Schematic of the fluorescent nanosensor platform showing rapid detection of indole-3-propionic acid (IPA) and differentiation between healthy and diseased samples. (Photo: NIE/NTU)

Researchers from the National Institute of Education, Nanyang Technological University (NIE NTU) Singapore, and the Singapore- Massachusetts Institute of Technology (MIT) Alliance for Research and Technology (SMART) in collaboration with clinicians from the National University Hospital (NUH) and Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), have developed a new fluorescent nanosensor capable of rapidly detecting indole-3-propionic acid (IPA), an emerging biomarker linked to gut health and disease.

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 mass spectrometry-based analytical techniques that are costly and time-consuming, making them impractical for routine screening or point-of-care use.

Pioneering optical nanosensor for IPA detection

The newly developed platform is the first reported optical nanosensor specifically designed to detect IPA, addressing a long-standing gap in gut metabolite sensing. Using a fluorescence-based approach, the sensor produces a rapid optical readout within minutes, providing a significantly faster and more accessible alternative to conventional analytical techniques.

The nanosensor demonstrates high selectivity, distinguishing IPA from closely related metabolites commonly found in the gut. This enables accurate detection even in complex biological environments such as blood serum.

According to Assistant Professor Mervin Ang of NIE, who is a co-first author and was formerly Associate Scientific Director at SMART DiSTAP when the research began, the technology represents the first direct and rapid optical measurement of IPA levels in biological samples. He explained that moving beyond traditional mass spectrometry could lead to faster and more accessible approaches for monitoring gut health in real-world settings.

From agricultural sensing to human health

The breakthrough nanosensor, which was detailed in the paper , Fluorescent Nanosensor for Indole-3-Propionic Acid Detection in Gut Health Monitoring, published in Advanced Healthcare Materials, builds on research conducted by SMART’s Disruptive & Sustainable Technologies for Agricultural Precision (DiSTAP) interdisciplinary research group. Originally developed to monitor plant health, including plant growth signals and stress responses, the technology was adapted for human health applications by redesigning the nano- and optical-sensing platform to detect IPA.

Professor Michael Strano, SMART DiSTAP Lead Principal Investigator and Carbon P. Dubbs Professor of Chemical Engineering at MIT, stated that the technology originated from molecular recognition techniques previously used to measure hormones and metabolites in living plants. Applying these techniques to the human gastrointestinal system enabled researchers to address a long-standing challenge in gut health monitoring.

Strano added that focusing molecular recognition on IPA had demonstrated a promising tool that could eventually support proactive and personalized healthcare by providing near-instant insights into gut wellness and chronic disease status, including IBD.

Dual-mode sensing capability

A key innovation of the technology is its dual-mode sensing capability. The nanosensor operates in a visible fluorescence mode, enabling rapid, low-cost, and high-throughput screening of biological samples. It also functions in a near-infrared mode, with wavelengths capable of penetrating deeper into tissues.

This near-infrared capability creates opportunities for in vivo applications and integration into wearable devices for home-based testing or continuous monitoring. Such applications could help patients with chronic conditions, including IBD, detect flare-ups earlier and manage their health more independently.

The platform’s flexibility enables use in a variety of settings, ranging from laboratory testing and hospital bedside diagnostics to wearable devices for real-time health monitoring.

Clinical validation

To assess its clinical relevance, the research team collaborated with clinicians from NUH to evaluate the nanosensor using 125 human plasma samples from multiple patient groups, including healthy individuals and patients 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 experiencing active gut inflammation exhibited lower IPA levels, consistent with established clinical findings.

Adjunct Associate Professor Jonathan Lee, Senior Consultant in the Division of Gastroenterology and Hepatology at NUH and NUS Medicine and a co-first author of the study, indicated that a rapid and minimally complex method for assessing metabolites such as IPA could be highly valuable in clinical settings. He suggested that the technology could complement existing diagnostic tools and provide additional insights into patients with inflammatory bowel diseases.

Potential for personalized healthcare

The research may pave the way for faster and more accessible gut health testing. Rather than relying on complex and time-intensive laboratory methods, the nanosensor could support rapid screening in clinics and potentially enable portable or home-based testing. Such capabilities may facilitate earlier disease detection and simplify treatment monitoring.

Unlike conventional microbiome tests that focus on identifying which bacteria are present, the nanosensor measures what those microbes are actively producing. This provides a more direct and functional assessment of gut health. Measuring metabolite output rather than bacterial composition alone may generate more meaningful insights into overall health and support personalized healthcare strategies.

Broader applications

Apart from clinical diagnostics, the technology could be used to evaluate the immediate effectiveness of dietary interventions. Users may be able to determine quickly whether specific foods or probiotics are promoting the production of anti-inflammatory molecules such as IPA.

The sensor also demonstrated reliable performance in complex biological fluids, including serum and plasma, marking an important step toward clinical deployment and broader translational applications.

In pharmaceutical and therapeutic research, the nanosensor could facilitate rapid functional testing of new therapeutics and probiotics. By providing immediate IPA measurements, the platform may allow researchers to confirm biological activity and effectiveness in real time, potentially accelerating drug screening and dosage optimization.

Assistant Professor Ang shared that the transition from laboratory discovery to a point-of-care clinical tool is already underway. With further development, the platform could be translated into clinical applications and, over the longer term, adapted into portable systems for routine health monitoring.