Biomedical Sensors Using Optical Fibres

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Rep. Prog. Phys. 59 (1996) 128. Printed in the UK

Biomedical sensors using optical fibres

Anna Grazia Mignani and Francesco Baldini

Istituto di Ricerca sulle Onde Elettromagnetiche Nello Carrara, CNR Via Panciatichi 64, I-50127, Firenze, Italy

Abstract

Optical techniques developed for sensing purposes proved to be essential in many application

fields, ranging from aerospace, industry, process control, to security, and also medicine.

The capabilities of these sensors are generally enhanced when a bulk-optical configuration

is replaced by optical fibre technology. In the past few years, research programmes and

also the market for fibre sensors have assumed a relevant role. This is undoubtedly due tothe growing interest in optoelectronics, but also to the very satisfactory performance and

reliability that optical fibre sensors are now able to provide. This paper focuses on the

advantages that optical fibre sensors offer to the biomedical field, recalls the basic working

principles of sensing, and discusses some examples.

This review was received in July 1995

E-mail address: [email protected]

E-mail address: [email protected]

0034-4885/96/010001+28$59.50 c 1996 IOP Publishing Ltd 1


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2 A G Mignani and F Baldini

Contents

Page

1. Introduction 3

2. The basic working principle of sensing 4

2.1. Architecture 4

2.2. Main problems 6

3. Sensors for physical parameters 6

3.1. Pressure 6

3.2. Temperature 8

3.3. Blood flow 9

3.4. Humidity 10

3.5. Cataract onset 10

3.6. Radiation dose 11

3.7. Biting force 124. Sensors for chemical parameters 12

4.1. Bile 12

4.2. pH 13

4.3. Oxygen 19

4.4. Carbon dioxide 21

4.5. Lipoproteins 21

4.6. Lipids 22

4.7. New aspects and perspectives of chemical sensors 22

5. Spectral sensors 23

6. Conclusions 24

Acknowledgments 25

References 25


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Biomedical sensors using optical fibres 3

1. Introduction

In the medical field, the opportunities offered by optical fibres have always been

advantageously exploited. In fact, the use of optical fibres in medicine goes back to the

sixties, when fibre bundles were successfully pioneered in endoscopy, both for illumination

and for imaging. Subsequently, cavitational laser surgery and therapy also benefited from

fibres, which proved to be the most flexible, and a low-attenuation delivery system inside

the ancillary channel of endoscopes, and inside the natural channels of the human body as

well. More recently, and especially since 1980, a great deal of research in optical fibres

has been dedicated to sensing, and again the medical field found good opportunities for

developing very promising sensors.

Two classes of clinical care procedures can be distinguished, in which conventional

methods present some drawbacks:

in vitro laboratory tests of blood or tissue samples, which means frequent sample-

takings for continuous checking, thus placing the patient under stress. In addition,

therapeutic intervention is delayed, and errors can also occur, due to sample handlingand photodegradation;

in vivo measurements of many physical and chemical parameters performed by electrical

devices (thermocouples, CHEMFET, semiconductor or piezoelectric elements), which are

fragile and expensive, and expose the patient to electrical connections.

Fibre optic sensors (FOSs) overcome some of these drawbacks, owing to the well known

inherent characteristics of optical fibres:

geometrical versatility, such as miniaturization, flexibility, and lightness, which allow

easy insertion in catheters and needles, and hence highly localized measurements inside

blood and tissues;

suitable material, glass or plastic, which is study, non-toxic and biocompatible, and can

be used for continuous measurements;

intrinsic safety for the patient, ensured by optical fibre dielectricity and by the low lightpower used for sensing purposes.

Furthermore, optical fibres present low attenuation, so that long fibre links can be used, if

the electronics must be located far from the bedside; in this case, fibres must be cabled,

so as to avoid handling problems. Another property is the absence of crosstalk between

close fibres, which suggests housing different sensors in the same catheter. In some cases

a single electro-optic unit can be utilized for all the sensors, naturally with an appropriate

illumination, detection and signal-processing scheme.

An overview of fibre optic sensors for biomedical applications is given, with particular

attention to the sensors developed for in vivo monitoring, and to the advantages that these

sensors are able to offer in different fields of application such as cardiovascular and intensive

care, angiology, gastroenterology, ophthalmology, oncology, neurology, dermatology and

dentistry.

Examples of FOSs are reviewed according to a classification in three main classes:

sensors for physical parameters, sensors for chemical parameters and spectral sensors, for

which spectral analysis is performed in order to know the state of health of a particular

organ or tissue.


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2. The basic working principle of sensing

The working principle of FOSs is based on the modulation of the fibre-guided light

produced in one of the optical properties (phase, intensity, wavelength, polarization state)

by the parameter under investigation. The complexity of the electro-optical system, the

type of components selected, and thus cost of the sensor are related to the operating

principle.

The ideal FOS for biomedical applications should possess the following characteristics:

reliability, automatic or semiautomatic operation for use by operators who have little or no technical

background,

low-cost installation and maintenance.

These requirements limit the selection of the sensors operating principle and impose

limitations to the complexity of the electro-optical system. FOSs for biomedical applications

are mostly of the intensity modulation type, owing to the low cost of their components and

the simplicity of their architectures. They can be either intrinsic or extrinsic, according to

whether the intensity modulation is produced by the fibre, which is sometimes modified, or

by an external transducer connected to the fibre (figure 1).

Figure 1. Working principle of intensity-modulated fibre-optic sensor.

2.1. Architecture

A FOS of the intensity modulation type can be viewed as a compact electro-optical module

connected to the measuring probe by a multimode optical fibre (figure 2). The module

houses source(s), detector(s), and all the electronics for signal processing.

The sources can be either lamps, lasers, LEDs, or laser diodes. Lamps and lasers

require beam focus optics and holders for the fibre alignment. If a halogen lamp is

used, interferential or dichroic filters may also be necessary when the sensor has a specific

operating wavelength. LEDs and laser diodes, the most compact, may be housed in special

receptacles that are easily connected to the fibre by commercial connectors. The most

recent LEDs and laser diodes offer a wide variety of wavelengths. Laser diodes have a high

emission power and can, in many cases, replace costlier and bulkier lasers.

The detectors are normally PIN-type photodiodes, which are also housed in proper

receptacles, sometimes with filters to provide spectral response.

The electro-optical module provides modulation of the source and amplification of the

detected signals. An analogue/digital interface that connects the electronic section to a


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Figure 2. Sketch of the instrumentation of a fibre-optic sensor.

PC can enhance system control and, in addition, is useful in calibration and in carrying

out and recording measurements over long periods. For standard procedures that require

no subsequent modification, a preprogrammed microprocessor can be used in place of

a PC.

The optical fibre connection carries the light intensity from the source to the probe and

returns the intensity modulated by the measuring parameter to the detector. Generally, fibres

having diameter larger than 100 m are used to maximize the sources coupling efficiency.

