Printed electronics and microfluidics are two emerging and developing technologies with the common attractive feature of scalability. Advancements in fabrication capabilities have evolved research questions from, “What can we build?” to, “What should we build?”. This work focuses on the combination of these two technologies and their application to biosensing. The motivating theme is to understand how integrated, functional materials interact, elucidate the underlying molecular phenomena, then utilize the emergent advantages to address the outstanding limitations of conventional biosensing strategies. Printed electronics have recently been applied to biological detection with a variety of techniques1 while microfluidics, since their inception, have been used to handle biological fluids.2 The work presented here outlines a patented sensing strategy based off Floating-Gate Transistors (FGTs). The FGT design physically separates the electronic materials and biological fluids and thus bypasses various compatibility obstacles limiting other next-generation sensor technologies.3 The specific changes in interfacial properties that lead to robust signal transduction are derived empirically.4 This is followed by a mechanistic investigation into the molecular origin of sensor operation when FGTs are used in biomolecular detection. Finally, the versatility and scalability engendered by facile prototyping of FGTs is exemplified by successful iterations to DNA,3 ricin,5 and gluten proteins. The first proof-of-principle experiments incorporated printed electronics with an elementary biological system of DNA oligonucleotides. The results successfully demonstrated the potential of FGTs but failed to solidify their concrete value. Systematic investigation into the complex dynamics at the interface of chemically functionalized electrodes and electrolytes uncovered the most attractive features of the FGT technology. The chemistry was tuned with molecules that range in complexity from simple, short-chain alkyl-thiols to reversible protein-protein interactions. The observed responses with well-controlled systems were generalized to real systems like protein capture in food matrices (e.g. ricin in milk, orange juice). The resulting versatility originated from the label-free, electronic sensing mechanism and opened a range of possibilities for FGTs’ impact. The fundamental insights into interfacial dynamics, device operation, and biomolecular interactions were made possible by the advancements in the materials science and fabrication techniques underlying the presented results. Future avenues of development are hypothesized along with the most promising strategies. The continued elucidation of the physical mechanism and engineering upgrades justify the proposed strategies and inspire the continued effort to fully realize the potential of FGT biosensors.