The modeling and analysis of hybrid nanofluid has much importance in industrial sector where entropy optimization is the key factor in different processes. This mechanism is also used in medical industry, where it can be used for separation of blood cells (red and white blood cells, platelets and plasma) by centrifuge process, treating cancers, and drug transport. In light of this importance, current study is focused on mathematical modeling and analysis of blood based hybrid nanofluid between rotating disks with various shapes of nanoparticles. The shape factors are taken into account with Hamilton–Crosser model as spherical, brick, cylinder and platelet in the current scenario, with special reference to entropy optimization. In order to solve modeled nonlinear and non-dimensional system, optimal homotopy analysis approach is utilized through Wolfram MATHEMATICA 11.3 software. Error estimation and convergence analysis confirms that obtained semi-analytical solutions are valid and reliable. Velocity, temperature and concentration profiles are analyzed against important fluid parameters. Fluid velocity decreased in all directions when unsteady parameter $$\mathbb {B}$$
B
and Darcy number Da increased while the slip parameters $$\zeta _{1}$$
ζ
1
and $$\zeta _{2}$$
ζ
2
decreased the nanofluid velocity. It is observed that in case of brick shaped nanoparticles, fluid temperature is enhanced as compared to other shape factors in the study. Minimal entropy generation is captured in case of spherical nanoparticles, while highest heat transfer is observed in platelet shaped nanoparticles. Furthermore, numerical optimization of entropy is performed against different values of $$\hbar$$
ħ
and volume fractions $$\varphi _{Rd}$$
φ
Rd
and $$\varphi _{Al}$$
φ
Al
. Minimized entropy is recovered to be zero when $$\hbar =-0.6$$
ħ
=
-
0.6
, $$\varphi _{Rd}=2\%$$
φ
Rd
=
2
%
and $$\varphi _{Al}=1\%$$
φ
Al
=
1
%
.