ISSN 1061-9348, Journal of Analytical Chemistry, 2009, Vol. 64, No. 5, pp. 524–532. © Pleiades Publishing, Ltd., 2009.
1 In flow analysis, the inner volume of the analytical path should be as low as possible in order to minimise broadening of the sample zone. Sample dispersion is then more efficiently controlled, and tailing effects play a less relevant role in sample throughput. Inclusion of large inner-volume devices in the manifold has then been discouraged [1], and this leads to the present ten- dency towards downsizing [2]. However, presence of a mixing chamber (MC) in the flow manifold is unavoid- able in relation to some specific applications, therefore advantages and limitations of this device should be taken into account for system design. This holds both for segmented and unsegmented flow analysis.
In segmented flow analysis [3–5], the main stream is segmented by a second phase (usually air) in order to limit sample broadening, to improve mixing conditions and to wash the tubing inner walls. For air removal, a relatively large de-bubbler is usually required and this device may act as a MC, thus impairing the system per- formance. This limitation is typical for old-fashioned instruments still in use. The bubble-gating approach [6]
can be exploited to circumvent this drawback, but it has not been overall implemented. In addition, MC are often used in segmented flow analysis for accomplish- ing specific steps such as e.g. dialysis, ion-exchange, and gas diffusion.
The second phase is not typical in unsegmented- flow analysis [7], therefore the main flowing stream behaves as an incompressible liquid column, allowing different approaches such as stream splitting, zone sampling, flow reversal, stopped-flow, etc to be effi-
1The article is published in the original.
ciently and reproducibly accomplished [8, 9]. Exploita- tion of commuting devices becomes then more feasible and enhanced system versatility is attained [10]. Sam- ple dispersion is the key parameter for system design, and different strategies for controlling it have been pre- sented [8], including those relying on use of a MC in the manifold. This device is important to promote high degree of sample dilution [11], to improve mixing con- ditions [12], and to attain exponential concentration lessening [13]. This latter feature is relevant in the con- text of generation of sample (or reagent) aliquots with different yet known concentrations. Thus, MC have been used in unsegmented flow systems to accomplish multiple tasks, often in relation to expeditious flow pro- cedures, namely those involving the standard addition method [14], flow titrations [15], analytical curve rely- ing on a single standard solution [16], time-based flow systems [17], etc. Furthermore, MCs have been used for specific tasks such as e.g. in-line sample preparation [18], reagent dissolution [19], analyte separation/con- centration [20], and integrated reaction/detection [21].
A critical discussion on the advantages and limita- tions of MC in the flow analyser is presented. Attain- ment of high degree of sample dilution, improvement of mixing conditions, and exploitation of the exponen- tial concentration lessening in function of time are dis- cussed. Moreover, some specific procedures relying on MC are highlighted as well as the utilisation of compo- nents that, although not directly considered as MC, may exhibit a general behaviour similar to them.
ARTICLES
Mixing Chambers in Flow Analysis: a Review
1E. A. G. Zagattoa, J. M. T. Carneiroa, S. Vicentea, P. R. Fortesa, J. L. M. Santosb, and J. L. F. C. Limab
a Centro de Energia Nuclear na Agricultura, Universidade de Sáo Paulo, P.O. Box 96, Piracicaba SP 13400-970, Brazil
b REQUIMTE, Departamento de Química-Física, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha 164, Porto 4099–030, Portugal
e-mail: ezagatto@cena.usp.br
Received August 13, 2007; in final form, February 27, 2008
Abstract—Inclusion of a mixing chamber in a flow system is critically rev−−iewed in−relation to sample dilu- tion, improvement of mixing conditions and exploitation of exponential concentration lessening. Analytical perspectives related to the use of a mixing chamber such as time-based flow analysis, flow titrations, and analyte separation/concentration are also discussed along with the examination of several ordinary manifold compo- nents that might act as mixing chambers. The possibility of using the mixing chamber in order to accommodate or to carry out the multiple steps inherent to the specific analytical procedure or, in other words, to behave as a mini-laboratory, is also highlighted. This aspect is foreseen as a logical evolution of the lab-on-a-valve and the flow-batch concepts.
DOI: 10.1134/S1061934809050165
MIXING CHAMBERS IN FLOW ANALYSIS: A REVIEW 525
THEORETICAL BACKGROUND
When a very low solution aliquot, VS, is introduced as a pulse directly into an ideal well-stirred MC (Fig. 1), immediate mixing with the MC inner solution is attained, leading to a sudden dilution. The concentra- tion of a given species in this aliquot, cS, is then less- ened to cD according to:
cD = cSVS/VMC, (1) where VMC—inner volume of MC. Analysis of (1) reveals that MC is a powerful tool for attaining high degrees of sample dilution, especially if one recalls that volumes of MC and of the introduced aliquot are not usually restricted.
If a MC is inserted into a chemically inert flowing stream of identical matrix as its inner solution, the con- centration inside MC undergoes a continuous lessening in function of time. Under ideal mixing conditions, the instant time-dependent concentration, c(t), is expressed by:
c(t) = c0e–kt, (2) where t—time interval elapsed after solution introduc- tion; k—VMC/Q; (Q—volumetricflowrate oftheflowing stream). Analysis of (2) reveals that tailing effects are inherent to MC.
In flow analysis involving MCs, an aqueous sample is introduced into the carrier stream that directs the established sample zone towards MC and detection (Fig. 2). This stream acts also as a wash stream. The c0 value is ideally proportional to the recorded peak height whereas the c(t) values reflect the continuous concen- tration lessening in function of time, that dictates the recorded peak shape.
