38723182 New Electrochemical Sensors

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366 ANALYTICAL PROCEEDINGS, NOVEMBER 1991, VOL 28

New Electrochemical Sensors

The following are summaries of eleven of the papers presented a t the Joint Analytical/Faraday Symposium a t the Annual Chemical Congress of the RS C held on April 8th-I2th,1991, in Imperial College, London.

Solid-state Gas Sensors: Prospects for Selectivity

David E. WilliamsDepartment of Chemistry, University College London, 20 Gordon Street, London WCI H OAJ

Metal oxides, such as tin dioxide and zinc oxide, fabricatedeither in the form of thin (=lo0 nm) films or as thicker porousbodies, show an electrical conductivity at temperatures ofabout 300C which is very sensitive to the presence of traceamounts (ppm level) of reactive gases (hydrocarbons, hydro-gen, carbon monoxide, methane, ammonia, oxides of sulphurand nitrogen, chlorine, hydrogen sulphide) in air. Thisphenomenon has been exploited for many years in warningdevices. Most commercial elements utilize porous, thick (==lo0pm) films of tin dioxide. Typically, the layer might be depositedont o the outside of a small alumina tube by successive dippinginto a tin salt solution and thermal decomposition. A heater isthreaded i nto the centre of the t ube. These devices are simple,robust and inexpensive. They are, however, if anything, toosensitive to too many things, although a certain degree ofselectivity can be obtained by control of the operating

temper ature. Th e question is, therefor e, whether, by choice ofoxide material or some other means, selectivity can beenhanced. 1, 2 M ~ r r i s o n , ~ n discussing this question, haspointed out that although the gas sensing phenomenon appearsto be intimately connected with the occurrence of a surface-catalysed combustion, t he notion of selectivity in a gas sensor isdifferent to that of the apparently related notion of selectivityin a catalyst: for a cat alyst, selectivity means a bias in favour ofa particular reaction product, whereas for a sensor it means abias in favour of a particular reactant, often in a complexmixture of potential reactants.

As far as the second part of t he question is concerned, it hasbeen pointed out' that the surface-catalysed combustion causesa gradient in the composition of reactant and product gasesthroughout a porous sensor structure , and that this can be used

to build in a degree of selectivity based on the differingreactivity of different gases. Hence, in a sufficiently thickstructure, the outer layers of the device ac t as a kind of filter,burning away the more reactive gases and leaving only the lessreactive gases to affect the conductivity in the vicinity ofelectrodes buried within the structure. There seems to beplenty of scope for using this kind of idea, the alteration ofrelative response by alteration of the geometry of the sensorlayer and of the measuring electrodes, to develop tailoreddevices.

In order t o address the first part of the question, anexperimental programme was carried ou t2 to investigate theresponse of several hundred different oxides to a range ofgases. Table 1 ndicates the range of materials investigated; thegases studied were: hydrogen, carbon monoxide, methane,propane, ethene, ammonia, hydrogen sulphide, nitrogendioxide, sulphur dioxide and chlorine, and changes in oxygenpartial pressure . The first conclusion of this work was strikinglysimple: most oxides respond to most gases. A few materialsshowed selectivity to some gases, most often ammonia and

Table 1 Range of materials investigated

Perovskite-type Pyrochlore-typecompounds compounds

of tin of tin NiobatesBronzes

A l - B,Snl - CXO3-A Ca, Sr, Ba Specific examples: Examp les:

B Ca, Sr, Ba , CaCeSnzO7

A2 - B,Sn2 - x C x 0 7 Al - xBxNb206

CaSnTi207 A , B-Pb , Ba, Sr

Pb Gd 2S n2 07 A6BxNblO - o 3 0La, Y , Gd La2Sn207 Example:

y 2 s n 2 0 7 Bi6Fe4Nb6030C Fe, Co Bi2Sn207

Ti, Zr, CeTransition metal

Fe, Co , Ni, CuTantalates compounds

Specific examples:BaSn0 3 FeTa04 niobatesBaSn0.5Ti0.503 CoTa206BaSn0,9Zr0,103 NiTa206BaSnO.8FeO. 0 3 CUTa206Ba0.9Gdo.1Sn03

hydrogen s~lphide,~ ut this was the exception rather t han therule. A second conclusion was that the re was a clea r rz-typelp-type classification of the oxides , even in the absence of aresponse to varying oxygen partial pressure, and correspond-ingly a classification of the gases into oxidizing and reducingagents. Exceptions to this classification stood out clearly: Tab le2 shows a part of i t, in which the response has been codedsimply in terms of its sign. The interpretat ion is that, in general,the response of oxides to gases, being a change in theconcentration of the charge carriers giving rise to the conduc-tivity, is controlled by the surface concentration of a single,reactive surface species, common to all oxides and presumed(following studies on tin dioxide and zinc to be anoxygen ion, 0 2 - , - . Response mechanisms have been fullydiscussed elsewhere , 1 3 2 3 5 nd, i ndeed, a model simply rational-izing the exceptions in the classification can be constructed.6The answer, the refore , to the first part of the question posedabove is that very strong selectivity seems rather rare, beingconfined to a few materials and a few gases: if a generalizationis require d, in the study these were those gases (NH3, H2S) thatcould be considered t o act as Lewis bases on mate rials in whichit is presumed that oxygen surface species were unreactive atthe measurement temperature. O n the other hand, there wassufficient variation in the relative magni tude of the response ofdifferent materials to different gases to allow ample scope forthe st rategy of using arrays of differently responding sensors toresolve the composition of mixtures.

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ANALYTICAL PROCEEDINGS, NOVEMBER 1991, VOL 28 367

Table 2 Classification of materials and responses: the response is coded simply by the sign of the resistance change on exposure to the gas.Exceptions to the general n-typelp-type classification of materials, showing opposite sign of response to oxidizing and reducing gases stand outclearly. A plus sign indicates a resistance increase with respect to the value in air ; a minus sign indicates a resistance decrease. In all atmospheres,except for the first listed, the gases are introduced as mixtures (1'70 except where stated) in air

Low 0 2 C2H4 H2SMaterial (100PPm) cH4 co H2 (0.7%) NH3 so2 (0.1%) Cl2 NO2

2. Effectively p-type oxides-Sr(SrNb) 0 3LiFeSn04Y2Ti20BaTi03SrTiO3LaO.9CaO. Fe03La6W012NdzZ1-207Y2BaZn05

++++++++ ++

+

+

+++ + + +

-+-

-+++

+ +

References1 Williams, D. E. , in Solid State G as Sensors,eds. Moseley, P. T.,

and Tofield, B. C. , Adam Hilger, Bristol and Philadelphia, 1987,

2 Moseley, P. T. , Stoneham, A. M., and Williams, D. E.,Techniques and Mechanisms in Gas Sensing,eds. Moseley, P. T.,Williams, D. E., and Norris, J. 0. W., Adam Hilger, Bristol andPhiladelphia, 1991, ch. 4.

pp. 71-123.

