Biomedical Sensors Using Optical Fibres PDF

Rep. Prog. Phys. 59 (1996) 1–28.
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 to
the 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: mignani@iroe.fi.cnr.it

‡ E-mail address: baldini@iroe.fi.cnr.it
0034-4885/96/010001+28$59.50
c 1996 IOP Publishing Ltd 1
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 12
4. 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
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 handling
and 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 light
power 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.
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 sensor’s 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
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 µm are used to maximize the source’s 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.
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 upsets
the 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 passive
components. 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 be
adversely 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
Figure 3. Fabry–Perot 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 Fabry–Perot cavity
at the fibre tip [1, 2]; the other has a small diaphragm in front of the fibre optic link [3–5].
The Fabry–Perot cavity for pressure sensing is a glass cube having a partially etched
face, 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].
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 35–45 ◦ 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 Fabry–Perot (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.

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 He–Ne 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.
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 patient’s 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 monitoring
of 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 early
detection 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 water–protein 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 α, β,
and γ 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 α-crystallin
aggregation, since the α-crystallins are of greater molecular weight and size, and thus scatter
more light than the β- and γ -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 He–Ne 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 distribution
of particle size, respectively corresponding to α-crystallins and their aggregation. The
probe can be easily incorporated into conventional ophthalmological instruments such as an
applanation tonometer mount [23–25].
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 of
coherence, 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].
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 a
microbending 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 1–1000 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 called
optrode, 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, ‘chemical’
gastritis, 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 λ = 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 Lambert–Beer 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 µmol/L (bilirubin concentration),
and the working range is 0 ÷ 100 µmol/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
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 pCO2
respectively. 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
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 sensor’s 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 conditions
must 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 µm). 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 µm), 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.
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 (λexc = 410 nm) and alkaline
(λexc = 460 nm) excitation bands of the fluorophore are used, since their emission bands are
centred on the same wavelength (λem = 520 nm). The ratio of the fluorescence intensity for
the two excitations appears to be relatively insensitive to optical fluctuations. Measurements
of 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) the
formation 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.
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 µm fibres with an overall diameter of 400 µm). 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.
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 Barrett’s 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 µm inside diameter cellulosic-dialysis tubing, attached to a
250 µm 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
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 the
CPGs 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 3.5 ÷ 7.5, 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 optical
sensor 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].
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 is
collected 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 [50–51].
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 systole
is 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 [54–56]. 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 patient’s fingers, which is used as a reference in determining the
tooth’s blood pulse. The resultant tooth plethysmogram also contains information on oxygen
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, decreases
the 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 (Überlingen, 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 exogenous
dyes) 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 O2
content 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
(λexc = 385 nm, λem = 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
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 [64–65]. It makes use of two fluorescent dyes dissolved in a
very thin layer (1–3 µm) 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 the
same 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 of
cardiovascular 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.
4.6. Lipids
One of the major dermatological requirements is knowing the condition of the skin, which
can be roughly determined by monitoring the skin’s 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 the
fibre 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
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 [70–71], 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 [74–75]. The
advantage 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 laser
spectroscopy (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 He–Ne 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].
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 reflectance
of which modulations range between 520–580 nm and 500–700 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 visual
comparison 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 tooth’s 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 patient’s 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
of FOSs, in some cases already exploited [2, 35, 40, 84, 85], of monitoring several parameters
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, Überlingen,
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.
References
[1] Wolthuis R A, Mitchell G L, Saaski E, Hartl J C and Afromowtiz M A 1991 Development of medical pressure
and temperature sensors employing optical spectrum modulation IEEE Trans. Biomed. Eng. BE-38 974–80
