Andrew M. EllisChristopher A. Mayhew

Proton Transfer Reaction Mass SpectrometryPrinciples and Applications

Proton TransferReaction MassSpectrometry

Proton TransferReaction MassSpectrometryPrinciples and Applications

ANDREW M. ELLIS

Department of Chemistry, University of Leicester, UK

CHRISTOPHER A. MAYHEW

School of Physics & Astronomy, University of Birmingham, UK

This edition first published 2014C© Andrew M. Ellis and Christopher A. Mayhew 2014

Registered officeJohn Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, United Kingdom

For details of our global editorial offices, for customer services and for information about how to apply for permission to reusethe copyright material in this book please see our website at www.wiley.com.

The right of the author to be identified as the author of this work has been asserted in accordance with the Copyright, Designsand Patents Act 1988.

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or byany means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs andPatents Act 1988, without the prior permission of the publisher.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available inelectronic books.

Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and productnames used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. Thepublisher is not associated with any product or vendor mentioned in this book.

Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book,they make no representations or warranties with respect to the accuracy or completeness of the contents of this book andspecifically disclaim any implied warranties of merchantability or fitness for a particular purpose. It is sold on the understandingthat the publisher is not engaged in rendering professional services and neither the publisher nor the author shall be liable fordamages arising herefrom. If professional advice or other expert assistance is required, the services of a competent professionalshould be sought.

The advice and strategies contained herein may not be suitable for every situation. In view of ongoing research, equipmentmodifications, changes in governmental regulations, and the constant flow of information relating to the use of experimentalreagents, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert orinstructions for each chemical, piece of equipment, reagent, or device for, among other things, any changes in the instructions orindication of usage and for added warnings and precautions. The fact that an organization or Website is referred to in this work asa citation and/or a potential source of further information does not mean that the author or the publisher endorses the informationthe organization or Website may provide or recommendations it may make. Further, readers should be aware that InternetWebsites listed in this work may have changed or disappeared between when this work was written and when it is read. Nowarranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall beliable for any damages arising herefrom.

Library of Congress Cataloging-in-Publication Data

Ellis, Andrew M. (Andrew Michael), 1963–Proton transfer reaction mass spectrometry : principles and applications / Andrew M. Ellis,

Christopher A. Mayhew.pages cm.

Includes index.ISBN 978-1-4051-7668-2 (cloth)

1. Proton transfer reactions. 2. Mass spectrometry. I. Mayhew, Christopher A. II. Title.QD501.E545 2014539′.60287–dc23

2013028864

A catalogue record for this book is available from the British Library.

Set in 10/12pt Times by Aptara Inc., New Delhi, India.

Contents

Preface xiii

SECTION 1 PRINCIPLES

1 Background 31.1 Volatile Organic Compounds in the Earth’s Atmosphere 31.2 Volatile Organic Compounds in Other Environments 51.3 Techniques for VOC Measurements 6

1.3.1 Gas Chromatography 61.3.2 Ion Mobility Spectrometry 91.3.3 The Flowing Afterglow Technique 111.3.4 The Selected Ion Flow Tube 14

1.4 Emergence of Proton Transfer Reaction Mass Spectrometry 151.4.1 Historical Background 151.4.2 Compound Identification Using PTR-MS 171.4.3 An Introduction to Quantitative Aspects of PTR-MS 211.4.4 A Comparison between PTR-MS and SIFT-MS 22

References 23

2 Chemical Ionization: Chemistry, Thermodynamics and Kinetics 252.1 Introduction 252.2 Proton Transfer 27

2.2.1 Energy Units 272.2.2 Thermodynamics of Proton Transfer 272.2.3 Kinetics of Proton Transfer 31

2.2.3.1 Background 312.2.3.2 Theoretical Prediction of Proton Transfer Rate

Coefficients 332.2.3.3 Illustrative Calculations of Proton Transfer Rate

Coefficients and Comparison with Experiment 372.2.4 Reagents and Mechanisms 38

2.2.4.1 Chemistry of H3O+ Reactions 382.2.4.2 Reactions of Hydrated Hydronium Clusters 422.2.4.3 Alternative Proton Donors 43

2.3 Other Chemical Ionization Processes 44References 45

vi Contents

3 Experimental: Components and Principles 493.1 Introduction 493.2 Ion Extraction and Ion Optics 50

3.2.1 Ion Acceleration 513.2.2 Ion Steering 533.2.3 Ion Lenses 543.2.4 Simulation of Ion Trajectories 56

3.3 Ion Sources 573.3.1 Hollow Cathode Discharge Ion Source 573.3.2 Ion–Molecule Chemistry Leading to H3O+ Production 593.3.3 Alternative Ion Sources 613.3.4 Generating Reagent Ions Other Than H3O+ 63

3.4 Drift Tubes 643.4.1 Practical Aspects 643.4.2 Ion Mobility and Transit Times 693.4.3 Ion–Molecule Collision Energies 713.4.4 Ion Cluster Distributions 73

3.5 Mass Spectrometry 763.5.1 Some Important Definitions 77

3.5.1.1 Ion Mass and Mass-to-Charge Ratio 773.5.1.2 Mass Resolution 783.5.1.3 Transmission and Dynamic Range 79

3.5.2 Quadrupole Mass Spectrometry 813.5.2.1 Basic Principles of the Quadrupole Mass Spectrometer 813.5.2.2 Practical Issues 83

3.5.3 Quadrupole Ion Trap Mass Spectrometry 853.5.3.1 Basic Principles 853.5.3.2 Collision-Induced Dissociation 873.5.3.3 Three-Dimensional Quadrupole Ion Traps in PTR-MS 883.5.3.4 The Linear Ion Trap in PTR-MS 90

