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Electroanalysis and Biosensors Joseph Wang Department of Chemistry and Biochemistry, New Mexico State Uniuersity, Las Cruces, New Mexico 88003 This renew covers primarily the development of biosensors and electroanalytical schemes of clinical significance during the years 1991 and 1992. The review is not a comprehensive coverage of these topics. I have attempted to critically select those references that offer significant clinical relevance. Much of the general activity in the areas of electroanalysis and sensors (theory,methodology, and instrumentation) has been documented in recent fundamental reviews in this journal (PI, P2). The interest in developing small sensing devices for use in health care is growing rapidly. The potential clinical applications of these devices are enormous, particularly when decentralized testings are concerned. Yet, due to various technical problems (particularly lack of long-term stability), only a few devices are routinely used in laboratory medicine. New analytical and biotechnological innovations over the past two years will certainly have a major impact on medical care during the 1990s.
BOOKS A N D R E V I E W S Several books have been published since the last review. The principles and applications of biosensors have been covered in books by Hall (P3) and Blum and Coulet (P4). Wise and Wingard (P5)edited a book on optical biosensors, while Edelman and Wang (P6)edited an ACS symposium volume on advanced polymeric materials for designing biosensors. A new volume in Turner's series Advances in Biosemors has been published (P7). Nakamura et al. (P8) edited a volume of immunochemical sensors, while Scheller and Schmid (P9) edited a volume on the status of biosensors in united Germany. Cosofret and Buck (PIO)described electrochemical sensors of pharmaceutical relevance, while Smyth (PII) summarized the applications of voltammetric techniques for measuring biological compounds. Another useful bwkcovers the in-vivo monitoringof neurotransmitters (pia. Biosensors continue to be a popular topic for review. Several overview-type papers have appeared concerning biosensori (P13-Pi6). More specific ones are covered under theappropriatesections in thisarticle. Future prospectsand challenges were discussed by Rechnitz (Pin.
ENZYME AND AFFINITY-BASED ELECTRODES The development of enzyme electrodes remains a prime focus of many researchers. Research in past years has focused on new methods of enzyme immobilization (particularly toward reagentless devices), the fabrication of smaller and smaller biocatalytic electrodes, improved glucose sensing, new measuring concepts, the search for new nonphysiological mediators, the utilityof new (isolated orengineered) enzymes, and operation in new environments (e.& organic media). The biosensing of glucose has continued to receive much attention in the past two years. Anexcellent report addressed the challenges of continuous glucose monitoring from both clinical and chemical prospectives (P18). The coupling of a microdialysis probe and a glucose biosensor for in-vivo monitoring of glucose has been described (Pig). Implantable glucose sensorshave been evaluated in vivo (PZO) and in vitro (El), withgood stability over severaldays. A new commercial amperometric card-sized meter for self-monitoring of blood glucose levels was introduced (P22). It offers the advantage of a wide linear range and small (5rL) sample volumes. New capillary fill coulometric devices were developed for assays of 20-@Lsamples (P23). The coimmobilization of glucose oxidase and horseradish peroxidase has been useful for eliminating major interferences (P24, P25). Enzyme-substituted polypyrrole-coated electrodes offered a greatly improved stability (P26). Active Langmuir-Blodgett films of glucose oxidase have been used for preparing glucose sensors (P2n. Microelectrodes responsive to glucose have been described by utilizingredox hydrogelsoncarbon fibers (P28), rhodium- (P29)and conducting-salt (P30)coated carbon fiber &OR
ANALYTICAL CHEMISTRY. VOL. 65, NO. 12, JUNE 15. 1993
Joseph Wang Is Professorof Chemistry at New Mexico State Unlvsrslty Heobtained h s nioner education a1 the Israel Institute of Tezhnolcgy. being awarded hls D.Sc. in 1978. From 1978 to 1980 he served as a research associate at the University of Wisconsin (Madison). Since 1980 he has ~
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been a facub member at New Mexico State Universihl. The research interests of Dr. Wang include the development of 5 electrochemlcaisensingdeviceslwclinical 1 and environmentai monitoring. the devec opment and characterization of new surfaces for electroanalysis.sensor coatings. the development of techniques for u!tra~wce measuremantr~adthadashnof owline fbwdetectm. Wang's .
