a century

and with the availability of miniaturisation techniques for electro-

nics and sensors, they are now becoming practical devices for

introduction into routine clinical practice. In this chapter we

have outlined the history of the development of capsule devices.

It is interesting to note that capsule developers have always been

quick to adopt the latest discoveries from other fields, from the

earliest germanium transistors to system-on-chip and laboratory-

on-a-chip techniques. Of the current crop of devices, the video

capsule in particular has drawn a great deal of attention, although

pH-sensing devices for use in the oesophagus have perhaps made

the greatest clinical impact. As new technologies develop and

mature, we can only speculate as to what extent diagnostic capsule

devices will become commonplace in hospitals, surgeries and per-

haps even the home.

Fig. 10.14. Diagram of the cross-section through a CHEMFET device in a recessed PCB,

encapsulated using a layer of polyimide and two layers of photoresist (56).

Wireless Endoscopy: Technology and Design 243

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