Biosensors and Bioelectronics 33 (2012) 233–240 Contents lists available at SciVerse ScienceDirect Biosensors and Bioelectronics j our na l ho me page: www.elsevier.com/locate/bios Detection of uncharged or feebly charged small molecules by field-effect transistor biosensors Chil Seong Ah a,∗ , Chan Woo Park a , Jong-Heon Yang a , Joon Sung Lee b , Wan-Joong Kim a , Kwang Hyo Chung a , Yo Han Choi a , In Bok Baek a , Jungho Kim c , Gun Yong Sung a a Biosensor Research Team, Electronics and Telecommunications Research Institute (ETRI), 218 Gajeong-ro, Yuseong-gu, Daejeon 305-700, Republic of Korea b Medical Convergence Component Research Team, Electronics and Telecommunications Research Institute (ETRI), 218 Gajeong-ro, Yuseong-gu, Daejeon 305-700, Republic of Korea c Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, Republic of Korea a r t i c l e i n f o Article history: Received 3 November 2011 Received in revised form 4 January 2012 Accepted 9 January 2012 Available online 17 January 2012 Keywords: Field-effect transistor Nanoparticle charge Mycotoxin Signal enhancement Small molecule detection a b s t r a c t This paper describes a new technique for the detection of uncharged or feebly charged small molecules (<400 Da) using Si field-effect transistor (FET) biosensors that are signal-enhanced by gold nanoparticle (NP) charges under dry measurement conditions. NP charges are quickly induced by a chemical deposi- tion (that is, Au deposition) and the indirect competitive immunogold assay, and strongly enhance the electrical signals of the FET biosensors. For the validation of signal enhancement of FET biosensors based on NP charges and detection of uncharged or feebly charged small molecules, mycotoxins (MTXs) of aflatoxin-B1 (AFB1), zearalenone (ZEN), and ochratoxin-A (OTA) were used as target molecules. Accord- ing to our experimental results, the signal is 100 times more enhanced than the use of the existing solution FET biosensing techniques. Furthermore, this method enables the FET biosensor to quantitatively detect target molecules, regardless of the ionic strengths, isoelectric points (pI), or pHs of the measured sample solutions. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Complementary metal oxide semiconductor (CMOS)- compatible field-effect transistor (FET) biosensors are useful tools for the diagnosis of various diseases, because they can electronically detect and analyze biomolecules, such as proteins, DNA, and small molecules, in real-time and with high sensitiv- ity. Therefore, these biosensors have been the subject of many studies worldwide (Elfström et al., 2008; Ryu et al., 2010; Stern et al., 2007; Zheng et al., 2008; Zheng et al., 2005). In particular, CMOS-compatible FET biosensors that are produced by a top-down method utilize conventional semiconductor processes, which pro- vide highly reproducible and uniform sensor characteristics that are suitable for mass production, however, despite the advantages of CMOS-compatible FET biosensors, most studies have been limited to the detection of biomolecules that have net electrical charges, such as proteins and DNAs (Elfström et al., 2008; Ryu et al., 2010; Stern et al., 2007; Zheng et al., 2008; Zheng et al., 2005). The FET approach for detecting small molecules, such as hormones, toxins, drugs, environmental pollutants, agrichemicals, and antibiotics is not applicable for a reproducible and portable ∗ Corresponding author. Tel.: +82 42 860 1898; fax: +82 42 860 6594. E-mail address: acs@etri.re.kr (C.S. Ah). sensor diagnosis because they are uncharged or feebly charged small molecules, despite their demands in many fields. In addition to the difficulty of detecting small molecules that have no charge, other issues remain as obstacles to the utiliza- tion of FETs as suitable biosensors in diverse fields. First, it should be possible to measure signals under dry conditions so that the noise caused by the numerous redundant ions that are present in an aqueous solution can be eliminated. In previous studies (Ah et al., 2010; Elfström et al., 2008; Kim et al., 2010; Stern et al., 2007; Zheng et al., 2005), measurement in an aqueous environ- ment was considered essential for keeping the net charges of the target biomolecules in a situation where the electrical sig- nal of the FET element is easily affected by the ionic strength, pI, and pH of the sample solution. Second, the biomolecules need to be directly detectable in highly concentrated ionic solutions without dilution (Ah et al., 2010; Kim et al., 2010). With current FET sensor technology, it is difficult to analyze signals directly from highly ionic concentrated (∼150 mM NaCl) physiological sam- ples, such as human serum, because of the short Debye length (Stern et al., 2007) and varying pH and ion concentrations. Even if a sufficient Debye length is achieved by dissolving to desalt or dilute the sample (Stern et al., 2007; Zheng et al., 2005), it is still difficult to use pH solutions of controlled ion concen- trations. Third, for ‘top-down’ fabrication techniques, enhancing sensitivity by reducing the channel dimension is limited because 0956-5663/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.bios.2012.01.010