3 Morrison, S. R., Sens. Actuators, 1987, 12, 425.4 Moseley, P. T., and Williams, D. E., Sens. Actuators, 1990, B1 ,

113.5 Heiland, G. , and Kohl, D . , in Chemical Sensor Technology,

Volume I , ed. Seiyama, T., Kodansha and Elsevier, Tokyo andAmsterdam, 1988, pp. 15-38.

6 Williams, D. E. , and Moseley, P. T., J . Muter. Chem ., in thepress.

Semiconductor Gas Sensors and Selectivity

Gary S. V. ColesDepartment of Electrical and Electronic Engineering, University of Wales, Swans ea SA2 8P P

The resistance of certain semiconductor materials has beenknown to change in the presence of reducing gases since theearly 1950s. Gas sensors exploiting this observation, initiallybased on zinc oxide but now usually based on the n-typesemiconductor tin dioxide, have been available commerciallyfor some two decade^.^.^ Early sensors received a great deal ofcriticism as they tended to be irreproducible and have poorselectivity, responding to a wide range of reducing gases. Itmight also be true that industry and commerce expected toomuch of this type of sensor, despite the fact that they canpossess many of the characteristics desirable in a gas sensingdevice, including high sensitivity, fast response speed, lowpower consumption and cost. However, it is the problem ofselectivity that is addressed in this paper.

Selectivity in Tin Dioxide Gas SensorsEarly workers in this area discovered that operating tin dioxidesensors at different temperatures conferred a degree of~electivity.~or example, operating a sensor at =300 "C gave adevice sensitive to the presence of carbon monoxide but

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$ 10B

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20 2 4 6

[Gas] ( l o3 ppm)

Fig. 1 Variation of conductivity with gas concentration for ahydrogen-selective sensor in hydrogen and carbon monoxide

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0 5 10

25

0 5 10 0[Gas] ( l o 2 ppm)

5 10

Fig. 2three different operating temperatures: ( a ) 400; ( b ) 280; and ( c ) 175 "C

Resistance versus contaminant gas concentration plots for a sensor fabricated from Sn02 pre-sintered at 1500 "C in air and maintained at

insensitive to the presence of methane . Producing a sensor withthe opposite selectivity required the addition of = l % platinumto the oxide and operation at a higher tempe rature of -600 "C.Initial work at Swansea produced two selective sensors .6 Thefirst, prepared from tin dioxide, aluminium silicate andpalladium chloride, gave a device sensitive to the presence ofthe lower hydrocarbons but insensitive to the presence ofcarbon monoxide. A second s ensor, formed by th e sintering oftin dioxide and bismuth oxide, gave a sensor with the oppositeselectivity. The notable feature of these sensors is that theselectivity is observed throughout th e viable opera ting temper -ature range (between =150 "C, below which resistancesbecome excessively high and surface reactions too slow, and-700 "C, above which conductivity by thermal excitationobscures the changes produced by the presence of a contami-

nant gas). A maximum sensitivity is observed at an operatingtemperature of =250"C. In an attempt to understand theproperties exhibited by these sensors the carbon monoxideselective device was studied in more detail.

Tin Dioxide-Bismuth Oxide SystemTin dioxide itself exhibits conductance changes in the pre senceof many reducing gases. However, as bismuth oxide is addedthe response to methane rapidly diminishes, falling to zero at-15% m/m. The response to carbon monoxide remainsunaltered. Above a concentration of =17% m/m Biz03 theresponse to CO also begins to fall and this reaches zero above-23% m/m. The optimum composition of this sensor istherefore 8345% m/m Sn02 1517% m/m Bi2 03. Althoughthe te rm selective has been used, in reality these sensors , andmany othe r types of sensor, will also respond to certa in othergases, notably hydrogen. When the Bi203 content of thesedevices is increased above that at which the carbon monoxideresponse has fallen to zero, the response to hydrogen isobserved t o persist undiminished until this also begins to fall tozero above -25% m/m. It is therefore possible to produce athird sensor which is sensitive to the presence of hydrogen butshows no resistance changes in the presence of carbonmonoxide or the lower hydrocarbon^.^ A remarkable featureof this sens or is its linear change in conductance with increasinggas concentration even up to s everal thousand ppm, as shownin Fig. 1. Sensors of this type usually tend towards saturation a tsuch high levels.

In the production of these se nsors the oxide mixture is fired

at 800C. It is known that bismuth oxide and tin dioxideundergo a solid-state reaction above -600 "C producingbismuth stannate, Bi2Sn207, which has a pyrochlore struc-ture.' In our senso rs all of the bismuth oxide reacts and the

final sensor element is composed of bismuth stannate and tindioxide only. There are several other stannates of generalformula M2Sn207 which also possess the pyrochlore s truct ure 9These were also studied in the hope that they would yield newselective sensors and further elucidate the properties e xhibitedby these devices. An immediate difference is the hightemperatures required t o produce these other stannates , beingtypically in the region of 1500 "C. Sensors produced f rom thesematerials in an analogous way to the tin dioxide-bismuth oxidesensors, but fired at higher temperatures, showed variousdegrees of selectivity and sensitivity but none comparedfavourably with the original devices. As a control , sensor s werealso produced from pure tin dioxide fired at 1500C. Thesedevices showed remarkable characteristics as shown in Fig. 2.At high operating temperatures ( ~ 4 0 0 C) the sensor shows

conventional decreases in resistance in the presence of all threegases as would be expected for this n-type material. At lowoperating temperatures (-175 "C) the device shows no re-sponse to carbon monoxide or methane but exhibits an increasein resistance in the presence of hydrogen as would be expec tedin a p-type material. At intermediate temperatures (-280 "C)no response is observed for methane; a conventional responseis observed in the presence of hydrogen but a resistanceincrease is observed in the presence of carbon monoxide.

ConclusionsIt is possible to produce tin dioxide based sensors with markedselectivity towards the common toxic and/or flammable gasesmethane, carbon monoxide and hydrogen. These sensors areselective throughout the viable operating tempera ture range. I t

is also possible t o produce a single sensor in which the selectivityand mode of operation can be switched and tuned by modulationof the operating temperature. The exact reasons for theseobservations are as yet not fully understood but are cur rentlybeing studied and will form the basis of a subsequent paper.

References1 Brattain, W. H. , and Bardeen, J., Bell Syst. T ech.J . , 1953,32,1.2 Heiland, G. , 2 . Phys . , 1954, 138, 459.3 Seiyama, T., Kato, A., Fukiishi, K., and Nagatini, M . , Ana l .

C h e m . , 1962, 34, 1502.4 Taguchi, N. , Br. Pat. , 1280809, 1288009, 1282993, 1970.5 Firth, J . G., Jones, A . , and Jones, T. A. , Environmental Sensors

and Applications, I ER E Conference Proceedings, 1974, p. 57.6 Coles, G. S . V. , Watson, J., and Gallagher, K . J . , Sens.

