Flow injection analysis micro-systems

The focusing bi-laminating micro mixer was realized in the framework of the development of a flow injection analysis (FIA) system [114,115]. The mixer is placed downstream of the two-fold injection of sample and reagent streams into the carrier. Thereafter, the mixed stream enters a reaction chamber and finally passes a detector. An easy integration is required, as the mixing element is part of an integrated system which has the minimization of size as one issue. 

Micro flow control devices open new possibilities for the miniaturization of conventional chemical and biochemical analysis systems. The micro total analysis system (pTAS) including microfabricated detectors (e.g. silicon based chemical sensors, optical sensors), micro flow control devices and control/detec-tion circuits is a practical micro electro mechanical system (MEMS). pTAS realize very small necessary sample volume, fast response and the reduction of reagents which is very useful in chemical and medical analysis. Two approaches of monolithic and hybrid integration of these devices have been studied. Monolithic and hybrid types of flow injection analysis (FIA) systems were already demonstrated [4, 5]. The combination of the partly integrated components and discrete components is useful in many cases [6]. To fabricate such systems, bonding and assembling methods play very important roles [7]. 

Cheng, S.B., Skinner, C.D., Harrison, D.J., Integrated serial dilution on a microchip for immunoassay sample treatment and flow injection analysis. Micro Total Analysis Systems 98, Proceedings pTAS 98 Workshop, Banff, Canada, 13-16 Oct. 1998, 157-160. 

FIGURE 1.3 Schematic manifolds of typical flow injection analysis (FIA) systems (a) single line manifold, (b) multiline configuration RCl, RC2—reaction coils. (Adapted from Ruzicka, J., 2009, Tutorial on Flow Injection Analysis (4th ed.). From Beaker to Micro fluidics, www.flowinjection.com.)... 

Some coupled systems allow measurement of the main N and P forms (nitrate, ammonia and orthophosphates) [22,27,29], among which is a system based on membrane technology in combination with semi-micro continuous-flow analysis (pCFA) with classical colorimetry. With the same principle (classical colorimetry), another system [30] proposes the measurement of phosphate, iron and sulphate by flow-injection analysis (FIA). These systems are derived from laboratory procedures, as in a recent work [31] where capillary electrophoresis (CE) was used for the separation of inorganic and organic ions from waters in a pulp and paper process. Chloride, thiosulphate, sulphate, oxalate,... 

These miniaturized sensors are suitable for flow-injection analysis [130]. Similar systems have also been used in portable instruments [56]. A micro-ISFET was constructed for intracellular determination of K [53]. 

M 20] [P 19] The pTAS module is made for performing colorimetric analyses as typically applied in cuvette tests, e.g. for on-site water analysis [30], A continuous test replaces copious manual pipetting of the sampling volumes. The module consists of a micro flow restrictor, a micro mixer and an optical microcuvette for colorimetric analysis. The sample is injected by a conventional FIA (flow injection analysis) system. By close connection, a dead volume of only 2.2 pi is given. 

Veenstra, T. T., Lammerink, T. S. J., van den Berg, A., Elwenspoek, M. C., Characterization method for a new diffusion mixer applicable in micro flow injection analysis systems, in Proceedings of the Micromechanics Europe (MNE)... 

Haswell, S.J., Development and operating characteristics of micro flow injection analysis systems based on electroosmotic flow. Analyst 1997, 122, 1R-10R. 

F.-Q. Nie, M. Macka, B. Pauli, Micro-flow injection analysis system on-chip sample preconcentration, injection and delivery using coupled monolithic electroosmotic pumps, Lab Chip 7 (2007) 1597. 

T. T. Veenstra, Characterization Method for a New Difiusion Mixer Applicable in Micro Flow Injection Analysis Systems. J. Micromedi. Microeng., 1999, 9, 199-202. 

