Flow biosensor applications

Liidi H, Gam M B, Bataillard P and Widmer H M 1990 Flow injection analysis and biosensors applications for biotechnology and environmental control J. Biotechnol. 14 71-9... 

Schaffar, B. P. H., B. A. A. Dremel, and R. D. Schmid. 1989. Ascorbic acid determination in fruit juices based on a fiber optic ascorbic acid biosensor and flow injection analysis. In Biosensors Applications in Medicine, Environmental Protection and Process Control, eds. R. D. Schmid, and F. Scheller, pp. 229-232. New York VCH Publishers. 

Liidi, H., M. B. Garn, P. Bataillard, and H. M. Widmer. 1990. Flow injection analysis and biosensors Applications for biotechnology and environmental control. /. Biotechnol. 14 71-79. 

Environmental Applications Although ion-selective electrodes find use in environmental analysis, their application is not as widespread as in clinical analysis. Standard methods have been developed for the analysis of CN , F , NH3, and in water and wastewater. Except for F , however, other analytical methods are considered superior. By incorporating the ion-selective electrode into a flow cell, the continuous monitoring of wastewater streams and other flow systems is possible. Such applications are limited, however, by the electrode s response to the analyte s activity, rather than its concentration. Considerable interest has been shown in the development of biosensors for the field screening and monitoring of environmental samples for a number of priority pollutants. 

On the other hand, if the hole flow in DNA could be artificially controlled to deposit at the desired site in DNA, it may enable site-selective oxidation and strand scission of DNA, which is desirable from a therapeutical standpoint. Furthermore, understanding DNA-mediated hole transfer is expected to lead to an additional application in the development of biosensors and bioelectronic devices [9]. Therefore, the regulation of the transfer rate and direction of the hole generated in DNA is of interest from the perspective of using DNA as a building block for electronic devices. 

A new cholesterol flow injection analysis biosensor has also been described as an application of the H2O2 ECL sensor56. In that work, the luminol electrochemiluminescence, previously studied in aqueous media, was implemented in Veronal buffer added of 0.3% triton X-100 (v/v), 0.3% PEG and 0.4% cholate to enable the solubilisation of the cholesterol and then its efficient oxidation catalyzed by the immobilized cholesterol oxidase. The ECL reaction occurred thus in a micellar medium and the performances of the H2O2 ECL sensor were investigated. 

In a second experiment, Cy5-labelled antiBSA antibodies were immobilised on a silanised glass slide precoated with metallic nanoislands using a polydimethylsiloxane (PDMS) flow-cell. The antibody solution was left for 1 hour to attach and then the cell was flushed with deionised water. The slide was then dried with N2. For this experiment, a portion of the slide was not coated with metallic nanoislands, in order to act as a reference. Figure 20 shows the image recorded using the fluorescence laser scanner mentioned previously. The enhancement in fluorescence emission between those areas with and without nanoislands (B and A, respectively) is again evident. For both chips, an enhancement factor of approximately 8 was recorded. There is considerable interest in the elucidation and exploitation of plasmonic effects for fluorescence-based biosensors and other applications. 

Immunosensors have been developed commercially mostly for medical purposes but would appear to have considerable potential for food analysis. The Pharmacia company has developed an optical biosensor, which is a fully automated continuous-flow system which exploits the phenomenon of surface plasmon resonance (SPR) to detect and measure biomolecular interactions. The technique has been validated for determination of folic acid and biotin in fortified foods (Indyk, 2000 Bostrom and Lindeberg, 2000), and more recently for vitamin Bi2. This type of technique has great potential for application to a wide range of food additives but its advance will be linked to the availability of specific antibodies or other receptors for the various additives. It should be possible to analyse a whole range of additives by multi-channel continuous flow systems with further miniaturisation. 

A wide variety of parameters can directly affect the chemical and physical characteristics of a plasma, which in turn affect the surface chemistry obtained by the plasma modification. Some of the more important parameters include electrode geometry, gas type, radio frequency (0-10 ° Hz), pressure, gas flow rate, power, substrate temperature, and treatment time. The materials and plasmas used for specific biomedical applications are beyond the scope of this text, but the applications include surface modification for cardiovascular, ophthalmological, orthopedic, pharmaceutical, tissue culturing, biosensor, bioseparation, and dental applications. 

Conventional calorimetric biosensors with thermistors as the transducer were invented early by proposing a thermal biosensor in a flow stream [10]. So far the design of enzyme thermistors does not entirely match the market demand well, but it seems well suited for special applications [10,11]. A number of devices have utilized discrete pairs of thermistors for differential measurements with immobilized enzymes or with separate enzyme columns [9,10,11],... 

For several reasons, most applications of chemo- and biosensors require flow through devices, for example in allowing analysis of samples from multiple sources, removing flow sensitivities, avoiding sterilization and biocompatibility problems, enabling recalibration or performing bioanalytical assays. 

Figure 9 Illustration of the combined SPR-based BIA/MS approach (139). Deriva-tized biosensor chips, having multiple (2-4) flow cells each, are used in the real-time SPR-BIA analysis of interactions between surface-bound receptors and solution-phase ligands. The sensor chips are removed from the biosensor after SPR-BIA, with ligands still retained within the flow cells, and prepared for MALDI-TOF by application of an appropriate matrix to the flow cells. The matrix solution disrupts the receptor-ligand interaction, liberating the ligand into solution for incorporation into the matrix crystals. With proper application of the matrix, the crystals settle onto the original location of the interaction and spatial resolution between flow cells is preserved. The flow cells are targeted individually during MALDI-TOF and the retained ligand(s) are detected at precise and characteristic m/z values.

The utilization of a DNA matrix to aid enzyme immobilization is a promising alternative for the development of new biosensors and its application in flow systems. A DNA-tyrosinase carbon paste electrode [95] showed excellent performance for detection of cathecol in a FIA system and suggests that other enzymatic biosensors can benefit from the presence of DNA. 

Even before the introduction of miniaturized biosensor arrays, however, some systems able to simultaneously measure glucose and lactate had been reported in the literature. One example is provided by Osborne et al. [157], who described plastic film carbon electrodes fabricated in a split-disk configuration and then modified to obtain a dual biosensor. They achieved a continuous monitoring of these metabolites by placing the dual electrode in a thin-layer radial flow cell coupled to a microdialysis probe. The stability of the sensors was sufficient for short-term in vivo experiments in which the crosstalk, i.e., the percentage of current measured by one biosensor but due to product generated by the partner biosensor, was acceptable for an in vivo application. 

The system showed short equilibration and response times, and was free of cross-talk, one of the major problems encountered when multiple ampero-metric biosensors are placed in an array within the same flow cell. Until now, the device has been shown to perform excellently in vitro, but several issues (such as the biocompatibility and the possibility of sterilization of the materials used) must be addressed before in vivo application. 

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