3.5.4 Time-of-flight Mass Spectrometry 903.5.4.1 Basic Principles of TOF-MS 903.5.4.2 Improving the Resolution: Spatial Focusing 923.5.4.3 Reflectron TOF-MS 933.5.4.4 Mass Calibration in TOF-MS 943.5.4.5 Advantages and Limitations of TOF-MS 953.5.4.6 TOF-MS Analysers in PTR-MS 96

3.6 Ion Detectors 973.6.1 Discrete Dynode Detector 983.6.2 Channel Electron Multiplier 1003.6.3 Microchannel Plate Detector 101

3.7 Analogue versus Digital Signal Processing 103References 106

4 Quantitative Analysis 1114.1 Introduction 1114.2 Extracting the Concentration of a Trace Gas from PTR-MS 111

Contents vii

4.3 Normalized Counts per Second 1134.4 Why Calibrate? 1134.5 Calibration Techniques 116

4.5.1 Static Gas Calibration 1164.5.2 Dynamic Methods 1174.5.3 Alternative Dynamic Calibration Procedures 119

4.6 Effect of Humidity 1204.7 Accuracy, Precision and Limit of Detection 1224.8 Validation of PTR-MS 125References 126

SECTION 2 APPLICATIONS

5 PTR-MS in the Environmental Sciences 1315.1 Background 1315.2 Use of Reagent Ions Other Than H3O+ 1385.3 Biogenic VOCs 141

5.3.1 General Details 1415.3.2 Forest Emissions 142

5.3.2.1 Tropical Rainforests 1425.3.2.2 Coniferous Forests 1445.3.2.3 Deciduous Forests 1465.3.2.4 Eddy Covariance Measuring Methodologies 1475.3.2.5 Forest VOCs and m/z Assignments 150

5.3.3 Plantations 1505.3.4 Various Land Emissions 151

5.3.4.1 Woodland and Grassland Savannahs 1515.3.4.2 Shrubland 1525.3.4.3 Alfalfa and Grass Fields 152

5.3.5 Oceans and Seas 1545.3.5.1 Norwegian Fjord 1545.3.5.2 Coastal Regions 1555.3.5.3 Indian Ocean 1565.3.5.4 Tropical Atlantic Ocean 156

5.4 Anthropogenic VOCs 1575.4.1 Background 1575.4.2 VOCs in Urban and Rural Sites 157

5.4.2.1 Innsbruck 1575.4.2.2 Caracas 1585.4.2.3 Houston 1585.4.2.4 Tokyo 1595.4.2.5 Barcelona 1595.4.2.6 Manchester and London 1605.4.2.7 Mexico City 1605.4.2.8 Toronto and Environs 1625.4.2.9 Paris 1635.4.2.10 Boston, New York and Los Angeles 163

viii Contents

5.4.3 Diesel Engine Emissions 1645.4.4 Aircraft Emissions 1645.4.5 VOC Emissions Associated with Farming 164

5.4.5.1 Cattle 1655.4.5.2 Pigs and Sheep 165

5.4.6 Other Studies of Anthropogenic VOCs 1665.4.6.1 Air Quality 1665.4.6.2 Firework Emissions 166

5.5 Biomass Burning 1665.6 Applications of PTR-MS to Laboratory Studies of Atmospheric

Chemistry 1695.6.1 Laboratory Studies of Biomass Burning 1715.6.2 Reaction Products and Reactive Species 1735.6.3 Simulation Chamber and Container Measurements 176

5.7 Plant Studies 1815.7.1 Isoprene Emissions 1825.7.2 Acetaldehyde Emissions 1855.7.3 Pollination 1875.7.4 Roots and Soil 1885.7.5 Other Plant Studies 189

5.7.5.1 Root-secreted VOCs 1895.7.5.2 Methanol Release and Bacterial Growth:

Plant-Methylobacterium Association 1905.7.5.3 Comparison of VOC Emissions from Young and Mature

Leaves 1905.7.6 Stress-Related Emissions 1905.7.7 VOC Emissions Linked to Plant Damage 193

5.7.7.1 Mechanical Wounding 1935.7.7.2 Weather Damage 1945.7.7.3 Harvesting and Mowing 1955.7.7.4 Biofuel Crops 1965.7.7.5 Herbivore Attack by Small Predators 1975.7.7.6 Large Herbivore Attack 202

5.7.8 VOC Uptake by Plants 2025.8 Outlook for Atmospheric and Environmental Applications

of PTR-MS 203References 203

6 PTR-MS in the Food Sciences 2216.1 Background 2216.2 Combined GC–MS and PTR-MS Studies for Food Analysis 2236.3 Mass Spectral Fingerprinting 2266.4 Flavour Release and Perception 227

6.4.1 Drinks 2286.4.1.1 Coffee 2286.4.1.2 Tea 231

Contents ix

6.4.1.3 Carbonated Drinks 2326.4.1.4 Fruit Juices 2336.4.1.5 Wine 2336.4.1.6 Vodka 2346.4.1.7 Infant Formula 235

6.4.2 Food 2356.4.2.1 Cheese 2356.4.2.2 Bread 2376.4.2.3 Onions 2376.4.2.4 Wheys 2376.4.2.5 Fruit 238

6.4.3 Flavour Release: Food Texture, Composition and PhysiologicalEffects 240

6.5 Food Classification, Food Quality and Food Control 2456.5.1 Geographical Location 245

6.5.1.1 White Truffles 2456.5.1.2 Butter 2466.5.1.3 Olive Oil 2476.5.1.4 Roe 2476.5.1.5 Dry-Cured Ham 2476.5.1.6 Cumin Cheese 248

