Separation of particles, biological cells and its combination for clinical applications has resulted in an increasing growth of microscale continuous-flow particles and cells manipulation techniques. To design and develop effective techniques, numerical simulation approach is more cost-effective. Numerical simulation can be treated to replicate the condition of physical experiment, as closely as possible, or they can be employed to study what-if scenarios in which can help to identify which factors are most influencing the physical outcomes. Simulation can provide details not available from experiments and taken together, will surely help to resolve the physical processes. In this talk, we will share the methodology and applications of i-MADE: Immersed Boundary Method for Micro-fluidics Advanced Design and Engineering. i-MADE implements a moving-least-square immersed boundary method for solving viscous incompressible flow involving deformable and rigid boundaries on a uniform Cartesian grid. i-MADE handles the fluid motion, the deformable interface motion and the interaction with the immersed rigid boundaries simultaneously in order to account for the complex interaction between the fluid and the immersed boundaries. For rigid objects, no-slip conditions at the rigid boundaries are enforced using the direct-forcing approach which utilizes moving least squares (MLS) method to reconstruct the velocity at the forcing points in the vicinity of the rigid boundaries. For deformable boundaries, MLS method is also employed to construct the interpolation and distribution operators for the immersed boundary points in the vicinity of the rigid boundaries. i-MADE uses the Jacobian-free Newton–Krylov method to advance the location of the elastic boundaries implicitly to greatly improve the time step. The large boundary deformation is taken into account by using a subdivision thin-shell model. i-MADE finds its application particularly useful in biological fluid dynamics or in any other application areas with large boundary deformations and moving boundaries.