July 21, 2026 | Indole-3-propionic acid (IPA) is increasingly recognized as a critical chemical shield and promising biomarker for gut inflammation. Levels of IPA are starkly deficient in the blood of patients with active ulcerative colitis (UC), but the gold standard measurement technique of liquid chromatography-mass spectrometry (LC-MS) is costly and requires highly trained technicians to run the equipment, limiting its use to specialized research cohorts and clinical trials, according to Mervin Ang, assistant professor at the National Institute of Education, part of Nanyang Technological University in Singapore.
These limitations have been resolved with a fluorescent nanosensor platform designed with two complementary optical modalities, one operating in the near-infrared (NIR) spectrum and the other in the visible light spectrum, says Michael Strano, Ph.D., professor of chemical engineering at MIT and lead principal investigator for the Disruptive & Sustainable Technologies for Agricultural Precision program of the Singapore-MIT Alliance for Research and Technology. The technology thereby has potential for in vivo tissue monitoring as well as rapid ex vivo testing of biological samples like blood plasma or serum in the clinic, as described in a research paper that was published recently in Advanced Healthcare Materials (DOI: 10.1002/adhm.202503434).
In this latest study, the sensor successfully and rapidly distinguished between blood samples from healthy individuals and those with active Crohn's disease or UC based purely on differing levels of IPA, Ang reports. Patients all maintained their normal, everyday diet and were not taking tryptophan supplements that can increase IPA levels.
Circulating levels of IPA are known to be heavily influenced by diet, with foods rich in dietary fiber and polyphenols (e.g., the Mediterranean diet) providing a boost while Western dietary patterns and high consumption of refined carbs driving down production. Low levels of the beneficial metabolite have been heavily implicated with a higher risk of type 2 diabetes and non-alcoholic fatty liver disease, says Ang, pointing to the “immense potential” to expand application of the nanosensor platform in future studies.
In this case, the polymer also, on its own, “self-assembles into polymeric nanoparticles that exhibit a highly selective fluorescent response to the IPA analyte in the visible region,” says Strano. “We have essentially engineered a single material that independently detects the exact same biomarker through two entirely different chemical mechanisms and optical channels simultaneously.”
Development of an optical nanosensor for a complex biological environment comes with several design hurdles, says Strano. Chief among these is that the sensor must be engineered to detect a molecule at low physiologically relevant concentrations and trigger a noticeable change in fluorescence once it binds to a target molecule.
“To find the perfect match, we have to run high-throughput screening libraries to isolate a candidate with the exact right sensitivity and specificity,” Strano says. “Furthermore, IPA is a relatively emerging biomarker that has only recently become highly relevant in clinical gut health,” which speaks to the timeliness of the novel diagnostic platform to complement LC-MS.
The backstory here is that the research team was originally screening a massive library of materials to find a sensor for auxin (IAA), a vital plant hormone used as an indicator of crop health which, chemically speaking, is “nearly identical” to the human gut biomarker IPA, says Strano. They differ in molecular structure by a single carbon group.
“When we analyzed our CoPhMoRe sensor library screening results, we noticed that interestingly, one specific corona unexpectedly performed much better at detecting the human biomarker IPA, which is comparatively irrelevant to plants,” he continues. “Once we learned about IPA’s clinical implications for human gut health, we subsequently initiated a collaboration with clinical researchers at NUS Medicine [National University of Singapore Yong Lee Lin School of Medicine] to evaluate its effectiveness in human blood samples.”
The “true beauty” of the nanosensor platform is that it requires minimal refinement, says Strano. “Plant cellular environments are also incredibly complex, so our sensor platform is already functional in noisy environments. While the human blood serum/plasma matrix does initially dampen the sensor’s baseline signal, our testing proved that when IPA is introduced, the sensor still triggers a distinct, highly visible change in fluorescence. It retains its functionality perfectly, even inside the complex human blood matrix.”
In the clinic, the fluorescent nanosensor could soon find utility in diagnosing gut inflammation early and precisely monitor how well a patient is responding to a treatment, says Strano. “It has promising potential for tracking dietary interventions, too,” he adds. “Instead of waiting weeks to see if a new probiotic, prebiotic, or medical diet is actually improving your gut health, this sensor could give patients and clinicians an objective assessment in near real-time to guide personalized gut healthcare.”
The underlying optical nature of the platform opens some “fascinating long-term avenues” as well, Strano says. “Because NIR light can safely pass through human tissue, the technology could theoretically be adapted in the future for wearable diagnostic patches or specialized internal monitoring devices to track chronic diseases continuously.”
Moving forward, the research team will be looking beyond IPA to “build an array of sensors capable of detecting critical gut metabolites simultaneously,” says Ang. “The gut microbiome is incredibly complex, and a single marker only tells part of the story.”
Thanks to a newly secured Innovation to Startup grant, funded by the Singapore government, the immediate next step is “translating this breakthrough from a laboratory success into a commercial, clinic-ready tool,” Ang shares. “This new phase will continue using the exact same robust nanosensor platform we developed in this IPA sensor study.”
The funding will allow the nanosensor array to be paired with machine learning algorithms that help in multiplexed sensor signal deconvolution to increase the diagnostic accuracy realized with the single IPA sensor, he explains. “The optical modulations will also be translated to a clear actionable gut health profile, following rigorous clinical validation with our clinical research partners, paving the way for our upcoming commercial spin-off strategy.”
This is “a powerful example of how nanotechnology can bridge completely different worlds,” Strano emphasizes. “By taking engineering principles and design approaches originally meant for plant biology and applying them to human health, we are opening up an entirely new frontier of personalized, real-time healthcare.”