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Recent advances in nanoscale manipulation and piconewton force detection provide a unique tool for studying the mechanical and thermodynamic properties of biological molecules and complexes at the single-molecule level. Detailed equilibrium and dynamics information on proteins and DNA have been revealed by single-molecule manipulation and force detection techniques. The atomic force microscope (AFM) and optical tweezers have been widely used to quantify the intra- and inter-molecular interactions of many complex biomolecular systems. In this article, we describe the background, analysis, and applications of these novel techniques. Experimental procedures that can serve as a guide for setting up a single-molecule manipulation system using the AFM are also presented.

This paper proposes a novel polarity-control junctionless tunnel field-effect transistor (PC-JL-TFET)-based biosensor for the label-free detection of biomolecule species in efficient ways. Unlike conventional designs, the polarity-control concept induces the generation of drain (n${}^{+}$) and source (p${}^{+}$) regions inside the proposed structure when a bias of $\mp 1.2$ V is applied at the polarity gates-1/2 (PG-1/2), to form a conventional TFET. To capture the biomolecules, a nano-cavity is created within the source region’s dielectric oxide toward the tunneling interface. The presence of biomolecules is electronically detected based on either solely the dielectric constant (neutral biomolecules) or the combination of charge density and dielectric constant (charged biomolecules). The proposed device can perform label-free recognition of biomolecules such as Uricase, Keratin, Biotin, Streptavidin and so on. To investigate the sensing performance of the proposed biosensor, significant biosensing metrics such as the electric field, energy band diagram, tunneling current, subthreshold slope, $I_{\mathrm{\text{ON}}}/I_{\mathrm{\text{OFF}}}$ ratio and threshold voltage have been studied. The proposed PC-JL-TFET biosensor achieves a maximum sensitivity of $5.31\times 10^{10}$ for neutral biomolecules with a dielectric constant of 12 and $1.11\times 10^{10}$ for negatively charged biomolecules $(-1\times 10^{12}{\mathrm{\text{C/cm}}}^2)$ with a dielectric constant of 8. The proposed biosensor’s selectivity, linearity and temperature-based analysis have also been evaluated for different biomolecules. Additionally, real-time practical scenarios, such as partially filled nano-cavities and the random position of biomolecules in the nano-cavity-based analysis, have also been incorporated.