Ambient Ionization Mass Spectrometry in Life Sciences: Principles and Applications

Ambient Ionization Mass Spectrometry in Life Sciences: Principles and Applications is a systematic introduction to this rapidly expanding area of study. Underlying principles of each technique are explained in detail, along with discussions on their applications across life science disciplines. Ambient ionization has recently emerged as one of the hottest and fastest growing topics in mass spectrometry, hence this book is not just for analysts and researchers who use and study mass spectrometry. This volume would be of interest to anyone who works in or studies analytical chemistry, omics sciences (including metabolomics), pharmacokinetics, forensic science or drug analysis.

• Covers the most up-to-date techniques, including DART, DCBI, DESI, PESI, PSI, REIMS and laser-based ambient ionization
• Includes easy-to-understand pros and cons of each ionization technique to aid in decision-making
• Provides plentiful examples of life science applications

• Language: English
• Publisher: Elsevier Science
• Release date: Nov 6, 2019
• ISBN: 9780128172216

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Ambient Ionization Mass Spectrometry in Life Sciences

Principles and Applications

Edited by

Kei Zaitsu

In Vivo Real-time Omics Laboratory, Institute for Advanced Research, Nagoya University, Nagoya, Japan

Table of Contents

Cover image

Title page

Copyright

Contributors

Preface

Acknowledgments

Chapter 1. Introduction to ambient ionization mass spectrometry

1.1. Definition of ambient ionization and classification

1.2. Overview of ambient ionization methods

1.3. Objectives of this book and brief explanation of each chapter

Chapter 2. Direct analysis in real time

2.1. Introduction

2.2. DART ion source

2.3. Ionization processes in DART

2.4. Technical applications for improving DART performance/sensitivity

2.5. Applications using argon gas: atmospheric pressure dark current argon discharge ionization with comparable performance of helium DART

Chapter 3. Desorption corona beam ionization

3.1. Introduction

3.2. Principles of DCBI

3.3. Features of DCBI

3.4. Applications of DCBI

3.5. Summary

Chapter 4. DESI-based imaging mass spectrometry in forensic science and clinical diagnosis

4.1. Principle of DESI

4.2. Application I: forensic science

4.3. Application II: metabolite imaging for clinical diagnosis

4.4. Application III: reactive DESI

4.5. Conclusion and perspective

Chapter 5. Ambient laser-based mass spectrometry analysis methods: a survey of core technologies and reported applications

5.1. Introduction

5.2. ELDI-MS

5.3. LAESI-MS

5.4. IR-MALDESI-MS

5.5. IR-LADESI-MS

5.6. LDSPI-MS

5.7. AIRLAB-MS

5.8. LEMS

5.9. AP-fsLDI-MS

5.10. LA-FAPA-MS

5.11. LA-APCI-MS

5.12. PAMLDI-MS

5.13. LIAD-ESI-MS

5.14. LIAD-APCI-MS

5.15. LIAD-APPI-MS

5.16. PIR-LAESI-MS

5.17. PIRL-MS

5.18. SpiderMass

Chapter 6. Probe electrospray ionization/mass spectrometry and its applications to the life sciences

6.1. Principle of probe electrospray ionization and the development of instruments

6.2. Applications of PESI to life sciences

Chapter 7. Design and construction of paper-spray ionization/mass spectrometry

7.1. Introduction

7.2. Paper spray ionization/mass spectrometry

7.3. Modifications

7.4. Applications

7.5. Future perspectives

Chapter 8. Rapid evaporative ionization mass spectrometry

8.1. Introduction

8.2. REIMS instrumentation

8.3. REIMS spectra and data handling

8.4. Applications

8.5. Summary

Index

Copyright

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Notices

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.