Equation 2 is within the scope of the tanks-in-series model with N = 1 [22]; therefore the related recorded peak is very skew. The concentration gradients formed during passage of a given solution through MC are worthwhile for several applications, as discussed fur- ther. However, measurements performed on the gradi- ent region of a dispersing solution tend to be less pre- cise, as demonstrated by Gisin and co-workers [23]
who theoretically investigated the hydrodynamically limited precision associated with each fluid element of a dispersing solution that flowed through a well-stirred MC or through a straight capillary tube. Measurement precision was ultimately limited by the N value, and could be improved by increasing this parameter in order to permit more Gaussian-shaped peaks to be recorded. Deterioration of measurement precision related to fluid elements located in regions with pro- nounced analyte concentration gradients was also noted by Gine and collaborators who exploited the zone sam- pling process to perform measurements at different por- tions of a dispersing sample [24].
Some aspects should be taken into account in apply- ing (1) and (2) to flow analysis. Perfect mixing is not MC
time F
C
Vs
Fig. 1. Schematic presentation of the behaviour of an ideal mixing chamber. Upper: equipment set-up [VS—solution aliquot; MC—mixing chamber; ∞—well-stirred character;
F—lowing stream]; Lower: time-dependent concentration inside MC.
S R D
F
MC
time M
Fig. 2. Schematic presentation of a simple flow system with a mixing chamber. S—sample; F—sample carrier stream;
R—eactor; MC—mixing chamber; ∞—well-stirred charac- ter; D—flow-through detector; M—time-dependent mea- surement.
526 ZAGATTO et al.
possible from the practical point of view; dispersion always takes place before the sample reaches MC (this is also inherent to the injection process [25, 26]);
instant sample introduction into MC is not feasible;
additional dispersion along the transmission line between MC and detector is unavoidable; the detector inner volume is also a chamber-like element; there is not an ideal detector. These aspects constitute them- selves in the main reason why the c(t) function in Fig. 1 tends to be a c-curve [27].
In this regard, (1) and (2) have been expanded in order to be applied to situations of large sample vol- umes and/or time spans needed for proper MC feed- ing/washing, as well as to include the non-ideal nature of the detector. Amongst the mathematical descriptions of flow systems with MC, the models given by Pardue and co-workers [28–33] and by Pungor et al. [34] could be highlighted. Variations of these MCs (or well-stirred tank) models have been proposed for titrations [35], calibration [36], kinetic studies [37], information on doublet peaks [38, 39], data processing [40] and disper- sion investigation [41, 42].
ANALYTICAL USEFULNESS
Sample dilution. MC is an expeditious and useful tool for attaining high degree of sample dilution in flow analysis (1). As illustration, the multisyringe system for single-point titrations of highly acidic or alkaline pro- tolytes [11] can be selected. Precise dilutions were car- ried out in two steps, first by splitting the sample zone and then by diluting it inside MC. Dispersion coeffi- cients as high as 1150 were efficiently attained.
Furthermore, the superior efficiency of a stirred MC for sample dilution relatively to a mixing coil of identi- cal inner volume was demonstrated [43]. With a dual- stage dilution strategy involving two sequentially placed MC, dispersion coefficients of up to 1 × 106 were obtained with excellent repeatability. Analogously, a flow injection system allowing a 240-fold dual-stage dilution was designed for determination of V(V) in the presence of V(IV) using 4-(2-pyridylazo)resorcinol as the colour-forming reagent [44]. The sample was added to a 200-µL MC and a sample aliquot was further selected and injected into the reagent carrier stream for reaction development and detection.
Variable-volume MCs are diluting elements that permit high and different dilution degrees to be effi- ciently attained, dependent on the MC selected volume (1). Wide range determinations are then straight for- wards implemented. The determination of copper by flame atomic absorption spectrometry can be selected for illustrative purposes [45].
Mixing. Introduction of mixers in flow systems dates back to the sixties when helical devices were used for improving mixing conditions in segmented-flow analyzers. The innovation has not been fully accepted, probably because in ordinary segmented flow systems, the slugs between air bubbles are already stirred due to the establishment of the typical flow pattern inherent to segmented flow analysis (Fig. 3). Moreover, presence of large inner volume devices in the analytical path has been always discouraged.
MC as means of improving mixing conditions becomes more important in relation to unsegmented flow analysis, especially flow injection analysis, and this feature is noteworthy in relation to spectrophotom- etry and related techniques. Under bad mixing condi- tions, a myriad of transient mirrors are randomly formed, leading to a pronounced Schlieren effect that may impair detection [46]. Moreover, the interaction between sample and reagent (dictated by the mixing conditions) becomes less reproducible, as the spectro- photometric analytical signal is usually dependent on both analyte and reagent concentrations. These short- comings are minimised by including a MC in the flow manifold [16].
In sequential injection analysis, mixing conditions tend to be worse relatively to flow injection analysis, as the manifold is usually designed in the single-line con- figuration [47]. Exploitation of a chemically inert car- rier streams is then not practical and the Schlieren effect is more likely to manifest itself. Use of a MC may result then in improved measurement repeatability [48], as demonstrated in the catalytic determination of iodide in nutrition salts [49] or in the direct determination of iron in edible oils [50] relying on formation of the red- dish hexacyanoferrate(III) complex. Although an 85 : 15 (v/v) methanol : chloroform solution was used as sample carrier stream, the Schlieren effect did not limit measurement in a pronounced manner. Further-
Fig. 3. Typical flow pattern inherent to segmented flow anal- ysis. Empty arrow—overall flow rate direction; other arrows—flow direction; ellipses—air-bubbles; main traces—tubing inner wall.
MIXING CHAMBERS IN FLOW ANALYSIS: A REVIEW 527 more, experiments carried out in model system relying
on the fast complexation of Fe(III) by Tiron [51] con- firmed that, for higher MC volumes, sample dispersion was increased and sample-reagent interaction was improved, but a longer time for baseline restoration was needed.
Exponentialdilution. Exploitation of the c(t) func- tion (2), related to the continuous lessening of the con- centration inside the MC versus time, has lead to an increasing expansion of the application range of flow analysis [52]. Theoretical models were already pro- posed to describe the time-dependent concentration under ordinary situations, as above mentioned, but the related theory is yet far from being complete.
