Public defence in Electronics integration and reliability, M.Sc.(Tech.) Samuel Rantataro

The title of the thesis: Ultrasensitive and selective real-time detection of neurotransmitters for brain-on-a-chip applications 

Doctoral student: Samuel Rantataro
Opponent: Prof. Jill Venton, University of Virginia, US
Custos: Prof. Tomi Laurila, Aalto University School of Electrical Engineering, Department of Electrical Engineering and Automation

Neurological diseases account annually up to 10 million deaths and the number is expected to increase as the population ages. Up to date, drug discovery has had 0% success rate to find disease modifying treatment for central nervous system diseases, mainly arising from extremely poor translation of results from animal studies to us humans. To overcome this limitation, human cell -based brain models are being rapidly adopted into academic neuroscientific research but also in the pharmaceutical industry. Unfortunately, the use of these brain models is limited by the lack of high-throughput characterization methods. 

Electrochemical measurements can be used to examine the condition of specific cell types in the brain models. Once the electrodes are patterned by conventional microfabrication means, electrochemical sensors can be used to characterize brain models in vitro with high throughput. In this dissertation, single-walled carbon nanotube (SWCNT) based electrodes were used to measure neurotransmitters with nanomolar sensitivity at real-time, as recorded inside the cell culture medium. In addition, these sensors were found to be extremely biocompatible, allowing long-term culturing of the highly sensitive in vitro brain models, such as neuronal cultures and brain organoids originally derived from human stem cells. 

As many biological characterization techniques are based on inverse microscopy, optical transparency is a necessary feature for the sensors. Accordingly, the SWCNT films were manufactured with 90 % transparency, whereas pertaining high electrical conductivity. This enables the use of one material in producing both the electrochemical electrodes, but also the conductive path from electrodes to a readout system. Whereas many materials are claimed to meet the requirements of brain-on-a-chip devices, more thorough investigation reveals that such claims are mistakenly made and actually only concern individual components from the ensemble of strict specifications. Furthermore, these earlier claims have been made based on highly simplified and misleading experimental settings. 

Detection of neurotransmitters from complex brain models is highly challenging. The SWCNT-based sensors offer thus very unique capabilities, as they fulfill all the requirements of brain-on-a-chip devices, paving way for broader adoption of the technology.

Keywords: Brain-on-a-chip, Neurotransmitter, Electrochemistry, Sensor, Transparent, Dopamine

Thesis available for public display 10 days prior to the defence at: https://aaltodoc.aalto.fi/doc_public/eonly/riiputus/

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Doctoral theses in the School of Electrical Engineering: https://aaltodoc.aalto.fi/handle/123456789/53