Novel Fluorescent Nanosensor Enables Rapid, First-of-Its-Kind Detection of Gut Health Biomarker IPA
Key Insights
Researchers from NIE NTU Singapore, SMART, MIT, NUH, and NUS Medicine developed the first optical nanosensor specifically designed to detect indole-3-propionic acid (IPA), a key gut health biomarker.
The dual-mode platform operates in visible fluorescence for rapid screening and near-infrared for potential in vivo and wearable applications, delivering results within minutes.
Validated in 125 human plasma samples, the sensor revealed significantly lower IPA levels in patients with active inflammatory bowel disease (search), including Crohn's disease (search) and ulcerative colitis (search).
A collaborative research team spanning Singapore and the United States has developed a first-of-its-kind fluorescent nanosensor capable of rapidly detecting indole-3-propionic acid (IPA), an emerging biomarker intimately linked to gut health and disease. The breakthrough, published in Advanced Healthcare Materials, represents the first reported optical nanosensor specifically designed to detect IPA, addressing a long-standing gap in gut metabolite sensing.
The sensor was developed by researchers from the National Institute of Education, Nanyang Technological University, Singapore (NIE NTU, Singapore) and the Singapore-MIT Alliance for Research and Technology (search) (SMART), in collaboration with clinicians from the National University Hospital (NUH) and the Yong Loo Lin School of Medicine at the National University of Singapore (NUS Medicine).
"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," said Professor Michael Strano, SMART DiSTAP Lead Principal Investigator, 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 healthcare."
A Dual-Mode Platform for Rapid Testing and Future Monitoring
A key innovation of the technology is its dual-mode sensing capability. The nanosensor operates in a visible fluorescence mode, enabling rapid, low-cost, high-throughput screening of biological samples. Simultaneously, it offers a near-infrared mode with wavelengths that can penetrate deeper into tissues, allowing the technology to be adapted for in vivo applications and integration into wearable devices for home-based testing or continuous monitoring.
This flexibility positions the platform for use across diverse environments, from laboratory tests to hospital bedside use and wearable devices for real-time health monitoring. The sensor produces a rapid optical readout within minutes, offering a significantly faster and more accessible alternative to conventional mass spectrometry-based analytical techniques, which are costly and time-consuming.
Validated in Patient Samples
To evaluate clinical relevance, the research team partnered 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 (search) and ulcerative colitis (search). 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," said Adjunct Associate Professor Jonathan Lee, Senior Consultant, Division of Gastroenterology and Hepatology, Department of Medicine, NUH and NUS Medicine, and co-first author. "It has the potential to complement existing diagnostic tools and provide additional insights into patients with inflammatory bowel diseases."
Faster, More Accessible Gut Health Testing
Unlike conventional microbiome tests that focus on identifying which bacteria are present, the nanosensor measures what those microbes are actively producing, offering a more direct and functional snapshot of gut health. IPA is a metabolite produced by gut bacteria during the breakdown of dietary tryptophan and plays an important role in regulating inflammation and oxidative stress. It has been associated with conditions such as inflammatory bowel disease (search) (IBD), type 2 diabetes (search), and liver disease (search).
Beyond clinical diagnostics, the technology can track the immediate efficacy of dietary interventions, allowing users to see rapidly if specific foods or probiotics are successfully fueling 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.
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 researchers to demonstrate in real-time that their therapeutics are biologically active and effective, significantly accelerating drug screening and dosage optimization processes.
Towards Point-of-Care Diagnostics
"The transition from laboratory discovery to a point-of-care clinical tool is already underway," said Assistant Professor 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.
The research team has been awarded an Innovation to Startup (I2Start) Innovation Grant to incubate a Singapore proto-startup to advance validation and development. The focus will be to translate the sensor into a point-of-care clinical diagnostic tool, with plans to expand the platform to detect multiple gut metabolites simultaneously and incorporate 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) programme.