A MALDI-chip integrated system with a monitoring window

Brivio, Monica; Tas, Niels Roelof; Goedbloed, M.H.; Gardeniers, Han; Verboom, Willem; Berg, Albert van den; Reinhoudt, David N.

doi:10.1039/b418986h

Cited by 52 publications

(35 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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].…”

mentioning

confidence: 99%

“…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].…”

mentioning

confidence: 99%

See 1 more Smart Citation

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.

View full text Add to dashboard Cite

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...

show abstract

mentioning

confidence: 99%

mentioning

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.

View full text Add to dashboard Cite

show abstract

“…More recently, the vacuum-driven reaction chip concept was further refined by integrating a monitoring window into the microfluidic system [68]. This window consisted of an optically transparent membrane fabricated by anisotropic bulk silicon etching using a boron-doped etch stop, and a 500 nm square hole machined into the membrane by focused ion beam milling.…”

Section: Microfluidic/target Integrationmentioning

confidence: 99%

Microfluidic technologies for MALDI‐MS in proteomics

DeVoe

Lee

2006

Electrophoresis

View full text Add to dashboard Cite

The field of microfluidics continues to offer great promise as an enabling technology for advanced analytical tools. For biomolecular analysis, there is often a critical need to couple on-chip microfluidic sample manipulation with back-end MS. Though interfacing microfluidics to MS has been most often reported through the use of direct ESI-MS, there are compelling reasons for coupling microfluidics to MALDI-MS as an alternative to ESI-MS for both online and offline analysis. The intent of this review is to provide a summary of recent developments in the integration of microfluidic systems with MALDI-MS, with an emphasis on applications in proteomics. Key points are summarized, followed by a review of relevant technologies and a discussion of outlook for the field.

show abstract

“…In other off-line approaches, the sample is dispensed from the chip using a piezoelectric dispenser [25], pumped through a spinning microfluidic disk [26], or sample droplets moved on a dielectric chip surface by electrowetting [27,28]. In a unique on-line approach, the vacuum of the mass spectrometer source is used to pull fluid through a microfluidic chip where it is subjected to UV MALDI as it exits the device [29,30]. A second on-line approach uses a rotating stainless steel ball coupled to an on-chip capillary electrophoresis for the separation of peptides [31].…”

mentioning

confidence: 99%

Interfacing capillary gel microfluidic chips with infrared laser desorption mass spectrometry

Little

Murray

2006

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

We report on the fabrication and performance of a gel microfluidic chip interfaced to laser desorption/ionization (LDI) mass spectrometry with a time-of-flight mass analyzer. The chip was fabricated from poly(methylmethacrylate) with a poly(dimethyl siloxane) cover. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed in the channel of the microfluidic chip. After electrophoresis, the cover was removed and either the PDMS chip or the PMMA cover was mounted in a modified MALDI ion source for analysis. Ions were formed by irradiating the channel with 2.95 m radiation from a pulsed optical parametric oscillator (OPO), which is coincident with IR absorption by N-H and O-H stretch of the gel components. No matrix was added. The microfluidic chip design allowed a decrease in the volume of material required for analysis over conventional gel slabs, thus enabling improvement in the detection limit to a pmol level, a three orders of magnitude improvement over previous studies in which desorption was achieved from an excised section of a conventional gel. ( T he rapid expansion of the field of proteomics has created an increased demand for selective, sensitive, and high-throughput methods of analysis. Soft ionization methods, such as matrix-assisted desorption/ionization (MALDI) [1,2] and electrospray (ESI) [3,4] are suitable for achieving the goal of identification and structural determination of proteins. Mass spectrometry (MS) has become the primary analysis method in this area because of its high throughput, sensitivity, and high mass accuracy. However, the large number and broad concentration range of the proteins present in the expressed proteome of a typical organism requires that one or more fractionation or separation steps be performed on the sample before mass spectrometry analysis.One of the most commonly utilized techniques for protein separation is sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) [5][6][7][8][9]. The molecular weight of a protein is determined by the migration distance after electrophoretic separation together with several marker proteins of known molecular weights that bracket the protein of interest. Currently, most proteome analyses are based on the separation of complex protein mixtures by 1D or 2D gel electrophoresis, followed by mass spectrometric analysis of proteolytic digests of gel spots to identify individual proteins [10 -13]. However, this protocol requires intermediate sample processing steps such as extraction of the protein from the gel [13], blotting the protein onto a membrane [14], or electroelution [15], which introduces a number of laborious and time-consuming manual steps that are difficult to automate.Various efforts have been directed toward direct analysis of gel and planar chromatography separations by laser desorption ionization (LDI) mass spectrometry. The mass spectrometric analysis of peptides and proteins by UV-MALDI directly from polyacrylamide gels has been reported previously [16]. Here, ultrathin gels (less than 10 m) ...

show abstract

A MALDI-chip integrated system with a monitoring window

Cited by 52 publications

References 11 publications

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

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

Microfluidic technologies for MALDI‐MS in proteomics

Interfacing capillary gel microfluidic chips with infrared laser desorption mass spectrometry

Contact Info

Product

Resources

About