Photonic crystal fiber with cascaded fiber Bragg gratings for plasmonic refractometry and biosensing

Over the last decade, optical fibers have been increasingly considered for point-of-care
medical diagnostics by ways of so-called lab-on-fiber probes. Biodetection at the pico-
and even femto-mole level has become possible through cladding mode resonance
sensing combining tilted fiber Bragg grating (FBG) technology with surface plasmon
resonance (SPR). FBG-based sensors feature a tremendous advantage in terms of
enabling wavelength-multiplexing several of such sensors in a single optical fiber.
However, multiplexing of two or more cladding mode-based biosensors within a single
optical fiber and reading out all the sensors simultaneously has been a long-standing
challenge when using regular step-index fibers, given the extended spectrum covered
by the resonances of a single tilted FBG. Multiplexing such biosensors would enable
enhancing the reliability of the biodetection, given that the sensors could be made to
target each a different biomarker, or alternatively the same biomarker, in view of
excluding either positive or false negative outcomes.
We address the biosensor multiplexing challenge by means of microstructured optical
fibers (MOFs), and in particular, photonic crystal fibers (PCFs). The ability to adapt
the microstructure of the PCF indeed introduces an additional degree of freedom
into the design of fiber-based biosensors and provides access to extended spectral
multiplexing capabilities, combined with the cladding mode-based SPR-enhanced
sensing approach, which would be unattainable with regular step-index fibers.
The specific objectives of this PhD thesis are therefore as follows:
1) Designing and fabricating a PCF that yields FBG-coupled cladding mode
resonances with three specifications: effective matching with the refractive
index of typical biosensing buffers; spectral span covering a few tens of
nanometers only; non-zero sensitivity to refractive index changes in the
surrounding medium.
2) Demonstrating the ability of cascaded wavelength-multiplexed sensors to
detect picometer changes resulting from incremental refractive index changes
in aqueous solutions.
3) Demonstrating the proof-of-concept for cascaded wavelength-multiplexed
biosensors in an actual biodetection experiment.
A key accomplishment of this PhD thesis is the development of an approach to control
the effective refractive index span of cladding modes guided in hexagonal lattice PCFs,
achieved through adapting the parameters that define the microstructure such as the
lattice pitch and the air-filling factor. This enables designing a PCF with a cladding
mode spectral range as narrow as 20 nm, which is a substantial improvement over
the typical spans of 100 nm encountered in regular step-index fibers.
Furthermore, the modal effective index values fit the range of 1.32-1.34 which is
commonly required for biosensing applications. We demonstrate successful
implementation of three cascaded FBGs in a single PCF with wavelength-multiplexed
cladding mode resonances that fit into the operational spectral bandwidth of state-of-
the-art spectral interrogation systems. Our study unveils the trade-off between spectral
span and transmission amplitudes of the cladding mode resonances, as influenced by
the PCF’s air-filling factor, which in its turn leads to new insights that are crucial for
PCF-based refractometry.
The second achievement involves demonstrating cladding mode resonances from two
cascaded FBGs in a single PCF for refractometry of aqueous solutions. This plasmonic
PCF-based double-FBG sensor features the largest experimentally determined
values in terms of wavelength sensitivity (up to 60 nm/RIU), amplitude sensitivity
(up to 800 dB/RIU), and figure-of-merit (up to 160 RIU -1
) amongst all other
reported MOF-based refractometers. The fundamental core resonance offers
inherent temperature referencing, whilst the extrinsic sensing approach facilitates the
fabrication, calibration, and re-use of the sensor, thus greatly enhancing the practicality
of such PCF-based sensor.
The third major contribution of this PhD thesis is the proof-of-concept demonstration
of cascaded cladding mode biosensors for the detection of a breast cancer
biomarker, specifically HER2-protein, in a single spectral readout, with a
reproducible minimum detectable concentration of 1 μg/mL, or 8.6 nM, from
both biosensors. This indicates the potential of PCF-based cladding mode resonance
sensing in biomedical applications, particularly in view of reference-compensated
single-analyte detection or multiple-analyte detection scenarios.
We hope that our research results will encourage the fiber optic sensor and biosensing
communities to re-evaluate the use of cladding modes in MOFs for refractometric and
especially biomedical applications, and to leverage on that for bringing fiber-optic
biosensors to the next technology readiness level.