We are developing a variety of tools that leverage nanotechnology for biomedical applications. One such tool involves using a picometer-diameter pore (i.e. picopores) as a non-optical sensor which relies on a distinctive electrical signal that develops when a single analyte, immersed in electrolyte, translocates across a membrane through the pore. My research group has shown that it is now possible to produce pores with a sub-nanometer diameter in a solid-state dielectric embedded in a microfluidic device. Sub-nanometer precision affords exquisite control of the electric field in and beyond the lumen of the pore, while the microfluidic device reduces the parasitic membrane capacitance that adversely affects noise while at the same time reducing the amount of material required for detection. We have shown that such precise control of the electric field and the forces in a picopore facilitate discrimination between different proteins and nucleic acids, and enables the transfection of single cells via electroporation.