Dopamiinin sähkökemiallinen mittaaminen timantinkaltaisella hiili/platina -yhdistelmäelektrodilla

Dopamine (DA) is an important neurotransmitter in the central nervous system. It conveys cognitive, behavioral and motor functions, and it is involved in several neurological disorders, such as schizophrenia and Parkinson’s disease that affect millions of people worldwide. Although DA is implicated in so many functions, the precise mechanisms by which it mediates these effects are largely unknown. Thus, the development of a sensitive sensor for DA measurement in living systems would greatly contribute to understanding the specific role of DA and the functions it imparts. The electrode material is a key factor determining the feasibility of these kinds of sensors. DA occurs as an electroactive cation in the brain and it can thus be detected directly by electrochemical methods. Cyclic voltammetry (CV) has been widely used to detect neurotransmitters, because it combines good selectivity and high temporal resolution to detect small, transient fluctuations in the concentrations of analytes in the brain. Carbon allotropes have several advantages and are often superior to noble metals in electrochemical measurement of biological molecules. Especially, diamond-like carbon (DLC) has many attractive properties as an electrochemical sensor. It is chemically inert, has a low background current and a wide potential window. Its electrochemical properties can be tailored widely by adjusting its sp2/sp3 ratio and doping. In this work, the electrochemical properties and performance of DLC/Pt composite electrodes in DA detection were investigated. Pt wires exhibiting good electron transfer kinetics were coated with thin layers of inert DLC. These electrodes were used to measure DA using CV. DLC showed a wide potential window and a low background current. The partly uncovered Pt underneath the DLC layer provided the necessary catalytic sites for the redox reactions to occur. The DA detection limit was 10 μM, which is better than that of DLC or Pt separately. The enhanced detection is expected to result from the combination of the active Pt with the passive DLC thin film material.Dopamiini on yksi tärkeimmistä välittäjäaineista keskushermostossa. Se toimii esimerkiksi ihmisen käyttäytymiseen liittyvien sekä kognitiivisten ja motoristen toimintojen välittäjänä. Lisäksi dopamiinin tiedetään vaikuttavan useisiin neurologisiin sairauksiin, kuten skitsofreniaan ja Parkinsonin tautiin. Dopamiinin vaikutusmekanismeja ei kuitenkaan tunneta tarkasti ja niiden ymmärtämiseksi on tärkeää kehittää riittävän herkkä anturi, joka soveltuisi myös elimistössä suoritettaviin mittauksiin. Näissä sovelluksissa mittauselektrodi on avainasemassa. Sähkökemiallisia menetelmiä on käytetty laajalti dopamiinin mittauksessa, koska dopamiini on sähkökemiallisesti aktiivinen kationi elimistössä. Erityisesti syklistä voltammetriaa (SV) on käytetty laajalti välittäjäaineiden mittaamiseen, sillä se on selektiivinen ja nopea menetelmä äkillisten pitoisuusmuutoksien mittaamiseen aivoissa. Hiilen allotroopit soveltuvat usein jaloja metalleja paremmin biologisien molekyylien sähkökemialliseen mittaamiseen ja niitä onkin käytetty paljon näissä sovelluksissa. Erityisesti timantinkaltaisella hiilellä (DLC) on laaja vesi-ikkuna, matala taustavirta ja se on sähkökemiallisesti hyvin inertti, mikä tekee siitä kiinnostavan elektrodimateriaalin. Lisäksi sen ominaisuuksia voidaan laajasti muuttaa säätämällä hiilen sp2/sp3 –suhdetta sekä seostamalla. Tässä työssä valmistettiin yhdistelmäelektrodeja, joissa sähköisesti aktiivisen platinasubstraatin pinnalle päällystettiin inertti DLC-kerros. Elektrodeja käytettiin dopamiinin mittaamiseen SV:llä. Havaitsemisrajaksi saatiin 10 μM, mikä oli parempi kuin platinan tai DLC:n havaitsemisrajat erikseen. DLC-pinnoitteen ansiosta elektrodit olivat inerttejä, niillä oli laaja vesi-ikkuna ja alhainen taustavirta. DLC-kerroksen alta paikallisesti paljastunut Pt taas tarjosi hapetus-pelkistysreaktioille katalyyttisen alustan. Yhteenvetona voidaan todeta, että passiivisen DLC:n yhdistäminen aktiiviseen platinaan paransi elektrodin kykyä havaita dopamiinia

