A Neural Device with Individually Addressable Microelectrode Array Suitable for Simultaneous Measurement of Catecholamines: Fabrication and Characterization

Investigation of catecholamines (dopamine: DA, norepinephrine: NE and epinephrine EP) has been of importance of the crucial roles that these molecules play in neurological function and related diseases. Due to the similar chemical structures and oxidation potentials of these compounds, it has been a challenge to use simple electrochemical techniques to differentiate them in mixtures.¹ Redox cycling is known to have the capability to differentiate between species based on the propensity of the compounds to diffuse to and produce an electrochemical response at the neighboring electrode.² The oxidized species generated at an electrode (generator) can diffuse to neighboring electrodes held at a reducing potential (collector) that will yield the original species. This process can occur multiple times and can produce an amplified signal. If the oxidized form of the species is electrochemically inactive or inactivated through following chemical reactions, selectivity can be achieved for the electroactive molecules arriving at the collector. This can be the basis of separating and detecting species using redox cycling.

The ECC' mechanism of catecholamines takes place at different rates, in the order of EP > NE > DA, and can lead to differentiation based on the spatial distribution that is probed by the electrode array undergoing redox cycling.⁴

The purpose of our research is to study the fundamental electrochemical redox cycling behavior of DA, NE and EP. By understanding this behavior, it can then be determined whether their simultaneous detection in more complex samples will be feasible. We will report on miniaturized probes designed to meet requirements of a redox cycling approach for in vivo measurements. These are: 1) mechanical robustness for insertion in the brain without breakage or bending, 2) suitable dimensions to minimize damage to brain tissue and 3) suitable number and design of electrodes for optimal electrochemical performance. The substrate of the fabricated probe is an 80 µm thick SU-8 polymer. The shank is 100 µm wide and 6 mm long to reach deep areas of the rat's striatum. The probe has an array of nine parallel gold electrodes each of which are 4µm wide with a gap of 4 µm in between.

We will report the process, results, and challenges for design, fabrication, and implementation of a probe, suitable for neural studies. The characterization of the probe with a model compound and the results from CA measurements using redox cycling will be shown. We will discuss the next steps to improve the design of electrodes and experiments to achieve desirable limits of detection and sensitivity for in vivo measurements.

References

1. Hawley, M. D.; Tatawawadi, S. V.; Piekarski, S.; Adams, R. N. Journal of the American Chemical Society 1967, 89, 447-450.

2. Hu, Mengjia; Fritsch, Ingrid. Analytical Chemistry 2015, 87, 2029−2032.

3. Ciolkowski, E. L.; Maness, K. M.; Cahill, P. S.; Wightman, R. M.; Evans, D. H.; Fosset, B.; Amatore, C. Analytical Chemistry 1994, 66, 3611-3617.

4. Ciolkowski, E. L.; Cooper, B. R.; Jankowski, J. A.; Jorgenson, J. W.; Wightman, R. M. Journal of the American Chemical Society 1992, 114, 2815-2821.