The human brain remains mysterious, and any progress towards solving that mystery may bring enormous benefits. For one thing, millions of people are afflicted with brain disorders that today are poorly understood and often difficult to treat.

How much light could be shed if we had a technology for making chemical “movies” of brain activity, showing “frame” by “frame” how brain chemistry changes over time—for example, during an epileptic seizure, or in response to delivery of a drug?

Since 2018, Yurii Vlasov has led a team that is striving to answer that question under NIH BRAIN Initiative® (“Brain Research Through Advancing Innovative Neurotechnologies”) funding. They have just received a second, $3.2 million BRAIN grant to build on the success of their previous 3-year BRAIN-funded effort, bringing the total NIH investment in this promising neural probe technology to $6M.

Vlasov explains that “the approach we’ve taken is making the implantable neural probes that are used to analyze the chemical content of the brain much, much smaller than usual. We are decreasing the size of all the components significantly, for three reasons.”

First, the smaller a neural probe is, the less damage it causes when inserted into the brain. Second, the envisioned tiny device would offer unprecedented sensitivity, minimizing the number of molecules that must be gathered to determine what chemical events happened in the brain. Finally, the device would collect chemical samples that are precisely time-stamped, so it can record sequences of rapid changes in the concentrations of various chemicals.

Vlasov notes that it’s tricky to optimize all three parameters in the same device. “That’s where engineering has come in; we need to engineer a system that can simultaneously satisfy all those three requirements. Engineering trade-offs in the system design are needed.”

The idea is to build a system-on-a-chip that collects minute chemical samples from the brain of an awake, active animal and uses microfluidics to separate the chemicals into different compartments in which time is also tracked. The time information will be used to correlate the chemical events with external events, such as behaviors of the animal or introduction of a medication.

Under the initial 3-year BRAIN grant, “we developed parts and pieces of this technology,” says Vlasov. For example, “we demonstrated that silicon microfabrication technology enables scaled microfluidic channels with the very small cross-section... [and] we can separate the analyte into individual time-stamped compartments.” The new project will integrate these separate devices and subsystems into a single system that can be deployed for use in neuroscience and neurobiology research. The team will test the performance of the integrated probes on mice.

Translation to larger animals, and eventually to human medical applications, will be left to future work.

The project has demanded breakthroughs in areas ranging from silicon micro/nanofabrication and microelectronics manufacturing to microfluidics and sensitive chemical methods. Because of that need for transdisciplinary collaboration, Vlasov and his co-PIs hail from a range of UIUC units. Vlasov is the John Bardeen Endowed Chair in Electrical & Computer Engineering and Physics; Rashid Bashir (CGD, M-CELS) is the Grainger Distinguished Chair in Engineering and a professor of Bioengineering; Martha Gillette (M-CELS Affiliate – GNDP) is Alumni Professor of Cell & Developmental Biology and director of the Neuroscience Program; Catherine Christian-Hinman is an associate professor of Molecular & Integrative Physiology; and Jonathan Sweedler (MMG, CABBI Affiliate – BSD) is the James R. Eiszner Family Endowed Chair in Chemistry.

“Engineering can have a strong say in... understanding of brain function and disease,” says Vlasov.

He adds that there’s strong interest in neuroengineering among students, and that UIUC’s Bioengineering department is launching a new undergraduate program in Neuroengineering. He has contributed by developing a new course (ECE 421/NE 420, “Neural Interface Engineering”), which he will teach for the first time in Fall 2022.