Rapid Droplet Sampling Interface for Low-Volume, High-Throughput Mass Spectrometry Analysis

Cahill, John F.; Kertesz, Vilmos

doi:10.1021/acs.analchem.3c04015

Rapid Droplet Sampling Interface for Low-Volume, High-Throughput Mass Spectrometry Analysis

Journal Article · Fri Oct 27 00:00:00 EDT 2023 · Analytical Chemistry

DOI:https://doi.org/10.1021/acs.analchem.3c04015· OSTI ID:2338282

^[1]; ^[1]

Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

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. Further, 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.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 2338282

Journal Information:: Analytical Chemistry, Journal Name: Analytical Chemistry Journal Issue: 44 Vol. 95; ISSN 0003-2700

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

References (27)

Leucine enkephalin-A mass spectrometry standard Sztáray, Judit; Memboeuf, Antony; Drahos, László Mass Spectrometry Reviews, Vol. 30, Issue 2 https://doi.org/10.1002/mas.20279	journal	July 2010
An open port sampling interface for liquid introduction atmospheric pressure ionization mass spectrometry: Open port sampling interface Van Berkel, Gary J.; Kertesz, Vilmos Rapid Communications in Mass Spectrometry, Vol. 29, Issue 19 https://doi.org/10.1002/rcm.7274	journal	August 2015
Rapid sample classification using an open port sampling interface coupled with liquid introduction atmospheric pressure ionization mass spectrometry: Sample classification using an open port sampling interface Van Berkel, Gary J.; Kertesz, Vilmos Rapid Communications in Mass Spectrometry, Vol. 31, Issue 3 https://doi.org/10.1002/rcm.7792	journal	January 2017
Quantitation of amiodarone and N-desethylamiodarone in single HepG2 cells by single-cell printing-liquid vortex capture-mass spectrometry Cahill, John F.; Kertesz, Vilmos Analytical and Bioanalytical Chemistry, Vol. 413, Issue 28 https://doi.org/10.1007/s00216-021-03652-6	journal	October 2021
A novel nonmetallized tip for electrospray mass spectrometry at nanoliter flow rate Fong, Karen W. Y.; Chan, T. -W. Dominic Journal of the American Society for Mass Spectrometry, Vol. 10, Issue 1 https://doi.org/10.1016/S1044-0305(98)00127-5	journal	January 1999
Biases in ion transmission through an electrospray ionization-mass spectrometry capillary inlet Page, Jason S.; Marginean, Ioan; Baker, Erin S. Journal of the American Society for Mass Spectrometry, Vol. 20, Issue 12 https://doi.org/10.1016/j.jasms.2009.08.018	journal	December 2009
A high-throughput MALDI-TOF MS biochemical screen for small molecule inhibitors of the antigen aminopeptidase ERAP1 Müller, Leonie; Burton, Amy K.; Tayler, Chloe L. SLAS Discovery, Vol. 28, Issue 1 https://doi.org/10.1016/j.slasd.2022.11.002	journal	January 2023
Comparison of Drug Distribution Images from Whole-Body Thin Tissue Sections Obtained Using Desorption Electrospray Ionization Tandem Mass Spectrometry and Autoradiography Kertesz, Vilmos; Van Berkel, Gary J.; Vavrek, Marissa Analytical Chemistry, Vol. 80, Issue 13 https://doi.org/10.1021/ac800546a	journal	July 2008
Ultrahigh-Throughput ESI-MS: Sampling Pushed to Six Samples per Second by Acoustic Ejection Mass Spectrometry Häbe, Tim T.; Liu, Chang; Covey, Tom R. Analytical Chemistry, Vol. 92, Issue 18 https://doi.org/10.1021/acs.analchem.0c01632	journal	August 2020
Operational Modes and Speed Considerations of an Acoustic Droplet Dispenser for Mass Spectrometry Liu, Chang; Van Berkel, Gary J.; Cox, David M. Analytical Chemistry, Vol. 92, Issue 24 https://doi.org/10.1021/acs.analchem.0c02999	journal	October 2020
Fluid Dynamics of the Open Port Interface for High-Speed Nanoliter Volume Sampling Mass Spectrometry Liu, Chang; Van Berkel, Gary J.; Kovarik, Peter Analytical Chemistry, Vol. 93, Issue 24 https://doi.org/10.1021/acs.analchem.1c01312	journal	June 2021
Single-Cell Analysis Using Drop-on-Demand Inkjet Printing and Probe Electrospray Ionization Mass Spectrometry Chen, Fengming; Lin, Luyao; Zhang, Jie Analytical Chemistry, Vol. 88, Issue 8 https://doi.org/10.1021/acs.analchem.5b04749	journal	April 2016
