Fluorescent nanosensor enables rapid, first-of-its-kind detection of key gut health biomarker

An international team of researchers has developed a novel fluorescent nanosensor powered by carbon nanotubes that is capable of rapidly detecting an emerging biomarker linked to gut health and disease. This important development could eventually lead to faster and more accessible gut-health testing. Indole-3-propionic acid (IPA) is a metabolite produced by gut bacteria during the breakdown of dietary tryptophan, an amino acid essential for protein synthesis. It plays an important role in regulating inflammation and oxidative stress, and has been associated with conditions such as inflammatory bowel disease (IBD), Type 2 diabetes, and liver disease. However, current detection methods rely on traditional mass spectrometry-based analytical techniques, which are costly and time-consuming, making it impractical for routine screening or point-of-care use.The new platform addresses a longstanding gap in gut metabolite sensing. Using a fluorescence-based approach, the sensor produces a rapid optical readout within minutes, offering a significantly faster and more accessible alternative to conventional analytical techniques. It demonstrates high selectivity, distinguishing IPA from closely related metabolites commonly found in the gut, which enables accurate detection even in complex biological environments such as blood serum.“This is the first time we are able to directly and rapidly measure IPA levels in biological samples using an optical nanosensor,” says co-first author Mervin Ang, assistant professor at the National Institute of Education (NIE) within Nanyang Technological University in Singapore, who was also associate scientific director at the Disruptive and Sustainable Technologies for Agricultural Precision (DiSTAP) interdisciplinary research group within the Singapore-MIT Alliance for Research and Technology (SMART) when the research was initiated. “This novel approach, which moves away from traditional mass spectrometry, can pave the way towards faster and more accessible ways of monitoring gut health in real-world settings.”This latest breakthrough is described in the research team’s open-access paper, “Fluorescent Nanosensor for Indole-3-Propionic Acid Detection in Gut Health Monitoring,” in the journal Advanced Healthcare Materials. The work was led by researchers at NIE, MIT, and SMART, in collaboration with clinicians from the National University Hospital (NUH) and Yong Loo Lin School of Medicine within the National University of Singapore (NUS Medicine). From monitoring plants to sensing human healthThe new nanosensor builds on SMART DiSTAP’s research into nano and optical sensor technologies. Originally developed to monitor plant health — including plant growth signals and stress responses —  the technology has now been adapted for human health applications by redesigning the nano- and optical-sensing platform to detect IPA.“This work builds on technology at SMART DiSTAP on molecular recognition. We have used techniques like this to measure hormones and metabolites in living plants for agriculture, and have now applied it to the human gastrointestinal system. We were able to apply it to this long-standing challenge in gut health,” says Michael Strano, SMART DiSTAP lead principal investigator, the Carbon P. Dubbs Professor of Chemical Engineering at MIT, and corresponding author. “By focusing our molecular recognition on this important gut health biomarker, we’ve demonstrated a powerful new tool that could one day enable proactive, personalized health care. The tool promises near-instant insights into gut wellness, or the status of chronic diseases like IBD.”A dual-mode platform for rapid testing and future monitoringA key innovation of the technology is its dual-mode sensing capability. The nanosensor operates in both a visible fluorescence mode, enabling rapid, low-cost, high-throughput screening of biological samples; and a near-infrared mode, with wavelengths that can penetrate deeper into tissues. The near-infrared capability, enabled by carbon nanotubes, allows the technology to be adapted for in vivo applications and integration into wearable devices that could be used for home-based testing or continuous monitoring. This could, for example, help patients with chronic conditions like IBD detect flare-ups earlier and manage their health with greater autonomy. This flexibility allows the platform to be utilized in various environments, from laboratory tests to hospital bedside use, and wearable devices for real-time health monitoring. Validated in patient samplesTo evaluate its clinical relevance, the research team collaborated with NUH clinicians to test the nanosensor on 125 human plasma samples across multiple patient groups, including healthy individuals and those with gastrointestinal diseases.The study revealed significant differences in IPA levels between healthy individuals and patients with inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis. Patients with active gut inflammation showed lower IPA levels — consistent with established clinical findings.“From a clinical perspective, having a rapid and minimally complex way to assess metabolite levels like IPA could be very valuable,” says Jonathan Lee, senior consultant in the Division of Gastroenterology and Hepatology within the Department of Medicine at NUH; adjunct associate professor at NUS Medicine; and co-first author of the work. “It has the potential to complement existing diagnostic tools and provide additional insights into patients with inflammatory bowel diseases.”Faster, more accessible gut health testingBeyond the laboratory, this research could pave the way for faster and more accessible gut health testing. Instead of relying on complex and time-intensive laboratory methods, the new nanosensor could enable rapid screening in clinics, or even portable or home-based testing, helping to detect gut diseases earlier and monitor treatment progress more easily.Unlike conventional microbiome tests that focus on identifying which bacteria are present, this nanosensor measures what those microbes are actively producing, offering a more direct and functional snapshot of gut health. Directly measuring metabolite output, rather than bacterial composition alone, could provide more meaningful insights into overall health and support more personalized approaches to health care. Beyond clinical diagnostics, the technology can be used to track the immediate efficacy of dietary interventions. Users can see rapidly if specific foods or probiotics are successfully fueling their gut bacteria to produce anti-inflammatory molecules like IPA. The sensor also demonstrated reliable performance in complex biological fluids such as serum and plasma, an important step toward real-world clinical deployment and further translational applications. For pharmaceutical and therapeutic research, the nanosensor could be used to conduct rapid functional tests to determine the efficacy of new therapeutics or probiotics. By providing an instant readout of IPA levels, the platform could enable them to demonstrate in real time that their therapeutics are biologically active and effective, significantly accelerating drug screening and dosage optimization processes.Toward point-of-care diagnostics, and beyond“The transition from laboratory discovery to a point-of-care clinical tool is already underway,” says Ang. “With further development, the platform has the potential to be translated into clinical applications, and in the long term, adapted into portable platforms for routine health monitoring.”Looking ahead, the research team has been awarded an Innovation to Startup Innovation Grant to incubate a Singapore proto-startup to advance validation and development. The focus would be to translate the sensor into a point-of-care clinical diagnostic tool, and aim to expand the platform to detect multiple gut metabolites simultaneously and AI-driven signal deconvolution, enabling more accurate, comprehensive and personalized gut health monitoring. Future developments may also explore integration into wearable devices, microneedle systems, or microfluidic platforms for continuous, real-time sensing.The research was supported by the Intra-CREATE Seed Collaboration Grant, and research conducted at SMART was supported by the National Research Foundation Singapore under its Campus for Research Excellence and Technological Enterprise (CREATE) program.