Biosensors and Bioelectronics: X 1 (2019) 100015

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Biosensors and Bioelectronics: X

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Trends in the design of wavelength-based optical fibre biosensors T

(2008–2018)
A.B. Socorro-Leránoza,b,∗, D. Santanoa, I. Del Villara,b, I.R. Matiasa,b
a
Department of Electrical, Electronic and Communication Engineering, Universidad Publica de Navarra (UPNA), Ed. Los Tejos, Campus of Arrosadia S/n, 31006,
Pamplona, Spain
b
Institute of Smart Cities, Jeronimo de Ayanz R&D Center, Campus of Arrosadia, 31006, Pamplona, Spain

A R T I C LE I N FO A B S T R A C T

Keywords: During the last decades, both governments and companies have been committed to the continuous checking of
Biosensors biological parameters, which can prevent extra costs to administrations. A very efficient way to address this issue
Optical fibre is by designing biosensors. This contribution reviews the advances made using optical fibre technology, which
Interferometry have lately agglutinated much of the scientific interest related to the development of biosensors. However, the
Fabry–Pérot
wide number of publications describing the use of optical fibre for detecting biomarkers has probably blurred the
Fibre Bragg gratings
Long-period fibre Bragg gratings
main goal: obtaining portable, simple, easy-to-handle and cost-effective biosensors. With this purpose, this
Surface plasmon resonance contribution presents some optical fibre structures which have been analysed in terms of several optical para-
Localized surface plasmon resonance meters of interest from a photonics point of view: sensitivity, quality factor, full width at half minimum, limit of
Lossy mode resonance detection and figure of merit. This has made it possible to classify the most advanced optical fibre sensing
techniques and, hence, their suitability when developing biosensing applications.

1. Introduction defence (6%), environmental applications (5%), research laboratories

(3%) and robotics (2%), among others. According to the Scopus re-
In recent decades, the biosensors market has experienced a great search browser, more than 66800 contributions related to biosensors
development, above all regarding medical healthcare (P&S Market have been written since the 1960s. In spite of this, for the sake of
Research, 2015). The principal causes motivating this situation are the simplicity, this contribution will only focus on the development of
increase of diabetes and the aging of the population, which can be biosensors for medical applications.
corroborated currently in both developed and developing countries. A biosensor detects a chemical or biochemical substance by trans-
Behind this market, major global companies, in collaboration with the ducing a biological interaction into a variation of any sort of signal that
different administrations, are clearly investing in producing applica- can be measured easily. Its structure consists of three clearly defined
tions that allow patients to manage their own health at home. At the parts: the substrate, the biofunctionalization interface and the bior-
same time, both companies and governments are promoting point-of- eceptors (Holzinger et al., 2014). Typical bioreceptors are, generally,
care testing and self-care applications rather than having patients sa- antibodies, enzymes, proteins, aptamers, cells or microorganisms. All of
turating hospital waiting rooms. In this respect, the development of a them are specifically designed to detect other target molecules, also
recent type of sensor, known as biosensors, facilitates this work, since called “analytes” or “biomarkers”. The substrate transduces these bio-
they are designed to detect a specific malfunction on time and therefore logical interactions into measurable variables and converts them into
to help physicians heal patients. In fact, by summing the benefits ob- optical, electrical, mechanical or acoustic signals that can be processed
tained by the biosensors market when used in clinical diagnostics and afterwards. Finally, the biofunctionalization interface is the inter-
medical instrumentation alone, 64% of the total market is covered, as mediate layer. It consists of one or several sublayers that attach the
indicated in Fig. 1. bioreceptors to the substrate by means of nanotechnology-based tech-
However, healthcare is not the only application field of biosensors. niques.
The same report also highlights biosensing applications in the control of As is well known, there are numerous techniques to develop bio-
industrial processes (11%), veterinary and agriculture testing (8%), sensors, such as those based on micro-(opto)-electromechanical systems

∗
Corresponding author. Department of Electrical, Electronic and Communication Engineering, Universidad Publica de Navarra (UPNA), Ed. Los Tejos, Campus of
Arrosadia S/n, 31006 Pamplona, Spain.
E-mail address: [email protected] (A.B. Socorro-Leránoz).

https://doi.org/10.1016/j.biosx.2019.100015
Received 8 February 2019; Received in revised form 23 April 2019; Accepted 13 May 2019
Available online 31 May 2019
2590-1370/ © 2019 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/BY/4.0/).
A.B. Socorro-Leránoz, et al. Biosensors and Bioelectronics: X 1 (2019) 100015

Fig. 1. Global biosensors market pie chart. 64% of the money involved in this market is due to activities related to medicine: home healthcare and point-of-care
testing.

Fig. 2. Contributions related to different kinds of biosensing technologies (a search in Scopus by: “Electrochemical AND biosensor”, “MEMS OR MOEMS AND
biosensor” or “Optical fibre AND biosensor” was performed to obtain the data): (a) MEMS/MOEMS, electrochemical and optical fibres evolution from 2008 to 2018.
(b) Comparison between the contributions related to electrochemical and optical fibre-based biosensors since the 1970s. *At the publication date, Scopus was
probably still collecting and classifying the corresponding data for 2018, so the data presented here may not coincide with the exact values for this year.

(MEMS/MOEMS) (Alvarez and Lechuga, 2010), electrochemistry on capturing the electrons released by redox reactions taking place
(Weltin et al., 2016) or optics (Hawk and Armani, 2015). The operating between the analytes and the bioreceptors. Some of them are based on
principle of MEMS is the detection of the mechanical vibrations ex- direct interactions between analytes and bioreceptors (Carneiro et al.,
perienced by tiny structures called microcantilevers as a function of the 2017), whereas others are based on detecting the electrons released by
interaction between the bioreceptors and the target biomolecules. an additional substance that takes advantage of the analyte-bioreceptor
However, though they constitute a sensing technology with high po- interaction to produce them (Yang et al., 2018). It is quite easy to
tential, their current production cost is high and that is why they are functionalize electrodes specifically designed to address biodetection,
still under research. In fact, Fig. 2a shows that the number of con- since the manufacture of planar integrated electrical technology has
tributions related to MEMS/MOEMS has not increased during the last experienced a wide expansion during the last decades. This has made
decade. this technology the most attractive in terms of costs and the most ef-
This is not the case of electrochemical biosensors, which are based ficient in terms of reducing the limit of detection of the analytes.

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Therefore, current electrochemical-based biosensors represent the only have a major drawback, which is the need for a stable signal reference,
technology that is ready to satisfy the demands of the biosensors since the sources may vary their intensity as a function of time. Some
market. Concerning research, they have presented a sustained growth techniques have been developed for compensating this issue (Wang
over the last 10 years, which indicates that this technology is being et al., 2001).
progressively improved (see Fig. 2a). The second method is wavelength detection-based techniques. It is
Regarding optical biosensors, they are the second most explored based on tracking the wavelength shift of the transmission or attenua-
group. Some of the most relevant configurations are those based on tion bands in the spectrum. These configurations are usually more ro-
photonic crystals (Gharsallah et al., 2018; Shafiee et al., 2014), optical bust with respect to intensity-based techniques, since they avoid the
resonators (rings, toroids, cylinders, spheres, …) (Pongruengkiat and instability of optical intensity signals. However, they are more ex-
Pechprasarn, 2017; Tavousi et al., 2018), integrated optics (planar pensive, since they need a spectrometer or an interrogator to monitor
waveguides, Mach–Zehnder or Michelson interferometers, …) (Nabok the wavelength shift. In spite of this, the present work will focus on
et al., 2019) and optical fibres. Focusing on optical fibres, the number analysing these configurations, since they are more reliable in terms of
of contributions over the last decades related to optical fibre biosensors noise and present a high versatility when using different optical con-
has increased greatly, especially since 2013 (see Fig. 2a and b). This figurations that optimize the sensor performance.
increasing interest can be partially explained by the progressive in- However, precisely due to the many existing contributions dealing
troduction of this technology in medicine. Nowadays, it is quite with different procedures to obtain wavelength-based optical fibre
common to find optical fibres in interesting applications such as en- biosensors, there is a need to synthesize the main parameters that in-
doscopy (Krans, 2015), laser applications allowing the removal of dicate the quality of the main optical biosensor platforms used nowa-
varicose veins (Sroka et al., 2010) or to protect elderly men from benign days. In this respect, a selection of the most relevant contributions of-
prostatic hyperplasia (BPH) (Martyn-Hemphill et al., 2017). This suc- fering an “all-in-one” solution in terms of simple fabrication, sensitivity,
cess is explained by several properties that make optical fibres suitable resolution and limit of detection (LOD) is done in this work. For this
for medical applications: purpose, the second part of the manuscript will introduce the latest
trends in wavelength-based techniques used when developing optical
A. Biocompatibility: optical fibres are mostly made of silica and plastic. fibre biosensing platforms, with a brief theoretical explanation of their
These materials seem not to present side-effects when interacting working principles. Then, the third section will classify and compare
with or being immersed in biological substances (Monton et al., these sets of sensors on the basis of several parameters analysed.
2012; Jiang et al., 2018). Finally, some conclusions will be extracted on the optimum way to
B. Reduced size, flexibility and low weight: these properties allow fi- develop such kind of biosensors, as well as an outlook to the future
bres to be introduced into the organism in order to illuminate its research lines that can be taken into account to address this topic.
inner cavities (Rosenthal et al., 2014) or to monitor physical vari-
ables with a catheter (Carotenuto et al., 2018). In this way, it is
feasible to reach places in the human body that are otherwise in- 2. Wavelength-based optical fibre sensing platforms
accessible without open surgery.
C. Low cost: the success of optical fibre-based communications has Three different groups of wavelength-based optical fibre sensing
enabled the reduction of the manufacturing costs. Consequently, it is platforms can be observed in Fig. 3. The first one involves any kind of
nowadays cheaper to develop medical equipment based on this sensor based on generating a Bragg grating inside its core: short/long
technology. fibre Bragg gratings (FBGs and LPFGs) and tilted FBGs (TFBGs). A
D. Capability to work in hazardous media: optical fibre has demon- second group consists of all kind of interferometers, either fabricated by
strated good performance working in nuclear environments fusing different types of fibres (they will be called “all fibre”) or based
(Cheymol et al., 2011) or in the ocean (Hou et al., 2015). Therefore, on a Fabry–Pérot (FP) cavity on the tip of an optical fibre. This last
it is necessary to keep on optimizing the operation of this technology group will consider FP interferometers made by fusing optical fibres or
in complex biological matrices such as blood (Wang and Wolfbeis, by depositing a thin-film on the fibre tip to form nanoFabry–Pérot in-
2016). terferometers (NFPs). Finally, the third group joins those platforms
E. Electromagnetic interference (EMI) immunity: optical fibre sensors, based on the deposition of a thin-film onto the optical fibre substrate in
unlike electrochemical sensors, are not affected by EMIs. The fre- order to generate resonances.
quency variations of the electromagnetic fields surrounding the fi-
bres are several orders of magnitude below the light frequencies
propagated inside.
F. Multiparameter sensing: optical fibre has the ability to multiplex
and integrate signals from different sensors in optical networks, in
either time or wavelength domains (Lismont et al., 2014; Liu et al.,
2016).
G. Diversity of light propagation configurations: the optical fibre, as a
cable, guides the light, but it is possible to mould the light flux by
modifying the fibre structure with different configurations
(Zamarreño et al., 2015).

