Sensory perception governs how we as humans interact with the world around us. On a biological level, our cells interact with their extracellular environment oftentimes via transmembrane proteins, located at the plasma membrane. These proteins can respond to changes in cellular homeostasis, and as such can be considered natural biosensors. Disruptions to cellular homeostasis, however, can result in pain or disease at the systemic level, manifesting in clinical signs and patient hospitalization. Therefore, identifying disease onset at an early stage is critical for a favorable prognosis. By exploiting the natural sensitivity and selectivity of integral membrane proteins involved in sensory perception, it could be possible to create an early-stage biosensor for detecting disease. However, membrane proteins are notoriously challenging to recombinantly produce using traditional cell-based approaches, requiring additional detergent solubilization and reconstitution steps to create such a tool. In this thesis, I explore the use of cell-free protein synthesis (CFPS) for applications in early disease detection and pain management. Using both the olfactory system and clinically relevant nociceptors as a model, I demonstrate the functional expression of complex transmembrane sensory receptors using CFPS and characterize their activity. By intersecting protein engineering with bioelectronics, I have been able to design a platform that enables the rapid screening of subtype specific channel antagonists for pain relief applications, with a focus on the P2X family of purinergic receptors. The cell-free expression of functional Transient Receptor Potential Vanilloid 1 (TRPV1), implicated in multiple pain subtypes and activated by multiple agonists, further demonstrates the utility of this platform as a potential pain sensor using optical readout methods. Integrating machine learning with CFPS can provide additional perspectives on both sensor design and signal interpretation, particularly within the context of early disease detection. Here, I also discuss such approaches with a focus on the insect olfactory system for the detection of early-stage disease biomarkers. This work highlights the translational potential of CFPS, envisioning the development of a sensory array and providing a fresh perspective on the future of biosensing.