Time-based flow systems. Limited dispersion can be attained in flow systems with MC in the analytical path by using very large sample inserted volumes. The rise and fall regions of the recorded peak are then exponen- tially time-dependent (regarding fall region, see Eq. 2) allowing time-based flow systems [13] to be designed (Fig. 4). In these systems, the parameter for estimating the analyte concentration is the time interval, ∆t, asso- ciated with the sample passage through the detector [17]. The ∆t value is the time interval during which the monitored analytical signal surpasses a given threshold value, usually close but distinct from baseline. As a MC (thus exponential dilution) is involved, the analyte con- centration, cA, is determined by considering that [41]:
∆t = k (3)
where k—experimentally estimated constant. For low injected volumes, the rise and fall curves may overlap, and more elaborated equations should be derived (see e.g. [29]) in order to describe the recorded peak shape.
Time-based flow systems constitute themselves in a unique tool for extending the dynamic concentration range of an analytical procedure. The advantage of using peak width, rather than peak height or peak area measurements, has been demonstrated [36]. In contrast to ordinary flow systems, time-based systems are not subject to limitations such as narrow dynamic range of the detector, upper detectable concentration, loss of lin- earity of the response curve, lack of reagent at the most concentrated region of the sample zone, etc. The approach has been low accepted, probably due to its inherent low sampling rate and to the uncertainties associated with the ∆t value.
Pseudo titrations. Flow injection titrations relying on exponential dilutions were initially implemented for the determination of calcium involving complexation with EDTA [53]. The injected sample was passed through a MC placed between the injector and the detector and a time-dependent concentration was gen- erated. The dispersed sample was subsequently merged with a titrant confluent stream of fixed concentration, and directed towards detection. Titration was accom- plished by measuring the time interval between two pre-selected points of the recorded peak, corresponding
logcA,
to fluid elements analogous to end-points of an ordinary titration. This time interval or, in other words, the
∆t-value, was proportional to the logarithm of sample concentration (3) and was the support for the calibra- tion procedure. Attainment of physical or chemical equilibrium was not required. The approach has been often exploited, and the determination of strong and weak acids (ascorbic acid, aminopolycarboxylic acids) and calcium in pharmaceutical samples and/or natural waters [54] can be considered for illustrative purposes.
Since some characteristics of the approach do not com- ply with the classical concept of titration recommended by IUPAC [55], Pardue and Fields [28] suggested that the innovation might be regarded as a modality of a kinetic method and Stewart and Rosenfeld [13] named this approach as pseudo-titration.
The MC can be integrated with the detector, in order to get a more compact system, as demonstrated in flow injection coulometric titrations [56]. The MC acted as gradient chamber, reagent generation chamber, and detector cell. Furthermore, a multiple MC was designed for carrying out Karl Fisher titrations in a cou- lometric flow injection system [57]. The MC acted as detection unit and was accountable also for solutions mixing and viscosity reduction.
True titrations. In flow-based true titrations, some essential requisites such as e.g. end point taken into account for analyte determination, and not required previous calibration, should be in attendance, as dem- onstrated in the pioneer article by Blaedel and Laessig [15]. Two peristaltic pumps were used for delivering the sample solution at a constant the flow rate and the titrant solution at a variable flow rate. Both streams were directed towards a MC and an indicator electrode monitored the final mixture at the MC outlet. End point was determined according to the final titrant flow rate.
An analogous strategy relying on constant flow rates was proposed for the potentiometric titration of sul- phide ion [35]. By setting the sum of flow rates of the solutions reaching the MC as half of the outlet flow
M
time
∆t
Fig. 4. Time-based flow analysis. M—time-dependent mea- surement; ∆t—signal appearance time related to a given threshold value (broken line).
528 ZAGATTO et al.
rate, a known linear relationship between titrant con- centration and time is attained. In this way, end point was found in function of the elapsed time.
A flow titration relying on a MC without requiring previous calibration was proposed by Bartroli et al.
[58]. Furthermore, an improved assembly [59] incorpo- rating the sensor unit was proposed. These innovations were also useful in designing a flow batch system for titration of iron in alloys [60]. End point was deter- mined by taking advantage on a unidimentional optimi- zation algorithm.
Evaluation of rate constants. The exponential con- centration lessening inside a MC can be exploited also for evaluating rate constants. To this end, a two-line manifold with a well-stirred MC was designed, and the time-dependent concentrations of reagents and prod- ucts were taken into account. The approach was ini- tially applied to first order reactions [37], the reaction rate constant being calculated after taking into consid- eration the physical dispersion of the involved solu- tions. As illustrations, titration of oxalic and ascorbic acids by Ce(IV) and Cr(VI), respectively, were selected. Furthermore, a similar flow manifold was designed for determining equilibrium constants for reactions of the 1 : 1 stoichiometry [61]. The experi- mental procedure was significantly simpler in relation to those involving the Job’s method or the continuous variation method.
Formation constants were also spectrophotometri- cally determined by using a flow system with MC [62].
Only two injections were needed, and the spectral shifts due to the variations in time-dependent concentrations of the reacting species were evaluated. For illustrative purposes, chemical species formed after reactions of micromolecules with cyclodextrins were considered;
different compounds such as phenolphthalein, p-nitro- phenolate and naproxen, as well as different buffer sys- tems were assayed.
MC-like components. Some specific components commonly used in the implementation of a flow mani- fold, although not directly considered as MC, might present a behaviour resembling MC, mostly as a conse- quence of their inner dead-volume. In this way, the con- cept of MC (as well as Eqs. 1 and 2) holds in relation to several analytical situations, including when the pres- ence of a MC is not expressly stated. In this context, some analytical steps relying on specific MC-like devices are highlighted as follows.
