Charged Aerosol Detection for Liquid Chromatography and Related Separation Techniques

Paul H. Gamache

• Publisher: Wiley
• Year: 2017
• Print ISBN: 9780470937785
• eBook ISBN: 9781119390701
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Analytic Chemistry

The first book devoted exclusively to a highly popular, relatively new detection technique

Charged Aerosol Detection for Liquid Chromatography and Related Separation Techniques presents a comprehensive review of CAD theory, describes its advantages and limitations, and offers extremely well-informed recommendations for its practical use. Using numerous real-world examples based on contributors' professional experiences, it provides priceless insights into the actual and potential applications of CAD across a wide range of industries.

Charged aerosol detection can be combined with a variety of separation techniques and in numerous configurations. While it has been widely adapted for an array of industrial and research applications with great success, it is still a relatively new technique, and its fundamental performance characteristics are not yet fully understood. This book is intended as a tool for scientists seeking to identify the most effective and efficient uses of charged aerosol detection for a given application. Moving naturally from basic to advanced topics, the author relates fundamental principles, practical uses, and applications across a range of industrial settings, including pharmaceuticals, petrochemicals, biotech, and more.

• Offers timely, authoritative coverage of the theory, experimental techniques, and end-user applications of charged aerosol detection
• Includes contributions from experts from various fields of applications who explore CAD's advantages over traditional HPLC techniques, as well its limitations
• Provides a current theoretical and practical understanding of CAD, derived from authorities on aerosol technology and separation sciences
• Features numerous real-world examples that help relate fundamental properties and general operational variables of CAD to its performance in a variety of conditions

Charged Aerosol Detection for Liquid Chromatography and Related Separation Techniques is a valuable resource for scientists who use chromatographic techniques in academic research and across an array of industrial settings, including the biopharmaceutical, biotechnology, biofuel, chemical, environmental, and food and beverage industries, among others.

Section 1
Fundamentals of Charged Aerosol Detection

1
Principles of Charged Aerosol Detection

Paul H. Gamache¹ and Stanley L. Kaufman²

¹ Thermo Fisher Scientific, Chelmsford, MA, USA

² Retired from TSI Inc., Shoreview, MN, USA

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CHAPTER MENU

1. 1.1 Summary
2. 1.2 History and Introduction to the Technology
3. 1.3 Charged Aerosol Detection Process
4. 1.4 CAD Response Model
5. 1.5 Performance Characteristics
6. References

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1.1 Summary

This chapter provides a brief history and detailed overview of charged aerosol detection (CAD) and a semiempirical model describing its response and expected performance under various analytical conditions. CAD and other evaporative aerosol detectors involve the same successive steps of primary spray droplet formation from an eluent stream, conditioning by inertial impaction to remove droplets too large to evaporate during passage through the instrument, and evaporation of remaining droplets to form residue particles each comprised of nonvolatile background impurities and any nonvolatile analyte present. Detection of the residue particles produces the detector signal. In CAD, the aerosol is given a charge dependent on the particle size, and the total charge carried by the aerosol is measured as a current; in ELSD, the aerosol is detected by its light scattering properties. Both detection methods produce a response that is approximately mass‐flow dependent. The analyte dry bulk density affects the residue particle size for a given eluting mass, which has a minor effect on the mass sensitivity of both detector types. Other analyte properties in particular optical properties (e.g., refractive index (RI)) for the ELSD likewise affect the sensitivity. Detection selectivity for evaporative aerosol detectors is based on differences in vaporization of components within an eluent. Accordingly, these techniques are expected to have very similar detection scope, eluent requirements, and solvent dependency of response. The unique characteristics of CAD are due to the aerosol measurement technique, which includes diffusion charging of residue particles and detection of the current due to deposition of particles with their charge in an aerosol‐electrometer filter. Aerosol charging by diffusion mechanisms is well known to have only a minor dependence on particle material (i.e., analyte properties), which is the basis for uniform response capabilities of CAD. Like ELSD, CAD response (e.g., peak area vs. mass injected (m_inj)) can be described by a power law function with a variable exponent b. Linear response, never perfectly achieved by either methods, would correspond to b = 1. For both techniques, the exponent b is at its maximum at the lowest m_inj and decreases with increasing m_inj. This is attributed to smaller residue particles that have a higher power law exponent (β₁) of response and are more prevalent with low m_inj and the low concentration that occurs near the edges of any peak. For ELSD this corresponds to Rayleigh light scattering for particle diameters (d) typically < 50 nm where β₁ = 6, while for CAD corresponds to aerosol charging of d < ~9 nm where β₁ ~ 2.25. For CAD, the lower d transition and smaller β₁ (closer to 1) underlies the widely observed lower detection limits, wider dynamic range, and less complex response curve than ELSD. Newer CAD designs produce an even smaller relative proportion of residue particles of d < ~9 nm, thus further simplifying the response curve, enabling lower sensitivity limits and a wider quasi‐linear response range.

1.2 History and Introduction to the Technology

The technique that is now most commonly called charged aerosol detection (CAD) was first described in 2001 by Kaufman at TSI Inc. in a provisional patent application that ultimately led to US patent 6,568,24 [1]. This device was termed an evaporative electrical detector (EED) and was based on coupling liquid chromatography (LC) and other separation techniques with TSI’s well‐established electrical aerosol measurement (EAM) technology [2]. Around the same time, Dixon and Peterson at California State University were pursuing a similar avenue of innovation with a laboratory‐built device that coupled LC with an earlier generation of TSI’s EAM instruments. Dixon and Peterson described their device, termed aerosol charge detector (ACD), in the Journal of Analytical Chemistry in 2002 [3]. In both instances, the primary objective was to exploit the advantages, well described in aerosol science literature [4], of EAM over direct light scattering for measuring the very small (i.e., low nm diameter range) particles typically produced by LC detectors. The approach was therefore mainly geared toward addressing some of the limitations of evaporative light scattering detection (ELSD), which at the time had been used for LC detection for about 20 years. Subsequent collaboration between TSI and ESA Biosciences, Inc. led to the introduction of the first commercial instrument, the Corona® CAD®, in 2005 [5]. While there are some differences among these early EAM‐based LC devices and with newer commercial instruments, the basic detection process remains the same. Therefore, Kaufman’s patent disclosure and Dixon’s article are acknowledged as the primary theoretical descriptions of CAD.

Since its commercial introduction in 2005, CAD has been widely adopted for a broad range of chromatographic applications. CAD and other aerosol techniques, including ELSD and condensation nucleation light scattering detection (CNLSD) [6], are described as “universal” since response depends primarily on aerosol particle size and number concentration (e.g., number of particles/cubic centimeter of gas) rather than individual analyte properties. These “common property” measurement characteristics provide significant advantages over other devices whose detection scope (viz., range of chemicals for which a useful response can be obtained) and sensitivity (viz., signal output per unit mass or per unit concentration) are highly dependent on analyte nature such as optical properties (e.g., ultraviolet (UV) absorption, fluorescence (Fl)) or propensity to form gas‐phase ions (e.g., electrospray ionization with mass spectrometry (ESI‐MS)). While UV detection remains a primary technique for many LC analyses, its detection scope is limited to compounds with a sufficient UV chromophor...

Table of contents

• Cover
• Title Page
• Table of Contents
• List of Contributors
• Preface
• Acknowledgment
• Section 1: Fundamentals of Charged Aerosol Detection
• Section 2: Charged Aerosol Detection of Specific Analyte Classes
• Section 3: Industrial Applications of Charged Aerosol Detection
• Index
• End User License Agreement