Brain probes for neurotransmitter monitoring

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A new type of implantable microprobe for in vivo neurotransmitter detection was developed by a team led by Professor Anne Andrews at UCLA. 

The paper titled “Implantable aptamer-field-effect transistor neuroprobes for in vivo neurotransmitter monitoring” was published in the November 24 issue of the journal Science Advances. Andrews is on the faculty of Psychiatry & Biobehavioral Sciences in the David Geffen School of Medicine and the College of Arts and Letters Department of Chemistry & Biochemistry. The lead authors are recent UCLA Chemistry doctoral alumni Dr. Chuanzhen Zhao and Dr. Kevin Cheung.

To investigate normal brain function and the underlying causes of neuropsychiatric and neurodegenerative disorders, scientists need to monitor neurotransmitter signaling over biologically relevant concentrations and timescales in behaving animals. Other neurotransmitter sensing strategies are limited in terms of temporal resolution or specificity. Moreover, for many neurotransmitters or neuromodulators, there are no methods available for in vivo monitoring.

Andrews Team 2021

Professors Anne Andrews and Paul Weiss, Dr. Chuanzhen Zhao, Dr. Kevin Cheung, Dr. Nako Nakatsuka, Wenfei Liu.

Andrews and coworkers designed and developed miniaturized sensors for neurotransmitters. The sensors are based on transistors, similar to common electronics, such as cell phones and computers. However, their sensors have DNA-based receptors that enable neurotransmitters to be uniquely identified. In the current publication, these sensors were fabricated on the same type of silicon microprobes that neuroscientists use for electrophysiological recordings. This study translates previous work from the Andrews’ group, on aptamer-field-effect transistor biosensors to in vivo applications. 

Neuroprobes outfitted with receptors for serotonin detected this neurotransmitter across physiologically relevant concentrations and under a variety of conditions. After neuroprobes were validated, a probe was implanted into the brain of a behaving mouse and serotonin was detected.

In addition to serotonin, the fabrication and sensing strategies are straightforward and can be generalized to other neurotransmitters paving the way for studies on the electronic detection of multiple neurotransmitters. Many transistors can be fabricated on the same neuroprobe; the sensing strategy has been demonstrated for the neurotransmitter dopamine, the amino acid phenylalanine, which is elevated in the neurodevelopmental disorder phenylketonuria (PKU), and blood glucose.

“Neurotransmitter neuroprobes are powerful tools for monitoring neurotransmitters in vivo, which is critical to advancing understanding of brain activity. We developed a high-throughput microfabrication process for nanoscale field-effect transistors on silicon, which is compatible with other silicon-based implantable probes for integrated neural activity recording,” said Zhao.

This work was carried out in collaboration with Professor Harold Monbouquette in the Department of Chemical Engineering, and Professor Paul Weiss in the Department of Chemistry & Biochemistry. Other coauthors of the study include UCLA Chemistry alumna Dr. Nako Nakatsuka and graduate student Wenfei Liu, as well as Dr. I-Wen Huang, Dr. Hongyan Yang, Yan Cao, and Dr. Tianxing Man.

About the Lead Authors

Professor Anne Milasincic Andrews leads basic and translational research on anxiety and depression at the nexus of neuroscience and nanoscience. She is a Fellow of the American College of Neuropsychopharmacology and the American Institute for Medical and Biological Engineering and is President of the International Society for Serotonin Research. Andrews has received an NIH Director’s Transformative Research Award, a California Neurotechnologies Research Award, a NARSAD Independent Investigator Award, an Eli Lily Outstanding Young Analytical Chemist Award, and an NIH Fellows Award for Research Excellence.

Dr. Chuanzhen Zhao, a Ph.D. graduate from the Department of Chemistry at UCLA under the mentorship of Professor Anne Andrews and Professor Paul Weiss, is the first author of the paper. Zhao is now a postdoctoral scholar in Professor Zhenan Bao’s group at Stanford University. His research interests focus on developing translational biosensors, including implantable neuroprobes and wearable devices, to monitor chemical signaling in and on the body. He recently received the MRS gold graduate student award, the Dimitris N Chorafas Foundation Award, a Dissertation Year Fellowship, and a Thomas and Ruth F. Jacobs Dissertation Award. Zhao has co-authored 24 peer-reviewed publications, including nine first-author papers in Science Advances, ACS Nano, Nano Letters, and iScience.

Dr. Kevin Cheung is a Materials Chemistry Ph.D. alumnus from the Andrews and Weiss groups. Cheung is a current postdoctoral fellow in Professor Hongkun Park’s lab at Harvard University. His current research involves investigating nano-bio interfaces, particularly neuroelectronic interfacing with CMOS electrode arrays.  

Article written by Dr. Kevin Cheung, Harvard,