LIQUID-liquid extraction. This step can be effi- ciently implemented in both segmented and unseg- mented flow analysis [63]. For this task, MC can be used as phase-separation units, as demonstrated in the pioneer flow-injection system incorporating in-line liq- uid-liquid extraction for spectrophotometric determina- tion of molybdenum in plant materials [64]. Although other strategies using liquid-phase separating mem- branes, holding drops, etc have been proposed, MC are still largely used, as emphasised e.g. in the copper and
gold FAAS determination [65] and in the iodide spec- trophotometric determination [66]. It is important to stress that both analyte separation/concentration and detection can be accomplished inside the MC, as a radi- ation source (LED) and a detector (photodiode) can be integrated in a single compact unity [67]. Recently, an automated extraction system using a micro-batch glass extraction MC was proposed and applied to the deter- mination of copper [68].
Gas-liquid separation. In unsegmented flow analy- sis, the pioneer works involving gas-liquid concentra- tion/separation relied on semipermeable membranes [69], isothermal distillation [70] and pervaporation [71]. Gas diffusion through membranes has found wide analytical applications in flow analysis [52]. Flat mem- branes have been usually preferred although concentric tubular reactors have been also used [72]. The species most commonly determined by resorting to a gas-diffu- sion unit are volatile organic compounds (e.g. phenols, ketones, alcohols, carboxylic acids), or chemical spe- cies convertible to gases such as e.g. ammonia, sulfur dioxide and carbon dioxide [73, 74]. Moreover, metal ions can be diffused after formation of metal hydrides or metal vapours [75, 76]. With other purpose, Oliveira et al. used a liquid-vapour separation MC to reduce the hydrodynamic pressure in the microwave-assisted determination of reducing sugars in wine [77]. In some circumstances, e.g. when heat is applied, a photo-oxi- dation unit is used, or gaseous species are delivered from the flowing solutions, MC’s are used as an air removal strategy that keeps good conditions for detec- tion [78].
Analytical pervaporation can be described as a com- bination of evaporation and gas-diffusion in a single component [79]. A pervaporation MC enables the direct analysis of solid or semi-solid samples without the need for any sample pre-treatment, such as diges- tion, extraction, mechanical separation, etc. As illustra- tion, the spectrophotometric procedure for determina- tion of acetaldehyde in food samples based on reaction with Fuchsin was selected [80]. The analyte was released inside the MC, collected into an acidic reagent stream, and mixed with sulphite to yield the coloured reaction product. Other examples to be mentioned are the amperometric determination of phenol in natural waters [81] and the conductimetric determination of carbonates in soils [82], the former involving the glassy carbon electrode, and the later involving sample weigh- ing directly in the pervaporation MC.
Dialysis. Flow-based dialysis is commonly used to eliminate interferences or to accommodate analytical signal within the detector range, and makes use of a two-channel sandwiched device containing a planar hydrophilic membrane between the donor and the acceptor streams. A dialyser was used [83] for in-line removal of proteins and other potential interfering spe- cies from serum samples in the enzymatic determina- tions of glucose and urea. Furthermore, a miniaturized
MIXING CHAMBERS IN FLOW ANALYSIS: A REVIEW 529 multipurpose MC able to implement dialysis, gas diffu-
sion, solid-phase extraction and precipitation/dissolu- tion, was proposed [84]. It was evaluated in relation to monitoring of carbon dioxide, ascorbic acid, caffeine, lactose, fat and protein in assorted food samples. The prototype consisted either of two cylindrical concentric chambers separated by a circular membrane (for dialy- sis and gas diffusion) or of a PTFE piece (for SPE or precipitation/dissolution), and exhibited high versatil- ity, reduced internal volume and a performance compa- rable to a sandwich analyser.
Solid-liquid extraction. A MC or a mini-column packed with a solid support has been frequently used mainly for enhancing sensitivity and selectivity and to eliminate undesirable matrix effects. In general, in-line separation/concentration procedures involve exploita- tion of ion-exchange, adsorption or precipitation/co- precipitation. Flow-based solid-liquid extraction pro- cesses coupled with spectrometric detection were reviewed by Reis and co-workers [85] who emphasized use of ion exchangers. A rapid and sensitive flow injec- tion procedure involving in-line concentration in a PTFE packed mini-column was proposed [86] for the determination of lead by flame atomic absorption spec- trometry (FAAS). Analogously, copper was determined in seawater at the µg/L level by using a flow injection system coupled to FAAS: the analyte was complexed with 5,7-dichloroquinoline–8-ol and subsequently in- line concentrated by adsorption onto a C–18 bonded silica gel column [87].
Recently, a novel strategy for using solid reagents was implemented in a multi-pumping flow system with a MC filled with an ion-exchange resin [88]. Instead of being packed, the solid particles were kept in constant floating, reflux and circulating motion by means of a pulsed flowing stream generated by a solenoid pump.
The approach minimised some hindrances usually associated with utilisation of solid-phase mini-columns in flow analysis, such as e.g. backpressure effects and preferential pathways, and was applied to the spectro- photometric determination of zinc in plant digests.
Sample dissolution. Homogeneous sample distri- bution is often a critical aspect in relation to the analysis of slurries. MC play a beneficial influence in this con- text, as demonstrated in the FAAS determination of lead in sewage sludge [89]. A stirred flask with the sam- ple/digestion mixture was positioned in a closed flow system and an aliquot was further directed towards a PTFE coil positioned inside a microwave oven. After complete dissolution, the sample digest passed through a rotary valve and reached the sampling loop, filtration being not required. The sample was then directed towards the FAAS nebulizer. Microwave ovens are effectively expeditious means for in-line sample prepa- ration [18]. In this regard, a sequential injection system comprising a digestion MC placed inside a microwave oven was designed for the spectrophotometric determi- nation of total phosphorus in food samples [90].