6.5.2 Food Classification and Quality 2496.5.3 Food Freshness and Ripening 250

6.5.3.1 Meat Degradation 2506.5.3.2 Fruit and Vegetables: Ripening, Storage and Monitoring 2516.5.3.3 Ripening of Cheese 253

6.5.4 Process Monitoring and Biochemical Processing 2536.6 Outlook for Food Science and Technology Applications 256References 257

7 PTR-MS in the Medical Sciences 2677.1 Background 2677.2 Breath Analysis 268

7.2.1 Smoking and Breath Volatiles 2717.2.2 Isoprene in Breath 2727.2.3 Acetone in Breath 2757.2.4 Lung Studies: Cancer and Emphysema 2767.2.5 Other PTR-MS Breath Studies 278

7.2.5.1 Crohn’s Disease and Ulcerative Colitis 2787.2.5.2 Carbohydrate Malabsorption 2787.2.5.3 High Mass-Resolution PTR-TOF-MS Breath Studies 2787.2.5.4 Kidney Function and PTR-MS 2807.2.5.5 Liver Disease 280

7.2.6 Drug Monitoring and Pharmacokinetics Using BreathAnalysis and PTR-MS 281

x Contents

7.2.7 Breath VOC Levels Measured Using PTR-MS versusBlood Concentrations 284

7.2.8 Breath Sampling and PTR-MS 2857.2.8.1 Offline Breath Sampling 2867.2.8.2 Online Breath Sampling 287

7.2.9 PTR-MS and Breath Analysis: Requirements andFuture Directions 287

7.3 Online PTR-MS Measurements of Volatile Emissionsfrom Microbial Cultures 2907.3.1 Bacteria 2907.3.2 VOC Emissions from Fungi 2967.3.3 Concluding Remarks on Microbial Emissions 297

7.4 Other Medical Applications 2977.4.1 Urine Headspace Analysis 3017.4.2 Skin Emissions 3017.4.3 VOC Emissions from Human Cells 3017.4.4 VOCs in Clinical Environments 302

References 302

8 Applications of PTR-MS to Homeland Security: The Detectionof Threat Agents 3118.1 Background 3118.2 Explosives 312

8.2.1 Forensic Issues 3128.2.1.1 The Unambiguous Detection of TNT 3158.2.1.2 High Mass Resolution PTR-TOF-MS

Measurements of TNT 3188.2.1.3 Reagent Ion Switching and Explosives Detection 3198.2.1.4 PTR-MS and the Detection of Traces of Explosives 320

8.2.2 Environmental Aspects and Explosives 3208.3 Chemical Warfare Agents and Toxic Industrial Chemicals 3218.4 Narcotics 3228.5 Date Rape Drugs 3258.6 Ion Mobility Mass Spectrometry and PTR-MS: A Brief Comparison

for Homeland Security Applications 3268.7 Future Directions 327References 328

9 Liquid Analysis Using PTR-MS 3319.1 Determination of Henry’s Law Constants Using PTR-MS 3319.2 Analysis of Liquids 333References 336

Index 337

Nothing tends so much to the advancement of knowledge as the application of a new instrument.Sir Humphry Davy

Preface

Proton transfer reaction mass spectrometry (PTR-MS) is widely used for the detectionof volatile organic compounds in air. The historical development of this technique canbe traced back to measurements of the rates of ion–molecule reactions in the 1960s and1970s using flow tube methods. The technology introduced for measuring the kinetics ofthese reactions morphed into the analytical technique we now know as PTR-MS in themid-1990s. The seminal work in this area was performed by Werner Lindinger and histeam at the University of Innsbruck.

Remarkably, the development of PTR-MS by the Innsbruck group very nearly did nothappen! Early requests for funding of this work were rejected by various research agencies,as the acknowledgements in some of the early PTR-MS research papers forcibly testify. Itwas only through Lindinger’s perseverance, support from Fa. Nestle (Nestec Ltd, Switzer-land) and initial funding from the “Gesellschaft fur Strahlenforschung” (GSF, Neuherberg,BRD), that made it possible for the developmental work on PTR-MS to be pursued. Withlimited resources, and together with Armin Hansel, Alfons Jordan and other colleagues,PTR-MS as we know it today began to emerge. This developmental work was followed upwith pioneering applications in the environmental sciences, food science and medicine, allin collaboration with colleagues at Innsbruck and external establishments. By the time of hisuntimely death in 2001, Werner Lindinger had demonstrated the applicability of PTR-MSas an analytical tool for monitoring trace gases in several different environments and hadestablished a spin-out company for the commercial exploitation of this novel technology.

The initial growth of PTR-MS research was so fast that by the beginning of the twenty-first century it warranted its own international conference. The first took place in 2003 inInnsbruck and it has now become a regular event taking place every two years, usuallyin Obergurgl, Austria. These conferences are a testament to the growth of PTR-MS as ananalytical technique, with new applications being regularly reported and new researchersfrom many disciplines becoming involved in this exciting technology. The various booksof abstracts for these conferences provide a unique summary of the activities pursued andthe diverse range of applications, as well as an illustration of how fast the technology isevolving. For the interested reader, these books of abstracts are available as downloadablepdf files and they provide a valuable resource which is impossible to duplicate in this book.

PTR-MS has become a remarkably versatile tool, with applications in many areas of sci-ence and technology. A review of the research literature at the time of writing indicates thatapproximately 50% of all reported activities are based on studying VOCs (anthropogenicand biogenic) in the environment, and in particular for atmospheric science. Approximately30% of publications are based in the area of food science/technology while another majorfield of application is to be found in the health sciences, representing approximately 15%

xiv Preface

of PTR-MS publications to date. The remaining 5% of publications deal with a multitudeof topics.

