A

Seminar Report on

INDUCTIVELY COUPLED PLASMA MASS

SPECTROMETER
Submitted In Partial Fulfilment of Requirement for

DEGREE COURSE IN BACHELOR OF CHEMICAL

ENGINEERING

Submitted By

Mr. Sumit Shridhar Katkar

(Roll No. 18)

Under the guidance of

Prof. Umakant Khandalkar

Mahatma Gandhi Mission’s College of Engineering & Technology,

Kamothe , Navi Mumbai

2018-2019
 CERTIFICATE

This is to certify that the seminar work entitled “Inductively Coupled Plasma Mass

Spectroscopy” is a bonafide work carried out by Mr. Sumit Shridhar Katkar (UID
No. 115CH1310A) towards the partial fulfilment of Bachelor of Chemical Engineering
from MGM’S COLLEGE OF ENGINEERING, KAMOTHE during academic year 2018-
2019.

Prof. Umakant Khandalkar Dr. N.S. Kohle

Seminar Guide Head of
Department

Dr. S.K. Narayankhedkar

Principal

ii
 ACKNOWLEDGEMENT

It is my privilege and duty to acknowledge the kind of help and guidance received
from several peoples in preparation of this report. It would not have been possible to
prepare this report in this form without their valuable help, co-operation and guidance.

I express my sincere gratitude to my guide, Prof. Umakant Khandalkar, Faculty

of Chemical Engineering Department, MGMCET, Navi Mumbai, for guiding me in
investigation for this seminar. My numerous discussions with his was extremely helpful. I
hold his in esteem for guidance, encouragement and inspiration received from this.

I wish to thanks my friends for their valuable help in preparing this seminar report.
I wish to thanks my parents for financing my studies in this college as well as for constantly
encouraging me to learn engineering. Their personal sacrifice in providing this opportunity
to learn engineering is gratefully acknowledge.

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 ABSTRACT

Inductively coupled plasma mass spectrometry (ICP-MS) is undoubtedly the fastest-

growing trace element technique available today. Since its commercialization in 1983,
approximately 5000 systems have been installed worldwide, carrying out many varied and
diverse applications. The most common ones, which represent approximately 80% of the
ICP-MS analyses being carried out today, include environmental, geological,
semiconductor, biomedical, and nuclear application fields. There is no question that the
major reason for its unparalleled growth is its ability to carry out rapid multielement
determinations at the ultra trace level. Even though it can broadly determine the same suite
of elements as other atomic spectroscopical techniques, such as flame atomic absorption
(FAA), electrothermal atomization (ETA), and inductively coupled plasma optical
emission spectroscopy (ICPOES), ICP-MS has clear advantages in its multielement
characteristics, speed of analysis, detection limits, and isotopic capability.

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 CONTENTS

Abtract……………………………………………………………………………………. iv

List of figures…………………………………………………………………………….. vii

1. INTRODUCTION………………………………………………………………………1

1.1 Introduction………………………………………………………………………...1

2. Literature survey…………………………………………………………………….......2

3. Principle of Operation …………………………………………………………………3

4. ICP-MS Components ……………………………………………..……………………5

4.1Sample Introduction …………………………………………….....………………5

4.2 Inductively Coupled Plasma …………………………………………………….6

4.3 Argon Plasma/Sample Ionization……………………………………………….6

4.4 Plasma Torch……………………………………………………………………....7

4.5 ICP-MS Interface…………………………………………………………………....8

4.6 Mass Spectrometer………………………………………………………………....8

4.7 Detector……………………………………………………………………………..10

4.8 Detection limits …………………………………………………………………...12

4.9 Sample Preparation ………………………………………………………………12

4.10 Elemental Analysis………………………………………………………………12

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5. Pharmaceutical Application…………………………………………………………..13