Results confirmed that the MC acted also as a mixing device promoting efficient homogenization regardless of the number of required reagents. A microwave- heated flow-through digestion chamber was also used for the analysis of metals in biological samples by ICP−AES [91].
Electrolytic dissolution is an expeditious procedure for direct metal determination in solid samples relying on ion release by a DC current. An important feature of the approach regards the possibility of analysing a spe- cific spot of the solid sample for the evaluation of sam- ple homogeneity, given that the electrolysis process can be carried out in a precisely controlled position. More- over, sample contamination is minimal.
The approach was implemented in a flow injection system with a MC in relation to the direct determination of aluminium in allows [92]. The solid sample was placed on the MC, and acted as anode, thus enabling a noteworthy reduction of the time required for the anal- ysis. The MC included a de-bubbler channel for remov- ing the gas bubbles produced during electrolysis. In subsequent works, electrolytic dissolution MC’s with different geometries aiming at reducing the chamber dead volume or the clean-up time or the utilisation of a more intense electric current, were developed [93–96].
MC downsizing was possible by using a higher current density, as the anode (part of the sample exposed to electrolysis) was about 500-fold smaller in relation to Ref. 92. From the MC, the electro-dissolved ions were air propelled towards a second MC that was used to dilute and homogenize the sample solution prior to detection by ICP-OES [97].
Detector as a MC-like component. A flow through detector with a large inner volume behaves as a MC, and this aspect was recognized at the beginning of the development of flow-injection analysis [98]. In fact, with a too large detector, sample dilution and broaden- ing becomes more pronounced (Eqs. 1 and 2) impairing sensitivity and sample throughput, thus increasing reagent consumption and waste generation. Moreover, the beneficial aspects of the pulsed flows characteristic of multi-pumping flow systems [99, 100] may be sup- pressed.
MC as a minilaboratory. The operational versatil- ity of a MC, whether its complexity, is evident in the multiple tasks they could be assigned to, and the dis- tinct positioning they could assume in a flow manifold.
Among the different roles they could play in an analyt- ical process, more advanced methodologies have envis- aged the utilisation of a MC not merely as a component but as a whole small-scale laboratory. Based on an active chamber module, flow batch and lab-on-valve systems can be included in this perspective, as they can perform diverse and relatively complex functions that constitute the core building block of the analysis.
Flow-batch systems. Flow-batch systems are hybrid systems combining the favourable advantages of flow analysis, such as low sample and reagent con-
530 ZAGATTO et al.
sumption and high sampling rate, with those inherent to batch analysis, such as e.g. the wide application range.
The main component of the manifold is a MC into which different solutions can be added or removed, allowing the steps inherent to the specific application such as sample conditioning, reagent addition, detec- tion, etc. to be reproducibly carried out. Consequently, the MC can be regarded as a mini-laboratory. Reagent addition can optionally be defined according to the characteristics of every individual sample, thus individ- ual sample conditioning is in-line accomplished according to a concentration-oriented feedback mecha- nism. Analytical steps such as sample dilution, homog- enization, analyte concentration/separation, matrix matching, etc. take place inside the MC. After detec- tion, the MC is flushed out. Likewise a discrete analy- ser, sample integrity can be maintained throughout the entire analytical process, which extends the potential of application range of the flow-batch systems.
Flow-batch systems have been exploited for individ- ual sample conditioning [101, 102], titrations [60, 103], standard additions [104, 105], water hardness screening [106], generation of concentration gradients [107], cap- sule analyses [108], etc. It is usually operated similarly as a sequential injection analysis strategy, thus resem- bling a large lab-on-valve system.
Lab-on-valve system. The concept of lab-on valve was been presented by Ruzicka in 1990 [109] and can be considered was a miniaturization of a sequential injection analysis relying on a holding coil that plays a role similar to that of the MC in the flow-batch system.
The innovation utilizes small volumes and confined spaces bringing the assays to micro- and sub-microlitre level. The channels and the flow cell are build-up as a compact structure incorporated in a multi-position valve that can perform a variety of sample manipula- tions. Generally, the systems utilize UV-Vis spectro- photometry and optical fibres technology [110]. The potential of these “mini-laboratories” has been put in evidence in distinct analytical circumstances and the lab-on-valve systems proved to be particularly effective in the management of solid particles (beads) [111], leading to the inception of bead injection analysis [112]. Apart from spectrophotometric detection several other techniques have been exploited, such potentiom- etry [113], inductively coupled plasma mass spectrom- etry [114] and electrothermal atomic absorption spec- troscopy [115].
When designing a flow analyser, particularly when considering its versatility, portability or scope of appli- cation, a relevant limiting factor affecting instrument capability is the size of the mixing coil. In fact, this parameter is associated to system performance (includ- ing sample volume, flow rate, detection, reagent con- sumption) and remains usually unchanged during the entire run of the sample lots. In order to modify this parameter, physical manifold re-configuration is usu- ally required. Utilisation of a variable-volume MC, par-
ticularly under computer control, allowed a versatile handling of the sample zone [116], both in terms of dis- persion and reaction time, which could be used to gen- erate user-defined concentration gradients, to provide assorted dilution factors or to guarantee increased reac- tion development in stopped-flow procedures. This is presently an important endeavour in relation to MC’s in flow analysis.
ACKNOWLEDGMENTS
Financial support from the bi-national consortium CNPq (Brazil)/GRICES (Portugal) is greatly appreci- ated.
REFERENCES
1.Ruzicka, J., and Hansen, E.H., Flow Injection Analysis, 2nd ed., New York: Wiley-Interscience, 1988.
2.Nishihama, S., Yoshizuka, K., Scampavia, L., and Ruz- icka, J., Bunseki Kagaku, 2003, vol. 52, no. 12, p. 1187.
3.Skeggs Jr., L.T., Am. J. Clin. Pathol., 1957, vol. 28, no. 3, p. 311.
