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Sequential Injection Analysis Hyphenated with Other Flow Techniques: AReviewPaula C. A. G. Pintoa; M. Lúciaa; M. F. S. Saraivaa; José L. F. C. Limaa

a REQUIMTE, Serviço de Química-Física, Faculdade de Farmácia da Universidade do Porto, Porto,Portugal

Online publication date: 18 February 2011

To cite this Article Pinto, Paula C. A. G. , Lúcia, M. , Saraiva, M. F. S. and Lima, José L. F. C.(2011) 'Sequential InjectionAnalysis Hyphenated with Other Flow Techniques: A Review', Analytical Letters, 44: 1, 374 — 397To link to this Article: DOI: 10.1080/00032719.2010.500780URL: http://dx.doi.org/10.1080/00032719.2010.500780

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Flow and Sequential Injection—General Approaches

SEQUENTIAL INJECTION ANALYSIS HYPHENATEDWITH OTHER FLOW TECHNIQUES: A REVIEW

Paula C. A. G. Pinto, M. Lucia, M. F. S. Saraiva, andJose L. F. C. LimaREQUIMTE, Servico de Quımica-Fısica, Faculdade de Farmacia daUniversidade do Porto, Porto, Portugal

In the last two decades, sequential injection analysis (SIA) became an important auto-

mation tool in several analytical fields as it provided advantages in terms of versatility,

robustness, and consumption of samples and reagents.

The noteworthy versatility of an SIA selection valve allowed its association with

several units, including devices typically associated with other flow techniques, resulting

in generally better analytical performance.

This review discusses the hyphenization of SIA with other flow approaches outlining

its advantages and motivations, which are related mainly with sample manipulation and

solutions management. The future trends and perspectives in this field are also addressed.

Keywords: Flow techniques; Hyphenization; Review; SIA

INTRODUCTION

Flow techniques are nowadays consolidated as powerful tools in analyticalchemistry, mainly due to their simple configuration, easy operation, low cost, andcompatibility with any detection system (Trojanowicz 2008; Cerda and Cerda 2009).

The evolution of flow techniques in the last three decades illustrates their sig-nificance and importance in the field of automation and opened immense possibilitiesin analytical perspective. The origination of this family of analytical methods wasflow injection analysis (FIA) in 1975 (Ruzicka and Hansen 1975), almost 20 yearsafter the appearance of air-segmented flow systems (Skeggs 1957). By that time,FIA arose as a consequence of the ever increasing demands for analysis in severalfields and industries. The appearance of sequential injection analysis (SIA), as analternative to FIA, broadened the scope of flow techniques for chemical analysisby overcoming some of the drawbacks that hindered its routine utilization (Ruzicka

Received 9 February 2010; accepted 11 March 2010.

This paper was submitted as part of a Special Issue on Flow Injection Analysis.

Address correspondence to Paula C. A. G. Pinto, REQUIMTE, Servico de Quımica-Fısica,

Faculdade de Farmacia da Universidade do Porto, Rua Anıbal Cunha, 164, 4099-030 Porto, Portugal.

E-mail: [email protected]

Analytical Letters, 44: 374–397, 2011

Copyright # Taylor & Francis Group, LLC

ISSN: 0003-2719 print=1532-236X online

DOI: 10.1080/00032719.2010.500780

374

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and Marshall 1990). Due to the simplicity of the manifolds and its inherent charac-teristics, SIA exhibited high potential for sample manipulation providing interestingpossibilities in terms of automated analysis (Lenehan et al. 2002). In 1994, multicom-mutation appeared with the aim of increasing the versatility of flow systems, facilitat-ing automation, and decreasing reagent consumption (Reis et al. 1994). Thisanalytical strategy seemed to embrace some of the advantages of both FIA andSIA, overcoming, at the same time, their disadvantages. Multisyringe flow injectionanalysis (MSFIA) was developed in 1999, claiming to combine the advantaged of theaforementioned techniques (Albertus et al. 1999). More recently multipumping flowsystems (MPFS) were proposed as a novel strategy for solutions management basedon pulsed flow.

Even though these modalities of flow analysis rely on the use of specific devicesthat are usually associated in the literature to specific flow approaches, they are all, insome way, based on the same initial principles inherent to FIA by its appearance:reproducible sample insertion, reproducible timing, and controlled dispersion(Ruzicka and Hansen 1978).

During the development of new methodologies, the search for solutions forconcrete analytical problems has frequently justified the incorporation of conceptsand devices of more than one solution management approach in the same manifold,in order to maximize the advantages of each one (V. Cerda et al. 1999; A. Cerda andCerda 2009). This hyphenization is usually associated with increased possibilities interms of solutions and sample management and with better analytical performanceof the resulting systems.

This review intends to summarize and discuss the motivations and advantagesof the association of SIA with other flow techniques with the aim of further increas-ing research in the field of hyphenated techniques.

Sequential Injection Analysis (SIA) in the Flow Context

Even though the functioning of a SIA system relies on the same basic principlesof FIA, based upon controlled dispersion of a sample introduced into a movingcarrier stream, this technique soon proved to be a powerful and versatile solutionhandling approach. The basic functioning of a SIA system involves the sequentialaspiration of solutions through a selection valve (Perez-Olmos 2005). In severalinstances, this feature has been pointed out as a disadvantage in terms of mixing con-ditions. However, the operation mode, based on forward and reversed flow, facilitatesthe use of different chemistries and strategies without reconfiguration of the manifoldso that the technique can constitute a useful analytical tool (Lenehan et al. 2002).