6. Next Generation of ICP-MS (NexION 300 ICP-MS)…………………………….15

6.1Introduction ………………………………………………………………………...15

6.2 Mode of Operation………………………………………………………………….15

6.2.1 Standard Mode……………………………………………………………..15

6.2.2 Collision Mode ……………………………………………………………...16

6.2.3 Reaction Mode ……………………………………………………………...16

6.3 Stabilization ……………………………………………………………………...16

6.3.1 Triple Cone Interface ………………………………………………………...17

6.3.2 Quadrupole Ion Deflector …………………………………………………...17

6.4 Features and Benefits of the NexION 300 ICP-MS ……………………………...18

7. Conclusion …………………………………………………………………………...20

8. References …………………………………………………………………………...21

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 List of figures

Fig. 1.1 Detection limits capability of ICP-MS ………………………………………...1

Fig. 4.1 Generation of Aerosol by nebulizer …………………………………………...5

Fig. 4.2 Photo of argon plasma in operation processes ………………………………...7

Fig. 4.3 ICP Torch Body ………………………………………………………………...7

Fig. 4.4 ICP Torch showing the fate of the sample ……………………………………...8

Fig. 4.5 Animation of quadrupole mass filter separating ions ………………………...9

Fig. 4.6 Photo of quadrupole rods from mass spectrometer …………………………...9

Fig. 4.7 Schematic of quadrupole mass filter ………………………………………...10

Fig. 4.8 Electron Multiplier Schematic ………………………………………………...10

Fig. 4.9 Electron Multiplier Removed for Cleaning …………………………………...11

Fig. 6.1 NexION 300 ICP-MS ………………………………………………………...15

Fig. 6.3 Schematic of Stabilization process ………………………………………...16

Fig. 6.3.1 Triple Cone Interface …………………………………………………...17

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Chapter 1

INTRODUCTION

1.1 Introduction
Inductively coupled plasma mass spectrometry (ICP-MS) is the most widely used method
today for determination of metal concentrations in both biological and inorganic samples. The
capability of ICP-MS to simultaneously measure the majority of elements in the periodic table
has lead to its replacement of element-specific techniques such as atomic absorption or
emission spectrometry. Other advantages of ICP-MS include its high sensitivity (down to
concentrations subfemtogram metal per gram matrix solution) and large linear dynamic range
(over several orders of magnitude). Several recent texts covering ICP-MS in great detail are
available (Nelms, 2005; Taylor, 2001; Thomas, 2008). The simplest ICP-MS sample
introduction method is as a solution in dilute nitric acid. The solution is pumped into the
instrument and nebulized into a fine spray before hitting the plasma. This sample introduction
method requires complete digestion of samples in concentrated acid (most commonly nitric,
hydrochloric, and/or hydrofluoric) on hot plates. To avoid metal contamination, samples are
digested in acid-washed Teflon containers with extremely low metal blanks in laminar flow
hoods. Recently, other sample introduction methods have been optimized, allowing undigested
rock samples and dried protein gels to be analyzed via laser ablation and liquid metalloprotein
samples to be first separated by HPLC before ICP-MS analysis (). Quantification of metal
concentrations in samples is performed by correlation of metal isotope counts detected by the
instrument to known concentrations in an ICP-MS calibration solution. Generally, a dilution
factor is applied to convert the sample concentration introduced to the ICP-MS to the metal
concentration in the original sample. Figure 1.1 shows approximate detection limits of all the
elements that can be detected by ICPMS, together with their isotopic abundance

Fig.1.1 Detection limit capability of ICP-MS

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Chapter 2

LITERATURE SURVEY
2.1 An Overview of ICP – Mass Spectrometry

Inductively coupled plasma mass spectrometry (ICP-MS) not only offers extremely low
detection limits in the sub parts per trillion (ppt) range, but also enables quantitation at the high
parts per million (ppm) level. This unique capability makes the technique very attractive
compared to other trace metal techniques such as electrothermal atomization (ETA), which is
limited to determinations at the trace level, or flame atomic absorption (FAA) and inductively
coupled plasma optical emission spectroscopy (ICP-OES), which are traditionally used for the
detection of higher concentrations.
Inductively coupled plasma mass spectrometry (ICP-MS) is undoubtedly the fastest-growing
trace element technique available today. Since its commercialization in 1983, approximately
5000 systems have been installed worldwide, carrying out many varied and diverse
applications. The most common ones, which represent approximately 80% of the ICP-MS
analyses being carried out today, include environmental, geological, semiconductor,
biomedical, and nuclear application fields. There is no question that the major reason for its
unparalleled growth is its ability to carry out rapid multielement determinations at the ultra
trace level. Even though it can broadly determine the same suite of elements as other atomic
spectroscopical techniques, such as flame atomic absorption (FAA), electrothermal
atomization (ETA), and inductively coupled plasma optical emission spectroscopy (ICPOES),
ICP-MS has clear advantages in its multielement characteristics, speed of analysis, detection
limits, and isotopic capability.
It is important to emphasize that because of the enormous interest in the technique, most ICP-
MS instrument companies have very active R&D programs in place, in order to get an edge in
a very competitive marketplace. This is obviously very good for the consumer because not only
does it drive down instrument prices, but also the performance, applicability, usability, and
flexibility of the technique are improved at an alarming rate. Although this is extremely
beneficial for the ICP-MS user community, it can pose a problem for a textbook writer who is
attempting to present a snapshot of instrument hardware and software components at a
particular moment in time.

