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In this paper, we proposed to enhance a signal-to-noise (S/N) ratio for detecting a primary stress marker, serotonin, using a potentiometric biosensor modified by a well-designed nanofilter film. An extended-Au-gate field-effect transistor (EG-Au-gate FET) biosensor exhibits highly sensitive electrochemical detection toward various small biomolecules, including serotonin. Therefore, to enhance the S/N ratio for the serotonin detection, we designed an appropriate nanofilter film on the Au electrode by combining the aryldiazonium salt reduction strategy and boronate affinity. That is, only serotonin can approach the Au sensing surface to generate an electrical signal; interfering biomolecules are prevented from penetrating through the nanofilter, either because large interfering biomolecules cannot permeate through the highly dense, nanoporous multilayer film, or because phenylboronic acids included in the nanofilter captures small interfering biomolecules (e.g., catecholamines). The potentiometric biosensor modified by such a nanofilter film detected serotonin in a model sample solution containing catecholamines, cortisol, and human serum albumin with a high S/N ratio for the serotonin levels in the blood. Furthermore, we found that the effect of the nanofilter directly reflects the binding affinity of the receptors such as phenylboronic acids included in the nanofilter; thus, the selectivity and dynamic range of small target biomolecules can be tuned freely by designing the appropriate receptors for the nanofilter. The results show that a well-designed nanofilter biointerface can be a versatile biosensing platform for point-of-care testing, particularly for a simple stress check.

In this paper, we propose a novel concept of a biointerface, a polymeric nanofilter, for the potentiometric detection of small biomolecules using an extended-Au-gate field-effect transistor (EG-Au-FET). A Au electrode has the potential capability to detect various small biomolecules with ultrasensitivity at nM levels on the basis of a surface redox reaction, but it exhibits no selective response to such biomolecules. Therefore, a suitable polymeric nanofilter is designed and modified on the Au electrode, so that a small target biomolecule reaches the Au surface, resulting in an electrical signal, whereas low-molecular-weight interferences not approaching the Au surface are captured in the polymeric nanofilter. The polymeric nanofilter is composed of two layers. The first layer is electrografted as an anchor layer by a cyclic voltammetry method. Then, a filtering layer is precisely polymerized as the second layer by a photo-mediated surface-initiated atom transfer radical polymerization method. The thickness and density of the polymeric nanofilter are controlled to specifically detect a small target biomolecule with high sensitivity. As a model case, l-cysteine as the small target biomolecule at nM levels is specifically detected by filtering l-DOPA as a low-molecular-weight interference using the polymeric nanofilter-grafted EG-Au-FET on the basis of the following mechanism. The phenylboronic acid (PBA) that copolymerizes with the polymeric nanofilter captures l-DOPA through diol binding, whereas l-cysteine reaches the Au surface through the filter layer. The polymeric nanofilter can also effectively prevent the interaction between biomacromolecules such as albumin and the Au electrode. A platform based on a polymeric nanofilter-grafted EG-Au-FET biosensor is suitable for the ultrasensitive and specific detection of a small biomolecule in biological samples such as tears and sweat, which include small amounts of low-molecular-weight interferences, which generate nonspecific electrical signals.

In this paper, we demonstrate the use of a monolayer film electrografted via diazonium chemistry for controlling the potential response of a field-effect transistor (FET)-based sensor. 4-Nitrobenzenediazonium salt is electrografted on an extended-Au-gate FET (EG-Au-FET) with or without using a radical scavenger by cyclic voltammetry (CV), resulting in the formation of a monolayer or multilayer. In particular, the surface coverage of the aryl-derivative monolayer on the Au gate electrode gradually increases with increasing number of potential cycles in CV. Here, Au exhibits a strong catalytic action, resulting in the oxidation of organic compounds. Uric acid is used as a low-molecular-weight biomolecule for interference. The denser the surface coverage of the grafted monolayer, the smaller the potential response of the EG-Au-FET because the redox reaction of uric acid with the Au gate surface is suppressed. On the other hand, the effect of the aryl-derivative multilayer on the suppression of the potential response was smaller than that of the monolayer because the electrogenerated aryl radicals did not react with the Au surface but with the grafted species, resulting in an exposed part of the Au surface among the grafted aryl molecules. Thus, a platform based on such a monolayer film electrografted via diazonium chemistry is suitable for controlling the potential response based on the interference of low-molecular-weight biomolecules in biosamples.

