Abstract <p>The research focuses on the development of a novel, cost-effective, three-layer droplet microfluidic device fabricated using Polymethyl methacrylate (PMMA) engineered for high-throughput screening in healthcare applications. PMMA offered improved optical transparency, chemical resistance, low absorption, and high scalability. Here, we evolved a T-junction integrated microchannel with a squeezer mechanism for consistent monodisperse droplet generation. Device fabrication was achieved via a laser ablation technique followed by an ethanol-enhanced UV-irradiation method for strong and leak-free bonding between the PMMA layers. The surface properties of the PMMA layer revealed an increased surface energy and uniform wettability. The tensile strength of fabricated PMMA microfluidic devices demonstrated superior bonding strength and structural integrity compared to the existing fabrication methods. The device reliably generated uniform monodisperse droplets up to a 100&#xa0;ml/hr flow rate, confirming its robustness and suitability for high-throughput screening. Overall, this PMMA-based Microfluidics platform offers a scalable and reliable solution for droplet generation suitable for applications such as drug delivery, single-cell analysis, and diagnostic assays.</p> Graphical abstract <p></p>