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Chapter 3

PRINCIPLES OF OPERATION

A number of different ICP-MS designs are commercially available today, each with its own
strengths and limitations. They all share similar components such as the nebulizer, spray
chamber, plasma torch, interface and detector but can differ significantly in the design of the
mass spectrometer and in particular the mass separation device[2]. This chart describes those
differences in greater detail. But first, here is an overview of the principles of operation of ICP-
MS. Figure 2 shows the basic instrumental components that make up an ICP-MS system. The
sample, which must be in a liquid form, is pumped at 1 mL/min (usually with a peristaltic
pump) into a nebulizer, where it is converted into a fine aerosol with argon gas at about 1
L/min. The fine droplets of the aerosol, which represent only 1 - 2% of the sample, are separated
from larger droplets using a spray chamber [2]. The fine aerosol then emerges from the exit tube
of the spray chamber and is transported into the plasma torch via a sample injector. The plasma
torch plays a very different role in ICP-MS. In this technique, the plasma is produced by the
interaction of an intense magnetic field (produced by radio frequency [rf] passing through a
copper coil) on a tangential flow of gas (normally argon), at about 15 L/min flowing through a
concentric quartz tube (torch). This ionizes the gas and when seeded with a source of electrons
from a high-voltage spark, forms a very high temperature plasma discharge (~10,000 K) at the
open end of the tube. In ICP-MS, the plasma torch is positioned horizontally, and is used to
generate positively charged ions rather than photons. In fact, every attempt is made to stop the
photons reaching the detector because they have the potential to increase signal noise. It is the
production and detection of large quantities of these ions that gives ICP-MS its characteristic
ultratrace detection capability - about three to four orders of magnitude better than ICP-OES2.
Once the ions are produced in the plasma, they are directed into the mass spectrometer via the
interface region, which is maintained at a vacuum of 1 - 2 torr with a mechanical roughing
pump. This interface region consists of two metallic cones (usually made of nickel)3, called the
sampler and a skimmer cone. Each cone features a small (0.6 - 1.2 mm) orifice to allow the
ions through to the ion optics, where they are guided into the mass separation device.
The interface region is one of the most critical areas of an ICP mass spectrometer. Its role is to
help the ions to be transported efficiently and with electrical integrity from the plasma, which
is at atmospheric pressure (760 torr) to the mass spectrometer analyzer region at approximately
10 -6 torr. Unfortunately, there is capacitive coupling between the rf coil and the plasma,
producing a potential difference of a few hundred volts. If this wasn’t eliminated, an electrical
discharge (called a secondary discharge or pinch effect) would appear between the plasma and
the sampler cone [3]. This discharge increases the formation of interfering species and also
dramatically affects the kinetic energy of the ions entering the mass spectrometer, making
optimization of the ion optics very erratic and unpredictable. For this reason, the secondary
charge must be eliminated by using some kind of rf coil grounding mechanism. A number of
approaches have been used over the years to achieve this, including placing a grounding strap
between the coil and the interface; balancing the oscillator inside the rf generator circuitry;
positioning a grounded shield or plate between the coil and the plasma torch; or using a double-
interlaced coil where RF fields go in opposing directions. They all work differently but achieve

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY
a similar result - reducing or eliminating the secondary discharge3. Once the ions have been
successfully extracted from the interface region, they are directed into the main vacuum
chamber by a series of electrostatic lenses called ion optics. A turbo molecular pump maintains
the operating vacuum in this region at about 10 -2 torr. There are many different designs of the
ion optic region4, but they serve exactly the same function to electrostatically focus the ion
beam towards the mass separation device and to stop photons, particulates, and neutral species
from reaching the detector.
The ion beam containing all the analyte and matrix ions exit the ion optics and now pass into
the heart of the mass spectrometer - the mass separation device, where a second turbo molecular
pump maintains an operating vacuum of approximately 10 -6 torr. There are many different
mass separation devices, all with their own benefits and limitations. Five of the most common
types are quadrupole, magnetic sector, time of flight, collision/reaction cells, and dynamic
reaction cell technology4. They all work differently but all serve the same basic purpose - to
allow analyte ions of a particular mass-to-charge ratio (m/z) through to the detector and to filter
out all the non-analyte, interfering and matrix ions. Depending on the design of the mass
spectrometer, this is either a scanning process where the ions arrive at the detector sequentially
or a simultaneous process where the ions are sampled at the same time. In the final process, an
ion detector converts the ions into an electrical signal. The most common design used today is
a discrete dynode detector, which contains a series of metal dynodes along the length of the
detector.
In this design, when the ions emerge from the mass filter, they impinge on the first dynode and
are converted into electrons. As the electrons are attracted to the next dynode, electron
multiplication takes place, resulting in a very high stream of electrons emerging from the final
dynode. This electronic signal is then processed by the data handling system in the conventional
way and converted into analyte concentration using ICP-MS calibration standards. Most
detection systems used can handle up to eight orders of dynamic range, which means they can
be used to analyze samples from low parts-per-trillion (ppt) levels, up to hundreds of parts-per-
million (ppm)4. Most commercial ICP mass spectrometers, particularly the quadrupole models,
use just one detector. However, specialized magneticsector ICP-MS instrumentation with
multiple detectors.

