在電噴灑游離質譜中，通常會在金屬毛細管上施加直流電位，以輸送液體樣品並進行游離。然而，在某些情況下，特別是使用奈米電噴灑游離時，可能會採用不導電的毛細管來輸送樣品。這時，電位的施加方式就需要調整，例如，可將金屬接頭放置於毛細管出口附近，或是在毛細管入口附近的樣品儲存槽內設置電極。這兩種施加電位的方式會影響質譜訊號的強度。當電極距離毛細管出口較遠時，必須施加較高的電位才能獲得良好的訊號。此外，樣品的導電性也會影響最佳電位，若電解質的導電性較高，則所需電位較低。因此，透過直流電壓掃描來尋找最佳條件是必要的。值得注意的是，將電位施加於樣品儲存槽內的電極，而非金屬接頭，可以顯著降低分析物氧化產物的生成。此外，我們發現，若在金屬接頭或樣品儲存槽內的電極施加單極方波交流電位，且頻率足夠高，則其效果與降低直流電位相似，並可透過調整工作週期來達到數位化控制電噴灑。另外，當交流信號的頻率達到一定水準後，泰勒錐的振盪頻率便不再受其影響。在特定條件下，施加交流電位甚至能夠穩定電噴灑羽流。這些觀察結果顯示，電噴灑游離樣品輸送系統的行為與 RC 電路類似。

In electrospray ionization (ESI) mass spectrometry (MS), an electric DC potential is often applied to a metal capillary used to infuse a liquid sample. However, in some cases, especially when employing nanoelectrospray ionization (nanoESI), it is convenient to use a nonconducting capillary for sample delivery and spraying. In these cases, the potentials can be applied—for example—using a metal union placed in the proximity of the capillary outlet, or to an electrode located in the sample reservoir near the capillary inlet. The optimum potential values—which warrant high MS signals—are different in these two operational conditions. A higher potential needs to be applied when the electrode is placed further away from the capillary outlet. Moreover, sample conductivity has a strong influence on the optimum potential values. Lower potentials must be used with highly conductive electrolytes. Thus, DC voltage scans are required to determine the optimum potentials. Applying electric potential to the electrode located in the sample reservoir—rather than metal union—significantly decreases the appearance of oxidized analyte peaks. We also show that a single-polarity square AC waveform can be applied to the union or sample reservoir electrode, and—if its frequency is sufficiently high—it has a similar effect as decreasing DC voltage, allowing for digital control of electrospray with square waves (by varying duty cycle). Interestingly, the liquid meniscus oscillation frequency is independent of the AC signal frequency if the frequency is sufficiently high. Applying the AC signal—in certain conditions—stabilizes electrospray plume. These observations reveal resemblance of the ESI sample line to an RC circuit.

1. MS0D13~1. Stfx.ca. https://people.stfx.ca/tsmithpa/chem361/labs/ms.html (accessed 2024-07-17).
2. Alymatiri, C. M.; Kouskoura, M. G.; Markopoulou, C. K. Decoding the Signal Response of Steroids in Electrospray Ionization Mode (ESI-MS). Anal. Methods 2015, 7, 10433–10444.
3. Konermann, L.; Ahadi, E.; Rodriguez, A. D.; Vahidi, S. Unraveling the Mechanism of Electrospray Ionization. Anal. Chem. 2013, 85, 2–9.
4. McMahon, W. P.; Dalvi, R.; Lesniewski, J. E.; Hall, Z. Y.; Jorabchi, K. Pulsed Nano-ESI: Application in Ion Mobility-MS and Insights into Spray Dynamics. J. Am. Soc. Mass Spectrom. 2020, 31, 488–497.
5. Crouch, S.; Skoog, D.; Holler, F. Principles of Instrumental Analysis, 7th ed.; Cengage Learning Custom Publishing: Mason, OH, 2017.
6. Urban, P. L.; Chen, Y.-C.; Wang, Y.-S. Time-Resolved Mass Spectrometry: From Concept to Applications; Wiley: Chichester, 2016.
7. Mirzaei, H., Carrasco, M., Eds.; Modern Proteomics - Sample Preparation, Analysis and Practical Applications; Springer International Publishing: Cham, Switzerland, 2018.
8. Domon, B.; Aebersold, R. Mass Spectrometry and Protein Analysis. Science 2006, 312, 212–217.
9. Cloupeau, M.; Prunet-Foch, B. Electrohydrodynamic Spraying Functioning Modes: A Critical Review. J. Aerosol Sci. 1994, 25, 1021–1036.
10. Sony Semiconductor Solutions Group. Common technology of image sensors. https://www.sony-semicon.com/en/technology/is/index.html (accessed 2024-06-03).
11. McLafferty, F. W. A Century of Progress in Molecular Mass Spectrometry. Annu. Rev. Anal. Chem. 2011, 4, 1–22.
12. Dronsfield, A. Mass spectrometry - the early days. RSC Education. https://edu.rsc.org/feature/mass-spectrometry-the-early-days/2020189.article (accessed 2024-04-08).
13. Griffiths, J. A Brief History of Mass Spectrometry. Anal. Chem. 2008, 80, 5678–5683.
14. Garg, E.; Zubair, M. Mass Spectrometer; StatPearls Publishing, 2023.
15. Urban, P. L. Quantitative Mass Spectrometry: An Overview. Philos. Trans. A Math. Phys. Eng. Sci. 2016, 374, 20150382.