In connection with the latter property, researchers have defined the

concept of “lab on fibre” (Principe et al., 2017; Vaiano et al., 2016),
which comprises any kind of modifications, depositions, printing pro-
cesses, etc., that can be done in, on and around the optical fibres to
achieve biodetection. Basically, there are two main detection methods.
The first one is based on monitoring light intensity changes at a de-
termined wavelength. Here, absorption (Arnold, 1985) and lumines-
cence (Elosua et al., 2015) are the most used techniques. They are quite Fig. 3. Conceptual map of the wavelength-based optical fibre biosensing plat-
simple to manage and, therefore, the most cost-effective. However, they forms analysed in this contribution.

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Fig. 4. Schematic representation of the fibre Bragg grating-based structures analysed and their corresponding spectral response. (a) Simple FBG, (b) tilted FBG and (c)
LPFG.

2.1. Optical fibre sensors based on gratings be deposited onto the etched structure, leading to an increase in the
effective indices of the modes propagating inside the new waveguide
2.1.1. Fibre Bragg gratings (Luo et al., 2017).
Fibre Bragg gratings are single-mode fibres where a periodic per-
turbation of the core refractive index has been practised (nlow - nhigh), as
2.1.2. Tilted Fibre Bragg gratings
shown in Fig. 4. Depending on the grating period generated inside the
A special mention is deserved by those FBGs where the periodic
fibres, optical fibre sensors based on gratings can be divided into short-
variation of the core refractive index is induced by tilting the grooves of
period fibre Bragg gratings (FBGs) and long-period fibre Bragg gratings
the fabrication mask by an angle θ with respect to the propagation axis.
(LPFGs). For FBGs, the periodicity of the grating structure is typically
This makes it possible to obtain tilted FBGs (TFBGs) (Laffont and
below 100 μm, whereas for LPFGs the periodicity ranges from 100 μm
Ferdinand, 2001). Unlike original FBGs, where the bands corresponding
to 1 mm. This classification obeys the fact that, depending on the
to coupling to counterpropagating cladding modes are negligible
grating period, there is a coupling to copropagating and counter-
compared to the band coupling to the counterpropagating core mode,
propagating modes at specific wavelengths (Erdogan, 2000).
the fact of tilting the grooves in a TFBG also makes it possible to vi-
In the case of FBGs (Fig. 4a), the short period allows a coupling from
sualize the bands coupling to different counterpropagating cladding
the core mode to the counterpropagating core mode. This coupling is
modes (see Fig. 4b). In addition, in TFBGs the Bragg condition given in
translated into a quite sharp attenuation band of just a few picometers
expression 1 has to be rewritten taking into account the resonance
wide obtained in the optical spectrum at λB , as shown in expression 1:
wavelength λrm of each m-th cladding mode, as indicated in expression
λB = 2nceff Λ 2 (Albert et al., 2013):
(1)
eff eff Λ
where nceff is the effective index of the fibre core mode and Λ the period λrm = (ncore + nclad −m) (2)
cosθ
of the refractive index variation along the FBG.
eff
Regarding the typical applications of FBGs, they can sense tem- where θ is the tilt angle of the grating and nclad − m is the effective re-
perature (Zhou et al., 2018), strain (Rodriguez-Cobo et al., 2014) or fractive index of the m-th cladding mode. The plus sign indicates the
torsion (Budinski and Donlagic, 2017), important variables to be con- addition of the counterpropagation of the cladding modes obtained
trolled in biosensing applications. However, FBGs are not sensitive to after tilting. It is simple to observe that by setting θ = 0 and when a
the surrounding refractive index (SRI), a key element in an optical fibre coupling to the counterpropagating core mode is performed, expression
biosensor, because its cladding diameter is typically 125 μm. Conse- 2 turns into expression 1.
quently, the core is too far separated from the external medium, so The fact of owning bands that can be coupled to cladding modes
those changes occurring outside cannot affect the effective index of the makes this optical structure sensitive to SRI changes, since the effective
core mode. Indeed, only by reducing the FBG diameter (i.e. by an indices of cladding modes depend on the SRI. By monitoring the
etching process) is it possible to obtain a refractometer (Liang et al., changes of the cladding mode effective index, an accurate measurement
2005). In order to keep on improving the SRI sensitivity, a thin-film can of the external refractive index can be obtained (Chan et al., 2007;

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A.B. Socorro-Leránoz, et al. Biosensors and Bioelectronics: X 1 (2019) 100015

In LPFGs, as in TFBGs, there is a dependence of the resonance wa-

velength on the cladding modes (see expression 3) and, consequently,
on the SRI. A maximum sensitivity can be attained by combining three
phenomena. First, the turn-around point or dispersion turning point
(TAP/DTP) (Shu et al., 1999), a region where the slope of one or several
phase matching curves extracted from expression 3 reaches a maximum
value. Second, the mode transition (MT) (Cusano et al., 2006; Del Villar
et al., 2005), a phenomenon that can be observed when a high re-
fractive index coating is deposited on the cladding of the LPFG. Finally,
the third is a combination of MT, DTP (this leads to sensitivities of circa
10000 nm/RIU in the water region (Pilla et al., 2012)) and cladding
etching (Chen et al., 2007). This combination can lead theoretically to
more than 100000 nm/RIU in water (Del Villar, 2015) and experi-
mentally to values approaching this record sensitivity (Śmietana et al.,
2016).

2.2. Optical fibre sensors based on interferometry

An optical interferometer is a phase-modulation device based on the

superposition of several modes propagating inside an optical waveguide
(Boudoux, 2017). Such waveguide is designed so that the input light is
propagated through two or more optical paths and then recombined at
the output. After the recombination, all paths converge, but those
modes propagating through different paths experience a different phase
shift. This induces attenuation and transmission bands in the optical
spectrum. Considering two monochromatic waves overlapping spatially
Fig. 5. Schematic representation of optical fibre-based interferometers varying and applying the principle of superposition of waves, the general so-
(a) the core diameter, (b) the alignment, (c) the shape and (d) the type of the lution for the intensity of an interferometer is shown in expression 4
fibres. (Boudoux, 2017):

I = I1 + I2 + 2 I1 I2 ·cos (ϕ) (4)

Caucheteur and Mégret, 2005). Moreover, in (Zhou et al., 2017), the
development of an absolute refractive index sensor based on a TFBG is where I1 and I2 are the intensities of each of the original monochro-
proved. In addition, by accessing the propagation of the higher order matic waves and ϕ = ϕ1 - ϕ2 is the phase delay between those original
cladding modes, the capability of TFBGs to detect SRI changes is en- waves. This is the working principle of every basic interferometer.
hanced (Chen et al., 2005). Some strategies will be presented in the next subsections in order to
Also, increasing the tilt angle of a TFBG makes it possible to obtain obtain simple fibre interferometric structures.
structures based on coupling to copropagating modes, as occurs in long
period gratings (Luo et al., 2018, 2016; Zhou et al., 2006), the device
2.2.1. All-fibre interferometers
presented in the next section. Moreover, highly tilted FBGs are in-
As previously suggested, all-fibre interferometers refer to a class of
herently very sensitive to the surrounding medium's refractive index,
interferometers made by fusing fibres or fibre segments. A first simple
but with temperature sensitivities of 4–7 p.m./°C in the C-L band. This
example of this structure can be obtained by splicing two standard
result is significantly lower than those of the LPFGs and FBGs and is, of
multimode or monomode optical fibre pigtails to a coreless fibre seg-
course, interesting when designing biosensors. Finally, it is always
ment (Fig. 5a). In such structures, light in the input fibre couples to
possible to keep increasing this sensitivity, either by mismatching the
several modes within the intermediate fibre and recouples in the output
cores of the input fibre and the TFBG segment (Guo et al., 2009) or by
fibre. As a result, several transmission and attenuation bands are cre-
depositing thin-films that gently enhance the effective indices of the
ated in the resulting optical spectrum, corresponding to constructive
cladding modes propagating inside the fibre (Jiang et al., 2015).
and destructive interferences in the intermediate fibre. Single-mode –
Therefore, there are several degrees of freedom to enhance the possi-
multimode – single-mode (SMS) structure (Silva et al., 2012; Socorro
bility of detecting changes in the outermost medium without greatly
et al., 2014a) is an example of such interferometers, as well as its
compromising the spectral width of the dips generated. In this sense,
corresponding etched, polished and/or thin-film deposited versions for
TFBGs are potentially good platforms for detecting chemical and bio-
improving their sensitivity to SRI (Cardona-Maya et al., 2017; Socorro
chemical species.
et al., 2014a; Wu et al., 2011). The same occurs when using multimode
– coreless – multimode (MCM) structures (Jung et al., 2006).
2.1.3. Long-period fibre gratings A second way to obtain all-fibre interferometers is by inducing
LPFGs present a longer periodicity between refractive index varia- misalignments (Fig. 5b). Here, the cylindrical symmetry of the optical
tions within the core, which allows a coupling to be obtained between fibre is broken. Consequently, there are mode beatings provoking in-
the core mode and the copropagating cladding modes (Erdogan, 1997). terferometry inside the waveguide and, thus, attenuation and trans-
As a result, several dips can be observed in the transmission spectrum mission bands that can be used for sensing (Luna-Moreno et al., 2007;
(see Fig. 4c), whose location is ruled by expression 3 (Anemogiannis Villatoro and Monzón-Hernández, 2006). Other strategies change the
et al., 2003; James and Tatam, 2003): shape of the intermediate optical fibre segment between the input and
eff
λrm = (ncore eff
− nclad output pigtails. This is the case of non-adiabatic tapers (see Fig. 5c)
−m) Λ (3)
(Yadav et al., 2014), which can be used for generating a spectral in-
eff
where ncore is the effective refractive index of the propagating core terferometry pattern that can be conveniently modulated in order to
eff
mode, nclad − m is the refractive index of the m-th cladding mode, and Λ is obtain narrow resonant bands for detection. There is also the possibility
the period of the LPFG. of repeating the same interferometric pattern several times along the

