Healthcare (Commonwealth Union) – The fundamental processes that sustain life depend on a group of compounds known as metabolites. These molecules play a crucial role in generating energy, regulating cellular activity, and maintaining the body’s overall equilibrium. Monitoring metabolites provides valuable insights into disease progression, general health, treatment responses, and the complex mechanisms of biological systems.
Despite their importance, current methods for detecting metabolites have significant drawbacks. Most techniques rely on labor-intensive laboratory tests that offer only momentary glimpses from isolated samples. The limited number of sensors capable of continuous metabolite tracking primarily focus on measuring blood sugar.
A multidisciplinary team of researchers from the California NanoSystems Institute at UCLA (CNSI) may have developed a solution to these challenges. In a recent study published in the Proceedings of the National Academy of Sciences, they introduced a sensor technology inspired by natural biochemical processes, capable of consistently and accurately monitoring multiple metabolites simultaneously across a diverse range.
Sam Emaminejad, the senior corresponding author and associate professor of electrical and computer engineering at the UCLA Samueli School of Engineering, as well as a CNSI member pointed out that to fully grasp how metabolites influence biological functions or indicate health status, we must observe various groups of metabolites based on specific needs. He further indicated that their goal was to create a sensor platform adaptable to a broad spectrum of metabolites while maintaining dependable performance within the body—and to achieve that, they harnessed nature’s own metabolic pathways.
He does not see this technology as a substitute for traditional lab-based techniques like mass spectrometry but rather as a complementary tool. Scientists could still rely on mass spectrometry to identify potential compounds of interest and then use the sensor to track those compounds within living systems.
These sensors are integrated into electrodes composed of microscopic cylinders known as single-wall carbon nanotubes. Acting as miniature biochemical laboratories, these electrodes use enzymes and cofactor molecules to carry out reactions that mimic the body’s metabolic functions. Depending on the specific metabolite being analyzed, the sensors either detect it directly or first transform it into a measurable form through a sequence of enzymatic reactions.
The detection process relies on enzymes that catalyze electron-exchange reactions. On the electrode surface, these reactions produce an electrical current, which is then measured to determine metabolite concentrations. At the same time, additional enzymes work to prevent false readings by neutralizing interfering molecules, much like how enzymes in the body detoxify harmful substances.
Because this technology can conduct multiple reactions both sequentially and in parralel, the research team has named it “tandem metabolic reaction-based sensors,” or TMR sensors for short.
“Decades of research have mapped natural metabolic pathways linking metabolites to specific enzymatic reactions,” explained Emaminejad. “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.”
Through a series of experiments, researchers showcased the technology’s capability to continuously and sensitively measure a set of 12 clinically significant metabolites. They analyzed metabolites in sweat and saliva samples from epilepsy patients undergoing treatment and individuals with conditions resembling diabetes-related complications. Additionally, the team identified a gut bacteria-derived metabolite in the brain, which, if accumulated, could contribute to neurological disorders.
The researchers stated that the ability of these sensors to monitor a diverse range of metabolites in various biological environments paves the way for advancements in healthcare and scientific research. They have the potential to revolutionize the management of metabolic and cardiovascular diseases by facilitating early, accurate diagnoses and enabling personalized treatment plans based on an individual’s metabolic profile. Furthermore, this technology could enhance athletic performance and fitness optimization by tracking how the body processes energy under different conditions.