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_.authored over 250 research papers. seven chapters, and three books and presented numerous invited lectures In different countries. He Is currently sewing as the ChiefIdnor of the lnlernatlonai journal Eiechoanalysls and as a member of the Advisory Edhor Board of the Analyiica Chimica Acta. Analyst. Talanta. AnalyiicalLeners. Anatyilcal Instrumentation. EncychyxMia of Anatyilcal Sciences. and Croatisn Chemica Acta. enzyme surfaces, glucose oxidase immobilized in a poly(phenol) film (P3I),silicon oxide deposited gold band (P32),and cobalt porphyrin-Njafion coating (P33). New viologen derivatives were explored as electron-transfer mediators for amperometric glucose sensing (P34), while anewphenoxazine derivative has been used in connection with glucose dehyrogenase electrodes (P35). Such enzyme electrodes also benefited froman internalsupply ofthe NAD+cofactor (P36). New designsand improved performance have been reported for electrodes for many other clinically important substrates. Several papers focused on disposable screen-printed electrodes for acetaminophen (P37)and glutathione (P38). Novel enzyme-based microelectrochemical devices, based on changes in the conductivity of polypyrrole layers, were developed for hiosensing of NADH (P39) and penicillin (P40). The innovative concept of electrical wiring of enzymes has been expanded toward the detection of L-lactate (P41). Enzyme/ mediator-containing carbon paste electrodes have continued to receive considerable attention in connection with the fabrication of reagentless devices for L-lactate (P42), acetylcholine (P43),,and nucleosides (P44). Efficient mediation has been achieved by using carbon pastes containing a polymericrelay system and the enzyme (P4.5). Bulk-modified, polishable, graphite epoxy bioelectrodes were designed as renewablealcohol sensors (P46).Substrate recycling was used for the detection of nanomolar concentrations of ADPIATP (P47). A new redox-active polymeric film was employed for measurementsof free cholesterol (P48). An improved urease electrode was applied for the determination of urea in serum (P49). The recent isolation of thyophilline oxidase has led to a new amperometric electrode for theophylline (P50). Flavocytochrome bp was used for the preparation of a new lactate electrode (P51). Anew analyzer for monitorin blood lactate during physical exercise has been characterizei(P52). Enzyme electrodes were developed for the determination of creatinine (P53)and glutamine (P54) in serum and of urate in undiluted whole blood (P55). A catechol electrode was evaluated in connection with the diagnosis of neural crest tumors (P56).The unique biosensing opportunities, accrued from the activity of enzymes in organic media, have been reviewed (P57). Additional biocatalytic sensors based on the replacement of isolated enzymes with natural materials have been developed. A tissue (papaya) electrode was employed for eliminating protein interferences (P58). The multienzyme (polyamine oxidaselperoxidase) activity of the oat seedling tissue has been exploited for the hiosensing of polyamines (P59). A disposable bacterial sensor was developed for amperometric monitoring of carbon dioxide (P60). The coupling of hiocatalytic electrodes with a nonflow batch injection technique resulted in a high-speed biosensing operation (P61). I
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Electrochemical sensors employing natural binding molecules as the molecular recognition element continue to receive considerable attention. A otentiometric immunosensor, based on the enzyme channeing strategy, was developed for the detection of proteins (such as I G) (P62). An enzyme immuno-ISFETsensor for hepatitis was designed, utilizing urease as the marker enzyme (P63). A tantalum capacitance flow detector was developed for real-time monitoring of immunochemical interactions (P64). The incorporation of antibodies into conducting polymeric coatings was employed for developing a sensor for human serum albumin (P65).IgGcoated membranes have been prepared and characterized for use in enzyme immunosensors (P66).Electrochemiluminescence was employed for immunoassays of digoxin and thyrotropin (P67). A relatively new, novel, and promising sensing strategy is based on s ecific bindings between membrane receptor proteins anttarget analytes that tri ger or modulate cellular events. A coulometric biosensor or lutamatic acid was developed using glutamate receptor ion cf&nel protein (P68). Other chemoreceptors were used successfully as molecular recognition elements for monitoring various drugs ( B O ,P70). Intact chemoreceptors, based on aquatic species, offered extremelyhigh sensitivitytoward stimulant compounds (P71). A reliable and reproducible method was described for the preparation bilayer lipid membranes (P72). The control of ion trans ort through such film has been discussed (P73). The syntiesis and utility of artificial molecules that mimic bioreceptor functions have been reviewed (P74). Prospects of developing receptor sensor arrays, mimicking natural sensory systems, have been discussed (P75).