The fibres can be all silica (AS) or plastic silica (PCS), either bare or cabled, according to

application.

The connection can be either single fibre, in which case the fibre serves for both

lighting and detection, or two fibre, in which case one fibre serves for lighting and one

for detection. The single-fibre connection, which is evidently more compact and thus

reduces probe dimensions, requires a device upstream of the fibre that separates the lighting

and detection channels. However, the beam divider should always be characterized by

intrinsic low losses and crosstalk to avoid covering up the measuring signal and also

impairing the signal-to-noise ratio. Often bi- or trifurcated fibre bundles are used, with

random distribution of the fibres inside the bundle or with special distributions (linear,

semicircles, concentric circles, etc). In such case, the source(s) and detector(s) are connected

to the branches of the bundle and the common termination is connected to the measuring

probe.

The optical architecture can be either all fibre or hybrid:

In the all-fibre architecture, all the optical components connected to the fibre (X-, Y-,

or star couplers, WDM, gratings, etc) are optical fibre based and the components are

connected simply and compactly with commercial type connectors; In the hybrid architecture, used when optical fibre components with less than satisfactory

characteristics are available, the miniaturized optical components, such as lenses, filters,

gratings, mirrors, etc, must be specially aligned and connected.


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2.2. Main problems

The main problems regarding intensity modulation FOSs are:

Sensitivity to light propagation. A problem common to all intensity modulation FOSs is

sensitivity to propagation conditions. Since the information is contained in the intensity of

the guided light, any modulation not correlated to the state of the measuring parameter upsetsthe measurement. For example, an incorrect interpretation can be caused by fluctuations in

the source or attenuations introduced by fibre curvatures. To solve this problem, a reference

system must be used to compensate for the undesired intensity fluctuations, despite the

increase in system complexity and thus the cost it entails. Source intensity fluctuations can

be offset by normalizing the measurement signal S with a reference signal R proportional

to the source intensity. Other spurious fluctuations such as those produced by propagation

accidents can be offset by a lighting signal with two wavelengths, one of which is modulated

in intensity by the investigated parameter and the other of constant intensity. Since they both

travel on the same fibre, their ratio provides a measurement devoid of propagation accidents.

Insufficient lighting power. The main problem determined by active and passive optical

components is insufficient lighting power in the FOS. This depends somewhat on the

power emitted by the source, and also on the quantity and quality of the required passivecomponents. The requisites of the source, i.e. compactness, adequate power, and suitable

wavelength, are not always fulfilled, especially when a source that is visible or beyond the

range of typical telecommunication wavelengths is required. The requisites of the optical

components are compactness and the capacity of each to perform several functions. The

number of passive components should be minimized by accurate assessment of system

power requirements.

Design and manufacturing specifications. The probes require accurate workmanship

and hand assembly and must be designed to produce a high back-transmitted signal

simultaneously with a fast response time. Major requisites are optimized housing,

miniaturization, seal, and transducer stability. Particular attention must be devoted to the

requisites of biocompatibility: i.e. the probe must not adversely affect the body nor must beadversely affected by it. The latter consideration should not be taken lightly; in fact, often

we think only about the dangerous effect that an invasive sensor can have on the human

body, and do not consider that (especially in chemical sensors, where a chemistry is fixed

at the end of the fibres) the local environment can notably impair sensor performance.

3. Sensors for physical parameters

The physical parameters of medical interest that have been successfully measured by FOSs

are mainly pressure, temperature, blood flow, humidity, as well as cataract onset, radiation

dose and biting force.

3.1. Pressure

Head trauma patients require continuous monitoring of intracranial pressure. During the

post-operative and drainage monitoring phases, it is essential to know, respectively, the

subdural and ventricular pressures, as well as the pressure waveform display. Non-optical


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Figure 3. FabryPerot fibre-optic pressure sensor.

instruments make use of catheters tipped with miniaturized piezoresistive or capacitive

transducers, whose main drawbacks are long-term drifts, electrical-shock hazard, fragility

and costliness. FOSs, being relatively easy to manufacture and therefore inexpensive enough

to be disposable, overcome these drawbacks. In addition, they perform as well as or better

than electric instrumentation. Main measurement requirements are: (i) a working range

from 50 to 300 mmHg; (ii) a sensitivity of at least 0.1 mmHg; (iii) an accuracy of at least

1%; (iv) a flat frequency response up to 1 kHz. Among the many proposed pressure FOSs,

two types fulfil the low-cost, high-performance requirements. One has a FabryPerot cavity

at the fibre tip [1, 2]; the other has a small diaphragm in front of the fibre optic link [35].

The FabryPerot cavity for pressure sensing is a glass cube having a partially etchedface, covered by a pressure sensitive silicon diaphragm (figure 3). The pressure, deflecting

the diaphragm, alters the cavity depth and thus the optical cavity reflectance at a given

wavelength. If an LED source is used, the spectrally modulated reflected light can be split

into two wavebands by a dichroic mirror. The ratio of the two signals provides a pressure

measurement immune to the typical light level changes occurring in FOS systems. A sensor

of this type, together with the complete intracranial pressure monitoring system, is currently

available from the American company Innerspace [6].

The other pressure sensing approach, characterized by a diaphragm in front of the fibre

optic link, is based on the light intensity modulation of the reflected light caused by the

pressure-induced position of the diaphragm. Two schemes can give immunity to false

fluctuations: (i) a dichroic coating on the diaphragm and the dual-wavelength referencing

technique, and (ii) a dual-beam referencing using a second fibre optic path, which is joined

to the pressure measuring fibre link, but unaffected by pressure fluctuations. The low-cost

disposable FOS manufactured by the American company Camino Labs [7], which uses a

bellow as a transducer, is interrogated by the intensity modulation technique with dual-

beam referencing (figure 4) [8].


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Figure 4. Fibre-optic pressure sensor based on a mechanical transducer.

3.2. Temperature

Fibre-optic thermometers are used when electrical insulation and EMI immunity are neces-

sary [9]. The most relevant application involves tissue-heating control during MW or RF

hyperthermia therapy for cancer treatment. For this application, conventional thermistors

or thermocouples can perturb the incident field and produce localized hot spots. Other

applications of thermometry by fibre-optic sensors are the mapping of thermal distribu-

tion in cancer phototherapy, patient monitoring during magnetic-resonance imaging, and

cardiac-output monitoring by means of the thermodilution technique. The possibility of

simultaneous monitoring with arrays of multiple sensors is also desirable. For these ap-plications, the restricted working range 3545 C is sufficient, with a sensitivity of at least

0.1 C. Because of the many applications, fibre-optic thermometers have been widely pro-

posed, either using all-fibre mechanisms [10], and transducers undergoing intensity [11] or

wavelength modulation [12, 13], or operating in the time domain [14].