16. Schiller, J. MALDI-TOF MS in Lipidomics. Front. Biosci. 2007, 12, 2568.
17. Criscuolo, A.; Zeller, M.; Cook, K.; Angelidou, G.; Fedorova, M. Rational Selection of Reverse Phase Columns for High Throughput LC–MS Lipidomics. Chem. Phys. Lipids 2019, 221, 120–127.
18. Shen, Y.; Tolić, N.; Masselon, C.; Paša-Tolić, L.; Camp, D. G., II; Lipton, M. S.; Anderson, G. A.; Smith, R. D. Nanoscale Proteomics. Anal. Bioanal. Chem. 2004, 378, 1037–1045.
19. Lesur, A.; Domon, B. Advances in High-Resolution Accurate Mass Spectrometry Application to Targeted Proteomics. Proteomics. 2015, 15, 880–890.
20. Zhang, X.-W.; Li, Q.-H.; Xu, Z.-D.; Dou, J.-J. Mass Spectrometry-Based Metabolomics in Health and Medical Science: A Systematic Review. RSC Adv. 2020, 10, 3092–3104.
21. Specht, H.; Slavov, N. Transformative Opportunities for Single-Cell Proteomics. J. Proteome Res. 2018, 17, 2565–2571.
22. Kandiah, M.; Acosta-Martin, A. E.; Lane, L. Combining Bioinformatics and MS-Based Proteomics: Clinical Implications. Expert Rev. Proteomics 2014, 11, 269–284.
23. Van Schepdael, A.; Cabooter, D. Quantitative Mass Spectrometry Methods for Pharmaceutical Analysis. Phil. Trans. R. Soc. A. 2016, 374, 20150366.
24. Tokumura, M.; Miyake, Y.; Wang, Q.; Nakayama, H.; Amagai, T.; Ogo, S.; Kume, K.; Kobayashi, T.; Takasu, S.; Ogawa, K. Methods for the Analysis of Organophosphorus Flame Retardants—Comparison of GC-EI-MS, GC-NCI-MS, LC-ESI-MS/MS, and LC-APCI-MS/MS. J. Environ. Sci. Health A Tox. Hazard. Subst. Environ. Eng. 2018, 53, 475–481.
25. Abd-El-Aziz, N. M.; Hifnawy, M. S.; Lotfy, R. A.; Younis, I. Y. LC/MS/MS and GC/MS/MS Metabolic Profiling of Leontodon Hispidulus, in Vitro and in Silico Anticancer Activity Evaluation Targeting Hexokinase 2 Enzyme. Sci. Rep. 2024, 14, 1– 26.
26. Prabhu, G. R. D.; Williams, E. R.; Wilm, M.; Urban, P. L. Mass Spectrometry Using Electrospray Ionization. Nat. Rev. Methods Primers 2023, 3, 1–22.
27. Kandiah, M.; Urban, P. L. Advances in Ultrasensitive Mass Spectrometry of Organic Molecules. Chem. Soc. Rev. 2013, 42, 5299-5322.
28. Alberici, R. M.; Simas, R. C.; Sanvido, G. B.; Romão, W.; Lalli, P. M.; Benassi, M.; Cunha, I. B. S.; Eberlin, M. N. Ambient Mass Spectrometry: Bringing MS into the “Real World.” Anal. Bioanal. Chem. 2010, 398, 265–294.
29. Vestal, M. L. Methods of Ion Generation. Chem. Rev. 2001, 101, 361–376.
30. Zeleny, J. The Electrical Discharge from Liquid Points, and a Hydrostatic Method of Measuring the Electric Intensity at their Surfaces. Phys. Rev. 1914, 3, 69–91.
31. Taylor, G. Disintegration of Water Drops in an Electric Field. Proc. R. Soc. Lond. 1964, 280, 383–397.
32. Dole, M.; Mack, L. L.; Hines, R. L.; Mobley, R. C.; Ferguson, L. D.; Alice, M. B. Molecular Beams of Macroions. J. Chem. Phys. 1968, 49, 2240–2249.
33. Yamashita, M.; Fenn, J. B. Electrospray Ion Source. Another Variation on the Free-Jet Theme. J. Phys. Chem. 1984, 88, 4451–4459.
34. Kebarle, M. L.; Gall, L. N.; Krasnov, N. V.; Nikolaev, V. I.; Pavlenko, V. A.; Shkurov, V. A. Extraction of Ions from Solutions under Atmospheric Pressure as a Method for Mass Spectrometric Analysis of Bioorganic Compounds. Doklady Akad. Nauk. SSSR 1984, 277, 379–383.
35. Lord, R. XX. On the Equilibrium of Liquid Conducting Masses Charged with Electricity. Lond. Edinb. Dublin Philos. Mag. J. Sci. 1882, 14, 184–186.
36. Kebarle, P.; Peschke, M. On the Mechanisms by Which the Charged Droplets Produced by Electrospray Lead to Gas Phase Ions. Anal. Chim. Acta. 2000, 406, 11–35.
37. Crotti, S.; Seraglia, R.; Traldi, P. Some Thoughts on Electrospray Ionization Mechanisms. Eur. J. Mass Spectrom. 2011, 17, 85–99.
38. Kebarle, P.; Verkerk, U. H. Electrospray: From Ions in Solution to Ions in the Gas Phase, What We Know Now. Mass Spectrom. Rev. 2009, 28, 898–917.