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Fig. 6. Schematic of a typical experimental set-up for

either a Fabry–Pérot or a nanoFabry–Pérot based
optical fibre interferometer (FPI), together with the
internal reflections and an obtained spectrum before
and after detection. The addition of layers, particu-
larly when detecting bioreceptor–analyte complexes,
induces a red-shift in wavelength.

sensing area (Xiong et al., 2014), or fusing specialty fibres such as film of determined materials on the tip of an optical fibre creates the
suspended core (Lopez-Torres et al., 2018), photonic crystal (Dash necessary conditions to induce light reflections inside the nanocavity so
et al., 2015) or hollow core fibres (Abdallah, 2018) (see Fig. 5d). that an interferometer is constructed. In this respect, either FPIs or
All the previous structures present different geometries and types of nFPIs are interesting alternatives when designing medical devices, since
splicing in order to change the propagation symmetry inside the fibre. their reduced size and reflective configuration permits their introduc-
This excites higher order modes that interact with the surrounding tion in ferrules or catheters inside the body (Hernández-Romano et al.,
medium, giving the possibility to subtract more or less optical power to 2016; Wallner et al., 2013) or even testing microtiter plates such as
the original propagation modes, as occurs in Mach–Zehnder inter- those used in ELISAs.
ferometry (MZI). The numerous recent contributions reporting the As occurs in Bragg gratings, optical fibre-based interferometers are
generation of all kinds of MZIs inside a single fibre structure have widely reported for biosensing since they can provide a low-cost plat-
baptized the state-of-the-art as ‘in-fibre MZI’ (Zhao et al., 2019). form with well-defined bandwidths due to the mode beatings inside the
sensing area. Their sensitivity is not so high in comparison to grating-
2.2.2. Fabry–Pérot and nanoFabry–Pérot interferometers based sensors. However, strategies such as including microcavities,
This group of interferometers uses a reflective set-up whose sche- reducing the diameter of the interferometric cavity or depositing thin-
matic is reflected in Fig. 6 (Islam et al., 2014). An FPI sensor consists of films of higher refractive index than that of the optical waveguide
a cavity between at least one semi-reflective surface and another either (Cardona-Maya et al., 2017) can help enhance it.
semi-reflective or fully-reflective surface. Both surfaces create two re-
flected paths that allow the interference of the light modes between 2.3. Optical fibre sensors based on resonances
them. In this way, the reflected power obtained at the detector is de-
termined analytically by expression 5: Inside a standard optical fibre, the core mode transmits light mostly
confined within the core (the guided field), and some part is trans-
Pr = Pi⋅(R1 + R2 − 2 R1 R2 ⋅cos(ϕFPI )) (5) mitted through the cladding (the evanescent field). The penetration
depth (dp) of this evanescent wave is a key parameter when sensing. It is
where Pi and Pr are the incident and reflected optical powers, respec-
defined as the distance from the interface at which the amplitude of the
tively, and R1 and R2 are the reflection coefficients in the surfaces. ϕ is
electric field is decreased by a 1/e factor (Gouveia et al., 2013). Fol-
the phase shift between reflective surfaces (for instance, between points
lowing the approximation of geometrical optics, this can be expressed
T1 and T2 in Fig. 6) and, according to expression 6:
as indicated in expression 7 (Leung et al., 2012):
4πnL
ϕFPI = λ
λ (6) dp =
2 2
2π ncore sin2 (θ) − nclad (7)
where L is the distance between interfaces, λ is the operational wave-
length and n is the refractive index of the medium between interfaces of where ncore and nclad are the core and cladding refractive indices re-
the Fabry–Pérot cavity (Islam et al., 2014). Also, FPIs can be divided spectively, θ the incidence angle at the core-cladding interface and λ
into extrinsic or intrinsic sensors, depending on whether the inter- the incidence wavelength.
ferometry is done externally (Chen et al., 2010; Poeggel et al., 2015) or The penetration depth is crucial in terms of evaluating the inter-
the own structure generates an internal interferometry (Domingues action of light with the medium surrounding the optical fibre and it can
et al., 2018; Wang et al., 2018). In both cases, the goal is to obtain peaks be modulated by thin-films or nanostructures deposited onto the fibre.
based on varying either the length of the interferometry or the re- Moreover, depending on the parameters of the waveguide, the thin-film
fractive index of the reflecting interfaces. and the surrounding medium, it is possible to generate attenuation
Another way of obtaining similar results is by generating bands at certain wavelength ranges (i.e. resonances), as shown in Fig. 7.
nanoFabry–Pérot interferometers (nFPIs). The fact of depositing a thin- Three types of resonances can be distinguished: long-range surface

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A.B. Socorro-Leránoz, et al. Biosensors and Bioelectronics: X 1 (2019) 100015

Fig. 7. Schematic representation of the working principle of an optical resonance generated onto an optical fibre where a thin-film has been deposited. It can be
observed how the thin-film causes the incident light to couple light modes inside it to generate the corresponding resonance. If the light mode is coupled to a surface
plasmon, the obtained resonance will be an SPR, whereas if there are subsequent light modes that are coupled inside the thin-film, a lossy mode resonance (LMR) will
be obtained.

Fig. 8. Schematic comparison between (a) SPRs and (b) LSPRs generation after depositing either a gold thin-film or gold nanoparticles onto the fibre, with their
corresponding spectra. In (b), depending on the aspect ratio of the gold nanoparticles, more than one LSPR can be generated with enhanced sensitivity as a function
of the SRI. The red spectrum is typical of nanospheres, whereas the blue spectrum indicates the presence of different shapes (nanorods, for instance).