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OPTICAL AND MASS SENSORS Fiber-optic sensors possess an enormous potential for biomedical applications. Accordingly, the optical mode of transduction has received considerableattention over the past two years. Various recognition rocesses have been coupled with optical devices. Recent a vances in optical biosensors were reviewed by Wolfbeis (P76), Arnold (P77), and Narayanaswam (P78), while fundamental and practical aspects of ion opto&s were treated by Janata (P79). The prospects and challenges of using fiber-optic sensors for continuous clinical monitoring were discussed by Walt (P80). Kar and Arnold (P81) reported the development of a fiberoptic ammonia sensor with nanomolar detection limits. The same group described a dual-enzyme fiber-optic sensor for glutamate (P82). Fiber-optic probes based on bioluminescent enzymatic reactions have been designed. Coulet and coworkers (P83)described a reagentless bioluminescent fiberoptic sensor based on entrapment within a poly(viny1alcohol) layer. Girotti’s grou developedbioluminscent flow detectors for lactate (P84) an! lutamate (P85).Another optical flow sensor was designed y! Guilbault and co-workers (P86)for flow injection analysis of penicillin. A fiber-optic enzyme sensor, with electrochemical generation of the indicator, was developed for monitoring glucose (P87).Wolfbeis and coworkers described selective o tical sensors for thiamin (P88) and propranolol (P89) base on molecular recognition. Immunoprobes represent another important group of o tical biosensors. Bright and co-workers (P90)improved t f e performance of fiber-optic immunosensors using refunctionalized fluoropolymersas the substratum. The same group described a selective fiber-o tic immunoprobe for ha tens (P91).A fluorescent probe for ferritin was designed {ased on a Langmuir-Blodgett thin film of anti-ferritin IgG (P92). The rinciple of the sandwich bindin technique was applied for &eloping a fluorescent sensor or mouse IgG (P93).A new approach for fiber-optic sensing, based on hydrophobic associations, was described by Ogasawara et al. (P94). Optical sensingof ions has also received a rowing attention. Simon and co-workers (P95) developed a %ighly sensitivity optical sensor for lead based on a neutral ionophore. Similar sensors for chloride (P96)and sodium (P97) were designed and ap lied for assays of human plasma. Another optical sensor 8 r sodium, with reversible and selective response, was described by Buchholz et al. (P98). Surface plasmon resonance, Le., the detection of changes in refractive index on a surface, is another promising biosensing strategy that has reached the commercial stage.
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Surface lasmon resonance sensors were employed for realtime an3ysis of various biospecific interactions (P99,P100). The signal enhancement associated with this strategy holds great promise for attaining very low detection limits (PIOI). Several useful schemes have relied on piezoelectric crystal devices. Coated piezoelectriccrystals were employed for rapid monitoring and control of anaesthetic gases during a surgical procedure (P102). A quartz crystal viscosity sensor was applied for monitoring coagulation reactions (P103). A biosensor utilizing an acoustic plate mode in a piezoelectric crystal plate was used for the detection of DNA hybridization (P104).
