Biosensors for determination of multiple neurotransmitters in vertebrate retina

Information

  • Research Project
  • 10300675
  • ApplicationId
    10300675
  • Core Project Number
    R21EY031405
  • Full Project Number
    1R21EY031405-01A1
  • Serial Number
    031405
  • FOA Number
    PA-20-195
  • Sub Project Id
  • Project Start Date
    9/1/2021 - 3 years ago
  • Project End Date
    8/31/2023 - a year ago
  • Program Officer Name
    WRIGHT, CHARLES BAKER
  • Budget Start Date
    9/1/2021 - 3 years ago
  • Budget End Date
    8/31/2022 - 2 years ago
  • Fiscal Year
    2021
  • Support Year
    01
  • Suffix
    A1
  • Award Notice Date
    7/30/2021 - 3 years ago
Organizations

Biosensors for determination of multiple neurotransmitters in vertebrate retina

Project Summary: The long-term goal of this project is to develop a paradigm-shifting neurosensing technology for direct, simultaneous monitoring of the activity of multiple neurotransmitters for understanding brain function. The retina is selected as our model system due to its easy accessibility and well-established neurophysiology and the urgent needs in such tool to understand the roles of neurotransmitters in various eye diseases such as diabetic retinopathy. Retinal photosensitive cells (rods and cones) convert light into an electrical signal. The electrical signal is transmitted through bipolar cells to ganglion cells, the output neurons of the retina, and then to the brain. Signal transmission through this pathway is modulated by amacrine cells, which are retinal interneurons. There are multiple types of amacrine cells, but all synthesize and release neuromodulators such as dopamine (DA), gamma-aminobutyric acid (GABA) and acetylcholine (ACh). Specifically, dopaminergic amacrine cells (DACs) co-release GABA and DA, which play a critical role in modulating retinal light sensitivity and eye development. Starburst amacrine cells co-release GABA and ACh, which initiates the motion direction of the visual system. Historically, the release of neurotransmitters from retinal neurons and amacrine cells has been studied indirectly, through electrophysiological methods and/or redox detection using electroanalytical techniques employing carbon fiber microelectrodes. However, electrical activity in a cell does not always match the release of neurotransmitter from the cell. Redox methods only work for a relatively small number of analytes such as DA. We have constructed a novel biosensor that employs complementary electrochemical and piezoelectric sensors, and our preliminary results show that it can differentiate between redox and non-redox active neurotransmitters. The objective of this R21 project is to develop a miniaturized multimodal biosensor to measure multiple neurotransmitters simultaneously with high spatial and temporal resolution in real time, label- and reagent-free with two Aims: 1. Design, fabrication, and characterization of a miniaturized multimodal electrochemical (E) and piezoelectric sensor (thin film bulk acoustic resonator (FBAR) (i.e. E-FBAR) neurosensing probe; and 2: Validation of the neurosensing probe through monitoring dopamine, GABA, and ACh in living normal and diabetic retinal neurons. Successful completion of this project will certify a reagent-free, label-free and real-time simultaneously detection of both redox active and non-redox active neurotransmitters in retina with multifaceted information in high sensitivity and selectivity. Such a tool will be invaluable to research aimed at understanding the causes and mechanisms responsible for retinal neurodegenerative diseases such as diabetic retinopathy, and also to test therapeutic agents for the treatment of such diseases. This novel technology could also be adapted to monitor other important neurotransmitters in the brain, increasing our understanding of brain functions. Our well- established, highly skilled, multidisciplinary team has the expertise in electrochemical and acoustic biosensors, microdevice and microsensor design and fabrication, and visual neuroscience to develop and validate the proposed neurosensing technology.

IC Name
NATIONAL EYE INSTITUTE
  • Activity
    R21
  • Administering IC
    EY
  • Application Type
    1
  • Direct Cost Amount
    169724
  • Indirect Cost Amount
    60500
  • Total Cost
    230224
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    867
  • Ed Inst. Type
    SCHOOLS OF ARTS AND SCIENCES
  • Funding ICs
    NEI:230224\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    OAKLAND UNIVERSITY
  • Organization Department
    CHEMISTRY
  • Organization DUNS
    041808262
  • Organization City
    ROCHESTER
  • Organization State
    MI
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    483094422
  • Organization District
    UNITED STATES