RapidFire Mass Spectrometry with Enhanced Throughput as an Alternative to Liquid–Liquid Salt Assisted Extraction and LC/MS Analysis for Sulfonamides in Honey Veach, Brian T.; Mudalige, Thilak K.; Rye, Peter Analytical Chemistry, Vol. 89, Issue 6 https://doi.org/10.1021/acs.analchem.6b04889	journal	March 2017
Acoustic Mist Ionization Platform for Direct and Contactless Ultrahigh-Throughput Mass Spectrometry Analysis of Liquid Samples Sinclair, Ian; Bachman, Martin; Addison, Daniel Analytical Chemistry, Vol. 91, Issue 6 https://doi.org/10.1021/acs.analchem.9b00142	journal	February 2019
Rapid, Untargeted Chemical Profiling of Single Cells in Their Native Environment Cahill, John F.; Riba, Julian; Kertesz, Vilmos Analytical Chemistry, Vol. 91, Issue 9 https://doi.org/10.1021/acs.analchem.9b00680	journal	April 2019
Online Aerosol Chemical Characterization by Extractive Electrospray Ionization–Ultrahigh-Resolution Mass Spectrometry (EESI-Orbitrap) Lee, Chuan Ping; Riva, Matthieu; Wang, Dongyu Environmental Science & Technology, Vol. 54, Issue 7 https://doi.org/10.1021/acs.est.9b07090	journal	March 2020
High-Throughput Characterization and Optimization of Polyamide Hydrolase Activity Using Open Port Sampling Interface Mass Spectrometry Cahill, John F.; Kertesz, Vilmos; Saint-Vincent, Patricia Journal of the American Society for Mass Spectrometry, Vol. 34, Issue 7 https://doi.org/10.1021/jasms.3c00097	journal	June 2023
Field-Induced Droplet Ionization Mass Spectrometry Grimm, Ronald L.; Beauchamp, J. L. The Journal of Physical Chemistry B, Vol. 107, Issue 51 https://doi.org/10.1021/jp037099r	journal	November 2003
Dynamics of Field-Induced Droplet Ionization: Time-Resolved Studies of Distortion, Jetting, and Progeny Formation from Charged and Neutral Methanol Droplets Exposed to Strong Electric Fields Grimm, Ronald L.; Beauchamp, J. L. The Journal of Physical Chemistry B, Vol. 109, Issue 16 https://doi.org/10.1021/jp0450540	journal	April 2005
High-throughput matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry–based deubiquitylating enzyme assay for drug discovery De Cesare, Virginia; Moran, Jennifer; Traynor, Ryan Nature Protocols, Vol. 15, Issue 12 https://doi.org/10.1038/s41596-020-00405-0	journal	November 2020
Acoustic ejection mass spectrometry: fundamentals and applications in high-throughput drug discovery Liu, Chang Expert Opinion on Drug Discovery, Vol. 17, Issue 7 https://doi.org/10.1080/17460441.2022.2084069	journal	May 2022
MALDI-TOF Mass Spectrometry-Based High-Throughput Screening for Inhibitors of the Cytosolic DNA Sensor cGAS Simon, Roman P.; Winter, Martin; Kleiner, Carola SLAS DISCOVERY: Advancing the Science of Drug Discovery, Vol. 25, Issue 4 https://doi.org/10.1177/2472555219880185	journal	October 2019
Automated MALDI Target Preparation Concept: Providing Ultra-High-Throughput Mass Spectrometry–Based Screening for Drug Discovery Winter, Martin; Ries, Robert; Kleiner, Carola SLAS Technology, Vol. 24, Issue 2 https://doi.org/10.1177/2472630318791981	journal	April 2019
Acoustic Ejection/Full-Scan Mass Spectrometry Analysis for High-Throughput Compound Quality Control Zhang, Jun; Zhang, Yong; Liu, Chang SLAS Technology, Vol. 26, Issue 2 https://doi.org/10.1177/2472630320967625	journal	April 2021
Immediate drop on demand technology (I-DOT) coupled with mass spectrometry via an open port sampling interface Van Berkel, Gary J.; Kertesz, Vilmos; Boeltz, Harry Bioanalysis, Vol. 9, Issue 21 https://doi.org/10.4155/bio-2017-0104	journal	November 2017
Online molecular characterisation of organic aerosols in an atmospheric chamber using extractive electrospray ionisation mass spectrometry Gallimore, Peter J.; Giorio, Chiara; Mahon, Brendan M. Atmospheric Chemistry and Physics, Vol. 17, Issue 23 https://doi.org/10.5194/acp-17-14485-2017	journal	December 2017
Probe Electrospray Ionization (PESI) and Its Modified Versions: Dipping PESI (dPESI), Sheath-Flow PESI (sfPESI) and Adjustable sfPESI (ad-sfPESI) Hiraoka, Kenzo; Ariyada, Osamu; Usmanov, Dilshadbek T. Mass Spectrometry, Vol. 9, Issue 1 https://doi.org/10.5702/massspectrometry.A0092	journal	December 2020