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Contributors

Emma Bluemke

Techna Institute for the Advancement of Technology for Health, University Health Network, Toronto, ON, Canada

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

Present address: Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Old Road Campus Research Building, Oxford, United Kingdom

Cheng-Huang Lin,     Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan

Yea-Wenn Liou,     Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan

Tasuku Murata,     MS Business Unit, Life Science Business Department, Analytical & Measuring Instruments Division, Shimadzu Corporation, Nakagyo-ku, Kyoto, Japan

Thanai Paxton,     Nihon Waters K.K., Shinagawa-ku, Tokyo, Japan

Kanako Sekimoto,     Yokohama City University, Graduate School of Nanobioscience, Yokohama, Japan

Makoto Suematsu,     Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan

Yuki Sugiura,     Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan

Eiji Sugiyama,     Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan

Wenjian Sun,     Shimadzu Research Laboratory (Shanghai) Co., Ltd., Pudong New District, Shanghai, China

Alessandra Tata,     Techna Institute for the Advancement of Technology for Health, University Health Network, Toronto, ON, Canada

Michael Woolman

Techna Institute for the Advancement of Technology for Health, University Health Network, Toronto, ON, Canada

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

Kei Zaitsu,     In Vivo Real-time Omics Laboratory, Institute for Advanced Research, Nagoya University, Chikusa-ku, Nagoya, Japan

Arash Zarrine-Afsar

Techna Institute for the Advancement of Technology for Health, University Health Network, Toronto, ON, Canada

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

Department of Surgery, University of Toronto, Toronto, ON, Canada

Keenan Research Center for Biomedical Science & the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada

Preface

Approximately 20   years ago, the two core ionization methods—desorption electrospray ionization (DESI) and direct analysis in real time (DART)—opened the door to a new mass spectrometric field: ambient ionization. Since then, this field has grown rapidly. To date, numerous ambient ionization techniques have emerged, although this situation appears to be utterly chaotic, at least to me. Almost all analytical chemists and biologists who apply mass spectrometry in their research, including me, know the importance and convenience of ambient ionization techniques. However, most encounter difficulty understanding the techniques A to Z because of the vastness of the field.

In 2016, I received an email from Katy, who is an Elsevier acquisition editor. She provided me the opportunity to edit and write a book on ambient ionization. Approximately 3   years have passed since I met her at ASMS 2016. We have developed this book on ambient ionization mass spectrometry with great assistance from world-renowned experts in ambient ionization techniques. In this book, we have attempted to make it easy for readers to systematically grasp the point of ambient ionization techniques. In particular, it is necessary for us to understand the critical applications of ambient ionization techniques in the life sciences because many such techniques can potentially become essential tools in the life sciences. Fortunately, world-renowned experts in ambient ionization techniques provide the latest information and analytical/technical applications on selected topics, which makes the book highly valuable.

I hope this book will be helpful for readers to not only understand ambient ionization techniques and their applications in the life sciences but also to become deeply interested in ambient ionization techniques.

Kei Zaitsu

Acknowledgments

I would like to dedicate this book to my loving wife, Miwa, and our sons, Yu, Sho, and Kou. Moreover, I would like to express my gratitude to the continuous support from my loving parents, my father Nobuyuki and my mother Yayoi.

I would like to offer my special thanks to my mentor, Dr. Hitoshi Tsuchihashi, and my best comrades, Dr. Y. Hayashi and Mr. T. Murata.

Lastly, I am deeply grateful to all the people who have helped me with the preparation of this book.

Chapter 1

Introduction to ambient ionization mass spectrometry

Kei Zaitsu     In Vivo Real-time Omics Laboratory, Institute for Advanced Research, Nagoya University, Chikusa-ku, Nagoya, Japan

Abstract

Because the number of studies on ambient ionization techniques and their applications continues to increase, especially with respect to the life sciences, a systematic understanding of numerous emerging ambient ionization techniques becomes necessary. In this chapter, we briefly outline ambient ionization techniques to improve readability for readers. First, we discuss the definition of ambient ionization by referring to previously reported papers on this topic and then classify numerous ambient ionization methods into six groups on the basis of the principle of each method, as follows: (1) spray desorption/ionization-based methods; (2) laser ablation/desorption-based methods; (3) thermal desorption-based methods; (4) plasma-based methods; (5) substrate-based methods; and (6) hybrid/other methods. According to such classification, we briefly explain the mechanisms and features of the representative methods in each group. We lastly present the objective of this book and provide a brief explanation of each chapter; additionally, we introduce some useful review articles on ambient ionization techniques for reference.

