J. Biomedical Science and Engineering, 2009, 2, 312-317
doi: 10.4236/jbise.2009.25046 Published Online September 2009 (http://www.SciRP.org/journal/jbise/
JBiSE
).
Published Online September 2009 in SciRes. http://www.scirp.org/journal/jbise
Recent advances in fiber-optic DNA biosensors
Yi-Ming Wang1,2*, Xiao-Feng Pang1, Yu-Yu Zhang2
1College of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China; 2College of
Material and Chemistry & Chemical Engineering, Chengdu University of Technology, Chengdu, China.
Received 1 December 2008; revised 13 May 2009; accepted 18 May 2009.
ABSTRACT
Fiber-optic DNA biosensors are a kind of ana-
lytic setups, which convert the Waston-Crick
base pairs matching duplex or Hoogsteen’s tri-
plex (T/A-T, C/G-C) formation into a readable
analytical signals when functionalized single-
strands DNA (ssDNA) or double-strands DNA
(dsDNA) of interest are immobilized on the sur-
face of fiber-optic hybrids with target DNA or
interacts with ligands. This review will provide
the information about the fiber-optic DNA bio-
sensors classified into two categories depend-
ing on the end fiber and side fiber with or with-
out the labels—label-free fiber-optic DNA bio-
sensors and labeled fiber-optic DNA biosensor
in recent years. Both are dissertated, and em-
phasis is on the label-free fiber-optic DNA bio-
sensors. Fiber-optic DNA biosensors had got
great progresses because fiber-optic has more
advantages over the other transducers and are
easily processed by nanotechnology. So fiber-
optic DNA biosensors have increasingly at-
tracted more attention to research and develop
the new fiber-optic DNA biosensors that inte-
grated with the “nano-bio-info” technology for
in vivo test, single molecular detection and
on-line medical diagnosis. Finally, future pros-
pects to the fiber-optic DNA biosensors are
predicted.
Keywords: DNA Hybridization; Fiber-Optic Biosen-
sors; Label-Free; Nanotechnology
1. INTRODUCTION
Fiber-optic DNA biosensors are a kind of analytic setups,
which convert the Waston-Crick base pairs matching
duplex or Hoogsteen’s triplex (T/A-T or C/G-C) forma-
tion into a readable analytical signals when functional-
ized single-strands DNA (ssDNA) or double-strands
DNA (dsDNA) [1,2] of interest are immobilized on the
surface of side or end of fiber-optic hybrids with target
DNA or interacts with ligands, for example pollutants [3]
in the solution. This review will provide the information
about the application and potential of fiber-optic DNA
biosensors classified into two categories depending on
the fiber with or without labels—label-free fiber-optic
DNA biosensors and labeled fiber-optic DNA biosensor
in recent years. With the development of nanotechnology,
fiber-optic DNA biosensors have got great progresses
because fiber-optic can be easily miniatured to the
nanometer scale size by chemical etching [4] or tube
etching [5] and mechanically pulled with CO2 laser
heating setup [6], they are immune to electromagnet [7],
disposability [8] and long-distance transmission [9]. Be-
cause of these properties, fiber-optic DNA biosensors
have increasingly attracted more attention to research
and develop the new fiber-optic DNA biosensors that
integrated with the “nano-bio-info” technology so that
they can be employed for in vivo or within single cell
test [10], especially in the intracellular measurement for
real-time or on-line medical diagnosis [11,12]. On the
basis of optical techniques that correlate changes in
concentration, mass, number of molecules, or other
properties to direct changes in the characteristics of light
for detection of DNA hybridization or damage [13], dif-
ferent label-free fiber-optic DNA biosensors are depicted
in details. Finally, future prospects to fiber-optic DNA
biosensors are brought forward.
2. ADVANTAGES AND DISADVANTAGES
OF FIBER-OPTIC DNA BIOSENSORS
Nanoparticles [14,15], nanotubes [16,17], nanowires
[17,18,19,20,21,22,23] and fiber-optics as the matrices
of DNA biosensors to detect DNA specific sequence and
DNA hybridization have been reported. Fiber optic-
based DNA biosensors have many advantages over other
matrices-based DNA biosensors as following:
1) Fibers have a flexible geometry and can be tracta-
bly miniaturized at low cost to nanosacle structure for in
vivo measurements.
2) Fibers are immune to electromagnet, lower tem-
perature-dependence and low loss over long distance
transmission [7,8,9].