A typical SIA manifold is comprised of a selection valve, which operates insynchronization with a propelling device, and a detector (Fig. 1). The computer con-trol mode operation of the systems allows the aspiration of precise volumes and aneffective utilization of solutions, minimizing the consumption of sample and reagentsolutions and the generation of effluents. Furthermore, the effective control of themost relevant analytical parameters at run-time assures a great operational flexibilityand facilitates system optimization.

The most important feature of SIA is its versatility, which is centered on theselection valve whereby each port can be dedicated to a specific purpose or

SIA HYPHENATED TECHNIQUES 375


operation. Thus, in this kind of system reagents, samples, standards, as well as detec-tors and other devices are placed around the valve in order to accomplish a specifictask. Since the early utilization of SIA, researchers made use of this intrinsic charac-teristic by coupling all kinds of devices to the selection valve. It is possible to findSIA manifolds that incorporate gas diffusion units, solid phase and enzyme reactors,mixing chambers and micro-wave ovens, among many others, with the aim ofincreasing system profitability (Economou 2005).

Hyphenization of SIA with Other Flow Techniques

After several decades of remarkable evolution in the flow analysis area, the ideathat each flow technique is better than the last one is misplaced andmust be reviewed. Itis obvious nowadays that flow techniques are all complementary, and their rentabiliza-tion passes through their association in analytical systems that combine the most sig-nificant features of the independent approaches, resulting in increased potential tomanipulate complex samples with high accuracy and analytical efficiency. This ismainly related to the similarities among flow techniques, in terms of basic principles,that will result, in the author’s perspective, in a relativization of the technique’s denomi-nation and in a rational utilization of all the approaches in specific analytical situations.

As mentioned previously, the peculiar mode of operation of SIA and its inherentversatility enable its association with all kinds of devices and flow approaches. Thisassociation can be related to increased analytical efficiency but can also be the keyto solve some of the problems associated with the analysis in SIA systems, namely,the difficulties arising from the sequential aspiration of solutions.

The next sections include a critical description of the flow approaches resultingfrom the successful hyphenization of SIA with FIA, multicommutation, multi-pumping, and multisyringe. This will embrace the methodologies in which the princi-ples and strategies of SIA were associated to that of other flow techniques in the sameflow assembly in order to solve concrete analytical problems, enhance the sensitivityof the determinations, or enable the coupling to specific detection systems.

Hyphenization with Flow Injection Analysis (FIA)

The proposal of FIA in the 1970s as a tool for the automation of analyticalprocedures represented a step forward in this challenging area. It relied on the

Figure 1. Configuration of a basic SIA system. C: carrier, PP: peristaltic pump; SV: selection valve; HC:

holding coil; RC: reaction coil; D: detector; W: waste; R: reagent; S: sample.

376 P. C. A. G. PINTO ET AL.


reproducible injection of a sample aliquot in a reagent flow stream enabling the analy-sis in the absence of chemical equilibrium (Ruzicka and Hansen 1978). This mode ofoperation, based on constant volume allowed the insertion of sample aliquots withhigh precision, resulting in procedures with less associated errors compared to thosestrategies in which solutions were inserted on a time basis. A typical FIA systemincorporated an injection valve, whose loop defined the volume of the sample aliquot,a propulsion device, and a detector. The main drawbacks of FIA are related to thecontinuous flow of reagents that result in increased consumption and with the needof system reconfiguration for adaption to different analytical determinations thatare not entirely acceptable in industrial analysis (Ruzicka and Marshall 1990).

The association of the FIA and SIA concepts in the same flow network hasbeen performed several times in the last decades, resulting in manifolds withincreased versatility and analytical efficiency. Several times, this hyphenization wasperformed, aiming the implementation of sample pretreatment procedures thatresulted in methodologies with reduced operator intervention (Crespı, Forteza andCerda 1995, Oms et al. 1996a, Oms et al. 1996b, Costa Cardoso, and Araujo,2003, Zarat, Araujo, and Perez-Olmos 2004, Chen et al. 2008, Ma, Yuan, and Liang2008, Costa et al. 2003, Chen et al. 2008, Ma et al. 2008, Oliveira et al. 1998, Oliveira,Sartini, and Zagatto 2000, Mateos et al. 2000). In these cases, the association allowedthe simultaneous implementation of distinct operations in separate channels wherebythe fluids could flow in opposite directions and increasing the separation rates.Moreover, it also permitted the connection of the flow manifold to some detectionsystems through the re-injection of treated samples in the detector with reduced dis-persion (Wang and Hansen 2005).

Crespı, Forteza, and Cerda (1995) developed a flow assembly in which the con-cepts of SIA and FIA were explored with the aim of preparing a reaction pre-formbefore injection in the amperometric detector. A mixer-reactor was connected toboth selection and injection valves and worked in synchronization with a syringepump. The configuration of the system based on the unidirectional circulation ofthe solutions in the reactor resulted in an efficient mixing of sample and reagent,as demanded by the reaction particularities, allowing the injection of the formedproduct in the detector with reduced dispersion.

