Alexander Zestos is a new assistant professor in the Department of Chemistry at American University. He began in August, teaching biochemistry and doing research with eight graduate and undergraduate students on construction of carbon fiber electrodes for the detection of neurotransmitters through fast scan cyclic voltammetry. He and his team plan to improve the sensitivity of carbon-microfiber electrodes for the detection of dopamine in order to find a targetable site for medical treatment. The research has implications that extend into treating amphetamine abuse, Parkinson’s disease, and other diseases.
Zestos completed his bachelor’s and master’s degrees at the College of William and Mary. He earned his PhD from the University of Virginia and has spent the last three years as a postdoctoral research fellow at the University of Michigan, where he had a joint appointment in the chemistry and pharmacology departments.
Trained as an analytical chemist, he decided to apply those skills to neuroscience. “If you just turn on the news today, you’ll see that Parkinson’s disease, drug abuse, all these neurological disorders are very prevalent,” Zestos said. “[My research is] using practical chemical tools to help solve problems that are still plaguing today’s society.”
Zestos’ main project is the fabrication of carbon fiber microelectrodes that can be used to detect a wide variety of ionizable neurotransmitters such as dopamine, serotonin, and adenosine. His research focuses specifically on the detection of dopamine since it can be found in high concentrations and is important for a wide variety of neurological applications and biological responses like appetite and sex. Fast scan cyclic voltammetry is used to test these carbon fiber microelectrodes in vitro.
The carbon fiber microelectrodes are constructed by aspirating a single carbon fiber strand into a glass capillary through vacuum suction. The glass capillary is pulled to a fine taper using a vertical capillary puller. The product is a microelectrode with carbon fiber sticking out, cut short to prevent overloading of electrical signal. Carbon fiber microelectrodes are epoxied to prevent leaking of conductive solution, making them less fragile and more amenable to mass production.
Currently, Zestos’ research is focused on in vitro studies, which allows him to test the carbon fiber microelectrodes for their response to dopamine, but eventually he would like to take his research to in vivo studies. There are a few challenges in doing this since the concentrations in vivo are often much lower. They also require more selectivity since, in the body, there are other interfering molecules. This means that the electrodes have to be much more selective to the designated neurotransmitter.
The selectivity and the sensitivity of the microelectrodes can be modified using various polymer coatings to change the electrostatic properties of the electrode. Dopamine is attracted to negatively charged materials. Zestos has worked with coating the carbon microelectrodes in negatively charged polymers such as Nafion, which causes an electrostatic attraction, allowing dopamine and other positively charged amines to pre-concentrate on the surface of the electrode, thereby increasing the sensitivity of the electrode. Other coatings, such as PEDOT, can be used to change the selectivity of the electrode towards other neurotransmitters that might have different electrostatic interactions.
Zestos is also looking at carbon nanotubes, sheets of graphene that are rolled in on themselves to modify cylindrical microstructures. These have superior properties to the carbon microfibers as they have lower detection limits, faster temporal resolution, and antifouling properties. Changing the waveforms used for the electrochemical analysis can also change and improve the selectivity.
Zestos hopes to be able to detect the molecules DOPAC (3,4-dihydroxyphenylacetic acid) and 3-methoxytyramine once he has fabricated the carbon fiber microelectrodes. These molecules are metabolites of dopamine, and by changing the waveform and the sensor used for analysis, Zestos believes he can selectively detect them. “Everyone thinks that dopamine is all important for drug abuse, Parkinson’s disease, depression, appetite, sex, reward, and locomotor movement. But we think that these metabolites of dopamine are important for these neurological disorders as well,” he said. He believes that being able to detect these metabolites will grant researchers a more complete picture of various neurological disorders.
In his research, Zestos has also used liquid chromatography and mass spectro-scopy for neurotransmitter detection. These techniques don’t allow for as high temporal resolution, but they do allow for detection of multiple species at once.
Zestos’ research has already borne fruits, both while he was working at Michigan and in his short time here at American University. He and his fellow researchers at the University of Michigan have recently published in Nature Medicine on the research they conducted using liquid chromatography and mass spectroscopy to detect acetylcholine in beige fat adipocytes. His success has led to him being selected to receive the Faculty Research Support Grant from American University to do research over the summer. Zestos is also one of eight finalists to receive the Csaba Horváth Young Scientist Award from the international HPLC conference this summer in Washington, DC.
We are excited to welcome Zestos to our campus. In the year he has been here, he has already had a profound impact on his students and on the department. We know he will be a great addition to the chemistry department and the university.