1077-260X (c) 2016 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See http://www.ieee.org/publications_standards/publications/rights/index.html for more information. This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI 10.1109/JSTQE.2016.2633819, IEEE Journal of Selected Topics in Quantum Electronics > REPLACE THIS LINE WITH YOUR PAPER IDENTIFICATION NUMBER (DOUBLE-CLICK HERE TO EDIT) < 1 Abstract— A novel and high sensitive IgG – anti-IgG biosensor based on multimode interference (MMI) induced through a single-mode – multimode – single-mode (SMS) optical fiber structure is developed in this contribution. First, an improvement of the performance of a basic 125-micron-diameter SMS structure is carried out by etching the optical waveguide cladding to a diameter of 15 micrometers. This leads to sensitivity values 8 times higher than the original SMS structure. Then, 3- glycidopropyl-trimethoxysilane (GPTMS) is used to attach the IgGs to the optical substrate. Finally, a phosphate buffer saline solution (PBS) containing an increasing concentration of anti-goat IgGs is used to detect biological interactions up to 104 g/ml. High resolution mass-spectrometry was used to corroborate the attachment of the biomolecules to the optic fiber. The analyzed bioprobe presents no cross-sensitivity to other biomolecules immersed in the same detection solution. Index Terms— fiber-optic biosensors, immunosensors; multimode interferometry; optical fiber. I. INTRODUCTION OWADAYS the development of biosensors is worldwide extended. In fact, the number of contributions addressing this topic is increasing due to the interest in applying this technology to the biomedical engineering field [1,2]. This supposes a real challenge because there is a need for generating new biosensors in order to provide an efficient early diagnose to the patients. As it is well-known, the variation range of the biological magnitudes is quite small and sometimes critical. This means that small variations in a biological magnitude can trigger important consequences for the health of the patient. That is why the designed devices must be capable of distinguishing Manuscript received May 27, 2016; This work has been supported by the Spanish Ministry of Economy and Competitiveness (TEC2013-43679-R, TEC2016-78047-R, SAF2014-59340-R) a postdoctoral fellowship by the Public University of Navarre (UPNA), and by the Government of Navarre through its projects with references: 72/2015, 2016/PI008, 2016/PC025 and 2016/PC026. The authors are with the Institute of Smart Cities, with the Electrical and Electronic Engineering Department, Public University of Navarre, 31006 Pamplona, Navarre, Spain and with the Navarre Institute for Health Research (IdiSNA), Pamplona, Navarre 31008, Spain. The Proteomics Unit of Navarrabiomed is a member of Proteored, PRB2-ISCIII., and is supported by grant PT13/0001, of the PE I+D+I 2013-2016 funded by ISCIII and FEDER. (e-mail: ab.socorro@unavarra.es; esantamma@navarra.es; jfernani@navarra.es; ignacio.delvillar@unavarra.es; jmcorres@unavarra.es; parregui@unavarra.es; natxo@unavarra.es). minimum changes in these magnitudes. A good example of common reactions currently used to detect biological compounds is the formation of antibody – antigen complexes [3], the main focus of this contribution. In this sense, type G antibodies or immunoglobulins (IgGs) are biological macromolecules, which protect the living beings against bacterial and viral infections. Two different parts can be distinguished and utilized when fabricating a biosensor based on IgGs. The first one (known as Fc) is similar in all of them and gives a structuration to the biomolecule. Normally this part is used to attach the IgGs when designing a biosensor. The second part (known as Fab) is specifically designed for each analyte (i.e. antigens or secondary antibodies). Thus, Fab gives the biomolecule the functionality to detect the antigen. Consequently, IgGs should be deposited so that most of their functional parts are available, since this will increase the sensing efficiency of the biosensor [4]. Due to the increasing interest of developing high quality biosensors, a much research is being devoted to detect biological variables. To this purpose, electronic [5], piezoelectric [6], electrochemical [7] or optical [8] approaches have been developed lately. Regarding this last group, there are also different ways to design biological detectors. First, it is important to consider the substrate, which permits to classify sensors in different groups: grating waveguides [9], semiconductor substrates [10] or photonic crystal fibers [11]. Second, the detection method can be intensity or wavelength- based, being the latter the most popular technique because of its versatility and robustness [12,13]. In particular, the working principle of wavelength detection-based sensors is to track the shift of a resonance in the transmission spectrum of the device. This shift is produced due to changes in the optical properties between the surrounding medium and the optical waveguide. Thus, it is important to focus on improving the resolution capability and sensitivity, so that a minimum change in the biological variable can be detected accurately [14]. One of the simplest ways to generate a resonance in the monitored spectrum is by using an optical fiber-based structure. It is well-known that optical fibers present interesting properties such as reduced dimensions, low transmission losses in the optical communications windows and broad bandwidth. They can also be used for the fabrication of devices sensitive to common physical magnitudes such as refractive index, stress or bending [15,16]. Moreover, if Fiber-optic immunosensor based on an etched SMS structure A.B. Socorro, E. Santamaría, J. Fernández-Irigoyen, I. Del Villar, J.M. Corres, F.J. Arregui, Member, IEEE, I.R Matias, Sr. Member, IEEE N