Key takeaways
- A UCLA-led team has developed an advanced sensor platform that measures metabolites — key molecules involved in sustaining life through metabolism — inside the body in real time.
- By mimicking natural metabolic pathways and using biological molecular toolkits, the sensors can track thousands of metabolites, far beyond the small set detectable by traditional sensors, while simplifying the technology development process.
- This advance opens up new possibilities for diagnosing and managing disease, developing new drugs and unlocking deeper insights into how biological systems function.
Life's essential functions are powered by a set of compounds called metabolites, which are involved in every natural process including producing energy, regulating cell activity and keeping the body's systems in balance. Tracking these molecules offers a window into the onset and status of many diseases, overall health, response to treatment and the intricate workings of biological systems.
However, today's metabolite sensing methods fall short. Most rely on resource-intensive lab tests that give only brief snapshots from isolated samples. The few sensors that can track metabolites continuously are largely limited to detecting blood sugar.
An interdisciplinary research team led by the California NanoSystems Institute at UCLA, or CNSI, may have overcome these limitations. In a recent study published in the Proceedings of the National Academy of Sciences, the researchers demonstrated a sensor technology based on natural biochemical processes that was able to continuously and reliably measure multiple metabolites at once from a wide range of options.
"To understand how metabolites affect biological processes or reflect health, we need to monitor different groups of metabolites based on our specific interest," said senior corresponding author Sam Emaminejad, an associate professor of electrical and computer engineering at the UCLA Samueli School of Engineering and a CNSI member. "So we aimed to develop a sensor platform that can be applied to a wide range of metabolites while ensuring reliable operation in the body — and for that, we tapped into natural metabolic processes."
He views this technology not as a replacement for current lab-based methods such as mass spectrometry, but as a complementary tool. Scientists could continue to use mass spectrometers for identifying potential compounds of interest and then use the sensor to monitor them in living systems.
Sensors trigger chemical reactions to broaden the menu of metabolites detected
The sensors are built onto electrodes made of tiny cylinders called single-wall carbon nanotubes. These electrodes function like miniature biochemistry labs, using enzymes and helper molecules called cofactors to perform reactions that mirror the body's metabolic processes. Depending on the target metabolite, the sensors either detect it directly or first convert it into a detectable form through a chain of intermediary enzymatic reactions.
Detection works through enzymes that specifically catalyze electron-exchanging reactions. On the electrodes' surface, these reactions generate an electrical current that can be measured to determine metabolite levels. Meanwhile, other enzymes work in parallel to prevent false signals by neutralizing interfering molecules, much like how enzymes detoxify substances in our bodies.
To reflect this ability to run multiple reactions in sequence and parallel, the research team is calling their technology "tandem metabolic reaction-based sensors," or TMR sensors for short.
"Decades of research have mapped natural metabolic pathways linking metabolites to specific enzymatic reactions," Emaminejad said. "By adapting carefully selected enzymes and cofactors for different functions, our electrodes replicate these complex reactions, enabling reliable detection of a far broader set of metabolites than conventional sensors. The robustness comes from evolution itself — enzymes and cofactors, refined over tens of millions of years, are highly sensitive, specific, and stable. We're harnessing nature's own blueprint and molecular machinery to track the very biochemical processes they sustain."
Traditional enzymatic sensors mostly support single-step reactions without cofactors. By incorporating cofactors, TMR sensors can directly detect over 800 metabolites and, with just one conversion step, cover more than two-thirds of the body's metabolites.
"The TMR electrode has additional special features for high-performance biosensing," said Xuanbing Cheng, the study's co-first author and a UCLA postdoctoral scholar at Emaminejad's Interconnected and Integrated Bioelectronics Lab. "Made from single-wall carbon nanotubes, it offers a large active area for loading enzymes and cofactors. Reactions occur efficiently at low voltage, reducing undesired side reactions while maximizing the utility of enzyme activity. This allowed us to achieve exceptionally high signal-to-noise ratio measurements across a wide range of applications."
In a series of experiments, the investigators demonstrated the technology's ability to measure continuously and with high sensitivity a sample set of 12 clinically important metabolites. The team measured metabolites in sweat and saliva samples from patients receiving treatment for epilepsy and from individuals with conditions resembling diabetes complications. The researchers also detected a gut bacteria-derived metabolite in the brain that could cause neurological disorders if it accumulates.
Potential applications of metabolite sensors for health, research and industry
The sensors' ability to track a wide range of metabolites across different biological settings opens new doors for human health and scientific discovery. They could transform care for metabolic and cardiovascular disorders by enabling early, precise diagnoses and tailoring treatments to an individual's unique metabolic profile. The technology could also optimize fitness and athletic performance by tracking how the body metabolizes energy under different conditions.
In drug development, the sensors could provide real-time insights into how therapies influence metabolic pathways — from evaluating cancer drugs that block tumor growth by inhibiting enzyme activity to tracking bacterial metabolite production to optimize antibiotics.
Beyond medicine, these sensors could support industrial processes by delivering continuous feedback to improve the yield and efficiency of engineered microbes used to produce pharmaceuticals, biofuels and other valuable chemicals.
Among the many possibilities, Emaminejad is particularly excited about the technology's potential to help unravel the gut-brain connection — an emerging frontier in biomedical research. The team is now focused on adapting their platform to tackle unanswered research questions and pursue new diagnostic opportunities.
"A major challenge in understanding how the gut and brain influence each other is capturing changes over time," he said. "A tool that tracks metabolites continuously, rather than relying on single lab measurements, could help reveal this two-way communication. We're finally equipped to test important hypotheses that lacked key data — helping us better understand how gut activity impacts overall health, from driving inflammation and affecting mental well-being to shaping chronic disease progression."
The other co-first authors are UCLA graduate students Zongqi Li and Jialun Zhu from Emaminejad's lab. Stanford biochemist Ronald Davis is a co-corresponding author. Other senior authors are Hilary Coller, a UCLA professor of molecular, cell and developmental biology and of biological chemistry; CNSI member Elaine Hsiao, a UCLA associate professor of integrative biology and physiology; Daniel Lu, a UCLA professor of neurosurgery; CNSI member Chong Liu, a UCLA professor of chemistry and biochemistry; pediatric nurse practitioner Beck Reyes and pediatric neurologist Joyce Matsumoto, both of UCLA Health; and Stanford pediatric pulmonologist Carlos Milla.
The study was funded by the National Institutes of Health, the Elisabeth K. Harris Foundation Trust, the Louis and Harold Price Foundation, the H&H Evergreen Foundation and the Jonathan and Susan Dolgen Foundation.
