Microfluidic systems in proteomics

Lion, Niels; Rohner, Tatiana C.; Dayon, Loı̈c; Arnaud, Isabelle L.; Damoc, Eugen; Youhnovski, Nikolay; Wu, Zhi‐Yong; Roussel, Christophe; Josserand, Jacques; Jensen, Henrik; Rossier, Joël S.; Przybylski, Michael; Girault, Hubert H.

doi:10.1002/elps.200305629

Cited by 255 publications

(202 citation statements)

References 214 publications

(213 reference statements)

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“…ESI coupled microfluidic devices (ECMDs) have been devised for numerous applications, particularly in the area of proteomics [2]. The complementary advantages of microfluidic liquid handling and ESI-MS based analysis make these devices a natural answer to the challenges of proteomic studies.…”

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confidence: 99%

A versatile microfluidic chip for millisecond time-scale kinetic studies by electrospray mass spectrometry

Rob

Wilson

2009

J. Am. Soc. Mass Spectrom.

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An electrospray coupled microfluidic reactor for the measurement of millisecond time-scale, solution phase kinetics is introduced. The device incorporates a simple two-channel design that is etched into polymethyl methacrylate (PMMA) by laser ablation. The outlet of the device is laser cut to a sharp tip, facilitating low dead volume 'on chip' electrospray. Fabrication is fast, straightforward and highly reproducible, supporting rapid prototyping and large-scale reproduction. Device performance is characterized using a cytochrome c unfolding reaction. Unfolding processes with rates in excess of 30 s Ϫ1 are easily measured, including the appearance of a 'native-like' intermediate that is maximally populated 180 ms post reaction initiation. To extract reliable rates from the data, a theoretical framework for the analysis of kinetics acquired under square-channel laminar flow is introduced. (J Am Soc Mass Spectrom 2009, 20, 124 -130)

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confidence: 99%

A versatile microfluidic chip for millisecond time-scale kinetic studies by electrospray mass spectrometry

Rob

Wilson

2009

J. Am. Soc. Mass Spectrom.

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“…ignificant progress has been made toward the development of microchip-based technologies for proteomics through the integration of analytical processes into platforms that can provide rapid identification of proteins and the subsequent characterization of various post-translational modifications [1][2][3][4]. The small sample and reagent requirements, rapid analysis times, high throughput processing capabilities, and low operating costs are among the driving forces for the development of these systems [5][6][7][8].…”

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confidence: 99%

Development of an automated digestion and droplet deposition microfluidic chip for MALDI-TOF MS

Lee

Musyimi

Soper

et al. 2008

J. Am. Soc. Mass Spectrom.

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An automated proteolytic digestion bioreactor and droplet deposition system was constructed with a plastic microfluidic device for off-line interfacing to matrix assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF MS). The microfluidic chips were fabricated in poly(methyl methacrylate) (PMMA), using a micromilling machine and incorporated a bioreactor, which was 100 ILm wide, 100 ILm deep, and possessed a 4 cm effective channel length (400 nL volume). The chip was operated by pressure-driven flow and mounted on a robotic fraction collector system. The PMMA bioreactor contained surface immobilized trypsin, which was covalently attached to the UV-modified PMMA surface using coupling reagents N-(3-dimethylaminopropyl)-N'-ethy1carbodiimide hydrochloride (EDC) and hydroxysulfosuccinimide (sulfo-NHS). The digested peptides were mixed with a MALDI matrix on-chip and deposited as discrete spots on MALDI targets. The bioreactor provided efficient digestion of a test protein, cytochrome c, at a flow rate of 1 ILL/min, producing a reaction time of -24 s to give adequate sequence coverage for protein identification. Other proteins were also evaluated using this solid-phase bioreactor. The efficiency of digestion was evaluated by monitoring the sequence coverage, which was 64%, 35%, 58%, and 47% for cytochrome c, Significant progress has been made toward the development of microchip-based technologies for proteomics through the integration of analytical processes into platforms that can provide rapid identification of proteins and the subsequent characterization of various post-translational modifications [1][2][3][4]. The small sample and reagent requirements, rapid analysis times, high throughput processing capabilities, and low operating costs are among the driving forces for the development of these systems [5][6][7][8]. Different microfluidic devices have been applied to specific aspects of protein processing, in particular, protein purification and separation, protein digestion, and protein identification by mass spectrometry [9].There have been a number of approaches to on-line and off-line matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) integrated to chipbased devices [10][11][12][13][14][15][16][17][18]. The primary advantage of the MALDI approach compared with electrospray ionization (ESI) when coupling to microfluidic chips is the potential for multiplexing [19]. The directional control Address reprint requests to Dr. Kermit K. Murray, Department of Chemistry, Louisiana State University, 232 Choppin Hall, Baton Rouge, LA 70802, USA. E-mail: kkmurray@!su.edu of the ESI spray can be difficult with a high-density array of spray tips. Furthermore, microfluidic chip interfaces to ESI can suffer from stability problems when sprays are started or stopped [20,21]. This limits the speed of moving from one sample to another and therefore, limits throughput.With recent advances in analytical methods for proteomics, attention has been directed toward development of effic...

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“…Residual convergence criteria were set to 10 À4 . The electroosmotic mobility was set to 5 Â 10 À8 m 2 /(V s) for guiding as well as the sample stream (Lion et al 2003). …”

Section: Setup and Methodsmentioning

confidence: 99%

A microfluidic device for array patterning by perpendicular electrokinetic focusing

Kohlheyer

Unnikrishnan

Besselink

et al. 2007

Microfluid Nanofluid

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This paper describes a microfluidic chip in which two perpendicular laminar-flow streams can be operated to sequentially address the surface of a flowchamber with semi-parallel sample streams. The sample streams can be controlled in position and width by the method of electrokinetic focusing. For this purpose, each of the two streams is sandwiched by two parallel sheath flow streams containing just a buffer solution. The streams are being electroosmotically pumped, allowing a simple chip design and a setup with no moving parts. Positioning of the streams was adjusted in real-time by controlling the applied voltages according to an analytical model. The perpendicular focusing gives rise to overlapping regions, which, by combinatorial (bio) chemistry, might be used for fabrication of spot arrays of immobilized proteins and other biomolecules. Since the patterning procedure is done in a closed, liquid filled flow-structure, array spots will never be exposed to air and are prevented from drying. With this device configuration, it was possible to visualize an array of 49 spots on a surface area of 1 mm 2 . This article describes the principle, fabrication, experimental results, analytical modeling and numerical simulations of the microfluidic chip.

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Microfluidic systems in proteomics

Cited by 255 publications

References 214 publications

A versatile microfluidic chip for millisecond time-scale kinetic studies by electrospray mass spectrometry

A versatile microfluidic chip for millisecond time-scale kinetic studies by electrospray mass spectrometry

Development of an automated digestion and droplet deposition microfluidic chip for MALDI-TOF MS

A microfluidic device for array patterning by perpendicular electrokinetic focusing

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