C H A P T E R

1
Milestones in the Development
of Gas Chromatography
Walter G. Jennings, Colin F. Poole

O U T L I N E

1.1. Introduction 2 1.5. Interfacing Glass Capillary Columns

to Injectors and Detectors 7
1.2. The Invention of Gas Chromatography 2
1.6. The Hindelang Conferences and the
1.3. Early Instrumentation 2
Fused-Silica Column 8
1.3.1. Early Commercial Instruments 3
1.7. Increasing Sophistication of
1.4. Early Column Developments 4
Instrumentation 10
1.4.1. Do-it-Yourself Glass Capillary
1.7.1. Column Heating 11
Columns 4
1.7.2. Sample Introduction 12
1.4.2. The Positive Results of Patent
1.7.3. Detectors 13
Enforcement 5
1.7.4. Data Handling 14
1.4.3. Mileposts in Coating WCOT
1.7.5. Comprehensive Gas
Capillary Columns 5
Chromatography 15
1.4.4. Commercial Column Manufacturers 6
1.4.5. Bonded, Crosslinked, and/or 1.8. Decline in the Expertise of the Average
Immobilized Stationary Phases 6 Gas Chromatographer 16
1.4.6. Further Improvements
in Stationary Phases 7

Gas Chromatography DOI: 10.1016/B978-0-12-385540-4.00001-8 1 Copyright 2012 Elsevier Inc. All rights reserved.
2 1. MILESTONES IN THE DEVELOPMENT OF GAS CHROMATOGRAPHY
1.1. INTRODUCTION
This article was started by the senior author
Walter Jennings who was unable to complete it
due to poor health. Sections 1.2e1.6 are
a personal account of the early days of gas chro-
matography seen through the eyes of one of the
major pioneers and innovators in this field.
With only minor editorial changes made by
the junior author, these are presented as Walter
intended. As the junior author I am responsible
for Sections 1.7 and 1.8. These sections extend
Walters comments on the early days of gas
chromatography to the present day.
1.2. THE INVENTION OF GAS
CHROMATOGRAPHY
In 1952 A.J.P. Martin and R.L.M. Synge were
both awarded Nobel Prizes for their work in the
field of liquid/solid chromatography. Martin, in
his award address, suggested it might be possible
to use a vapor as the mobile phase. Some years
later, James and Martin used ethyl acetate vapor
to desorb a mixture of fatty acids that had been
affixed to an adsorbent, and placed in a tube.
The vapor stream eluting from that tube was
directed to an automated titration apparatus,
resulting in a graph showing a series of steps
that reflected the sequential additions of base as
each eluted acid was neutralized by automated
titration [1]. Many practitioners have for far too
long considered this as the starting point of gas
chromatography.
In 2008 Leslie Ettre published an article in
which he stated, . the activities of Professor
Erika Cremer and her students at the University
of Innsbruck, Austria, in the years following the
Second World War, represented the true start of
their continuous involvement in gas chromatog-
raphy [2]. After exploring Ettres arguments
and conducting some research myself, I fully
agree with his conclusions. I now believe that
the theoretical basis for gas chromatography
was first conceived by Erika Cremer, an
Austrian scientist at the University of Inns-
bruck, Austria, in the late 1940s during the
period of the Second World War. As Ettre points
out, this was a period when women, especially
in Germanic countries, were expected to confine
their activities to children, church, and
kitchen. In spite of her superb Ph.D. thesis
work she had great difficulty in finding a posi-
tion. Her opportunity came in 1940 when the
war started, and university teachers were
drafted. She obtained an academic position at
the University of Innsbruck, Austria (then
a part of Germany) in the Institute of Physical
Chemistry. It was here that she and her students
(with major credit to Fritz Prior) constructed the
first prototype of a gas chromatograph
(Figure 1.1) and, after a long delay that was
probably attributable to the war, published the
results of their research in 1951 [3,4]. At this
time she was promoted to Professor and, some
twenty years later, to director of the Universitys
Institute of Physical Chemistry. Professor Dr.
Cremer, by all accounts a brilliant woman scien-
tist, died in 1996.
1.3. EARLY INSTRUMENTATION
By 1953, several petroleum companies,
primarily in Great Britain and the Netherlands,
were exploring this new analytical technique,
and in 1954, a few flavor chemists (including
this author) were building crude chromato-
graphs, many of them based on an article by
N. H. Ray [5]. Ray inserted thermal conduc-
tivity cells into a Wheatstone bridge, whose
outlet connected to a strip chart recorder, thus
generating a Gaussian peak for each eluting
solute; this was (to my knowledge) the first
gas chromatogram as we know them today.
The schematics and chromatograms published
by Ray encouraged a number of readers
(including the author) to build similar chro-
matographs. Almost every part of these crude
 1.3. EARLY INSTRUMENTATION 3