Y. M. Wang et al. / J. Biomedical Science and Engineering 2 (2009) 312-317 313
SciRes Copyright © 2009 JBiSE
3) Proper adjustment of the refractive index of the
waveguide and the surrounding media enables the per-
formance of surface-specific spectroscopy [25].
4) Fibers can guide light of different wavelengths at
the same time and in the different directions, so more
than one analyte can be responded simultaneously im-
mobilized multiple DNA probe molecules on the fiber
with a monitoring central unit.
5) Fibers have high Security and no reference elec-
trode.
6) They are highly stable with respect to calibration,
especially if one can measure the ratio of the intensities
at two wavelengths [26].
However, some disadvantages could confine their ap-
plicability and were present [25,26].
1) They are subjected to ambient light interference,
background absorbance, Raman scatter of fibers.
2) Limited stability of biological component immobi-
lized onto a fiber surface and limited availability of op-
timized commercial accessories for use with fiber-optic.
3) Immobilized chemistries are subjected to problems
with inadequate path length, path length instability due
to matrix swelling, reagent photolability and reagent
leaching.
4) They have a limited dynamic range in comparison
to electronic sensors.
5) Existing techniques are difficult to directly charac-
terize the functionalized surface of fiber because of
small size.
3. LABELD FIBER-OPTIC DNA
BIOSENSORS
Fluorescence labels were often used for biological re-
search protocols. Fluorescence measurement is readily
upscaled for multiplexing and can selectively associate
with dsDNA. Advances in the fluorescence-labeled fi-
ber-optic DNA biosensors-classified into two formats
depending on the interaction between fluorescent agents
and probe DNA sequence were introduced to detect
DNA hybridization, concentration, damage and single
base mismatch.
3.1. Fluorescent Reagents Intercalation into
dsDNA for Detection of Hybridization
Intercalators, such as ethidiun bromide (EB), acridine
orange (AO) and thiazole orange (TO), were selectively
tethered into DNA hydrids by noncovalent bond in these
DNA biosensors. Once these intercalators intercalated
with dsDNA, it will yield an increase in the intensity of
fluorescence by excitation (Figure 1).
Niu et al. [27] had designed a fluorescence fiber-optic
DNA biosensor using p-Hydroxyphenylimidazo[f] 1,
10-phenanthroline Ferrum(III) ([Fe(phen)2·PHPIP]3+) as
indicator to detect DNA hybridization. In this experi-
ment, 16*B (biotin-5′-CAC AAT TCC ACA CAA C-3′
S1) as capture probe was immobilized on the fiber-optic,
and hybridized with the different concentrations com-
plementary strand 16*C (5′-GTT GTG TGG AAT TGT
G-3′ S
2). After hybridization, fiber-optic obtained was
washed with doubly distilled water to remove oligonu-
cleotide bound nonspecifically. In order to detect non-
specific binding, a noncomplementary, 20-mer oligonu-
cleotide 20*N (5′-CTG CAA CAC CTG ACA AAC
CT-3′ S
3) was used. Then the DNA-modified optical
fiber was immersed in [Fe(phen)2·PHPIP]3+ aqueous
solution, and subsequently subjected to fluorescence
spectroscopy studies. The result showed that there was
no response at S1/fiber-optic and S1–S3/fiber-optic to
testify the selective hybridization and not absorption of
the target ssDNA on the fiber-optic (Figure 2 curve a
and b). While the enhancement of fluorescence indicated
that Fe(phen)2·PHPIP]3+ molecules were reconcentrated
on the S1–S2/fiber-optic surface for the binding interac-
tion (Figure 2 curve c-g).
=T
G
C



=T
=A
=
=
=T
G
C



=T
=A
A
C
G



A
T
=
=
=
=
A
C
G



A
T
Intercalator
A
C
G



A
T
=
=
Figure 1. Scheme of intercalators as fluorescent labels
tethered into dsDNA immobilization on the exposed
core of fiber-optic for detection of DNA hybridization.
Figure 2. Fluorescent intensity of Fe
(phen)2·PHPIP·3ClO4·2H2O on (a) S1/ fiber-optic; (b)
S1–S3/ fiber-optic; and (c-g) S1-S2/ fiber-optic. CPBS
(pH 6.0): 0.20 M, C[Fe（phen）2PHPIP]
3+: 8.0×10−6M, (c)
Cs2: 1.98×10−6 M; (d) Cs2: 2.96×10−6 M; (e) Cs2:
3.92×10−6 M; (f) Cs2: 4.89×10−6M; (g) Cs2:
58.25×10−6M [27].