Actuators, 1985, 7 , 89.

7 Coles, G. S. V. , Williams, G., and Smith, B., Sens. Actuators,1991, B3, 7 .8 Roth, J ., J. Res. Natl . Bur. Stand., 1956, 56, 17.9 Brisse, F. , and Knop, O. , Can. J. C h e m . , 1968, 46, 859.

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370 ANALYTICAL PROCEEDINGS, NOVEMBER 1991, VO L 28

X = polyaza

Fig. 1 Structural formula of bis(crowns)

and it has been postulated that the linker between the twocrown rings will form a p ~ c k e t . ~ t occurred to us that if thelinker was formed from a polyamino residue, as for exampleformula (I ) (Fig. l ) , hen in hydroxylic solvents at neutral pH,it should be capable of complexing the counter ion of itspotassium filling.

DiscussionAdenosine triphosphate (ATP) is a favourite anion forcomplexation studies. Suitable receptors for the phosphateresidues have been dete cted previously by examining the time-averaged 31P NMR signals for the a,P,y phosphorus atoms,which are shifted relative to those of the free AT P in solutionscontaining receptor in a suitable mole ratio t o the ATP.6,7

Molecular graphics studies indicated that diethylenet riaminein the extended, protonated conformation was an excellentsideways fit to the phosphates of a triphosphate chain, while aslightly longer chain, tetraethylenepentamine, likewiseextended and protonated, could wrap simultaneously roundthe y and residues; small cyclic polyamines (four nitrogens)were more likely to interact with the terminal y phosphateonly. The 31P shifts observed for 1 : 1 ratios of polyamine toATP were shifted for these situations in accordance with thisprediction. The size of cavity required to complex variousanions from chloride to ATP was also estimated by usingmolecular graphics for the bis(crown) designs.

The bis(crowns) (I) (Fig. 1) were shown by H NMR tosandwich potassium ions.5 The Schori-Grodzinski NMRmethod8 of determining rates of exchange of quadrupolarnuclei between solvated and complexed environments wasapplied with limited success, to show that the coreceptor isclearly binding potassium ions plus counter ionssimultaneously.

A synthetic route, and the separation and characterization ofthe bis(crowns) (I) , he first multi-receptors t o exhibit multiplebinding to cation and counter ion simultaneously, will bedescribed elsewhere. Further evaluation of the modifiedpotential of the assembly for recognition and binding of anionicsubstrates in the presence of potassium ions is proceeding,prior to development of the new materials as anion sensors.

Thanks are due to the SERC for financial support, and to Dr.N. P. Tompkinson, Dr. K . I. Kinnear, Dr. E. Arafa and D. P.Mousley for their help in this project.

ReferencesBrookhaven Protein Data Bank, Bernstein, F. C., Koetzle,T. F., Williams, G. J. B., Meyer, E. F., Jr., Brice, M. D.,Rodgers, J. R. , Kennard, O. , Shimanouchi, T. , and Tasumi, M .,J. MoI. Biol., 1977, 112, 535.Pflugrath, J. W., and Quiocho, F. A. , Nature (London), 1985,314, 257.

Cullinane, J. , Gelb, R. I., Margulis, T. N . , and Zompa, L. Z. ,J. Am. Chem. SOC.,1982, 104, 3048.

Lehn, J.-M., Meric, R., Vigneron, J. -P. , Bkouche-Waksman, I.,and Pascard, C. , J. Chem. SOC., Chem. Commun ., 1991, 62.

Handyside, T. M., Lockhart, J. C., McDonnell, M. B., andSubba Rao, P. V., J. Chem. SOC.,Dalton Trans., 1982, 2331.Hosseini, M. W., Lehn, J.-M., and Mertes, M. P., Helv. Chim.Acta, 1983, 66,2454.

Hosseini, M. W, Lehn, J.-M., and Mertes, M. P., Helv. Chim.Acta, 1985, 68, 818.

Shchori, E. , Jagur-Grodzinski, J ., Luz, Z. , and Shporer, M.,J. Am. Chem. SOC. ,1971, 93, 7133.

Control of Ion Transport Through Lipid Membranes

Ulrich J. Krull, Dimitrios P. Nikolelis, John D. Brennan, R. Stephen Brown, Michael Thompson,Vida Ghaemmaghami and Krishna M . KalluryChemical Sensors Group, Department of Chemistry, Erindale Campus, University of Toronto, 3359Mississauga Road North, Mississauga, Ontario L5 L IC6, Canada

The perturbation of the struc ture of artificial lipid membranescan be monitored by electrochemical methods, and offersopportunities for development of chemically selective biosen-sors. An important advantage of such an electrochemicalsensing system is the increased sensitivity which is derived froman intrinsic amplification process. A single selective bindingevent between a receptor and a target molecule can result in anincrease of the transmembrane conduction that involvesthousands of ions.

A large number of biochemical reactions based o n enzyme-substrate , antibody-antigen, lectin-saccharide , hormone-receptor and avidin-biotin interactions have been monitoredby observation of the transmembrane ion current. A further

extension of artificial lipid membranes for electrochemicalsensing was the construction of biomimetic ion-channelsensors.* These devices were based on Langmuir-Blodgettdeposition of multilayers of acidic lipid membranes on glassycarbon electrodes, More than three layers of lipid werenecessary to block the permeation of Fe(CN)64-, which wasused as a marker ion. In the presence of the stimulant Ca2+, achange in the alignment of t he lipid occurred on the glassycarbon surface owing to elect rostatic complexation of calciumions with acidic phosphate head groups of the lipids, resultingin an increase of the mar ker ion penetration to the electrode.When ethylenediaminetetraacetic acid was added to thesolution in slight excess of t hat r equired to complex the calcium

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ions, the electrode signal for Ca2+ was eliminated. Thisindicates that a conductive zone can be opened reversibly byinteraction of an analyte at a membrane in the absence of ion-channel proteins; however, the nature of such a conductivezone is poorly understood.

Determination of the mechanism of ion permeation andestablishment of control of the energetics associated withconductive pathways would permit optimization of the struc-ture of lipid membranes for biosensor development. Furtherdevelopment must include mechanical stabilization of a lipidmembrane onto a solid electrode , where covalent linkagesbetween the support and the lipidreceptor molecules aredesirable. In order to avoid the effects caused by accumulationof ions on one side of such a stabilized membrane, themeasurements must be made by driving the system with an a. c.voltage and by monitoring admittance with a phase-sensitiveamplifier. Progress towards a surface-stabilized a.c. admittancemodulation lipid membrane-based biosensor that operates onthe basis of control of ion permeat ion by artificial ion channelsis described.

