# Application of Single-Electron Transistor to Biomolecule and Ion Sensors
## 1 Introduction  
The detection and quantification of chemical and biological species are crucial to many areas of healthcare and life sciences, ranging from the diagnosis of disease to the discovery of new drug molecules. The need exists also in the security and environmental fields. Various types of devices are now in production and being developed to meet this need. For the devices, radioactive or fluorescent markers are used in many cases. Since the methods using such markers involve time-consuming and multi-stage processes that are expensive and unsuitable for real-time detections, devices without such markers are desired for detection and quantification. Field effect transistors (FETs) are sophisticated devices used for label-free and real-time detections of ions and charged molecules. Ion-sensitive FETs (ISFETs) were first reported by [PERSON] [1]. Electrical characteristics of ISFETs change in response to the concentration and type of ion present in the aqueous solution on the gate insulator surface. Following the report, ion sensors and biosensors based on Si metal-oxide-semiconductor FETs (MOSFETs) were developed for the detection of various chemical species and biomolecules. Detections based on an FET measure the charge change accompanied by the specific molecular recognition events on the gate or the gate insulator surface. [PERSON] _et al._ fabricated biosensors based on a Si MOSFET for the detection of adenosine-5\({}^{\prime}\)-triphosphate (ATP) [2]. [PERSON] _et al._ detected ribosomal protein using a Si MOSFET [3]. [PERSON] _et al._[4] and [PERSON] _et al._[5] detected target deoxyribonucleic acid (DNA) using Si MOSFETs with the probe DNA immobilized on the gate surface and the channel surface, respectively. FETs used for ion sensors and/or biosensors are not limited to Si MOSFETs. Graphene FETs were also used for detecting DNA [6], bacteria [6], protein and ions [7]. Organic FETs were also used for label-free DNA detection [8]. Compared with these non-Si FET sensors, sensors with a Si MOSFET have the merit of being able to be highly integrated on a single chip for the simultaneous detection and quantification of various ions and biomolecules by utilizing mature large scale integration (LSI) techniques. Nanowire FETs for the sensors are substantially more sensitive than the conventional FETs having a wide channel; this is because carriers in a narrow channel are more effectively affected by the charge on the gate insulator than those in a wide channel. Highly sensitive detections of target ions or biomolecules were reported using nanowire channels in FET sensors [9; 10; 11; 12; 13; 14; 15; 16; 17; 18; 19]. There are two types of nanowire fabrication methods. One is the bottom up method utilizing the self-assembled mechanism of atoms and molecules. The other is the top down method using electron beam (EB) lithography. For Si nanowires fabricated using the bottom up method, the following reports exist. [PERSON] _et al._ detected streptavidin using biotin-modified Si nanowire FETs [9]. Here, streptavidin and biotin are kinds of protein, and the ligand-receptor binding of biotin-streptavidin is well known. The Si nanowire was fabricated using the chemical vapor deposition with gold nanoclusters as catalysts. Using Si nanowire FETs fabricated with this method, electrical detections were also achieved for a single virus of influenza A [10], interactions between ATP and a protein [11], and prostate-specific antigen (PSA) [12]. Here, PSA is a widely used protein biomarker for prostate cancer. For Si nanowires fabricated using the top down methods, on the other hand, the following reports exist. [PERSON] _et al._ demonstrated immunodetections of mouse-immunoglobulin G and mouse-immunoglobulin A [13]. [PERSON] _et al._ detected target DNA in solution with the probe DNA (12-mer oligonucleotide) attached on the nanowire surface [14]. [PERSON] _et al._ detected PSA with the antibody of PSA (anti-PSA) immobilized on the nanowire surface [15]. [PERSON] _et al._[16] and [PERSON] _et al._[17] fabricated pH sensors.