The fibre optic thermometer commercialized by the American company Luxtron [15],

one of the first developed for this purpose (figure 5), performs time-domain measurements

and stands out for technical performance and patient safety. UV light guided by the fibre

is used to excite phosphors fixed at the fibre end and fluorescence decay-time is measured,

which results temperature modulated and intrinsically down-lead insensitive as well. Other

sensors based on a fibre FabryPerot (FFP) cavity coupled at the fibre tip [16, 17] and MID-IR

fibres used as pyrometers [18] are under development.

Figure 5. Luxtron 3000: an 8-channel fibre-optic temperature sensor.


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3.3. Blood flow

Laser Doppler flowmetry is a powerful tool for vasomotion monitoring, and the use of

optical fibres enhances the possibility of both invasive and contact measurements. The

basic scheme of fibre-optic laser Doppler flowmetry is illustrated in figure 6. The light

of a HeNe laser is guided by an optical fibre probe to the tissue or vascular network

being studied. The light is diffusely scattered and partially absorbed within the illuminated

volume. Light hitting moving blood cells undergoes a slight Doppler shift. The blood

flow rate is derived by the spectrum-analysis of the back-scattered signal, which presents a

flow-dependent Doppler-shifted frequency.

Various types of probes have been developed, either using a single fibre for illumination

and detection, or one fibre for illumination and two or three for detection [19]. An instrument

that is widely used in the clinical practice is produced by the Swedish company Perimed

(figure 7), which offers a wide selection of contact and endoscopic probes, with straight

or angular tips, as well as with channels for liquid flushing [20]. Typical applications are

in: (i) plastic and reconstructive surgery for monitoring flap quality; (ii) angiology for

Figure 6. Basic scheme of fibre-optic laser Doppler flowmetry.

Figure 7. PeriFlux PF3: the Perimed instrument for fibre-optic laser Doppler flowmetry.


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locating atherosclerosis and occlusions; (iii) dermatology for testing several types of skin

irritancies such as psoriasis, or produced by topical drugs or cosmetics; (iv) pharmacology

for detecting vasoactive drugs and dose response. Endoscopic and needle probes are used for

invasive and deep measurements, for example in gastroenterology and in vascular surgery,

respectively.

3.4. Humidity

A major requirement of intensive care is the continuous monitoring of breathing condition,

i.e. the cough, sneeze, and breathing count. It should be possible to monitor from the nurses

station so patients can be kept under observation without a nurse being physically at their

bedsides. An optical fibre with a moisture-sensitive cladding has been developed for this

purpose. It is simple to use and has given good performance results. The cladding of the

sensitive fibre-section is a plastic film doped with the umbelliferon dye, which is a moisture-

sensitive fluorescent material under UV-pumping. The sensitive fibre-section is placed over

the patients mouth and laterally excited with a halogen lamp. Since the water vapour in

human respiration exceeds that in the room, the patients expiration produces a fluorescent

signal which is detected by an electro-optical unit at the nurses station. This kind of

monitoring is particularly useful in detecting abnormal breathing in bedridden patients [21].

Another very simple humidity FOS has been developed for the continuous monitoringof the respiratory rate. The sensor is based on the change of light reflection at the fibre end

which is caused by a change in the condensed humidity from the airways during respiration.

An optical fibre is simply clasped inside the nostril. During inspiration, the air is dry and

cool, and there is maximum backreflected light. During expiration, a water film deposits

on the fibre and the backreflected light is reduced by about 50%, so that the respiration rate

can be monitored. Sensor output thus consists of a rhythmic signal, the frequency of which

represents the respiratory rate [22].

3.5. Cataract onset

A major ophthalmological application of FOSs is the recognition of the onset of eye lens

opacification, commonly known as cataracts. Since, in addition to ageing, cataracts can be

caused by diseases such as hyperglycaemia or injury such as exposure to radiations, the earlydetection of a warning condition is essential in preventing and testing the new therapies that

are now becoming available. As opposed to current clinical diagnostic methods, which only

detect cataracts when they are nearly irreversible, fibre-optic monitoring makes detection

possible at onset, in time for reversal.

The eye lens is a waterprotein system composed of water ( 65 weight percentage)

and proteins ( 35 weight percentage). About 10% of the proteins, called the albuminoid

fraction, are insoluble, while the remaining 90% of soluble proteins are divided into , ,

and crystallins. Cataract onset is attributed to crystallin aggregation and can be recognized

by periodic measurement of the crystallin dimensions.

A powerful and versatile tool for measuring particle size distribution in fluid systems

is the Dynamic Light Scattering (DLS) technique. In this case, the Brownian motion

of crystallins in the cytoplasm illuminated by a coherent light source produces temporal

fluctuations in the scattered light. The measured intensity autocorrelation function shows

an exponential decay, whose decay constant is related to the hydrodynamic radius of the

scattering particles. Cataract onset is recognized by DLS measurement of the -crystallin

aggregation, since the -crystallins are of greater molecular weight and size, and thus scatter


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more light than the - and -crystallins.

The non-invasive optical fibre probe is a stainless steel capillary (OD 5 mm)

ending in a face plate which houses two monomode fibres sloped at a fixed angle with

respect to the capillary axis (figure 8). One of the fibres is coupled to a HeNe laser

used for illuminating the scattering region inside the eye lens. The other collects the

backward scattered light, which is measured by a photomultiplier and processed by a

digital correlator. Intensity autocorrelation measurements show a nearly bimodal distributionof particle size, respectively corresponding to -crystallins and their aggregation. The

probe can be easily incorporated into conventional ophthalmological instruments such as an

applanation tonometer mount [2325].

Figure 8. Assembly for cataract onset monitoring by optical fibres and Dynamic Light Scattering

measurements.

In addition to allowing prompt, non-invasive monitoring of cataract onset, optical fibres

also enhance the efficiency of the DLS technique. By providing a beam of small numerical

aperture and dimensions, monomode fibres are able to produce an extremely small angle ofcoherence, and hence an optimal spatial coherence factor ( 0.9), which would be difficult

to obtain with bulk optics systems [26].

3.6. Radiation dose

The success of radiotherapy is related to the on-line monitoring of the dose to which

the tumour and the adjacent tissues are exposed. Conventional thermoluminescence

dosimeters only provide off-line monitoring, since they determine the radiation exposure

after completing irradiation. A short length of heavy metal-doped optical fibre coupled to

a radiation resistant fibre is an optimal system for the continuous monitoring of radiation

dosage in both invasive and non-invasive applications. The light propagating in the doped

fibre section undergoes an intensity attenuation in the presence of radiation, since the

attenuation is nearly linear to the radiation dose. Differential attenuation measurement

compensates for insensitivity due to cable and connector losses [27].


