Implantable aptamer-field-effect transistor neuroprobes for in vivo neurotransmitter monitoring

Chuanzhen Zhao; Kevin M Cheung; I-Wen Huang; Hongyan Yang; Nako Nakatsuka; Wenfei Liu; Yan Cao; Tianxing Man; Paul S Weiss; Harold G Monbouquette; Anne M Andrews

doi:10.1126/sciadv.abj7422

Implantable aptamer-field-effect transistor neuroprobes for in vivo neurotransmitter monitoring

Sci Adv. 2021 Nov 26;7(48):eabj7422. doi: 10.1126/sciadv.abj7422. Epub 2021 Nov 24.

Authors

Chuanzhen Zhao^{1

2}, Kevin M Cheung^{1

2}, I-Wen Huang^{2

3}, Hongyan Yang⁴, Nako Nakatsuka^{1

2}, Wenfei Liu^{1

2}, Yan Cao^{2

3}, Tianxing Man⁵, Paul S Weiss^{1

2

6

7}, Harold G Monbouquette^{2

3}, Anne M Andrews^{1

2

4}

Affiliations

¹ Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, Hatos Center for Neuropharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁶ Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁷ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Abstract

While tools for monitoring in vivo electrophysiology have been extensively developed, neurochemical recording technologies remain limited. Nevertheless, chemical communication via neurotransmitters plays central roles in brain information processing. We developed implantable aptamer–field-effect transistor (FET) neuroprobes for monitoring neurotransmitters. Neuroprobes were fabricated using high-throughput microelectromechanical system (MEMS) technologies, where 150 probes with shanks of either 150- or 50-μm widths and thicknesses were fabricated on 4-inch Si wafers. Nanoscale FETs with ultrathin (~3 to 4 nm) In₂O₃ semiconductor films were prepared using sol-gel processing. The In₂O₃ surfaces were coupled with synthetic oligonucleotide receptors (aptamers) to recognize and to detect the neurotransmitter serotonin. Aptamer-FET neuroprobes enabled femtomolar serotonin detection limits in brain tissue with minimal biofouling. Stimulated serotonin release was detected in vivo. This study opens opportunities for integrated neural activity recordings at high spatiotemporal resolution by combining these aptamer-FET sensors with other types of Si-based implantable probes to advance our understanding of brain function.

Grants and funding

R01 DA045550/DA/NIDA NIH HHS/United States