Control of Ion Permeability Through Planar BilayerLipid Membranes

Ion conductivities through solvent-free planar bilayer lipidmembranes (BLMs) formed from mixtures of egg phosphatidylcholine and dipalmitoylphosphatidic acid were evaluated todetermine the effect of surface charge and phase domainformation on the process of ion transloca tion. Ion conductivityin a small d.c. voltage field was controlled by the surfacedistribution of potassium ions (0.1 mol dmP 3 KC1 electrolyte)at the membrane-solution interface as predicted from electri-cal double layer theory. It was found that the conductivity ofthe membranes could be approximated as a linear function ofthe per cent. mass composition of the charged lipid. Theconductivity was observed to alter drastically at a lipidcomposition containing a minimum of 25% phosphatidic acidas this component within the membrane was increased. Thiswas attributed to the presence of a phase transit ion induced bythe phosphatidic acid. A t compositions of acid less than 25%,ion conduction occurred through zones that were enriched inthe charged lipid. At concentrations of the acid above 2 5 % , theaverage surface charge was the dominant factor which deter-mined the magnitude of ion conductivity. The adjustment ofpH t o control the degree of ionization of the phosphatidic acidhad a similar effect to the variation of the amount of the acidicphospholipid within the membrane for experiments carried outat fixed pH. The ion conductivity could be used to measureaccurately the pK, value associated with the acidic lipid withina planar BLM, and suggests a general method for evalua tion ofpK, for charged species in lipid membranes.

Based o n results of studies of cystic fibrosis which implicatedhydroxystearic acid (HSA) as a contributing factor in alteredbiomembrane function, solvent-free planar BLMs and mono-layer films were prepared from a lipid mixture (by mass)containing 34% phosphatidylcholine, 19% dipalmitoylphos-phatidylserine , 47% cholesterol and variable amounts of 10-and 12-hydroxystearic acid (0-50%). The structures of mono-layer films at the air-water interface of a Langmuir-Blodgetttrough were studied by pressure-area correlations and byfurther correlations with microscopic phase separation asrevealed by fluorescence microscopy. In order to elucida te therole of the hydroxyl moieties in ion permeability the transmem-brane ion current was corrected for the effect of the negativesurface charge of the carboxylic acid, and determined byreplacement of the HSA component with stearic acid. The ioncurrents were found to increase approximately exponentiallywith the mole ratio of HS A. Two models of ion conductionthrough BLMs were considered: hopping via hydrophilic siteswithin the hydrophobic zone of BLMs introduced by thehydroxyl moiety of 10- or 12-HSA; and transport throughinterfacial regions between phase domains which represent

areas of low steric density and structural order withinmonolayers. While the two mechanisms are not distinct, theion permeability and monolayer compression results didindicate that HSA had a large effect at low concentrations. Theresults suggested that the physical location of ion permeationthrough BLMs containing low concentrations of HSA waspredominantly at interfacial zones at the edges betweendomains, and that artificial ion channels had been generatedby virtue of the edge activity of HSA.

Electrochemistry of Surface-immobilized MembranesA portable admittance modulation measurement device wasconstructed, and was designed to measure both the in-phaseand out-of-phase signal components for determination ofeffective on current and membrane capacitance. The sensiti-vity and detection limit for the a.c. system were tested bystudying the interaction of the ionophore valinomycin withplanar BLMs. The electrochemical effects were observed asconductance changes of the membrane, with the limit ofdetection for valinomycin being at the 1 nmol dm-3 concen-tration level.

Metal electrodes were used as supports for covalent attach-ment of amphiphiles. Platinum electrodes with a surface areaof 1 cm2 were oxidized to provide a high density of surfacehydroxyl sites.3 Immobilization of amphiphiles was carr ied outby reaction of the hydroxyl sites with ~i l a n e . ~ old electrodeswere prepared by vacuum deposition of a 250 nm layer of themetal onto a 30 nm layer of chromium that covered borosilicateglass slides. Surface attachment of amphiphiles to this metalwas achieved by sulphur-gold interaction^.^

A wide variety of amphiphiles differing in hydrocarbon chainlength, number of chains (one or two), chain polarity, headgroup charge and head group size ( e . g . , acidic phosphate,carboxylic acid and ester, phosphatidylcholine) were attachedto both the platinum and gold surfaces. Two-step attachment

procedures, as exemplified by the initial deposition of amino-propyltriethoxysilane (APTES) on to platinum followed bylinkage of a 10-carbon phosphatidylcholine through an amidebond to the amino group of APTES, often provided greatersurface coverage than if an equivalent 16-carbon phosphatidyl-choline had been deposited directly by the reaction of hydroxylmoieties with silane at the metal surface. Surface coverage formost experiments was in the range 40-85% as determined byX-ray photoelectron spectroscopy, and was dependent on thedeposition procedure, the chain length and the number ofchains. The electrochemical results indicated that the bestblockage of ion conductivity occurred when the amphiphilescontained long hydrocarbon chains. Species such as trichloro-octadecylsilane and octadecylthiol provided the best blockage,reducing the in-phase signal component by 95% for both typesof metal electrode. Analogues of natural lipids such asdimyristoylphosphatidylcholine reduced the in-phase compo-nent by values of about 50%. Subsequent incubation of lipid-coated electrodes in solutions containing membrane-solublespecies such as cholesterol greatly reduced the magnitude ofthe in-phase component of the signal to values approachingthose found for BLMs. These latter electrodes were tested forresponse to the presence of valinomycin, and achieveddetection limits in the range 10-100 nmol dm-3.

A furt her series of analytical experiments were carried out t odevelop electrodes that were sensitive to pH variations toextend the concept of control of phase domain structure toimmobilized membranes. Linear 10-carbon silane and thiolcarboxylic acids were immobilized onto platinum and goldsurfaces, and both systems showed good sensitivity to pH (e.g. ,a pH change from 7 to 8 caused a conductivity change of 25% ).Modification of this system to evaluate a biosensing strategywas then carried out. Enzymically active urease has beenadsorbed onto these acidic surfaces, and has also beencovalently immobilized through the acidic functional group.

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The intent was to use the urease-urea reaction to generate alocal transient p H gradient which would perturb t he membranestructure. Tentative electrochemical results, and definitivespectroscopic results, indicate that this has been accomplishedand that sub-micromolar detection levels can be achieved forthe substrate with good reversibility and longevity.

We are grateful to the Canadian Defense Research Establish-ment-Suffield and the Natural Sciences and EngineeringResearch Council of Canada for financial support of this work.

References1 Krull, U. J ., and Thompson, M. ,ZEEE Electron Devices, 1985,

32 , 1180.2 Sugawara, M., Kojima, K., Sazawa,H . , and Umezawa, Y . ,

Anal . Chem. , 1987, 59, 2842.3 Moody, G. J. , Sanghera, G . S . , and Thomas, J. D . R., Analyst,

1986,111,

1235.4 Ghaemmaghami, V., Kallury, K. M., Krull, U. J. , Thompson,

M ., and Davies, M. C . , Anal . Chim. Acta , 1989, 225, 369.

