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Miniaturized probe on polymer SU-8 with array of individually addressable microelectrodes for electrochemical analysis in neural and other biological tissues

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Abstract

An SU-8 probe with an array of nine, individually addressable gold microband electrodes (100 μm long, 4 μm wide, separated by 4-μm gaps) was photolithographically fabricated and characterized for detection of low concentrations of chemicals in confined spaces and in vivo studies of biological tissues. The probe’s shank (6 mm long, 100 μm wide, 100 μm thick) is flexible, but exhibits sufficient sharpness and rigidity to be inserted into soft tissue. Laser micromachining was used to define probe geometry by spatially revealing the underlying sacrificial aluminum layer, which was then etched to free the probes from a silicon wafer. Perfusion with fluorescent nanobeads showed that, like a carbon fiber electrode, the probe produced no noticeable damage when inserted into rat brain, in contrast to damage from an inserted microdialysis probe. The individual addressability of the electrodes allows single and multiple electrode activation. Redox cycling is possible, where adjacent electrodes serve as generators (that oxidize or reduce molecules) and collectors (that do the opposite) to amplify signals of small concentrations without background subtraction. Information about electrochemical mechanisms and kinetics may also be obtained. Detection limits for potassium ferricyanide in potassium chloride electrolyte of 2.19, 1.25, and 2.08 μM and for dopamine in artificial cerebral spinal fluid of 1.94, 1.08, and 5.66 μM for generators alone and for generators and collectors during redox cycling, respectively, were obtained.

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Acknowledgements

MLM is grateful for a Fulbright Dissertation Research Award. We thank Dr. Ben J. Jones for designing the graphical abstract. We acknowledge Errol Porter for consultation on microelectrode fabrication and the High-Density Electronics Center for use of microfabrication facilities. Scanning electron microscopy images were obtained in the Arkansas Nano & Biomaterials Characterization Facility at the University of Arkansas. We are grateful to Dr. Jonathan Moldenhauer and Professor David Paul at the University of Arkansas for designing and providing the circuit board for mounting the edge connector.

Source of biological material

Male Sprague−Dawley rats were obtained from Charles River, Raleigh, NC.

Funding

Research was supported partially through the National Institutes of Health (R21NS086107) and the University of Pittsburgh Center for Biological Imaging (1S10RR028478-01), the Royal Society for an Industry Fellowship (J.V.M., INF/R1/180026), and the Centre for Doctoral Training in Diamond Science and Technology (EP/ L015315/1) with the Defense Science and Technology Laboratory (Dstl) (S.J.C.), the University of Arkansas’s Women’s Giving Circle, the National Science Foundation (CMI-1808286), and the Arkansas Biosciences Institute, the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR, 72701, USA

    Mahsa Lotfi Marchoubeh, Miguel Abrego Tello, Mengjia Hu & Ingrid Fritsch

  2. Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK

    Samuel J. Cobb

  3. Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    Andrea Jaquins-Gerstl, Elaine M. Robbins & Adrian C. Michael

  4. Department of Chemistry and Centre for Doctoral Training in Diamond Science and Technology, and Department of Physics, University of Warwick, Coventry, UK

    Samuel J. Cobb & Julie V. Macpherson

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  1. Mahsa Lotfi Marchoubeh
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Correspondence to Ingrid Fritsch.

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The University of Pittsburgh’s Institutional Animal Care and Use Committee reviewed and approved all procedures involving animals.

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All animal procedures were in compliance with USDA laboratory animal use regulations. Additionally, all procedures were approved by the Institutional Animal Care and Use Committee of the University of Pittsburgh, the location of the laboratory where all experiments involving animals took place.

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Published in the topical collection Electrochemistry for Neurochemical Analysis with guest editors Ashley E. Ross and Alexander G. Zestos.

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Lotfi Marchoubeh, M., Cobb, S.J., Abrego Tello, M. et al. Miniaturized probe on polymer SU-8 with array of individually addressable microelectrodes for electrochemical analysis in neural and other biological tissues. Anal Bioanal Chem 413, 6777–6791 (2021). https://doi.org/10.1007/s00216-021-03327-2

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