ION-SELECTIVE ELECTRODES Ion-selective electrodes (ISEs) are widely used for direct otentiometric measurements of important electrolytes in ody fluids. The clinical a plications of ISEs have been reviewed (P105).Consideraile effort has been given to the synthesis and characterization of new macrocyclic structures with improved selectivity and detection limits (P106-P110). In particular, sodium-selectiveelectrodes based on calixarene compounds have continued to receive considerable attention (P111).The lifetime of a neutral-carrier-based liquid membrane in whole blood has been investigated (P112). Flowthrough cells for improved on-line monitoring of ionized calcium have been described (P113, P114). A minielectrode was developed for the determination of calcium in saliva (P115).Commercial electrodes were employed successfully for real-time monitoring of plasma lithium in patients attending lithium clinics (P116). A highly stable symmetric measuring system was used for calibration-freemeasurements of potassium and sodium in serum (PI17). Bachas and coworkers (PI18) developed new anion-selective electrodes based on electropolymerizedcoatings. The effect of different roteins on the properties of anion-selective electrodes has een ex lored by the same group (P119). Indium- orphrinbased erectrodes have been used to determine cfioride in serum samples (P120). Improved performance of coated wire electrodes was achieved by using a olypyrrole mediating layer (~121).~n ion-selective fieldleffect transistor was employed for in-vivo pH measurements (P122). Various groups (P123,P124)reported on multisensor arrays for potentiometric, sodium, calcium, and pH measurements. Im roved selectivity has been reported by coupling arrays of higby and sparin ly selective electrodes with a chemometric approach (PI%).beyckens et al. (PI261evaluated the utility of disposable miniature ISEs as test slides for the determination of sodium in plasma. Schelter et al. (P127) described low-cost disposable multiparameter devices for on-line blood monitoring, based on coupling of potentiometric and amperometric sensors. In addition to electrolyte measurements, ISEs have been a plied for measurements of cationicdrugs for local anesthesia (JIB),for the reco ition of guanosine nucleotides (P129), for monitoring of DftA polymerase reactions (P130), for the detection of heparin (P131),and for the determination of cholinesterase in blood serum (P132).
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VOLTAMMETRY AND AMPEROMETRY The inherent sensitivity of controlled-potential techniques, coupled with the portable nature of the instrumentation, holds great promise for clinical analysis. Recent developments in the field of voltammetry, particularly new advances in ultramicroelectrodes and tailored electrodes, have the potential to make significant contributions for biomedical applications. The introduction of smaller and smaller voltammetric electrodes offers si ificant spatial and temporal advanta8es (P133). In particug, Wightman’s group reported the utility of etched carbon-fiber electrodes for monitoring the release of catecholamines from biological cells (P134), while Ewing and co-workers (P135)employed ultrasmall ring electrodes for measuring oxy en in single neurons. Pretreated carbon fiber microelectro!es were ap lied for in-vivo voltammetric detection of neuropeptides ($136). Bowyer et al. (P137) described a microcell, based on microband electrodes, for voltammetric measurements in 0.05-pL solutions. Bard‘s group (P138)extended the scope of scanning electrochemical ANALYTICAL CHEMISTRY, VOL. 65, NO. 12, JUNE 15, 1993