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3.7. Biting force

A FOS for dentistry measures biting force, which is an essential parameter in studying

disturbances of the masticatory system and in the case of patients with osseointegrated

implants or dentures. Unlike conventional piezoelectric crystals, quartz crystals, and strain

gauges, which are unsuitable due to the high conductivity of the oral cavity, optical fibres

are intrinsically safe.

The FOS is constituted by a mouthpiece made of two stainless steel plates with amicrobending FOS placed in between. The optical fibre results squeezed in between two

plates inducing a periodic deformation in the fibre and giving a light intensity attenuation

as the biting force increases. The system is managed by a personal computer with software

providing display, zeroing, and calibration. The dynamic range is 11000 N with a resolution

of 10 N, which is satisfactory for the application [28].

4. Sensors for chemical parameters

In fibre-optic chemical sensors the light transported by the fibre may be directly modulated

either by the parameter being investigated (spectrophotometric sensors), or by a special

reagent connected to the fibre, whose optical properties vary with the variation in the

concentration of the parameter under study (transducer sensors). The probe is often calledoptrode, as it represents an optical electrode. The main physical phenomena exploited for

the realization of chemical sensors are fluorescence and absorption, even if chemical optical

fibre sensors have been realized by exploiting other physical phenomena, such as chemical

luminescence, Raman scattering, evanescent-wave coupling, and plasmonic resonance.

4.1. Bile

The demand for FOSs for in vivo monitoring of foregut functional diseases is notably

on the increase. The first and, to-date, only FOS available on the market for such an

area of application is the Bilitec 2000 (manufactured by Prodotec, Firenze, Italy, and

commercialized by Synectics, Stockholm, Sweden), for the detection of enterogastric and

nonacid gastroesophageal refluxes [29] which are considered to be contributing factors

to the development of several pathological conditions such as gastric ulcer, chemicalgastritis, upper dyspeptic syndromes, and severe oesophagitis. Under certain conditions, the

enterogastric reflux may also increase the risk of gastric cancer. Optical detection is based

on the optical properties of bile which is always present in such refluxes [30].

Basically, the Bilitec 2000 (figure 9) utilizes the light emitted at = 465 nm and

570 nm (reference) by two LEDs, and an optical fibre bundle that transports the light from

the sources to the probe, (which is actually a miniaturized spectrophotometric cell whose

external diameter is 3 mm) and from the probe to the detector. The instrument evaluates the

logarithm of the ratio between the light intensities collected by the detection system. Since,

according to the LambertBeer law, the difference in the logarithms measured in the sample

and in pure water is proportional to the bilirubin concentration, said difference is related to

the bile-containing reflux in the stomach and/or oesophagus. The method has been validated

on numerous patients by inserting the optical fibre bundle into the stomach or oesophagus via

the nasal cavity [31]. The sensitivity of the sensor is 2.5 mol/L (bilirubin concentration),

and the working range is 0 100 mol/L. This range fits well with the range which can be

encountered in the stomach or in the oesophagus: even if the bilirubin concentration in pure

bile can be as high as 10 mmol/L, it is progressively diluted to its final concentration in


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Figure 9. Bilitec 2000: the only instrument for the direct detection of gastric refluxes.

the refluxate by pancreatic enzymes, duodenal secretion and, lastly, by the gastric content.

Clearly, the characteristics of the above mentioned sensor refer to in vitro tests; as for in

vivo measurements, since the gastric content is inhomogeneous with both mucus and solid

particles suspended, although the absorbance values could numerically express the bilirubin

concentration, they can only make possible an approximate quantitative assessment of the

overall bile reflux concentration. In any case, the sensor is able to measure accurately the

contact time between the refluxate and the gastric and/or oesophageal mucosa.

4.2. pH

pH is a very important quantity; our knowledge of it, however, is strictly related to the

diagnosis of the good working of many organs and parts of the human body. pH is

generally detected by a chromophore which changes its optical spectrum as a function

of the pH; absorption-based indicators or fluorophores are used for this.

4.2.1. Blood pH. Real-time monitoring of pH in the blood should be always accompanied

by measurement of the oxygen and carbon dioxide partial pressures, pO2 and pCO2respectively. Continuous and real-time knowledge of these parameters is of paramount

importance in operating rooms and intensive-care units, in order to determine the quantity

of oxygen delivered to the tissues and the quality of the perfusion. Conventionally,

these parameters are measured by benchtop blood-gas analysers on manually-withdrawn

blood samples. In any case, significant changes may occur in blood samples after their

removal from the body and before measurement is carried out by means of a blood-gas

analyser. Thanks to their ability to provide continuous monitoring, FOSs represent a welcome


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Figure 10. Fibre-optic probe based on phenol-red dye for blood pH monitoring.

improvement in patient management.

Invasive sensors must fulfil the following requirements: (i) they must be suitably

miniaturized so as not to slow down blood flow and thus give rise to clotting; (ii) they must

not be thrombogenic; and (iii) they must be resistant to platelet and protein deposit. Since

deposit resistance is primarily related to the sensors shape and to its chemical and physical

properties, probes with smooth surfaces and coated with materials such as anticoagulants,

and antiplatelet agents (e.g. heparin) are commonly used. It is apparent that these conditionsmust be satisfied not only by pH sensors, but by all sensors inserted in the circulatory

system.

The first pH sensor was developed at NIH (Bethesda, Maryland) and made use of

phenol red as its acid-base indicator, covalently bound to polyacrylamide microspheres; such

microspheres are contained inside a cellulose dialysis tubing (internal diameter: 0.3 mm)

connected to two plastic fibres (core diameter: 500 m). The probe was inserted into tissue

or a blood vessel through a 22-gauge hypodermic needle (figure 10). The probe was tested

in vivo on animals for the detection of extracellular acidosis during regional ischemia in

dog hearts [32], of transmural pH gradients in canine myocardial ischemia [33], and of

conjunctival pH [34].

The first intravascular sensor for the simultaneous and continuous monitoring of pH,

pO2, and pCO2 uses three optical fibres (fibre diameter = 125 m), and was developed by

CDI-3M Health Care (Irvine CA, USA) on the basis of a system designed and tested by

Figure 11. Sketch of the fibre-optic probe for the in vivo simultaneous detection of pH, pO2,

and pCO2 in human blood.


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Gehrich et al [35]. The fibres are encapsulated in a polymer enclosure, that also contains

a thermocouple embedded for temperature monitoring (figure 11). pH measurement is

carried out by means of a fluorophore, hydroxypyrene trisulphonic acid, covalently bonded

to a cellulose matrix attached to the fibre tip. Both the acidic (exc = 410 nm) and alkaline

(exc = 460 nm) excitation bands of the fluorophore are used, since their emission bands are

centred on the same wavelength (em = 520 nm). The ratio of the fluorescence intensity for

the two excitations appears to be relatively insensitive to optical fluctuations. Measurementsof pO2 and pCO2 are described in the following sections.