Gas Sensors Using the Work Function of Organic Semiconductors

Jiii Janata and Jan LangmaierDepartment of Materials Science and Engineering, University of Utah, Salt Lake City, UT 841 12, USA

The key issue in the development of chemical sensors is thedesign of new chemically selective layers. Organic semiconduc-tors have attracted considerable attenti on as the materials forsuch diverse applications as power sources, non-linear optics,superconductors and molecular electronics. Not surprisingly,they ar e also being investigated as possible sensor materials in awide range of applications. The parameters that a re modulatedby the chemical interactions include mass, optical absorptivity,conductance, Galvani potential and work function (WF). Thispaper will be restricted to a discussion of the interactions oforganic semiconductors with the gaseous phase and will focusparticularly on the chemical modulation of the WF.

The electron WF is one of the fundamental material

constants. It plays a key role in the distribution of electrons insolid-state structures, affects the catalytic properties of solidmaterials and determines the rate of corrosion and chemicalresistance of materials. It is defined as the work that has to beused in order to extract a n electron from the interior of a phaseand place it outside the reach of image forces, in the so-calledvacuum refe rence level. There are two components of the WF:the bulk contribution, which is related to the chemical potentialof a n electron in the phase and represents the affinity of theelectron for the matrix; and the surface contribution, which isrelated to the electric field resulting from the surface dipolelayer.

Measurement of the WF provides information about theelectronic properties of a material. For example, organicsemiconductors prepared by electro-oxidation under differentconditions have a different WF , which is further affected by thepresence of other electron donors/acceptors. This phenom-enon is the basis for a new class of electrochemical sensors,particularly for the sensing of gases. To date , the WF has beenused analytically only rarely. The best known device whichmeasures the WF is the vibrating capacitor (Kelvin probe).Because of its size it is impractical as a sensor, although it wasproposed as a gas chromatographic detector almost 40 yearsago. The operating characteristics of solid-state devices basedon metal-insulator-semiconductor junctions, such as insulatedgate field-effect transistors or metal-insulator-semiconductordiodes, depend directly on the WF of the gate metal. This facthas been exploited in the design and development of well-known potentiometric sensors for hydrogen, which use palla-dium as the gate metal, and in transistors using organicsemiconductors which have been shown to respond to a varietyof organic vapours. In this paper the fundamental aspects ofthe WF will be reviewed, its potential for chemical analysis ofgases assessed and examples of general solid-state chemicalsensors based on its chemical modulation will be given.

It is necessary to realize that organic semiconductors can bedeposited in different ways, e.g., by sublimation, solventcasting or electrochemical deposition. The choice of thedeposition technique used is determined by the constraintsgiven by the sensor itself. In W F sensors it is a necessity that atleast one interface of the selective layer is capacitively coupledto the remainder of the sensor structure.' This condition issatisfied in a suspended gate field-effect transistor (SGFET)2and in its macroscopic counterpart the vibrating capacitor. Thelatte r has been used in this work to develop and characterize aselective layer for hydrogen cyanide based on electrochemi-cally prepared polyaniline (P ANI) .

Aniline can be easily polymerized from acidic media3 on th e

Pt plate of the vibrating capacitor and its WF can be measuredagainst a suitable reference plate, e.g., stainless steel. Aconsiderable advantage of this approach is that t he film on theworking plate can be examined by a variety of auxiliaryspectroscopic and microscopic techniques.

The WF of PANI itself is not affected by HCN. However,when the Ag-AgCN system is incorporated in PANI th e layerbecomes sensitive to HCN. The kinetics and the polarity of thechange of t he WF depend on several factors. When thePANI*Ag layer is prepared in the reduced state (PANI *Ag isa heterogeneous system; the asterisk signifies the heterogen-eity) its WF decreases on exposure to HCN. The responsebecomes reversible when the electropolymerization is carriedout from a glycerine-1 mol dm-3 HZS04 mixture. Glycerinefacilitates proton transfer from the silver clusters to the PANIbackbone :

eSlow 1 c-- ~ '

[Pt-PANI-Ag] + HCN - Pt-PANI-H+,AgCN]T -

Glycerine

On the other hand when the film is prepared in the oxidizedstate and/or when the AgCN complex is present the reactionproceeds according to the scheme:

Fast[Pt-PANI-Ag-AgCN] + HCN -

e --1

[Pt-PANI-H+ ,Ag( CN)2]?-A

tilycerine

In this instance the HCN molecule dissociates forming astrong Ag(CN)* complex and the proton is again transferred to

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the PANI backbone. The electroneutrality of PANI is main-tained by the inflow of electrons from t he reference plate whichis equivalent to t he increase of the WF. This result confirms themechanism of charge transfer between the guest molecule andthe m a t r i ~ : ~f the matrix is reduced (high value of WF) it actsas an electron donor and the WF decreases. When the matrix isoxidized (low WF) it can accept electrons and the WFincreases. For polypyrrole and polythiophene this protontransfer reaction is absent and the response to HCN isirreversible.

The response is logarithmic in the range 5-50 ppm and hassquare-root-time dependence, indicating predominantly bulkinteraction. The selectivity of this material to a variety ofenvironmentally important gases remains to be tested.

This work was supported by a contract from BWB and by agrant from the EPA Office of Exploratory Research, GrantNO. R-816491-01-0.

References

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Janata, J . , Principles of Chemical Sensors, Plenum Press, NewYork, 1989.Josowicz, M., and Janata, J., in Chemical Sensor Technology,ed. Seiyama, T. , Elsevier, Amsterdam, 1988.Zotti, G. , Cattarin, S . , and Comisso, N . , J. Electroanal. Chem.,1987, 235, 59.Blackwood, D., and Josowicz, M ., J . Phys. Chem., 1991, 9 5 ,493.

Applications of Electropolymerized Films in Electrochemical Sensors

Philip N. BartlettDepartment of Chemistry, University of Warwick, Coventry CV4 7AL

Electrochemical polymerization is a very convenient techniquefor the production of modified elec trode surfaces. The methodis simple to carry out and the deposition of the film is readilycontrolled by control of the electr ode potential. The method iswell suited to the deposition of films onto microelectrodeelectrode structures formed by photolithography.'

We have investigated the application of electropolymerizedfilms as a method for producing modified electr ode surfaces foruse in chemical sensors and biosensors. Much of this work hasconcentrated on the use of conducting polymer films formedfrom substituted pyrroles or other heterocyclic monomers butwe have also made use of poly(pheno1ic) films.

