Ultrasensitive Quantification of Thyroid-Stimulating Hormone and Thyroxine by Nanoelectronic SnS2 Transistor Sensors

Abstract

The measurement of thyroid hormones in serum is widely regarded as the most valuable single laboratory tool for assessing thyroid function. This study presents a highly sensitive tin disulfide nanosheet-fabricated field-effect transistor (SnS₂-FET) designed for the detections of human thyroid-stimulating hormone (hTSH) and thyroxine (T4). By co-modifying an antibody (Ab_TSH for detecting hTSH), or a DNA aptamer (Apt_T4 for detecting T4), with polyethylene glycol (PEG) on the SnS₂-FET channel surface, the PEG:Ab_TSH/SnS₂-FET and PEG:Apt_T4/SnS₂-FET devices achieve highly sensitive and selective detections of hTSH and T4, respectively, even in a high ionic strength buffer (1× PBS) or undiluted serum. With a low limit of detection (in the femtomolar level) and a wide linear working range (spanning at least 6 orders of magnitude of analyte concentration), the PEG:Ab_TSH/SnS₂-FET immunosensor and PEG:Apt_T4/SnS₂-FET aptasensor can detect the hTSH and T4 levels encountered in the spectrum of thyroid disorders. Notably, these specific receptor-modified SnS₂-FET devices display negligible cross-reactivity with other pituitary hormones or serum components. This research indicates that the nanoelectronic SnS₂-FET sensor platforms hold significant potential for point-of-care clinical diagnostics, particularly for the ultrasensitive detection and early screening of medical conditions.

Keywords: antibody; aptamer; field-effect transistor biosensor; point-of-care diagnostics; polyethylene glycol; thyroid-stimulating hormone; thyroxine.

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(a) A schematic illustration of the experimental setup of an antibody- or aptamer-modified SnS₂-FET device for detecting hTSH or T4. (b,c) The chemical modification procedures of immobilizing (b) the anti-TSH antibody and (c) the T4 DNA-aptamer on the SnS₂-FET surface to form a PEG:Ab_TSH/SnS₂-FET immunosensor and a PEG:Apt_T4/SnS₂-FET aptasensor, respectively. The drawing is not to scale. Chemicals used in the surface modification include 3-aminopropyl trimethoxysilane (APTMS), 3-mercaptopropyl trimethoxysilane (MPTMS), propyl trimethoxysilane (PTMS), polyethylene glycol (PEG)-silane, and N,N′-disuccinimidyl carbonate (DSC).

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(a) The XRD spectrum of the SnS₂ bulk crystal reveals a hexagonal crystal structure. (b) The Raman scattering spectrum of mechanically exfoliated SnS₂ nanosheets exhibits the A_1g phonon mode of the SnS₂ crystal at 313.9 cm^–1. (c) The TEM image and SAED pattern (in the inset) further indicate the single-crystalline hexagonal structure of SnS₂ nanosheets. (d) The EDS spectrum and elemental mappings (insets) were obtained to characterize the compositional distributions of the Sn and S atoms in the as-prepared SnS₂ nanosheets. (e) The output curve (the black I _sd–V _sd trace) and electrical leakage (the red I _sg–V _sg trace) of an SnS₂-FET device were investigated. The electrical leakage of an SnS₂-FET device was measured, as shown in the inset. (f) The transfer curve (i.e., the I _sd–V _g plot) of an SnS₂-FET device, measured by scanning the solution-gate voltage (V _g) with V _sd = 10 mV, reveals a transconductance of ∼6 μS and an on–off ratio of ∼10⁵.

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(a) Real-time electrical response and (b) the calibrated response of a PEG:Ab_TSH/SnS₂-FET immunosensor to various concentrations of hTSH (C _TSH = 1 aM to 1 μM) in 1× PBS at pH 7.4. The PEG:Ab_TSH/SnS₂-FET device exhibits a very wide probing range with an LWR at C _TSH = 1 fM to 1 nM and an ultrahigh detection sensitivity with an LOD of ∼1 fM. (c) The target selectivity of a PEG:Ab_TSH/SnS₂-FET immunosensor was tested by measuring hTSH (1 pM) against several structural homologues of TSH (10 nM). (d) Real-time electrical response and (e) the calibrated response of a PEG:Apt_T4/SnS₂-FET aptasensor to C _T4 = 1 aM to 100 μM in 1× PBS at pH 7.4. The PEG:Apt_T4/SnS₂-FET device exhibits an LWR at C _T4 = 1 fM to 10 nM and an LOD of 1 fM. (f) The target selectivity of a PEG:Apt_T4/SnS₂-FET aptasensor was tested by measuring T4 (1 pM) against several serum components and Bisphenol A (10 nM). The black dashed lines in (b) and (e) are a guide to the eye, indicating the LWR. Error bars are the mean ± standard deviation with an average from three independent experiments (n = 3).

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(a) Real-time measurement and (b) the calibrated response of a PEG:Ab_TSH/SnS₂-FET immunosensor in the detection of hTSH at C _TSH = 1 aM to 100 μM in serum at pH 7.4. (c) Real-time measurement and (d) the calibrated response of a PEG:Apt_T4/SnS₂-FET aptasensor in the detection of T4 at C _T4 = 10 aM to 100 μM in serum at pH 7.4. (e) A table summarizes the performance metrics for detecting hTSH and T4 in 1× PBS or serum using the PEG:Ab_TSH/SnS₂-FET and PEG:Apt_T4/SnS₂-FET devices, respectively. The black dashed lines in (b) and (d) are a guide to the eye representing the LWR. Error bars are the mean ± standard deviation with an average from three independent experiments (n = 3).