Patent Application: US-26799608-A

Abstract:
a sensor for the detection of chemical messengers is described herein . in particular a sensor for the detection of catecholamines , for example dopamine , epinephrine or norepinephrine , is reported . catecholamines play pivotal roles as neurotransmitters and hormones in the human body . an electrode for detecting a catecholamine comprising a conducting or semi - conducting substrate , and a polymer comprising polyethylenedioxythiophene on said substrate is disclosed . the polymer is doped with a cyclodextrin macrocycle . suitable cyclodextrin macrocycles include anionic cyclodextrin macrocycles , for example sulfonated β - cyclodextrins . also , disclosed in sensor capable of selectively detecting a catecholamine in the presence of ascorbic acid .

Description:
the poor solubility of the 3 , 4 - ethylene dioxythiophene ( edot ) monomer in aqueous solution , has led to the electropolymerisation of this monomer being predominantly performed in organic media . 55 surfactants , such as sodium dodecyl sulphate ( sds ), have been reported to improve the solubility of edot in aqueous and organic media . 7 in general , it has been communicated that a critical micellar concentration ( cmc ) of surfactant is required in solution if polymerisation of edot is to occur . cyclodextrins ( cds ) have been used in place of surfactants , 8 . 9 owing to the ability of cyclodextrins to form a host guest interaction with edot , thus increasing the solubility of the edot monomer in water . in the example disclosed herein , sulfonated β - cyclodextrin ( β - cd ) was utilised as the dopant anion necessary for film formation to occur . the films were electropolymerised onto gold electrodes from an aqueous solution of 0 . 1 m ethylenedioxythiophene and 0 . 01 m sulfonated β - cyclodextrin , sodium salt . polymerisation was carried out by cycling the potential between − 0 . 5 and 1 . 06 v / sce at a scan rate of 50 mv s − 1 for a total of three cycles . a ) the edot : sulfonated β - cd solution concentrations ( and ratio ); and b ) the polymerisation technique utilised — when cyclic voltammetry is utilised the following parameters can be modified to vary the pedot / sulfonated β - cyclodextrin film properties ; i ) the upper ( anodic ) potential of the voltammetric sweep used when fabricating the polymer film . this upper potential is important for system optimisation ; and ii ) the sweep rate . a polymerisation solution of 0 . 1m edot : 0 . 01m sulfonated β - cd ; this 10 : 1 ratio is important ; cyclic voltammetry ( cv ) is important to ensure that a homogeneous thin film is formed . films grown using this technique exhibit enhanced dopamine signals when compared to potentiostatic growth films ; sweeping from − 0 . 5 to + 1 . 06 v vs sce at a scan rate of 50 mv s - 1 ; and three electropolymerisation cycles to form a thin but a homogeneous film . all scans were completed on a solartron 1285 potentiostat . the data provided herein and in the figures were obtained using cyclic voltammetry . for example , in fig1 we see a cyclic voltammagram of three electropolymerisation cycles of a solution of 0 . 1m edot : 0 . 01m sulfonated β - cd . irreversible oxidation , i . e . electropolymerisation of the monomer occurs at approximately 0 . 8v and leads to film formation ( 101 ). no peak in the reverse sweep direction indicates that this is essentially an irreversible process . in order to detect very small concentrations of dopamine using the electrode array of the present invention , the shape of the sulfonated β - cd doped pedot film current profile in background electrolyte is vital . suitable electrolyte solutions may comprise 0 . 1m na 2 so 4 , or 0 . 1 m nacl . desirably , the electrolyte solution comprises 0 . 1 m nacl . the sulfonated β - cd doped pedot polymer exhibits a narrow trough or current decay in the mid - region of the oxidative sweep , as shown in fig2 . in fig2 the trough arises at approximately 0 . 38v . the position of this trough can be fine tuned by varying the parameters involved in the formation of the electrode array so that the small dopamine signal ‘ sits ’ in it , as shown in fig3 . the oxidation potential of dopamine is at approximately 0 . 38v , as shown by the detection of a 1 μm solution of dopamine . thus , the position of the trough should be located so that the region proximate to the oxidation potential of dopamine is not obscured by the current profile of the sulfonated β - cd doped pedot film . the pedot / sulfonated β - cd film on a gold electrode of the present invention exhibits excellent peak separation between the peak for dopamine and that of ascorbate ( aa ), as shown in fig4 . fig4 comprises a cyclic voltammagram illustrating simultaneous detection of 1 × 10 − 6 , 1 × 10 − 5 & amp ; 2 . 5 × 10 − 3 m da ( 402 ) in the presence of 1 × 10 − 3 m aa ( 401 ). the center trace is the bare gold response to a 1 × 10 − 3 m da solution ( 403 ). the signal from dopamine is independent of the presence of ascorbic acid even at high concentrations . this selectivity also extends to other common interferants such as uric acid , dopac and homovanillic acid . the exclusion of these last two species is particularly advantageous as these are metabolites of dopamine which are known to poison other prior art electrodes reducing their sensitivity . α - cyclodextrins have a smaller cavity than β - cds and , therefore , should exhibit different selectivity properties than those of the β form . initial experiments have indicated that , the sulfonated α - cyclodextrin does not exhibit selectivity towards dopamine over ascorbic acid , similar to the sulfonated β - cyclodextrin discussed above . fig5 shows the voltammetric response of the sulfonated α - cyclodextrin