Open Access
Fiber-based label-free D-dimer detection for early diagnosis of venous thromboembolism
(SPIE, 2020) Zubiate Orzanco, Pablo; Urrutia Azcona, Aitor; Ruiz Zamarreño, Carlos; Fernández Irigoyen, Joaquín; Giannetti, Ambra; Baldini, Francesco; Díaz Lucas, Silvia; Matías Maestro, Ignacio; Arregui San Martín, Francisco Javier; Santamaría Martínez, Enrique; Del Villar, Ignacio; Chiavaioli, Francesco; Ingeniaritza Elektrikoa, Elektronikoaren eta Telekomunikazio Ingeniaritzaren; Institute of Smart Cities - ISC; Ingeniería Eléctrica, Electrónica y de Comunicación
D-dimer is a useful diagnostic biomarker for deep vein thrombosis or pulmonary embolism, collectively referred to as venous thromboembolism (VTE). The ability to detect in real-time the amount of D-dimer with a fast and reliable method is a key step to anticipate the appearance of these diseases. The combination of fiber-optic-based platforms for biosensing with the nanotechnologies is opening up the chance for the development of in situ, portable, lightweight, versatile, reliable and high-performance optical sensing devices towards lab-on-fiber technology. The generation of lossy mode resonances (LMRs) by means of the deposition of nm-thick absorbing metal-oxide films on special geometric-modified fibers allows measuring precisely and accurately surface refractive index changes, which are due to the binding interaction between a biological recognition element and the analyte under investigation. This approach enhances the light-matter interaction in a strong way, thus turning out to be more sensitive compared to other optical technology platforms, such as fiber gratings or surface plasmon resonance. Here, the results of a highly specific and sensitive biosensor for the detection of D-dimer based on LMR in fiber-optics are presented by monitoring in real-time the shift of the LMR related to the biomolecule interactions thanks to a conventional wavelength-interrogation system and an ad-hoc developed microfluidics. A detection limit of 100 ng/mL, a value 5-fold below the clinical cutoff value, has been attained for D-dimer spiked in human serum. The comparison of the results achieved with proteomics-based methodologies, which allows for the identification of betaand gamma-chains of fibrinogen, demonstrates the ability of our platform to specifically (>90%) recognize D-dimer.
Open Access
Fiber-based early diagnosis of venous thromboembolic disease by label-free D-dimer detection
(Elsevier, 2019) Zubiate Orzanco, Pablo; Urrutia Azcona, Aitor; Ruiz Zamarreño, Carlos; Egea Urra, Josune; Fernández Irigoyen, Joaquín; Giannetti, Ambra; Baldini, Francesco; Díaz Lucas, Silvia; Matías Maestro, Ignacio; Arregui San Martín, Francisco Javier; Santamaría Martínez, Enrique; Chiavaioli, Francesco; Del Villar, Ignacio; Ingeniaritza Elektrikoa, Elektronikoaren eta Telekomunikazio Ingeniaritzaren; Institute of Smart Cities - ISC; Ingeniería Eléctrica, Electrónica y de Comunicación; Gobierno de Navarra / Nafarroako Gobernua
D-dimer is a useful diagnostic biomarker for deep vein thrombosis or pulmonary embolism, collectively referred to as venous thromboembolism (VTE). The ability to detect in real-time the amount of D-dimer with a fast and reliable method is a key step to anticipate the appearance of these diseases. Here, the results of a highly specific and sensitive biosensor for the detection of D-dimer based on lossy mode resonance in fiber optics are presented. The unique features of specialty fibers in light management integrated with microfluidics allow detecting D-dimer in human serum with a detection limit of 100 ng/mL, a value 5-fold below the clinical cutoff value. Comparison of the results achieved with mass-spectrometry-based proteomics, which allows for the identification of beta- and gamma-chains of fibrinogen, demonstrates the ability of our platform to specifically (>90%) recognize D-dimer. Therefore, this technology potentially represents a paradigm shift in the development of a simple, high-specificity and label-free biosensing platform, which can be applied to speed up diagnostic healthcare processes of venous thromboembolism toward an early diagnostic and personalized treatment system.