314 Y. M. Wang et al. / J. Biomedical Science and Engineering 2 (2009) 312-317
SciRes Copyright © 2009 JBiSE
Piunno et al. [28] had established a fluorescence fiber-
optic DNA sensor system to detect the DNA hybridiza-
tion using EB as an intercalation. In order to test the
reproducibility of the sensor, another same DNA sample
was determined by same experimental condition, and the
fluorescence intensity was again measured. The results
indicated that an increase in fluorescence intensity was
observed which was similar in magnitude to that ob-
served from the first dsDNA analysis. It demonstrated
that the detection system was shown to be reproducible.
In addition, many experiments [29,30,31,32] had been
performed by Svanvik research group using intercalators
for the detection of DNA hybrid. Piunno et al. [33] had
investigated a fiber-optic biosensor for detection of DNA
hybridization using fluorescent DNA stain ethidium bro-
mide. These biosensors didn’t require traditional labeling
step prior to analysis of a sample [34], but they are influ-
enced to ambient temperature and solution ionic strength.
3.2. Fluorescent Agents Covalently Bind to
ssDNA for Detection of DNA Hybridization
The detection of DNA hybrid was performed using fluo-
rescent agents immobilized on the ssDNA through the
format of covalent bond. The fluorescent enhancement or
quenching was occurred when the complementary DNA
was associated with the probe sequence (Figure 3).
Wang and Krull [35,36,37] had investigated thiazole
orange dyes were covalently linked to the 5'- end of the
oligonucleotides, providing for a self-contained labeling
strategy for detection of hybrids. The biosensors provided
changes in steady-state fluorescence intensity signals
upon hybridization that reached saturation in seconds to
minutes, and were able to provide a quantitative determi-
nation of hybridization at nanomolar detection limits.
Some important parameters, the length of tether, density
of the probe molecules and ionic strength had been dis-
cussed to characterize the thermodynamic and kinetic
performance of these biosensors in their papers. Rogers et
al. [13] had established a method for detection of DNA
damage exposed to ionizing radiation with fluorescently
labeled complementary DNA sequence in the solution.
A
C
G



A
T
Labeling
A
C
G



A
T
Complementary DNA
=T
G
C



=T
=A
=
=
=
=
Fluorescent agent
A
C
G



A
T
Figure 3. Scheme of fluorescent agents covalently bond
to probe sequence immobilization on the exposed core
of fiber-optic for detection of DNA hybridization.
These biosensors can be employed repeatedly and not
require fluorescent agents in subsequent experiments.
These fluorescence-label fiber-optic DNA biosensors
had been extensively researched to detect the DNA hy-
bridization or determine the DNA quantities, yet it was
not to avoid the side effect on photoleaching that is in-
trinsic flaw. So some researchers had begun to study the
label-free fiber-optic DNA biosensors.
4. LABEL-FREE FIBER-OPTIC DNA
BIOSENSORS
Comparing with the large variety of labeled methods,
few label-free methods, such as optical [38,39] acoustic
[40,41] and electrochemical analytical methods [42,43,
44,45,46,47] could be applied to detect DNA hybridiza-
tion. Label-free detection could remove experimental
uncertainty induced by the effect of the label on mo-
lecular conformation, blocking of active binding epi-
topes, steric hindrance, inaccessibility of the labeling site,
or the inability to find an appropriate label that functions
equivalently for all molecules in an experiment, and
greatly simplify the time and effort required for assay
development, while removing experimental artifacts
from quenching, shelf life and background fluorescence
[48]. Optical DNA biosensors are easy to develop and
commercialize for the detection of DNA hybridization,
so fiber-optic will play an important role in label-free
detection of DNA hybridization or single base mismatch.
Here several fiber-optic DNA biosensors based surface
plasmon resonance (SPR) [2,49,50,51], ellipsometry,
evanescent wave are depicted below.
4.1. Surface Plasmon Resonance (SPR)
Fiber-Optic DNA Biosensors
SPR is an optical reflectance procedure which is sensi-
tive to changes in the optical properties of the medium
close to a metal surface [52] and was employed for gene
mutation [53], DNA hybridization [54,55] and virus [56].
In SPR fiber-optic DNA biosensors, ssDNA was immo-
bilized onto the surface of ultrathin metal (Au or Ag)
film of a lower refractive index deposited on the side of
fiber-optic. When light penetrates through fiber-optic
and on the metal surface satisfying the condition of sur-
face plasmon resonance, the refractive index will be al-
tered between metal film and solution interface to result
in the change of resonant angle after DNA hybridization.
The angle at which minimum reflection occurs is moni-
tored and converted to the refractive index units for
DNA quantification depending on notably refractive
index, wavelength of incident light and properties of
metal film [57].
Lin et al. [58] had investigated a multimode fiber sen-
sor based on surface plasmon resonance with a halogen
light source for detection of DNA hybridization. The
side of fiber was polished and coated with 37nm gold

