  Microscopic particle separation plays vital role in various scientific and
industrial domains. In this Letter, we propose a universal non-equilibrium
thermodynamic approach, employing the concept of Shortcuts to Isothermality, to
realize controllable separation of overdamped Brownian particles. By utilizing
a designed ratchet potential with temporal period $\tau$, we find in the
slow-driving regime that the average particle velocity
$\Bar{v}_s\propto\left(1-D/D^*\right)\tau^{-1}$, indicating that particles with
different diffusion coefficients $D$ can be guided to move in distinct
directions with a preset $D^*$. Furthermore, we reveal that there exists an
extra energetic cost with a lower bound
$W_{\rm{ex}}^{(\rm{min})}\propto\mathcal{L}^{2}\Bar{v}_s$, alongside a
quasi-static work consumption. Here, $\mathcal{L}$ is the thermodynamic length
of the driving loop in the parametric space. We numerically validate our
theoretical findings and illustrate the optimal separation protocol (associated
with $W_{\rm{ex}}^{(\rm{min})}$) with a sawtooth potential. This study
establishes a bridge between thermodynamic process engineering and particle
separation, paving the way for further explorations of thermodynamic constrains
and optimal control in ratchet-based particle separation.