FIGURE 1.1 The gas chromatographic system used in Prior work, in 1945e1947. A adsorbent for purification of the
carrier gas (hydrogen); B sample inlet system; C buret containing mercury with niveau glass for sample introduction;
D Dewar flask; E separation column (containing silica gel on activated carbon); and F thermal conductivity detector.
Source: From ref. [4] copyright Friedr. Vieweg & Sohn.

instruments had to be self-designed and self-
made, but this introduced the days of the
packed column; supports, such as granules of
diatomaceous earth, were coated with a variety
of high boiling fluids (e.g. diethylene glycol
succinate, DEGS) and, in our earliest efforts,
packed into copper columns, typically 3e6 m
long with internal diameters of about 6 mm,
and (usually) coiled. It was soon recognized
that copper columns were quite active and
most workers switched, first to stainless steel,
and then to coiled glass tubing of similar
dimensions. The reminiscences of many of the
early pioneers in gas chromatographic instru-
mentation are summarized in [6].
1.3.1. Early Commercial Instruments
The first companies to manufacture gas
chromatographs (GCs) in Europe were Griffin
and George (London) and Metropolitan
Vickers Electric (Manchester), but the U.S.
instrument companies had a greater impact
on the development of this new area [7]. Per-
kin Elmer was one of the first companies to
market a gas chromatograph; in May of
1954, they introduced their Model 154 Vapor
Fractometer. The temperature of the column
oven was adjustable from room temperature
to 150
C, and it offered a flash vaporizer
with a rubber septum permitting syringe
injection into the carrier gas stream. The
detector was a thermal conductivity cell. The
instrument was a great success and sold
widely [8]. In early 1956, Perkin Elmer fol-
lowed up with their Model 154-B, with
a temperature range from room temperature
to 225
C and could be fitted with an optional
rotary valve offering a variety of sample loops
for the injection of gas samples.
4 1. MILESTONES IN THE DEVELOPMENT OF GAS CHROMATOGRAPHY
1.4. EARLY COLUMN
DEVELOPMENTS
All of the early instruments utilized packed
columns, some coiled, some U-shaped. Packed
columns all have one thing in common: they
possess a high resistance to gas flow, and this
limits the practical length of the column, usually
to a few meters. In much later days, some
packed columns approached an efficiency
equivalent to our current 0.32 mm internal
diameter capillary columns (ca. 3000 plates per
meter), but because of their length limitations,
they could achieve perhaps 35,000 theoretical
plates while a 30 m open-tubular 0.25 mm
internal diameter column should be capable of
three times that efficiency, merely because it is
three times longer.
It was at the 1958 Second International
Symposium on Gas Chromatography in
Amsterdam that Marcel Golay, who was then
a consultant to Perkin Elmer, introduced the
theory of open-tubular capillary columns and
demonstrated their superiority to packed
columns [9]. (There is no connection between the
old Perkin Elmer referred to here and the Perkin
Elmer of today, they are entirely different compa-
nies.) These columns demanded much smaller
sample injections, necessitating more sensitive
detectors than the thermal conductivity detec-
tors that were in common use at the time. Fortu-
nately, James E. Lovelock had invented an
electron-capture detector in 1957 [10], and in
1958 the flame ionization detector appeared;
some credit this to Harley, Nel, and Pretorious
[11], and others to McWilliams and Dewer
[12,13]; these increased detector sensitivities by
ca. 103e106. The invention and development of
the flame ionization detector is discussed in
more detail in [14]. Early capillary columns
were of plastic and copper tubing; the former
had serious temperature limitations and the
latter was active; this led to stainless steel
tubing. Perkin Elmer had filed for and been
granted patents on the open-tubular concept,
essentially worldwide. I purchased two Perkin
Elmer wall-coated open-tubular (WCOT)
columns at different times, only to find that
the columns available from them produced
abominable results. Perkin Elmer apparently
recognized this fact, because they essentially
abandoned their research efforts on WCOT
columns, outsourced their production, and re-
directed their efforts to columns whose interiors
were first coated with a support material (e.g.
diatomaceous earth) and then with the
stationary phase. These were dubbed support
coated open-tubular (SCOT) columns. Perkin
Elmer continued to rigorously enforce the
patent on WCOT (and SCOT) columns, but
under considerable pressure (especially from
the applicant) they were forced to issue one
license, to Hansjurg Jaeggi, a former assistant
of Kurt Grob in Switzerland. Under Swiss law,
if a patent bars a Swiss from conducting his or
her business, a license must be issued. Jaeggi
had been and still was making excellent glass
WCOT columns. The high quality of his
columns led Perkin Elmer to later propose that
they collaborate, but, probably because of the
acrimonious battle he had gone through to