Ion-sensitive PolymersFilms of poly(5-carboxyindole) can be grown from acetonitrilesolutions. The resulting conducting polymer has a carboxylicacid substituent on every monomer unit of the chain. When thepolymer is transferred into aqueous solution the degree ofionization of these groups varies with the solution p H and this,in turn, alters the electrochemistry of the film. Th e films arestable at pH values less than 5 but dissolve slowly in aqueoussolution above pH 7. The pH dependency of the electro-chemistry of poly(5-carboxyindole) can be used t o make smallpH-sensitive electrodes. These were made by the electropoly-merization of the monomer from acetonitrile onto 125 pmdiameter platinum wires sealed in heatshrink PTFE. Thecoated electrodes were then transferred into buffered aqueoussolution at pH 2 and cycled until a stable response was attai ned,and then held at +800 mV versus SCE and the curre nt allowedto decay t o zero to convert the film into its oxidized form. p Hmeasurements were mad e using the oxidized electrodes with acommercial pH meter and calomel reference el ectrode.

At pH 7 some portion of the carboxylate groups in thepoly(5-carboxyindole) are deprotonated and can be used tohydrogen bond to protonated lysine residues around the haemedge in cytochrome c. This leads to the adsorption ofcytochrome c at the polymer surface in the correct orientationfor electron transfer between the polymer and the haemgroup 2 This interaction between the carboxylate groups andthe lysine residues mimics the hydrogen bonding interactionswhich are believed to play an important role in electrontransfer between cytochrome c and cytochrome oxidase, itsnatural redox partner.

In principle, it should be possible to confer ion selectivity ona conducting polymer film by attaching suitable substit uents to

the polymer. This might be advantageous because the mixedionic and electronic conductivity of the resulting conductingpolymer could then be utilized to make small ion-selectivesensors. We have investigated this approach by synthesizingpyrrole subst ituted in th e N-position with a benzo-15-crown-5derivative. Th e resulting monomer can be electropolymerized,and the properties of the resulting conducting polymer filmshave been in~est igat ed.~

Immobilization of Glucose Oxidase

The electropolymerization of pyrrole and N-methylpyrrolefrom buffered aqueous solutions can be used to immobilizeglucose oxidase and othe r enzymes at elect rode surfaces. In theresulting enzyme-loaded films the behaviour is determined bythe balance of the diffusion of reactants and products withinthe film and the kinetics for the immobilized enzyme. In orderto understand the behaviour of these films it is necessary tomodel these processes and t o compare the predictions of thesemodels with the experimental r e s ~ l t s . ~

Studies of glucose oxidase immobilized in poly( N-methyl-pyrrole) films show that when the natural redox partner,oxygen, is used as the media tor species the hydrogen peroxideproduced is not oxidized on the polymer but rather mustdiffuse to the underlying elect rode to be detected.' By usingtritium-labelled glucose oxidase we have determined theconcentrat ion of enzyme entrapped within our electropolymer-ized films and, by using these data and data from the kineticanalysis of the response of these films to glucose, we haveestimated the kinetics for the oxidation of glucose by theimmobilized enzyme. It was found that these kinetics are notsignificantly different from the values obtained in homo-geneous solution.

Studies in which oxygen is replaced by ferrocenecarboxylicacid or hexacyanoferrate(rI1) as an artificial mediator speciesshow similar behaviour. In each instance the polymer appearsto be electro-inactive towards re-oxidation of the mediator.Fourie r transform infra red studies of the polymer films indicatethat this loss of conductivity of the film is caused by reactionswith hydrogen peroxide generated by the enzyme.

Electrochemically polymerized films of phenols can also beused to immobilize glucose oxidase at an electrode surface.6The immobilized enzyme remains active and glucose can bedetec ted by using electrodes of this type either with oxygen asthe mediat or or when using an artificial redox mediator such asferrocenecarboxylic acid. Analysis of the responses of such

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electrodes enables the rate constants for the enzyme-catalysedreactions to be estimated and the effect of the substituents onthe phenol on the properties of the immobilized enzyme to beinvestigated.

This work was supported by the SERC (Gran t G R E 67108)and by MediSense. I thank the following colleagues andstudents who have contributed to this work: P . Moore, P .Tebbutt, A . Benniston, L-Y. Chung, R. Whitaker, Z . Ali, J.Farrington, D. Dawson, V. Eastwick-Field, D. Caruana, P.Birkin, V. Rhodes and C. Tyrrell.

References1 Bartlett, P. N., Gardner, J. W., and Whitaker, R. G. , Sens.

Actuators, 1990, A21-A23, 911.2 Bartlett, P . N ., and Farrington, J . , J . Electroanal. Chem., 1989,

261, 51.3 Bartlett, P . N. , Benniston, A. C., Chung, L-Y., Dawson, D. H . ,

and Moore, P . , Electrochim. Acta, 1991, 36, 1377.

4 Bartlett, P . N., and Whitaker, R. G., J . Electroanal. Chem.,1987, 224, 27.5 Bartlett, P. N., and Whitaker, R. G. , J . Electroanal. Chem.,

1987, 224, 37.6 Bartlett, P. N., and Whitaker, R. G., Biosensors, 1987/88, 3 ,

359.

Disposable Single-use Sensors

Monika J. Green and Paul 1. HilditchMediSense Inc., Units 3 & 4, 14/15 Eyston Way, Abingdon, Oxfordshire OX14 ITR

For a medical diagnostic product , the advantages of a single-use disposable sensor are clear. Most importantly, problemswith contamination or carryover are eliminated and steriliz-ation by the user is unnecessary. Further, with a re-usablesensor there might be concerns with drift and the need forrecalibration, which are not an issue with a disposable device.In addition, t he low cost of disposable sensors reduces the fe arof expensive damage associated with a re-usable device.

The principal criterion for successfully producing or adapt-ing a diagnostic test in disposable form is that a means must befound of constructing a device containing all the necessarycomponents for the tes t, avoiding the need t o add reagents atthe time of use. The device should have a stable shelf-life of a tleast 12 months, and the whole should be capable ofmanufacture in large numbers relatively cheaply.

Where the addition of reagents at the time of the test seemsunavoidable, the usual solution has been to employ one of thelarge automated analysers to perform the test. This type ofinstrument, however, has little part to play in the rapidlyexpanding market of decentralized testing, which offers muchfor improved efficiency and quality of patient care.

Glucose MonitoringThe basic concept of a biosensor for personal glucosemonitoring is simple: reagents and biochemicals necessary fordetection are deposited on a disposable sensor device; this canbe interfaced with an electronic meter system which monitors

(and may control) the progress of the reaction, and interpretsand displays the results.

The detection chemistry which has been most successful inthis area is that based on the interaction between glucoseoxidase (GO D) and derivatives of ferrocene [bis(cyclopentadi-enyl)iron] . The oxidized forms of ferrocenes (ferriciniumions) are capable of accepting electrons from GOD which hasbeen reduced by the reaction with glucose. It is thereforepossible to set up a system whereby ferrocene, oxidized at anelectrode to form ferricinium, is reduced by GOD in thepresence of glucose, and re-oxidized at the elect rode producingan electrical current depende nt on t he glucose concentration:

Glucose + GOD,, - luconolactone + GODred (1)G0Dp-d + Fe(cp)2+ + GOD,, + Fe(cp)2

F e ( ~ p ) ~ Fe(cp)2f + e-(2)

(3)This chemistry is produced commercially in the form of adisposable sensor 2 A poly(viny1 chloride) (PVC) substrate isprinted with several layers (Fig. l ) , ome of which provide the

PV C substrateConductive Workingsilver track elec!rode

\ - ,Contacts I I

I II

Dielectriclayer

Conductivecarbon track

IAg-AgCI reference

electrode

Fig. 1 Schematic representation of a disposable glucose sensor strip

two electrodes (working and reference) necessary for theelectrochemical reaction, and transmit current and potentialinformation to the m eter during the measurement, and one ofwhich contains enzyme and mediator in a labile matrix.