Keywords

Ambient ionization; Hybrid/other methods; Laser ablation/desorption-based methods; Plasma-based methods; Spray desorption/ionization-based methods; Substrate-based methods; Thermal desorption–based methods

1.1 Definition of ambient ionization and classification

1.2 Overview of ambient ionization methods

1.2.1 Spray desorption/ionization-based method

1.2.2 Laser ablation/desorption-based methods

1.2.3 Thermal desorption–based methods

1.2.4 Plasma-based methods

1.2.5 Substrate-based methods

1.2.6 Hybrid/other methods

1.3 Objectives of this book and brief explanation of each chapter

References

1.1. Definition of ambient ionization and classification

In a broad sense, ambient ionization is understood as the ionization method under atmospheric pressure, which does not require tedious sample pretreatment, though the definition of ambient ionization differs slightly among researchers. Indeed, Ifa et al. proposed a working definition of ambient ionization as "ionization occurs externally to the mass spectrometer and that ions are introduced into the mass spectrometer" [1]. Here, electrospray ionization (ESI), atmospheric-pressure chemical ionization (APCI), and atmospheric-pressure matrix-assisted laser desorption ionization (AP-MALDI) are excluded by this definition, although the scientific reasoning for excluding these methods is unclear. By contrast, Huang et al. defined ambient ionization mass spectrometry as a set of useful techniques for the analysis of samples under open-air conditions, and it allows direct, rapid, real-time, and high-throughput analyses with little or no sample pretreatment [2].

More recently, Javanshad and Venter have updated the definition of ambient ionization from no sample preparation to sample preparation proximal and in real time with the ionization and analysis step; that is, they have defined ambient ionization as a form of ionization where sample preparation takes place in real-time and proximal to the ionization and during the analysis of analytes [3].

Among the aforementioned definitions, that by Huang et al. may be more intuitive than the others because some ambient ionization techniques require little sample pretreatment (e.g., solid-phase microextraction (SPME), solvent addition, etc.); thus, in the present chapter, we define the ambient ionization technique as an ionization technique for the analysis under open-air conditions allowing direct analysis of samples with little or no sample preparation, consistent with the definition by Huang et al.

To date, more than 90 ambient ionization methods have been reported, although no exact method exists for classifying them because of their variation; thus, different researchers have proposed various categorization schemes [2–4].

On the basis of the principles of ionization, Huang et al. sorted ambient ionization methods into three main groups: (1) direct ionization methods, where analytes are directly ionized in a high electric field; (2) direct desorption/ionization methods, where analytes are desorbed/ionized by charged species such as electrosprayed droplets; and (3) two-step ionization methods, where analytes are desorbed/ablated using techniques such as laser irradiation, followed by ionization via postionization techniques [2].

Venter et al. demonstrated flowergrams [4], which are visually easy for readers to understand, to classify ambient ionization methods on the basis of the ionization mechanism and summary of the major classes of ambient ionization methods, where the methods are categorized on the basis of spray desorption, laser ablation, thermal desorption, liquid microjunction and substrate spray [3].

Harris et al. surveyed previous reports on ambient ionization and then adopted two-step grouping to categorize the reports [5]; they first categorized their selected references on the basis of technique principles and then assigned specific applications to each reference. Ambient ionization techniques were consequently grouped into the following categories: (1) spray- and solid-liquid extraction-based techniques that involve ESI or similar methods; (2) direct- and alternating-current plasma-based techniques involving chemical ionization (CI) mechanisms; (3) plasma-based techniques involving chemical sputtering-like desorption steps followed by CI; (4) multimode techniques; (5) laser desorption/ablation methods; (6) acoustic desorption methods; and (7) other techniques that do not fit into one of the aforementioned categories. Following technique-centric categorization, each reference is tagged with a specific application name as follows: (1) environmental samples; (2) food flavor and fragrances; (3) forensics; (4) homeland security; (5) molecular imaging; (6) pharmaceuticals; (7) oil, polymers, and additives; or (8) bioanalysis (e.g., clinical, metabolomics, or proteomics).

