Implantable Microarray Probe for Real-Time Glutamate and GABA Detection

Project SummaryThere is an enormous need for the development of a new class of neurotransmitterNTsensors that are versatileselectivesensitive and reliable to allow investigation of the neurobiological mechanisms of behavior and disease symptomsThis STTR proposal will focus on implementing a novel microarray probe for in vivoreal time sensing of glutamateGLUand gamma aminobutyric acidGABAGLU and GABA are NTs that are essential for normal brain functionneuronal activityinformation processing and plasticityand network synchronizationGLU is a major excitatory NT and GABA is a major inhibitory NTand they must maintain a proper balance for the brain to operate normallyA GLU GABA dysregulation plays a critical role in several brain disordersincluding epilepsya disorder affectingof Americansdementiaa disorder that will affectmillion worldwide byand Parkinson sa disorder affectingmillion Americans todayA fundamental understanding of NT homeostasis would likely lead to new and effective therapeutic strategies for patientsExisting monitoring methods suffer from the inability to measure dynamics continuouslyin real timeCurrentlythe primary method being used is microdialysiswhich has very poor temporal resolution and is therefore not suitable to evaluate behavioral events that occur on a timescale of seconds or lessIn contrastbiosensors are easy to miniaturize and are suitable for in vivo studiesthey selectively oxidize GLU GABA into a secondary electroactive product in the presence of enzymeswhich is then detected by amperometryUnfortunatelypreviously available biosensors have been cumbersomehave relied on externally applied reagentsand have been grossly inaccurate because their calibration has been carried out in vitro and not in vivoWe overcame these problems with GLU GABA detection and demonstrated a biosensor array probe capable of afold higher sensitivity to GABAa four fold higher sensitivity to GLUand no need for external reagentsHerewe propose to develop the next generation of our biosensor microelectrode arrayMEAprobe technology that will allow GLU GABA detection in real time with the highest sensitivityselectivityand reliabilityThe probes will have the following new featuresAt leastGABA andGLU sites for measuring concentrations at different positions within the brainAlsoit will feature a microfluidic channel for the introduction of chemicals in the immediate vicinity of the microelectrodesFinallywe will incorporate an On Demand In situ CalibratorODICthat runs in situ sensor calibration for accurate detectionThe specific aims of this project areimicrofabrication and characterization of platinum MEAs with ODIC on a silicon probeiisurface modification and optimization of GLU GABA probe in vitro andiiidemonstrate real time GLU GABA detection in an epileptic rat brainThe proposed research would also enable alternative applications for the technologyincludingpoint of use sensors for neurotoxinsreactive oxygen speciesand disease biomarkersThe estimated market based on neurostimulation devices is $billion byIf onlyof that market is accessible by biosensor probe technologyit would still be sufficient justification for the proposed work Project Narrative This project will advance basic neuroscience research tools by developing a novel implantable microarray probe for real time glutamate and gamma aminobutyric acid detectionThe multiplexing and in vivo capabilities of the probe will allow researchers to develop more effective animal models and therapeutics for brain diseases and certain psychological disordersThese tools address critical healthcare issues with costs due to mental disease exceed $trillion annuallyAlzheimer s Disease affectingmillion Americansof Americans suffering from Epilepsyandmillion suffering from Parkinson s disease