Abstract: The invention provides a microfluidic system and method to rapidly analyze large numbers of compounds or complex mixtures of compounds, particularly, low abundance cellular proteins involved in cell signaling pathways. In one aspect, an integrated microfluidic system comprises an upstream separation module (preferably, a multi-dimensional separation device), a microfluidic device for on-device protein digestion of substantially separated proteins received from the upstream separation module, a downstream separation module for separating digestion products of said proteins, a peptide analysis module and a processor for determining the amino acid sequence of said proteins. Preferably, the system comprises an interfacing microfluidic device between the downstream separation module and the peptide analysis module.

Abstract: The invention relates to an apparatus for coupling microfluidic systems with electrospray ionization mass spectrometry utilizing a hydrodynamic flow. The invention also relates to a method of preventing a sample in a main channel of a microfluidic device from migrating down either a first side channel or a second side channel by rapidly alternating a voltage being applied to the first side channel and the second side channel.

Abstract: A microfluidic device is disclosed wherein a hydrodynamic flow restrictor is positioned in a main channel; a make-up flow channel engages the main channel at a position between the hydrodynamic flow restrictor and an output channel. The hydrodynamic flow restrictor substantially negates a hydrodynamic backpressure in the main channel to the extent that low electroosmotic flow may be utilized in the main channel. Further, a method is disclosed wherein a sample is delivered to the main channel and low EOF drives the sample through the main channel. The method comprises positioning a hydrodynamic flow restrictor in the main channel and delivering a make-up solution via hydrodynamic flow to the main channel at a position between a hydrodynamic flow restrictor and the output channel. The hydrodynamic flow restrictor substantially negates a hydrodynamic backpressure in the main channel to the extent that low electroosmotic flow may be utilized in the main channel.

Abstract: The present invention provides an apparatus and a method wherein the movement of analytes on a chromatographic separation column is controlled by the manipulation of isocratic and gradient flow. Such manipulation allows for a distinct set of analytes to be eluted from the chromatography column and delivered downstream for further separation and/or processing while the remainder of the sample remains in a “holding pattern” on the chromatography column. As such, the present invention allows for a small portion of the sample to be processed downstream of the column while substantially eliminating undesirable isocratic elution from the column during such downstream processing. Once the downstream processing has been completed, the column of the present invention elutes a second distinct analyte and the remainder of the sample is maintained in a holding pattern. The process may be repeated until the entire sample has been eluted from the chromatography column.

Abstract: The present invention comprises an electroosmotic flow pump with both anion and cation exchange beads packed in separate channels that pump towards an intersection. Combining the two flow streams results in higher flowrates for the pump and allows operation of the pump over a wide pH range. The pump can be used to deliver solutions ranging from a pH of about 2 to about 12. In a preferred embodiment, the electroosmotic pump of the present invention is fabricated on a microfluidic device capable of Edman degradation. In a preferred embodiment of the present invention, the beads are immobilized in the channels using weirs and membranes, eliminating the need for frits. The pump may be comprised of capillaries. Additionally, the electroosmotic flow pump of the present invention may be integrated into an Integrated Microfluidic Proteome Analysis System.