Toward Industrialization on Semiconductor-Based Biosensors in Health and Medical Fields

Abstract

Development of diagnostic technology in preventive medicine plays an important role for health maintenance in coming aged society as well as creation of an emerging industry. Industrialization of biosensing devices for health check will contribute to the improvement of quality of life. As one of promising devices for biosensing, in the recent decade, we have succeeded in the development of the SiO2-gate field effect transistor (FET) with a high degree of chemical durability by covering its surface with a self-assembled monolayer (SAM) [1], and have successfully achieved the transfer of fabrication technology of the FET biosensors to a company. The semiconductor-based biosensor can detect the intrinsic charge of target proteins, which bind specifically to receptors on the sensing surface, with high sensitivity. The FET biosensor would be applied to various health and medical diagnoses, just by choosing the appropriate receptors for the target proteins. To date, we have demonstrated the applications of the FET biosensors to the detection of tumor marker [2,3,7], influenza virus related proteins [4] and neuropsychiatric disorder related proteins [5,6] etc. Detection of tumor marker [2,3,7]A tumor marker, which increases with progression of cancer in the blood, is a biogenic factor for cancer screening. We have developed the FET biosensor for tumor marker detection by using antibody or antigen binding fragment (Fab) as a receptor. We succeeded in the quantitative detection of a tumor marker of liver cancer, α-fetoprotein (AFP), in blood serum. Detection of influenza virus related proteins [4]Influenza virus binds to host cells by using a viral surface protein, hemagglutinin (HA), to recognize the glycan on their cellular surface. Generally, human influenza virus HA (e.g. H1HA) and avian influenza virus HA (e.g. H5HA) binds to the glycans terminating in sialic acid-α2,6-galactose (6′-sialyllactose) and in sialic acid-α2,3-galactose (3′-sialyllactose), respectively. We have succeeded in the development of the glycan-immobilized FET biosensors for the discrimination of H1HA and H5HA at the atto molar level. Detection of neuropsychiatric disorder related proteins [5,6]Alzheimer’s disease, which is classified as a type of dementia, is known to be due to nerve cell death caused by aggregates and deposits of amyloid β protein (Aβ) in brain. Especially, the aggregation of Aβ42 isoform induces neuronal death. We have demonstrated that the FET biosensor having the gate modified with Congo red (CR), which interact specifically with amyloid aggregate containing cross-β-structure, could detect the Aβ42 aggregates at femto molar level.Based on the above-mentioned results, we are now in the earliest stages of commercialization of the FET biosensors toward their industrialization, and try to promote the collaboration with companies, healthcare professionals and so on.AcknowledgementThis work is partly supported by the Center of Innovation Program from Japan Science and Technology Agency, JST, Japan.ReferencesD. Niwa, K. Omichi, N. Motohashi, T. Homma, T. Osaka, Sens. Actuators B, 108, 721–726 (2005).S. Hideshima, R. Sato, S. Kuroiwa, T. Osaka, Biosens. Bioelectron., 26, 2419–2425 (2011).S. Hideshima, R. Sato, S. Inoue, S. Kuroiwa, T. Osaka, Sens. Actuators B, 161, 146–150 (2012).S. Hideshima, H. Hinou, D. Ebihara, R. Sato, S. Kuroiwa, T. Nakanishi, S. Nishimura, T. Osaka, Anal. Chem., 85, 5641–5644 (2013).S. Hideshima, S. Wustoni, S. Kuroiwa, T. Nakanishi, A. Koike, T. Osaka, ChemElectroChem, 1, 51–54 (2014).S. Hideshima, M. Kobayashi, T. Wada, S. Kuroiwa, T. Nakanishi, N. Sawamura, T. Asahi, T. Osaka, Chem. Commun., 50, 3476–3479 (2014).S. Cheng, K. Hotani, S. Hideshima, S. Kuroiwa, T. Nakanishi, M. Hashimoto, Y. Mori, T. Osaka, Materials, 7, 2490–2500 (2014).