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microscopy for mapping localized biological activities. AnalIP4) . . Blum. L.: Coubt. P. R. 6bsensom Prjncbks 8ndA~u1hbbne: M. Dekker: New Yo&, 1991; observations were carried out by scanning tunneling(P5) Wise, D., Wngard, L., Eds. Bksenaars and Fibetuptlcs; Humana: New niicroscopy (P139). York. 1981. The rationale design of electrodes with controlled surface (W Edeimcln, P., Wang, J., EL. t3bsmsm end ChemkalAmerican roperties offers unique possibilities for bioanalysis (P140Chemical Society:Washlngton, DC. 1992. 5142). Considerable attention has been focused on self(P7) Tuner, A. P., Ed. Advances h Bkssnsaa: JAI Press: London, 1991; Vol. 2. assembled monolayers. For example, the selectivity advan(Pa) Nakamura,R., Kashahara. Y .,Rechnltr, G.. Eds. ImmunodwmrMA-9 tages accrued from films of thioctic acid on gold electrode for Bkssnsor T & m for the 1900s;Amerlcan Society of MicroMology: have been described (P143). Self-assembled monola era of Washlngton, DC, 1992. carboxylic acid-terminated alkanethiol facilitated t i e vol( W )Schdkr, F., Schmld, R. D., Eds. Bbmnsws: Fundamentals. TsdndogJss tammetry of cytochrome c (P144). Screen-printeddisposable and AppYcsbbns; VCH Publishers: Welrthelm, Qmmany, 1992. (PlO)cOWfret,V.; B U d ( . R . F h ~ m c c w t l c s l A p p P l c s b b n s o f A n e ~ chemically modified electrodes have been developed (P145). CRC Press: Boca Raton, FL, 1992. New catalytic surfaces, based on highly stable inorganiclayers (PI 1) Smyth, W. F. Vhmmetrlc Determlnatkm of Mdscuks of B/do&al (P146) or metal-dispersed carbon pastes (P147), have been w n a k @ % i J. Wky: Chlchester, UK, 1992. used to facilitate the electron transfer (and the detection) of (P12) Rollema, R., Westerlng. B., Drijfhout. Eds. Monhlng Mobcubs In many biological compounds. Nevar&w Q o n l w n UnIverrHy Center: Qonlngm, 1991. (P13) Thompson, M.; Krull, U. J. Anal. Cbm. 1991. 63,393A. Effective voltammetric sensors have been develo ed by Koochakl. 2. h A p p L Chem. 1991. (P14)Vadgama.P.; Desal, M.; Chrlstb. I.; Malinski’s group based on the judicious tailoring o f ultra63, 1147. microelectrodes. For example, a carbon fiber, coated with (P15)oUllbault, G.; Kauffmann. J. M.; Pablarche, G. &bprwsss Tech&. 1991, porphyrin and Nafion la era, has been developed for in-situ 14, 209. monitoring of nitric oxidr, release from a single cell ( ~ 1 4 ) . (Pl6) Taykr, R. F. Bkproosss Technd. 1991, 14, 263. (P17) Rechnltr, 0. A. Ekclrosnam 1991, 3, 73. A porphyrin-modified carbon-fiber electrode was employed (P18) Reach, F.; Wilson, G. S. Anal. chem. 1992. 64, 381A. by the same group for intracellular measurements of nickel (P19) Moclcone, 0.; Paslni, M.; Masclnl, M. Tabnta 1992, 8, 1039. (P149). (P20) Moem, D.; Capton, F.; POnout. V.; Reach. G.; Bindra, D.; Zhang, Y.; The enhanced sensitivit offered by the in-situ preconWllson, G.; movenot. D. Dabto&& 1992, 35, 224. centration step of electrocgemical stripping analysis holds (P21) h w , G.; C l a r m n t , D.; Pickup, J. Ekxwns. Bbekfnm. 