To understand how the brain functions and what disruptions underlie neurological diseases and disorders, analytical methods are needed that can succeed in the complexity of the native brain environment. To make a measurement in functioning, live tissue, these methods must be selective for specific analytes in a matrix that has over 1000 different chemical species, be able to measure chemical changes on multiple timescales (10-3 s to 104 s), have a high spatial resolution (μm), and be sensitive (pM to μM). The work described within, details the development and application of a voltammetric method, fast-scan controlled adsorption voltammetry (FSCAV) that is capable of monitoring baseline levels of serotonin and dopamine, as well as monitoring changes on multiple time scales with high sensitivity and selectivity. Because FSCAV is performed using a carbon-fiber microelectrode, the same sensor can be used for fast-scan cyclic voltammetry to monitor rapid (phasic) changes of dopamine and serotonin in the extracellular space. Thus a single-sensor strategy for measuring tonic and phasic concentrations of these important neurotransmitters is developed and used to elucidate important insight into the differences of serotonin and dopamine regulation. Additionally it is revealed that dopamine exhibits a coaction between tonic and phasic signaling where serotonin does not. Using this approach, a method for evaluating pain processing in a preclinical model is developed, which reveals an important relationship between chronic pain and dopamine signaling. Furthermore, a mathematical model to describe mass-transport limited adsorption is developed and used to determine the diffusion coefficient of both dopamine and serotonin in situ. The work described within details an important advancement in neuroanalytical methodology that will provide new insights both short-term and long-term for studying fundamental chemical mechanisms of neurotransmission.

Fast Scan Cyclic Voltammetry (FSCV) is an electrochemical technique, based on ramping a voltage through a microelectrode and measuring the resulting redox current to obtain information about an electroactive molecule. FSCV can be used for the detection of dopamine, which is a vital neurotransmitter. Dopamine is central to conditions such as Parkinson’s disease. The purpose of this thesis was to evaluate if a new type of highly biocompatible microelectrode, called tube electrode, can be used to detect dopamine using FSCV and determine how they compare to standard carbon fibre microelectrodes (CFMEs). In order to achieve this, three main tasks were set and fulfilled. First, a station for in-vitro FSCV was set up and CFMEs of varying sizes were used to detect dopamine at different concentrations. Secondly, the same trials were done with tube electrodes. Finally, the results of the tubes were compared to the CFMEs. In total, four CFMEs and four tube electrodes were investigated. The dopamine concentrations ranged from 20 nM to 40 μM. In short, the results indicate that the tubes generally have lower sensitivity than the CFMEs but better linearity between the increasing dopamine concentration and the resulting current. The tubes also had a marginally higher concentration threshold for dopamine detection. The main challenge encountered was a decrease in sensitivity over time. Here, further investigations are necessary to map the causes responsible. In conclusion, the tube electrodes are able to detect dopamine in-vitro, with concentrations relevant for in-vivo sensing, with a performance comparable to CFMEs. However, further studies are necessary before the tube electrodes can be used for dopamine detection in-vivo. / Fast Scan Cyclic Voltammerey (FSCV) är en elektrokemisk teknik, baserad på att ändra en spänning genom en mikroelektrod och sedan mäta den resulterande redox-strömmen för att få information om en elektroaktiv molekyl. FSCV kan användas för detektering av dopamin, som är en livsviktig signalsubstans. Dopamin har en central roll vid tillstånd så som Parkinsons sjukdom. Syftet med detta examensarbete var att utvärdera om en ny typ av mycket biokompatibel mikroelektrod, kallad tubelektrod, kan användas för att detektera dopamin genom FSCV och fastställa hur de jämför sig med vanliga kolfibermikroelektroder (KFME). För att uppnå detta sattes och uppfylldes tre huvuduppgifter. Först upprättades en station för in-vitro FSCV där KFME med varierande storlek användes för att detektera olika koncentrationer dopamin. Sedan gjordes samma försök med tubelektroder. Slutligen jämfördes resultaten med de från KFME. Totalt testades fyra KFME och fyra tubelektroder. Dopaminkoncentrationerna sträckte sig från 20 nM till 40 μM. Kort sagt indikerar resultaten att tuberna generellt hade lägre känslighet än KFME men bättre linjäritet mellan den ökande dopaminkoncentrationen och den resulterande strömmen. Tuberna hade även något högre koncentrationströskel för detektionen av dopamin. Den största utmaningen som påträffades var en minskning i känslighet över tid. Här krävs vidare undersökningar för att helt förstå de bakomliggande anledningarna. Slutsatsen är att tuberna kan detektera dopamin in-vitro, med koncentrationer som är relevanta för mätningar in-vivo, och med en prestation jämförbar med den för KFME. Dock krävs mer studier innan tubelektroderna kan användas för att detektera dopamin in-vivo.

The work presented in the thesis is about the evaluation of Organic Electrochemical Transistors (OECTs) for fast scan cyclic voltammetry (FSCV). FSCV is a method which has been used for real time dopamine sensing both in vivo and in vitro. The method is sensitive to noise and could therefore benefit from signal preamplification at the point of sensing, which could be achieved by incorporation of OECTs. In this study the OECTs are based on the conductive polymer poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS). The gate consists of gold microelectrodes of different sizes to be used one at a time. When dopamine is reacted at the gate electrode, the redox state of the PEDOT:PSS OECT channel is modulated and the resulting change in drain current can be measured. The gate current, which contains the sensing information, is after filtering obtained by differentiating the channel potential with respect to time. The derived gate current is plotted in cyclic voltammogram for different dopamine concentrations and the amplitude of the oxidation/reduction peaks can be used to determine the dopamine concentration. In this thesis for the first time it is demonstrated that OECTs can be used for FSCV detection of dopamine. The results are discussed and an outlook on future work is given.