Interfacing microfluidics to LDI-MS by automatic robotic spotting

Abstract

We developed a method of interfacing microfluidics with mass spectrometry (MS) using a robotic spotting system to automate the contact spotting process. We demonstrate that direct and automated spotting of analyte from multichannel microfluidic chips to a custom microstructured MALDI target plate was a simple, robust, and high-throughput method for interfacing parallel microchannels using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Using thermoplastic cyclic olefin copolymer (COC) polymer microfluidic chips containing eight parallel 100 lm 9 46 lm microchannels connected to a single input port, spotting volume repeatability and MALDI-MS signal uniformity are evaluated for a panel of sample peptides. The COC microfluidic chips were fabricated by hot embossing and solvent bonding techniques followed by chip dicing to create open ends for MS interfacing. Using the automatic robotic spotting approach, microfluidic chip-based reversed-phase liquid chromatography (RPLC) separations were interfaced with electrochemically etched nanofilament silicon (nSi) target substrate, demonstrating the potential of this approach toward chip-based microfluidic separation coupled with matrix-free laser desorption/ionization mass spectrometry.

The application of a new microfluidic device for the simultaneous identification and quantitation of midazolam metabolites obtained from a single micro‐litre of chimeric mice blood

“…Liquid chromatography (LC) devices were later developed during the 1990s, first for capillary electrophoresis/electro‐chromatography and later for electrospray ionisation mass spectrometry . More recently, the coupling to matrix‐assisted laser desorption ionisation has been reported . Commercial microfluidic devices for LC/MS applications often comprise of a trapping column, an analytical column and an electrospray ionisation emitter all combined into a single chip design .…”

“…[14,15] More recently, the coupling to matrix-assisted laser desorption ionisation has been reported. [16] Commercial microfluidic devices for LC/MS applications often comprise of a trapping column, an analytical column and an electrospray ionisation emitter all combined into a single chip design. [17][18][19] The trapping column allows for the clean up or concentration of a sample before switching it to the analytical column.…”

Microfluidic concentration-on-demand combinatorial dilutions

“…The IC 50 value is 1.28 lg/ml, which is similar to our previous work (Lee et al 2010b), and the magnitude has small discrepancy with reported results (Pirnia et al 2002;Sagara and Katoh 2000). Full integration with suitable cell culture devices (Hattori et al 2011) or microfluidic based patterning devices (Tsao et al 2010) will provide a useful tool requiring more specific and various combinatorial dilutions of samples for advanced screening and optimization experiments.…”

Microfluidics-to-mass spectrometry: A review of coupling methods and applications

“…In one example [56], a COC microfluidic device was developed for contact spotting the outlets of 8 parallel channels to a MALDI plate. Spotting was performed by moving the outlet of these channels within 200 μm of the MALDI plate.…”