39. Banerjee, S.; Mazumdar, S. Electrospray Ionization Mass Spectrometry: A Technique to Access the Information beyond the Molecular Weight of the Analyte. Int. J. Anal. Chem 2012, 2012, 1–40.
40. Iribarne, J. V.; Thomson, B. A. On the Evaporation of Small Ions from Charged Droplets. J. Chem. Phys. 1976, 64, 2287–2294.
41. Ahadi, E.; Konermann, L. Modeling the Behavior of Coarse-Grained Polymer Chains in Charged Water Droplets: Implications for the Mechanism of Electrospray Ionization. J. Phys. Chem. B. 2012, 116, 104–112.
42. Konermann, L.; Rodriguez, A. D.; Liu, J. On the Formation of Highly Charged Gaseous Ions from Unfolded Proteins by Electrospray Ionization. Anal. Chem. 2012, 84, 6798– 6804.
43. Wilm, M. Principles of Electrospray Ionization. Mol. Cell. Proteomics 2011, 10, M111.009407.
44. Iavarone, A. T.; Williams, E. R. Mechanism of Charging and Supercharging Molecules in Electrospray Ionization. J. Am. Chem. Soc. 2003, 125, 2319–2327.
45. Chowdhury, S. K.; Katta, V.; Chait, B. T. Probing Conformational Changes in Proteins by Mass Spectrometry. J. Am. Chem. Soc. 1990, 112, 9012–9013.
46. Wilm, M. S.; Mann, M. Electrospray and Taylor-Cone Theory, Dole’s Beam of Macromolecules at Last? Int. J. Mass Spectrom. Ion Process. 1994, 136, 167–180.
47. Wilm, M.; Mann, M. Analytical Properties of the Nanoelectrospray Ion Source. Anal. Chem. 1996, 68, 1–8.
48. Wickremsinhe, E. R.; Singh, G.; Ackermann, B. L.; Gillespie, T. A.; Chaudhary, A. K. A Review of Nanoelectrospray Ionization Applications for Drug Metabolism and Pharmacokinetics. Curr. Drug Metab. 2006, 7, 913–928.
49. Gibson, G. T. T.; Mugo, S. M.; Oleschuk, R. D. Nanoelectrospray Emitters: Trends and Perspective. Mass Spectrom. Rev. 2009, 28, 918–936.
50. Schmidt, A.; Karas, M.; Dülcks, T. Effect of Different Solution Flow Rates on Analyte Ion Signals in Nano-ESI MS, or: When Does ESI Turn into Nano-ESI? J. Am. Soc. Mass Spectrom. 2003, 14, 492–500.
51. Tang, X.; Bruce, J. E.; Hill, H. H., Jr. Characterizing Electrospray Ionization Using Atmospheric Pressure Ion Mobility Spectrometry. Anal. Chem. 2006, 78, 7751–7760.
52. Juraschek, R.; Dülcks, T.; Karas, M. Nanoelectrospray—More than Just a Minimized-Flow Electrospray Ionization Source. J. Am. Soc. Mass Spectrom. 1999, 10, 300–308.
53. Li, H.; Allen, N.; Li, M.; Li, A. Conducting and Characterizing Femto Flow Electrospray Ionization. Analyst, 2022, 147, 1071–1075.
54. Allen, N. R.; Li, H.; Cheung, A.; Xu, G.; Zi, Y.; Li, A. Femtoamp and Picoamp Modes of Electrospray and Paper Spray Ionization. Int. J. Mass Spectrom. 2021, 469, 116696.
55. Lu, Y.; Zhou, F.; Shui, W.; Bian, L.; Guo, Y.; Yang, P. Pulsed Electrospray for Mass Spectrometry. Anal. Chem. 2001, 73, 4748–4753.
56. Kertesz, V.; Van Berkel, G. J. Control of Analyte Electrolysis in Electrospray Ionization Mass Spectrometry Using Repetitively Pulsed High Voltage. Int. J. Mass Spectrom. 2011, 303, 206–211.
57. Fu, X.; Liang, H.; Xia, B.; Huang, C.; Ji, B.; Zhou, Y. Determination of Sulfonamides in Chicken Muscle by Pulsed Direct Current Electrospray Ionization Tandem Mass Spectrometry. J. Agric. Food Chem. 2017, 65, 8256–8263.
58. Xu, Z.; Wu, H.; Tang, Y.; Xu, W.; Zhai, Y. Electric Modeling and Characterization of Pulsed High‐voltage Nanoelectrospray Ionization Sources by a Miniature Ion Trap Mass Spectrometer. J. Mass Spectrom. 2019, 54, 583–591.
59. Ninomiya, S.; Hiraoka, K. Pulsed Nano-Electrospray Ionization with a High Voltage (4000 V) Pulse Applied to Solutions in the Range of 200 Ns to 1 Ms. J. Am. Soc. Mass Spectrom. 2020, 31, 693–699.
60. Liu, Q.; Ahmed, E.; Kabir, K. M. M.; Huang, X.; Xiao, D.; Fletcher, J.; Donald, W. A. Pulsed Nanoelectrospray Ionization Boosts Ion Signal in Whole Protein Mass Spectrometry. Appl. Sci. 2021, 11, 10883.
61. Gao, Y.; Zhang, M.; Feng, H.; Huang, K.; Xia, B.; Pan, Y. Pulsed Direct Current Arc-Induced Nanoelectrospray Ionization Mass Spectrometry. Anal. Chem. 2024, 96, 6106–6111.
