Mapping Surface Potential in DNA Aptamer-Neurochemical and Membrane-Ion Interactions on the SOS Substrate Using Terahertz Microscopy

Abstract

In this study, we utilized a terahertz chemical microscope (TCM) to map surface potential changes induced by molecular interactions on silicon-on-sapphire (SOS) substrates. By functionalizing the SOS substrate with DNA aptamers and an ion-selective membrane, we successfully detected and visualized aptamer-neurochemical complexes through the terahertz amplitude. Additionally, comparative studies of DNA aptamers in PBS buffer and artificial cerebrospinal fluid (aCSF) were performed by computational structure modeling and terahertz measurements. Beyond neurochemicals, we also investigated calcium ions, measuring their concentrations in PDMS-fabricated micro-wells using minimal sample volumes. Our results highlight the capability of TCM as a powerful, label-free, and sensitive platform for the probing and mapping of surface potential arising from molecular interactions, with broad implications for biomedical diagnostics and research.

Keywords: DNA aptamer–neurochemical complexes; SOS substrate; artificial cerebrospinal fluid; membrane–ion interactions; surface potential; terahertz chemical microscope.

Figure 1

Schematic diagram of SOS substrate (a) and TCM optical setup (b).

Figure 2

(a) Surface functionalization on SOS substrate with serotonin-binding DNA aptamers; (b) AFM image of serotonin-binding DNA aptamers.

Figure 3

(a) Terahertz amplitude distribution at increasing serotonin concentrations; (b) concentration-dependent THz amplitude response to serotonin; (c) real-time THz response to 1 ppb serotonin; (d) real-time THz response to 100 ppb serotonin; (e) real-time THz response to 1000 ppb serotonin.

Figure 4

Molecular interactions and experimental analysis of DNA aptamer–serotonin complexes in aCSF and PBS. (a) Structural modeling in aCSF; (b) structural modeling in PBS; (c) experimental results in aCSF and PBS (over 200 data points measured on a single SOS substrate and averaged); (d) terahertz amplitude distribution mapping in aCSF and PBS.

Figure 5

Molecular interactions and experimental analysis of DNA aptamer–dopamine complexes in aCSF and PBS. (a) Structural modeling in PBS and aCSF; (b) experimental results in aCSF and PBS (over 100 data points measured on a single SOS substrate and averaged); (c) terahertz amplitude distribution mapping in aCSF and PBS.

Figure 6

The results of calcium ion concentration measurements using PDMS microwells. (a) shows the differences before and after the calcium ion reaction. This confirms the change in terahertz wave intensity in the PDMS wells. (b) The mean value and standard deviation of each plot in (b), (c) presents THz intensity distribution maps for three different SOS substrates (samples 1, 2, and 3) exposed to varying Ca²⁺ concentrations (10⁻¹ to 10⁻⁴ mol/L). The images depict how THz amplitude responds to increasing ion concentrations, demonstrating a highly linear correlation over a wide concentration range in (d).