[2] Wolthuis R, Mitchell G, Hartl J and Saaski E 1993 Development of dual function sensor system for measuring
pressure and temperature at the tip of a single optical fiber IEEE Trans. Biomed. Eng. BE-40 298–302
[3] Lindström L H 1970 Miniaturized pressure transducer intended for intravascular use IEEE Trans. Biomed.
Eng. BE-17 207–19
[4] Hansen T E 1983 A fiberoptic micro-tip pressure transducer for medical applications Sens. Act. 4 545–54
[5] He G and Wlodarczyk M T 1993 Catheter-type disposable fiber optic pressure transducer Proc. Ninth Optical
Fiber Sensors Conf. (Florence) pp 463–66
[6] Innerspace Inc 1923 Southeast Main Street, Irvine, CA 72714
[7] Camino Laboratories, 5955 Pacific Center Blvd, San Diego, CA 92121
[8] Trimble B 1993 Fifty thousand pressure sensors per year: a successful fiber sensor for medical applications
Proc. Ninth Optical Fiber Sensors Conf. (Florence) pp 457–62
[9] Christensen D A 1988 Fiberoptic temperature sensing for biomedical applications Proc. SPIE: Optical Fibers
in Medicine III 906 108–13
[10] Brenci M, Conforti G, Falciai R, Mignani A G and Scheggi A M 1986 All-fibre temperature sensor Int. J.
Opt. Sens. 1 163–9
[11] Domanski A W, Wolinski T R and Borys W 1990 Fiber-optic liquid crystalline high-sensitivity temperature
sensor Proc. SPIE: Fiber Optic and Laser Sensors VIII 1169 573–81
[12] Ovren C, Adolfsson M and Hok B 1984 Fiberoptic systems for temperature and vibration measurements in
industrial applications Opt. Las. Eng. 5 155–61
[13] Kist R, Drope S and Wolfelschneider H 1984 Fiber-Fabry–Perot (FFP) thermometer for medical applications
Proc. 2nd Int. Conf. on Optical Fiber Sensors (OFS ’84) ed R Th Kersten and R Kist (Berlin: VDE)
pp 165–70
[14] Wickersheim K A and Sun M H 1987 Fiberoptic thermometry and its applications J. Microwave Power
pp 85–94
[15] Luxtron, 2775 Northwestern Parkway, Santa Clara, CA 95051-0941
[16] Wolthuis R A, Mitchell G L, Hartl J C and Afromowtiz M A 1991 Development of medical pressure and
temperature sensors employing optical spectrum modulation IEEE Trans. Biomed. Eng. BE-38 974–81
[17] Wolthuis R, Mitchell G, Hartl J and Saaski E 1993 Development of a dual function sensor system for
measuring pressure and temperature at the tip of a single optical fiber IEEE Trans. Biomed. Eng. BE-40
298–302
[18] Shenfeld O, Belotserkovsky E, Goldwasser R and Katzir A 1993 Silver halide fiber optic radiometry for
temperature monitoring and control of tissues heated by microwave Opt. Eng. 32 216–21
[19] Nilsson G E, Tenland T and Öberg P Å 1980 Evaluation of a laser Doppler flowmeter for measurement of
tissue blood flow IEEE Trans. Biomed. Eng. BE-27 597–604
[20] Perimed, box 5607, S-114 86 Stockholm, Sweden
[21] Muto S, Fukusawa A, Ogawa T, Morisawa M and Ito H 1990 Breathing monitor using dye-doped optical
fiber Japan. J. Appl. Phys. 29 1618–9
[22] Öberg P Å, Pattersson H, Lindberg L and Begfors M 1995 Evaluation of a new fibre-optic sensor for
respiratory rate measurements Proc. SPIE Sensors II and Fiber Optic Sensors 2331 98–109
[23] Dhadwal H S, Ansari R R and Dell Vecchia M A 1993 Coherent fiber optic sensor for early detection of
cataractogenesis in a human eye lens Opt. Eng. 32 233–7
[24] Ansari R R, Dhadwal H S, Cheung H M and Meyer W V 1993 Microemulsion characterization by the use
of a noninvasive backscatter fiber optic probe Appl. Opt. 32 3822–7
[25] Hamano K, Kuwahara N, Chin B and Kubota K 1991 Dynamic light scattering measurement for a salt-induced
cataract in the eye lens of a chicken Phys. Rev. A 43 1054–60
[26] Macfayden A J and Jennings B R 1990 Fibre-optic systems for dynamic light scattering—a review Opt. Las.
Tech. 22 175–87
[27] Bueker H, Haesing F W and Gerhard E 1992 Physical properties and concepts for applications of attenuation-
based fiber optic dosimeters for medical instrumentation Proc. SPIE Fiber Optic Medical and Fluorescent
Sensors and Applications 1648 63–70
[28] Kopola H, Mäntylä O, Mäkiniemi M, Mähönen K and Virtanen K 1995 An instrument for measuring human
biting force Proc. SPIE Medical Sensors II and Fiber Optic Sensors 2331 149–55
[29] Falciai R, Scheggi A M, Baldini F and Bechi P 1990 USA Patent, 4 976 265
[30] Falciai R, Baldini F, Cosi F, Bechi P and Pucciani F 1993 Bile enterogastric reflux sensor using plastic
optical fibers Fiber Int. Opt. 12 215–22
[31] Bechi P, Pucciani F, Baldini F, Cosi F, Falciai R, Mazzanti R, Castagnoli A, Passeri A and Boscherini S 1993
Long-term ambulatory enterogastic reflux monitoring. Validation of a new fiber-optic technique Digestive
Diseases Sci. 38 1297–306
[32] Tait G A, Young R B, Wilson G J, Steward D J and MacGregor D C 1982 Myocardial pH during regional
ischemia: evaluation of a fiber-optic photometric probe Am. J. Physiol. 243 H1027–031
[33] Watson R M, Markle D R, Ro Y M, Goldstein S R, McGuire D A, Peterson J I and Patterson R E 1984
Transmural pH gradient in canine myocardial ischemia Am. J. Physiol. 246 H232–8
[34] Abraham E, Fink S E, Markle D R, Plinholster G and Tsang M 1985 Continuous monitoring of tissue pH
with a fiberoptic conjunctival sensor Am. Energ. Med. 14 840–6
[35] Gehrich J L, Lübbers D W, Opitz N, Hansmann D R, Miller W W, Tusa K K and Yafuso M 1986 Optical
fluorescence and its application to an intravascular blood gas monitoring system IEEE Trans. Biomed.
Eng. BE-33 117–32
[36] Miller W W, Yafuso M, Yan C F, Hui H K and Arick S 1987 Performance of an in-vivo, continuous blood-gas
monitor with disposable probe Clin. Chem. 33 1358–65
[37] Hansmann D R and Gehrich J L 1988 Practical perspectives on the in-vitro and in-vivo evaluation of a fiber
optic blood gas sensor Proc. SPIE Optical Fibers in Medicine III 906 4–10
[38] Khalil G, Yim J and Vurek G G 1994 In-vivo blood gases: problems and solutions Proc. SPIE Biomedical
Fiber Optic Instrumentation 2131 437–51
[39] Schlain L and Spar S 1994 Continuous arterial blood gas monitoring with transmitted light sensors and LED
light sources Proc. SPIE Biomedical Fiber Optic Instrumentation 2131 452–8
[40] Walt D R and Bronk K S 1992 Spatially resolved photo-polymerized image-ready single fiber sensor for
blood gas analysis Proc. SPIE Fiber Optic Medical and Fluorescent Sensors and Applications 1648 12–14
[41] Champion G, Richter J E, Vaezi M F, Singh S and Alexander R 1994 Duodenogastroesophageal reflux,
relationship to pH and importance in Barrett’s esophagus Gastroenterology 107 747–54
[42] Posch H E, Leiner M J P and Wolfbeis O S 1989 Towards a gastric pH-sensor: an optrode for the pH 0–7
range Fres. Z. Anal. Chem. 334 162–5
[43] Baldini F, Bracci S, Cosi F, Bechi P and Pucciani F 1994 CPG embedded in plastic optical fibers for gastric
pH sensing purposes Appl. Spectrosc. 48 549–52
[44] Netto E J, Peterson J I and Wang B 1993 Fiber-optic pH sensor for gastric measurements—preliminary
results Proc. SPIE Fiber Optic Sensors in Medical Diagnostics 1886 109–17
[45] Baldini F, Bechi P, Bracci S, Cosi F and Pucciani F 1995 In vivo optical fibre pH sensor for gastro-esophageal
measurements Sens. Act. B 29 164–8
[46] Netto E J, Peterson J I, McShane M and Hampshire V 1995 A fiber-optic broad-range pH sensor system for
gastric measurements Sens. Act. B 29 157–63
[47] Mordon S, Maunoury V, Devoisselle J M, Abbas Y and Coustaud D 1992 Study of normal/tumorous
tissue fluorescence using a pH-dependent fluorescent probe in vivo Proc. SPIE Fiber Optic Medical and
Fluorescent Sensors and Applications 1648 181–91
[48] Devoisselle J M, Maunoury V, Mordon S and Coustaut D 1993 Measurement of in-vivo tumorous/normal
tissue pH by localized spectroscopy using a fluorescent marker Opt. Eng. 32 239–43