62. Alexander, M. S.; Paine, M. D.; Stark, J. P. W. Pulsation Modes and the Effect of Applied Voltage on Current and Flow Rate in Nanoelectrospray. Anal. Chem. 2006, 78, 2658–2664.
63. Wei, J.; Shui, W.; Zhou, F.; Lu, Y.; Chen, K.; Xu, G.; Yang, P. Naturally and Externally Pulsed Electrospray. Mass Spectrom. Rev. 2002, 21, 148–162.
64. Chao, B.-F.; Chen, C.-J.; Li, F.-A.; Her, G.-R. Sheathless Capillary Electrophoresis‐mass Spectrometry Using a Pulsed Electrospray Ionization Source. Electrophoresis 2006, 27, 2083–2090.
65. De Hoffmann, E.; Stroobant, V. Mass Spectrometry: Principles and Applications, 3rd ed.; Wiley-Blackwell: Hoboken, NJ, 2013.
66. Haag, A. M. Mass Analyzers and Mass Spectrometers. In Modern Proteomics – Sample Preparation, Analysis and Practical Applications; Springer International Publishing: Cham, 2016; pp 157–169.
67. Batey, J. H. The Physics and Technology of Quadrupole Mass Spectrometers. Vacuum 2014, 101, 410–415.
68. Paul, W.; Steinwedel, H. Ein neues Massenspektrometer ohne Magnetfeld. Z. Naturforsch A 1953, 8, 448–450.
69. Henchman, M.; Steel, C. Understanding the Quadrupole Mass Filter through Computer Simulation. J. Chem. Educ. 1998, 75, 1049.
70. Gross J.H. Mass Spectrometry: A Textbook. Springer, Berlin, 2004.
71. Dawson, P. H. Quadrupole Mass Analyzers: Performance, Design and Some Recent Applications. Mass Spectrom. Rev. 1986, 5, 1–37.
72. El-Aneed, A.; Cohen, A.; Banoub, J. Mass Spectrometry, Review of the Basics: Electrospray, MALDI, and Commonly Used Mass Analyzers. Appl. Spectrosc. Rev. 2009, 44, 210–230.
73. Stephens, W. E.; Serin, B.; Myerhof, W. E. Erratum: A Method for Measuring Effective Contact E.m.f. between a Metal and a Semi-Conductor. Phys. Rev. 1946, 69, 244–244.
74. Cameron, A. E.; Eggers, D. F., Jr. An Ion ``velocitron’’. Rev. Sci. Instrum. 1948, 19, 605–607.
75. Glish, G. L.; Vachet, R. W. The Basics of Mass Spectrometry in the Twenty-First Century. Nat. Rev. Drug Discov. 2003, 2, 140–150.
76. Cornish, T. J.; Bryden, W. A. Johns Hopkins APL Tech. Dig.1999, 20, 335−342.
77. Graduate Students. Linea and reflector. Auburn.edu. https://www.auburn.edu/cosam/departments/chemistry/facilities/massspec1/education/malditof/linear_and_reflector.htm (accessed 2025-03-21).
78. Horio, T.; Arakawa, M.; Terasaki, A. Improvement of Reflectron Time-of-Flight Mass Spectrometer for Better Convergence of Ion Beam. Int. J. Mass Spectrom. 2020, 451, 116311.
79. Mamyrin, B. A. Time-of-Flight Mass Spectrometry (Concepts, Achievements, and Prospects). Int. J. Mass Spectrom. 2001, 206, 251–266.
80. McLafferty, F. W. Tandem Mass Spectrometry. Science 1981, 214, 280–287.
81. Kind, T.; Tsugawa, H.; Cajka, T.; Ma, Y.; Lai, Z.; Mehta, S. S.; Wohlgemuth, G.; Barupal, D. K.; Showalter, M. R.; Arita, M.; Fiehn, O. Identification of Small Molecules Using Accurate Mass MS/MS Search. Mass Spectrom. Rev. 2018, 37, 513–532.
82. B. G. Prajapati and M. Patel, A Technology Update: Electro Spray Technology, Int. J. Pharm. Sci. Rev. Res. 2010, 1, 12–13.
83. Marginean, I. Classification of Electrospray Axial Regimes as Revealed by Spray Current Measurements. Int. J. Mass Spectrom. 2024, 495, 117150.\
84. Panahi, A.; Pishevar, A. R.; Tavakoli, M. R. Experimental Investigation of Electrohydrodynamic Modes in Electrospraying of Viscoelastic Polymeric Solutions. Phys. Fluids 2020, 32, 012116.
85. Jaworek, A.; Krupa, A. Classification of the Modes of Ehd Spraying. J. Aerosol Sci. 1999, 30, 873–893.
86. Wang, S.; Yazdekhasti, A.; Alizadeh, A.; Basem, A.; Jasim, D. J.; Al-Rubaye, A. H.; Salahshour, S.; Toghraie, D. Calculating Minimum Droplet Diameter in Dripping, Spindle, and Cone-Jet Modes Based on Experimental Data in the Electrospray Process. Exp. Therm. Fluid Sci. 2024, 154, 111154.
87. Ninomiya, S.; Sakai, Y.; Chuin Chen, L.; Hiraoka, K. Characteristics of Charged Droplet Beams Produced from Vacuum Electrospray. J. Surf. Anal. 2014, 20, 171–176.
88. Camera sensors explained. Canon-europe.com. https://www.canon-europe.com/pro/infobank/image-sensors-explained/ (accessed 2024-06-03).
