Brain-Implantable Multifunctional Probe for Simultaneous Detection of Glutamate and GABA Neurotransmitters: Optimization and In Vivo Studies
Imbalances in levels of glutamate (GLU) and gamma-aminobutyric acid (GABA) and their sub-second signaling dynamics occur in several brain disorders including traumatic brain injury, epilepsy, and Alzheimer’s disease. The present work reports on the optimization and in vivo testing of a silicon (Si)...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Micromachines |
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| Online Access: | https://www.mdpi.com/2072-666X/13/7/1008 |
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| author | Sanjeev Billa Yaswanthi Yanamadala Imran Hossain Shabnam Siddiqui Nicolaie Moldovan Teresa A. Murray Prabhu U. Arumugam |
| author_facet | Sanjeev Billa Yaswanthi Yanamadala Imran Hossain Shabnam Siddiqui Nicolaie Moldovan Teresa A. Murray Prabhu U. Arumugam |
| author_sort | Sanjeev Billa |
| collection | DOAJ |
| description | Imbalances in levels of glutamate (GLU) and gamma-aminobutyric acid (GABA) and their sub-second signaling dynamics occur in several brain disorders including traumatic brain injury, epilepsy, and Alzheimer’s disease. The present work reports on the optimization and in vivo testing of a silicon (Si) multifunctional biosensor probe for sub-second simultaneous real-time detection of GLU and GABA. The Si probe features four surface-functionalized platinum ultramicroelectrodes (UMEs) for detection of GLU and GABA, a sentinel site, and integrated microfluidics for in-situ calibration. Optimal enzyme concentrations, size-exclusion phenylenediamine layer and micro spotting conditions were systematically investigated. The measured GLU sensitivity for the GLU and GABA sites were as high as 219 ± 8 nA μM<sup>−1</sup> cm<sup>−2</sup> (<i>n</i> = 3). The measured GABA sensitivity was as high as 10 ± 1 nA μM<sup>−1</sup> cm<sup>−2</sup> (<i>n</i> = 3). Baseline recordings (<i>n</i> = 18) in live rats demonstrated a useful probe life of at least 11 days with GLU and GABA concentrations changing at the levels of 100′s and 1000′s of μM and with expected periodic bursts or fluctuations during walking, teeth grinding and other activities and with a clear difference in the peak amplitude of the sensor fluctuations between rest (low) and activity (higher), or when the rat was surprised (a reaction with no movement). Importantly, the probe could improve methods for large-scale monitoring of neurochemical activity and network function in disease and injury, in live rodent brain. |
| first_indexed | 2024-03-09T06:11:31Z |
| format | Article |
| id | doaj.art-59e64c22ee844d17bec6db61ae8e2fca |
| institution | Directory Open Access Journal |
| issn | 2072-666X |
| language | English |
| last_indexed | 2024-03-09T06:11:31Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Micromachines |
| spelling | doaj.art-59e64c22ee844d17bec6db61ae8e2fca2023-12-03T11:57:26ZengMDPI AGMicromachines2072-666X2022-06-01137100810.3390/mi13071008Brain-Implantable Multifunctional Probe for Simultaneous Detection of Glutamate and GABA Neurotransmitters: Optimization and In Vivo StudiesSanjeev Billa0Yaswanthi Yanamadala1Imran Hossain2Shabnam Siddiqui3Nicolaie Moldovan4Teresa A. Murray5Prabhu U. Arumugam6Institute for Micromanufacturing (IfM), Louisiana Tech University, Ruston, LA 71272, USACenter for Biomedical Engineering and Rehabilitation Science (CBERS), Louisiana Tech University, Ruston, LA 71272, USAInstitute for Micromanufacturing (IfM), Louisiana Tech University, Ruston, LA 71272, USADepartment of Chemistry and Physics, Louisiana State University Shreveport, Shreveport, LA 71115, USAAlcorix Co., Plainfield, IL 60544, USACenter for Biomedical Engineering and Rehabilitation Science (CBERS), Louisiana Tech University, Ruston, LA 71272, USAInstitute for Micromanufacturing (IfM), Louisiana Tech University, Ruston, LA 71272, USAImbalances in levels of glutamate (GLU) and gamma-aminobutyric acid (GABA) and their sub-second signaling dynamics occur in several brain disorders including traumatic brain injury, epilepsy, and Alzheimer’s disease. The present work reports on the optimization and in vivo testing of a silicon (Si) multifunctional biosensor probe for sub-second simultaneous real-time detection of GLU and GABA. The Si probe features four surface-functionalized platinum ultramicroelectrodes (UMEs) for detection of GLU and GABA, a sentinel site, and integrated microfluidics for in-situ calibration. Optimal enzyme concentrations, size-exclusion phenylenediamine layer and micro spotting conditions were systematically investigated. The measured GLU sensitivity for the GLU and GABA sites were as high as 219 ± 8 nA μM<sup>−1</sup> cm<sup>−2</sup> (<i>n</i> = 3). The measured GABA sensitivity was as high as 10 ± 1 nA μM<sup>−1</sup> cm<sup>−2</sup> (<i>n</i> = 3). Baseline recordings (<i>n</i> = 18) in live rats demonstrated a useful probe life of at least 11 days with GLU and GABA concentrations changing at the levels of 100′s and 1000′s of μM and with expected periodic bursts or fluctuations during walking, teeth grinding and other activities and with a clear difference in the peak amplitude of the sensor fluctuations between rest (low) and activity (higher), or when the rat was surprised (a reaction with no movement). Importantly, the probe could improve methods for large-scale monitoring of neurochemical activity and network function in disease and injury, in live rodent brain.https://www.mdpi.com/2072-666X/13/7/1008biosensorglutamateGABAreal-time sensorin-situ calibrationin vivo recording |
| spellingShingle | Sanjeev Billa Yaswanthi Yanamadala Imran Hossain Shabnam Siddiqui Nicolaie Moldovan Teresa A. Murray Prabhu U. Arumugam Brain-Implantable Multifunctional Probe for Simultaneous Detection of Glutamate and GABA Neurotransmitters: Optimization and In Vivo Studies Micromachines biosensor glutamate GABA real-time sensor in-situ calibration in vivo recording |
| title | Brain-Implantable Multifunctional Probe for Simultaneous Detection of Glutamate and GABA Neurotransmitters: Optimization and In Vivo Studies |
| title_full | Brain-Implantable Multifunctional Probe for Simultaneous Detection of Glutamate and GABA Neurotransmitters: Optimization and In Vivo Studies |
| title_fullStr | Brain-Implantable Multifunctional Probe for Simultaneous Detection of Glutamate and GABA Neurotransmitters: Optimization and In Vivo Studies |
| title_full_unstemmed | Brain-Implantable Multifunctional Probe for Simultaneous Detection of Glutamate and GABA Neurotransmitters: Optimization and In Vivo Studies |
| title_short | Brain-Implantable Multifunctional Probe for Simultaneous Detection of Glutamate and GABA Neurotransmitters: Optimization and In Vivo Studies |
| title_sort | brain implantable multifunctional probe for simultaneous detection of glutamate and gaba neurotransmitters optimization and in vivo studies |
| topic | biosensor glutamate GABA real-time sensor in-situ calibration in vivo recording |
| url | https://www.mdpi.com/2072-666X/13/7/1008 |
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