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Chapter 4
ICP-MS COMPONENTS
4.1 Sample Introduction
The first step in analysis is the introduction of the sample. This has been achieved in ICPMS
through a variety of means. ICP-MS spectrometers can accept solid as well as liquid samples.
Solid samples are introduced into the ICP by way of a laser ablation system which can usually
be purchased as an accessory. Aqueous samples are introduced by way of a nebulizer which
aspirates the sample with high velocity argon, forming a fine mist. The aerosol then passes into
a spray chamber where larger droplets are removed via a drain (fig 2). The most common
method is the use of a nebulizer. This is a device which converts liquids into an aerosol, and
that aerosol can then be swept into the plasma to create the ions. Nebulizers work best with
simple liquid samples (i.e. solutions). However, there have been instances of their use with
more complex materials like slurry. Many varieties of nebulizers have been coupled to ICP-
MS, which includes pneumatic, cross-flow, Babington, ultrasonic, and desolating types. The
aerosol generated is often treated to limit it to only smallest droplets, commonly by means of
a double pass or cyclonic spray chamber. Use of auto samplers makes this easier and faster.
Less commonly, the laser ablation has been used as a means of sample introduction. In this
method, a laser is focused on the sample and creates a plume of ablated material which can be
swept into the plasma. This is particularly useful for solid samples, though can be difficult to
create standards for leading the challenges in quantitative analysis. Other methods of sample
introduction are also utilized. Electro thermal vaporization (ETV) and in torch vaporization
(ITV) hot surfaces (graphite or metal, generally) are used to vaporize samples for introduction.
These can use very small amounts of liquids, solids, or slurries. Other methods like vapor
generation are also known.

Fig.4.1: Generation of Aerosol by nebulizer

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY
4.2 Inductively Coupled Plasma
Inductively coupled plasma is plasma that contains a sufficient concentration of ions and
electrons to make the gas electrically conductive. The plasmas used in spectrochemical analysis
are essentially electrically neutral, with each positive charge on an ion balanced by a free
electron. In these plasmas the positive ions are almost all singly charged and there are few
negative ions, so there are nearly equal amounts of ions and electrons in each unit volume of
plasma. Inductively coupled plasma (ICP) for spectrometry is sustained in a torch that consists
of three concentric tubes, usually made of quartz. The end of this torch is placed inside an
induction coil supplied with a radiofrequency electric current [5]. A flow of argon gas (usually
14 to 18 liters per minute) is introduced between the two outermost tubes of the torch and an
electric spark is applied for a short time to introduce free electrons into the gas stream. These
electrons interact with the radio-frequency magnetic field of the induction coil and are
accelerated first in one direction, then the other, as the field changes at high frequency. The
accelerated electrons collide with argon atoms, and sometimes a collision causes an argon atom
to part with one of its electrons. The released electron is in turn accelerated by the rapidly
changing magnetic field. The process continues until the rate of release of new electrons in
collisions is balanced by the rate of recombination of electrons with argon ions (atoms that
have lost an electron). This produces a ‘fireball’ that consists mostly of argon atoms with a
rather small fraction of free electrons and argon ions. The temperature of the plasma is very
high, of the order of 10,000 K5.The ICP can be retained in the quartz torch because the flow of
gas between the two outermost tubes keeps the plasma away from the walls of the torch.A
second flow of argon (around 1 liter per minute) is usually introduced between the central tube
and the intermediate tube to keep the plasma away from the end of the central tube. A third
flow (again usually around 1 liter per minute) of gas is introduced into the central tube of the
torch. This gas flow passes through the center of the plasma, where it forms a channel that is
cooler than the surrounding plasma but still much hotter than a chemical flame. Samples to be
analyzed are introduced into this central channel, usually as a mist of liquid formed by passing
the liquid sample into a nebulizer6. As a droplet of nebulized sample enters the central channel
of the ICP, it evaporates and any solids that were dissolved in the liquid vaporize and then
break down into atoms. At the temperatures prevailing in the plasma a significant proportion
of the atoms of many chemical elements are ionized, each atom losing its most loosely bound
electron to form a singly charged ion.

4.3 Argon Plasma/Sample Ionization

Once the sample passes through the nebulizer and is partially de solvated, the aerosol moves
into the torch body and is mixed with more argon gas. A coupling coil is used to transmit radio
frequency to the heated argon gas, producing an argon plasma "flame" located at the torch.The
hot plasma removes any remaining solvent and causes sample atomization followed by
ionization. In addition to being ionized, sample atoms are excited in the hot plasma, a
phenomenon which is used in ICP-atomic emission spectroscopy. Shown to the right is an ICP
torch. The aerosol moves into the bottom of the torch body. The green ports on the right side
of the body are where more argon is introduced to the flow. At the top are two high quality
quartz tubes and an inner alumina injector tube (fig 3).

