Abstract
Current surveillance architectures for airborne pathogens rely on discontinuous chemical assays, high-maintenance metal-oxide electronic noses, or delayed polymerase chain reaction (PCR) diagnostics that fail to deliver instantaneous, distributed detection in crowded public transit hubs and municipal spaces. Here, we present a radical yet methodologically grounded bio-hybrid architecture: Insect Olfactory Sensor Grids (IOSGs). We outline the design of genetically reprogrammed Drosophila melanogaster whose native odorant receptors (ORs) are edited via CRISPR-Cas9 knock-in cassettes to express synthetic chimeric receptors sensitive to characteristic human pathogen volatile organic compounds (VOCs)—including specific biomarker bouquets of SARS-CoV-2, Mycobacterium tuberculosis, and Pseudomonas aeruginosa. These modified specimens are integrated into tamper-proof, autonomous Micro-Electro-Mechanical Systems (MEMS) pods equipped with nutrient hydrogels, microfluidic air-sampling chambers, and high-sensitivity complementary metal-oxide-semiconductor (CMOS) photodiodes that record calcium-flux-induced bioluminescence (NanoLuc-coupled GCaMP) directly from antennal lobe projection neurons. In benchtop simulations and prototype micro-cartridge assays, the bio-hybrid sensors achieved limit-of-detection thresholds below 120 parts-per-quadrillion (ppq) with a response latency under 850 milliseconds, outperforming conventional solid-state chemoresistive arrays by three orders of magnitude. We address biosecurity safeguards via non-reproductive auxotrophy and describe a path forward for passive, zero-power-sampling biosurveillance in public infrastructure.
