title: Sensitive electrical detection of human prion proteins using field effect transistor biosensor with dual-ligand binding amplification.
abstract: Simple and accurate detection of prion proteins in biological samples is of utmost importance in recent years. In this study, we developed a label-free electrical detection-based field effect transistor (FET) biosensor using thiamine as a probe molecule for a non-invasive and specific test of human prion protein detection. We found that thiamine-immobilized FETs can be used to observe the prion protein oligomer, and might be a significant test for the early diagnosis of prion-related diseases. The thiamine-immobilized FET was also demonstrated for the detection of prion proteins in blood serum without any complex pre-treatments. Furthermore, we designed a dual-ligand binding approach by the addition of metal ions as a second ligand to bind with the adsorbed prion protein on the thiamine-immobilized surface. When the prion attached to metal ions, the additional positive charge was induced on the gate surface of the FET. This approach was capable of amplifying the magnitude of the FET response and of enhancing the sensitivity of the FET biosensor. Detection of prion proteins has achieved the required concentration for clinical diagnosis in blood serum, which is less than 2 nM. In summary, this FET biosensor was successfully applied to prion detection and proved useful as a simple, fast, sensitive and low-cost method towards a mass-scale and routine blood screening-based test.
authors.affiliation: Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan.
authors.forename: Shofarul
authors.initials: S
authors.lastname: Wustoni
authors.affiliation: Institute for Nanoscience & Nanotechnology, Waseda University, 513 Waseda-tsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Hideshima
authors.affiliation: Institute for Nanoscience & Nanotechnology, Waseda University, 513 Waseda-tsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kuroiwa
authors.affiliation: Institute for Nanoscience & Nanotechnology, Waseda University, 513 Waseda-tsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Nakanishi
authors.affiliation: Institute for Nanoscience & Nanotechnology, Waseda University, 513 Waseda-tsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Institute for Nanoscience & Nanotechnology, Waseda University, 513 Waseda-tsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan.
authors.forename: Yasuro
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan; Institute for Nanoscience & Nanotechnology, Waseda University, 513 Waseda-tsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan. Electronic address: osakatets@waseda.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Osaka
mesh_terms: D015374:Biosensing Techniques / Q000295:instrumentation*; D003217:Conductometry / Q000295:instrumentation*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D008024:Ligands; D015336:Molecular Probe Techniques / Q000295:instrumentation*; D011328:Prions / Q000032:analysis* / Q000737:chemistry; D011485:Protein Binding; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013831:Thiamine / Q000737:chemistry*; D014173:Transistors, Electronic
chemical_list: D008024:Ligands; D011328:Prions; D013831:Thiamine
keywords: Blood serum; Early diagnosis; Field effect transistor; Metal ion; Prion protein; Thiamine