New electrochemically improved tetrahedral amorphous carbon films for biological applications

Carbon based materials have been frequently used to detect different biomolecules. For example high sp3 containing hydrogen free diamond-like carbon (DLC) possesses many properties that are beneficial for biosensor applications. Unfortunately, the sensitivities of the DLC electrodes are typically low. Here we demonstrate that by introducing topography on the DLC surface and by varying its layer thickness, it is possible to significantly increase the sensitivity of DLC thin film electrodes towards dopamine. The electrode structures are characterized in detail by atomic force microscopy (AFM) and conductive atomic force microscopy (C-AFM) as well as by transmission electron microscopy (TEM) combined with electron energy loss spectroscopy (EELS). With cyclic voltammetry (CV) measurements we demonstrate that the new improved DLC electrode has a very wide water window, but at the same time it also exhibits fast electron transfer rate at the electrode/solution interface. In addition, it is shown that the sensitivity towards dopamine is increased up to two orders of magnitude in comparison to the previously fabricated DLC films, which are used as benchmarks in this investigation. Finally, it is shown, based on the cyclic voltammetry measurements that dopamine exhibits highly complex behavior on top of these carbon electrodes.The authors T.L, V.P., S.S., T.P., and J.K., would like to acknowledge the National Agency for Technology and Innovation (grant number 211488) and Aalto University (grant number 902380) for the financial support

Electrochemical reactions of catechol, methylcatechol and dopamine at tetrahedral amorphous carbon (ta-C) thin film electrodes

The electrochemical reactions of dopamine, catechol and methylcatechol were investigated at tetrahedral amorphous carbon (ta-C) thin film electrodes. In order to better understand the reaction mechanisms of these molecules, cyclic voltammetry with varying scan rates was carried out at different pH values in H2SO4 and PBS solutions. The results were compared to the same redox reactions taking place at glassy carbon (GC) electrodes. All three catechols exhibited quasi-reversible behavior with sluggish electron transfer kinetics at the ta-C electrode. At neutral and alkaline pH, rapid coupled homogeneous reactions followed the oxidation of the catechols to the corresponding o-quinones and led to significant deterioration of the electrode response. At acidic pH, the extent of deterioration was considerably lower. All the redox reactions showed significantly faster electron transfer kinetics at the GC electrode and it was less susceptible toward surface passivation. An EC mechanism was observed for the oxidation of dopamine at both ta-C and GC electrodes and the formation of polydopamine was suspected to cause the passivation of the electrodes.Authors wish to acknowledge the financial support by the Finnish Parkinson Foundation (T.P.), the Finnish Funding Agency for Innovation (grant number 211488) (T.P., S.S. and T.L.), the Academy of Finland (grant number 285015) (T.L.) and MINECO project CTQ2013-44083-P (J.F.M.)

Finnish late adolescents' physical activity during COVID-19 spring 2020 lockdown

Background Physical activity (PA) is recognised as one of the leading and effective strategies to prevent non-communicable diseases that boosts the immune system to fight against diseases. Closures of schools, sport clubs and facilities because of COVID-19 reduced the opportunities to participate in PA. We aimed to examine physical activity levels of late adolescents, the contexts to be physical active and its changes during the spring 2020 lockdown. Methods A national representative sample of late adolescents in general upper secondary school (n = 2408, females = 64%, mean age = 17.2y, SD = 0.63) completed self-report online surveys on PA behaviours between March and June 2020. Multinominal logistic regression analyses were performed to identify correlates with PA, and decision tree analyses to ascertain the perceived changes on PA during lockdown based on sport club aspirations and levels of PA. Results Among the late adolescents, the distribution of PA frequency was 23% (0-2 days/week), 35% (3-4 days/week), 30% (5-6 days/week) and 12% (7 days/week), and differences between males and females were not statistically significant. Participation in both indoor and outdoor PA were 50 times more likely to report daily PA (OR = 54.28, CI = 15.16-194.37) than non-participation. A quarter of late adolescents were not part of a sports club, yet their PA levels increased. Although sports club members generally perceived they did less PA during lockdown, over a third of sport club members with competitive aspirations reported daily PA. Conclusions Overall, most late adolescents reported their PA levels decreased during lockdown. Findings from this study continue to demonstrate factors associated with PA in the context of the COVID-19 lockdown