89. Damjanovski, V. CCTV: From Light to Pixels, 3rd ed.; Butterworth-Heinemann: Oxford, 2013.
90. Photokonnexion. Definition: Photosite; Photosites; Photo-site; (occ. pixelsite). https://www.photokonnexion.com/definition-photosite/ (accessed 2024-06-03).
91. Zhang, L.; Jin, Y.; Lin, L.; Li, J.; Du, Y. The Comparison of CCD and CMOS Image Sensors. In International Conference on Optical Instruments and Technology 2008, Proceedings of SPIE 2008, Beijing, China, 2009.
92. Sander, B.; Golas, M. M.; Stark, H. Advantages of CCD Detectors for De Novo Three-Dimensional Structure Determination in Single-Particle Electron Microscopy. J. Struct. Biol. 2005, 151, 92–105.
93. Overview of CCD Detectors. Hawaii.edu. https://starlink.eao.hawaii.edu/docs/sc5.htx/sc5se4.html (accessed 2024-06-05).
94. Understanding the digital image sensor - LUCID vision labs. LUCID Vision Labs - Modern Machine Vision Cameras. https://thinklucid.com/tech-briefs/understanding-digital-image-sensors/ (accessed 2024-06-05).
95. Litwiller, D. CCD vs. CMOS: Facts and Fiction. Photonics Spectra 2001, 35, 154-158.
96. Waltham, N. CCD and CMOS sensors. In Observing Photons in Space.; Huber, M.C.E., Pauluhn, A., Culhane, J.L., Timothy, J.G., Wilhelm, K., Zehnder, A. Eds.; Springer: New York, NY, 2013; pp 423-442.
97. Cadence PCB Solutions. CMOS power amplifier. Cadence.com. https://resources.pcb.cadence.com/blog/2023-cmos-power-amplifier (accessed 2024- 06- 05).
98. Protein structure. Nature.com. https://www.nature.com/scitable/topicpage/protein-structure-14122136/ (accessed 2024-06-19).
99. Branden, C. I.; Tooze, J. Introduction to Protein Structure, 2nd ed.; Garland Science: London, England, 2012.
100. Lehninger, A. L.; Cox, M.; Nelson, D. L. Lehninger Principles of Biochemistry, 4th ed.; Palgrave Macmillan: Basingstoke, England, 2004.
101. Berg, J. M.; Tymoczko, J. L.; Stryer, L. Biochemistry, 5th ed.; W. H. Freeman and Company, New York, USA, 2002.
102. Structure Prediction Flowchart. Protein. Edu.tw. http://juang.bst.ntu.edu.tw/BCbasics/Protein1.htm (accessed 2024-06-19).
103. Finkelstein, A. V.; Gutin, A. M.; Badretdinov, A. Y. Perfect Temperature for Protein Structure Prediction and Folding. Proteins 1995, 23, 151–162.
104. Sogbein, O. O.; Simmons, D. A.; Konermann, L. Effects of pH on the Kinetic Reaction. J. Am. Soc. Mass Spectrom. 2000, 11, 312–319.
105. Masson, P.; Lushchekina, S. Conformational Stability and Denaturation Processes of Proteins Investigated by Electrophoresis under Extreme Conditions. Molecules 2022, 27, 6861.
106. Liu, H.-L.; Hsu, J.-P. Recent Developments in Structural Proteomics for Protein Structure Determination. Proteomics 2005, 5, 2056–2068.
107. Mass Spectrometry of Proteins and Peptides: Methods and Protocols, Second Edition, 2nd ed.; Lipton, M. S., Paša-Tolic, L., Eds.; Humana Press: Totowa, NJ, 2008.
108. Jayathirtha, M.; Dupree, E. J.; Manzoor, Z.; Larose, B.; Sechrist, Z.; Neagu, A.-N.; Petre, B. A.; Darie, C. C. Mass Spectrometric (MS) Analysis of Proteins and Peptides. Curr. Protein Pept. Sci. 2021, 22, 92–120.
109. Karas, M.; Hillenkamp, F. Laser Desorption Ionization of Proteins with Molecular Masses Exceeding 10,000 Daltons. Anal. Chem. 1988, 60, 2299–2301.
110. Meng, C. K.; Mann, M.; Fenn, J. B. Of Protons or Proteins - “A Beam’s a Beam for a’’ That.″ (O.S. Burns). Zeitschrift für Phys. D Atoms, Mol. Clust. 1988, 10, 361– 368.
111. Tanaka, K.; Waki, H.; Ido, Y.; Akita, S.; Yoshida, Y.; Yoshida, T.; Matsuo, T. Protein and Polymer Analyses up to m/z 100 000 by Laser Ionization Time‐of‐flight Mass Spectrometry. Rapid Commun. Mass Spectrom. 1988, 2, 151–153.
112. Nadler, W. M.; Waidelich, D.; Kerner, A.; Hanke, S.; Berg, R.; Trumpp, A.; Rösli, C. MALDI versus ESI: The Impact of the Ion Source on Peptide Identification. J. Proteome Res. 2017, 16, 1207–1215.
113. Fitzgerald, M. C. A Solid Sample Preparation Method That Reduces Signal Suppression Effects in the MALDI Analysis of Peptides. Anal. Chem. 2001, 73, 625–631.