4.Snyder, L., Levine, J., Stoy, R., and Conetta, A., Anal.
Chem., 1976, vol. 48, no. 12, p. 943A.
5.Skeggs, Jr., L.T., Clin. Chem., 2000, vol. 46, no. 9, p. 1425.
6.Habig, R.L., Schlein, B.W., Walters, L., and Thiers, R.E., Clin. Chem., 1969, vol. 15, no. 11, p. 1045.
7.Zagatto, E.A.G. and Worsfold, P.J., Flow Analysis: Over- view. In: Worsfold, P.J., Townshend, A., and Poole, C.F.
(Eds), Encyclopedia of Analytical Science, 2nd ed., Ox- ford: Elsevier, 2005.
8.Valcarcel, M. and Castro, M.D.L., Flow Injection Analysis.
Principles and Applications, Chichester: Ellis Horwood, 1987.
9.Trojanowicz, M., Flow Injection Analysis: Instrumentation and Applications, London: World Scientific, 2000.
10.Zagatto, E.A.G., Reis, B.F., Oliveira, C.C., et al., Anal.
Chim. Acta, 1999, vol. 400, nos. 1–3, p. 249.
11.Albertus, F., Horstkotte, B., Cladera, A., and Cerda, V., Analyst, 1999, vol. 124, no. 9, p. 1373.
12.Jacintho, A.O., Zagatto, E.A.G., Reis, B.F., et. al., Anal.
Chim. Acta, 1981, vol. 130, no. 2, p. 361.
13.Stewart, K.K. and Rosenfeld, A.G., Anal. Chem., 1982, vol. 54, no. 13, p. 2368.
14.Silva, E.C., Araujo, M.C.U., Honorato, R.S., et al., Anal.
Chim. Acta, 1996, vol. 319, nos. 1–2, p. 153.
15.Blaedel, W.J. and Laessig, R.H, Anal. Chem., 1964, vol. 36, no. 8, p. 1617.
16.Veras, G., Honorato, R.S., Sarinho, V.T., and Arau- jo, M.C.U., Anal. Chim. Acta, 1999, vol. 401, nos. 1–2, p. 215.
17.Stewart, K.K., Anal. Chim. Acta, 1986, vol. 179, no. 1, p. 59.
18.Burguera, M., and Burguera, J.L., Anal. Chim. Acta, 1998, vol. 366, nos. 1–3, p. 63.
19.Marshall, G., Wolcott, D., and Olson, D., Anal. Chim. Acta, 2003, vol. 499, nos. 1–2, p. 29.
20.Bergamin, F.H., Medeiros, J.X., Reis, B.F., and Zagat- to, E.A.G., Anal. Chim. Acta, 1978, vol. 101, no. 1, p. 9.
MIXING CHAMBERS IN FLOW ANALYSIS: A REVIEW 531 21.Lazaro, F., Castro, M.D.L., and Valcarcel, M., Anal. Chim.
Acta, 1988, vol. 214, no. 1, p. 217.
22.Ruzicka, J., and Hansen, E.H., Anal. Chim. Acta, 1978, vol. 99, no. 1, p. 37.
23.Gisin, M., Thommen, C., and Mansfield, K.F., Anal.
Chim. Acta, 1986, vol. 179, no. 1, p. 149.
24.Gine, M.F., Reis, B.F., Zagatto, E.A.G., et al., Anal. Chim.
Acta, 1983, vol. 155, no. 1, p. 131.
25.Ramsing, A.U., Ruzicka, J., and Hansen, E.H., Anal.
Chim. Acta, 1981, vol. 129, no. 1, p. 1.
26.Hull, R.D., Malick, R.E., and Dorsey, J.G., Anal. Chim.
Acta, 1992, vol. 267, no. 1, p. 1.
27.Levenspiel, O., Chemical Reaction Engineering, 2nd Ed., New York: John Wiley & Sons, 1972.
28.Pardue, H.L. and Fields, B., Anal. Chim. Acta, 1981, vol. 124, no. 1, p. 39.
29.Pardue, H.L. and Fields, B., Anal. Chim. Acta, 1981, vol. 124, no. 1, p. 65.
30.Pardue, H.L. and Jager, P., Anal. Chim. Acta, 1986, vol. 179, no. 1, p. 169.
31.Jager, P. and Pardue, H.L., Anal. Chim. Acta, 1986, vol. 187, no. 1, p. 343.
32.James, M.J. and Pardue, H.L., Anal. Chim. Acta, 1992, vol. 270, no. 1, p. 195.
33.James, M.J., Hoke, S.H., and Pardue, H.L., Anal. Chim.
Acta, 1993, vol. 272, no. 1, p. 115.
34.Pungor, E., Feher, Z., Nagy, G., et al., Anal. Chim. Acta, 1979, vol. 109, no. 1, p. 1.
35.Fleet, B., and Ho, A.Y.W., Anal. Chem., 1974, vol. 46, no. 1, p. 9.
36.Tyson, J.F., Appleton, J.M.H., and Idris, A.B., Anal.
Chim. Acta, 1983, vol. 145, no. 1, p. 159.
37.Echols, R.T., and Tyson, J.F., Talanta, 1994, vol. 41, no. 10, p. 1775.
38.Tyson, J.F., Analyst, 1987, vol. 112, no. 4, p. 523.
39.Echols, R.T., and Tyson, J.F., Anal. Chim. Acta, 1994, vol. 286, no. 2, p. 169.
40.Jordan, J.M., Hoke, S.M., and Pardue, H.L., Anal.
Chim. Acta, 1993, vol. 272, no. 1, p. 115.
41.Tyson, J.F., Anal. Chim. Acta, 1986, vol. 179, no. 1, p. 131.
42.Stone, D.C. and Tyson, J.F., Analyst, 1989, vol. 114, no. 11, p. 1453.
43.Garn, M.B., Gisin, M., Gross, H., et al., Anal. Chim.
