Liquid chromatography chips

The first experimental investigation and performance demonstration of an integrated liquid chromatography chip was carried out by Ocvirk et al. [84]. The device is shown schematically in Fig. 15 and comprises a split injector, a smallbore separation column, a frit, and a detector cell, all integrated in a monolithic manner. An electron micrograph of the silicon chip is also depicted in Fig. 15. The whole device was composed of two 350 pm Si chips and a 50 pm interme-... 

Liquid Chromatography Chips. Most attempts of implementing LC separations on microfluidic devices involved the fabrication of the separation channel on the chip but made use of external pumping/valving systems to drive the fluids. Initially, the LC analysis of caffeine, with UV and amperometric detection, was demonstrated on a silicon substrate incorporating microfluidic channels of various dimensions (20-200 pm in width, 0.5-10 pm in depth, and 15-50 cm in length) coated with... 

Fig. 9. Schematic layout of the structured liquid chromatography chip (LC). Shown are (a) the layout of the channel system in silicon, (b) a cross-section along the separation channel axis, and (c) a cross-section along the detector cell axis. IS inlet for sample peak and mobile phase, S split injector, OS outlet for the rejected portion of the sample peak and mobile phase, C separation channel (column), F frit, D optical detector cell, OD outlet, P positioning grooves for optical fiber...

Cowen, S. and Craston, D. H., An on-chip miniature liquid chromatography system design, construction and characterization, in Micro Total Analysis Systems, van den Berg and Bergveld, Eds., Kluwer Academic, The Netherlands, 1995, 295. 

With the introduction of modern electronics, inexpensive computers, and new materials there is a resurgence of voltammetric techniques in various branches of science as evident in hundreds of new publications. Now, voltammetry can be performed with a nano-electrode for the detection of single molecular events [1], similar electrodes can be used to monitor the activity of neurotransmitter in a single living cell in subnanoliter volume electrochemical cell [2], measurement of fast electron transfer kinetics, trace metal analysis, etc. Voltammetric sensors are now commonplace in gas sensors (home CO sensor), biomedical sensors (blood glucose meter), and detectors for liquid chromatography. Voltammetric sensors appear to be an ideal candidate for miniaturization and mass production. This is evident in the development of lab-on-chip... 

Protein toxins such as botulism, staphylococcal enterotoxin B, or ricin can be separated with gas or liquid chromatography, electrophoresis, or a combination. The pChemLab (Sandia National Laboratories Albuquerque, NM) series of instruments includes a hand-held Bio Detector. Proteins in the sample are labeled with fluorescent tags, and nanoliter volumes of samples are separated by microchannels etched into a glass chip. The separation occurs as the sample moves through the channels and identification is based on retention times. The analyses can be completed within 10 min. 

Very low flow electrospray is called nanoelectrospray [26] where the samples are infused into the mass spectrometer at the nanoliter flow rate range. The infusion of a few microliters will result in a stable signal for more then 30 min, using pulled capillaries or chip-based emitters [27]. With infusion, signal averaging allows to improve the limit of detection in tandem mass spectrometry. Nanoelectrospray is particularly important in combination with nanoflow liquid chromatography or chip-based infusion for the analysis of peptides and proteins. 

Hopfgartner, G. The combination of liquid chromatography/tandem mass spectrometry and chip-based infusion for improved screening and characterization of drug metabolites. Rapid Commun. Mass Spectrom. 2005, 19, 618-626. 

H. Irth A microfluidic-based enzymatic assay for bioactivity screening combined with capillary liquid chromatography and mass spectrometry. Lab Chip 2005, 5,... 

Lab-on-a-chip/high-performance liquid chromatography 2005 LOC/HPLC 215 Collins, 13.4... 

Q. He, Integrated nano liquid chromatography system on a chip, Ph.D. thesis, California Institute of Technology, Pasadena, CA, June 21 (2005). 

Q. He, C. Pang, Y.-C. Tai, T.D. Lee, Ion liquid chromatography on-a- chip with beads-packed parylene column. Proceedings of the 17th IEEE International Conference on Micro Electro Mechanical Systems (MEMS 2004). Maastricht, The Netherlands, Jan 25-29 (2004). 

More recently, the description of a small-bore liquid chromatography by Manz et al. [83] on a 5 x 5 mm silicon chip revived the interest of the analytical chemical community. The chip incorporated an open tubular column of 6x2 pm cross section (column volume 1.8 nl) and a conductometric detector with a detection volume of only 1.2 pi. Although this work was an important benchmark study, the actual functioning of the chromatograph was never demonstrated with separations. 

Optical absorbance detection was also achieved using a CCD-based spectrophotometer. Two food dyes (FD C Blue 1 dye and FD C Red 3 dye) were first separated by open-tubular liquid chromatography and then detected on a PDMS chip. The LODs for the blue and red dyes were determined to be 80 pM and 200 pM, respectively [569]. 

O Neill, A.P., O Brien, P., Alderman, J., Hoffman, D., McEnery, M., Murrihy, J., Glennon, J.D., On-chip definition of picolitre sample injection plugs for miniaturised liquid chromatography.. /. Chromatogr. A 2001, 924, 259-263. 

W. R. Alley, Y. Mechref, and M. V. Novotny, Use of activated graphitized carbon chips for liquid chromatography/mass spectrometric and tandem mass spectrometric analysis of tryptic peptides, Rapid Commun. Mass Spectrom., 23 (2009) 495-505. 

Flamini, R., De Rosso, M. Smaniotto, A. Panighel, A, Vedova, A.D. Seraglia, R. Traldi, P. 2009. Fast analysis of isobaric grape anthoeyanins by Chip-liquid chromatography/mass speetrometry. Rapid Comm. Mass Spectrom. 23 2891-2896. 

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