[49] Kapany N S and Silbertrust N 1964 Fiber optics spectrophotometer for in-vivo oximetry Nature 208 138–45
[50] Milano M J and Kim K Y 1977 Diode array spectrometer for the simultaneous determination of hemoglobin
in whole blood Anal. Chem. 49 555–61
[51] Lubbers D W 1993 Chemical in vivo monitoring by optical sensors in medicine Sens. Act. B 11 253–62
[52] Scoggin C, Nett L and Petty T L 1977 Clinical evaluation of a new ear oximeter Heart and Lung 6 121–6
[53] Merrick E B and Hayes T J 1976 Continuous, non-invasive measurements of arterial blood oxygen levels
Hewlett Packard J. 28 2–9
[54] Mendelson Y and Ochs B D 1988 Noninvasive pulse oximetry utilizing skin reflectance photoplethysmogra-
phy IEEE Trans. Biomed. Eng. BE-35 798–805
[55] Cui W, Ostrander L E and Lee B Y 1990 In vivo reflectance of blood and tissue as a function of wavelength
IEEE Trans. Biomed. Eng. BE-37 632–9
[56] Ugnell H and Öberg P Å 1995 The time variable photoplethysmographic signal. Its dependance on light
wavelength and sample volume Proc. SPIE Medical Sensors II and Fiber Optic Sensors 2331 89–97
[57] Schmitt J M, Webber R L and Walker E C 1991 Optical determination of dental pulp vitality IEEE Trans.
Biomed. Eng. BE-38 346–52
[58] Makinlemi M, Kopola H, Oikarinen K and Herrala E 1995 A novel fibre optic dental pulp vitalometer Proc.
SPIE Medical Sensors II and Fiber Optic Sensors 2331 140–8
[59] Frank K, Kessler M, Appelbaum K, Zundorf J, Albrecht H P and Siebenhaar G 1990 In situ monitoring
of organs Handbook of Critical Care ed J L Ber and J E Sampliner (Boston, MA: Little, Brown and
Company) pp 145–9
[60] Frank K H, Kessler M, Appelbaum K and Dümmler W 1989 The Erlangen micro-lightguide
spectrophotometer Empho I Phys. Med. Biol. 34 1883–900
[61] Peterson J I, Fitzgerald R V and Buckhold D K 1984 Fiber-optic probe for in vivo measurement of oxygen
partial pressure Anal. Chem. 56 62–7
[62] Stefansson E, Peterson J I and Wang Y H 1989 Intraocular oxygen tension measured with a fiber optic sensor
in normal and diabetic dogs Am. J. Physiol. 256 H1127–33
[63] Holst G A, Köster T, Voges E and Lübbers D W 1995 FLOX-an oxygen-flux-measuring system using a
phase modulation method to evaluate the oxygen dependent fluorescence lifetime Sens. Act. B 29 231–9
[64] Wolfbeis O S, Weis L J, Leiner M J P and Ziegler W E 1988 Fiber-optic fluorosensor for oxygen and carbon
dioxide Anal. Chem. 60 2028–30
[65] Klimant I, Kovacs B and Wolfbeis O S 1993 Sensor material for carbon dioxide and oxygen, with potential
use for respiratory gas analysis SPIE Abstract Book, Biomedical Optics Europe ’93 pp 86–87
[66] Cassis L A and Lodder R A 1993 Near-IR imaging of atheromas in living arterial tissue Anal. Chem. 65
1247–56
[67] Takeo T and Hattori H 1991 Application of a fiber optic refractometer for monitoring skin condition Proc.
SPIE Chemical, Biochemical, and Environmental Fiber Sensors III 1587 284–7
[68] Takeo T and Hattori H Quantitative evaluation of skin surface lipids by a fiber-optic refractometer Sens. Act.
B 29 318–23
[69] Pickup J C and Alcock S 1991 Clinicians’ requirements for chemical sensors for in vivo monitoring: a
multinational survey Biosens. Bioelect. 6 639–46
[70] Schultz J S, Mansouri S and Goldstein I J 1982 Affinity sensor: a new technique for developing implantable
sensors for glucose and other metabolites Diab. Care 5 245–52
[71] Meadows D L and Schultz J S 1993 Design, manufacture and characterization of an optical fiber glucose
affinity sensor based on an homogeneous fluorescence energy transfer assay system Anal. Chim. Acta 280
21–30
[72] Schaffar B H and Wolfbeis O S 1990 A fast responding fiber optic glucose biosensor based on an oxygen
optrode Biosens. Bioelectr. 5 137–48
[73] Trettnak W, Leiner M J P and Wolfbeis O S 1988 Fibre-optic glucose sensor with a pH optrode as the
transducer Biosensors 4 15–26
[74] Rabinovitch B, March W F and Adams R L 1982 Noninvasive glucose monitoring of the aqueous humor of
the eye: Part II. Animal studies and the scleral lens Diab. Care 5 259–65
[75] Coté G L, Fox M D and Northrop R B 1992 Noninvasive optical polarimetric glucose sensing using a true
phase measurement technique IEEE Trans. Biomed. Eng. BE-39 752–6
[76] Simhi R, Bunimovich D, Sela B and Katzir A 1995 Multicomponent analysis of human blood using fiberoptic
evanescent wave spectroscopy Proc. SPIE Medical Sensors II and Fiber Optic Sensors 2331 166–72
[77] Stepanov E V, Kouznetsov A I, Zirjanov P V, Skurpskii V, Shulagin Y and Galgan M E 1995 Detection
of small trace molecules in human and animal’s exhalations by tunable diode lasers Proc. SPIE Medical
Sensors II and Fiber Optic Sensors 2331 173–83