Acta, 1988, vol. 207, no. 1, p. 225.
44.Taylor, M.J.C., Marshall, G.D., Williams, S.J.S., et al., Anal. Chim. Acta, 1996, vol. 329, no. 3, p. 275.
45.El Azouzi, H., Jordan, M.Y.P., Salvador, A., and Guardia, M., Spectrochim. Acta B, 1996, vol. 51, no. 14, p. 1747.
46.Zagatto, E.A.G., Arruda, M.A.Z., Jacintho, A.O., and Mat- tos, I.L., Anal. Chim. Acta, 1990, vol. 234, no. 1, p. 153.
47.Bergamin, F.H., Reis, B.F., and Zagatto, E.A.G., Anal.
Chim. Acta, 1978, vol. 97, no. 2, p. 427.
48.Dias, A.C.B., Borges, E.P., Zagatto, E.A.G., and Wors- fold, P.J., Talanta, 2006, vol. 68, no. 4, p. 1076.
49.Araujo, A.N., Lima, J.L.F.C., Saraiva, M.L.M.F.S., etal., J. Flow Injection Anal., 1997, vol. 14, no. 2, p. 151.
50.Pinto, P.C.A.G., Saraiva, M.L.M.F.S., and Lima, J.L.F.C., Anal. Chim. Acta, 2006, vol. 555, no. 2, p. 377.
51.Cormack, T., and Staden, J.F., Anal. Chim. Acta, 1998, vol. 367, nos. 1–3, p. 111.
52.Ukeda, H., J. Flow Injection Anal., 2006, vol. 23, no. 2, p. 38.
53.Ruzicka, J., Hansen, E.H., and Mosbaek, H., Anal.
Chim. Acta, 1977, vol. 92, no. 2, p. 235.
54.Koupparis, M.A., Anagnostopoulou, P., and Malm- stadt, H.V., Talanta, 1985, vol. 32, no. 5, p. 411.
55.International Union of Pure and Applied Chemistry, Com- pendium of Analytical Nomenclature, Definitive Rules 1997, 3rd ed., Oxford: Blackwell Scientific Publications, 1998.
56.Taylor, R.H., Ruzicka, J., and Christian, G.D., Talanta, 1992, vol. 39, no. 3, p. 285.
57.Chen, R., Ruzicka, J., and Christian, G.D., Talanta, 1994, vol. 41, no. 6, p. 949.
58.Bartroli, J. and Alerm, L., Anal. Lett., 1995, vol. 28, no. 8, p. 1483.
59.Alerm, L. and Bartroli, J., Anal. Chem., 1996, vol. 68, no. 8, p. 1394.
60.Honorato, R.S., Araujo, M.C.U., Lima, R.A.C., et al., Anal. Chim. Acta, 1999, vol. 396, no. 1, p. 91.
61.Echols, R.T. and Tyson, J.F., Analyst, 1995, vol. 120, no. 4, p. 1175.
62.Georgiou, M.E., Georgiou, C.A., and Koupparis, M.A., Anal. Chem., 1995, vol. 67, no. 1, p. 114.
63.Zagatto, E.A.G., and Dias, A.C.B., In-line sample prepara- tion in flow analysis. In: Arruda, M.A.Z. (Ed.), Trends in Sample Preparation. N. York: N. Science Pub. Inc., 2007.
64.Bergamin, F.H., Medeiros, J.X., Reis, B.F., and Zagat- to, E.A.G., Anal. Chim. Acta, 1978, vol. 101, no. 1, p. 9.
65.Lin, S., and Hwang, H., Talanta, 1993, vol. 40, no. 7, p. 1077.
66.Maleki, N., Haghighi, B., and Safavi, A., Microchem.
J., 1996, vol. 53, no. 2, p. 147.
67.Comitre, A.L.D., and Reis, B.F., Anal. Chim. Acta, 2003, vol. 479, no. 2, p. 185.
68.Diniz, M.C.T., Fatibello, F.O., and Rohwedder, J.J.R., Anal. Chim. Acta, 2004, vol. 525, no. 2, p. 281.
69.Baadenhuijsen, H. and Seurenjacobs, H.E.H., Clin.
Chem., 1979, vol. 25, no. 3, p. 443.
70.Zagatto, E.A.G., Reis, B.F., Bergamin, F.H., and Krug, F.J., Anal. Chim. Acta, 1979, vol. 109, no. 1, p. 45.
71.Mattos, I.L., Castro M.D.L., and Valcarcel, M., Talan- ta, 1995, vol. 42, no. 5, p. 755.
72.Motomizu, S., Toei, K., Kuwaki, T., and Oshima, M., Anal. Chem. 1987, vol. 59, no. 24, p. 2930.
73.Moskvin, L.N. and Nikitina, T.G., J. Anal. Chem., 2003, vol. 59, no. 1, p. 2.
74.Frenzel, W. and Liu, C.Y., Fresenius’ J. Anal. Chem., 1992, vol. 342, nos. 4–5, p. 276.
75.Tsalev, D.L., Spectrochim. Acta B, 2000, vol. 55, no. 7, p. 917.
76.Vargas-Razo, C. and Tyson, J.F., Fresenius’ J. Anal.
Chem., 2000, vol. 366, no. 2, p. 182.
77.Oliveira, A.F., Fatibello, F.O., and Nobrega, J.A., Tal- anta, 2001, vol. 55, no. 4, p. 677.
532 ZAGATTO et al.
78.Pons, C., Toth, I.V., Rangel, A.O.S.S., et al., Anal.
Chim. Acta, 2006, vol. 572, no. 1, p. 148.
79.Castro, M.D.L. and Papaefstathiou, I., Trends Anal.
Chem., 1998, vol. 17, no. 1, p. 41.
80.Papaefstathiou, I., Bilitewski, U., and Castro, M.D.L., Fresenius’ J. Anal. Chem. 1997, vol. 357, no. 8, p. 1168.
