High-Throughput Liquid-Liquid Extractions with Nanoliter Volumes

Area of Science:

• Analytical Chemistry
• Microfluidics
• Separation Science

Background:

• Traditional liquid-liquid extraction methods are solvent- and time-intensive, requiring manual procedures and larger sample volumes.
• Implementing efficient extraction techniques at the nanoliter scale in microfluidic systems has been challenging.

Purpose of the Study:

• To develop a novel microfluidic method, slug-flow nanoextraction (SFNE), for rapid and efficient liquid-liquid extractions at the nanoliter scale.
• To demonstrate SFNE's capability in determining partition coefficients and analyzing analytes in complex biological matrices.

Main Methods:

• SFNE utilizes droplet microfluidics in a capillary tube, creating segmented two-phase slugs for simultaneous extractions with minimal sample and solvent volumes (5 nL).
• The method was validated by determining octanol-water partition coefficients (Kow) and applied to extract analytes from plasma, urine, and CSF prior to ESI-MS/MS.

Main Results:

• SFNE achieved rapid extractions (<5 s) with partition coefficients comparable to larger-scale methods.
• Accurate Kow determination for acetaminophen (2.48 ± 0.02) was completed in 5 min using <150 nL of sample and solvent.
• Analyte detection in biological samples showed up to a 19-fold improvement in signal-to-noise ratio, with limits of detection as low as 7 nM.

Conclusions:

• SFNE offers a highly efficient, rapid, and low-volume microfluidic approach for liquid-liquid extractions.
• The method is suitable for accurate Kow determination and sensitive analyte quantification in complex biological samples.
• SFNE significantly enhances detection limits and throughput for analyses coupled with mass spectrometry.