114. Singhal, N.; Kumar, M.; Kanaujia, P. K.; Virdi, J. S. MALDI-TOF Mass Spectrometry: An Emerging Technology for Microbial Identification and Diagnosis. Front. Microbiol. 2015, 6, 791.
115. McIver, R. T., Jr; Li, Y.; Hunter, R. L. High-Resolution Laser Desorption Mass Spectrometry of Peptides and Small Proteins. Proc. Natl. Acad. Sci. U. S. A. 1994, 91, 4801–4805.
116. Harvey, D. J. Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry of Carbohydrates. Mass Spectrom. Rev. 1999, 18, 349–450.
117. Clark, A. E.; Kaleta, E. J.; Arora, A.; Wolk, D. M. Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry: A Fundamental Shift in the Routine Practice of Clinical Microbiology. Clin. Microbiol. Rev. 2013, 26, 547–603.
118. Susa, A. C.; Xia, Z.; Williams, E. R. Native Mass Spectrometry from Common Buffers with Salts That Mimic the Extracellular Environment. Angew. Chem. Weinheim Bergstr. Ger. 2017, 129, 8020–8023.
119. Sterling, H. J.; Batchelor, J. D.; Wemmer, D. E.; Williams, E. R. Effects of Buffer Loading for Electrospray Ionization Mass Spectrometry of a Noncovalent Protein Complex That Requires High Concentrations of Essential Salts. J. Am. Soc. Mass Spectrom. 2010, 21, 1045–1049.
120. Honarvar, E.; Venter, A. R. Comparing the Effects of Additives on Protein Analysis between Desorption Electrospray (DESI) and Electrospray Ionization (ESI). J. Am. Soc. Mass Spectrom. 2018, 29, 2443–2455.
121. Ho, C. S.; Lam, C. W. K.; Chan, M. H. M.; Cheung, R. C. K.; Law, L. K.; Lit, L. C. W.; Ng, K. F.; Suen, M. W. M.; Tai, H. L. Electrospray Ionisation Mass Spectrometry: Principles and Clinical Applications. Clin. Biochem. Rev. 2003, 24, 3–12.
122. Van Berkel, G. J.; Kertesz, V. Using the Electrochemistry of the Electrospray Ion Source. Anal. Chem. 2007, 79, 5510–5520.
123. Van Berkel, G. J.; McLuckey, S. A.; Glish, G. L. Electrochemical Origin of Radical Cations Observed in Electrospray Ionization Mass Spectra. Anal. Chem. 1992, 64, 1586– 1593.
124. Jackson, G. S.; Enke, C. G. Electrical Equivalence of Electrospray Ionization with Conducting and Nonconducting Needles. Anal. Chem. 1999, 71, 3777–3784.
125. Tang, K.; Page, J. S.; Smith, R. D. Charge Competition and the Linear Dynamic Range of Detection in Electrospray Ionization Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2004, 15, 1416–1423.
126. Kang, Y.; Schneider, B. B.; Bedford, L.; Covey, T. R. Design Characteristics to Eliminate the Need for Parameter Optimization in Nanoflow ESI-MS. J. Am. Soc. Mass Spectrom. 2019, 30, 2347–2357.
127. Van Berkel, G. J.; Asano, K. G.; Schnier, P. D. Electrochemical Processes in a Wire-in-a-Capillary Bulk-Loaded, Nano-Electrospray Emitter. J. Am. Soc. Mass Spectrom. 2001, 12, 853–862.
128. Cao, W.; Cheng, S.; Yang, J.; Feng, J.; Zhang, W.; Li, Z.; Chen, Q.; Xia, Y.; Ouyang, Z.; Ma, X. Large-Scale Lipid Analysis with C=C Location and Sn-Position Isomer Resolving Power. Nat. Commun. 2020, 11, 375.
129. Bushey, J. M.; Kaplan, D. A.; Danell, R. M.; Glish, G. L. Pulsed Nano-Electrospray Ionization: Characterization of Temporal Response and Implementation with a Flared Inlet Capillary. Instrum. Sci. Technol. 2009, 37, 257–273.
130. Chetwani, N.; Cassou, C. A.; Go, D. B.; Chang, H.-C. Frequency Dependence of Alternating Current Electrospray Ionization Mass Spectrometry. Anal. Chem. 2011, 83, 3017–3023.
131. Sarver, S. A.; Chetwani, N.; Dovichi, N. J.; Go, D. B.; Gartner, C. A. A Comparison of Alternating Current and Direct Current Electrospray Ionization for Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2014, 25, 524–529.
132. Chen, H.-P.; Li, C.-H.; Chang, Y.; Hsieh, W.-S.; Wang, S.-C. Effect of Solution Acidity on Cytochrome c Conformations of Alternating Current Electrospray Ionization Mass Spectrometry. J. Chin. Chem. Soc. 2023, 70, 1348–1354.
133. Wei, Z.; Xiong, X.; Guo, C.; Si, X.; Zhao, Y.; He, M.; Yang, C.; Xu, W.; Tang, F.; Fang, X.; Zhang, S.; Zhang, X. Pulsed Direct Current Electrospray: Enabling Systematic Analysis of Small Volume Sample by Boosting Sample Economy. Anal. Chem. 2015, 87, 11242–11248.
134. Chetwani, N.; Cassou, C. A.; Go, D. B.; Chang, H.-C. High-Frequency AC Electrospray Ionization Source for Mass Spectrometry of Biomolecules. J. Am. Soc. Mass Spectrom. 2010, 21, 1852–1856.