The optoelectronic system consists of three modules, one for each sensor. A Xenon

lamp (operating at 20 Hz), suitably filtered, provides illumination for the three modules.

The light from the source is focused through a GRIN lens onto a prism beam-splitter and

is coupled by means of a fibre to the sensor tip, while the deflected light is collected by a

reference detector for source control. The returning fluorescence is deflected by the prism

beam-splitter onto the signal detector through a filter selecting the fluorescence light. A

microprocessor processes all the detected signals, giving the read-out of the three measurands

on a monitor. The described probe (OD = 0.6 mm) has been tested in vivo on animals

[36, 37], exhibiting satisfactory correlation with data obtained ex vivo from electrochemical

blood gas analysers.

In clinical trials on volunteers in intensive care and on surgical patients, among the

problems that have emerged with the use of intravascular optical fibre sensors are: (i) theformation of a thrombus around the sensor tip which alters the value of all the analytes and

(ii) the so-called wall effect which primarily affects the oxygen count since, if the fibre tip

touches the arterial wall, it measures the oxygen in the tissue, which is lower than arterial

blood oxygen.

These problems are clearly avoided in a system working in an extracorporeal blood

circuit, developed by CDI-3M and available on the market since 1984. Figure 12 shows the

connection between the fibre link and the blood circuit. A disposable probe, which makes

use of the same chemistry as the intravascular optrode previously described, is inserted on

line in the blood circuit on one side and connected to the fibre bundle on the other. The

Figure 12. Exploded view of the optrode of the CDI-3M blood-gas analyser for extracorporeal

analysis.


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system is currently serving in open-heart measurements; more than 10 000 disposable probes

are produced by CDI-3M monthly.

Figure 13. Intravascular probe with bent fibre and side-window sample chamber.

Other intravascular-probe systems have been proposed by Abbott (Mountain View, CA)

[38] and by Optex Biomedical (Woodlands, TX) [39], as the structure of the probe is similar

to the CDI one previously described, i.e. three different multimode fibres, each of which is

associated with the specific chemistry and charged with the detection of a single measurand.

In the Optex Biomedical approach, the configuration is somewhat different: each single fibre

is bent, and a side-window sample chamber is built up to contain the appropriate chemistry

(figure 13). The use of plastic fibres ensures that the bundle will not break during insertion,

routine patient manipulations and removal. There are basically three advantages in this lat-

eral configuration: (i) the real optrode does not suffer any mechanical stress during insertion

through the arterial catheter, (ii) there exists the possibility of avoiding the wall effect by

rotating the probe into areas where the blood flow is good, and (iii) there is an increased

sensing-element washability in the presence of a thrombus or other fouling phenomena.A different approach, recently proposed but still not tested in vivo [40], makes possible

simultaneous multi-analyte detection with a single bundle of imaging fibres (1500 individual

10 m fibres with an overall diameter of 400 m). Spatial discrimination is obtained by

creating, at the distal end of the bundle, separate portions with different indicating chemistry

obtained by means of the photopolymerization process. The same optoelectronic system is

used for both photodeposition and detection (figure 14). The white light from a mercury

Xenon lamp suitably collimated passes through a dichroic filter, is removed during the

photodeposition and is replaced by a pinhole, followed by a microscope objective. By

adjusting the pinhole size and objective magnification, it is possible to illuminate a given

portion of the fibre bundle distal end which is then dipped into a polymerization solution

containing the appropriate fluorophore (fluorescein for pH and pCO2 and a ruthenium

complex for pO2). Photopolymerization allows the immobilization of the fluorophore only

in the illuminated region. Detection of the return fluorescent signal is performed by using

appropriate excitation and emission filters for the different sensing spots, and a CCD camera.

An image-process approach is necessary in order to discriminate between the responses

coming from the different sensitive spots.


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Figure 14. Multianalyte detection with an imaging fibre bundle: scheme of the optoelectronic

system used for both optrode photodeposition and detection.

4.2.2. Gastric and oesophageal pH. The gastric and oesophageal pH is an important pa-

rameter for the study of the human foregut. Monitoring gastric pH for long periods (for ex-

ample, 24 hours) serves to analyse the physiological pattern of acidity, provides information

regarding changes in the course of a peptic ulcer, and makes it possible to assess the effect

of gastric antisecretory drugs. In the oesophagus gastrooesophageal reflux, which causes a

pH decrease in the oesophagus content from pH 7 to pH 2, can determine oesophagitis with

possible strictures and Barretts oesophagus, which is considered a preneoplastic lesion.

In addition, in measuring the bile-containing reflux, the bile and pH should be measured

simultaneously, since the accuracy of bile measurements decreases by about 30% for pH

< 3.5 due to a shift in the bilirubin absorption peak to lower wavelengths [41].

Current practice is to insert a miniaturized glass electrode mounted on a flexible catheter

into the stomach or oesophagus through the nostrils, an impractical system due to the size and

rigidity of the glass electrode, as well as to the possibility of electromagnetic interference.FOSs eliminate these drawbacks, although the broad range of interest (from 1 to 8 pH units)

requires the use of more than one chromophore, which thus complicates the optrode design

and construction. Most likely this is why almost all the fibre-optic pH sensors developed

for biomedical applications have been proposed for blood pH detection, and why only a

few have been proposed for the detection of gastric or oesophageal pH [42, 43, 44].

The first sensor proposed for this application made use of two fluorophores, fluorescein

and eosin, immobilized in fibrous particles of amino-ethyl cellulose fixed on polyester foil.

The sensor, characterized by a satisfactory response time (about 20 s), was only tested in

vitro. First in vivo measurements have been performed only very recently [45, 46], but none

of the proposed systems appears completely satisfactory.

John Peterson proposed a sensor based on two absorbance dyes, meta-cresol purple and

bromophenol blue, bound to polyacrylamide microspheres. The configuration of the probe

is similar to the one for blood pH measurement previously described (figure 10): the dyed

particles are enclosed in 300 m inside diameter cellulosic-dialysis tubing, attached to a

250 m diameter acrylic optical fibre. The fibre is connected to a laboratory optical system

arrangement consisting of a lamp coupled to filters, a CCD spectrometer and a personal


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computer. The sensor was tested on samples of human gastric fluid, and was also tested

in vivo by inserting the optical probe into the stomach of a dog. The accuracy, better

than 0.1 pH units, satisfies clinical requirements, but the response time is much too long,

between 1 and 6 minutes depending on the pH step; such a long response time would

prevent detection of any rapid change of pH, and makes the sensor useless for the detection

of gastro-oesophageal reflux in which pH changes are very often extremely rapid (less than

1 minute).Another sensor makes use of two dyes, bromophenol blue (BPB) and thymol blue (TB),

to cover the range of interest. The chromophores, immobilized on controlled pore glass,

are fixed at the end of plastic optical fibres: the distal end of the fibres is heated and theCPGs form a very thin pH-sensitive layer on the tip of the fibres. Figure 15 shows a sketch

of the probe: four fibres are used (two for each chromophore) and a Teflon reflector was

placed in front of the fibres. A small fine steel wire was used in order to have a better

coupling of the modulated light. An optoelectronic unit, similar to that used for bilimetric

monitoring, has been developed: it consists of two similar channels, separately connected

with the fibres carrying TB and BPB for the detection of pH in the range 1 3.5 and in the

range 3.57.5, respectively. The use of light-emitting diodes as sources and of an internal

microprocessor has made it possible to construct a truly portable sensor. In vitro accuracy

was 0.05 pH units. On the other hand the in vivo accuracy is still not satisfactory since

in some cases, a step of some tenths of pH is present between the response of the opticalsensor and the pH electrode.