One can find a couple of SIA systems in which an injection valve was connec-ted to the selection valve as support of gas diffusion (Oms et al. 1996b) and precon-centration (Oms et al. 1996a) units being good examples of systems that allow theimplementation of different tasks in distinct channels. In these systems the pretreat-ment devices were placed in the loop of the injection valve that was connected to thedetector channel, enabling the re-injection of the concentrated sample in the detectorpathway with reduced dispersion and high yield. Moreover, with this disposition,the acceptor channel of the analyte forms a closed loop avoiding problems relatedwith pressure differences. Several authors adopted this strategy during the develop-ment of analytical methodologies based on preconcentration (Costa, Cardoso, andAraujo 2003; Zarate, Araujo, and Perez-Olmos 2004; Chen et al. 2008; Ma, Yuan,and Liang 2008). In some of these methodologies, to reach an adequate sensitivity,volumes of sample in the mL range were introduced in the system by means of aperistaltic pump that was connected to the injection valve (Costa et al. 2003; Chenet al. 2008; Ma et al. 2008). As before, the loop accommodated the concentration



column and by continuous flow of the sample, the analyte was concentrated. Then,elution was performed by passage of the eluent by a reversed flow extraction scheme.

Two SIA methodologies involving wetting film extraction comprised theinjection of air-segmented organic solvent in the extraction coil for the elution ofthe wetting film (Nakano et al. 1996, 1997). Other work from the same research groupfor the determination of Cr (VI and III) was based on a similar system and principle(Luo et al. 1997), but, in this situation, the system included a second injection valve,connected to a peristaltic pump, for the introduction of a sample=reagent mixture inthe flow system.

Oliveira et al. developed two similar SIA procedures comprising on-line micro-wave sample digestion of food samples (Oliveira et al. 1998; Oliveira, Sartini, andZagatto 2000). The procedure involved the insertion of food samples as a slurry orsuspension in a digestion bomb together with nitric acid. An injection valve, function-ing as a two position valve was connected to the digestion bomb with the aim of clos-ing it or connecting it to waste in order to eliminate gases resulting from the digestionprocess.

A flow assembly that associates the concepts of SIA and FIA was developed toperform analytes separation prior to radioactivity determination. The separationstep was carried out by means of a MnO2 impregnated cotton filter that was placedin the loop of an injection valve being the later connected to one of the inlets of theselection valve (Mateos et al. 2000). After adsorption, the analytes were removedfrom the cotton filter by the passage of hydroxylamine through the cartridge afterchanging the position of the injection valve. The obtained solution was then treatedand analyzed outside the flow system.

Miro and co-workers proposed a SIA methodology based on flow reversalwetting-film extraction in which an injection valve, connected to the selection valve,was placed in the extraction coil outlet allowing the introduction of sample, in themL range, by flow reversal (Miro et al. 2002). By changing the valve position, thesample was again dispensed to the extraction coil. This particular functioningallowed not only the reversal of the sample flow without disturbing the extractionprocess but also an additional washing out of the analyte by an organic solvent.

Several SIA methodologies involving extraction and preconcentration of metalsprior to detection by ICP-MS (Wang andHansen 2001; Jimenez, Velarte, and Castillo2002; Wang and Hansen 2002, 2002, 2003; Sabarudin et al. 2006; Sabarudin et al.2007) and ETAAS (Nielsen and Hansen 2000; Wang and Hansen 2000, 2002b,2002d; Long et al. 2004; Chomchoei et al. 2005; Wang and Hansen 2005; Anthemidis2008; Lemos et al. 2008; Anthemidis and Adam 2009; Anthemidis and Ioannou 2009)resorted to the injection of the treated sample into the detector by means of an injec-tion valve. With this strategy, it was possible to avoid the insertion of the sample afterflow reversal that could result in high dispersion of the analytes and, consequently, ina decrease of the sensitivity. This approach was also followed by several reports onminiaturized SIA systems, named lab-on-valve (LOV) by the original author(Ruzicka 2000), coupled to distinct detection systems, namely ICP-MS (Wang andHansen 2001), ETAAS (Long et al. 2004), and spectrophotometry (Vogt et al.2000). Similarly, Elsholz and co-workers developed a SIA system in which aliquotsof sample and digestion reagent, consisting of a bromide=bromated mixture, filedthe loop of the injection valve used (Elsholz et al. 2000). By changing the valve



position the treated sample was sent to detection by cold vapor atomic absorptionspectrometry.

On an identical basis, several SIA systems coupled to high-performance liquidchromatography (HPLC) were responsible for the automated sample preparation; thefinal eluent filled the loop of an injection valve and was injected into the HPLCdetector (Lenghor et al. 2003; Theodoridis et al. 2004; Zacharis, Theodoridis, andVoulgaropoulos 2004, 2006).

Anthemidis and co-workers proposed a methodology that hyphenates SIA andFIA in a very peculiar way (Fig. 2) (Anthemidis, Zachariadis, and Stratis 2004). Thecentral channel of the selection valve was connected to a gas-liquid separator (GLS)and not to a propulsion device as usually occurs in these systems. Thus, it was neces-sary to couple a peristaltic pump to each solution to be inserted in the GLS, namely,a sample and reductant solution. An injection valve was used for sample insertionand GLS evacuation. A second injection valve managed the flow of the argon inthe system avoiding its passage through the gas-liquid separator that would increasethe analyte dispersion.

A SIA system interfaced with capillary electrophoresis made use of an injectionvalve to flush the sample through the interface between the system and the capillary(Kulka, Quintas, and Lendl 2006). This step was most important for the perform-ance of the system as it ensured that the sample was close to the capillary inlet justbefore the pressurization of the system and injection.

