Single Embryo-Coupled Gate Field Effect Transistor for Elective Single Embryo Transfer Toshiya Sakata,* ,† Akiko Saito, † Jinji Mizuno, ‡ Haruyo Sugimoto, † Kaori Noguchi, § Eiko Kikuchi, § and Hiroaki Inui § † Department of Materials Engineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan ‡ Kato Ladies Clinic, 7-20-3 Nishi-Shinzyuku, Shinzyuk-ku, Tokyo 160-0023, Japan § Inui Maternity Clinic, 3-5-18 Namiki, Koriyama, Fukushima 963-8026, Japan ABSTRACT: In this study, we have proposed and demonstrated experimentally a novel monitoring device of single mouse embryo activity after in vitro fertilization (IVF) using a semiconductor-based field effect transistor (FET). The FET biosensor realized to detect it noninvasively, quantitatively, and continuously by change of hydrogen ions with positive charges, which were induced by dissolved carbon dioxide due to cellular respiration activity during cleavage. The electrical signal of FET biosensor should become an effective indication to evaluate objectively single embryo activity as its morphology is observed subjectively after IVF. The platform based on the FET biosensor will contribute to promote elective single embryo transfer (eSET) in human assisted reproductive technology (ART). R ecently, assisted reproductive technology (ART) has been expected to be one of therapeutic methods of sterility. Engineers other than obstetricians have been required for assured success of ART programs. For in vitro fertilization (IVF) of one of ART programs, how to evaluate embryo quality and select an embryo in good condition are significant. Morphological evaluation has been widely used to rank embryo quality because microscopic analysis is noninvasive and useful in predicting pregnancy rates. 1,2 However, the standard of classification for embryo quality seems to be ambiguous among operators because it is a subjective method. Moreover, elective single embryo transfer (eSET) will be recommended in the future in order to prevent a multiple pregnancy. 3 Therefore, a novel principle to evaluate the quality of a single embryo quantitatively and noninvasively in a real-time manner is required for practical use in ART. In our previous work, the respiration activity of a fertilized ova of a sea urchin was monitored noninvasively, quantitatively, and continuously as the change of pH by the use of the principle of a semiconductor-based ion sensitive field effect transistor (IS-FET). 4 The detection principle of IS-FET is based on the potentiometric detection of charge density changes at the gate insulator 5 and is applied for various biosensing. 6-9 Since the gate insulator usually consists of Si 3 N 4 or Ta 2 O 5 with hydroxyl group at the surface in solutions, furthermore, the IS-FET is sensitive to the concentration of hydrogen ion with positive charge and should be utilized as the pH sensor. Therefore, pH variation based on respiration activity of the embryo will be monitored quantitatively and noninvasively in a real-time manner using a single embryo- coupled gate FET for eSET (eSET-FET), because pH at the interface between the embryo and gate membrane of FET will change sensitively according to dissolution of carbon dioxide into medium generated by metabolism and respiration activity in an embryo. Thus, the platform based on the eSET-FET sensor will be valuable for the development of an evaluation system to select a single embryo with good quality for eSET in the future. On the other hand, oxygen consumption has been considered to be the parameter that provides the best indication of overall metabolic activity of a single embryo, 10-14 although embryo metabolism has previously been assessed by measurement of nutrient consumption, such as glucose, pyruvate, and amino acids. 15-18 As one of the detection methods for the evaluation of embryo quality, the electro- chemical system is being developed. Shiku et al. reported previously the detection concept of oxygen consumption based on the respiration activity of an embryo. 19 In this method, the oxygen reduction current was detected near the surface of a single embryo using the cyclic voltammetry technique. However, this method is unsuitable for real-time measurement for a long-term such as cleavage of mammalian embryo. In this paper, we propose a semiconductor-based embryo sensing device for eSET (eSET-FET) to monitor single mouse embryo activity based on cellular respiration in a real-time, Received: January 11, 2013 Accepted: June 19, 2013 Published: June 19, 2013 Article pubs.acs.org/ac © 2013 American Chemical Society 6633 dx.doi.org/10.1021/ac4001018 | Anal. Chem. 2013, 85, 6633-6638