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Fig.4.3: Photo of argon plasma in operation processes

4.4 Plasma Torch
The plasma used in an ICP-MS is made by partially ionizing argon gas (Ar → Ar+ + e−). The
energy required for this reaction is obtained by pulsing an electrical current in wires that
surround the argon gas. After the sample is injected, the plasma's extreme temperature causes
the sample to separate into individual atoms (atomization). Next, the plasma ionizes these
atoms (M → M+ + e−) so that they can be detected by the mass spectrometer (fig 4).

Fig.4.4.1: ICP Torch Body

Inductively coupled plasma (ICP) for spectrometry is sustained in a torch that consists of three
concentric tubes, usually made of quartz. The end of this torch is placed inside an induction
coil supplied with a radiofrequency electric current. A flow of argon gas (usually 14 to 18 liters
per minute) is introduced between the two outermost tubes of the torch and an electrical spark
is applied for a short time to introduce free electrons into the gas stream. These electrons
interact with the radio-frequency magnetic field of the induction coil and are accelerated first
in one direction, then the other, as the field changes at high frequency (usually 27.12 MHz).
The accelerated electrons collide with argon atoms, and sometimes a collision causes an argon
atom to part fraction of free electrons and argon ions.

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY
An ICP-MS combines a high-temperature ICP (Inductively Coupled Plasma) source with a
mass spectrometer. The ICP source converts the atoms of the elements in the sample to ions.
These ions are then separated and detected by the mass spectrometer. Figure 5 shows a
schematic representation of an ICP source in an ICP-MS. Argon gas flows inside the concentric
channels of the ICP torch. The RF load coil is connected to a radiofrequency (RF) generator.
As power is supplied to the load coil from the generator, oscillating electric and magnetic fields
are established at the end of the torch (fig 5). The sample is typically introduced into the ICP
plasma as an aerosol, either by aspirating a liquid or dissolved solid sample into a nebulizer or
using a laser to directly convert solid samples into an aerosol. Once the sample aerosol is
introduced into the ICP torch, it is completely desolvated and the elements in the aerosol are
converted first into gaseous atoms and then ionized towards the end of the plasma.

Fig.4.4.2: ICP Torch showing the fate of the sample

4.5 ICP-MS Interface

Because atomization/ionization occurs at atmospheric pressure, the interface between the ICP
and MS components becomes crucial in creating a vacuum environment for the MS system.
Ions flow through a small orifice, approximately 1 millimeter in diameter, into a pumped
vacuum system. Here a supersonic jet forms and the sample ions are passed into the MS system
at high speeds, expanding in the vacuum system. The entire mass spectrometer must be kept in
a vacuum so that the ions are free to move without collisions with air molecules. Since the ICP
is maintained at atmospheric pressure, a pumping system is needed to continuously pull a
vacuum inside the spectrometer. In order to most efficiently reduce the pressure several pumps
are typically used to gradually reduce pressure to 10-5 mbar before the ion stream reaches the
quadruple. If only one pump were used, its size would be excessive to reduce the pressure
immediately upon entering the mass spectrometer.

4.6 Mass Spectrometer

In the first stage of the mass spectrometer ions are removed from the plasma by a pumped
extraction system. An ion beam is produced and focused further into the actual unit. There are
several different types of mass analyzers which can be employed to separate isotopes based on
their mass to charge ratio. Quadrupole analyzers are compact and easy to use but offer lower
resolution when dealing with ions of the same mass to charge (m/z) ratio. Double focusing
sector analyzers offer better resolution but are larger and have higher capital cost. The
quadrupole mass filter is made up of four metal rods aligned in a parallel diamond pattern. A
combined DC and AC electrical potential is applied to the rods with opposite rods having a net

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY
negative or positive potential. Ions enter into the path between all of the rods. When the DC
and AC voltages are set to certain values only one particular ion is able to continue on a path
between the rods and the others are forced out of this path. This ion will have a specific m/z
ratio. Many combinations of voltages are chosen which allows an array of different m/z ratio
ions to be detected.
Shown below is animation of this process. Three mass fragments enter into the quadrupole
vacuum chamber. The voltage of the rods is set so that only the pink mass fragment passes
completely through the quadrupole rod array and into the detector. The green and blue
fragments are unstable at this voltage combination and their path eventually brings them into
contact with the rods so that they never reach the detector (fig 6).

Fig.4.6.1: Animation of quadrupole mass filter separating ions

Quadrupole rods require periodic maintenance and cleaning due to the buildup of ions which
are removed during the mass discrimination process. These ions form a film which eventually
builds up and dulls the metallic surface. To remove this film the vacuum chamber must be
repressurized and disassembled. This process can be time consuming and very delicate but is
essential to keep a mass spectrometer performing well (fig.7).

Fig.4.6.2: Photo of quadrupole rods from mass spectrometer

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY
Once the ions enter the mass spectrometer, they are separated by their mass-to-charge ratio.
The most commonly used type of mass spectrometer is the quadrupole mass filter. In this type,
4 rods (approximately 1 cm in diameter and 15-20 cm long) are arranged as in (Fig 8).