Ayora-Canada and Lendl (2000) developed a SIA methodology that wasconnected to a novel sheath-flow cell comprising three stream lines where solutionflowed adjacent to each other in a laminar mode. The system incorporated an injec-tion valve that was used as switching device, allowing all three flow lines to be

Figure 2. Scheme of the hyphenated SIA system developed by Anthemidis et al. (2004) for the

determination of mercury.SV: selection valve; IV1, IV2: injection valve; PP1, PP2: peristaltic pump;

GLS: gas-liquid separator; AAFC: atomic absorption flow cell; R: reagent;W: waste; DW: deionized water.



stopped simultaneously in the detection cell which avoided changes in the analyteconcentration during measurement.

The sampling rate of two distinct SIA methodologies was increased resorting tothe FIA concept in some of the essential steps of the analytical procedures (Guzmanand Compton 1993; Segundo and Rangel 2002). Guzman and Compton (1993)proposed a system in which the main channel of the selection valve was not connec-ted to the propulsion device but rather to an injection valve. Depending on the pos-ition of the valve, either a peristaltic or syringe pump was activated. The aspirationof sample and reagents was performed by activation of the syringe pump takingadvantage of its high volume accuracy. The peristaltic pump was used to fill the sys-tem and clean it at the end of each analytical cycle. Furthermore, this dispositionallowed the filling of the syringe at the same time that the system was being washedby pump functioning. Also, with the aim of increasing sample throughput, Segundoand Rangel (2002) developed a SIA system embracing an injection valve thatsupported two enzymatic reactors. This valve worked in synchronization with anauxiliary pump and while sample and reagent were sent to one reactor, the otherwas continuously washed with carrier propelled by the pump. This operation moderesulted in an increment of sample throughput as it allowed performing the detectionof ethanol while the glycerol reactor was loaded.

The advantages of the hyphenization of SIA with FIA are very well illustrated ina methodology for the analysis of edible oils that intends to be a flow sampling strat-egy for the analysis of this kind of sample without pretreatment (Pinto, Saraiva andLima 2006). The flow system was designed by incorporation of an injection valve thatwas responsible for the introduction of the sample in the system, avoiding the pro-blems associated with its viscosity that resulted in inaccuracy of the inserted volumes.

The monosegmentation approach was explored in a novel strategy forcalibration by the combined action of a selection and an injection valve in a systemsimilar to the one developed by Guzman and Compton (1993) and describedpreviously in this section (Kozak et al. 2008). A syringe pump was responsible forthe aspiration of air, diluent, and sample from the selection valve to perform on-linedilution. At the same time the carrier was continuously propelled to the detector bythe peristaltic pump through the injection valve. Then, the flow was reversed and themonosegment was partially sent to waste and homogenized. By changing the positionof the injection valve, the monosegment was propelled to the detector by the peristal-tic pump. By hyphenization of SIA with FIA, the authors managed to implement anautomated calibration procedure with reduced associated errors by using one stocksolution.

Hyphenization with Multicommutation

Since it was proposed in 1994 (Reis et al. 1994), multicommutation has beenthe basis for the development of numerous applications with increased complexity.The successful application of the multicommutation concept in distinct analyticalsituations has confirmed this approach as a versatile solution handling strategy. Thisdiverse application profile is probably related with the different interpretations ofmulticommutation in the scientific community; it has been simply considered a meth-odology based on solenoid valves (Icardo, Mateo, and Calatayud 2002) and on the



other side has been explored, by some of the authors of the original proposal, in amuch more broader perspective as a concept or attribute of a given flow system(Feres et al. 2008). The original authors mainly highlight the use of binary sampling,considering that tandem streams constitute a driving force toward improved mixingconditions. In this review, we tried to make a broad analysis of the multicommuta-tion approach in order to contemplate its diverse interpretations.

The association of multicommutation with SIA in the same flow network hasincreased in the last years, probably, as the key to circumvent some of the limitationsof SIA, mainly the ones associated with the mixing conditions of the solutionsaspirated sequentially. As a result, the systems are generally more versatile, and itis possible to control the operations within the system more efficiently.

Since 1998, solenoid valves have been used in SIA systems and in its miniatur-ized versions as part of a mechanism which controls the peristaltic pump operation(Fig. 3) (Araujo et al. 1998; Araujo, Costa, and Lima 1999; Costa et al. 2000; Costaand Araujo 2001b; Costa et al. 2002; Costa et al. 2003; Pinto, Lima, and Saraiva2003; Pena, Lima, and Saraiva 2005; Santos, Araujo et al. 2004; Passos et al.2005; Pinto, Saraiva, Reis et al. 2005; Pinto et al. 2005; Garcia, Saraiva, and Lima2006; Pinto et al. 2006; Amorim, Araujo, and Montenegro 2007; Amorim et al.2008; Araujo, Saraiva, and Lima 2008; Passos, Saraiva and Lima 2008; Passos,Saraiva, Lima, and Korn 2008; Perez-Olmos et al. 2008; Zarate et al. 2008; Passoset al. 2009; Zarate et al. 2009). With this mechanism it is possible to guarantee thatin the beginning of each determination the position of the pump rollers is constant,thereby minimizing the effect of systems inertia at the beginning of the pump’s

Figure 3. Schematic representation of the mechanism for the control of peristaltic pump’s functioning. PP:

peristaltic pump head; SV: selection valve; EC: electric contact.



rotation and guaranteeing reproducibility of the aspirated volumes, especially whendealing with reduced volumes. Thus, a magnet (Passos, Saraiva, Lima, and Korn2008) or a copper wire (Araujo et al. 1998) was positioned on the head of the peri-staltic pump; during the movement of the pump, these devices established a briefcontact with two opposed electrical contacts that were connected to the digital-inport of the interface card and the ground. This contact originated an electric signalthat was detected by the computer, which assures that in each step of the analyticalcycle, the pump always started from the same position. Thus, in the beginning ofeach step the solutions circulated in a closed circuit until the activation of a3-way solenoid valve placed between the pump and the holding coil, as schematizedin Figure 3. At the end of each cycle, the solenoid valve changed its position, block-ing the flow through the holding coil and the pump stops when the magnet and theelectric device were in contact again.