135. Gañán-Calvo, A. M.; López-Herrera, J. M.; Herrada, M. A.; Ramos, A.; Montanero, J. M. Review on the Physics of Electrospray: From Electrokinetics to the Operating Conditions of Single and Coaxial Taylor Cone-Jets, and AC Electrospray. J. Aerosol Sci. 2018, 125, 32–56.
136. Kaltashov, I. A.; Abzalimov, R. R. Do Ionic Charges in ESI MS Provide Useful Information on Macromolecular Structure? J. Am. Soc. Mass Spectrom. 2008, 19, 1239– 1246.
137. Konermann, L. Addressing a Common Misconception: Ammonium Acetate as Neutral pH “Buffer” for Native Electrospray Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2017, 28, 1827–1835.
138. Susa, A. C.; Xia, Z.; Tang, H. Y. H.; Tainer, J. A.; Williams, E. R. Charging of Proteins in Native Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2017, 28, 332–340.
139. Konermann, L.; Liu, Z.; Haidar, Y.; Willans, M. J.; Bainbridge, N. A. On the Chemistry of Aqueous Ammonium Acetate Droplets during Native Electrospray Ionization Mass Spectrometry. Anal. Chem. 2023, 95, 13957–13966.
140. Marginean, I.; Kelly, R. T.; Moore, R. J.; Prior, D. C.; LaMarche, B. L.; Tang, K.; Smith, R. D. Selection of the Optimum Electrospray Voltage for Gradient Elution LC-MS Measurements. J. Am. Soc. Mass Spectrom. 2009, 20, 682–688.
141. Valaskovic, G. A.; Murphy, J. P., 3rd; Lee, M. S. Automated Orthogonal Control System for Electrospray Ionization. J. Am. Soc. Mass Spectrom. 2004, 15, 1201–1215.
142. Stachewicz, U.; Dijksman, J. F.; Burdinski, D.; Yurteri, C. U.; Marijnissen, J. C. M. Relaxation Times in Single Event Electrospraying Controlled by Nozzle Front Surface Modification. Langmuir 2009, 25, 2540–2549.
143. Li, H.-I.; Prabhu, G. R. D.; Buchowiecki, K.; Urban, P. L. High-Speed Schlieren Imaging of Vapor Formation in Electrospray Plume. J. Am. Soc. Mass Spectrom. 2024, 35, 244– 254.
144. Zeleny, J. Instability of Electrified Liquid Surfaces. Phys. Rev. 1917, 10, 1–6.
145. Kim, H.-H.; Kim, J.-H.; Ogata, A. Time-Resolved High-Speed Camera Observation of Electrospray. J. Aerosol Sci. 2011, 42, 249–263.
146. Wang, Q.; Wang, Z.; Yang, S.; Li, B.; Xu, H.; Yu, K.; Wang, J. Experimental Study on Electrohydrodynamic Atomization (EHDA) in Stable Cone-Jet with Middle Viscous and Low Conductive Liquid. Exp. Therm. Fluid Sci. 2021, 121, 110260.
147. Hsu, C.-Y.; Prabhu, G. R. D.; Chang, C.-H.; Hsu, P.-C.; Buchowiecki, K.; Urban, P. L. Are Most Micrometer Droplets (>10 μm) Wasted in Electrospray Ionization? An Insight from Real-Time High-Speed Imaging. Anal. Chem. 2023, 95, 14702–14709
148. Ochirov, O.; Urban, P. L. Spontaneous Recycling of Electrosprayed Sample by Retrograde Motion of Microdroplets. J. Am. Soc. Mass Spectrom. 2024, 35, 631–635.
149. Chang, C.-H.; Urban, P. L. Does the Formation of a Taylor Cone in a Pulsating Electrospray Directly Impact Mass Spectrometry Signals? ACS Omega 2024, 9, 43211– 43218.
150. Nemes, P.; Marginean, I.; Vertes, A. Spraying Mode Effect on Droplet Formation and Ion Chemistry in Electrosprays. Anal. Chem. 2007, 79, 3105–3116.
151. Jing, Y.; Xie, M.; Wang, C.; Li, J.; Gao, W.; Yu, J.; Tang, K. In Searching of Optimum Electrospray Ionization Using Both Spray Image and Electric Current Measurement. Int. J. Mass Spectrom. 2023, 492, 117113.
152. Han, Z.; Hishida, S.; Omata, N.; Matsuda, T.; Komori, R.; Chen, L. C. Feedback Control of Electrospray with and without an External Liquid Pump Using the Spray Current and the Apex Angle of a Taylor Cone for ESI-MS. Anal. Chem. 2023, 95, 10744–10751.
153. Marginean, I.; Parvin, L.; Heffernan, L.; Vertes, A. Flexing the Electrified Meniscus: The Birth of a Jet in Electrosprays. Anal. Chem. 2004, 76, 4202–4207.
154. Pei, J.; Hsu, C.-C.; Wang, Y.; Yu, K. Corona Discharge-Induced Reduction of Quinones in Negative Electrospray Ionization Mass Spectrometry. RSC Adv. 2017, 7, 43540–43545.
155. Witkowski, D.; Łysko, J.; Karczemska, A. Joule Heating Effects in Capillary Electrophoresis—Designing Electrophoretic Microchips. J. Achiev. Mater. Manuf. Eng. 2009, 37, 592–599.