Open Access
Fiber-optic lossy mode resonance sensors
(Elsevier, 2014) Arregui San Martín, Francisco Javier; Del Villar, Ignacio; Corres Sanz, Jesús María; Goicoechea Fernández, Javier; Ruiz Zamarreño, Carlos; Elosúa Aguado, César; Hernáez Sáenz de Zaitigui, Miguel; Rivero Fuente, Pedro J.; Socorro Leránoz, Abián Bentor; Urrutia Azcona, Aitor; Sánchez Zábal, Pedro; Zubiate Orzanco, Pablo; López Torres, Diego; Acha Morrás, Nerea de; Matías Maestro, Ignacio; Ingeniería Eléctrica y Electrónica; Ingeniaritza Elektrikoa eta Elektronikoa; Gobierno de Navarra / Nafarroako Gobernua
In the last 4 years, experimental evidences about the potential use of optical sensors based on Lossy Mode Resonances (LMR) have been presented in the literature. These LMR sensors have some similarities with Surface Plasmon Resonance (SPR) sensors, the gold standard in label-free, real-time biomolecular interaction analysis. In these new LMR sensors, if the non-metallic nanocladding of an optical waveguide fulfills the conditions explained in this work, coupling of light to the cladding modes happens at certain resonance wavelengths, which enables the use of LMR devices as refractometers and opens the door to diverse applications such as in biology and proteomics research. These highly sensitive refractometers have already shown sensitivities higher than 20,000 nm/RIU or 5x10-7 RIU and, given the youth of this field, it is expected to achieve even better values.
Open Access
Optical fiber sensors based on gold nanorods embedded in polymeric thin films
(Elsevier, 2018) Urrutia Azcona, Aitor; Goicoechea Fernández, Javier; Rivero Fuente, Pedro J.; Pildain Lería, Ander; Arregui San Martín, Francisco Javier; Ingeniería Eléctrica, Electrónica y de Comunicación; Ingeniaritza Elektrikoa, Elektronikoa eta Telekomunikazio Ingeniaritza; Institute of Smart Cities - ISC; Ingeniería; Ingeniaritza; Institute for Advanced Materials and Mathematics - INAMAT2
In this work, we present a study about the generation and analysis of optical resonances caused by gold nanorods (GNRs) embedded in films. GNRs were embedded in polymeric thin films using the Layerby-Layer nanoassembly (LbL) deposition technique. Polymer/GNRs thin films of different thicknesses were deposited on the surface of cladding removed optical fibers for sensing. The spectral responses of the optical fiber sensors were monitored during the build-up of the thin films. The generation of two Localized Surface Plasmon Resonances (LSPRs) associated to the GNRs was observed in thinner coatings. These devices with around 12 polymer/GNRs bilayers were characterized as refractometers, providing an intensity-based sensitivity up to 75.69 dB/RIU. For thicker polymer/GNRs overlays, both LSPRs bands were also generated and, additionally, it was observed a new Lossy Mode Resonance (LMR) band due to modes coupled to the sensitive coating. The dependence of these three resonance bands with the surrounding refractive index was studied. Finally, these sensors were tested in a climatic chamber in the 20-90% relative humidity (RH) range and the LMR showed a good sensitivity to RH changes while the LSPR bands remained very stable in comparison. Results showed an excellent sensitivity of 11.2 nm/%RH for the LMR, confirming the potential of this type of optical fiber sensor based on the combination of LSPRs and LMRs bands.
Open Access
Polymer-functionalized fiber-optic optrode towards the monitoring of breathing parameters
(Institute of Electrical and Electronics Engineers Inc., 2023) Álvarez-Jiménez, A.; Acha Morrás, Nerea de; Aginaga Etxamendi, Concepción Isabel; Urrutia Azcona, Aitor; Socorro Leránoz, Abián Bentor; Matías Maestro, Ignacio; Ingeniería Eléctrica, Electrónica y de Comunicación; Ingeniaritza Elektrikoa, Elektronikoa eta Telekomunikazio Ingeniaritza; Institute of Smart Cities - ISC
An innovative application of lossy mode resonances (LMRs) is presented in this work, pursuing the detection of biomedical variables. In this case, the detection of pH and breathing signal events is shown by means of a reflective fiber-optic optrode consisting of a poly(allylamine chloride) / poly (acrylic acid) polymer matrix deposited on the tip of a 200-micron-core bare multimode optical fiber. The proposed sensor is capable of detecting pH values between 6.5 and 8.0 (saliva pH range) with quite stability and repeatability. Moreover, when monitoring the breathing signal, the proposed sensor presents quite good real time detection of the different events occurring during the inspiration-expiration cycle, different breathing rates and detecting apneas.