Van Berkel et al. sorted the vast array of ambient techniques into a few categories based on the approaches for surface sampling and ionization [6]: (1) thermal desorption/ionization; (2) laser desorption (ablation)/ionization; (3) atmospheric-pressure laser desorption (ablation) with secondary ionization (AP-LD/SI); (4) atmospheric-pressure matrix-assisted laser desorption ionization (AP-MALDI); (5) liquid and gas jet desorption/ionization; and (6) liquid extraction surface-sampling probe/ionization.

These reports are useful for understanding and overviewing ambient ionization methods; however, variants of ambient ionization methods such as hybrid-type and/or methods based on new concepts have been increasing. Thus, in this chapter, we more simply categorize the already-reported ambient ionization methods into the following six groups on the basis of their basic principles: (1) spray desorption/ionization-based methods; (2) laser ablation/desorption-based methods; (3) thermal desorption-based methods; (4) plasma-based methods; (5) substrate-based methods; and (6) hybrid/other methods.

Fig. 1.1 shows a conceptual schematic of ambient ionization; analytes are directly desorbed/ionized by a high-speed jet of ESI spray and a high-voltage impression via a substrate, whereas analytes are desorbed/ablated by laser irradiation, thermal energy, plasma, and other techniques such as acoustic irradiation, followed by ionization via a postionization method.

Figure 1.1 Conceptual schematic of ambient ionization techniques.

On the basis of this categorization concept, we classify the previously reported 93 ambient ionization methods into their respective groups, as shown in Table 1.1, where the classification name, acronym for each ionization method, technical name, and references regarding each ionization method are presented. Following such classification, we will outline the characteristics of each class in the next section.

1.2. Overview of ambient ionization methods

1.2.1. Spray desorption/ionization-based method

We classify desorption electrospray ionization (DESI) [7], DESI-related methods such as EADESI (EA-DESI) [10], LADESI (LA-DESI) [11], and extractive electrospray ionization (EESI) [12], air flow-assisted ionization (AFAI) [15], easy ambient sonic-spray ionization (EASI) [19], desorption electrospray/metastable-induced ionization (DEMI) [18], desorption ionization by charge exchange (DICE) [17], electrostatic spray ionization (ESTASI) [23], and similar methods into the group of spray desorption/ionization-based methods. The classification of ambient ionization methods is listed in Table 1.1.

DESI is one of the best-known ambient ionization techniques, as is direct analysis in real time (DART) [65]. DESI was developed by Cooks and coworkers in 2004 and it uses an electrosprayed jet of charged solvent droplets; analytes are ionized through interactions of the charged droplets with the desorbed analytes, as shown in Fig. 1.2. Notably, nanospray desorption electrospray ionization (nano-DESI) is classified into a different category in this chapter because the sampling and ionization principles of nano-DESI differ from those of DESI, as discussed later [111]. In DESI, ion suppression is reduced because analytes are ionized by such interactions, and the mass spectra obtained from DESI are similar to normal ESI mass spectra, demonstrating that the ionization principle of DESI is based on ESI. DESI has had a high impact not only in mass spectrometry but also in medical/pharmaceutical fields because of its strong applicability to imaging mass spectrometry; thus, applications and modified methods related to DESI have been increasing. In particular, matrix-free imaging mass spectrometry is achieved with DESI, which is advantageous in comparison with MALDI-based imaging mass spectrometry. More detailed information and applications of DESI are described in Chapter 4.

Table 1.1

Figure 1.2 Schematic of the ionization mechanisms of DESI.

DESI and other desorption methods such as EASI, DEMI, and DICE are applicable only to solid samples because a liquid layer is necessary to ionize analytes with these methods. Dried spots on paper or other surfaces can also be used with these methods, although analyzing intact liquid samples with these methods is difficult.

