Platelets (PLTs) are responsible for stopping bleeding. They are small cell fragments produced from megakaryocytes (MKs) in the bone marrow. Low platelet count is a significant health problem for a patient. PLTs can usually be stored for up to 5 days prior to transfusion. Instantaneous production of PLTs from isolated and stored MKs is crucial for the patient’s health. Thanks to microfluidic platforms, PLTs can be produced instantaneously from MKs. Herein, we have computationally studied fluid dynamics in the microchannels with slit structures and different inlet geometries. Analysis of the flow dynamics was performed by the commercial analysis software. The effects of flow rates and the angle between the inlet channels on the MKs trapping were investigated. The optimization of the angle between inlet channels and flow rates of main and pressure flows was done with response surface methodology (RSM) by counting the trapped MKs. The optimum conditions lead to the percentage of trapped MKs being 100 with a relative deviation of <1%. We also concluded that flow rates to trapping a higher amount of MKs are as important as the angle between the inlet channels.