1991, 6, 401. (P22) Lewb, B. clh. Chem. 1992, 38, 2093. great promise for measurements of trace metals. Recent (P23) Monls, N.; Cardosl, M.; Birch, B.; Turner, A. P. Ekcmnaiysk 1992, 4, advances in stri ping analysis, aticularly the introduction 1. of new electrofe systems a n a ultrasensitive adsorptive1 (P24) Maiden. R.; Helkr, A. J. Am. Chem. Soc. 1991, 713, 9003. catalytic stripping schemes, have further enhanced its ca(P25) J h s w n Petteason. G. Ekcmnal)rslr 1991, 3,741. pabilities for laborator medicine. The growin needs for (P26) Wobwacz, S.; Yon, B.; Lowe. C. Anal. Chem. 1992, 64, 1541. mass screening of lead %vela in children’s bloodtave led to (P27) Sun, S.; phoc, H.; Ha(errleon,J. Lef?@Wk1991, 7. 727. (P28) PisNto, M.; Michael, A.; Helkr, A. Anal. Chem. 1991, 63,2288. the development of low-cost screen- rinted electrodes for (P29) Wang, J.; Angnes, L. Anal. Chem. 1992, 64, 456. decentralized testing of trace lead ( h 5 0 ) . Another novel (P30) K a w a p , J.; Nbhaus. D.; Wlghtman, W. Anal. chem.1991. 63,2961. electrode was developed for facilitatin medium exchange in (P31) Bartktt, P.; Caruana, D. Anal)rst 1992, 117, 1287. connection with microliter sample vofumes (P151). Poten(P32) Yokoyoma, K.; Tamlya, E.; Karuk. I. E k c l r o s ~ m1991, 3, 469. tiometric stripping analysis was used for direct determination (P33) Dong. S.; Kuwana. T. EbcmnaILgls 1991, 3, 485. (PN) k b . P.; Bogwhvsky, L.; Wan, H.; Lan, H.p; Lee, H.; Okamoto, Y.: of cadmium and lead in whole blood,followinga simple sam le Skothelm. T. AMI. Chh. Acta 1991, 248, 155. pretreatment and short preconcentration times (P152). &e (P35) Pohsek, M.; W o n , L.; Appkqvlst, R.; Marko-Varga, 0.;Johanwon, G. dual-amplification effect resulting from the coupling of Anal. chkn.Acta 1991, 246. 283. adsorptive accumulation and catalytic effects resulted in an (P36) skoog. M.; Johsnsson, G. Bbssns. Bkdecb.on. 1991. 6.407. extremely sensitive stripping procedure for picomolar con(P37) Vaughsn, P.; Scott, L.; M A W , J. AMI. chkn.A m 1991, 248, 361. (P38) Wrhg, S.; Hart, J.; Blrch, B. Ekclrosnalyds 1992, 4. 299. centrations of vanadium (P153) and molybdenum (P154). (P39) chew, H.; Ueno, A.; Yamada, H.; Matsue, T.; Uchkk, I.AnaILgt 1991, Ultrasensitive stripping procedures have been developed for 176. 793. measuring clinically important organic compounds such as (P40) Nlshhlzawa, M.; Matswt. T.; Uchida, I. AMI. Chem. 1992, 64, 2642. folic acid (P155),the dr s clotio ine (P156)and ciprofloxacin Helkr, A. Anal. Chem. 1992, 64, 1008. (P41) Ketekls, I.; (P157), or I-phenyl-3,3!%methykriazene carcinogens (P158). (P42) Kulys, J.; Schuhmann, W.; Schmidt, H. Anal. Len. 1992, 25, 1011. L.; Skothdm. t. .€bcmna&sb 1991, 3, 751. 0 ‘ 4 3 ) Hab, P.; Uu, Sensitive pulse voltammetric procedures (without prior (P44) Ikeda. T.; HashlmOtO, Y.: Senda, M.; Isono, Y. fbC&CXlM&& 1901. 