Our group is collaborating with Geoppert Labs and NASA to enhance the fabrication of nanopore meshes for resistive pulse sensing, a crucial technique for biomolecule analysis. The primary objective is to develop improved methods for creating precise and reliable pores, ensuring optimal sensitivity and stability in sensing applications. To achieve this, we are exploring and implementing advanced pore fabrication techniques. One key approach involves Focused Ion Beam (FIB) patterning, which enables high-resolution nanopore structuring with exceptional control over size and shape. Our team developed a new drilling pattern that could produce pores substantially smaller than the ION beam’s spotsize. Additionally, we are leveraging laser direct writing to create nanopore structures with a high degree of precision and scalability. By using a femtosecond laser, we can ablate material with minimal thermal effects, producing clean, high-aspect-ratio pores. This method offers rapid prototyping capabilities and the flexibility to pattern complex geometries on various substrates. Furthermore, we are developing masking strategies using the Focused Ion Beam to create a mask with pores smaller than the spot size of the femtosecond laser. This technique will be used in conjunction with a sacrificial masking process. By depositing and selectively removing sacrificial layers, we can fine-tune pore dimensions and optimize the fabrication process for enhanced performance. Through these combined efforts, we aim to advance nanopore technology, enabling more effective biomolecule detection while improving the reproducibility and scalability of fabrication techniques.