Abstract
Here, we present a rapid droplet sampling interface (RDSI) electrospray ionization mass spectrometry (ESI-MS) system as a high-throughput, low-volume, noncontact, and minimal-carryover approach for characterization of liquids. Liquid characterization was achieved by combining droplet ejection with an open-face microflow capillary with a 2.5 μL/min continuous flow of carrier solvent. Through this implementation, single 0.3 nL droplets containing the analyte effectively mix with 4-8 nL of carrier solvent and create a combined electrospray plume. The carrier solvent continuously cleaned the system, eliminating carryover. A sampling rate of 5 Hz was achieved for droplets containing 1 μM propranolol or 5 μM leu-enkephalin with each droplet fully baseline-resolved (138 ± 32 ms baseline-to-baseline). Using a SCIEX API4000 mass spectrometer, a lower limit of quantification (LLOQ) of propranolol was 15 nM, corresponding to 1.16 fg of propranolol in the droplet, and was linear across 3 orders of magnitude. Quantitation could be achieved by adding an isotopically labeled internal standard, as done in conventional ESI. Signal transients were faster than the acquisition speed of the mass spectrometer, resulting in artificially high reproducibility of 15-30% RSD droplet-to-droplet. Analyte-solvent mixing ratios could be controlled by adjusting droplet positioning along the open-face capillary with an optimal position about 0.4 mm from the tip end. The range of analyte coverage was exemplified by measures of peptides and drugs in methanol, water, and buffer solutions. In a comparison to the Open Port Sampling Interface (OPSI) implemented on the same system, the RDSI had 78× greater sensitivity, 6× greater throughput and used significantly less carrier solvent.
| Original language | English |
|---|---|
| Pages (from-to) | 16418-16425 |
| Number of pages | 8 |
| Journal | Analytical Chemistry |
| Volume | 95 |
| Issue number | 44 |
| DOIs | |
| State | Published - Nov 7 2023 |
Funding
This research reported in this publication and all authors were supported by the Technology Innovation Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the US Department of Energy and the National Institute of General Medical Sciences of the National Institutes of Health under award number 1R21GM146085. This manuscript has been authored by UT-Battelle, LLC, under contract DE-AC05–00OR22725 with the US Department of Energy (DOE). The US government retains and the publisher, by accepting the article for publication, acknowledges that the US government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for US government purposes. DOE will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan ( https://www.energy.gov/doe-public-access-plan ). Funding was provided by the Technology Innovation Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the US Department of Energy and the National Institute of General Medical Sciences of the National Institutes of Health under award number 1R21GM146085. This research reported in this publication and all authors were supported by the Technology Innovation Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the US Department of Energy and the National Institute of General Medical Sciences of the National Institutes of Health under award number 1R21GM146085. This manuscript has been authored by UT-Battelle, LLC, under contract DE-AC05-00OR22725 with the US Department of Energy (DOE). The US government retains and the publisher, by accepting the article for publication, acknowledges that the US government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for US government purposes. DOE will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (https://www.energy.gov/doe-public-access-plan). Funding was provided by the Technology Innovation Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the US Department of Energy and the National Institute of General Medical Sciences of the National Institutes of Health under award number 1R21GM146085.