The diverse range of applications inevitably means that the users of PTR-MS come froma variety of backgrounds. While we suspect that the majority of users are likely to havereceived strong training in the chemical sciences, others may be drawn into the field from,for example, the environmental, biological or medical sciences. To learn about PTR-MS,one can turn to the research literature and consult the original publications that describe keydevelopments in the technique or focus on a certain application. Equally, there are severalexcellent reviews on PTR-MS available in the published research literature. However, theresearch literature can be a rather terse and fragmented source of information, geared as itis towards specialists in the subject field. Furthermore, there have been several importantnew developments in PTR-MS in recent years, especially with regard to instrumentation.It would therefore seem timely to gather much of this information in one place.

Given the diverse user community and the increasing maturity of PTR-MS as a techniquefor gas monitoring and gas analysis, it is surprising that no book dedicated to PTR-MShas been published. Here we have attempted to fill this hole. Our primary aim has been toproduce a book that is particularly targeted at those who are relatively new to PTR-MS,although more seasoned investigators may also benefit in some ways from its content.Broadly speaking, this book is divided into two parts. In the first part, which consists ofChapters 1–4, we describe the underlying principles of the PTR-MS technique, includingthe relevant ion–molecule chemistry, thermodynamics and reaction kinetics. Details areprovided on practical aspects of PTR-MS, including a discussion of ion sources, drift tubesand mass spectrometers. As we proceed on this journey we give, where appropriate, somebrief historical narrative.

The second part of the book, which spans Chapters 5–9, turns its attention to some of themany applications of PTR-MS. Here we want to demonstrate the scope and benefits, as wellas the limitations, of PTR-MS. Our aim here has been to give a thorough but not exhaustivecoverage of applied PTR-MS. We particularly want to try and show that PTR-MS, whilealready in widespread use, is rapidly finding new avenues where it can be applied. Fourkey areas of application will be described, namely environmental science, topics associatedwith food/drinks, medicine and homeland security, and each of these receives a dedicatedchapter (Chapters 5–8). A short chapter (Chapter 9) will also deal with the applications ofPTR-MS in liquid analysis. Chapters 5–9 build upon the material presented in Chapters1–4 and are essentially self-contained reviews of the specific topics mentioned above.Consequently, the reader can dip into those that are of particular interest to him/her and ifdesired can safely ignore those of more peripheral interest.

Overall, we have tried to pitch the content of the book at a level which can be followedby an advanced undergraduate or early stage graduate student with a decent backgroundin chemistry, and in particular physical chemistry. However, we also hope that peopleapproaching PTR-MS from other disciplines who have a more modest knowledge of phys-ical chemistry can follow much of the text. Our overarching aim has been to provide thereader, particularly one who is relatively new to PTR-MS, with a level of understanding ofthe technique which will then allow them to approach the research literature in this fieldwith confidence. If we have come anywhere near this aim, then we will be delighted.

We need to thank several people for assisting with the preparation of the manuscriptincluding Dr Peter Watts, Professor Paul Monks, Dr Franco Biasioli, Dr Philipp Sulzer,

Preface xv

Dr Valerie Gros, Dr Jens Herbig, Dr Margaret O’Hara, Dr Robert Blake, Dr WilfriedSzymczak, Shane Barber, Vicky Orson-Wright and Kathleen Hynes. We are also gratefulto the publisher, and in particular our primary contact at Wiley, Sarah Tilley, for patience aseach revised deadline came and went! Most of all, we are grateful for the enduring supportand patience of our families while this book was being written.

Andrew M. EllisChristopher A. Mayhew

April 2013

Section 1Principles

1Background

1.1 Volatile Organic Compounds in the Earth’s Atmosphere

Air usually contains many volatile organic compounds (VOCs).1 These VOCs can derivefrom numerous sources, including emissions from plants and animals, as well as man-made sources such as motor vehicles and factories. The air we breathe consists mainlyof inorganic gases: predominantly nitrogen and oxygen, but there are also other inorganicgases at lower concentrations, such as argon, water and carbon dioxide (see Table 1.1). Bycomparison the quantity of organic compounds in air is extremely small, of which the mostabundant organic gas by far, methane, forms only around 1 part per million by volume(ppmv). At much lower concentrations still are other organic compounds such as methanol,acetone and isoprene. The exact quantities of these and other VOCs can vary dependingon where any measurement is made. However, given that such compounds are usuallypresent at extremely low levels (often referred to as trace levels) relative to the inorganiccompounds in air, with even the more abundant VOCs often being in the low parts perbillion by volume (ppbv) range,2 it would seem safe to assume that VOCs are of negligibleimportance in almost any context. This assumption is incorrect.

There are many reasons why it is important to know the identities and the quantities ofVOCs in the Earth’s atmosphere. One of the major motivations is the desire to understandthe impact of human activities on the natural atmosphere. Broadly speaking, the sourcesof VOCs in air can be divided into two groups: natural sources, also known as biogenicemissions, and man-made sources, known as anthropogenic emissions [2–4].

After methane the principal biogenic compounds are isoprene and monoterpenes. It is therelease of monoterpenes that is responsible for the characteristic smell of forests, particularly

1 The distinction is sometimes made between volatile and semi-volatile organic compounds but no such distinction is employedin this book.2 A billion here refers to a multiplier of 109, so 1 ppbv is one part in 109 by volume. For an ideal gas this implies one gasatom/molecule out of a total of 109 atoms/molecules.

Proton Transfer Reaction Mass Spectrometry: Principles and Applications, First Edition. Andrew M. Ellis and Christopher A. Mayhew.

© 2014 Andrew M. Ellis and Christopher A. Mayhew. Published 2014 by John Wiley & Sons, Ltd.