A second-generation sen sor, which is also available in desk-top format, has several improved features including automaticdetection of blood application (no button pressing), tempera-ture com ensation and almost complete freedom from inter-ferences. The last of these has been achieved by theincorporation on the sensor strip of a third electrode, whichcontains all the components of the normal working electrodeexcept for the enzyme. Any redox-active interferents presentin the sample will affect the response of this dummy electrodein the same way as the working electrode, and a correction isperformed by the meter to give the glucose value. The linearityand accuracy of this system are illustrated in Fig. 2.

AcetaminophenKnown in the UK as paracetamol and in the US as tylenol,acetaminophen is a widely used analgesic. Its ready availabilityand toxic effect in overdose make this a substance which isfrequently suspected in emergency room admissions. In anacetaminophen ~ e n s o r , ~ he enzyme aryl acylamidase catalysesthe deacylation of acetaminophen to yield p-aminophenol,which can be oxidized at an electrode to yield quinoneiminewith consequent measurable curre nt:

NHCOCH3 NH 2I I

0 H 2 0 - @ CH3COOH (4)OH O H

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Table 1 Design specifications for the bacterial assay system

Alternative to 'standard plate count'Capable of producing results rapidly (< 1 h)Moderate sensitivity (10s cfu ml-' or better)Economical (


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2.2 100C

0CL)

[r10

ANALYTICAL PROCEE DINGS, N OVEMBER 1991, VOL 28

-

-

and that redox-active substances in the sample will interfere.The system described overcomes these problems by concen-trating bacterial cells on a filter in close proximity to themeasurement electrodes. This allows amplification of theresponse as cells from a relatively large volume of sample areconcentrated into a small reaction volume; moreover, th e cellscan be washed when on the filter, removing soluble redoxinterferents.

Filter and electrodes are contained in a disposable assembly(Fig. 3) formed from PVC; the lower half has printedelectrodes while the upper half has a recess to contain a disc ofglass-fibre filter material. The disposable assembly fits into ahousing built into the meter which automatically interfaceswith the fluid handling and electrical contacts. The meterpumps sample, wash buffer and mediator solution as appropri-ate through the disposable assembly, which is maintained atconstant temperature. After loading sample onto the dispos-able assembly, and washing with buffer, the assembly isflooded with mediator solution (which also contains carbonsource for the bacteria) and is incubated for 10 min. During thistime bacterial respiration is converting benzoquinone intohydroquinone, which is measured for 30 s at the end of theincubation. The total assay time is therefore of the orde r of 15min.

The performance of the assay has been validated with aconsiderable range of aerobic bacte rial species; it has been

Embossed an dtextured P V C A

Filter discc->

with electrodes

Fig. 3assay system

Disposable sensor element for use in a biosensor bacterial

typically found to give a linear response with a sensitivity ofabout lo4cfu ml-' (Fig. 4). n a ddition to pure cult ures, results

loo0i

0

r = 0.988

11 I I I

10 3 104 10 5 106 107 108Se nsit vi yk fu m - 1

Fig. 4 Response of the bacterial assay system to bacteria (Pseudo-mon as cepacia)

have been obtained with mixed bacterial cultures, yeasts andfood and environmental samples.

ConclusionSingle-use biosensor diagnostics are characterized by con-venience of use, rapidity, accuracy and freedom from samplepre-treatment. Application of the technology to other areassuch as bacterial monitoring promises to extend further theboundaries of analytical chemistry.

ReferencesGreen, M. J. , and Hill, H . A . O ., J . Chem. SOC. ,Faruday Trans.,1986, 82, 1237.Matthews, D. R., Holman, R . R., Bown, E., Steemson, J.,Watson, A., Hughes, S . , and Scott, D., Lancet , 1987, 1 , 778.

Matthews, D. R., Burton, S. F., and Smith, E., in Proceedings,Artijicial Insulin Delivery Systems Pancreas and Islet Transplan-tation, European Association for the Study of Diabetes,Amsterdam, 1991.Jones, A. F., McAleer, J. F. , Braithwaite, R. A . , Scott, L. D. ,Brown, S . S . , and Vale, J. A., Lancet , 1990, 335, 793.Frew, J. E . , Bayliff, S. W., Gibbs, P. N. B., and Green, M. J .,Anal . Chim. Actu,1989, 224, 39.Foulds, N. C. , Wilshere, J. M ., and Green, M. J. , Anal . Chim.Ac tu , 1990, 229, 57.Hilditch, P. I. , Carter, N. F., Barrett, C. B., Sullivan, D. J. ,Charman, K . M., Green, M. J ., and Williams, S. C . , n Advancesin Bioreactor Monitoring, ed. Wang, N. S . , Academic Press,New York, 1991, in the press.

Applications of Amperometric BiosensorsAnthony P. F. TurnerBiotechnolog y Centre, Cran ield Ins titute of Technology, Cran ield, Bedford MK43 OAL

Numerous definitions of a biosensor pervade the recentscientific literature.' Taking a pragmatic view, a biosensor canbe consi dered as one possible solution to a particular analyticalproblem. Whether this technical route should be pursued ornot depends on the relevance of the features offered bybiosensors to the problem. Biosensors generally providecontinuous information about the concentration of a chemicalor group of chemical^.^,^ They are capable of considerablespecificity and sensitivity even when used directly in realsamples, without necessarily incurring the need for complexand expensive instrumentation. Coupled with modern micro-electronics they form the basis for a new generation of

'sensitive' computers. This pape r will review t he require mentsof several areas where amperometric biosensors are likely tomake an impact. A few recent or new examples of biosensortechnology that are likely to prove a commercial success4 willbe illustrated.

Clinical diagnostics have dominated biosensor developmentto dat e and are likely to continue to be the focus for commercialsuccesses over the next five years 5 Clinical applications aredriven by the need for cost effective patient care. Analyticalinstruments can be comprehensive and automated ordecentralized a nd specialized. Some conditions , for examplediabetes, benefit from self-tests usable in the home.6 Indeed,

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the world's most successful biosenso r is a pen-shap ed bloo dglucose monitor which addresses this market. A key issue intackling large markets is the requirem ent for inexpensive andreproducible mass production of the disposable biosensorelement. O nce investment has been mad e in such a productionfacility it is desirable to find further applications for thetechnology. Diagnostic tests that mak e sense to perform in thehom e are few and far between. Pregnancy test ing is an obviousexample, but the frequency with which these tests areperformed makes an instrumented assay uncompeti t ive withthe elegant visual assays now marketed. Other promisinganalytes that are at tracting commercial developmentofpocket-sized devices include total cholesterol, ethanol andlactate.