Figure 15. Sketch of the optical probe for in vivo gastric pH monitoring.

4.2.3. Tissue pH. Twin-fibre probes are generally used for in vivo mapping of normal

and tumoural areas by means of pH measurements, since malignant tumours induce a

decrease in the pH of the interstitial fluid and depression caused by the administration

of glucose. Dual-wavelength fluorometry using optical fibres provides a new diagnostic

tool for highly-localized measurements. A nontoxic pH-dependent indicator (fluorescein

derivatives) is injected in the tissues to be analysed, and the twin-fibre probe illuminates

the tissue and measures the fluorescence intensities at 465 and 490 nm. The ratio of these

fluorescence intensities is related to the pH of the tissue, thus providing normal-neoplastic

tissue-mapping [47, 48].


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4.3. Oxygen

Together with pH, oxygen is surely the chemical parameter most investigated for in vivo

applications, as its knowledge and continuous monitoring are very important in many fields,

such as those of circulatory and respiratory gas analysis.

4.3.1. Blood oxygen. As outlined previously, a knowledge of the oxygen content in blood is

essential in order to know how the cardiovascular and cardiopulmonary systems work. This

measurement can be performed either spectroscopically by exploiting the optical properties

of haemoglobin, the oxygen-carrying pigment of erythrocytes, or by using an appropriate

fluorophore, the fluorescence of which is quenched by oxygen.

Spectroscopic analysis. Oxygen saturation, i.e. the amount of oxygen carried by the

haemoglobin (Hb) in the erythrocytes in relation to its maximum capacity, was the first

quantity measured with FOSs [49]. This parameter is measured optically by exploiting the

different absorption spectra of the Hb and the oxyhaemoglobin (OxyHb) in the visible/near

infrared region.

Numerous artery and vein insertion models are now commercially available, for example

the instruments made by Oximetric Inc., Mountain View, CA; BTI, Boulder, CO; Abbott

Critical Care, Mountain View, CA. In the simpler version, reflected or absorbed light iscollected at two different wavelengths and the oxygen saturation is calculated via the ratio

technique on the basis of the isobestic regions of Hb and OxyHb absorption. On the other

hand, the presence of other haemoglobin derivates, such as carboxyhaemoglobin, carbon

monoxide haemoglobin, methemoglobin and sulphaemoglobin, makes preferable the use of

multiple wavelengths or of the whole spectrum, which allow their discrimination [5051].

Non-invasive optical oximeters, which calculate oxygen saturation via the light

transmitted through the earlobes, toes, or fingertips have also been developed, primarily

for neonatal care [52]. In this case, particular attention has to be paid to differentiating

between the light absorption due to arterial blood and that due to all other tissues and blood

in the light path. This implies the use of multiple wavelengths, such as the eight wavelength

Hewlett Packard ear oximeter [53].

Such a drawback can be avoided by using a pulse oximeter. This original approach

is based on the assumption that a change in the light absorbed by tissue during systoleis caused primarily by the arterial blood. By an appropriate choice of two wavelengths,

it is possible to measure non-invasively the oxygen saturation by analysing the pulsatile,

rather than the absolute transmitted or reflected, light intensity [5456]. The detection

of blood absorbance fluctuations that are synchronous with systolic heart contractions is

called photoplethysmography. One application is in dentistry where, by means of a pulse

oximeter, it is possible to obtain information on whether the pulp is vital or necrotic: the

tooth is squeezed between the termination of an optical fibre bundle and two reflective

prisms, to illuminate the tooth and to collect the light transmitted through it. The ratio

between the recorded AC (at 0.5 Hz) and DC components of the detected signal at 570 nm

constitutes the sensor output, i.e. the tooth plethysmogram. Vitality is indicated by a

rhythmic plethysmogram; necrosis, by a random plethysmogram [57]. In another dental-pulp

vitalometer, the oxygen saturation content of dental blood is obtained by an optical-fibre

probe placed in contact with the tooth that performs reflectance measurements at 660 nm

and 850 nm. The signal ratio is processed together with a non-optical plethysmogram

signal from one of the patients fingers, which is used as a reference in determining the

tooths blood pulse. The resultant tooth plethysmogram also contains information on oxygen


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saturation, thereby allowing pulp vitality to be assessed [58].

Spectrophotometric measurements performed directly on the skin tissue and on the organ

surface provide essential information on the microcirculation in tissue and skin and on the

metabolism of an organ, respectively [59]. For example, on-line monitoring of the oxygen

supply in peripheral organs has considerable importance. It is apparent that a perfect and

adequate perfusion of all the organism is basic to the safety of the patient. In the presence

of pathological changes in the oxygen transport chain, the organism, by itself, decreasesthe perfusion in peripheral organs (e.g. skin, skeletal muscles, gut) in favour of central

organs such as the brain and the heart (centralization). This mechanism is one of the most

effective and important ones during different shock forms. Spectra from biological tissues

are able to detect the beginning of centralization before any external, physical and more

dangerous symptoms become visible. On the other hand, during the early stages of shock,

such an alteration of oxygen transport does not occur homogeneously on the tissue surface:

therefore, only fibre optics offer a sufficient spatial resolution for immediate detection. A

special algorithm is generally used, since the spectra of the Hb and its derivatives are

unevenly distributed in a highly scattering medium, and thus are notably altered.

With the spectrophotometer analyser developed by BGT (Uberlingen, Germany)

[60], important parameters such as intracapillary haemoglobin oxygenation, intracapillary

haemoglobin concentration, local oxygen uptake rate, local capillary blood flow, changes

in subcellular particle sizes, and capillary wall permeability (via the injection of exogenousdyes) can be measured in real time. Light from a Xenon arc lamp illuminates the tissue via

a bifurcated fibre bundle. The back-scattered light, filtered by a monochromator, impinges a

photomultiplier connected to a computer that records the spectra resulting from the biological

tissue. Thanks to the use of fibres, only small volumes of tissue are investigated, thus making

possible the resolution of spatial heterogeneities. The instrument is able to record spectra

of high quality even in moving organs.