4 Proton Transfer Reaction Mass Spectrometry

Table 1.1 The most abundant gaseous constituents of airand their typical mixing ratios

Gasa Mixing ratiob (ppmv)

Nitrogen 781 000Oxygen 209 000Argon 9 300Carbon dioxide 387Neon 18Helium 5.2Methane 1.7Hydrogen 0.53

Source: Numerical data extracted from Reference 1.aThe amount of water vapour (not shown in the table) strongly varies dependingon the humidity and can range from near-zero up to 40 000 ppmv (i.e. 4% ofatmospheric gas).bMixing ratio (volume fraction) expressed in parts per million by volume (ppmv).

pine forests. Much of the emission of these compounds is linked to the photosynthesis cyclein plants, but there are other reasons for their emission, including as a defence mechanismagainst insect damage. However, many other compounds, including oxygenated VOCssuch as alcohols, aldehydes and ketones, can be emitted from plants in response to variousstimuli. In addition to their obvious biological interest, the emission of biogenic VOCs isextremely important in atmospheric chemistry. Biogenic emission is the dominant sourceof VOCs in the Earth’s atmosphere and many of these compounds play an important rolein atmospheric oxidation processes leading, among other things, to the formation of ozone.

Anthropogenic VOCs can disturb the natural atmospheric oxidation processes. Sourcesrange from fossil fuel emissions to industrial solvent emissions and biomass burning. Sig-nificant compounds can include a variety of hydrocarbons, both aliphatic and aromatic,as well as oxygenated compounds. One of the well-known detrimental aspects of anthro-pogenic VOC emission is the production of photochemical smog, which forms when thereare excessive levels of both nitrogen oxides and VOCs in combination with sunlight. Therelatively high levels of ozone and particulate matter that this produces can make breathingdifficult for many people and in worst-case scenarios can lead to serious injury or even deaththrough respiratory diseases, such as chronic asthma. More generally, many anthropogenicVOCs may be highly toxic, carcinogenic and/or mutagenic, and emissions in the urbanenvironment, in factories, or perhaps even in the home are of considerable concern.

Given the importance of VOCs in the environment, a variety of techniques have beendeveloped for their measurement. The ideal technique does not currently exist, and thusone must assess the pros and cons of each available method in order to decide whichis the most suitable for a given application. For example, the requirement might be todetermine the amount of one or more compounds in the atmosphere on a large scale,perhaps over a region, a country or even a continent. In such circumstances, one must looktowards techniques like satellite observation, which can explore large areas very rapidly,albeit only for a relatively small number of compounds. Aircraft measurements offer acompromise, where small-scale instruments can be carried over large ranges, but with

Background 5

limited coverage. On the more local scale, there is a greater variety of instrumentation thatcan be deployed, ranging from differential optical absorption spectroscopy (DOAS) to evenmore local techniques such as gas chromatography (GC), ion mobility spectrometry (IMS)and proton transfer reaction mass spectrometry (PTR-MS), all of which essentially sampleair in the immediate vicinity of the instrument. However, in addition to spatial distribution,time-resolved VOC measurements may also be important to the atmospheric scientist. Aremeasurements every hour satisfactory, or might information be required every minute ofevery day? In some circumstances, it is important to be able to follow transitory events andthus a slow measurement technique may be of little or no use.

The focus in this book is on one particular technique, PTR-MS, which is widely usedfor measuring trace-level VOCs. Along with other applications, we aim to show that thisis an important and versatile technique for atmospheric scientists. It provides a meansof making local measurements with good sensitivity and at relatively high speeds. How-ever, in this chapter we shall also describe complementary techniques, most notably gaschromatography–mass spectrometry (GC–MS), and competitor techniques such as selectedion flow tube mass spectrometry (SIFT-MS), to give some context. In each case, we willprovide an assessment of the major strengths and weaknesses of each technique.

1.2 Volatile Organic Compounds in Other Environments

Instruments that can identify and quantify trace levels of VOCs have many potentiallyimportant applications beyond atmospheric science. For example, VOC emissions fromfoods and drinks are critical in our perception of their taste and smell. Food manufacturersare keen to understand the factors that contribute to flavour perception, and correlating VOCmeasurements with human trials of sensory perception is an important way of doing this.VOC emissions from foods and drinks can also be an indicator of quality. In particular, theonset of serious degradation may be characterized by the excessive emission of one or moreVOCs, and these marker compounds therefore offer the key to an automated indication offood and drink decay. This is an area of investigation that is still very much in its infancy,but which may have very considerable implications for the food and drinks industries.

Another area where VOC measurements are still in their infancy is in the diagnosis ofdiseases through the measurement of the VOC composition of human breath. Breath is amixture dominated by the common inorganic constituents of air, but it also contains a smallfraction of VOCs in the ppbv to pptv (parts per trillion by volume) range. VOCs can beproduced anywhere in the body and may be transported via the bloodstream to the lungs,where they are exhaled in breath. It has long been known by the medical community thata characteristic smell on the breath of a patient can sometimes indicate a specific medicalcondition. However, until recently no technique was available which could reliably andquickly assess the identities and quantities of the many VOCs present in human breath.That barrier is beginning to disappear and with it comes the prospect of using breath analysisas a serious means of non-invasive screening for specific diseases.

The above list of applications is by no means complete, and there are many other areasof science and technology that might benefit from rapid and sensitive VOC measurements,such as botany, forensic science and security screening. Some of these topics are consideredin detail in the later chapters of this book (Chapters 5–9). In this short overview, we hope to

6 Proton Transfer Reaction Mass Spectrometry

have convinced the reader that trace VOC measurements are beneficial across a wide rangeof science and industry.

