Harnessing the Chirality-Induced Spin Selectivity Effect in Biosensors: Bridging Spin-Selective Transduction and Computational Modeling

Abstract

The sensitivity of classical electrochemical biosensors is constrained by noise processes at the electrode–electrolyte interface: low-frequency 1/f noise, thermal noise and capacitance fluctuations degrade the signal-to-noise ratio in ways that circuit-level mitigation reduces but does not remove. Chirality-Induced Spin Selectivity (CISS) has been proposed as a route past that limit, by shifting transduction from the scalar quantity of charge to the vector property of electron spin. Spin polarizations of up to approximately 60% have been reported at room temperature for double-stranded DNA monolayers in spin-resolved photoemission, while spin-dependent electrochemistry on smaller chiral adsorbates typically yields values in the range of about 5–30%; the reported magnitude is therefore system-, geometry-, technique- and analysis-dependent rather than a universal property of biological helices. Analyte binding modulates this efficiency through changes in helical pitch, dipole and structural integrity. This review unites the physics of CISS with the surface chemistry of spin-selective sensor layers, compares the competing mechanistic accounts of the effect, and then examines a persistent quantitative gap: the polarizations obtained from first-principles transport calculations on isolated chiral molecules remain well below the measured values. Non-relativistic, spin-restricted calculations on closed-shell helices in vacuum yield no polarization by construction, and although spin-polarized and relativistic implementations that treat spin–orbit coupling explicitly are available, they typically still underestimate experiments by orders of magnitude. We argue that a substantial part of this deficit is attributable to the widespread use of static, vacuum-based or implicitly solvated models, and that multiscale quantum mechanics/molecular mechanics (QM/MM) frameworks with explicit solvents are one necessary—though probably not sufficient—correction.