Injectable Biosensors Convert Brain Activities into Detectable Optical Signals

Technology for monitoring neuronal activity noninvasively could allow scientists to study the brain without the need for surgery or implanted devices. The newly developed nanotechnology, called NeuroSWARM³ by its inventors at the University of California, Santa Cruz (UCSC), could even provide a bridge to more effective communication and interaction for those who are physically challenged.

“NeuroSWARM³ can convert thoughts (brain signals) to remotely measurable signals for high-precision brain-machine interfacing,” professor Ali Yanik said. “It will enable people suffering from physical disabilities to effectively interact with [the] external world and control wearable exoskeleton technology to overcome limitations of the body. It could also pick up early signatures of neural diseases.”

NeuroSWARM³ — short for neurophotonic solution-dispersible wireless activity reporters for massively multiplexed measurements — is made up of engineered electro-plasmonic nanoparticles that convert electrical signals in the brain to optical signals that can be tracked with an optical detector located outside the body. The “system on a nanoparticle,” which is similar in size to a viral particle, includes wireless powering, electrophysiological signal detection, and data broadcasting capabilities all in one device.

To enable contactless measurement of brain activity, the nanoparticles that make up NeuroSWARM³ are injected into the bloodstream or directly into the cerebrospinal fluid. Once in the brain, the nanoparticles are highly sensitive to local changes in the electric field and can function indefinitely without a power source or wires.

The nanoparticles consist of a silicon oxide (SiO₂) core measuring 63 nm across and a thin layer of electrochromically loaded poly (3, 4-ethylenedioxythiophene). A 5-nm-thick gold coating covers the nanoparticles and enables them to cross the blood-brain barrier.

The optical signals generated by the nanoparticles are detected using near-infrared light at wavelengths between 1000 and 1700 nm.

Experiments showed that in vitro prototypes of NeuroSWARM³ could generate a signal-to-noise ratio of over 1000 — a sensitivity level that is high enough to detect the electrical signal generated when a single neuron fires.

The researchers compare NeuroSWARM³ to a nanosize, electrochromically loaded plasmonic (electro-plasmonic) antenna operated in reverse. Its optical properties are modulated by the spiking electrogenic cells within its vicinity, rather than by a predefined voltage.

“We pioneered [the] use of electrochromic polymers — for example, PEDOT:PSS — for optical, wireless detection of electrophysiological signals,” Yanik said. “Electrochromic materials known to have optical properties that can be reversibly modulated by an external field are conventionally used for smart glass/mirror applications.”

Although other methods are available for tracking the brain’s electrical activity, most require surgery or implanted devices to penetrate the skull and interface directly with neurons.

A similar approach to NeuroSWARM³ uses quantum dots to respond to electrical fields. When the UCSC researchers compared the two technologies, they found that NeuroSWARM³ generated an optical signal that was four orders of magnitude larger than the quantum dot technology, and that the quantum dots required 10× higher light intensity and 100× more probes to generate an equivalent signal.

“We are just at the beginning stages of this novel technology, but I think we have a good foundation to build on,” Yanik said. “Our next goal is to start experiments in animals.”

The researchers presented NeuroSWARM³ at the virtual OSA Optical Sensors and Sensing Congress.