Fig.4.6.3: Schematic of quadrupole mass filter

In a quadrupole mass filter, alternating AC and DC voltages are applied to opposite pairs of
the rods. These voltages are then rapidly switched along with an RF-field. The result is that an
electrostatic filter is established that only allows ions of a single mass-to-charge ratio (m/e)
pass through the rods to the detector at a given instant in time. So, the quadrupole mass filter
is really a sequential filter, with the settings being change for each specific m/e at a time.
However, the voltages on the rods can be switched at a very rapid rate. The result is that the
quadrupole mass filter can separate up to 2400 amu (atomic mass units) per second.

4.7. Detector
The most common type of ion detector found in an ICP-MS system is the channeltron electron
multiplier. This cone or horn shaped tube has a high voltage applied to it opposite in charge to
that of the ions being detected. Ions leaving the quadrupole are attracted to the interior cone
surface. When they strike the surface additional secondary electrons are emitted which move
farther into the tube emitting additional secondary electrons (fig 9).

Fig.4.7.1: Electron Multiplier Schematic

As the process continues even more electrons are formed, resulting in as many as 108 electrons
at the other end of the tube after one ion strikes at the entrance of the cone. The drawing below
is an illustration of electron multiplying and the photograph is an actual electron multiplier
removed from a mass spectrometer for cleaning. Importance of cleaning is similar to that of the
quadrupole rods (fig 10).

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Fig.4.7.2: Electron Multiplier Removed for Cleaning

A few things to remember about the ICP-MS detector

1. It is a consumable item. As ions hit the surface of the detector and are converted to
electrons, the active film coating will be consumed. Depending on usage, a typical
discrete dynode detector will last 6-18 months in a quadrupole ICP-MS.
2. It should be protected from high signal count rates. Most manufacturers' design the
detector circuitry to protect it from potentially fatal ion count rates. However, the users
can further this by diluting samples with known high concentration values or choosing
a less abundant isotope for their analysis.
3. They are expensive. A new detector will cost on the order of $1500-2500 depending on
the specific type. Care should be taken to protect it.
4. They are light sensitive. Most detectors are as sensitive to photons as they are to ions.
Care should be taken to store spare detectors in the dark and never expose a detector to
the light while the high voltage power supply to it is on.

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

4.8 Detection Limits

One of the great advantages to ICP-MS is extremely low detection limits for a wide variety
of elements. Some elements can be measured down to part per quadrillion range while most
can be detected at part per trillion levels. The table below shows some common detection
limits by element.
Element Detection Limit
(ppt)
U, Cs, Bi less than 10
Ag, Be, Cd, Rb, Sn, Sb, Au 10-50
Ba, Pb, Se, Sr, Co, W, Mo, 50-100
Mg
Cr, Cu, Mn 100-200
Zn, As, Ti 400-500
Li, P 1-3 ppb
Ca less than 20 ppb

4.9 Sample Preparation

For most clinical methods using ICP-MS, there is a relatively simple and quick sample prep
process. The main component to the sample is an internal standard, which also serves as the
diluent. This internal standard consists primarily of deionized water with nitric or hydrochloric
acid, and Indium and/or Gallium. Depending on the sample type, usually 5 ml of the internal
standard is added to a test tube along with 10–500 micro liters of sample. This mixture is then
vortexed for several seconds or until mixed well and then loaded onto the auto sampler tray.
For other applications that may involve very viscous samples or samples that have particulate
matter, a process known as sample digestion may have to be carried out, before it can be
pipetted and analyzed. This adds an extra first step to the above process, and therefore makes
the sample prep more length.

4.10 Elemental Analysis

The ICP-MS allows determination of elements with atomic mass ranges 7 to 250. This
encompasses Li to U. Some masses are prohibited such as 40 due to the abundance of argon in
the sample. Other blocked regions may include mass 80 (due to the argon dimer), and mass 56
(due to ArO), the latter of which greatly hinders Fe analysis unless the instrumentation is fitted
with a reaction chamber. A typical ICP-MS will be able to detect in the region of Nano grams
per liter to 10 or 100 milligrams per liter or around 8 orders of magnitude of concentration
units.