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exciton-polaritons (LRSEPs) (Zhang, 2011), surface plasmon resonances is that the electric field intensity drops more strongly with the distance
(SPRs) (Špačkova et al., 2016), and lossy mode resonances (LMRs) (Del from the surface than in SPRs. Consequently, the penetration depth in
Villar et al., 2017a,b; Wang and Zhao, 2018). LRSEPs are still under LSPRs is much lower than in SPRs. A greater penetration depth in SPRs
basic research, though some advances are being made in this area. can be good in terms of sensitivity to SRI variations as a whole, but at
Given the more advanced state of the art in SPRs and LMRs, this con- the same time it is also possible to detect other variables such as tem-
tribution will focus on SPRs and LMRs henceforward. perature or refractive index and other external changes that interfere
with the analytes and can be considered as noise (Jatschka et al., 2016).
2.3.1. Surface plasmon resonances (SPRs) Consequently, LSPRs are more resistant to these effects.
As is well known, an SPR is a resonance that occurs when depositing Finally, LSPRs are more versatile than SPRs when generating re-
a metallic thin-film (typically gold or silver) on a dielectric waveguide. sonances. For instance, a spherical nanoparticle normally shows a
Metals are suitable for SPR generation because the real part of the single absorption band, whose central wavelength depends on the na-
deposited thin-film permittivity is negative and higher in magnitude noparticle size. However, a non-spherical nanoparticle can present
than both its own imaginary part and the permittivity of the material different absorption bands according to its shape (see Fig. 8b). Thus,
surrounding the thin-film (Yang and Sambles, 1997). Under these gold nanorods usually present two absorption bands: one normally
conditions, there is a charge density wave associated with an electro- centred near 520 nm and the other varying in wavelength according to
magnetic field which reaches its maxima at the metal–dielectric inter- its aspect ratio (the quotient between the longitudinal and transversal
face and then decays evanescently into both media (Homola et al., dimensions of the rod). The second absorption band is more sensitive to
1999). This charge density wave is called a surface plasmon polariton the surrounding medium changes, so it can be used to develop LSPR-
(SPP) and it is generated within the penetration depth of the optical based biosensors with enhanced sensitivity (Pérez-Juste et al., 2005;
substrate as a transverse magnetic (TM) wave. Consequently, SPPs are Rycenga et al., 2011; Yuan et al., 2016).
typically excited with TM polarized light. These SPPs propagate with a
wave vector (kSP) related to the dielectric constants of both the di- 2.3.3. Lossy mode resonances (LMRs)
electric and the metallic film. On the other hand, the evanescent field of Lossy mode resonances (LMRs), also named by some authors as
the light guided in the substrate propagates with a wave vector kEV by guided mode resonances (Yang and Sambles, 1997), are based on the
means of total internal reflection (TIR) in a direction parallel to the generation of lossy modes in a waveguide with a lossy cladding
light propagation. The only way to produce an SPR is to equal kSP to (Batchman and McWright, 1982; Marciniak et al., 1993). Unlike SPPs,
kEV, since then is when the SPP can be excited by the evanescent wave lossy modes (LMs) are generated when the real part of the thin-film
and thus obtain the SPR. This is known as the “phase-matching” con- permittivity is positive and higher in magnitude than both its own
dition. In this respect, there is a determined range of excitation angles imaginary part and the permittivity of the material surrounding the
where the SPR shows up and can be used for sensing purposes. When thin-film (Yang and Sambles, 1997). Under these conditions, LMRs are
this happens, the intensity of the reflected light decreases and the induced when a mode guided in the substrate experiences a transition
spectrum shows an attenuation band at those angles where the SPR can to guidance in the thin-film. This causes a reorganization of the effec-
be excited (Tang et al., 2010). This set of angles can be achieved using tive indices of the rest of the modes guided in the substrate at the same
the Kretschmann configuration (Liedberg et al., 1995), and the same time as their evanescent field is increased (Corres et al., 2015). Con-
resonance phenomenon can be observed by fixing the angle of in- sequently, transmission losses are increased, which can be observed in
cidence and analysing a range of wavelengths (see Fig. 8a). the form of several dips in the transmission spectrum that are red-
In optical fibres, the process of exciting an SPP is quite similar to the shifted as a function of the coating thickness (see Fig. 10).
Kretschmann configuration, but presents some particularities. First, the Many materials other than pure metals (typical of SPRs) can induce
light is guided by the optical fibre, so it is not possible to control the LMRs. Thus, several contributions have reported generating LMRs with
incidence angle. Moreover, the numerical aperture of the fibre strongly metal oxides (Andreev et al., 2005; Śmietana et al., 2018), polymer
limits the range of incidence angles that meet the SPR generation coatings (Del Villar et al., 2012; Zamarreño et al., 2011), two-layer-
condition. Consequently, tracking the wavelength shift of the resonance coated structures combining both materials (Zamarreño et al., 2010) or
in the optical spectrum is the basis of the detection. Apart from this, even immunosensors consisting of multilayers of polymers and anti-
SPPs are obtained when TM polarized light is transmitted. However, the bodies (Socorro et al., 2014b, 2012).
cylindrical symmetry of the fibre is not prepared to maintain a polar- Two relevant reviews on the topic have already been published (Del
ization state (Zubiate et al., 2015). Therefore, there is a need to use Villar et al., 2017a,b; Usha et al., 2018) and a thorough analysis on the
either a polarization maintaining fibre or a system based on an in-line rules for optimizing the performance of LMR-based sensors can be
polarizer and a polarization controller, with the corresponding increase found (Del Villar et al., 2012), where two basic rules are given: the first
in the final cost of the device. In general, the SPRs generated in optical LMR is the most sensitive one. Unlike in SPRs, several resonances can
fibre sensors are not as sensitive as SPRs in Kretschmann configuration, be obtained and their position in the optical spectrum is controlled by
where sensitivities of 57000 nm/RIU are achieved (Radan and Homola, means of the coating thickness. As a result, the sensitivity of the device
2006). increases as the refractive index of the thin-film increases and as the SRI
approaches that of the substrate (Del Villar et al., 2012). In addition,
2.3.2. Localized surface plasmon resonances (LSPRs) LMRs can be obtained with both TE and TM polarized light. Conse-
LSPRs have demonstrated enhanced properties with respect to SPRs, quently, it is possible to avoid the use of a polarizing system (Del Villar
which typically use planar gold thin-films. The reason for calling these et al., 2012, 2010; Zamarreño et al., 2011), although it is true that
resonances “localized” is the fact of being generated in metal nano- polarizing the light involves selecting only its TE or TM component and
particles and, therefore, localizing the phenomenon in a reduced space the bandwidth of the obtained resonance is reduced (Del Villar et al.,
limited to the own nanoparticle (see Fig. 8b). This allows a confinement 2017a,b). This has made it possible, in the case of thin-film coated D-
of the SPP in a space comparable to or smaller than the wavelength of shaped fibre, to convert this optical platform into a good candidate for
light used to excite the SPP (Rycenga et al., 2011). biosensing (Del Villar et al., 2017a,b; Zubiate et al., 2017).
Two important effects can be extracted from this phenomenon. They Several contributions have shown a comparison between the ap-
are shown in Fig. 9. First, the electric field in the proximity of the plication of nanoparticles or thin films to generate LMRs for different
particle's surface is strongly enhanced and, unlike thin-film-generated sensing purposes (Mishra et al., 2016; Usha et al., 2015a,b), but perhaps
SPRs, the LSPR presents a non-linear dependency on the nanocoating the most interesting publication consisted in comparing an SPR with an
thickness (Jatschka et al., 2016). As a result, the second effect in LSPRs LMR, showing that a better sensitivity is obtained in the case of the LMR

8
A.B. Socorro-Leránoz, et al. Biosensors and Bioelectronics: X 1 (2019) 100015

Fig. 9. Numerical SPR comparison among several circumstances involving the deposition of planar gold thin-film (top), 40 nm-radius (medium) and 15 nm-radius
(bottom) embedded gold nanoparticles. Right – normalized electric field values, where the location of the maximum values depending on the gold thin-film can be
observed. Left – non-linear effect visible of the proximity of the nanoparticles with respect to the response of a planar gold thin-film. Reproduced with permission of
Elsevier (Jatschka et al., 2016) with Creative Commons Attribution License (CC BY 4.0).

(Usha et al., 2015a,b). Finally, it has been proved that it is possible to the optical fibre.
obtain both LSPRs and LMRs with the same device, using the LSPR as a
reference for tracking the LMR shift as the sensitive thin-film reacts 3. Optical parameters analysed
(Rivero et al., 2016, 2013). For this purpose, the corresponding LSPR-
generating nanoparticles are embedded in a matrix before depositing When designing biosensors, there are some generic parameters such

Fig. 10. (a) Schematic representation of the LMRs formation with the corresponding spectrum as a function of the increasing thin-film thickness.

9
A.B. Socorro-Leránoz, et al. Biosensors and Bioelectronics: X 1 (2019) 100015

as uncertainty, accuracy, precision or response time to be taken into A high Q value indicates that its FWHM is small in comparison with
account when designing and, overall, calibrating them. However, these its central wavelength, which denotes a good capability of distin-
parameters strongly depend on the measurement method, the config- guishing between similar SRI values. Therefore, the Q-factor is a good
uration set-up, the materials deposited as thin-films (if used) and even indicator of the resolution of the measurements, together with the re-
on how good the instrumentation is. Additionally, capabilities such as solution of the detector. Moreover, since Q is a relative measurement,
cross-sensitivity or selectivity depend on the affinity between the bio- the effect of dealing with a higher or lower λ 0 is minimized.
marker and the bioreceptor, as well as the actual conditions in which
the experiment is being carried out. For instance, experiments can be 3.3. Figure of merit (FOM)
done under controlled buffer conditions, or in more complex matrices
such as blood serum, plasma or blood itself. As the complexity of the After defining the sensitivity and FWHM, the Figure of Merit can be
testing matrix increases, so does the potential number of difficulties calculated as the quotient between these two, as indicated in expression
that it is necessary to handle, since there are many other molecules that 10. It is normally expressed in RIU−1.
can interfere with the detection of the analyte. Finally, parameters like
S
regeneration, repeatability or reproducibility also depend on the ex- FOM =
FWHM (10)
perimental kit and, therefore, on the possibility of introducing external
agents, like enzymes, that can unbind the already created bior- This value is an idea of how much the sensor is approaching the
eceptor–biomarker bonds to start the detection process again ideal situation (i.e. the highest sensitivity and the lowest FWHM).
(Chiavaioli et al., 2017). Though it is true that the FOM is obtained as a function of the SRI, in
In view of the previous issues, the focus will be centred on those the biosensors field the wavelength shifts are due to the analyte–bior-
parameters that lead to a more objective evaluation of an optical sen- eceptor recognition. A strategy that may simulate this behaviour is to
sing platform. These parameters are provided in most of the articles obtain the FOM as a function of thickness, but as stated for the sensi-
published on optical fibre biosensors and they are the sensitivity to the tivity, it is easier to operate with the SRI.
surrounding refractive index (SRI), the spectral bandwidth and, finally,
as a derived magnitude of the previous two, the Figure of Merit (FOM). 3.4. Limit of detection (LOD))
In order to contrast the adequateness of these parameters in terms of
evaluating the performance of an optical fibre biosensor, their re- The LOD is one of the main parameters analysed when addressing
lationship with the limit of detection (LOD) will be analysed. the design and characterization of biosensors. It indicates the hy-
pothetical minimum value of the analyte concentration that the sensor
3.1. Sensitivity is capable of detecting under ideal experimental conditions. There are
three main criteria to calculate the LOD (Chiavaioli et al., 2017). The
The sensitivity is the ratio of the wavelength shift experienced by first method is based on the use of the standard deviations at low
the resonance wavelength of the transmission or attenuation band as concentration. After taking up to 10 measurements of both the blank
the SRI changes: sample (before taking actual measurements) and several discrete con-
centrations between 1 and 5 times the suspected LOD, the standard
Δλ
S= deviation σy is calculated. After that, expression 11 can be used to ob-
Δn (8)
tain the experimental LOD:
It must be pointed out that the biomarker–bioreceptor interaction is yLOD = y¯blank + tα, k − 1 σy (11)
basically the adhesion of thin-film progressively deposited over the
bioreceptor layer and, consequently, the wavelength shift is due to where tα, k − 1 σy is the α-quantile of the t-Student function with k − 1
variations of the refractive index and thickness of the material sur- degrees of freedom at (1 − α) confidence interval. The second approach
rounding the waveguide. Consequently, another good parameter could is based on the use of the calibration curve of the biosensor and on
also be the sensitivity to thickness changes in the coating. However, this recommendations by the IUPAC. According to this method, the LOD can
parameterization will also depend on the refractive index of the ma- be obtained by performing expression 12:
terial selected for testing this sensitivity. By contrast, the sensitivity to yLOD = f −1 (y¯blank + 3σmax ) (12)
the refractive index, though not an exact prediction of the further
performance of the biosensor, is easier to obtain and is independent which stands for the inverse of the fitting function (typically a sig-
from additional variables. Therefore, the sensitivity to the SRI is a re- moidal curve) evaluated in the point ( yblank + 3σmax ) , which means
ference value for assessing the biosensor before using it for detecting a ȳblank plus three times the maximum standard deviation obtained among
specific analyte (Chiavaioli et al., 2017). all the measurements. Finally, the third strategy is to calculate the
quotient in expression 13:
3.2. Full width at half maximum/minimum (FWHM) and Q-factor R R
yLOD = =
Ssurf Δn/ ρmax (13)
The central wavelength of a transmission or attenuation band is the
wavelength location of the maximum or minimum value of that band. where R is the sensor resolution and Ssurf is the quotient between the RI
This central wavelength, also called the resonance wavelength, will be change (Δn) and the maximum surface density concentration ( ρmax ) of
named λ 0 henceforward. the target analyte. Given the fact that there are no ideal or absolute
Once λ 0 has been defined, the full width at half minimum or max- measurements and even more so when talking about the bio disciplines,
imum (FWHM) is the wavelength range covered by the resonant band at it seems that the best way to determine LOD is the first or the second
a level 3 dB above/below its minimum/maximum, depending on whe- one, although the third approach is common for SPR-based biosensors
ther the measurements are in transmission or in absorption (Socorro (Chiavaioli et al., 2017). Both of them are statistically calculated, which
et al., 2014b). gives added value to the investigations. The second offers an approx-
Another parameter closely related to the FWHM is the quality factor imation based on IUPAC standards, which means that it may be more
(Q-factor), which is basically the quotient between λ 0 and the FWHM: rigorous from a scientific point of view and it is globally accepted.
As shown, a good calculation of the LOD needs a statistical analysis
λ0
Q= and it depends on many characteristics such as the affinity between the
FWHM (9)
bioreceptor and the analyte. Therefore, it is important to take a look at