81.Sheikheldin, S.Y., Cardwell, T.J., Cattrall, R.W., et al., Anal. Chim. Acta, 2000, vol. 419, no. 1, p. 9.
82.Kamogawa, M.Y., Nogueira, A.R.A., Miyazawa, M., etal., Anal. Chim. Acta, 2001, vol. 438, nos. 1–2, p. 273.
83.Gorton, L. and Ogren, L., Anal. Chim. Acta, 1981, vol. 130, no. 1, p. 45.
84.Lucena, R., Cardenas, S., Gallego, M., and Valcarcel, M., Anal. Chim. Acta, 2004, vol. 509, no. 1, p. 47.
85.Reis, B.F., Miranda, C.E.S., and Baccan, N., Quim. Nova, 1996, vol. 19, no. 6, p. 623.
86.Zachariadis, G.A., Anthemidis, A.N., Bettas, P.G., and Stratis, J.A., Talanta, 2002, vol. 57, no. 5, p. 919.
87.Gladis, J.M., Biju, V.M., and Rao, T.P., Atom. Spectrosc., 2002, vol. 23, no. 5, p. 143.
88.Ribeiro, M.F.T., Dias, A.C.B., Santos, J.L.M., et al., Anal.
Bioanal. Chem., 2006, vol. 384, no. 4, p. 1019.
89.Carbonnel, V., Guardia, M., Salvador, A., et al., Anal.
Chim. Acta, 1990, vol. 238, no. 1, p. 417.
90.Oliveira, C.C., Zagatto, E.A.G., Araujo, A.N., and Li- ma, J.L.F.C., Anal. Chim. Acta, 1998, vol. 371, no. 1, p. 57.
91.Stewart, L.J.M. and Barnes, R.M., Analyst, 1994, vol. 119, no. 5, p. 103.
92.Bergamin, F.H., Krug, F.J., Zagatto, E.A.G., et al., Anal. Chim. Acta, 1986, vol. 190, no. 1, p. 177.
93.Bergamin, F.H., Krug, F.J., Reis, B.F., et al., Anal.
Chim. Acta, 1988, vol. 214, no. 1, p. 397.
94.Gervasio, A.P.G., Luca, G.C., Menegario, A.A., et al., Anal. Chim. Acta, 2000, vol. 405, nos. 1–2, p. 213.
95.Packer, A.P., Gervasio A.P.G., Miranda, C.E.S., et al., Anal. Chim. Acta, 2000, vol. 485, no. 2, p. 145.
96.Silva, J.B.B., Giacomelli, M.B.O., Lehmkuhl, A., et al., Quim. Nova, 1999, vol. 22, no. 1, p. 18.
97.Souza, I.G., Bergamin, F.H., Krug, F.J., et al., Anal.
Chim. Acta, 1991, vol. 245, no. 1, p. 211.
98.Reijn, J.M., Linden, W.E., and Poppe, H., Anal. Chim.
Acta, 1980, vol. 114, no. 1, p. 105.
99.Lapa, R.A.S., Lima, J.L.F.C., Reis, B.F., et al., Anal.
Chim. Acta, 2002, vol. 466, no. 1, p. 125.
100.Prior, J.A.V., Santos, J.L.M., and Lima, J.L.F.C., Anal.
Bioanal. Chem., 2003, vol. 375, no. 8, p. 1234.
101.Carneiro, J.M.T., Honorato, R.S., and Zagatto, E.A.G., Fresenius J. Anal. Chem., 2000, vol. 368, no. 5, p. 496.
102.Carneiro, J.M.T., Dias, A.C.B., Zagatto, E.A.G., and Honorato, R.S., Anal. Chim. Acta, 2002, vol. 455, no. 2,p. 327.
103.Aquino, E.V., Roohwedder, J.J.R., and Pasquini, C., Anal. Bioanal. Chem., 2006, vol. 386, no. 6, p. 1921.
104.Silva, J.E., Silva, F.A., Pimentel, M.F., et al., Talanta, 2006, vol. 70, no. 3, p. 522.
105.Almeida, L.F., Martins, V.L., Silva, E.C., et al., Anal.
Chim. Acta, 2003, vol. 486, no. 1, p. 143.
106.Lima, R.A.C., Santos, S.R.B., Costa, R.S., et al., Anal.
Chim. Acta, 2004, vol. 518, nos. 1–2, p. 25.
107.Medeiros, E.P., Nascimento, E.C.L., Medeiros, A.C.D., et al., Anal. Chim. Acta, 2004, vol. 511, no. 1, p. 113.
108.Carneiro, J.M.T., Dias, A.C.B., Zagatto, E.A.G., et al., Anal. Chim. Acta, 2005, vol. 531, no. 2, p. 279.
109.Ruzicka, J., Analyst, 2000, vol. 125, no. 6, p. 1053.
110.Ohno, S., Teshima N., Sakai, T., et al., Talanta, 2006, vol. 68, no. 3, p. 527.
111.Ampan, P., Ruzicka, J., Atallah, R., et al., Anal. Chim.
Acta, 2003, vol. 499, nos. 1–2, p. 1167.
112.Ruzicka, J., and Scampavia, L., Anal. Chem., 1999, vol. 71, no. 7, p. 257A.
113.Jakmuneea, J., Patimapornlert, L., Suteerapataranon, S., et al., Talanta, 2005, vol. 65, no. 3, p. 789.
114.Wang, J., Hansen, E.H., and Miro, M., Anal. Chim. Acta, 2003, vol. 499, nos. 1–2, p. 139.
115.Long, X., Hansen, E.H., and Miro, M., Talanta, 2005, vol. 66, no. 5, p. 1326.
116.Lipe, L.L., Purinton, S.M., Mederios, E., et al., Anal. Chim.
Acta, 2002, vol. 455, no. 2, p. 287.