By contrast, liquid-DESI and EESI have been improved to accommodate liquid samples [9,12]. EESI uses two separate sprayers, where one nebulizes the sample solution and the other produces an electrosprayed jet, and liquid–liquid interactions between the sample solution and the electrosprayed jet occur, followed by ionization of analytes in the liquid sample in the space in front of a mass spectrometer inlet. Chen in Zenobi group achieved sampling of living objects by combining EESI with a neutral gas desorption method [13,14], where the surface of human skin was directly analyzed in vivo.

1.2.2. Laser ablation/desorption-based methods

We classify electrospray-assisted laser desorption ionization (ELDI) [42,43], laser-ablation electrospray ionization (LAESI) [28,29], picosecond infrared laser-LAESI (PIRL-LAESI) [30–32], matrix-assisted laser desorption electrospray ionization (MALDESI) [44], charge-assisted laser desorption/ionization (CALDI) [50], laser-induced acoustic desorption electrospray ionization (LIAD-ESI) [51], and remote infrared matrix-assisted laser desorption ionization (Remote IR-MALDI, SpiderMass) [56,57] into the group of laser ablation/desorption-based methods. Because we provide more detailed information about laser-based ambient ionization methods in Chapter 5, an overview of the methods is presented in this section.

In general, the ionization process of the laser ablation/desorption-based ambient ionization methods is as follows: analytes are first ablated or desorbed under laser irradiation, followed by being ionized with postionization techniques such as electrospray plume. There are, however, several different technical terms (e.g., ELDI, LAESI, PIRL-LAESI, MALDESI, and IR-MALDESI) are found in the literature, which often confuses readers. Thus, Liu et al. have proposed that these techniques using various types of lasers (ultraviolet (UV) or infrared (IR) wavelength) for ablation/desorption and different postionization techniques (e.g., electrospray, sonic spray, electrosonic spray, desorption electrospray) can be merged under the term laser desorption spray post-ionization (LDSPI) [47].

Among the LDSPI methods, ELDI and LAESI are well known; a schematic of ELDI and LAESI is shown in Fig. 1.3. The ionization mechanism of ELDI and LAESI, which are two-step ionization techniques, differ from that of DESI. Unlike UV-MALDI and IR-MALDI, ELDI and LAESI do not require an external matrix because electrosprayed charged droplets ionize the ablated analytes, which are generated by laser irradiation.

ELDI was developed by Shiea and coworkers in 2005 [42]. A pulsed nitrogen laser of 337   nm, which is in the UV wavelength range, is used to ablate analytes, and the ablated particulates are ionized using electrospray plume. Shiea et al. succeeded in separating the desorption process from the ionization process.

Nemes and Vertes developed LAESI for in vivo and imaging mass spectrometry in 2007 [28]. This technique is now commercially available. As its name suggests, LAESI combines midinfrared laser ablation with ESI as a novel ionization source under atmospheric pressure. The use of a midinfrared laser enables the water in samples to act as a matrix because the asymmetric O–H stretching vibration is excited by such a laser, facilitating desorption of analytes in the samples. Postionization using electrospray plume enhances ionization of the ablated molecules, many of which are neutral. Thus, because of its postionization technique, LAESI shows higher sensitivity than AP IR-MALDI.

Figure 1.3 Schematic of the ionization mechanisms of ELDI/LAESI.

More recently, Arash and coworkers coupled picosecond infrared laser (PIRL) with ESI to improve LAESI, which led to PIR-LAESI [30–32]. Although the details of PIR-LAESI are described in Chapter 5, PIR-LAESI demonstrated a threefold higher lateral resolution compared with that of conventional LAESI with a nanosecond optical parametric oscillator source at comparable laser fluence.

Sampson in the Muddiman group proposed MALDESI [44], in which a matrix method is required for enhancement of the ionization efficiency, and they examined whether a matrix is required for laser desorption-based ionization. Consequently, they demonstrated that MALDESI is a hybrid mechanism of MALDI, ESI, and ELDI, following which can be still disputable to research. They also demonstrated IR-MALDESI, where a mid-IR laser is used for ablation of analytes [45,46].

Jorabchi et al. used a pulsed corona discharge technique as a postionization technique in conjunction with UV-laser desorption; this technique is termed CALDI [50] because droplet charging is responsible for the generation of ions rather than