Some of the aforementioned works explored multicommutation to solvespecific issues related with the determinations. By implementation of the multicom-mutation concept in SIA systems, it was possible to introduce samples in the mLrange, to perform preconcentration of specific analytes, overcoming the impossibilityof performing such aspiration in a conventional SIA system (Araujo et al. 1999;Costa and Araujo 2001a,b Costa et al. 2002). The preconcentration device wasplaced into the detector channel, which allowed loading and elution steps to occurby propulsion of the solutions through the column. Two solenoid valves wereconnected by a confluence and one of them was linked to the detector. The analytewas eluted by propulsion of the eluent through the referred confluence point; bychanging the position of the solenoid valve, the eluate was sent to detection.

The binary sampling strategy was implemented in a SIA methodologydeveloped by the same group for the determination of chloride and iodide by titration(Araujo et al. 2004). The titration cycle was performed by intercalation of aliquots ofsample and volumetric solutions by means of a solenoid valve positioned in one of theinlets of the selection valve. The mutually dispersed zones were sent to a detectorenabling the titration to be carried out. This methodology overcame the limitationsof the conventional method for the determination of chloride and iodide that couldnot discriminate between more than one halogen species.

Our research group also implemented the binary sampling strategy in SIAmeth-odologies with the objective of overcoming the problems associated with the mixtureof sequentially aspirated zones in SIA systems (Pena et al. 2004; Passos et al. 2005;Pinto et al. 2006). A tandem stream of sample and triton X-100 was generated bymeans of a solenoid valve placed in one of the inlets of the selection valve in a SIAsystem for the determination of cationic surfactants (Passos et al. 2005). With thisit was possible to solubilize water insoluble complexes formed for high concentrationsof cationic surfactants. This same approach was also followed for on-line reagentpreparation to overcome a problem of instability of a derivatization reagent (Pinto,Saraiva, Santos et al. 2005). The very small volume of the inserted reagents segments,through the selection valve into the holding coil, facilitated mixing, and the formationof a homogenized reagents zone.

The same strategy was adopted in a series of works involving on-linepreparation of analyte standard solutions from a concentrated solution (Fernandeset al. 2001; Pimenta, Araujo, and Montenegro 2002; Pimenta et al. 2004; Santos,



Montenegro et al. 2004; Perez-Olmos et al. 2008). As before, the incorporation of themulticommutation strategy enabled the on-line mixing of concentrated solution andwater or other dilution solution. This strategy further increased the automationpotential of the developed systems.

In a slightly different approach, in a SIA system proposed by Pena et al. (2004),a tandem stream of chromogenic reagent and treated sample was generated by theinsertion of reagent in a confluence point due to the impossibility of performing flowreversal of the treated sample through the enzymatic columns. This strategy guaran-teed a good mixture of the different zones and a reduced dispersion of the reactionproduct.

In 1995 Shu, Hakanson, and Mattiasson (1995) developed a procedure basedon a flow network in which the multicommutation concept was explored for themanagement of flow between the selection valve, enzyme and blank reactors, andspectrophotometric detector (Fig. 4).

The advantages related with the incorporation of the multicommutation strat-egy in SIA systems are very well illustrated in a system proposed by Luo andco-workers for the determination of gaseous ammonia in air samples using a glassdiffusion denuder (Luo et al. 1995). Two solenoid valves allowed precise controlof the sampling procedure through a gas permeation tube, redirection of samplesto the detector, and system cleaning at the end of each analytical cycle. The peculiarmode of operation of the selection valve allowed the utilization of small volumes ofreagent so that the color development was limited to a small zone, which resulted inhigher sensitivity.

Figure 4. SIA system exploring the multicommutation concept for solution management (Shu et al. 1995).

SV: selection valve; SP: syringe pump; SoV1, SoV2, SoV3: solenoid valve; ER: enzyme reactor; BR: blank

reactor; D: detector; W: waste.



Hedenfalk and Mattiasson (1996) developed a SIA methodology integrating asolenoid valve, in the holding coil, that functioned as an interface between the selec-tion valve and the enzymatic reactor. The methodology was applied to the determi-nation of ethanol in fermentation broths and proved to be robust and easy tooperate, leading to a reduction in the consumption of the expensive co-factor.

A SIA flow assembly exploiting the multicommutation concept was developedfor the implementation of an on-line digestion procedure based on microwaves(Neira et al. 2000). In order to increase the number of solutions to be used, a networkof solenoid valves was used for the selection of sample and reagents. The multicom-mutation approach allowed not only control of the conditions of the digestion pro-cedure in the oven but also allowed the handling of the gases resulting from theentire process.

