Fig. 2

Summary of progress in BWBCs for the detection of diseases and disorders. In 2006, an AHL biosensor was developed for ex vivo detection of inflammatory bowel disease (IBD). Representation of AHL-dependent regulation of quorum sensing in LuxR/LuxI-type systems from [33]. Design of induction-dependent invasion of a cancer cell in 2006. Schematic of the activation of biosensor at a critical bacterial cell density or in a hypoxic environment resulting in the synthesis of invasin and the bacterial invasion of tumor cells [25]. In 2012, E. coli was engineered to detect and respond to gut inflammation in mouse ileum explants through nitric oxide sensing. Representation of biosensor where sensing nitric oxide results in switching of the core circuit and causes a permanent change in gene expression output [32]. In 2013, the first the use of the GDH-bacteria for sensitive amperometric glucose biosensor was reported. Schematic of the construction of genetically engineered bacteria displaying GDH and INP. GDH catalyzes the transformation of glucose to gluconolactone in the presence of coenzyme NAD + , which is reduced to NADH [34]. Development of BWCB based on the detection of quorum sensing molecule AI-2 for the quantitative detection of IBD in saliva, stool, and intestinal samples of IBD patients. Representation of the hypothesized mechanism of quorum sensing-regulated bioluminescence in V. harveyi [24]. In 2014, the development of bistable transcriptional switches for in vivo detection of gut inflammation through ATC. Schematic of the memory circuit. Representation of the lambda cI/Cro-based transcriptional memory and the tetP-Cro trigger elements [22]. In 2015, probiotics were engineered for detection of cancer in urine [10]. Programming controlled adhesion of E. coli to target tumors with synthetic adhesins [35]. Development of quorum sensing switch in Salmonella for in vivo detection of tumors. Schematic of lux quorum sensing system. [26] Detection of biomarkers in human clinical samples via amplifying genetic switches and logic gates. Schematic architecture of the biosensor. A sensor module enables multiplexed detection of pathological biomarkers. These control signals induce a Boolean integrase logic gate module. Boolean integrase logic gates enable signal digitization, amplification, and storage of the diagnosis test’s outcome in a stable DNA register [9]. In 2016, development of BWCB based on V. cholerae quorum sensing receptors and CRISPRi for cholera diagnosis [18]. In 2017, development of the first tetrathionate sensor. Establishment of two-component systems of tetrathionate and thiosulfate for the detection of IBD in fecal and colon samples. Schematic of thiosulfate sensor and the schematic of ligand-induced signaling for thiosulfate sensor characterization [13]. In 2018, development of Ingestible Micro-Bio-Electronic Device (IMBED) for gastrointestinal bleeding sensing in porcine model. Schematic of the blood sensor gene circuit [16]. Development of BWCB for cholera sensing and reporting by engineered L. lactis in vitro and in vivo. Engineered CAI-1–dependent signaling in L. lactis [36]. In 2019, development of the biological equivalent of the latex agglutination test. Representation of cell agglutination using a BWCB surface-displaying nanobodies which bind selectively to a target protein analyte [19]. In 2020, development of AND logic gate with nitrate and thiosulfate for ex vivo sensing of IBD. Schematic of AND logic gate that uses nitrate and thiosulfate genetic circuits [14]. Development of BWCB bioluminescence-based assay for the diagnosis of urinary tract infection. Schematic representation of TuBETUr and CUBET diagnosis platforms [20]. In 2022, use of magnetic living hydrogels for in vivo detection of gastrointestinal bleeding. Schematic of the mechanism of the magnetic living hydrogels localized and retained in the intestine [37]. Development of multiplexed biosensors-based logic gate circuits for bacterial tropism enhancement. Schematic of biosensors for specific oxygen, lactate and pH levels detection to enable bacteria tropism in vivo [17]. In 2023, the development of intelligent responsive bacteria for diagnosis and therapy (i-ROBOT) for in vivo IBD monitoring. Schematic of i-ROBOT for thiosulfate sensing. Fluorescence and inheritable signals (genomic molecular recording and colorimetric output) enable IBD detection and monitoring [23]. A biosensor was developed for the detection of calprotectin, the gold standard biomarker of gut inflammation, with sensitivity and specificity in IBD patients. Schematic of the identification of calprotectin-responsive genes in E. coli Nissle 1917 using RNA-sequencing method [21]