Date of Graduation

7-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Degree Level

Graduate

Department

Chemistry & Biochemistry

Advisor

Ingrid Fritsch

Committee Member

Julie Stenken

Second Committee Member

Charles Wilkins

Third Committee Member

David Paul

Fourth Committee Member

Suresh Thallapuranam Kumar

Keywords

neurotransmitters, neural probe, microelectrodes, dopamine levels

Abstract

Redox cycling is an electrochemical technique that utilizes closely spaced generator and collector electrodes to cycle reversible redox species between their oxidative states. With advantages in signal amplification, selectivity of species based on their electrochemical reaction mechanism, and limited or no background subtraction, this technique is well suited for selective detection of important electrochemically active molecules such as dopamine at basal or slowly changing levels.

Miniaturized medical devices have become an area of great interest for measurement of chemicals in limited volumes with low concentrations or in sensitive tissues. A probe on a polymeric SU-8 substrate with suitable dimensions and robustness for in vivo neural measurements was developed and tested in vitro. The probe’s unique construction using microfabrication processes and a laser-machining procedure is described in detail. The probe features an array of individually addressable electrodes, each 100 μm long, 4 μm wide and with a 100 μm gap in between, on a shank that is 6 mm long and 100 μm wide. The probe is insulated by a thin layer of SU-8 with only the electrodes near the tip and the contact pads exposed. Evaluation of tissue after probe insertion into a rat brain indicates minimal damage comparable to FSCV electrodes and less extensive than the microdialysis probe.

The electrodes on the probe were characterized electrochemically and redox cycling on the array was evaluated in vitro in the presence of model compounds (potassium ferricyanide and ruthenium (III) hexamine chloride) and dopamine, and the responses were compared to theory. The amplification factors, percent collection efficiencies and detection limits are determined from calibration curves. The best detection limits obtained for dopamine at the generator electrodes and collector electrodes during redox cycling are 800 nM and 1.10 μM, respectively. These values lie in the physiological concentration range of dopamine. The features and the results suggest that the probe is ready for further analysis in vivo.

Finally, potential future designs for the probe are proposed and their expected current is calculated using theoretical approximations. All of the proposed designs fit on the same footprint as the current probe (70-μm wide and 100-μm long window) and have dimensions achievable with available micro and nanofabrication tools.

Available for download on Saturday, September 10, 2022

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