In the nineties, several works resorting to the hyphenization of SIA with multi-commutation made use of a set of two-position valves to control the loading and wash-ing of separation columns as well as the elution of the retained elements to the detector(Grate et al. 1996; Egorov et al. 1998; Grate and Egorov 1998; Egorov, Fiskum 1999;Grate, Egorov, and Fiskum 1999; Grate, Fadeff, and Egorov 1999). In a similarscheme, the same research group found the analytical potential of manifolds involvingthe hyphenization of SIA with the multicommutation concept through the develop-ment of a renewable separation column apparatus based on two two-position valves(Fig. 5) (Egorov, O’Hara 1999). These were connected by the column body and oneof them was connected to two ports of the selection valve to collect sample, reagent,and sorbent slurries for the separation step. A frit disk was placed in one of the portsof the second valve to retain sorbent beads within the column. Sample and reagentsplaced in the selection valve were then introduced in the column and the analytes wereseparated and sent to the detector. By changing the valve position the sorbent beadswere expelled from the system.

Bruckner-Lea et al. (2002) utilized the same concept in a SIA system developedwith the aim of performing studies of DNA hybridization. In this case, the valve wasconnected to the selection valve through a coil and to a renewable column beingresponsible for the introduction of oligonucleotides solution in the system.

Figure 5. Schematic representation of the SIA system with a renewable separation column based on two

two-position valves (Egorov et al. 1999). SV: selection valve; SP: syringe pump; TPV1, TPV2: two-position

valve; FR: frit restriction; SCB: separation column body; D: detector; W: waste.



The monitorization of bioprocesses was tested by means of a SIA system inwhich the multicommutation strategy allowed the effective management of the solu-tions through the reactor (Shu and Ling 2000). A solenoid valve, positioned in one ofthe inlets of the selection valve, worked in synchronization with a peristaltic pumpenabling the insertion of peroxidase substrate in the reactor pathway mixing it withthe other solutions that were aspirated from the selection valve.

A binary sampling strategy was implemented in a SIA system by Pasekova et al.(2001) with the aim of performing the alternated insertion of small slugs of buffersolution and sample. This approach allowed the on-line pH adjustment of thereaction zone, before its propulsion to the detector, which was mandatory for asuccessful application of the methodology to the determination of acetylsalicylicacid. The analytical efficiency of a SIA system for the determination of copper inseawater with sample pre-treatment was greatly enhanced by the incorporation ofthe multicommutation strategy (Yu, Du, and Wang 2007). A solenoid valve wasplaced in one of the inlets of the selection valve and was responsible for the additionof the complexing reagent to the sample just before the PTFE-beads-packed micro-column, where the complexed analyte was retained. With this configuration, it waspossible to perform a prewashing procedure to eliminate sample matrix, whichallowed the determination of ultra-trace copper in high-salinity seawater withoutdilution. A similar scheme was followed by Lee et al. (2005) that positioned a solen-oid valve in one of the selection valve inlets and connected it to an on-line filtrationunit coupled to a bioreactor. By means of an additional pump, a sample was aspi-rated, through the solenoid valve, from the bioreactor, in order to fill the tubingbefore sample insertion by the selection valve.

Lopes et al. (2007) conceived a fully automated procedure combining the specialfeatures of SIA with the automation potential of multicommutation. The method-ology comprised an on-line sample clean-up=preconcentration step, and the systemembraced two solenoid valves: one managed the propulsion of water and eluent fromthe peristaltic pump allowing a precise control of the conditions for the loading andelution of the column; the other valve was linked to the detector allowing the continu-ous aspiration of water to the nebulizer by means of a second peristaltic pump.

The combination of a selection valve, a solvent distributor, and six 3-wayvalves resulted in an automatic separation and preconcentration procedure of radio-nuclides in which the separation time was shortened (Kim et al. 2008). The solenoidvalves were connected to the solvent distributor and were responsible for the man-agement of the solutions coming into and out of the separation columns. The selec-tion valve held the elution reagents and was linked to the solvent distributor thatdiverted the solution to the correct column. By increasing the number of columnsand tubing lines, the system could process several samples simultaneously.

An interesting approach to increase the robustness of a SIA system applied inthe determination of sorbitol in Pichia pastoris cultivation was designed byHorstkotte, Arnau et al. (2008). In this system, a solenoid valve was placed betweenthe propelling device and the holding coil for the aspiration of acetonitrile to rinsethe holding coil and to expulse stacked air bubbles.

The accuracy of a SIA methodology for the determination of both hypox-anthine and potassium in vitreous humor samples was greatly enhanced by theutilization of a solenoid valve that permitted interference elimination and enabled



the analysis of samples without drastic batch pretreatments (Passos et al. 2009). Thedetermination of hypoxanthine was based on its oxidation to uric acid catalyzed byimmobilized xanthine oxidase. The system also comprised a reactor with activatedglass beads that was used to perform a sample blank. The referred solenoid valve,connected to both reactors, was used to direct the samples to the enzyme reactoror to the glass beads reactor in the case of the sample blank estimation.

Ogata et al. (2002, 2004) proposed two miniaturized SIA methodologies inwhich a solenoid valve allowed an effective management of the passage of the samplethrough the column and of the elution of the retained elements to the detector. Thedescribed systems showed excellent performances due to their versatility and reducedanalysis time.