Optrode analysis. The disadvantage of utilizing haemoglobin as an indirect indicator for

the measurement of oxygen is its full saturation at 100 Torr: this fact prevents, for

example, the use of this method in the case of the respiration of gas mixtures with an O 2content larger than 20% as routinely used in anaesthesia. Therefore the use of a chemical

transducer becomes necessary in some cases.The first optrode-based oxygen sensor was described by John Peterson, and makes use

of a fluorophore, perylene-dibutyrate, the fluorescence of which is efficiently quenched by

oxygen [61]. The dye, adsorbed on amberlite resin beads, was fixed at the distal end of

two plastic optical fibres with a hydrophobic membrane permeable to oxygen. The probe

described was tested in vivo for the measurement of the arterial pO2 level in dog eyes [62].

Other optrodes have been developed and tested in vivo, all of them using a fluorophore,

the fluorescence of which is quenched by oxygen. In the intravascular sensor developed

by CDI, previously described, a specially synthesized fluorophore, a modified decacyclene

(exc = 385 nm, em = 515 nm), is combined with a second reference-fluorophore that

is insensitive to oxygen, and is incorporated into a hydrophobic silicon membrane that is

permeable to oxygen.

A new type of non-invasive sensor has been proposed to measure the local oxygen

uptake through the skin. The direct measurement of the oxygen flow on the skin surface

provides information regarding the oxygen flow inside the tissue, which can help physicians

to diagnose circulatory disturbances and their consequences. Two optrodes, which make

use of a ruthenium complex, measure the difference in oxygen pressure across a membrane


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placed in contact with the skin. In vivo tests performed on the left lower forearm of a

patient gave good results [63].

4.3.2. Respiratory oxygen. A knowledge of the concentration of oxygen, as well as of

many other gases, in exhalation analysis is very important, since it may provide important

information on the correct metabolism of the human body. An optrode for the simultaneous

detection of oxygen and carbon dioxide, potentially suitable for respiratory gas analysis,has recently been proposed [6465]. It makes use of two fluorescent dyes dissolved in a

very thin layer (13 m) of a plasticized hydrophobic polymer which is fixed at the distal

end of optical fibres. A wavelength discrimination by appropriate interference filters makes

possible the simultaneous monitoring of O2 and CO2, as the emission wavelengths of the

two fluorophores are sufficiently separated.

4.4. Carbon dioxide

As for oxygen, the measurement of CO2 is capable of providing important information in

regard to the working of the circulatory and respiratory systems. Its detection is based on

the detection of the pH of a carbonate solution, since its acidity depends on the quantity of

CO2 dissolved therein. Therefore, all optrodes developed for blood CO2 make use of thesame dye utilized for blood pH detection, fixed at the end of the fibre and covered by a

hydrophobic membrane permeable to CO2. In the intravascular CDI system the fluorophore,

hydroxypyrene trisulphonic acid (the same one used in the pH optrode), is dissolved in

a bicarbonate buffer solution which is encapsulated in a hydrophobic silicon membrane

permeable to CO2 and attached to the fibre tip.

4.5. Lipoproteins

A knowledge of the lipoprotein content in the blood is of paramount importance, as

this protein is the carrier of cholesterol. Epidemiological studies have indicated that

a reduction in blood cholesterol levels significantly reduces the risk of atherosclerosis,

ischemia, myocardial infarction, and death. On the other hand, it has been well demonstrated

that measuring the total cholesterol in the blood is not sufficient for predicting the risk ofcardiovascular diseases; but a knowledge of the type of lipoproteins, which can be different

in size, density and lipid and apolipoprotein composition is essential. For example, high-

density lipoproteins, the second largest carriers of plasma cholesterol, have been recognized

as being able to remove cholesterol from tissue and, consequently, of being capable of

carrying on a protective action against arterial disease.

The use of optical fibres allows an in vivo investigation of arterial lesions. Fluorescence

spectroscopy with optical fibres makes the imaging of the intimal surfaces of arteries

possible. On the other hand, interferences from the whole blood make preferable the use

of near-IR wavelengths in which such interferences are noticeably reduced. Collection

of the many whole near-IR spectra from one location at a time has recently allowed

the chemical analysis of arterial lesions in living tissues, with the aid of an appropriate

processing of the data based on a new experimental clustering technique that uses a parallel

vector algorithm [66]. Such an in vivo qualitative (recognition of the different types of

lipoproteins) and quantitative (concentration evaluation) analysis appears fundamental both

for monitoring changes in arterial wall composition and for testing important new hypotheses

of lesion formation, growth, and regression.


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4.6. Lipids

One of the major dermatological requirements is knowing the condition of the skin, which

can be roughly determined by monitoring the skins hydration state and, more precisely, by

determining lipid content. The latter parameter is of special importance in studies of acne.

An inexpensive fibre-optic refractometer has been developed for both tasks.

The sensor comprises a plastic fibre with a short section stripped of its cladding, where

it is bent into a U-shape. With the U-shaped tip on the skin, the skin surface acts as thefibre cladding. Since the skin surface is not perfectly smooth, some gaps are created around

the fibre core. At probe contact, the gaps are filled with air, but during the time the probe

is in contact with the skin, they fill up with skin moisture. Consequently, sensor output

decreases with time, at a rate dependent on the hydration state. The skin moisture content

is obtained in relation to pre-fixed threshold values [67].

It has been noted that, the higher the lipid contents, the higher the light reflection, thus

reducing sensor output. This disturbance has been used for estimating lipid quantity, through

comparisons of sensor outputs relative to defatted and unprepared skin. By comparing this

difference with pre-fixed values, the lipid content has been successfully monitored, with the

experimental results in good agreement with those obtained using a traditional gravimetric

technique [68].

4.7. New aspects and perspectives of chemical sensors

Almost all the chemical sensors described above were tested in vivo or are being tested. As

already pointed out, some of them are available on the market, and are capable of providing

satisfactory answers to clinicians requirements while others are still at an experimental

stage.

A recent survey has made evident the main areas in which in vivo chemical sensors

would be helpful [69], as can be seen from table 1, which reports the results of this survey.

The number in parentheses for each analyte is the number of physicians who answered the

survey.

Table 1. Main clinical problems and related analytes for which a continuous in vivo monitoring

should be performed.

Clinical problem Analyte

Diabetes mellitus glucose (24), K+ (3), ketones (2), insulin (2), lactate (1), pH

(1)

Vital function monitoring in O2 (15), CO2 (10), pH (8), haemoglobin (3), K+ (2), glucose

intensive care/anaesthetics/ (2), electrolytes (unclassified) (1), gases (unclassified) (1),

prolonged surgery Na+ (1), osmolality (1), lactate (1)

renal failure/monitoring dialysis urea (4), creatinine (2), K+ (2), atrial natriuretic peptide (1),

pH(1)

Some of the required analytes are already being monitored on-line with FOSs, and have

been described here. Other FOSs have been proposed and seem promising, although none

has as yet undergone in vivo testing (glucose, potassium, urea, lactate).