10
A.B. Socorro-Leránoz, et al. Biosensors and Bioelectronics: X 1 (2019) 100015

those parameters that can be used for determining the performance of

Ribaut et al. (2016)

Ribaut et al. (2017)

Voisin et al. (2014)

Zhang et al. (2017)
the device independently of the conditions that affect the LOD. This is

Lepinay et al.
the aim of the next section: to compare the different optical structures

Reference
with parameters such as the FOM, the Q-factor and the sensitivity,

(2014)
which will be the basis for the assessment of the different types of
biosensors found in the literature.

CK7 pep 0.4 nM (1.04 ng/ml)

Streptavidin: 2 pM (0.11 ng/

CK7FP 1 pM (0.078 ng/ml)
4. Assessment of latest trends in optical fibre wavelength-based

10−12 g/mL (0.001 ng/ml)

AuNs 11 pM (2.69 pg/ml)

AuNc 8 pM (1.95 pg/ml)

Transferrin: 10−7 g/ml

15.56 nM (1.59 μg/ml)
biosensors

Limit of detection
Monitoring the change of a biomarker in real time allows the
identification of the susceptibility to different therapies and interactive

(0.1 μg/ml)
optimization of medical treatments with reduced time and costs, com-
pared to clinical validation of therapies (Liang et al., 2017). Different

ml)
protein biomarkers are correlated with the presence of pathogenic
processes and diseases. Usually, the performance of a new optical fibre

FOM (RIU−1)
biosensor is evaluated by direct binding model assays. According to the
reviewed literature, the most standardized biological measurements

2618

5000
involving the detection of bioreceptor–analyte complexes are IgG/anti-

–
–
IgG, (strept)avidin/biotin and BSA/anti-BSA. They are normally chosen

RIU range

1.32–1.35

1.31–1.34

1.32–1.42
because of their low purchase price, ease of handling, availability and
widely studied binding and immobilization process. Once adequate

–
performance of the biosensor is proved, the biomarkers associated with
specific pathologies are employed in order to identify a specific use for

500 (assuming the values provided by

350 (assuming the values provided by

the biosensor.
This section summarizes the results achieved in the literature using
wavelength-based optical fibre biosensors. The publications have been
selected and analysed considering the parameters described in section

Bialiayeu et al., 2011)

3, in order to see if the optical structure determines the values obtained
Sensitivity (nm/RIU)

500 (authors report)

Voisin et al., 2014)
for each of the studied parameters. All these data are collected in Tables
1–4, corresponding to the different optical platforms described in sec-
tion 2 (there were some references where no information on some of the
parameters was given. This especially affected TFBG-based sensors,
576

where in some cases the amplitude of the resonant peaks envelope is

–

used for sensing instead of the wavelength shift).

Q-factor

̴ 15382

̴ 15600
̴ 7000

̴ 7712

̴ 5142

4.1. Optical fibre biosensors based on gratings

FWHM (nm)

According to section 2, TFBG-based sensors should be one of the

structures that provide the best performance in the domain of bio-
0.22

0.30

sensors. In addition, TFBGs are combined with other phenomena in

0.2

0.1

0.1

order to improve their performance. A good example is the deposition

λ0 (nm)

of gold thin-films, which increase the inherent sensitivity of the TFBG

1545

1542

1543
1538

1560

by means of an SPR. In this respect, TFBG-SPR sensors have been re-

cently developed for many bio-sensing applications, such as the de-
tection of Newcastle virus (Luo et al., 2018) or porcine circovirus type 2
Glycoprotein: concanavalin

Cytokeratin 7 full protein

(PCV2) (Luo et al., 2016) and to detect different cancer biomarkers like
Analysed parameters for TFBG-based optical fiber biosensors.

cytokeratin 7 and 17 (Ribaut et al., 2017, 2016), urinary proteins (Guo

et al., 2016), breast cancer biomarker (Sun et al., 2017), thyroglobulin
Cytokeratin 17

(Quero et al., 2016), etc. The optical platforms employed to detect

CK7 peptide

Streptavidin
Transferrin
Biomarker

cytokeratin 7 and 17 achieved the best Q-factors: Q ̴ 7712 (Ribaut et al.,

CK7FP

Biotin

2016) and Q ̴ 5142 (Ribaut et al., 2017) respectively.

Another technique that has been applied to TFBG-SPRs consists of
A

an interrogation with circularly polarized light to the optical fibre

10° TFBG-LSPR with Au nanocages and Au

surface, which maximizes the optical coupling with the SPR. This
method allowed Q values of 15600 to be obtained in a work where
7°–9° TFBG-SPR coated with Au film
10° TFBG-SPR coated with Au film

6° TFBG -SPR coated with Au film

7° TFBG-SPR coated with Au film

streptavidin and human transferrin were detected (Voisin et al., 2014).

The FOM of this work was around 5000 RIU−1, the best FOM achieved
so far with a wavelength-based optical fibre biosensor (see Fig. 11).
Following the same principle, TFBGs can excite localized surface
plasmon resonances (LSPR) when gold nanoparticles are used instead of
nanospheres

gold thin-films (Bialiayeu et al., 2011). As a proof of concept, an ana-

lysis of TFBGs modified with several types of gold nanoparticles for
Substrate

protein detection was performed by Lepinay et al. (2014), which led to

Table 1

an increased Q-factor of 15000. In these conditions, the LOD for biotin

decreased from 21.99 ng/ml without nanoparticles to 1.95 pg/ml with

11
 Table 2
Analysed parameters for LPFG-based optical fiber biosensors. Excessively tilted FBGs can be considered as a specific case of LPFGs, as mentioned in section 2.1.2. The sensitivity in DTP-LPFGs has been obtained by
tracking the separation of both bands at DTP, which typically increases the sensitivity of each single band by a factor of 2.
Substrate Biomarker λ0 (nm) FWHM (nm) Q-factor Sensitivity (nm/RIU) RIU range FOM (RIU−1) Limit of detection Reference

LPFG AmpC β- lactamase 1635 12.11 135 ̴ ∼1500 124 few tens of nM (Quero et al., 2016b)
LPFG Bacterial lipopolysaccharide 1612 21 76.76 ̴ 6900 – 328.57 0.6 uM Brzozowska et al. (2015)
A.B. Socorro-Leránoz, et al.