[78] Baryshev M V and Loshohenov V B 1994 Optimization of optical fibre catheter for spectral investigations
in clinics Proc. SPIE Biomedical Optoelectronic Devices and Systems 2084 106–18
[79] Artjushenko V G, Afanasyeva N I, Lerman A A, Kryukov A P, Kuzin E F, Zharkova N N, Plotnichenko
V G, Frank G A, Didenko G I, Sokolov V V and Neuberger W 1993 Medical applications of MIR-fiber
spectroscopic probes Proc. SPIE Biochemical and Medical Sensors 2085 137–42
[80] Baraga J J, Feld M S and Rava R P 1992 Infrared attenuated total reflectance spectroscopy of human artery:
a new modality for diagnosing atherosclerosis Lasers in Life Sciences 5 13–29
[81] Kopola H, Lahti A, Myllylä R A and Hannuksela M 1993 Two-channel fiber optic skin erythema meter Opt.
Eng. 32 222–6
[82] Myllylä R, Marszalec E and Kopola H 1993 Advances in color measurement for biomedical applications
Sens. Act. B 11 121–8
[83] Ono K, Kanda M, Hiramoto J, Yotsuya K and Sato N 1991 Fiber optic reflectance spectrophotometry system
for in vivo tissue diagnosis Appl. Opt. 30 98–105
[84] Anderson C D, Vokovich D and Wlodarczyk M T 1992 Fiber optic sensor for simultaneous oxygen saturation
and blood pressure measurement Proc. SPIE Fiber Optic Medical and Fluorescent Sensors and Applications
1648 116–29
[85] Sun M and Kamal A 1991 A small single sensor for temperature, flow, and pressure measurement Proc.
SPIE Optical Fibers in Medicine VI 1420 44–52