Glucose is surely the analyte most in demand, because its control is of vital importance

in diabetic patients, and a glucose sensor is an integral part of an artificial pancreas with its

controlled insulin release. Patients affected by diabetes mellitus need a monitoring of blood

glucose levels during the whole day; but so far, no continuous sensor is available, obliging


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patients to self-monitoring of their blood glucose by periodic sampling and to the use of

chemistry reagent strips. Different approaches with fibre-optics have been presented, but at

the moment some problems for their in vivo utilization still exist.

Reversible competitive binding of glucose with fluorescence labelled-dextran for sugar

binding sites of a lectin, concanavalin A [7071], has been proposed. The probe consists

of an appropriate hollow fibre, coupled to fibre-optics, capable of preventing the exit of

reagents, but permeable to glucose (selection made on the basis of the molecular weight).Problems still open are the lifetime of the probe and the response time. Another approach

makes use of glucose oxidase, an enzyme that catalyzes the oxidation of glucose; by

exploiting the enzymatic reaction, it is possible to indirectly monitor glucose levels with

the measurement of oxygen [72] or pH [73]. Although sensitive and for some aspects

satisfactory (for example, fast response time), this approach seems even more appropriate

for laboratory diagnostics than for in vivo sensing, mainly due to the deterioration of the

chemicals utilized, which strongly limits the lifetime of the probes.

An interesting technique is the exploitation of properties of the glucose as an optically-

active substance, and therefore one capable of inducing a rotation of linearly-polarized light.

The amount of rotation, detected by measuring the phase shift of the output voltage of the

signal detector, can be related to the glucose concentration. Although at the moment it

is not used with optical fibres, this optical method seems very promising and has already

been tested for the non-invasive monitoring of the aqueous humour of the eye [7475]. Theadvantage of this plain spectrophotometric technique is apparent and enormous: detection

of the analyte is made without chemical reactions; consequently, fouling problems caused

by the biological medium are avoided, and the problem of the lifetime of the probe is

eliminated.

Identical advantages are presented by IR-spectroscopy. The advent of IR-transmitting

fibres provides the possibility of seeing, by means of fibre-optics, the rotational/vibrational

bands which univocally characterize each molecule. The use in biomedicine of infra-

red spectroscopy coupled with the use of IR fibres for in vivo monitoring is now taking

its first steps, but preliminary tests are very encouraging. In vitro spectral analysis of

human blood serum performed with IR-transmitting non-toxic silver halide fibres connected

to an FTIR spectrometer, has recently been proposed [76], making possible the simultaneous

monitoring of cholesterol, urea, total protein, uric acid and calcium. Continuous monitoring

of respiratory gases could be performed in situ by coupling IR-fibres with tunable diode laserspectroscopy (TDLS). TDLS has recently been applied with good results for the determination

of trace gases such as CO, CO2, NH3, CH4, NO in the exhalation of both humans and

animals [77].

5. Spectral sensors

FOSs are also used in in vivo applications for checking the optical properties of organs

without the measurements being related to the detection of any definite chemical/physical

parameters.

Spectral analysis of tissue can provide important information on its health. Fibre-ring

catheters are used for the spectral-autofluorescence analysis of tissues during endoscopy.

Tissue autofluorescence, excited by an HeNe laser, is spectrally analysed in the 660

850 nm range. The differences in spectral distribution between normal, cancerous, and

necrotic tissues allow for real-time diagnostics, without the necessity for biopsy. Stomach,

bronchial, and lung tissues have been diagnosed by fibre catheters that combine coherent

fibre bundles with custom bundles optimized for fluorescence measurements [78].


24/28


MID-IR fibre-based systems have been tested for in vitro tissue spectra measurements,

with evanescent fibre probes coupled to Fourier Transform spectrometers. Such systems

have demonstrated the possibility of recognizing differences in normal and malignant tissue

spectra (kidney, stomach, lungs) [79] and their suitability for diagnosing atherosclerosis [80].

In dermatological applications, the erythema meter (figure 16) aids in quantifying

erythema in allergy and irritancy testing, as well as in measuring UV-induced erythema.

Skin colour is mostly the result of blood quantity and melanin content, the reflectanceof which modulations range between 520580 nm and 500700 nm, respectively. Skin

colour measurements are performed by a fibre-optic bundle coupled with a dual-wavelength

reflectometer, which measures the ratio of skin reflectance at 555 nm, modulated by blood

quantity, to 660 nm, melanin sensitive but not influenced by blood quantity and hence used

as a reference. The sensor head (OD 5 mm) can be equipped with two mechanical

components for 45 and 0 no-contact measurements [81, 82].

Figure 16. Fibre-optic erythema meter.

In dentistry, tooth-colour matching is a constant problem in restorative dentistry. The

many disadvantages of the conventionally-used method, which is based on the visualcomparison of natural tooth colour with standard colours, can be overcome by using a

fibre-optic reflectance spectrometer. Originally developed for tissue diagnosis, this sensor

can be a great help in selecting the material that best replicates the appearance of natural

teeth. A slender, flexible PMMA fibre-optic bundle is used to illuminate a portion of the tooth

with white light, and guides the tooths reflected light to a portable grating spectrometer.

The reflectance spectrometer can also be used for diagnosing gingiva by means of bent

probe heads inserted in the patients oral cavity [83].

6. Conclusions

The FOSs described above have given good results in in vivo testing. Some of these are

already commercially available, while others are being developed in response to demands

from the medical profession and encouraging market studies.

The utilization of FOSs is increasing continuously, and this fact makes it feasible to

imagine their more and more widespread diffusion for in vivo monitoring. The possibility

ofFOSs, in some cases already exploited [2, 35, 40, 84, 85], of monitoring several parameters


25/28


with a single instrument makes them still more competitive in comparison with the other

techniques and is continuously encouraged by physicians, who greatly appreciate the

possibility of having a multitest portable unit with low-cost disposable probes, that can

be easily managed by both doctors and patients.

Acknowledgments

The authors are grateful to Professor Annamaria Scheggi for her many helpful discussions

and constructive suggestions. Thanks are also due to Dr Klaus Frank, BGT, Uberlingen,

Germany; Professor Harri Kopola of the University of Oulu, Oulu, Finland; Dr Gordon

Mitchell of Future Focus, Woodinville, WA; Dr John Peterson of the National Institutes of

Health, Bethesda, MD; Dr Mei Sun of Luxtron, Santa Clara, CA; and, lastly, to Professor

Takashi Takeo of the Nagoya Municipal Industrial Research Institute, Nagoya, Japan, for

providing illustrative material.

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