Y. M. Wang et al. / J. Biomedical Science and Engineering 2 (2009) 312-317 315
SciRes Copyright © 2009 JBiSE
Advantages of ellipsometry are present as follow:
thin film to immobilize the probe DNA that hybrid with
complementary DNA. The characteristics of SPR DNA
biosensor, including the stability, repeatability and reso-
lution calibration were examined as well. The resolution
was 3×10−6 refractive index units and the SPR dip shift
in wavelength which was hybridized at 0.1 μM of the
target DNA to the probe DNA, was 8.66 nm.
4.2. Ellipsometry-Based Fiber-Optic DNA
Biosensors
Ellipsometry is a versatile, sensitive and powerful
optical technique for determining the properties of a
material from the characteristics of light reflected from
its sensing surface, which is non-d estructive and con-
tactless. Once the sample’s properties, for example
thickness, complex refractive index of thin films at in-
terfaces were changed, the ellipsometry parameter was
determined to calculate the surface concentration, and
solution concentration. Wang [59] had elucidated the
principle of waveguide ellipsometry sensors including
light propagation in waveguide and ellipsometry pa-
rameter analysis, its arrangement and instrumentation,
and preliminary experimental results are given as well.
Ellipsometry-based sensors had been proposed for bio-
sensor applications for monitoring protein-protein inter-
actions [60,61].
1) The measurement is independent of light intensity
and the waveguide coupler quality [60].
2) Optic fibers are feasible to fabricate the waveguide
ellipsometry sensors because of their properties of
low-cost, low loss, high performance, multicapability
and security for application commercially.
3) Ellipsometry is less affected by intensity instabili-
ties of the light source or atmospheric absorption.
4) High sensitivity and accuracy because of simulta-
neous determination of two parameters-relative phases
and amplitudes.
Emma Hitt [62] thought imaging ellipsometry is
suited for the detection of DNA hybridization to measure
the change in the state of polarization of the light re-
flected, according to the EP3 ellipsometer. However, few
information were occurred to directly study the DNA
hybridization on the surface of fiber-optic by ellipsome-
try which was used to characterize the thickness of thin
film or DNA interaction with surfactant [63,64,65].
4.3. Evanescent Wave-Based Fiber-Optic
DNA Biosensors
Light transmits through fiber with different refractive in-
dex (n2<n1) at an angle beyond the critical angle for Total
Internal Reflection (TIR), it will produce a limited attenu-
ated electric filed transversely transporting though the side
of fiber to form an evanescent waves (EW) that the inten-
sity of evanescent waves decreases exponentially with
short distance from the interface (see formula).
2
22
1
1
2sin
p
n
n
dn





λ-Incident wavelength, dp-Thickness of sensitivity, β-
Critical angle of total internal reflection, n1-Refractive
index of core, n2 -Refractive index of coating.
The evanescent energy has an effect on DNA mole-
cules in its sensitive distance. When the EW transmits
through the sensitive element attached to the side of fi-
ber-optic, the frequency, phase or intensity of light in
fiber-optic will be altered with the quantity or the con-
figuration of DNA molecules (Figure 4).
David Hradetzky et al. [66] had presented an evanes-
cent wave sensing system based on the interferometric
approach using Young's double slit configuration for
detecting biomolecular interactions without labels. With
refractometric measurements, a mean resolution of the
effective refractive index was 0.9×10-6 and a reproduci-
bility was below 0.1×10-6. The hybridization of 21-mer
DNA was detected using this highly sensitive biosensor.
Rindorf et al. [67] have first presented incorporation of a
microstructured optical fiber (MOF) into biochip. The
MOF is functionalized towards the capture of a specific
ssDNA by immobilizing a sensing layer on the internal
surfaces of the fiber. Optical detection of the captured
DNA was carried out using the evanescent-wave-sensing
principle.
5. TRENDS
Fiber-optic-based DNA biosensors have been studied in
all country providing much information about biological
properties of DNA molecular recognition for medical
diagnosis. The sensitivity, stability and response time are
not optimal to the application and commercialization. It
is necessary to develop the high-performance or new
fiber-optic DNA biosensors. An efficient method will be
applied to improve the sensitivity, stability and selectiv-
ity of fiber-optic DNA biosensors coupled with sin-
gle-photon counter or optical computer. Combining with
the nanoelectromechanical systems and nanotechnology,
the portable, miniature and intelligent fiber-optic DNA
nanobiosensors are exploited for in vivo measurement or
in single cell monitoring to realize the single molecule
Figure 4. Schemes of evanescent field-based fiber-optic
DNA biosensors without labeling.

316 Y. M. Wang et al. / J. Biomedical Science and Engineering 2 (2009) 312-317
SciRes Copyright © 2009 JBiSE
detection. The kinetic studies demonstrated this surface
modification to be superior to other methods of immobi-
lization [68], so surface modification will be improved
with advanced surface chemistry technique and new
assembly technique to increase the stability, homogene-
ity, lifetime and frequency of fiber-optic DNA biosen-
sors.
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