J. Lee, S.A. Soper, K.K. Murray, “A solid-phase bioreactor with continuous sample deposition for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry,” Rapid Commun. Mass Spectrom. 25 (2011) 693โ€“699. doi:10.1002/rcm.4921.

Abstract: We report the development of a solid-phase proteolytic digestion and continuous deposition microfluidic chip platform for low volume fraction collection and off-line matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Tryptic peptides were formed in an on-chip bioreactor and continuously deposited onto a MALDI target plate using a motor-driven xyz stage. The bioreactor consisted of a 4โ€‰cmโ€‰ร—โ€‰200โ€‰ยตmโ€‰ร—โ€‰50โ€‰ยตm microfluidic channel with covalently immobilized trypsin on an array of 50โ€‰ยตm diameter micropost structures with a 50โ€‰ยตm edge-to-edge inter-post spacing. A 50โ€‰ยตm i.d. capillary tube was directly attached to the end of the bioreactor for continuous sample deposition. The MALDI target plate was modified by spin-coating a nitrocellulose solution containing a MALDI matrix on the surface prior to effluent deposition. Protein molecular weight standards were used for evaluating the performance of the digestion and continuous deposition system. Serpentine sample traces 200โ€‰ยตm wide were obtained with a 30โ€‰fmol/mm quantity deposition rate and a 3.3โ€‰nL/mm volumetric deposition rate.

A schematic of different deposition modes using the PMMA microfluidic chip and immobilized trypsin bioreactor: (a) continuous deposition mode and (b) spot deposition mode. The channel measured 40 mm x 200 mm x 50 mm and had an array of 50 mm diameter posts with a 50 mm inter-post spacing.