1.3 Techniques for VOC Measurements

It is not the aim of this book to provide an exhaustive account of analytical techniques thatcan be used to determine trace levels of VOCs in the gas phase. Our focus is, of course,on PTR-MS. However, like any measurement technique, PTR-MS has its strengths andweaknesses and it is important to put these into context by making a comparison withother types of instrumentation. As we will see, important criteria to be considered by anypotential user include sensitivity, linearity of response, accuracy, specificity and speed ofmeasurement, together with the cost and size of the instrumentation. Some of the majoralternatives to PTR-MS for trace VOC measurements are described in this section.

We start with a description of what is currently the single most important and widelyused technique for VOC gas analysis, gas chromatography. We will then turn our atten-tion to techniques that typically show a much faster response, starting with ion mobilityspectrometry and its variants. Flowing afterglow and selected ion flow tube studies of ion–molecule reactions are then considered, since these set the scene for the two main directmass spectrometry techniques for quantifying gaseous VOCs, PTR-MS and SIFT-MS. Thechapter closes with an introductory account of both PTR-MS and a comparison of PTR-MSwith SIFT-MS.

1.3.1 Gas Chromatography

Gas chromatography (GC) is, in many respects, the ‘gold standard’ for trace gas analysis.The basic principle behind GC is that the constituents of a flowing gas mixture (the mobilephase) can be separated by passage over a suitable liquid or solid (the stationary phase).Partitioning between the mobile and stationary phases can lead to different retention timesfor different compounds due to differences in the way each compound in the gas interactswith the stationary phase. It is this difference in retention times that underlies GC.

In the early days of GC, the stationary phase was a particulate solid and would be packedinto a tube known as a column. Nowadays much narrower diameter columns, known ascapillary columns, are prevalent and the stationary phase is frequently a thin layer (typically1 μm thick) of viscous liquid coated on the inside of the column wall. The columns arecoiled and are normally very long, with lengths up to 60 m not being uncommon. Asillustrated in Figure 1.1, the analyte mixture is injected into a flowing carrier gas, usuallyhelium, upstream of the column and then proceeds through the column and onwards to adetector at the end of the instrument. The column is located within an oven to maintain awell-regulated temperature for the elution process. Whatever type of column is used, theaim is to ensure that the gas constituents are able to interact intimately and frequently withthe stationary phase as they make their way through the column, with those interactingmost strongly taking the longest time to reach the detector. Consequently, a plot of detectorsignal versus time should give a series of peaks at retention times that are characteristic forspecific compounds. Such a plot is known as a gas chromatogram.

There are a number of important issues to consider in the practical application of GC forair analysis. First and foremost is the sensitivity, which is insufficient to measure the very

Background 7

Figure 1.1 Schematic diagram of a GC instrument with an FID. An analyte gas is injected intoa flow of inert carrier gas at the injector. The gradual separation of compounds in the columnleads to elution of distinct compounds at different (retention) times, as measured by the FID,leading to a chromatogram such as that shown in the upper right of the diagram.

small quantities of VOCs in a single syringe injection of air. Instead a pre-concentrationprocess is required, in which the desired analyte gas is accumulated over a period of timein an appropriate vessel before rapid release in a concentrated burst into the GC column.One way of doing this is to collect the analyte in a cryogenic trap. This will not condensethe common constituents of air, such as O2 and N2, but will condense organic compounds.If this approach is adopted, a suitable collection container is required. One possibility isa stainless steel canister, but the inside surfaces must be coated with some relatively inertmaterial, such as Teflon or silica, to minimize the possibility of surface-catalysed reactions.Once sufficient material is in the trap, it can be released by flash heating, which can bedone electrically or by simply immersing the trap in hot water. Relatively simple cryogenictraps are rarely used for pre-concentration, partly because they are indiscriminate and thuscollect all condensable materials, including water. Furthermore, it is relatively inconvenientto rely on a cryogenic approach, particularly if measurements are made in environmentswell away from standard laboratory facilities. As an alternative, traps consisting of suitableadsorbent materials, such as a carbon-based material (e.g. charcoal) or a polymer, can beemployed. An example of the latter is a material known as Tenax, which works well fortrapping compounds such as aromatics and terpenes and is widely used.

Another important issue is the column. The length of the column is one significant factor,since a longer column should improve the separation, but the choice of the stationary phaseis critical. No single stationary phase is suitable for all types of compounds. For example,a stationary phase composed of a non-polar substance is best for separating hydrocarbons,particularly volatile hydrocarbons, whereas a polar stationary phase is essential for oxy-genated VOCs such as alcohols, aldehydes and ketones. There are many types of stationaryphases available and an important aspect of GC is selecting the right one for the particularapplication.

Water from the analyte is a major problem in GC work, not least because it interfereswith the performance of the column. Consequently, efforts are made to remove as much

8 Proton Transfer Reaction Mass Spectrometry

water as possible before it reaches the column. Cold traps or traps packed with dryingagents can be used for this purpose, but one must always take care to ensure that these trapsdo not also remove the organic constituents of the analyte gas.

There are several types of detectors that can be coupled to a gas chromatograph. Oneexample is the flame ionization detector (FID), where, as the name implies, the effluentflows through a flame as it leaves the column, which generates ions as one of the products.These ions are then detected via an electrical current monitor. When coupled with suitablepre-concentration of the analyte, GC-FID can approach compound detection sensitivitiesas low as a few pptv. However, the FID works best for compounds such as hydrocarbonsand is therefore not a universal detector. Other types of well-known GC detectors includethe electron capture detector (ECD) and the thermal conductivity detector (TCD), and aswith FID these alternatives also have their strengths and weaknesses but we will not discussthese in this book.