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Chapter 5
PHARMACEUTICAL APPLICATIONS

1. One of the largest volume uses for ICPMS is in the medical and forensic field,
specifically, toxicology. A physician may order a metal assay for a number of reasons,
such as suspicion of heavy metal poisoning, metabolic concerns, and even hepatological
issues. Depending on the specific parameters unique to each patient's diagnostic plan,
samples collected for analysis can range from whole blood, urine, plasma, serum, to
even packed red blood cells.
2. Another primary use for this instrument lies in the environmental field. Such
applications include water testing for municipalities or private individuals all the way
to soil, water and other material analysis for industrial purposes.
3. This technique is also widely used the field of radiometric dating, in which it is used to
analyze relative abundance of different isotopes. ICP-MS is more suitable for this
application than the previously used Thermal Ionization Mass Spectrometry, as species
with high ionization energy such as Osmium (Os) and Tungsten (Hf-W) can be easily
ionized.
4. In the field of flow cytometry, a new technique uses ICP-MS to replace the traditional
fluorochromes. Briefly, instead of labeling antibodies (or other biological probes) with
fluorochromes, each antibody is labeled with a distinct combination of lanthanides.
5. Regardless of the sample type, blood, water, etc., it is important that it be free of clots
or other particulate matter, as even the smallest clot can disrupt sample flow and block
or clog the sample tips within the spray chamber. Very high concentrations of salts, e.g.
sodium chloride in sea water, can eventually lead to blockages as some of the ions
reunite after leaving the torch and build up around the orifice of the skimmer cone. This
can be avoided by diluting samples whenever high salt concentrations are suspected,
though at a cost to detection limits.
6. Quantification of proteins and bio molecules by icp-ms: There is an increasing trend of
using ICP-MS as a tool in speciation analysis normally involves a front end
chromatograph separation and an elemental selective detector such as AAS and ICP-
MS. For example, ICP-MS may be combined with size exclusion chromatography and
quantitative preparative native continuous polyacrylamide gel electrophoresis for
identifying and quantifying native metal in bio fluids. Also the phosphorylation status
of proteins can be analyzed.
7. A new type of protein tagging reagents called metal coded affinity tags (Me CAT) were
introduced to label proteins quantitatively with metals, especially lanthanides. The Me
CAT labeling allows relative and absolute quantification of all kind of proteins or other
biomolecules like peptides. Me CAT comprises a sitespecific biomolecule tagging
group with at least a strong chelate group which binds metals.
8. The Me CAT labeled proteins can be accurately quantified by ICP-MS down to low
attomol amount of analyte which is at least 2–3 orders of magnitude more sensitive than
other mass spectrometry based quantification methods.

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

9. By introducing several Me CAT labels to a biomolecule and further optimization of

LC-ICP-MS detection limits in the zeptomol range are within the realms of possibility.
By using different lanthanides Me CAT multiplexing can be used for pharmacokinetics
of proteins and peptides or the analysis of the differential expression of proteins e.g. in
biological fluids.

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Chapter 6
NEXT GENERARION OF ICP-MS (NexION 300 ICP-MS)
6.1 Introduction

The NexION 300 offers 3 modes of operation (Standard, Collision and Reaction) and can be
quickly switched from 1 mode to another. So, every analysis can be performed on the same
instrument. It’s the only ICP-MS that lets you maximize productivity without compromising
sensitivity or performance. And, for the first time ever, a single ICP-MS instrument offers both
the simplicity and convenience of a collision cell and the exceptional detection limits of a true
reaction cell. Stability is optimized by incorporating a unique Triple Cone Interface and
Quadrupole Ion Deflector. Designed to remove an unprecedented level of un-ionized material
(and preventing it from entering the Universal Cell), this innovative ion path keeps the
instrument clean, minimizing drift and eliminating the need for cell cleanings.

Fig. 6.1 NexION 300 ICP-MS

6.2 Modes of Operation

Only PerkinElmer Sciex™ offers a collision cell (with Kinetic Energy Discrimination) and a
true reaction cell (with a scanning quadrupole), to bring together the two most powerful
polyatomic interference removal techniques in the same instrument for the first time. Together
with the instrument’s Standard setting, this Universal Cell Technology (UCT) allows the
instrument to be run in three different modes depending on the level of interference removal
and detection limits required.

6.2.1 Standard Mode

Unlike other systems, the NexION 300’s cell is actively vented to remove residual gases. This
enables the instrument to run in true Standard mode—with the cell turned off—so you
experience none of the decreased sensitivity encountered with passively vented systems.
Without being able to quickly vent their cells, instruments from other manufacturers are forced
to use KED even in Standard mode because of potential interferences, and are limited to using

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY
only a single gas. For elements not requiring interference correction, Standard mode can
provide sensitivity equal to that of Collision or Reaction mode when done properly.

6.2.2 Collision Mode

Ideal for semi-quantitative analyses, environmental sample monitoring, and the testing of
unknown samples, the NexION 300’s Collision mode offers the perfect mix of performance
and simplicity. By using a simple nonreactive gas, Collision mode removes many interferences
to deliver better detection limits than Standard mode for some elements.

6.2.3 Reaction Mode

Universally recognized as the technique offering the ultimate detection limits (even with the
most difficult elements and matrices), the NexION 300’s Reaction mode removes any and all
interferences with little or no loss of analyte sensitivity. Unlike other instruments that claim to
have a Reaction mode, NexION features a scanning quadrupole that removes targeted
interferences and reaction products in the Universal Cell, enabling any reactive gas to be used
in the system, and allowing only the element of interest to pass to the analyzing quadrupole.

