Chip sample introduction

In CE, the principle detection schemes are spectrometric and electrochemical. Fluorescence is easy to implement (especially off-chip), is extremely sensitive, which is useful since the sample volumes are typically very small, and is well understood. However, some compounds may need to be fluorescently labelled . This can be done prior to, during or after separation. Renzi et al. from Sandia National Laboratories have reported a handheld microanalytical instrument for CE analysis of proteins using laser-induced fluorescence detection ". The fused silica chip is 2 X 2 cm and features on-chip sample introduction, inlet port filters and a 10 cm separation column. Nanomolar concentrations of fluores-camine-labelled proteins were detected. 

Reproducible sample introduction is a crucial factor in p-chip-based electrophoretic separations. Various p-chip sample introduction schemes are illustrated in Fig. 2. Of the many proposed injection methods, electrokinetic injection based on electro-osmotic flow (EOF) is most commonly encountered on chips, because electrically driven fluid flow is easier to generate and control than pressure-driven flow. Electrokinetic sample injection is generally... 

Fang, Q., Wang, F.-R., Wang, S.-L., Liu, S.-S., Xu, S.-K., and Fang, Z.-L., Sequential injection sample introduction microfluidic-chip based capillary electrophoresis system, Anal. Chim. Acta, 390, 27, 1999. 

In most cases, sample introduction on-chip is achieved using electrokinetic (EK) flow [3]. Two important EK injection modes, namely, pinched injection and gated injection, have been developed. Furthermore, some alternative injection methods are described. 

A wide sample exchange channel (1 mm wide, 200 pm deep) was interfaced to the shallow EK sample introduction channels (36 pm wide, 10 pm deep) in a glass chip. This allowed fast sample loading and replacement into a CE chip. This automated procedure was achieved by HDF, without disturbing the liquids within the shallower and narrower sample introduction channels [117]. 

In another report, an on-chip chamber containing a capture matrix was used for sample cleanup. A 2- dL unpurified sample is concentrated into a smaller volume ( 10 nL), and this yields a volumetric concentration factor of 200. Longer residence time can be achieved by using a doubly tapered chamber. Here, the electric field is 10-fold lower within the chamber than within the tapered channel. So, a high-field (fast) sample introduction is followed by a low-field (slow) sample flow past the capture matrix, increasing the residence time so that the binding kinetics are dominant over electromigration [971]. 

In one report, bidirectional FTP was achieved on a PMMA chip. A common terminating electrolyte (TE) was employed to achieve simultaneous cationic and anionic separations. Without a complex injector design, sample introduction was achieved hydrodynamically for FTP separation [638]. 

Fang, Q., Xu, G.-M., Fang, Z.-L., High throughput continuous sample introduction interfacing for microfluidic chip-based capillary electrophoresis systems. Micro Total Analysis Systems, Proceedings 5th XTAS Symposium, Monterey, CA, Oct. 21-25, 2001, 373-374. 

A microchip device with an attached nano-ESl emitter tip was developed to facilitate the introduction of tiyptic digests by means of nano-ESl [88-89]. Instead of off-line filling of the nano-ESl needle, the sample is transferred from a vial on the chip to the nano-ESl needle by electroosmosis. Detection limits of 2 fmol/pl were achieved for fibrinopeptide A (1699 Da). Further developments enabled sequential automated analysis of protein digests by ESl-MS [90]. On-chip sample pretreatment and desalting by either sample stacking via polarity switching or SPE prior to on-chip CE was described by Li et al. [91], and applied to the identification of 2D-GE separated proteins from Haemophilus influenzae using a Q-TOF instrument. 

Samples for trace metal analysis by A AS or ICP-OES must be presented to these instruments in liquid form. However, in some cases, samples are submitted as powders or solids (chippings, residues, etc.) requiring chemical decomposition prior to metal analysis that can lead to systematic errors in accuracy and precision of measurements. There have been many attempts to introduce samples as a slurry suspension and these were found to be successful for a limited number of samples provided that the particle sizes are suitably small. In most cases the nebulisation of the majority of samples analysed this way has shown that very low sample-introduction efficiency caused by variable particle sizes is in some cases difficult to dissociate, owing to the short residence times in the plasma. The availability of standards for this type of analysis is non-existent or difficult to obtain. 

With the on-line approach, the sample is continuously delivered to the vacuum in real time. Off-line sample introduction entails the running of microfluidic processes on the chip with later MS analysis. Therefore, the introduction of samples into the ion source generally requires breaking the ion source vacuum. 

IJ.-TAS) [4, 9,10], which strive to develop true lab on a chip , or fully integrated analytical systems involving sample introduction, preparation, analysis (may or may not include a separation) and result reporting on a single substrate. This field is still in its infancy, but has attracted many hundreds of researchers and now is the main topic of numerous international conferences and journals. Taken as a whole, development of chip-based separation capabilities helped establish the field of microfluidics, a branch of fluid mechanics devoted to fluid behavior in sub-millimeter diameter channels interconnected in simple and complex ways. Channels in this size range are commonly referred to as microchannels, whose cross sections are continually shrinking. A current hot research area deals with fluid behavior in nanochannels. 

Huang, X.)., Pu, Q. S., Fang, Z. L., Capillary electrophoresis system with flow injection sample introduction and chemiluminescence detection on a chip platform. The Analyst 2001,126(3), 281-284. 

High throughput continuous sample introduction interfacing for microfluidic chip-based capillary electrophoresis systems. Micro Total Analysis Systems... 

The term microfluidic sample jnanipulation refers to the processes involved in controlling the movement of small volumes of fluid or particles around a network of interconnected microcharmels. These processes include sample introduction, injection, mixing, reaction, dispensing, separation, and detection and are typically performed in a fully integrated micro total analysis system or a Lab-on-a-Chip device. 

Techniques for transferring samples to microfluidic chips are of crucial importance because they open the microchip to the macroworld. Sample introduction is the beginning of the process of microfluidic analysis on chips. Various techniques for transferring samples in the form of liquid, gas, or aerosol to an on-chip liquid environment have been reported for biochemical and environmental analysis. 

Chen et al. [7] have developed a CE system based on a PMMA electrophoretic microchip with an easy sample introduction interface. One side of the PMMA chip was sharpened to fabricate a sharp inlet tip, allowing rapid and reproducible sample introduction into CE microchip devices coupled to contactless conductivity detection. The new microfluidic interface relies... 

Techniques for transferring samples to microchips play a key role in the microchip-based system. Future directions for sample introduction will focus on the automation of the sample transfer to the microchips, the development of the world-to-chip interface for real-life applications, the integration of the sample pretreatment unit and sample introduction interfaces, the direct introduction of gaseous samples, and various designs for sample introduction. With the rapid development of microfluidic chips, it is highly desirable to develop new theoretical models, experimental methods, and new experimental devices for transferring samples to chips. 

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