156. Xuan, X.; Sinton, D.; Li, D. Thermal End Effects on Electroosmotic Flow in a Capillary. Int. J. Heat Mass Transf. 2004, 47, 3145–3157.
157. Zhao, F.; Matt, S. M.; Bu, J.; Rehrauer, O. G.; Ben-Amotz, D.; McLuckey, S. A. Joule Heating and Thermal Denaturation of Proteins in Nano-ESI Theta Tips. J. Am. Soc. Mass Spectrom. 2017, 28, 2001–2010.
158. Marginean, I.; Kelly, R. T.; Page, J. S.; Tang, K.; Smith, R. D. Electrospray Characteristic Curves: In Pursuit of Improved Performance in the Nanoflow Regime. Anal. Chem. 2007, 79, 8030–8036.
159. Jordan, J. S.; Miller, Z. M.; Harper, C. C.; Hanozin, E.; Williams, E. R. Lighting up at High Potential: Effects of Voltage and Emitter Size in Nanoelectrospray Ionization. J. Am. Soc. Mass Spectrom. 2023, 34, 1186–1195.
160. Marginean, I.; Nemes, P.; Parvin, L.; Vertes, A. How Much Charge Is There on a Pulsating Taylor Cone? Appl. Phys. Lett. 2006, 89, 064104.
161. Blades, A. T.; Ikonomou, M. G.; Kebarle, P. Mechanism of Electrospray Mass Spectrometry Electrospray as an Electrolysis Cell. Anal. Chem. 1991, 63, 2109–2114.
162. Van Berkel, G. J.; Zhou, F. Characterization of an Electrospray Ion Source as a Controlled-Current Electrolytic Cell. Anal. Chem. 1995, 67, 2916–2923.
163. Karancsi, T.; Slégel, P.; Novák, L.; Pirok, G.; Kovács, P.; Vékey, K. Unusual Behaviour of Some Isochromene and Benzofuran Derivatives during Electrospray Ionization. Rapid Commun. Mass Spectrom. 1997, 11, 81–84.
164. de la Mora, J. F.; Van Berkel, G. J.; Enke, C. G.; Cole, R. B.; Martinez-Sanchez. M.; Fenn, J. B. Electrochemical Processes in Electrospray Ionization Mass Spectrometry. J. Mass Spectrom. 2000, 35, 939–952.
165. Kertesz, V.; Van Berkel, G. J. Minimizing Analyte Electrolysis in an Electrospray Emitter. J. Mass Spectrom. 2001, 36, 204–210.
166. Plattner, S.; Erb, R.; Chervet, J. P.; Oberacher H. Ascorbic Acid for Homogenous Redox Buffering in Electrospray Ionization–Mass Spectrometry. Anal. Bioanal. Chem. 2012, 404, 1571–1579.
167. Pei, J.; Zhou, X.; Wang, X.; Huang, G. Alleviation of Electrochemical Oxidation for Peptides and Proteins in Electrospray Ionization: Obtaining More Accurate Mass Spectra with Induced High Voltage. Anal. Chem. 2015, 87, 2727–2733.
168. Lübbert, C.; Peukert, W. How to Avoid Interfering Electrochemical Reactions in ESI-MS Analysis. J. Mass Spectrom. 2019, 54, 301–310.
169. Han, Z.; Komori, R.; Suzuki, R.; Omata, N.; Matsuda, T.; Hishida, S.; Shuuhei, T.; Chen, L. C. Bipolar Electrospray from Electrodeless Emitters for ESI without Electrochemical Reactions in the Sprayer. J. Am. Soc. Mass Spectrom. 2023, 34, 728–736.
170. Keim, R. Low-Pass Filter a PWM Signal Into an Analog Voltage. All About Circuits. https://www.allaboutcircuits.com/technical-articles/low-pass-filter-a-pwm-signal-into-an-analog-voltage/. (accessed 2025-01-20).
171. Hoffman, N. M.; Gotlib, Z. P.; Opačić, B.; Huntley, A. P.; Moon, A. M.; Donahoe, K. E. G.; Brabeck, G. F.; Reilly, P. T. A. Digital Waveform Technology and the Next Generation of Mass Spectrometers. J. Am. Soc. Mass Spectrom. 2018, 29, 331–341.
172. Obe, F. O.; Chakravorty, S.; Groetsema, E.; Collings, B. A.; Hager, J. W.; Reilly, P. T. A. Experimental Validation of the Digital Tandem Mass Filter. J. Am. Soc. Mass Spectrom. 2023, 34, 154–160.
173. Hu, R.; Gundlach-Graham, A. Experimental Investigation of a Digital Quadrupole Inductively Coupled Plasma Mass Spectrometer for Elemental Analysis. J. Am. Soc. Mass Spectrom. 2024, 35, 1838–1845.
174. Marginean, I.; Nemes, P.; Vertes, A. Astable Regime in Electrosprays. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 2007, 76, 026320.
175. Li, Y.; Bouza, M.; Wu, C.; Guo, H.; Huang, D.; Doron, G.; Temenoff, J. S.; Stecenko, A. A.; Wang, Z. L.; Fernández, F. M. Sub-Nanoliter Metabolomics via Mass Spectrometry to Characterize Volume-Limited Samples. Nat. Commun. 2020, 11, 5625.
176. Vallejo, D. D.; Corstvet, J. L.; Fernández, F. M. Triboelectric Nanogenerators: Low-Cost Power Supplies for Improved Electrospray Ionization. Int. J. Mass Spectrom. 2024, 495, 117167.