Integrated silicon microfluidic chip for picoliter-scale analyte segmentation and microscale printing for mass spectrometry imaging (original) (raw)

A microfabricated silicon platform with 60 microfluidic chips for rapid mass spectrometric analysis

Lab on a Chip, 2011

Many biological processes are controlled by reversible phosphorylation of proteins. Identification of protein phosphorylation sites is crucial for thorough understanding of cell signaling pathways. This study aims at developing tools for phosphoproteomic research. Applicability of an integrated multi-tip photocatalytic micropillar nanoreactor electrospray ionization (µPESI) chip for phosphopeptide analysis has been preliminary studied. Easy and fast switching between individual tips allows rapid mass spectrometry (MS) analysis of large sample series. The titanium dioxide (TiO 2) coating of the chip allows rapid and simple enrichment of phosphopeptides as well as enables photocatalyzed oxidation reactions.

Microdevices in mass spectrometry

European Journal of Mass Spectrometry, 2007

Miniaturization of laboratory instrumentation is becoming critical in achieving the speed and throughput required by the current revolutionary progress in biology. This mini revie� critically summarizes the present status of microfluidic devices designed for use in mass spectrometry.

Analytical microdevices for mass spectrometry

TrAC Trends in Analytical Chemistry, 2000

The seemingly unlikely marriage between large mass spectrometers and small microchips is actually a good one. Micro£uidic devices have been coupled to mass spectrometers using electrospray ionization interfaces. Different interface designs and various integrated protein preparation and preconcentration procedures are reviewed. The potential role of chip-mass spectrometry in proteomics and drug discovery is also discussed.

Chip-based microfluidic devices coupled with electrospray ionization-mass spectrometry

ELECTROPHORESIS, 2005

Chip-based microfluidic devices coupled with electrospray ionization-mass spectrometry We present the current status of the development of microfluidic devices fabricated on different substrates for coupling with electrospray ionization-mass spectrometry (ESI-MS). Until now, much success has been gained in fabricating the ESI chips, which show better performances due to miniaturization when compared with traditional methods. Integration of multiple steps for sample preparation and ESI sample introduction, however, remains a great challenge. This review covers the main technical development of electrospray device that were published from 1997 to 2004. This article does not attempt to be exclusive. Instead, it focuses on the publications that illustrated the breath of the development and applications of microchip devices for MS-based analysis.

Chemical cytometry on a picoliter-scale integrated microfluidic chip

Proceedings of the National Academy of Sciences, 2004

An integrated microfluidic device has been fabricated for analyzing the chemical contents of a single cell (chemical cytometry). The device is designed to accomplish four different functions: (i) cell handling, (ii) metering and delivering of chemical reagents, (iii) cell lysis and chemical derivatization, and (iv) separating derivatized compounds and detecting them by laser-induced fluorescence. These functions are accomplished with only two valves, formed by multilayer soft lithography. A new kind of three-state valve and a picopipette are described; these elements are crucial for minimizing the reaction volume and ensuring optimal shape of the channel for electrophoresis injection. By using these valves, a reaction volume of Ϸ70 pl is achieved for the lysis and derivitization of the contents of a single Jurkat T cell (Ϸ10 m diameter). As a demonstration of the use of this integrated microfluidic device, electropherograms of amino acids from individual Jurkat T cells are recorded and compared with those collected from a multiple-cell homogenate.

Microchip technology in mass spectrometry

Mass Spectrometry Reviews, 2009

Microfabrication of analytical devices is currently of growing interest and many microfabricated instruments have also entered the field of mass spectrometry (MS). Various (atmospheric pressure) ion sources as well as mass analyzers have been developed exploiting microfabrication techniques. The most common approach thus far has been the miniaturization of the electrospray ion source and its integration with various separation and sampling units. Other ionization techniques, mainly atmospheric pressure chemical ionization and photoionization, have also been subject to miniaturization, though they have not attracted as much attention. Likewise, all common types of mass analyzers have been realized by microfabrication and, in most cases, successfully applied to MS analysis in conjunction with on-chip ionization. This review summarizes the latest achievements in the field of microfabricated ion sources and mass analyzers. Representative applications are reviewed focusing on the development of fully microfabricated systems where ion sources or analyzers are integrated with microfluidic separation devices or microfabricated pums and detectors, respectively. Also the main microfabrication methods, with their possibilities and constraints, are briefly discussed together with the most commonly used materials.

A silicon microfluidic chip integrating an ordered micropillar array separation column and a nano-electrospray emitter for LC/MS analysis of peptides

Sensors and Actuators B: Chemical, 2008

This article presents the development and performance of new silicon microfluidic devices, called Espray chips, integrating both a reversed-phase separation column and a nano-electrospray emitter. The microchips are made according to standard silicon microtechnology procedures including photolithography, deep reactive ion etching and molecular bonding. The separation column is a perfectly ordered 2-dimensional array of squared micropillars, directly etched in the silicon substrate, and the electrospray emitter is a planar nib-like nanotip. Two chemical procedures for the separation column reversed-phase coating were tested: (i) a liquid phase "chip by chip" process with a C18-alkylated silane and (ii) a vapour phase collective process with a C10-perfluorated silane. Analyses of standard tryptic digests of cytochrome c in hydrodynamic pumping mode have demonstrated good quality spray and effective separation performance of these microdevices with a higher retention capacity for C10-perfluorated coating. These new microchips, which can be produced on a very large scale by a mass production process, from microfabrication to chemical treatment, appear to be very promising analytical tools for proteomics research.

A polymeric microfluidic chip for CE/MS determination of small molecules

2001

A polymeric microfluidic chip made of Zeonor 1020 was fabricated using conventional embossing techniques to perform capillary electrophoresis for selected ion monitoring and selected reaction monitoring mass spectrometric detection of small molecules. A silicon master was microfabricated using photolithographic and dry etching processes. The microfluidic channel was embossed in the plastic from a silicon master. The embossed chip was thermally bonded with a Zeonor 1020 cover to form an enclosed channel. This channel (60-µm width, 20-µm depth, 2.0-and 3.5-cm length) provided capillary electrophoresis (CE) separation of polar small molecules without surface treatment of the polymer. A microsprayer coupled via a microliquid junction provided direct electrospray mass spectrometric detection of CE-separated components. An electric field of 0.5-2 kV/cm applied between the microsprayer and a separation buffer reservoir produced a separation of carnitine, acylcarnitine, and butylcarnitine with separation efficiencies ranging from 1650 to 18 000 plates. Injection quantities of 0.2 nmol of these compounds produced a separation of the targeted polar small molecules without surface treatment of the polymer-abundant ion current signals and baseline separation of these compounds in less than 10 s. These results suggest the feasibility of polymeric chip-based devices for ion spray CE/MS applications.

Integrated microchip methods for biological and environmental sample analysis

2015

The introduction of the “microscale total analysis system (μTAS)” concept in the late 80’s triggered the evolution of microfluidic devices that cover a vast range of applications. Automation, integration of multiple processes, and near zero dead volume for separation techniques are some benefits. Closing the gap between research and commercialization in a resource-limited environment is the main aim of this research. This project feeds into two main streams. The first is to integrate on-chip sample preparation for biological applications, like therapeutic drug monitoring (TDM) and diagnostics, using nanojunctions created by controlled dielectric breakdown (Chapters One - Five). The second part focuses on fast prototyping of microfluidic devices with multiple integrated functionalities using a consumer-based 3D-printer (Chapters Six & Seven). These two approaches were tailored to solve specific problems inherent to each sample type and application. Chapter One starts with a general i...