6.3 Stabilization

Before the ion beam even enters the Universal Cell, it is defined and focused more thoroughly
and effectively than on any other instrument by a revolutionary three-cone interface and a
proprietary Quadrupole Ion Deflector. By removing most neutrals and photons, this innovative
combination eliminates drift and delivers exceptional signal stability hour after hour, even
when running the most challenging matrices. Reproducible performance can only be attained
with a clean cell. And no other instrument does more to prevent sample deposition than the
NexION 300. In fact, the instrument has been engineered to remove un-ionized material so
effectively that its cell does not require routine cleaning. The end result is a system that rarely
needs to be recalibrated, delivering superior productivity and maximum uptime.

Quadrupole Ion Deflector

Detector Quadrupole Mass Filter Universal Cell

Triple Cone
Interface

Fig. 6.3 Schematic of Stabilization process

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY
6.3.1 Triple Cone Interface

In addition to the sampler cone and skimmer cone typically found on all other ICP-MS systems,
the NexION 300 also features a unique hyper skimmer cone for the most tightly defined ion
beam available. Pressure within the two-chambered design is reduced in smaller steps than in
other instruments, providing less dispersion of ions and preventing sample deposition on
internal surfaces. Voltages never need adjusting and all three cones are outside the vacuum
area so they can be quickly and easily removed, cleaned and replaced to minimize instrument
downtime.

Un-ionized
Material

Positively
Charged Ions

Fig.6.3.1 Triple Cone Interface

6.3.2 Quadrupole Ion Deflector

Designed around a proprietary, miniaturized quadrupole, this breakthrough filtering feature
turns ions 90 degrees, focusing those of a specified mass into the Universal Cell and discarding
all neutral species. The path through the Quadrupole Ion Deflector is aligned with the tightly
defined ion beam leaving the Triple Cone Interface. This ensures ions and neutrals never impact

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY
the component’s surfaces, keeping it clean for superior stability and eliminating cleaning
requirements.
6.4 Features and benefits of the NexION 300 ICP-MS
i) Simultaneous Dual Mode (Analog/ Digital) Detector
Provides over nine orders of dynamic range and measures both high- and low-level analytes
simultaneously. Also delivers the fastest data acquisition rates of any ICP-MS instrument on
the market, making the NexION 300 an ideal tool for the emerging nano materials field.
ii) Large, Open Sample Introduction Area
Accommodates a wide variety of sample introduction systems and is easily accessible to both
left- and right-handed users.
iii) Low liquid uptake Nebulizer
Saves money by reducing sample consumption and minimizing lab waste. Every NexION 300
ships with a concentric nebulizer and cyclonic spray chamber and can be user-defined for
specific applications.
iii) Free running RF plasma generator
Unlike other systems, the NexION 300’s RF generator features no moving parts for reliable,
robust performance, and instantly changes to accommodate any plasma—ideal for
petrochemical applications and speciation solvents.
iv) Benchtop design with no rear connections
Saves valuable laboratory space and allows operation and installation up against a wall.
v) Fastest-scanning quadrupole in the industry (>5000 amu/sec)
Offers the fastest peak hopping and highest analytical mass range available (all the way up to
280 amu).
vi) Universal Cell Technology
Offers three modes of operation (Standard, Collision or Reaction) depending on the level of
performance required. Switching between modes is quick and easy so users can select the best
mode for a particular analysis without compromising speed.
vii) Triple Cone Interface
Produces the most tightly focused ion beam in the industry, reducing build-up on internal
components (particularly the Quadrupole Ion Deflector) so maintenance and cleaning are
minimized.
viii) Quadrupole Ion Deflector
Allows only ions of a specified mass to pass into the Universal Cell, enhancing sensitivity
while keeping the cell clean—making it the only ICP-MS on the market with a cell that never
needs cleaning or replacing.

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY
ix) Custom-designed, four-stage vacuum system
Features the highest capacity turbo and roughing pumps and allows the use of any collision or
reaction gas in the Universal Cell. Pump down can be achieved in a fraction of the time of other
systems, allowing users to get back to running samples 2-3 times faster than with other
instruments.

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Chapter 7
CONCLUSION
It is important to remember that there are many criteria to consider when selecting a trace
element technique. It should be used as a guideline to evaluate the most commonly used trace
and ultratrace, atomic spectroscopy-based techniques. It has been done in a very simplistic way
and has not attempted to compare the many variations, features, and sampling accessories
offered by the different manufacturers. However, it is clear that there is no single technique
suitable for all applications. They all have their own strengths and weaknesses. It is therefore
important when making the comparison that all these avenues are explored. Maybe ICP-MS is
a technique that you would really like to have in your laboratory.

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INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Chapter 8
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