LPFG DNA 1590 15 ̴ 106 – – – 2 μM (9.22 μg/ml) Chen et al. (2007)

LPFG Streptavidin 1429 19 ̴ 75.16 – – < 0.0125 mg/ml Wang et al. (2009)
LPFG Streptavidin 1635 17 ̴ 96.18 1000 58.8 0.1 mg/ml Pilla et al. (2009)
LPFG with policarbonate and graphene oxide Biotinylated BSA 1575 5 ̴ 315 2000 1.334 400 < 0.2 aM (0.01 fg/ml) Esposito et al. (2018)
LPFG with atactic polystyrene Tg 1617 3 ̴ 539 ̴ 1700 1.34 566.67 0.08 ng/ml (Quero et al., 2016a)
LPFG Anti-IgG – – – 15 1.33 – 0.5, 7.6 mg/l (500, 7600 ng/ml) Chiavaioli et al. (2014b)
LPFG with titania-silica Anti-IgG 1535 15 ̴ 102.33 A −2044.5 1.333–1.334 472 A 25 μg/l (25 ng/ml) Chiavaioli et al. (2015)
B −7075.3 B 13 μg/l (13 ng/ml)
C (Serum) 8 μg/l (8 ng/ml)
LPFG with silica-titania Anti-IgG 1575 4.4 ̴ 358 7000 1.33–1.34 1590 0.025 mg/l (25 ng/ml) Biswas et al. (2017)
DTP-LPFG DNA 1535 1 ̴ 1535 154 – 154 10 nM (∼46 ng/ml) Delgado-Pinar et al. (2017)
DTP-LPFG IgG 1500 15 ̴ 100 1309 1.333–1.393 87.27 50 ng/ml Chiavaioli et al. (2014a)
DTP-LPFG with graphene oxide Anti-IgG 1320 19 ̴ 69.47 2538 1.333–1.347 133.58 7 ng/ml Liu et al. (2017)
DTP-LPFG DNA 1420 5.79 ̴ 245.25 1359 1.30–1.44 137.13 4 nM (∼18.4 ng/ml) Chen Liu (2015)
DTP-LPFG E. coli B (Bacteria) – – – 3000 1.3–1.5 – 107 cfu/ml (Krans, 2015)

̴ 81° TFBG coated with Au nanospheres Newcastle disease virus (NDV) 1585 6 ̴ 264 ̴ 180 1.33–1.38 ̴ 30 25 pg/mL (0.025 ng/ml) Luo et al. (2018)
̴ 81° TFBG Porcine circovirus type 2 1545 1.5 ̴ 1030 135 1.33–1.38 90 4.06 ng/ml Luo et al. (2016)

12
Table 3
Analysed parameters for interferometry-based optical fiber biosensors. All-fiber interferometers and Fabry-Pérot structures are included.
Substrate Biomarker λ0 (nm) FWHM (nm) Q-factor Sensitivity (nm/ RIU range FOM Limit of detection Reference
RIU) (RIU−1)

SMF – PCF – SMF Streptavidin 1552 10 ̴ 155.2 320 1.33–1.34 32 10 μg/ml Hu et al. (2012)
SMF – PCF – SMF Anti-BSA 1545 14 110.36
̴ 722.3 1.308–1.320 51.59 125 pg/ml (0.125 ng/ml) Betancur-Ochoa et al.
(2017)
SMF – exposed core fiber – SMF Streptavidin 1360 26.7 ̴ 50.94 - 3137 1.332–1.335 117.5 – (Lee et al., 2018)
In-fiber MZI (half SMF core) BSA 1500 9.8 ̴ 153 −10055 1.300–1.330 1026 2.57 × 10−4 mg/ml (257 ng/ml) Li et al. (2017)
SMF (core mismatch) IgG 1625 120 ̴ 13.54 ̴ 14000 1.332–1.339 116.66 47 ng/ml (B. T. Wang and Wang,
2018a)
Etched SMS Anti-IgG 1380 10 ̴ 138 280 1.32–1.41 28 0.2 mg/L (200 ng/ml) Cardona-Maya et al.
(2018)
Chitosan nickel-coated SMS Histidine tagged proteins 1570 10 157
̴ 69.12 – 6.9 0.8368 ng/ml Ravikumar et al. (2018)
Nonadiabatic tapered SMF combined with FBG (FBG for Breast cancer biomarker 1527 10 ̴ 152.7 2333 1.332–1.344 233.3 2 ng/ml Sun et al. (2017)
temperature control) (HER2)
Polymer-coated nonadiabatic tapered SMF DNA 1498 4 374.5 – – – < 10−10 M (0.79 ng/ml) Huang et al. (2000)
Tapered capillary optofluidic sensor μRNA 1530 10.71 ̴ 142.86 1300 – 121.38 212 pM (1.43 ng/ml) Liang et al. (2017)
FPI BSA 1565 25.4 ̴ 61.61 – – 0.48 ng Chen et al. (2012)
Biosensors and Bioelectronics: X 1 (2019) 100015
A.B. Socorro-Leránoz, et al. Biosensors and Bioelectronics: X 1 (2019) 100015

nanoparticles, as indicated in Table 1.

(B. T. Wang and Wang,

Chiavaioli et al. (2018)

Regarding LPFGs, the other major group presented in section 2 as a

(Q. Wang and Wang,

Sanders et al. (2014)

Zubiate et al. (2017)

Jia and Yang (2014)
suitable candidate for biosensing, one of the first works on a biosensing

Cao et al. (2013)

Lee et al. (2018)

Shi et al. (2015)

application based on this structure consisted of a standard LPFG in
which the fibre surface was functionalized by using methacrylic acid/
Reference

methacrylate copolymer (Eudragit® 100) for the implementation of an

2018b)

2018)
IgG/anti-IgG bioassay. The results showed a sensitivity of 15 nm/RIU
and an LOD of 500 ng/ml anti-IgG (Chiavaioli et al., 2014b). Later, the
12.0 pM (0.0048 ng/ml)

same authors presented a ten-fold performance enhancement by using

MMF SnO2: 0.9 ng/ml

SMF: 0.15 ng/l (1 fM)

MMF ITO: 3.5 ng/ml
1.6 nM (̴ 240 ng/ml)
an LPFG operating in the dispersion turning point (DTP). With this
Limit of detection

structure it was possible to obtain a Q-factor of 100, a sensitivity of

0.0625 ng/ml
1309 nm/RIU, an FOM of 87.27 RIU−1 and an LOD of 50 ng/ml
100 fg/ml

0.9 μg/ml
37 ng/ml

40 ng/ml

(23 pM)
(Chiavaioli et al., 2014a). Additionally, by applying the mode transition

(6 pM)
phenomenon, the same group designed sol−gel based titania−silica-
–

coated LPFGs, where a significant FOM, sensitivity and LOD improve-

ment was reported: 472 RIU−1, 7075.3 nm/RIU and 8 ng/ml respec-
tively for anti-IgG (Chiavaioli et al., 2015) and 1590 RIU−1, 7000 nm/
FOM (RIU−1)

60.7 (authors

24 (authors

19 (authors

(SnO2) 280
(ITO) 7.06

RIU and 25 ng/ml for anti-IgG (Biswas et al., 2017). The functionali-
report)

report)

report)

zation of the DTP-LPFG using graphene oxide nanosheets, tested by a

1.58

4.37

500
different group, resulted in similar sensitivity and LOD results: 2538
–

nm/RIU and 7 ng/ml of anti-IgG (Liu et al., 2017), proving the fine
1.333–1.442
1.341–1.368

1.333–1.373

1.333–1.373

1.333–1.359
RIU range

performance of coated DTP-LPFGs. Moreover, an LPFG biosensor

1.33–1.4

coated with a single layer of atactic polystyrene allowed the detection

1.335

of thyroglobulin, a protein biomarker of differentiated thyroid cancer,

–

with Q ̴ 539, 1690 nm/RIU of sensitivity and FOM 566.6 RIU−1 (Quero
et al., 2016). LPFG-based biosensors have also been used for biotin/
Sensitivity (nm/

(SnO2) 14000

streptavidin binding detection (Esposito et al., 2018; Lepinay et al.,

(GNs) 914
(GNr) 601

(ITO) 600

2014; Liu et al., 2018; Pilla et al., 2009; Voisin et al., 2014; Wang et al.,
601.05

2009), while the lowest LOD was obtained with a reflection config-
3915

3311

2054

6000
RIU)

̴ 226

595

uration, resulting in an LOD of 0.01 fg/ml of biotinylated BSA (Esposito

et al., 2018), though it must be stated that the size of the molecule plays
(SnO2) ̴ 29.8
(ITO) ̴ 6.7

a role in this low LOD achieved.

Q-factor

̴ 180.25

Another important application domain of biosensors is the detection

134.8
̴ 5.81

6.41
̴ 4.9

of nucleic acids, which are employed as biomarkers with diverse ap-

–

plications, including diagnosis, prognosis and selection of targeted

Analysed parameters for resonance-based optical fiber biosensors. SPR, LSPR and LMRs are included.

therapies. Currently, publications on the wavelength-based optical fibre

108.2 (authors
FWHM (nm)

biosensors for nucleic acids are scarce, but there are some papers that
(SnO2) 50
(ITO) 85

evidence the interest of the scientific community in the topic. The most
142.86

report)
137.5

sensitive optical structure among the different fibre gratings optical

6.6

12
–

platforms used to detect specific sequences of DNA was DTP-LPFG

(SnO2) 1490

(1359 nm/RIU), which reported the lowest LOD: 4 nM (∼18.4 ng/ml)

(GNs) 600
(GNr) 875

(ITO) 570

of DNA (Chen Liu, 2015).

