West LA Times

A team led by UCLA has developed a sensor platform capable of measuring metabolites in real-time within the body. These metabolites are essential molecules involved in metabolism, crucial for life-sustaining processes. By mimicking natural metabolic pathways and utilizing biological molecular toolkits, the new sensors can track thousands of metabolites, surpassing traditional sensors' capabilities.

Metabolites play a role in energy production, cell activity regulation, and maintaining bodily balance. Monitoring these molecules can provide insights into disease onset, health status, treatment responses, and biological systems' workings. However, current metabolite sensing methods are limited to brief snapshots from isolated samples or continuous tracking of only blood sugar.

The interdisciplinary research team from the California NanoSystems Institute at UCLA (CNSI) introduced a sensor technology based on natural biochemical processes that continuously measures multiple metabolites simultaneously. The study was published in the Proceedings of the National Academy of Sciences.

“To understand how metabolites affect biological processes or reflect health, we need to monitor different groups of metabolites based on our specific interest,” said Sam Emaminejad, senior corresponding author and associate professor at UCLA's Samueli School of Engineering. He added that this technology complements existing lab-based methods like mass spectrometry by allowing scientists to monitor compounds in living systems.

The sensors use electrodes made from single-wall carbon nanotubes functioning as miniature biochemistry labs. They employ enzymes and cofactors to perform reactions mirroring the body's metabolic processes. Depending on the target metabolite, detection occurs directly or through intermediary enzymatic reactions.

“Decades of research have mapped natural metabolic pathways linking metabolites to specific enzymatic reactions,” Emaminejad explained. “By adapting carefully selected enzymes and cofactors for different functions, our electrodes replicate these complex reactions.” This approach enables reliable detection of more than 800 metabolites with just one conversion step covering over two-thirds of the body's metabolites.

Xuanbing Cheng, co-first author and postdoctoral scholar at Emaminejad’s lab at UCLA, noted that using single-wall carbon nanotubes provides a large active area for enzyme loading while reducing undesired side reactions.

The researchers demonstrated high sensitivity measurements across various applications through experiments involving sweat and saliva samples from patients with epilepsy treatments or conditions resembling diabetes complications. They also detected a gut bacteria-derived metabolite in the brain potentially linked to neurological disorders if accumulated.

These sensors offer potential applications in healthcare by enabling early diagnoses for metabolic disorders or optimizing fitness performance tracking energy metabolism under different conditions. In drug development settings too — providing real-time insights into therapies influencing metabolic pathways such as cancer drugs inhibiting tumor growth via enzyme activity inhibition — they could prove invaluable beyond medicine supporting industrial processes improving yield efficiency engineered microbes producing pharmaceuticals biofuels other valuable chemicals alike among many possibilities Emaminejad expressed excitement about unraveling gut-brain connection emerging frontier biomedical research focusing adapting platform tackle unanswered questions pursue new diagnostic opportunities ahead

“A major challenge understanding how gut brain influence each other capturing changes over time,” he said “A tool tracks continuously rather than relying single lab measurements could help reveal two-way communication equipped test important hypotheses lacked key data helping better understand impacts overall health driving inflammation affecting mental well-being shaping chronic disease progression”

Co-first authors include UCLA graduate students Zongqi Li Jialun Zhu Emaminejad’s lab Stanford biochemist Ronald Davis co-corresponding author Other senior authors Hilary Coller professor molecular cell developmental biology biological chemistry CNSI member Elaine Hsiao integrative physiology Daniel Lu neurosurgery Chong Liu chemistry biochemistry pediatric nurse practitioner Beck Reyes neurologist Joyce Matsumoto both Health pulmonologist Carlos Milla Study funded National Institutes Health Elisabeth K Harris Foundation Trust Louis Harold Price H&H Evergreen Jonathan Susan Dolgen