doped pedot film on a gold electrode to 1 × 10 − 6 m dopamine , while fig6 shows the response of the sulfonated α - cyclodextrin doped pedot film on a gold electrode to 5 × 10 − 4 m dopamine ( 601 ) and a mixture of 5 × 10 − 4 m dopamine and 5 × 10 − 4 m ascorbic acid ( 602 ). fig6 clearly illustrates that there is no separation of the ascorbic acid and dopamine peaks but a combined peak for the oxidation of both analytes is observed . investigations with respect to the utility of other anionic β - cds were performed . results for a phosphated β - cd ( ph β - cd ) are disclosed below . akin to the sulfonated analogues , the ph β - cd was used to dope the pedot film , and the resultant polymer modified electrode was used to sense dopamine . fig7 depicts the cyclic voltammogram response of a ph β - cd modified gold electrode modified to a 1 × 10 − 6 m da solution ( 701 ). the background electrolyte contribution has been subtracted for clarity . the response is very well defined and quite substantial confirming that the film should be capable of detecting low dopamine concentrations . fig8 illustrates the voltammetric response of the ph β - cd / pedot modified gold electrode to a 5 × 10 − 4 m ascorbic acid solution ( 801 ), a 5 × 10 − 4 m dopamine solution ( 802 ) and a solution comprising 5 × 10 − 4 m dopamine & amp ; 5 × 10 − 4 m ascorbic acid ( 803 ). the cyclic voltammogram of dopamine 802 exhibits a well defined peak at e p ˜ 0 . 38v , which is ascribed to the catalytic oxidation of dopamine by the film . the film also catalyses the oxidation of ascorbic acid , with e p ˜ 0 . 16v , as observed in trace 801 . when the electrode was placed into the mixed solution ( trace 803 ), we observe that the oxidative response of the electrode to both species is evident as a single well defined peak at e p ˜ 0 . 4v . this peak current is of similar magnitude to the summation of peak currents for the two separate oxidations of dopamine and ascorbic acid . whilst the ph β - cd / pedot / au electrode was successfully used in the detection of dopamine , the selective detection of dopamine in the presence of ascorbic acid was unsuccessful as both analytes were oxidised at the same potential by the film . further experiments directed to polymerising the edot monomer in water using kcl as the dopant were completed . surprisingly , and contrary to literature reports that surfactants are necessary for polymerisation to occur in aqueous media , a polymer film was formed on the electrode . however , the sensing properties of this modified electrode were poor . fig9 compares the response of the sulfonated β - cyclodextrin ( 901 ) pedot film on a gold electrode versus the kcl doped pedot film on a gold electrode ( 902 ), to a 1 × 10 − 3 m dopamine solution . the same experimental parameters were used in the fabrication of both modified electrodes and the same background electrolyte , na 2 so 4 , was used to test the sensing properties . background scans for the sulfonated β - cd doped pedot film ( 903 ) and the kcl doped pedot film ( 904 ) can also be seen in fig9 . the sulfonated β - cyclodextrin doped pedot film modified gold electrode ( 901 ) exhibits higher oxidation currents , thus allowing the detection of lower dopamine concentrations at the pedot / cd electrode than is possible at the bare electrode , and also shows a catalytic oxidative response to the dopamine . the oxidative response of the film to dopamine is termed catalytic because it results in the oxidation of dopamine occurring at a lower potential than at the bare electrode ( bare = gold , platinum or glassy carbon , etc .). normally at the bare electrode we would see a dopamine peak at about 0 . 5v but with the pedot / cd film this potential is reduced to about 0 . 4v , and as such is considered to have a catalytic effect . the kcl doped pedot ( 902 ) behaves as a permeable membrane through which the dopamine diffuses and is oxidised at the electrode surface . that is , the response to dopamine oxidation is not catalytic and therefore is not specific to dopamine oxidation . in fig1 the voltammetric response of the pedot / cd film modified gold electrode to a 5 × 10 − 4 m ep solution ( trace 1002 ) and 5 × 10 − 4 m ep in the presence of 5 × 10 − 4 m aa ( trace 1001 ), obtained using cyclic voltammetry , is shown . there is a well defined peak due to ep oxidation at ˜ 0 . 45v . the ep oxidation peak is again evident in the presence of aa 1003 . in fig1 the voltammetric response of the pedot / cd film to a solution of 1 × 10 − 5 m norep and 1 × 10 − 3 m aa obtained using cyclic voltammetry is shown . there is a well - defined peak 1101 due to norep oxidation at ˜ 0 . 45v . the norep oxidation peak is evident in the presence of aa peak 1102 . the words “ comprises / comprising ” and the words “ having / including ” when used herein with reference to the present invention are used to specify the presence of stated features , integers , steps or components but do not preclude the presence or addition of one or more other features , integers , steps , components or groups thereof . it is appreciated that certain features of the invention , which are , for clarity , described in the context of separate embodiments , may also be provided in combination in a single embodiment . conversely , various features of the invention which are , for brevity , described in the context of a single embodiment , may also be provided separately or in any suitable sub - combination . 1 . y . f . zhao et al ., talanta , 66 , 51 - 57 ( 2005 ). 2 . s . b . hocevar et al ., electroanalysis , 17 , 417 ( 2005 ). 3 . n . izaoumen , d . bouchta , h . zejli , m . e l kaoutit , k . r . temsamani , analytical letters , 38 ( 2005 ), 1869 - 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