Scientists at Purdue University say they have built a small, flexible sensor that is faster and more precise than past attempts at tracking glutamate. The sensor, an implantable device on the spinal cord, is primarily a research tool for testing in animal models, but could find future clinical use as a way to monitor whether a drug for neurotrauma or brain disease is working.

The group’s study (“Facile fabrication of flexible glutamate biosensor using direct writing of platinum nanoparticle-based nanocomposite ink”) appears in a forthcoming issue of Biosensors and Bioelectronics.

implantable sensor
An implantable sensor has the speed and precision for tracking a brain chemical known to be elevated in certain brain diseases and after a spinal cord injury. [Purdue University image/Tran Nguyen]
“Glutamate excitotoxicity is a pathology in which excessive glutamate can cause neuronal damage and degeneration. It has also been linked to secondary injury mechanisms in traumatic spinal cord injury. Conventional bioanalytical techniques used to characterize glutamate levels in vivo, such as microdialysis, have low spatiotemporal resolution, which has impeded our understanding of this dynamic event. In this study, we present an amperometric biosensor fabricated using a simple direct ink writing technique for the purpose of in vivo glutamate monitoring,” write the investigators.

“The biosensor is fabricated by immobilizing glutamate oxidase on nanocomposite electrodes made of platinum nanoparticles, multi-walled carbon nanotubes, and a conductive polymer on a flexible substrate. The sensor is designed to measure extracellular dynamics of glutamate and other potential biomarkers during a traumatic spinal cord injury event.

“Here we demonstrate good sensitivity and selectivity of these rapidly prototyped implantable biosensors that can be inserted into a spinal cord and measure extracellular glutamate concentration. We show that our biosensors exhibit good flexibility, linear range, repeatability, and stability that are suitable for future in vivo evaluation.”

“When you feel like you’re running a fever, it doesn’t matter when you check your temperature—it will probably be the same for several hours. But a glutamate spike is so fast that if you don’t capture it at that moment, you miss the whole opportunity to get data,” said Riyi Shi, MD, PhD, a professor of neuroscience and biomedical engineering in Purdue’s department of basic medical sciences, College of Veterinary Medicine and Weldon School of Biomedical Engineering.

Impact, such as from a car accident or tackle in football, can injure the spinal cord, also injuring the nerve structures that transport glutamate, which sends signals to excite nerve tissue for performing functions such as learning and memorizing.

Damaged nerve structures mean that loads of glutamate leak out into spaces outside of cells, over-exciting and damaging them. Brain diseases, including Alzheimer’s and Parkinson’s, also show elevated levels of glutamate.

Devices so far either haven’t been sensitive enough to detect glutamate fast enough to capture its spike or affordable enough for long-term research projects, according to Shi.

Purdue researchers are addressing these issues through implantable sensors that they have 3D printed and laser-micromachined (processes that are already used regularly in the lab and industry).

“We wanted to create a low-cost and very fast way to build these sensors so that we can easily provide researchers with a means to measure glutamate levels in vivo,” said Hugh Lee, PhD, a Purdue assistant professor of biomedical engineering, who focuses on implantable microtechnologies.

The technique allows researchers to rapidly change the size, shape, and orientation of the sensors and then test in animal models without having to go through the more expensive process of microfabrication.

New sensor technology
New sensor technology implanted in animal models can help researchers understand the role that the brain chemical glutamate plays in neurotrauma, advising more specialized treatment. [Purdue University image/Tran Nguyen]
Measuring levels in vivo would help researchers to study how spinal cord injuries happen, as well as how brain diseases develop.

“How big of a problem is a migraine? Is too much glutamate really behind the pain, or is it that the system that cleans up glutamate is down?” Shi said.

The researchers implanted the device into the spinal cord of an animal model and then injured the cord to observe a spike. The device captured the spike immediately, whereas for current devices, researchers have had to wait 30 minutes to get data after damaging the spinal cord.

In the future, the researchers plan to create a way for the biosensors to self-clear of inflammatory cells that the body recruits to protect itself. These cells typically form a fibrous capsule around the biosensor, which blocks its sensitivity.

The technology could also allow for implanting more sensors along the spinal cord, which would help researchers to know how far glutamate spreads and how quickly.

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