Femtoliter-Droplet Mass Spectrometry Interface Utilizing Nanofluidics for Ultrasmall and High-Sensitivity Analysis.

Area of Science:

• Analytical Chemistry
• Biotechnology
• Nanotechnology

Background:

• High-sensitivity mass spectrometry (MS) is crucial for single-cell analysis in biology and medicine.
• Current MS methods face challenges interfacing with nanofluidic sample pretreatments (fL-pL volumes) without sample loss.
• Advancements in MS sensitivity require compatible interfaces for ultrasmall sample volumes.

Purpose of the Study:

• To develop a novel nanofluidic interface for mass spectrometry (MS).
• To achieve high-sensitivity detection of analytes from ultrasmall sample volumes.
• To overcome limitations of sample loss and dispersion in current MS interfaces.

Main Methods:

• Developed a nanofluidic device to create fL droplets from liquid samples.
• Utilized an applied voltage to charge analyte molecules within droplets.
• Designed a heat transfer module for droplet vaporization and ion generation.
• Implemented controlled droplet trajectory for 100% injection efficiency into the mass spectrometer.

Main Results:

• Achieved 100% sample injection efficiency into the mass spectrometer.
• Demonstrated a limit of detection of 1.52 amol for caffeine ions.
• Obtained a 290-fold increase in sensitivity compared to conventional electrospray ionization interfaces.
• Realized a two-orders-of-magnitude improvement in detection sensitivity.

Conclusions:

• The developed nanofluidic MS interface enables highly sensitive analysis of ultrasmall samples.
• This methodology is suitable for analyzing molecules from single cells, advancing biological and medical research.
• The 100% sample injection efficiency and efficient ionization are key to the enhanced sensitivity.