The printing technology that has been developed for themass production of one-shot devices mightfind application inreusable or continuous use devices. Recent work in ourlaboratories has shown that screen-printed enzyme electrodesfor glucose, using tetrathiafulvalene as mediator, ' can be usedover 2000 times. This has been achieved by using proprietaryme mb rane technology acting as a reservoir of the mediator. 'Such elements might be useful in larger machines where thethroughput permitted by biosensors can out-perform conven-tional systems or where a competi t ive advantage can beachieved by broadening the spectrumof analyses offered t oinclude, for example, glucose, urea, creatinine and lactate.Equally, simple amperometric devices can be constructedwhich ar e capable of highly sensitive imm unoass ay of analytessuch as thyroid st imulating horm one , prostat ic acid ph ospha-tase (a tum our mark er) or estradiol. '**" Some speculativework is underway to perform electrochemical detectionofD N A hybridization, furnishing the ossibility of detecting awide range of pathogenic organisms.

A further area of interest isin vivo m ~ n i t o r i n g . ' ~ediatedamperometric enzyme electrodes offer advantages over oxy-gen-consuming systems in their relat ive independence from

variat ions in oxygen tension. Concern has been expressed,however, about the toxicity of the media tors used . Newevidence suggests th at m ediators can b e less toxic than feared,for exam ple, th e LD50 in mice oftetracyan~quinodimethane'~a n d t e t r a t h i a f ~ l v a l e n e ~ ~ 'two recently discovered mediators) is1225 an d 710 mg kg-', respectively.lS While ma ny promisingsensors have be en de scribed, lack of biocompatibil i ty remainsa major hurdle t o the application of sensors inside the bod y forcritical care o r long-term therap eutic purp oses . 16.17 A n inter-esting compromise has recently been an nounced by an Ital iancompany; the proposed product consists of a wearablemicrodialysis system incorporating a non-mediated enzymeelectrode for continuou s monitoring in diabetics.

Much of the technology developed for clinical applicationswill find other uses in industry,l8 environmen tal monitoring"and defen ce. Industry is seeking sensors to im prove productiv-i ty, quali ty and compliance with legislat ion. Amperometricbiosensors have recently become commercially available foruse in situ in fermentation monitoring with broad consequencesfor the food and biotechnology industries. Amperometricdetection of microbial contamination2' of milk has reached themanufacturing prototype sta e in our hands with a detectionlimit of lo4 org anis ms ml-' ob tain ed within 20 min in acompletely 'handsoff' format.

Environm ental applications of biosensors are characterizedby a desire to protect workers and the public from toxic

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mate rial, an d compliance with legislation. O ne interesting newdevelopment with part icular relevance to this area is thediscovery of organic phase enzyme electrodes.21722Theseinstruments are capable of operating in oilsor fats23 and canalso offer improved perform ance in aqueo us samples by, forexample, automatically concentrating contam inants presentindrinking water.

As the academic l i terature on biosensors continues todiversify, a clear trend within indu stry critically t o evaluate a ndinvest in focused areas is emerging. Technical issues concern-ing the developers include fabrication technologies and ageneral drive towards miniaturization. Medicine and foodprovide the prime focus for new products, but many smallercompanies ar e searching for niche m arkets an d might furnishsome fascinating new gadgets, al lowing executives to transformthemse lves into skilled analytical ch emists overnight.

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ReferencesTurner, A. P. F. , Sens. Actuators, 1989, 17 . 433.Turner, A. P. F. , Karube, I. , and Wilson, G. S . , Biosensors:Fundamentals and Applications, Oxford University Press,

Oxford, 1989.Turner, A. P. F. , Advances in Biosensors, JAI Press, London,1991, vol. 1.Turner, A. P. F. , Int. Biotechnol. Lab., 1990, 8 (3A), 36.Anon, Biosensors: A New Realism, Cranfield Biotechnology,Cranfield, 1991.Cardosi, M . F. , and Turner, A. P. F. , in The Diabetes Annual ,eds. Alberti, K . G. M. M., and Krall, L. P. , Elsevier,Amsterdam, 1990, vol. 5 , pp. 254-272.Palleschi, G., and Turner, A. P. F. , Anal. Chim. Acta, 1990,234, 459.Turner, A. P. F., Hendry, S. P., and Cardosi, M . F . , inBiosensors, Instrumentation and Processing: The World BiotechReport, Online, London, 1987, vol. 1(3), pp. 125-137.D'Costa, E. J. , Br. Put. Appl., 9 019 126.3, 1990.Cardosi, M. F. , Birch, S . W., Stanley, C. J., Johannsson, A.,and Turner, A . P. F., Am . Biotechnol. La b., 1989, 7, 50.Bannister, J . V., Higgins, I. J., and Turner, A. P. F. , inBiosensors: Principles and Applications, eds. Blum, L. J., andCoulet, P. R., Marcel Dekker, New York, 1991, pp. 47-61.Downs, M. E. A., Warner, P. J., Fothergill, J. C., andTur ner,A. P. F. , Biomaterials, 1988, 9, 66.Cardosi, M. F. , and Turner, A. P. F. , n The Diabetes Annual ,eds. Alberti, K. G. M . M ., and Krall, L. P., Elsevier,Amsterdam, 1991, vol. 6, pp. 271-301.Hendry, S . P. , andTurner, A. P. F., Horm. Metab. Res., 1988,20, 37.Kulys, J. , and Higgins, I. J. , Biosens. Bioelectron., 1991, 6, inthe press.Reach, G. , Thevenot, D. , and Coulet, P . , Anal. Lett., 1989,22,2393.Coughlan, M . P . , and Alcock, S . J. , Biosens. Bioelectron.,1991, 6, 87.Brooks, S . L. , Higgins, I. J., Newman, J., andTurner, A. P. F . ,Enzyme Microb. Technol., 1991, in the press.Rawson, D. M . , Willmer, A. J., and Turner, A. P. F. ,Biosensors, 1989, 4, 299.Turner, A. P. F ., Allen, M., Schneider, B. H. , Swain, A. S . ,and Taylor, F., Int. Biodeterior. Bull., 1989, 2 5 , 137.Saini, S . , and Turner, A. P. F., Biochem. SOC. Trans., 1991,19,28.Saini, S . , Hall, G. F. , Downs, M . E. A.. and Turner, A. P. F. ,Anal. Chim. Acta, 1991, 249, 1.Hall, G. F. , and Turner, A. P. F. , Anal. Lett., 1991, 24(8), inthe press.

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38723182 New Electrochemical Sensors

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