A rotating enzyme-immobilized reactor and a flat pH electrode were incorporated into a sealed cell for use under continuous-flow/stopped-flow (SF) operation for the rapid determination of penicillins G and V in tablets and injectables [50]. A co-immobilization in a rotating bioreactor and amperometric detector resulted in a sensitive system for determination of succinylcholine and acetylcholine in pharmaceutical preparations [51]. A tandem system incorporating two rotating bioreactors into a continuous-flow/SF sample/reagentprocessing setup was apphed for the determination of alkaline phosphatase activity in serum samples [52]. By functional combination of the SF and flow-injection analysis (FIA), an automated micro apparatus was constructed resulting in significant reduction of the injection volumes of enzyme and substrate [53]. SF/continuous flow methods were apphed to acquire kinetic information also [54, 55]. 

Components incorporated in chemical analysis systems are rapidly being developed in micro scale. Today microstructured pumps, valves and flow channels are already available, [1]. Micro scaled flow transducers and temperature sensors as well as chemical sensors i.e. PO2, PCO2, pH, [2], have also been developed. Flow injection analysis systems commonly use enzyme reactors for the analysis of more complex components, and until recently little work has been done on the wafer integration of enzyme reactors [3,4]. 

The bead injection system was designed to operate in the sequential injection mode. It is possible to carry out bead injection analysis in a low-cost flow injection system with a unidirectional pump and without a computer, mainly for applications where samples and reagents are abundant and when there is no need for micro-volume control. To this end, it is necessary to use a flow cell able to achieve bead retention, accommodation of chemical reactions and detection [87,88]. 

We discuss in this chapter analysers that arc highly automated, such as flow injection and discrete analyzers. In addition, laboratory robotic systems that are becoming more and more commonplace for sample handling and preparation arc also described. The latest advances in automation involve the development of microlluidic systems, which are sometimes called lab-on-a-chip or micro total analysis systems. These recent developnienis are also described here. It is important to note that the same principles of automatic analysis discussed here also apply to process control systems, which analyze the current state of a process and then use feedback to alter experimental variables in such a way that the current state and the desired state are nearly identical,... 

A flow injection system with a micro-column of strong anion exchanger has been interfaced with an ICP-mass spectrometer via a microconeentrie nebulizer to perform on-line separation and trace determination of bromate in drinking waters (Elwaer, 1999 Elwaer et al, 2000). Method development studies examined the effect of sample injection volume, carrier stream flow rate and eluent concentration on system response. B asic performance data for this method were limit of detection, 0.13 ag/L (500 p-L sample injection) analysis time, 5 minutes per sample precision, 2.6%RSD (at5 g/L). 

It might seem incidental that BIA rhymes with FIA except that the prospectus and initial publication from Pharmacia [8] state that FIA is the backbone of the fluidic system, and point out how the "sample plug dispersion has been minimized through the design of an integrated microfluidic system that places sample loops and valves near the sensor chip surface" By combining macro components (pumps, optical systems) with micro fluidics, a flow injection system has been developed that allows real time kinetic analysis of biomolecules to be carried out under conditions which are well controlled in terms of... 

A novel method of valveless sample introduction in flow analysis systems called flow-diffusion analysis (FDA) is described Due to the reduction of mechanical parts, i e an injection valve is dispensable, the system becomes very simple and its transformation into the micro-scale should require less effort than the respective transfer of conventional flow-injection systems Additionally, due to the time based sampling, the method is more flexible in terms of sensitivity and linear range compared to established volume based methods... 

A new type of flow cell has been developed for detection of heavy metal ions in aqueous solutions, based on the flow injection method The cell contains two chemically modified field effect transistors (CHEMFETs) of which one is selective for the supporting electrolyte ion (in this case a 0 1 M potassium ion solution) and the other is selective for the heavy metal ion to be detected (Cd ", Pb " ) The differential signal of the reference electrode CHEMFET and the heavy metal ion CHEMFET in the flow cell system which has been presently developed will be evaluated for miniaturization and further integration in a micro total analysis system... 

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