obtain his license, he wanted nothing more to
do with Perkin Elmer, and refused their offer.
His obituary, written by Konrad Grob, makes
interesting reading [15].
1.4.1. Do-it-Yourself Glass Capillary
Columns
In 1965, Desty et al. invented an elegantly
simple machine for drawing long lengths of
coiled glass capillaries [16]. Besides the fact
that his was much less expensive tubing, it
also had a smoother interior and it was trans-
parent. For the first time, it was possible to scru-
tinize the layer of stationary phase as it existed
on the column wall; soon it was obvious that
when a new unused column exhibiting a thin
 1.4. EARLY COLUMN DEVELOPMENTS
uniform film of stationary phase was exposed to
higher temperatures, the stationary phase
collected into beads that were randomly scat-
tered over the inner surface. Almost immedi-
ately scores of scientists realized that many of
the low viscosity fluids that worked well in
packed columns were unsatisfactory for
WCOT columns and should be replaced with
high viscosity materials that would retain their
high viscosity even at higher temperatures.
Low-viscosity silicone fluids (e.g. OV 101)
were replaced with high viscosity silicones
(e.g. OV 30, a viscous paste-like silicone), and
experimenters soon began producing much
more stable columns.
1.4.2. The Positive Results of Patent
Enforcement
The low quality of the Perkin Elmer WCOT
columns and enforcement of their patent led
many scientists to begin making their own
columns for their own use. This caused investi-
gators in many other fields, who would have
preferred to purchase usable columns from an
outside source and confine their research to
some other field, to now have to make columns;
scores of scientists were now studying and
publishing on methods of pretreating, deacti-
vating, and coating columns. Their combined
results were responsible for many of the
advances in column improvements, and they
soon surpassed the results that had been gener-
ated by Perkin Elmer [17].
1.4.3. Mileposts in Coating WCOT
Capillary Columns
Golay had coated his original glass open-
tubular columns by completely filling them
with a dilute solution of stationary phase in
a low-boiling solvent, sealing one end, and
then drawing the column, open end first,
through an oven [18]. As used by Golay, the
5
column could be coiled only after coating,
a distinct drawback. The method was improved
by Ilkova and Mistrykov [19], who coiled, and
then filled the column and sealed one end. The
open end of the filled column was fed into
a heated oven by supporting the column on
a rotating rod fitted with a drive roller at the
entrance to the column oven, thus literally
screwing the rest of the column into the oven.
Up until just a few years ago, all chemistry
departments at the multicampus Universities
of California system frowned on applied
research, and chemistry department faculties
drifting away from pure organic chemistry or
pure physical chemistry rarely survived to
tenure. Analytical chemistry was essentially
forbidden. There were many faculty members
scattered through various other departments
who were analytical chemists, and eventually
they formed a Group in Analytical and Envi-
ronmental Chemistry, open to anyone in any
department who had interests in the analytical
side. At one time I chaired that group for
several years and it still exists. At this time,
my title was Professor of Food Science and
Technology and Chemist in the Experiment
Station. This had several advantages: for one
thing, those with just the academic title worked
nine months per year, while the Experiment
Station operated eleven months a year. My
department chairman tolerated what he called
my dabbling in gas chromatography, but
insisted that I should also be working on
subjects more aligned with the food indus-
tries; he suggested circulation cleaning
which was just emerging. Swallowing what I
wanted to say, I assigned a new Ph.D. student
(Malcolm Bourne) to the project, built a minia-
ture circulation pipeline, and helped him bake
radio-labeled tristearin onto glass microscope
slides and strips of stainless steel of similar
width and length. These were inserted into
the rapid circulating system, and the levels of
radioactivity measured every two minutes.
6 1. MILESTONES IN THE DEVELOPMENT OF GAS CHROMATOGRAPHY
Inevitably, semi-log plots of our cleaning
curves showed a rapidly dropping curve that
terminated in a straight line with a slight
downward slope. All at once Bourne realized
that he was looking at two first-order reactions
that were occurring simultaneously. The baked
film of tristearin existed only at one of two
energy levels, a loosely bound system, and
a much more tightly bound system e nothing
in between. Spatial estimates indicated that
the tightly bound form was not a monolayer,
but could be up to at least twenty molecular
thicknesses [20e22]. He also discovered that
by manipulating time and temperature, he
could change the ratio of the two species.
Bourne went on to study the kinetics of clean-
ing in much greater depth, and made quite
a name for himself. I went back to my