Individual- and environmental-related correlates of moderate-to-vigorous physical activity in 11-, 13-, and 15-year-old Finnish children

The objective of this study was to analyze the associations of various individual- and environmental-related factors with subgroups of daily, frequent, moderate and low moderate-to-vigorous physical activity (MVPA) among children and adolescents. Data were obtained from the Finnish School-age Physical Activity (FSPA) study 2016 from 4677 national representative 11-, 13-, and 15-year-old children and adolescents. MVPA and individual- and environmental-related factors were assessed by a questionnaire and analyzed by two-level logistic regression. Seventeen of the twenty-one variables were statistically significantly associated with MVPA. However, only three variables were statistically significant in all MVPA subgroups, whereby self-directed PA at least twice a week, fewer perceived barriers, and higher peer support increased the odds of participating in more MVPA. The results from this study showed essential differences among the MVPA subgroups, also supporting previous findings, whereby various individual- and environmental-based factors are associated with children and adolescents' levels of MVPA. Challenges to designing and implementing effective interventions are based on the need to account for individual differences within the population, as well as the varied connections between PA with different social and physical environments where children and adolescents' PA takes place. PA interventions with various actions at multiple levels are warranted

Amorfisten hiilimateriaalien sähkökemialliset ominaisuudet

The prevalence of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, will continue to increase as the population ages. This is expected to impose an increasing social and economic burden on societies. Parkinson's disease is characterized mainly by motor symptoms that are caused by the progressive degeneration of neurons that synthesize and release the neurotransmitter dopamine (DA). Current treatment methods, such as levodopa administration and deep brain stimulation, alleviate the symptoms but do not alter disease progression. Therefore, there is an evident need to understand the causes and progression of the disease and to develop new treatment methods. Since the abnormal neurotransmission of DA is linked to the onset of symptoms and progression of Parkinson's disease, the real-time in vivo monitoring of DA levels could provide new information to understand the disease. In this thesis, we have investigated the use of amorphous carbon (a-C) materials as electrochemical sensors for the sensitive and selective measurement of DA. There have been relatively few reports on the electrochemical properties of a-C, although it offers significant advantages, such as a wide potential window and a low background current, over commonly used electrode materials for sensor applications. We have studied the physical, chemical and electrochemical properties of different a-C materials using several bulk and surface characterization methods, computational simulations and electrochemical techniques with outer and inner sphere redox probes. We have shown that deposition parameters can be varied to obtain a-C films with markedly different electrochemistry ranging from graphite-like, highly sp2-bonded carbon to diamond-like, highly sp3-bonded carbon. The sp2/sp3 bonding ratio will define the physical properties, in particular the electronic configuration that strongly correlates with the electrochemistry of a-C materials. We have demonstrated the applicability of highly sp3-bonded tetrahedral amorphous carbon (ta-C) in electroanalytical applications by detecting physiologically relevant DA concentrations (40-85 nM) using cyclic voltammetry. The modification of ta-C with carbon nanotubes conferred the electrode the necessary selectivity to detect DA in the presence of its major interferents, ascorbic acid and uric acid, at physiological concentrations. Both the ta-C and the modified electrodes showed good biocompatibility, further emphasizing their potential as in vivo sensor materials.Neurodegeneratiivisien sairauksien, kuten Parkinsonin ja Alzheimerin tautien, yleisyys kasvaa väestön ikääntyessä, mikä aiheuttaa kasvavia kustannuksia terveydenhuollolle ja yhteiskunnalle. Parkinsonin tauti on parantumaton, hitaasti etenevä sairaus, jonka pääoireet ovat motoriset häiriöt kuten lepovapina, lihasjäykkyys ja liikkeiden hitaus. Taudin aiheuttajaa ei tiedetä, mutta motoriset oireet aiheutuvat dopamiinia tuottavien ja välittävien hermosolujen tuhoutumisesta aivoissa. Taudin oireita voidaan lievittää lääkehoidolla ja vakavimmissa tapauksissa syväaivostimulaatiolla, mutta ne eivät estä taudin etenemistä eivätkä paranna sitä. Koska Parkinsonin taudin oireet liittyvät dopamiinin pitoisuuteen ja välitykseen hermostossa, olisi erityisen tärkeää seurata dopamiinipitoisuuksia reaaliaikaisesti suoraan aivoissa. Tämä tiedon avulla voisi olla mahdollista ymmärtää paremmin taudin aiheuttajia, sen etenemistä ja kehittää tehokkaampia hoitomuotoja. Tässä väitöskirjassa olemme tutkineet amorfisen hiilen sähkökamiellisia ominaisuuksia ja sen käyttöä sähkökemiallisena anturina dopamiinin mittaamisessa. Dopamiinin havaitsemista varten anturin tulee olla tarpeeksi herkkä ja selektiivinen, jotta se voi havaita pieniä dopamiinikonsentraatioita häiriöaineiden läsnäollessa. Amorfista hiiltä on tutkittu niukasti, vaikka sillä on useita erinomaisia sähkökemiallisia ominaisuuksia kuten laaja potentiaali-ikkuna ja pieni taustavirta verrattuna muihin hiilipohjaisiin anturimateriaaleihin. Olemme tutkineet amorfisen hiilen fysikaalisia, kemiallisia ja sähkökemiallisia ominaisuuksia useilla erilaisilla rakenne- ja pintakarakterisointimenetelmillä, laskennallisella mallinnuksella ja sähkökemiallisilla menetelmillä käyttäen ulko- ja sisäkehän redox-molekyylejä. Tulokset osoittavat, että amorfisen hiilen sähkökemiallisia ominaisuuksia voidaan muokata merkittävästi säätämällä depositioparametreja pinnoituksen aikana. Ominaisuudet voivat vaihdella grafiittisen hiilen ja timantinkaltaisen hiilen välillä riippuen hiiliatomien sp2- ja sp3-sidoksien määrästä. Sidoksien sp2/sp3 -suhde määrää amorfisen hiilen fysikaaliset ominaisuudet ja erityisesti elektronikonfiguraation, joka korreloi voimakkaasti sähkökemiallisten ominaisuuksien kanssa. Osoitimme, että tetraedrinen amorfinen hiili soveltuu elektroanalyyttisiin anturisovelluksiin mittaamalla hyvin alhaisia ja fysiologisesti merkityksellisiä dopamiinipitoisuuksia (40-85 nM) syklisellä voltammetrialla. Muokkaamalla pintaa hiilinanoputkilla, anturi pystyi havaitsemaan dopamiinia myös askorbiinihappoa ja virtsahappoa sisältävässä liuoksessa. Nämä aineet ovat pääasialliset häiriötekijät dopamiinin havaitsemisessa. Sekä tetraedrinen amorfinen hiili että hiilinanoputkilla muokattu pinta olivat bioyhteensopivia. Väitöskirjan tuloksien perusteella amorfisella hiilellä voi olla potentiaalisia sovelluskohteita in vivo -anturimateriaalina