Hyphenization with Multisyringe Flow Analysis (MSFIA)

The MSFIA was introduced in 1999 as a robust multichannel manifold forperforming process flow analysis. The authors initially proposed this strategy asan alternative to multicommutation whose typical functioning under negative press-ure sometimes constitutes a major difficulty (Albertus et al. 1999). In this technique,a computer controlled multisyringe piston pump is employed as a multichanneldevice guaranteeing volume delivery within a very wide range of flow rates, readilystopped, or changed by software instruction. The authors considered that the mostimportant features of MSFIA are its increased flexibility and the significantreduction in reagent consumption. However, the peculiar mode of operation ofthe technique demands that the forward movement of the solutions in the manifoldshas to be stopped periodically to refill the syringes. This particularity introducessome delay in the analytical cycles resulting in lower analytical frequency.

The association of multisyringe modules to SIA has grown in the last yearsconfirming the potential of this strategy. Generally, the hyphenization of these twotechniques increases the versatility and flexibility of the resulting flow systems sinceit allows sample insertion on a time basis and so the analysis conditions can be chan-ged without systems reconfiguration. At the same time, the carryover risk associatedwith the utilization of the syringes for sample introduction is reduced (Segundo andMagalhaes 2006).

A selection valve was attached to a multisyringe module in a chemilumi-nescence methodology for the detection of glucose. The valve was responsible forsample management and supported also a glucose oxidase reactor that was connec-ted to the main flow line by confluence (Manera et al. 2004).

A selection valve and a supplementary syringe pump were associated with amultisyringe module in a flow assembly developed for on-line monitoring of ortho-phosphates in soils and sediments (Buanuam et al. 2007). The selection valve was usedto select the appropriate extractant and accommodated several reagents and a soilmicrocolumn, being connected to the multisyringe by means of a solenoid valve.

A MSFIA system for the evaluation of hypochlorite in commercial productswith on-line dilution incorporated a selection valve for the management of sampleand standards (Soto et al. 2008). The selection valve accommodated a miniaturedilution chamber and was connected to a cobalt catalytic column where the analytewas decomposed to chloride and oxygen. The analytical signal was established from



the difference in absorbance at 290 nm registered when the sample passed throughthe column or was sent directly to the detector.

In 2008, Horstkotte and co-workers coupled MSFIA to selection, injection andsolenoid valves for the development of a methodology for the determination of nitro-phenols by capillary electrophoresis (CE) that constitutes an excellent practicalexample of the benefits of flow techniques hyphenization (Fig. 6). The resulting sys-tem allowed the advantageous automation of the total analytic procedure includingon-line sample modification, preconcentration and maintenance of the apparatus. Inthis system, an injection valve functioned as support of a solid phase extractioncolumn and was connected to one of the inlets of the selection valve and to theCE system. The selection valve was responsible for the introduction of sample inthe extraction column and accommodated also the reagents for column cleaningand elution. Auxiliary solenoid valves were used for pickup sample, redirect solu-tions to the SPE column, introduce air to reduce sample dispersion, and close theoutlet of one of the implemented capillary flow interfaces for pressure build-uptemporarily at the capillary inlet.

Maya, Estela, and Cerda (2008) developed a MSFIA methodology in which aselection valve was linked to one of the syringes and was responsible for the handlingof sample, eluent, and rinsing solution. The other syringes operated in the forwardflow mode avoiding the mixing problems typically associated with the sequentialaspiration of solutions in reverse mode in the SIA technique. Thus, the reagentsfor oxidation and subsequent spectrophotometric determination of the analytes were

Figure 6. Scheme of the MSFIA-SIA hyphenated system for the determination of nitrophenols

(Horstkotte, Arnau et al. 2008). SV: selection valve; IV: Injection valve; SoV1, SoV2, SoV3: solenoid

valve; MS: multisyringe module; EL1, EL2: eluent; D: detector; W: waste; AC: acidifier; SB: seperation

buffer.



inserted, by means of confluences, in the detector channel (that was positioned in oneof the inlets of the selection valve) before or after the photo-chemical reactor.

Very recently Mirabo, Forteza, and Cerda (2009) developed a multisyringesequential injection method for monitoring water quality. The SIA configurationminimized reagent consumption and the association with MSFIA maximized flexi-bility and robustness. The flow assembly comprised two 10-port selection valves thataccommodated the reagents needed for the evaluation of eight important physico-chemical parameters in water (pH, specific and acid conductivity, hydrazine,ammonium, phosphate, silicate, and total iron) with high degree of automation inreduced time. The valves also supported an auto sampler, a spectrophotometricdetector, a temperature probe, a cationic column, a pH meter, and a conductimeter.Two solenoid valves were responsible for the connection of the valves to the syringesof the multisyringe module.

In the last years, a few works involving the incorporation of multisyringepumps in miniaturized SIA systems have been published (Long et al. 2006;Quintana et al. 2006; Quintana et al. 2009). The objectives of this association aresimilar to the ones described for conventional SIA systems and are related withthe insertion of the sample in the flow networks and management of solutionswithin the system. The referred systems involved a pre-concentration or solid phaseseparation step by bead injection in which the beads are enclosed on a syringe inone of the inlets of the selection valve and other inlet served as microcolumn.One of the works was proposed by Long and co-workers in 2006 and was basedon a multisyringe system with atomic fluorescence spectrometry detection foron-line bead injection pre–concentration. The methodology besides the MSFIAand SIA approaches embraced also the multicommutation concept that allowedthe management of the passage of the solution through the microcolumn. The otherworks in the same line of research were developed by Quintana and co-workers andconsisted of two methodologies also based on pre–concentration by bead injectionprior to chromatographic separation (Quintana et al. 2006; Quintana et al. 2009).These systems also comprised an injection valve for quantitative injection of ametered eluate zone and one of them included also a solenoid valve to facilitaterinsing of the transfer line placed between the injection valve and chromatographicsystem (Quintana et al. 2009). The chromatographic systems in both cases are syn-chronized with the bead injection procedure allowing a sample to be analyzed whilethe ensuing one is being processed in the flow system. Due to their peculiar charac-teristics, the described systems showed to be extremely versatile and robustand opened new and interesting perspectives on the association of automated beadinjection separation with gas and liquid chromatography.

