Sensors and Actuators B 207 (2015) 97–104 Contents lists available at ScienceDirect Sensors and Actuators B: Chemical jo ur nal home page: www.elsevier.com/locate/snb Biomicrosystem design and fabrication for the human papilloma virus 16 detection Luisa F. Urrego, Diana I. Lopez, Katily A. Ramirez, Carolina Ramirez, Johann F. Osma ∗ Universidad de los Andes, Colombia a r t i c l e i n f o Article history: Received 3 July 2014 Received in revised form 5 October 2014 Accepted 8 October 2014 Available online 23 October 2014 Keywords: Biomicrosystem Biosensor HPV 16 a b s t r a c t In this paper, a biomicrosystem consisting of 98 biosensors based on the monoclonal antibody (mAb) 5051 immobilization for the detection of the human papilloma virus (HPV) 16 was designed and fabricated. The mAb 5051 immobilization was performed on a self-assembled monolayer of 4-aminothiophenol, on a polymethylmethacrylate substrate with a gold nanolayer. The biomicrosystem carries out 98 in situ different simultaneous tests without specialized equipment or personnel. The biomicrosystem charac- terization was performed by electrochemical impedance spectroscopy, cyclic voltammetry, impedance measurements, AFM and SEM. The biomicrosystem performance was verified by using positive and neg- ative HPV 16 real samples from women, after 1 h incubation process using 40 biosensors from 4 different biomicrosystems. The HPV 16 samples were verified by a standard PCR test. An analytic hierarchy process was performed based on costs, effectiveness, time and operative characteristics between the biomicrosys- tem and traditional techniques for the HPV detection, such as PCR-RT and Hybrid Capture 2; concluding that the biomicrosystem is a dominant alternative with the 38.8% in the global score compared to the 34.5% of PCR-RT and the 26.7% of HC2. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Biosensors are devices used for detection and biological recog- nition based on the immobilization of biomolecules on surfaces of transduction, creating a functional sensor. The immobilization of biomolecules is fundamental for the functionality and integrity of the biosensor, because the biomolecule orientation facilitates the union with the objective analyte. A steric impediment or the denat- uralization of the bio-receptor is a problem for the reproducibility and the sensibility of the biosensor [1]. Immune-sensors are biosen- sors of affinity based on antibodies as elements of bio-recognition, due to the specificity of antibodies to link a certain protein, another antibody, or even an entire virus with a high affinity [1–3]. Nowadays, the implementation of SAMs (self-assembled mono- layers) technology, offers one of the simplest ways to provide Abbreviations: 4-ATP, 4-aminothiophenol; AC, alternate current; AFM, atomic force microscope; CV, cyclic voltammetry; DC, direct current; EIS, electrochemi- cal impedance spectroscopy; HC2, Hybrid Capture 2; HPV, human papilloma virus; mAb5051, monoclonal antibody 5051; PAJ, analytic hierarchy process; PBS, phos- phate buffered saline; PCR, polymerase chain reaction; PCR-RT, chain reaction polymerase in real-time; PMMA, polymethylmethacrylate; SAMs, self-assembled monolayers. ∗ Corresponding author. Tel.: +57 13394949. E-mail address: jf.osma43@uniandes.edu.co (J.F. Osma). a suitable cap of orientated immobilization of antibodies [2,4,5]. SAMs are formed in a spontaneous way from the adsorption of a substance with specific affinity to a substrate, generating organized molecular structures [6,7]. One of the more studied self-organized systems in the last years, consists of alkanethiols monolayers (CH3CHn-SH) on gold thin layers [8,9]. Alkanethiols have a high affinity to golden surface, which properties of conductivity, reflec- tivity and affinity to react in a spontaneous way, allow to control the quantity and the orientation of the immobilized antibodies; where the site of recognition is available for a major accessibility of the antigens, allowing the kinetic interaction and recognition of the objective analyte to be less variable [6,10]. The use of microsystems has had an increased interest in the detection of analytes; and new technologies of micromanufac- turing have been introduced for mass production [11]. The main advantages of microsystems are: short time of response, field detec- tion capacity, portability and low cost analysis, due to the minimal quantity of reagents needed given its size [12]. Moreover, human papilloma virus (HPV) is a DNA virus of double chain and the viral pathogen most commonly sexually transmitted. It infects epithelial cells and is associated with cervical lesions, can- dylomas and cervical cancer [13]. There are more than 100 types of HPV. Some of these are low risk types that are associate with the production of genital warts: HPV 6 and HPV 11, and the high risk HPV’s, which are associated with the development of cervical http://dx.doi.org/10.1016/j.snb.2014.10.036 0925-4005/© 2014 Elsevier B.V. All rights reserved.