Analysis of catechol, 4-methylcatechol and dopamine electrochemical reactions on different substrate materials and pH conditions

The electrochemical behavior of several structurally related catecholamine molecules has been investigated on different electrode materials with cyclic voltammetry, infrared spectroscopy and scanning tunnelling microscopy. Emphasis was on the identification of subsequent chemical processes that follow the main electron transfer step and complicate the interpretation of the mechanism, including the polymerization reaction and fouling of the electrode surface. Among the materials investigated, gold was found out to be the most active for the oxidation of catechol, 4-methylcatechol and dopamine. At the same time, it was also the electrode least sensitive to fouling after voltammetric cycling, exhibiting the highest reversibility. The effect of pH was also investigated. Increase in pH enhanced the processes of quinone hydroxylation and polymerization. Spectroscopic measurements allowed detection of both solution and adsorbed species participating in the oxidation and polymerization processes. Finally, STM results showed the formation of polydopamine granules on gold surfaces, which grew in size as the number of cycles increased. Measured height of the granules, less than 0.5 nm, suggests a flat orientation of the molecules conforming the polymer.The authors thankfully acknowledge financial support from the UA-FPU 2013-5796 grant (University of Alicante, Spain), the Ministerio de Economía, Industria y Competitividad, Spain (CTQ2016-76221-P), the European Framework Program-Marie Curie Actions under the ELECTRONANOMAT Project (Grant No. PIRSES-GA-2012-318990) and Academy of Finland, Finland (Project Number #285526)