λ0 (nm)

1370
̴ 890
700

800

525

694

4.2. Optical fibre biosensors based on interferometers

–
Prostate cancer biomarker

Among interferometers, an etched single-mode multimode single-

mode (E-SMS) optical fibre structure has proved to be an effective and
C reactive protein
Anti-human IgG

suitable optical platform for IgG/anti-IgG detection bioassays, with a Q ̴

Ochratoxin A

138, 280 nm/RIU sensitivity, 28 RIU−1 FOM and 200 ng/ml anti-IgG
Biomarker

Anti-BSA

Anti-IgG

LOD (Cardona-Maya et al., 2018) (Fig. 12). Here, due to the fact of
(f-PSA)

obtaining a periodic spectrum with several resonant bands available, a

IgG

IgG

IgG

dual measurement in both wavelength shift and phase is presented. A

SPR with Au nano-disks array on optical fiber tip

better sensitivity was obtained using a single-mode fibre with a longer

LSPRs with Au nanospheres and with nanorods
SPR with Au nanopattern on optical fiber tip

SPR + LSPR with Au on MMF – PCF – MMF

core-offset fusion splice based on an in-fibre MZI. This platform pre-

sented a high sensitivity (13936 nm/RIU) and low LOD (47 ng/ml anti-
IgG) (Wang and Wang, 2018). Furthermore, an immunosensor based on
SPR with electroless plated Au film

the Fabry–Pérot interferometer with a layer-by-layer (chitosan/poly-

SPR with Ag + graphene oxide

LMR with ITO and with SnO2

styrene sulfonate) membrane was also used to detect the anti-IgG. In

this case, an LOD of 0.78 ng/ml anti-IgG was obtained (Chen et al.,
LSPR with Au nanorods

on optical fiber tip

2013).
In addition, in-fibre MZIs have also been used for BSA/anti-BSA
biosensing. For instance, with a photonic crystal fibre taper an LOD of
LMR with ITO

0.125 ng/ml of anti-BSA was obtained (Betancur-Ochoa et al., 2017),

Substrate

while the sensitivity was 722.3 nm/RIU and the FOM 51.59 RIU−1. In
Table 4

another contribution based on an in-fibre MZI created on the core of an

SMF fibre, a higher FOM (1026 RIU−1) and a sensitivity of 10055 nm/

13
A.B. Socorro-Leránoz, et al. Biosensors and Bioelectronics: X 1 (2019) 100015

Fig. 11. (a) Transmitted spectrum of a TFBG-SPR immersed in salted water (SRI around 1.38) with its corresponding electrical and magnetic components. (b)
Wavelength shift and amplitude sensorgrams for 0 and + 2 modes as a function of streptavidin concentration. Reproduced with permission of Elsevier (Voisin et al.,
2014) with Creative Commons Attribution License (CC BY 4.0).

RIU was obtained. However, the LOD increased: 257 ng/ml of BSA (Li used in the detection of nucleic acids. A taper interferometer
et al., 2017). In addition, a PCF-based in-fibre MZI was used for biotin/ achieved < 10−10 M (0.79 ng/ml) LOD for a specific sequence of DNA
streptavidin detection, achieving a similar sensitivity of 320 nm/RIU (Huang et al., 2000). In the case of the microRNA, the optical structure
and lower FOM: 32 RIU−1 (Hu et al., 2012). The LOD reported with this employed was a modal interferometer, which achieved a sensitivity of
platform was 10 μg/ml of streptavidin (10000 ng/ml). The differences 1300 nm/RIU and allowed the detection of 1.43 ng/ml of microRNA
among these three biosensing platforms as well as in the characteristics (Liang et al., 2017).
of the analyte and its affinity to the bioreceptors are assumed to be the
reasons for the varying LOD results. In addition, in the three cases the 4.3. Optical fibre biosensors based on resonances
detected analyte was different: antiBSA, BSA and streptavidin respec-
tively (see Table 3). Regarding biosensors based on resonances, the generation of SPRs
Optical fibre biosensors based on interferometers have also been with metallic nanostructures deposited on fibre is one of the most

Fig. 12. Results corresponding to bioassay E-SMS 1 with different concentrations of goat anti-IgG, ranging from 2.9 mg/l to 195 mg/L a) Wavelength response curve,
b) calibration curve in wavelength. The solid line provides the best sigmoidal curve fitting of the experimental data with a 0.9981 correlation coefficient, c) phase
response curve, d) calibration curve of the phase shift. The solid line represents the best curve fitting for the sigmoidal Hill equation with a 0.9980 correlation
coefficient. Reproduced with permission of Elsevier (Cardona-Maya et al., 2018) with Creative Commons Attribution License (CC BY 4.0).

14
A.B. Socorro-Leránoz, et al. Biosensors and Bioelectronics: X 1 (2019) 100015

studied techniques (Lin et al., 2010). In spite of this, in most SPR sen- 4.4. Comparative study of parameters among biosensing platforms
sors based on optical fibre, the values of Q and FOM obtained are quite
low, because of the broad spectral width of the resonances. That is why After presenting the performance of the different optical structures,
it is more common to find SPRs in combination with other techniques it is time to compare the different biosensing optical platforms with the
(Caucheteur et al., 2017; Lepinay et al., 2014; Ribaut et al., 2017, 2016; aid of the parameters within Tables 1–4 Table 1 refers to TFBGs.
Voisin et al., 2014; Zhang et al., 2017) or with some improvements. Though TFBGs with higher tilt angles present moderate values of FOM
In particular, LSPRs have found application in the detection of (below 100 RIU−1), the rest of the TFBGs present Q values of the order
biological agents with a very low LOD. The implementation of an LSPR of 103 and 104, but their inherent sensitivity is very low, which is in-
optical fibre biosensor has been successfully used for detection of anti- adequate for obtaining high FOM values. However, the deposition of
BSA (Jia and Yang, 2014), a mycotoxin called ochratoxin A (Lee et al., either gold thin-films or nanoparticles allows the sensitivity to be in-
2018) and free prostate specific antigen cancer biomarker (Sanders creased and FOMs exceeding 104 RIU−1 can be obtained.
et al., 2014). The parameters obtained with this optical platform were The Q-factor achieved by LPFG-based optical structures ranges from
in the same order of magnitude in the different papers. The Q-factor 102 to 103, one order of magnitude lower than TFBGs. However, the
value was around 6 in the case of ochratoxin A and free prostate cancer sensitivity is of the order of hundreds to thousands of nm/RIU, which
biomarker (Lee et al., 2018; Sanders et al., 2014). In addition, the makes it possible to achieve FOMs of up to 1590 RIU−1 (Biswas et al.,
sensitivity was ̴ 600 nm/RIU in the detection of anti-BSA and ochratoxin 2017), very close to the values obtained with the best TFBGs. Moreover,
A (Jia and Yang, 2014; Lee et al., 2018) and ̴ 226 nm/RIU in the case of this value was just achieved with the mode transition (MT) phenom-
free prostate specific antigen detection (Sanders et al., 2014). These enon. If both MT and DTP were combined, this value could probably be
optical fibre biosensors allow the detection of 4.8 pg/ml of ochratoxin A improved, though it must be pointed out that in the DTP region the
(Lee et al., 2018) and 0.1 pg/ml of free prostate specific antigen spectral width is typically increased (Del Villar et al., 2018).
(Sanders et al., 2014). Interferometers are the most heterogeneous group because of the
Regarding LMRs, a comparison was done on the performance of wide differences among the different optical platforms. Their Q is in the
uncladded 200-micron-core silica fibres and D-shape SMF fibres coated range of hundreds and the sensitivity is quite variable, with a couple of
with indium tin oxide (ITO) or tin dioxide (SnO2) (Chiavaioli et al., specific cases with 10000 (Li et al., 2017) and 14000 nm/RIU (Wang
2018) (Fig. 13a). The nanocoating that shows the best performance is and Wang, 2018), whereas the FOM is in the range of hundreds of
SnO2, whereas the best optical structure is D-shaped SMF, with a sen- RIU−1 with an exceptional case of 1026 RIU−1 (Li et al., 2017).
sitivity of 14000 nm/RIU (Arregui et al., 2016) and an LOD of 0.15 pg/ A last technology for developing biosensors includes those struc-
ml (Chiavaioli et al., 2018). This result improves on the best value tures based on resonances (SPRs, LSPRs or LMRs). They normally pre-
obtained with uncladded 200-micron-core silica fibres (0.9 ng/ml) by sent low Q-factors. However, the sensitivity of LMRs is very high,
three orders of magnitude (see Fig. 13b and c). In addition, the detec- achieving values of 14000 nm/RIU in the water region in the case of
tion of C-reactive protein, an inflammation process biomarker, by ITO- nanocoated D-shaped fibres (Arregui et al., 2016). This fine property,
coated D-shape SMF fibre reported 6000 nm/RIU sensitivity, 500 combined with the improvement in the Q-factor by controlling the
RIU−1 FOM and 0.0625 ng/ml LOD (Zubiate et al., 2017) (see Table 4). polarization of light, allows FOM values of 280 and 500 RIU−1 to be
obtained (Chiavaioli et al., 2018; Zubiate et al., 2017).
The best devices in terms of sensitivity can be found in Table 4
(SPRs and LMRs), with several structures that exceed 1000 nm/RIU and

Fig. 13. (a) Comparison among calibration curves obtained with three kinds of LMR sensors: ITO-coated (triangles) and SnO2-coated (circles) unclad MMF bio-
sensors, and the SnO2-coated D-shaped SMF biosensor (rhombuses). (b) Sensorgram of the SnO2-coated unclad MMF biosensor starting from serum to all antigen
concentrations (1 μg/l – 500 mg/l). (c) Sensorgram of the SnO2-coated D-shaped SMF biosensor starting from the serum to all the antigen concentrations (0.001 μg/l –
1 μg/l). Reprinted with permission from (Chiavaioli et al., 2018). Copyright (2018) American Chemical Society.

