Picoliter sample preparation in MALDI-TOF MS using a micromachined silicon flow-through dispenser

Area of Science:

• Analytical Chemistry
• Microfluidics
• Mass Spectrometry

Background:

• Traditional sample preparation methods can be time-consuming and require larger sample volumes.
• On-line coupling of sample preparation with separation techniques is desirable for increased efficiency.
• Microfluidic devices offer miniaturization and precise control over sample handling.

Purpose of the Study:

• To develop and characterize a picoliter sample preparation technique for on-line coupling with chromatographic systems.
• To investigate the physicochemical properties of the sample preparation under typical mobile phase conditions.
• To demonstrate the utility of the technique for sensitive protein detection using mass spectrometry.

Main Methods:

• Fabrication of a pressure pulse-driven dispenser using silicon micromachining.
• Generation of picoliter droplets (30-200 pL) using a piezoceramic element.
• Analysis of deposited sample spots using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

Main Results:

• Detection of attomole (159-248 amol) quantities of proteins from single droplets.
• Successful sample enrichment via multiple depositions, enabling detection of 31 nM insulin.
• Optimization of MALDI sample spot size (100-500 µm) for improved throughput.

Conclusions:

• The developed picoliter sample preparation technique is effective for on-line coupling with µ-CLC.
• The technique enables highly sensitive protein detection and sample enrichment for MALDI-TOF MS.
• Optimized spot size and deposition strategy significantly increase sample throughput.