Hyphenization with Multi-Pumping

The multipumping concept, proposed in 2002, revolutionized the concept offlow analysis since, in contrast to the typical flow systems, it is characterized by apulsed flow that ensures a fast sample=reagent mixing which contributes to improv-ing the reaction sensitivity even in situations of limited dispersion. (Lapa et al. 2002).This technique is based on the utilization of solenoid micropumps which are the onlyactive devices acting simultaneously as liquid propelling units, sample insertion



ports, and commuting elements. Thus, the configuration and control of the flowsystem are greatly simplified.

The implementation of the pulsed flow approach in manifolds involving otherflow strategies can result in systems with increased versatility in which the automationof chemical reactions can be performed with advantages in terms of mixture and,consequently, of sensitivity. Furthermore, the utilization of solenoid micropumpscan result in many possibilities in terms of sample insertion including variable samplevolume, binary sampling, and merging zones, which could be exploited to manipulatereagents addition, sample zone homogenization, and reaction development.

Regarding the association of the pulsed flow and SIA concepts there are twoapproaches in which two solenoid micropumps were used as propelling devices(Pinto et al. 2005; Takayanagi et al. 2009). This configuration was revealed to bean interesting tool to solve the mixing problems associated with the sequentialaspiration of solutions in SIA, since the pulsed flow creates a chaotic movementof the solutions promoting a better mixture. Moreover, the use of solenoid micro-pumps as propelling devices helped to avoid some shortcomings related with theutilization of peristaltic and syringe pumps, such as periodic replacement of the tub-ing and interruption of the analytical cycle for filling or emptying the syringe,respectively. Pinto and co-workers developed a SIA system in which the utilizationof two solenoid micropumps for propelling and aspirating solutions originated apulsed flow that enhanced sample=reagent mixing (Pinto et al. 2005). This aspectwas favorable for the implementation of an automated methodology for the fluori-metric determination of indomethacin in pharmaceutical preparations upon alkalinehydrolysis in micellar medium as it enhanced the intermixing of the used viscoussolutions. The proposed flow system exhibited operational characteristics similarto those of a conventional SIA, and the obtained pulsed flow revealed both onthe zone penetration studies and in the analysis of pharmaceutical preparations,an enhanced solutions intermixing aptitude that resulted in a significant incrementin reaction zone homogenization, particularly in the case of low stroke volumemicropumps.

The hyphenization of multipumping with SIA in a methodology for the evalu-ation of metals as catalysts in the reaction between luminol and hydrogen peroxide,confirmed the possibility of associating profitably of the pulsed flow technique withthe chemiluminescence detection with a stable baseline (Takayanagi et al. 2009).

CONCLUSIONS AND FUTURE TRENDS

The large utilization of SIA for the implementation of analytical proceduresover the last decades has confirmed this technique as a versatile and robust analyticalapproach. The potentialities of SIA are very well exemplified in the works discussedin this review. The association of SIA with devices or approaches typical from otherflow techniques has led to the development of versatile flow methodologies for thedetermination of a large variety of analytes in distinct analytical fields.

Taking in consideration the strategies and devices of each flow technique, thepossible instrumental configurations and operation modes are immense and can beadapted to the needs of specific determinations resulting in hyphenated techniquesthat permit the automation of complex procedures. Indeed, as can be confirmed



in the different sections of this review, the hyphenization of SIA with other flow tech-niques has allowed the automation of sample pre–treatment procedures such asgas-diffusion, pre–concentration and dialysis among others, reducing the analysistime and the errors associated with extensive operator intervention.

Furthermore, the hyphenization of SIA with flow injection and multicommuta-tion approaches enables the coupling of flow networks to particular detection tech-niques such as ETAAS, ICP-MS, and HPLC. In these cases, injection and solenoidvalves functioned as an interface between the detection and the SIA system that wasresponsible for sample treatment and preparation of the detector for the measure-ment step. With this, the advantageous features of the systems could be exploredand the possible applications became uncountable.

A careful analysis of the literature reveals that the hyphenization of SIA withMSFIA is almost mandatory for the development of robust and versatile manifoldswith improved analytical aptitude, constituting an import tool for the developmentof new MSFIA methodologies.

Even though some researchers have already explored the potential of miniatur-ized SIA hyphenated techniques, the investigation in this field is very promising. Indetail, the association of these miniaturized systems with solenoid micropumps canconstitute an interesting work basis.

It is our belief that in the near future, the fundamentalisms related with flowtechniques and their denomination will naturally be absorbed by the need to solveconcrete and complex analytical situations and by the high demands in the field ofautomation of procedures. This will result in a rational development of flow mani-folds, involving the incorporation of specific approaches and devices according tothe determination specifications, in a scheme that is independent from the research-er’s specialization or preferences.

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