Coupling split-lux cassette with a toggle switch in bacteria for ultrasensitive blood markers detection in feces and urine

Cell-based biosensors have powerful abilities to sense a variety of signal chemical molecules. However, compared with commercialized methods, whole-cell biosensors cannot meet the requirements for the lower sensitivity and faster response. Here, we reprogrammed a gene circuit by coupling split-lux cassette with a toggle switch for detecting heme ultra-sensitively. The resultant biosensor (named YES601) exhibited improved detection limit (0.12 ppm) and satisfied maximum induction ratio (more than 4000 folds) for lysed blood detection. Furthermore, we harnessed YES601 to detect the blood signal in the human urine and feces from the mice with DSS-induced colitis, and the results indicated that YES601 showed more satisfied sensitivity and maximum induction ratio compared with chemical method. This ultrasensitive blood biosensor will be applied to detect trace blood in vitro for early-stage diagnosis of serious diseases, and aiding the rapid development for application in diagnosis in vivo in the future.