15
A.B. Socorro-Leránoz, et al. Biosensors and Bioelectronics: X 1 (2019) 100015

one reaching 14000 nm/RIU in the water region (Arregui et al., 2016). obtained in terms of sensitivity and the FOM. The sensitivity and FOM
In Table 3 (interferometers), it is possible to find high sensitivities ex- were improved from 600 nm/RIU and 7 RIU−1 with the cladding re-
ceeding 10000 nm/RIU (Wang and Wang, 2018), but there are also moved multimode fibre coated with ITO, to 14000 nm/RIU and 280
other devices with only tens of nm/RIU. In Table 2 (LPFGs), the sen- RIU−1 with the D-shaped structure coated with SnO2.
sitivities range from 500 to 7000 nm/RIU (the devices are slightly less The relationship between the LOD and the FOM indicates that the
sensitive than LMRs). Finally, in Table 1 (TFBGs), the sensitivity is re- FOM is a good parameter for testing optical structures used as bio-
duced to hundreds of nm/RIU in the best cases, when depositing gold sensors. However, probably in the future, with more publications and
thin-films or nanoparticles (Guo, 2017; Voisin et al., 2014). data (optical fibre biosensors is a technology that has exploded during
Although a good parameter, sensitivity becomes a disadvantage if the last years), it will be possible to use a more accurate expression
the biosensor film attached to the optical structure is very thick, be- parameter than the ratio between sensitivity and FWHM, which is the
cause a wide spectrum is necessary to monitor the wavelength shift. In one used by some authors nowadays (Gupta et al., 2015; Ozcariz et al.,
this respect, a lower sensitivity is better, as long as the resolution is 2017). For example, it could be possible that the squared sensitivity
maintained. Therefore, it is also important to consider either the full divided by the FWHM offers a better prediction of the performance of
width at half maximum (FWHM) or the Q-factor, because both of them the optical structures when used for biosensing. In this respect, there is
are related to the smallest wavelength shift that can be detected. Of a lot of work to do. This review has analysed this question in terms of
these two parameters, the Q-factor, as stated in section 3, minimizes the FOM in order to compare the performance of the most important optical
influence of the operating wavelength. That is why the focus will be fibre structures, which will serve to give designers an idea of what type
centred on this parameter instead of the FWHM. Regarding the Q- of structure they should use.
factor, according to Tables 1–4 it is clear that the order of best per-
formance observed when analysing sensitivity is inverted. Specifically, 5. Conclusions
TFBGs (the Q ranges from 103 to 104), LPFGs (the Q ranges from 102 to
103), interferometers (the Q is typically 102) and resonances (the Q In summary, this work has presented a review of the most re-
ranges from 101 to 102) is the ranking obtained. presentative scientific contributions on wavelength-based optical fibre
Apparently, TFBGs seem to be the best devices for biosensing in that biosensors. In first place, according to the literature, the most promi-
they present a very high Q-factor and an acceptable sensitivity. nent technologies addressing this topic are: grating-based optical fibres
However, cost is another important issue. Devices with a high Q-factor (tilted-FBGs and LPFGs), interferometers (in-fibre Mach–Zehnder in-
require detectors with a very high resolution that can be used for terferometers mainly) and resonances (SPRs, LSPRs and LMRs). All of
tracking very small wavelength shifts. Considering that question, re- them are based on the generation of resonant bands, either because
sonance-based sensors are easier to apply in a system with a detector of their own optical structure generates them or because a nanostructured
low resolution. That is why many authors use the FOM, a parameter material has been deposited onto the optical substrate to generate or
that balances the importance of the sensitivity and the FWHM (closely enhance the performance of such resonant band.
related to the Q-factor). Considering this parameter, the order observed Second, a classification of these main optical structures has been
for the Q-factor is not modified when analysing the best device in each made according to several parameters related to the optical structure:
group: TFBGs (5000 RIU−1), LPFGs (1590 RIU−1), interferometers full width at half maximum/minimum (FWHM), Q-factor, sensitivity,
(1026 RIU−1) and LMR-SPRs (500 RIU−1). However, it must be pointed figure of merit (FOM) and limit of detection (LOD). In terms of sensi-
out that the differences have been diminished compared with the Q- tivity the ranking from better to worse performance is: resonances,
factor. interferometers, LPFGs and TFBGs. However, this ranking is inverted
After understanding that the FOM balances the sensitivity and the Q regarding the Q-factor: TFBGs, LPFGs, interferometers and resonances.
factor, the final step is to identify the relationship between the FOM and Also, the ranking is maintained when the FOM is studied, though the
the LOD by comparing biosensors developed in different laboratories. differences are diminished because the FOM depends both on the
This is a difficult task because there are many additional parameters FWHM (closely related to the Q-factor) and on the sensitivity.
that play a role in the final results. Despite all this, anti-IgG allowed The relationship between a high FOM and a low LOD is difficult to
some specific cases to be seen where the FOM is an optical parameter establish if different works are compared, since the experimental con-
related with the LOD. When detecting anti-IgG, an SMS etching inter- ditions are different. However, in those works where the conditions are
ferometer-based biosensor achieved a 28 RIU−1 FOM and a 200 ng/ml the same it has been proved that improving the FOM allows attaining a
LOD (Cardona-Maya et al., 2018), whereas with titania–silica-coated better LOD. Consequently, FOM becomes a valid parameter for asses-
LPFG an improvement in the FOM up to 472 RIU−1 (Chiavaioli et al., sing the performance of an optical structure as a biosensor. It is possible
2015) and to 1590 RIU−1 (Biswas et al., 2017) resulted in lower LOD of that in the future, with more research, it will be possible to find a more
8 ng/ml (Chiavaioli et al., 2015) and 25 ng/ml (Biswas et al., 2017) exact parameter to achieve this purpose. At the moment, FOM is a good
respectively. However, it must be pointed out that if the two LPFG indicator that can be used to compare the performance of the optical
structures are compared, the FOM of the first one is lower than the platforms, as has been done in this work.
second one and the opposite is true if they are compared in terms of
LOD. Declaration of interests
Perhaps the best proof that the FOM is a good assessment parameter
for the performance of a biosensor can be found in (Chiavaioli et al., The authors declare that they have no known competing financial
2018), where two comparisons were made. The first one was the uti- interests or personal relationships that could have appeared to influ-
lization of the same structure, a cladding removed multimode fibre, ence the work reported in this paper.
coated with ITO and with SnO2. With ITO, a material of lower refractive
index than SnO2 and, consequently, lower sensitivity, a 3.5 ng/ml LOD CRediT authorship contribution statement
was obtained, whereas with SnO2 a 0.9 ng/ml LOD was achieved.
Moreover, the application of a D-shaped structure coated with SnO2, A.B. Socorro-Leránoz: Formal analysis, Investigation, Writing -
with a higher sensitivity than the cladding removed multimode fibre, original draft, Writing - review & editing, Resources, Supervision,
allowed a 0.15 pg/ml LOD to be attained. In other words, using a D- Validation. D. Santano: Formal analysis, Investigation, Writing - ori-
shaped fiber and a SnO2 coating permitted to improve the LOD by more ginal draft, Writing - review & editing. I. Del Villar: Funding acquisi-
than three orders of magnitude compared to the cladding removed tion, Resources, Supervision, Validation, Writing - review & editing.
multimode fibre coated with ITO. This was due to the improvement I.R. Matias: Funding acquisition, Resources, Supervision, Validation,

16
A.B. Socorro-Leránoz, et al. Biosensors and Bioelectronics: X 1 (2019) 100015

Writing - review & editing. (Chitosan/Polystyrene Sulfonate) Membrane-Based Fabry–Perot Interferometric

Fiber Optic Biosensor. IEEE Journal of Selected Topics in Quantum Electronics 18 (4),
1457–1464. https://doi.org/10.1109/JSTQE.2012.2185221.
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A.B. Socorro-Leránoz, et al. Biosensors and Bioelectronics: X 1 (2019) 100015

study and sensing applications of polarization-dependent lossy mode resonances

generated by D-shape coated optical fibres. J. Light. Technol. https://doi.org/10. Her research interests focus on the biomedical engineering field, including the devel-
1109/JLT.2015.2392791. opment of optical fibre biosensors.
Zubiate, P., Zamarreño, C.R., Sánchez, P., Matias, I.R., Arregui, F.J., 2017. High sensitive
and selective C-reactive protein detection by means of lossy mode resonance based
Ignacio Del Villar received his M.S. degree in Electrical and Electronic Engineering and
optical fibre devices. Biosens. Bioelectron. 93, 176–181. https://doi.org/10.1016/j.
his Ph.D. degree, specialising in Optical Fibre Sensors, in 2002 and 2006, respectively
bios.2016.09.020.
from the Public University of Navarra (UPNA). During 2004 he was a visiting scientist at
the Institute d’Optique (Orsay, France) and in 2005 he was a visiting scientist at the
Abián B. Socorro-Leránoz is an Electrical and Electronic Engineer (2010), M.Sc. in Applied Physics Department of the University of Valencia (Burjassot, Spain). He is pre-
Biomedical Engineering (2012) and Ph.D. in Engineering (2015) from the Public sently a Reader at the UPNA since 2008, an Associate Editor of the Optics & Laser
University of Navarre (PUN-UPNA), Pamplona, Navarre, Spain. He was at the Armani Technology Journal since 2012 and an Associate Editor of the Journal of Sensors since
Research Lab (University of Southern California, Los Angeles, CA, USA) as a visiting Ph.D. 2014.
student in 2014. Currently, he is working as Assistant Professor at PUN/UPNA, where he
has published more than 55 scientific contributions both in JCR journals and conferences
and he has been involved in more than 15 competitive research projects with both public His research interests include optical fibre sensors and the analysis of waveguides and
and private funding. Most of them have been related to the development of optical fibre nanostructured materials, where he has co-authored more than 100 book chapters,
sensors and their application to biomedicine. journals and conference papers.

Ignacio R. Matias received the M.S. degree in Electrical and Electronic Engineering and
His research interests are the development of optical fibre sensors, including biosensors
his Ph.D. degree in Optical Fibre Sensors from the Polytechnic University of Madrid
and, in general, the development of biomedical applications based on optical fibres.
(UPM), Spain, in 1992 and 1996, respectively. He became a Lecturer at the Public
University of Navarra (Pamplona, Spain) in 1996, where he is presently a Permanent
Desiree Santano Rivero is a Biologist (2013) and received her M.Sc. in Microbiology and Professor. He has co-authored more than 300 book chapters, journals and conference
Health from the University of the Basque Country (UPV/EHU), Spain. She has co-au- papers related to optical fibre sensors and passive optical devices and systems. He was co-
thored conference papers related to Microbiology and Biomedical Engineering. Currently, Founding Editor of the IEEE Sensors Journal. He is an IEEE Senior member.
she is working as researcher at PUN/UPNA.

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