Biomedical Sensors Using Optical Fibres PDF

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Biomedical Sensors Using Optical Fibres PDF

Uploaded by

Copyright:

Available Formats

Rep. Prog. Phys. 59 (1996) 1–28.

Biomedical sensors using optical fibres

Anna Grazia Mignani† and Francesco Baldini‡

This review was received in July 1995

† E-mail address: mignani@iroe.fi.cnr.it

2. The basic working principle of sensing

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

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

2.2. Main problems

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

Design and manufacturing specifications. The probes require accurate workmanship

3. Sensors for physical parameters

Figure 3. Fabry–Perot fibre-optic pressure sensor.

instruments make use of catheters tipped with miniaturized piezoresistive or capacitive

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

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

3.3. Blood flow

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

3.5. Cataract onset

more light than the β- and γ -crystallins.

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

3.6. Radiation dose

3.7. Biting force

4. Sensors for chemical parameters

improvement in patient management.

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

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

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

4.4. Carbon dioxide

4.7. New aspects and perspectives of chemical sensors

Clinical problem Analyte

Figure 16. Fibre-optic erythema meter.

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

tissue pH by localized spectroscopy using a fluorescent marker Opt. Eng. 32 239–43

Sensors II and Fiber Optic Sensors 2331 173–83

You might also like