The potential use of gene- modified cell therapy in hematologic malignancies is often limited by complications related to effectively engineering and manufacturing cells with conventional delivery systems and is challenge specifically for immune cells. In fact, this life-saving therapy requires use of inefficient reagents and specialized equipment that can drive up the price of the treatment. Herein, we compared two different approaches for gene transfer into target cells: Nucleofection as a 2D gene delivery and microfluidic device as a 3D gene transfer technology. In fact, we developed and used serpentine microfluidic chip for cell membrane penetration that permits delivery of DNA into Multiple myeloma cells. We achieved high transfection efficiency (55.7% GFP) in myeloma cells with high cell viability (by PI staining) 24-48 hours after microfluidic processing compared to nucleofection that is toxic and rate of dead cells is very high. The significant differences in outcomes from the two techniques underscores the importance of understanding the impact of intracellular delivery techniques on cell function for research and clinical applications. Altogether, these results highlight the use of microfluidic device as a rapid and gentle delivery method with promising potential to engineer primary human cells for research and clinical applications.