In this paper, we report the concept of an aptamer (Ap)-based nanofilter interface for the suppression of nonspecific signals generated by interfering species in biological samples. As a model of the target small biomolecule, l -3,4-dihydroxyphenylalanine ( l -DOPA) is used to demonstrate its electrical discrimination from dopamine (DA) despite their similar chemical structures using a DA–Ap nanofilter-coated Au gate field-effect transistor (FET). A Au gate electrode is employed to assess the electrical response of the FET to l -DOPA on the basis of oxidative reactions. In particular, the proposed nanofilter interface is based on the DA–Ap layer immobilized at the aryl-diazonium-based anchor monolayer, which is electrochemically grafted on the Au gate electrode via diazonium chemistry. As a result, the electrical signal from l -DOPA is clearly discriminated from that from DA at a concentration of 1 μM or higher using the DA–Ap nanofilter-coated Au gate FET. That is, DA is trapped by the DA–Ap nanofilter through the formation of complexes, the molecular charges of which are shielded by counter ions that are not in contact with the Au gate surface, whereas l -DOPA reaches and electrochemically reacts with the Au gate surface, generating an electrical signal regardless of the nanofilter. The surface properties of the DA–Ap nanofilter modified on the Au gate electrode are investigated by cyclic voltammetry, chronocoulometry, atomic force microscopy, and X-ray photoelectron spectroscopy. A platform based on the FET biosensor with the Ap-based nanofilter interface contributes to the electrical monitoring of small biomarkers while suppressing the nonspecific signals of interfering species in biological samples.

The origin of the unusually high stability of the sialic acid (SA) and phenylboronic acid (PBA) complex was investigated by a combined nuclear magnetic resonance (NMR) spectroscopy and density functional theory (DFT) study. SA is a glycan‐terminating monosaccharide, and its importance as a clinical target has long been recognized. Inspired by the fact that the binding properties of SA–PBA complexation are anomalously high relative to those of typical monosaccharides, great effort has been made to build a clinical platform with the use of PBA as a SA‐selective receptor. Although a number of applications have been reported in recent years, the ability of PBA to recognize SA‐terminating surface glycans selectively is still unclear, because high‐affinity SA–PBA complexation might not occur in a physiological environment. In particular, different forms of SA (α‐ and β‐pyranose) were not considered in detail. To answer this question, the combined NMR spectroscopy/DFT study revealed that the advantageous binding properties of the SA–PBA complex arise from ester bonding involving the α‐carboxylate moieties (C1 and C2) of β‐SA but not α‐SA. Moreover, the facts that the C2 atom is blocked by a glycoside bond in a physiological environment and that α‐SA basically exists on membrane‐bound glycans in a physiological environment lead to the conclusion that PBA cannot selectively recognize the SA unit to discriminate specific types of cells. Our results have a significant impact on the field of SA‐based cell recognition.

Semiconductor-based biosensors are suitable for the detection of small molecules such as saccharides as long as they have molecular charges. In this study, we developed molecularly imprinted polymer-based field effect transistor (MIP-gate FET) for selective sugar chain sensing in aqueous media. Choosing 3'-sialyl lactose (3'-SLac) and 6'-sialyl lactose (6'-SLac) as target sugars, we confirmed that they could be sensed quantitatively from 10uM. Moreover, the sensor showed selectivity to some extent, where the signal from competent was suppressed by 40% at maximum. We also found that the selectivity enhanced by MIP differs for 2 different template sugars, although these sugars are similar in structures. Moreover, the selective detection of other oligosaccharides was investigated using the MIP-gate FET. From these results, we showed the possibility of MIP-gate FET as selective sugar detecting sensor, which can be applied widely in medical fields.

In this study, we developed a molecularly imprinted polymer-based field-effect transistor (MIP-gate FET) for selectively detecting sugar chains in aqueous media, focusing on 3'-sialyllactose (3SLac) and 6'-sialyllactose (6SLac). The FET biosensor enables the detection of small molecules as long as they have intrinsic charges. Additionally, the MIP gels include the template for the target molecule, which is selectively trapped without requiring enzyme-target molecule reaction. The MIP gels were synthesized on the gate surface of the FET device, including phenylboronic acid (PBA), which enables binding to sugar chains. Firstly, the 3SLac-MIP-gate FET quantitatively detected 3SLac at µM levels. This is because the FET device recognized the change in molecular charges on the basis of PBA-3SLac binding in the MIP gel. Moreover, 3SLac was selectively detected using the 3SLac- and 6SLac-MIP-gate FETs to some extent, where the detecting signal from the competent was suppressed by 40% at maximum. Therefore, a platform based on the MIP-coupled FET biosensor is suitable for a selective biosensing system in an enzyme-free manner, which can be applied widely in medical fields. However, we need to further improve the selectivity of MIP-gate FETs to discriminate more clearly between similar structures of sugar chains such as 3SLac and 6SLac.