3, accumulation) have been developed for monitoring azido891. thymidine (AZT) in human blood (P159), for measuring (p45) Hab, P.; Bogus)evsky, L.; Inagakl, T.; Karan, H.; Lee, S. Skothelm, T.; metallothionein (P160),and for assays of tissue plasminogen OkanIOtO, Y. AMI. Cbm. 1991, 63,677. activator (t-PA) (P161). (P46) Wang, J.; Romero, E.; O m z , M. Ekclrosnalysls 1992, 4, 539. (P47) Yang. X.; Johansson, G.; Pfelffer, D.; Schelkr, F. Ebcwoanem 1991. The coupling of amperometric detectors with separation 3,659. techniques is particularly attractive when complex biological (P48) @a ‘m, N.; Ikeda, S.; Swukl. M.; Ohsaka, T. EkclrosnarLslp 1991. 3, matrices are concerned. Recent review articles describe the 655. utility of electrochemical detectors for capillary electro(P49) Narlneslngh, D.; MUngal, R.; Ngo, T. AMI. chln A m 1991, 248, 387. phoresis (P162), the use of am erometric detectors in (P50) Wang, J.; Dsmpsey, E.; O m z , M.; Smyth, M. A ~ l ) r s1001, t 176, 997. (P51) Staskevlcbne. S.; Cenas, N.; Kulys. J. Anal. Udm. A& 1991,243, 187. connection with microdialysis proies (P163),and the im(P52) ShlmolO, N.; Fujlno, K.; Klthashl, S.; Nakao. M.; Naka, R.; Okuda. K. CYn. provements accrued from the use of modified electrodes as Chem. 1991, 37, 1978. detectors for liquid chromatography (P164). Jorgenson’s (P53) Muyen, V.; WoM, C.; W,J.; Schwlng, J. Anal. Chem. 1991, 63,811. group (P165) reported on the determination of catecholamines (P54) VHlatta, R.; Palbschl, G.: Sulleman, A. Qullbault, 0.Ekclrosnalyslr 1992, in individual bovine adrenomedullary cells by liquid chro4, 27. (P55) KOW, F.Vadgama, P. Bkssns. Bbekfnm. 1991. 6, 491. matography with electrochemical detection (LCEC). Mod(P56) nl)Yer, C.; Gobln, P. Bksens. B l d m b n . 1991. 6, 569. ified electrodes were developed for monitoring myo lobin and (P57) Salnl. S.; Hall. 0.;Downs, M.; Turner, A. P. Anal. chkn.Acta 1991, 249, hemoglobin in flowing streams (P166). Metal& copper 1. electrodes were em lo ed for LCEC of polypeptides and (P58) Wang, J.; Wu, L.; Martinez, S.; Sanchez. S. Anal. chem.1991, 63,398. proteins (P167). L&$ was applied for the determination of (P59) L h M.; Hare, M.; Rschnltz, 0. Ekciroenam 1992. 4, 521. (P80) Swukl, H.; Tamlya. E.; Karube. I.EkCb0sMl)aQ 1991, 3, 53. morphine in human serum (P168), for measuring amino acids (Pel) Wang. J.; Wu, L.; Chen, L.; Taha, 2. GBFMonop. 1992, 17, 461. of neurochemical interest in biological samples (P169),and (P62) Drown, D.: Meyerhoff, M. Bkscwu. Bkdsctton. 1991, 6, 615. for monitoring aminohalo en benzophenones in urine and (P63) Hlrombu, S.; Norlakl, K.; Hlroshl. H. SCMB. Mater. 1991, 2, 265. serum (PI70). A simple L8EC method for the determination (P64) Qebbett. A.; Ahrarez, M.; Stockbin, W.; Schmld, R. Ana/. Chem, 1992, of N-acetyldopamine in urine of children with neuroblastoma 84.997. (P65) John R.: Spencer, M.; Wallam, G.; Smyth. M. Anal. chlm.Acta 1991, and nephroblastoma was described (P171). A carbon fiber 249, 38 1. detector was applied for LCEC measurements of salbutamol (P66) Wkr, S.; Rechnltr, G. Anal. Len. 1981, 24, 1347. in human plasma (PI72). (P87)Bladtbvn.Gi.;Sheh,H.;K~tsn,J.;Lebnd,J.;Kamh,R.;Unk,J.;Pe~n, I .
OPOUS
LITERATURE CITED (Pl) Ryan, M.; Chambers, J. Anal. Chem. 1992, 64. 79R. (P2)Janata, J. Anal. Chem. 1992. 84, I96R. (P3) Hall, E. Bbsensors; Ellls Horwood: Chlchester, UK, 1991.
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