Ingestible capsule for detecting labile inflammatory biomarkers in situ

Abstract

Transient molecules in the gastrointestinal (GI) tract, such as nitric oxide and hydrogen sulfide, are key signals and mediators of inflammatory bowel disease (IBD). Because these molecules are extremely short-lived in the body, they are difficult to detect. To track these reactive molecules in the GI tract, we have developed a miniaturized device that integrates genetically-engineered probiotic biosensors with a custom-designed photodetector and readout chip. Leveraging the molecular specificity of living sensors, we genetically encoded bacteria to respond to IBD-associated molecules by luminescing. Low-power electronic readout circuits (nanowatt power) integrated into the device convert the light from just 1 μL of bacterial culture into a wireless signal. We demonstrate biosensor monitoring in the GI tract of small and large animal models and integration of all components into a sub-1.4 cm3 ingestible form factor capable of supporting wireless communication. The wireless detection of short-lived, disease-associated molecules could support earlier diagnosis of disease than is currently possible, more accurate tracking of disease progression, and more timely communication between patient and their care team supporting remote personalized care.

Prebiotics-Controlled Disposable Engineered Bacteria for Intestinal Diseases

“…Most of the studies have addressed a single problem, such as the diagnosis, recording, or treatment of IBD. For example, several studies have used disease marker sensors, such as NO sensor, tetrathionate/thiosulfate two-component regulatory system to construct diagnostic systems, which can instantly report the situation of enteritis in bacteria for living diagnostics. ,, There are also studies focused on recording disease, converting transiently disease signals into long-term signals, especially recorded in genome DNA sequences. , In a newly published article, the author designed the digestible capsules that can quantitatively convert different stages of inflammation into wireless signals through engineered bacteria, which is extremely meaningful for patients to report the disease development timely . In addition, some studies have achieved certain effects on the treatment of IBD. , However, there is a defect that all the engineered systems are difficult to remove from the body, which results in a reduction in the recording capacity.…”

Intestinal Engineered Probiotics as Living Therapeutics: Chassis Selection, Colonization Enhancement, Gene Circuit Design, and Biocontainment

“…Although the long-term colonization of strains enables long-term monitoring, it also implies changes in the host microbiome. Therefore, for some scenarios in which long-term colonization is unnecessary, noncolonizing strains can be used and converted into IMBED. , More attention should also be paid to the accuracy and targeting of engineered bacterial colonization, which are currently provided, to some extent, by optogenetics and magnetogenetics. , Therefore, more robust physical control methods are needed to direct the colonization of engineered probiotics in vitro. These devices should also be simplified to improve their clinical application.…”

“…Therefore, for some scenarios in which longterm colonization is unnecessary, noncolonizing strains can be used and converted into IMBED. 191,192 More attention should also be paid to the accuracy and targeting of engineered bacterial colonization, which are currently provided, to some extent, by optogenetics and magnetogenetics. 175,178 Therefore, more robust physical control methods are needed to direct the colonization of engineered probiotics in vitro.…”

“…Engineered microorganisms convert environmental molecular signals into optical signals in real time, which are converted into electrical signals after being processed by the chip inside the device, and wirelessly transmitted to an external receiving device to be read out. A similar design now supports the detection of inflammatory responsive molecules such as NO and the accurate reporting of signal concentrations using an integrase-based analog-to-digital converter (Figure f), promising earlier and more accurate disease diagnosis than is currently possible …”

“…A similar design now supports the detection of inflammatory responsive molecules such as NO and the accurate reporting of signal concentrations using an integrase-based analog-to-digital converter (Figure 3f), promising earlier and more accurate disease diagnosis than is currently possible. 192 4.1.2. Sense-Therapy.…”