Unfortunately, compound resolution is not as easy as the discussion above implies. Manydistinct compounds are difficult to separate fully on a column. Even if the compounds canbe separated, the FID, ECD or TCD does not provide any compound identification: itmerely registers the fact that a compound is leaving the column at a given moment in time.As implied earlier, compounds can sometimes be identified on the basis of the time takento leave the column, that is, from their retention times. The retention time of a particularcompound can be pre-determined by adding that specific compound to the GC instrumentin a calibration procedure. Of course, there is the possibility, particularly with complexmixtures, that two or more compounds may have very similar retention times and thereforecannot be distinguished in this way. Furthermore, a calibration approach will only work ifyou already have a pretty good idea of what might be present in the analyte.

To get around these limitations, the FID, ECD or TCD can be replaced with a massspectrometer equipped with an electron impact ionization source. In most cases, the massspectrometer is of the quadrupole variety (see Chapter 3 for further details). The instrumentworks by recording a whole series of mass spectra, one after the other, as the analyte elutesthrough the column. In this way, important analytical information is obtained from boththe retention time and the mass spectrum. The mass spectrum recorded for a particular GCpeak can be compared with those stored in a library on the control computer, which usuallyallows compound identification. GC–MS is an extremely valuable analytical tool, but itsuffers from a lower detection sensitivity than GC-FID because of the scanning time of themass spectrometer, and so for air analysis it is often used more for compound identificationthan for quantification.

From the description above, some of the limitations with GC and its variants becomeclear. It is not a universal technique, since the choice of trap and column will affect thesensitivity and accuracy towards certain classes of compounds. In particular, oxygenatedVOCs are more of a problem than hydrocarbons for GC analysis. The principal problemwith oxygenated VOCs in GC stems from their polarity, which requires polar or semipolarcolumn materials to achieve sufficient compound separation. Unfortunately, these columnsalso easily degrade when they come into contact with water, and therefore stringent effortsmust be made to avoid any moisture. A particularly serious matter in GC analysis is thespeed of measurement which, because of the need for sample collection and also somedegree of pre-concentration, is often limited to a single measurement every few minutes, at

Background 9

best. Consequently, if rapidly evolving gas systems are being explored, GC techniques arenot suitable.

Despite these limitations, GC remains the analysis technique of choice for many appli-cations. It frequently achieves good compound separation, has good sensitivity, is reason-ably cheap, is very well established and is reliable. Furthermore, developments such astwo-dimensional GC techniques offer new scope [5]. The two-dimensional GC techniqueemploys two columns in series but the two columns have different separation characteris-tics. This allows resolution of a much wider range of compounds than standard GC and hasthe potential to allow the exploration of very complex VOC environments in great detail.

1.3.2 Ion Mobility Spectrometry

Ion mobility spectrometry (IMS) has become a widely used analytical technique in thepast two decades. It has found particular popularity in military and security circles becauserelatively cheap, simple, robust and compact IMS devices can be constructed which arecapable of rapidly detecting a wide range of VOCs with high sensitivity. Figure 1.2 showsthe basic structure of an IMS instrument. The analyte gas is injected and subjected toionization at one end of the instrument and an ion detector is located at the other end. Thetube in-between contains a series of electrodes which generate an electric field along itsaxis, drawing ions towards the detector. A tube equipped with these electrodes is called adrift tube and the underlying principle of IMS is the separation of ions according to theirmobilities through a gas, which is usually air at atmospheric pressure.

We can draw a very loose analogy with GC in that the ions in IMS act like the mobilephase and the neutral gas as the stationary phase. The mobility quantifies the ease with

Figure 1.2 Typical arrangement for a conventional ion mobility spectrometer. Ions are pro-duced in the upstream region (left-hand side of the figure), in this case via a radioactive source,and are then drawn from left to right by an electric field applied through a series of electrodes(the ‘guard rings’). Ions are injected in pulses using an electrical shutter (a Bradbury–Nielson(BN) gate) and the time taken to reach the detector is then determined. The ion detector inthe figure is a simple Faraday plate (see Section 3.6).

10 Proton Transfer Reaction Mass Spectrometry

which a particular ion can move through a specified buffer gas at a given temperature andpressure when drawn along by an electric field of known magnitude. Light ions will tendto have higher mobilities than heavy ions, and thus the mobility through a gas serves todiscriminate ions according to their masses. However, the size and structures of the ionsare also important, since they will affect the collision cross section between neutral gasmolecules and the ions. Consequently, large ions will tend to have smaller mobilities thansmall ions, but there is clearly room for some subtleties here because the collision crosssection is also influenced by intermolecular forces, which in turn can depend on factors suchas the charge distribution in the ion. Thus, while the mobilities of ions through the neutralgas may not always be easily predictable, they do offer a means of separating differenttypes of ions on the basis of the time they take to pass through the buffer gas.

A radioactive strip is commonly employed in IMS to create ions, although other sourcesare also in use including photoionization and corona discharge sources, with the latterbecoming increasingly popular for commercial instruments. In positive ion mode, the pres-ence of water vapour in the background gas leads to the formation of hydrated hydroniumions, H3O+ (H2O)n, where n = 0, 1, 2, etc.3 These ions are the initiators of ionization inthe analyte gas molecules and they do this by transferring charge to organic gases (M) byreactions of the type

H3O+(H2O)n + M → (H2O)mMH+ + (n + 1 − m)H2O (1.1)

To separate the different types of ions, a short burst of ions must be injected into the drifttube. This is achieved via a fast-acting electronic shutter, which is actually an ion deflectiondevice known as a Bradbury–Nielsen gate. Injection of this pulse of ions has the effect ofstarting a clock and the arrival of ions at the detector is then measured relative to this startingtime. Although there have been a number of different designs, the basic constituents of mostdrift tubes are a series of metal electrodes of circular cross section (sometimes called guardrings) interspersed by insulators. The electrical potential along the tube is chosen so as todraw the reagent and product ions towards the detector (see Figure 1.2). If the drift tube wasoperated under high vacuum conditions, such that ion–molecule collisions were essentiallyeliminated, then the speed of the ions would increase continuously as they travelled fromone end of the drift tube to the other. However, IMS devices are not operated under highvacuum conditions and therefore collisions with the background gas results in the ionsquickly reaching a constant, terminal velocity, the so-called drift velocity, which dependson the factors mentioned earlier and is directly proportional to the electric field strength.

