Microdialysis and microchip system

While the vast majority of microdialysis sampling to date has been achieved in conjunction with conventional systems, microdialysis has also been coupled online with biosensors and, more recently, to microchip-based separation devices. These devices can be fabricated using low cost materials and are amenable to mass production [11]. The smaller dimensions of microchip systems minimize sample and reagent volume requirements and allow placement of the analysis system closer to the aqueous sample or animal being sampled. Due to the planar nature of microchip devices, additional sample handling procedures such as preconcentration, mixing, extraction, or derivatization can also be carried out on the same platform [12-15]. Considerations for coupling microdialysis to microchip instrumentation systems will be discussed in Section 48.5. 

If a single analyte is to be detected, a simple flow-through microdialysis/microchip system may suffice. If multianalyte determination is needed, a separation-based microchip device can allow resolution and detection of several analytes in a single sample (Section 48.5.4). In flow-through devices, the perfusate is directed to an array of sensors, which may be also be modified to allow detection of different analytes and improve detection sensitivity. 

There have only been a few reports of coupling microdialysis to microchip-based separation systems. Ideally, the microchip system should allow the injection of discrete sample plugs from a continuously flowing stream of dialysate without disturbing the separation element of the analysis. This allows maximal temporal resolution and limits the effect of perfusion flow rate on system performance. 

Integration of a dialysis membrane or coupling to a microdialysis probe can help to exclude many of the larger molecules such as proteins that are typically responsible for fouling the sensor elements of microchip analysis systems. The nature of the analysis will dictate whether coupling to a flowthrough or separation-based sensor must be achieved and the kind of detection elements to be employed (optical, electrochemical, etc.). One of the issues with microchip devices is the very small... 

Impedance electrodes have also been investigated as detectors for microchip microdialysis applications. An on-chip microdialysis system with inline sensing electrodes for impedance detection was developed [41], Cr/Au electrodes were used to determine the electrical resistance of changes in the concentration of phosphate-buffered saline (PBS) solutions that were used to characterize the system. The system monitored concentration changes with a 210-s system response delay. The lag time was attributed to dead volume in the tubing between the syringe pumps and the microsystem. 

FIGURE 48.5 Layout and schematic of microdialysis/microchip CE system. (Reproduced from Huynh, B. H., et al., Anal. Chem., 76, 6440, 2004. With permission.)... 

In the future, capillary electrophoresis with electrochemical detection will continue to be important for the analysis of small volume samples. The direct coupling of microdialysis with CEEC yields a separation-based sensor that is capable of near real-time monitoring of drugs and neurotransmitters. New on-line systems for the detection of catecholamines and peptides are currently under development. Electrochemical detection is very amenable to miniaturization and, therefore, is uniquely compatible with the microchip format. In the future, the integration of microchip CEEC with microdialysis sampling will lead to truly portable separation-based sensors. 

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