The ion signal is measured as a function of time and should therefore consist of a seriesof peaks corresponding to ions with different mobilities arising from different chemicalcompounds in the analyte. Drift tube transit times depend on the length of the tube but aretypically on the order of several tens of milliseconds. By comparison, the injection time forions is <1 ms, and until all of the ions in the injected bunch reach the end of the drift tube, asecond bunch of ions cannot be injected. Consequently, the duty cycle, which is a measureof the fraction of ions that reach the detector out of the total number of ions that could reachthe detector if the experiment was not pulsed, is rather low and is typically 1%. This is animportant factor in limiting the sensitivity of IMS. Nevertheless, detection of compounds

3 The mechanism by which hydrated hydronium ions form in a radioactive or electrical discharge source is described in Chapter 3.

Background 11

Figure 1.3 An example of an ion mobility spectrum. In this example, the IMS was operatedin positive ion mode using air as the buffer gas. Di(propylene glycol) methyl ether (DPGME),which is a commercial solvent, was introduced into the reaction region of the drift tube. Movingfrom left to right the first peak corresponds to the reagent ions H3O+(H2O)n, while the secondand third peaks correspond to DPGME(H2O)nH+ and (DPGME)2(H2O)nH+, respectively. Onthe vertical axis cps = ion counts per second.

present in quantities as low as 1 ppbv or so can be reached, which is often adequate formany applications such as security and military uses. An illustrative ion mobility spectrumis shown in Figure 1.3.

The main drawback with IMS is its inherently poor selectivity. As with GC, manycompounds cannot be fully separated by IMS, and even if they are separated it may not beeasy to establish their identities. To try and rectify this, IMS has been coupled with massspectrometry [6], but this comes at the expense of increased cost, complexity and size ofthe instrument. A notable development is Hadamard transform IMS [7,8], which promisesto resolve the problem of the low duty cycle of conventional IMS and should thereforeresult eventually in a significantly improved sensitivity, although again this delivers a morecomplex instrument.

1.3.3 The Flowing Afterglow Technique

PTR-MS has its origins in the development of the flowing afterglow (FA) method for thestudy of ion–molecule reaction kinetics. This so-called ion-swarm technique was introducedin the 1960s by Ferguson and co-workers and it revolutionized the study of ion–moleculereaction kinetics and thermodynamics [9, 10].

Figure 1.4 shows a schematic of the apparatus. The main feature is a flow tube,4 whichprovides the means of extracting kinetic information from relatively fast reactions. The ideahere is that reactions between some atomic or molecular ion, X+, and neutral molecules,which we designate as Y, are explored. The production of reagent ions, X+, is a two-stage

4 A flow tube is distinct from a drift tube in that the transport mechanism in the former is gas flow driven by a pressure differencebetween the two ends of the tube, that is, no electric field is involved in transporting ions.

12 Proton Transfer Reaction Mass Spectrometry

Figure 1.4 Schematic of a flowing afterglow apparatus. With the apparatus shown reagentY can be added at any one of the inlet ports positioned along the flow tube. An off-axis iondetector, as shown in the figure, is often used in quadrupole mass spectrometers to minimizenoise from radiation and excited neutral molecules generated upstream in the ion source andin the flow tube. Ions are deflected towards the detector by electrodes (not shown).

process. First, ions are created in an inert buffer gas, which is usually helium. This isnormally achieved either by an electron impact using a heated filament electron source orvia an electrical discharge. These ions are then carried along a flow tube by the flowingbuffer gas (again usually helium) and further downstream they are mixed with gas X. Gas Xcan be ionized, typically by charge transfer from He+, but also by Penning ionization frommetastable electronic excited states of helium that are also produced in the initial ionizationregion. The advantage of keeping the gas X away from the initial point of ionization is thatit helps to minimize the formation of unwanted fragment ions, which would be more of aproblem if gas X was exposed directly to a highly energetic electrical discharge or directelectron bombardment.

A bright glow extends along the upstream part of the flow tube due to the light emitted byelectronically excited constituents of the discharged gas. The extensive glow of this plasmais the origin of the name flowing afterglow. An essential feature of the FA technique is thatit attempts to explore ion–molecule reactions at thermal energies. This is achieved by usinga large excess of buffer gas and ensuring that the reactant ions are formed well upstream ofthe point where the neutral reagent gas, Y, is added. The flow tube is usually fairly long, atypical length being 1 m, and with gas flow speeds in the region of 100 m s−1. This meansthat the ions have a period of several milliseconds to thermalize prior to reaction, althoughcases are still known where thermalization is incomplete due to slow collisional energytransfer from electronically excited and vibrationally excited states [11].

The neutral reactant gas, Y, is added at a specific entrance port along the flow tube.The pressure in the flow tube is maintained at approximately 1 mbar. After mixing withthe buffer gas and reactant ions, a portion of the flow tube effluent passes through a smallorifice at the end of the flow tube and enters a mass spectrometer, which is usually aquadrupole mass spectrometer (see Chapter 3). Reaction essentially stops as the mixturepasses through the orifice since this mass spectrometer chamber must be operated at a lowpressure (≤10−4 mbar), and therefore further reactive collisions virtually cease. One wayof determining the reaction kinetics is to vary the flow rate of the incoming neutral gaswhile monitoring the ion current of the reactant ions with the mass spectrometer. As the