dabbling, then slowly realized that my newly
gained knowledge on removal of thin films was
just the reverse of achieving more stable coat-
ings of stationary phases to the column surface.
This may have guided me as I attempted to
modify our column coating apparatus. After
replacing the opaque lid of the oven with a glass
lid, it was obvious that the solution was super-
heated and evaporated in a series of minor
explosions, leaving blotches of stationary phase
randomly scattered over the surface of the
column. I decided to introduce the column
into the oven through a preheater made from
a short curved length of 1/8 inch stainless steel
tubing lagged with an electrically heated wire
and heated to 150
C: the columns passage
through the curved preheater was not smooth;
indeed, it scraped the walls and vibrated. To
avoid breakage, I introduced graphite powder
into the loop. The column continued to vibrate,
but more gently. In retrospect, that vibration at
this point on its passage into the oven would
also discourage super-heating. It may have
been dumb luck, but from then on, the evapora-
tion of the solvent occurred smoothly. We were
routinely producing very stable columns with
uniformly thin coatings.
1.4.4. Commercial Column
Manufacturers
At this point, one of my Ph.D. students,
Robert Wohleb, suggested that we had a market-
able product and should establish a column
production company. When I broached this
suggestion with my department chairman, he
called in the dean. After much discussion, they
agreed that I could engage in this activity only
if I agreed to several restrictions: (1) as long as
I was a full time professor, I could receive no
remuneration from this venture; (2) there could
be no connection between my university
research and activities of the company; (3) I
could not get involved in the day-to-day activi-
ties of the company. I could, on my own time,
answer trouble-shooting questions and engage
in educational activities. J&W Scientific was
founded in 1974; I constructed two drawing
machines in my machine shop at home, and
left them with Wohleb as I departed on my
second sabbatical leave, this time in Karlsruhe,
Germany. Sandy Lipsky had launched his
company, Quadrex, slightly ahead of J&W.
1.4.5. Bonded, Crosslinked, and/or
Immobilized Stationary Phases
In 1975, J&W noticed a sudden drop in
column sales from several regular customers;
fortunately, we had been using (and saving)
bar codes to trace every step each column
went through. The bar codes on all of the
columns those customers had been buying
showed they had all gone through the same
coating machine in the same general time
period. I called several of the buyers and asked
if they were having problems with our
columns, and was shocked when they replied,
no, the columns are great e they never wear
out. This was serious, we were putting
ourselves out of business. In checking that
coating machine, it was discovered that the
thermocouple on the preheater through which
 1.5. INTERFACING GLASS CAPILLARY COLUMNS TO INJECTORS AND DETECTORS
the column entered the oven had failed some
time ago and was giving much lower readings.
Over the past few weeks, the technician on the
machine had simply compensated for the low
reading by boosting the voltage. Instead of
150
C, that preheater was close to 300
C. The
stationary phase we were using (SE-54) con-
tained 1% vinyl. Our R&D head, Rand Jenkins,
realized that serendipity had smiled on us! He
immediately ordered materials and began add-
ing vinyl-containing compounds, to our
coating solutions, hoping that the phase would
not only crosslink but also connect with some
surface hydroxyls. With some pretty harsh
testing, we found that the columns exposed to
these higher preheater temperatures were
much more rugged, and the deposited phase
could not be removed with solvent rinsing. At
the next Advances in Chromatography
meeting in Houston, we announced the
Bonded Phase Column. If the technician on
that machine had reported the failing thermo-
couple, we would simply have replaced it and
none of this would have happened. It turned
out that Kurt Grob in Switzerland had (inde-
pendently) been working along these same
lines. Checking on the dates that both parties
had ordered vinyl chemicals, Rand was just
about 5 days ahead.
1.4.6. Further Improvements
in Stationary Phases
In the late 50s and extending into the 60s, gas
chromatographers dealt with a plethora of
stationary phases. Petroleum chemists, dealing
with nonpolar products, favored phases such
as squalane, a fully saturated hydrocarbon
(C30H62) on the basis of like-attracts-like. The
upper temperature limit for Squalane is 125
,
and a higher temperature paraffin, Apolane 87
(C87H176), was sometimes used instead. Chem-
ists dealing with more polar products needed
more polar stationary phases, and they turned
to high boiling esters such as diethylene glycol
7
succinate (DEGS). As more and more scientists
entered the field, the range of stationary phases
exploded to over 200 different phases, most of
which were gradually discarded. The polysilox-
ane stationary phases are now widely used and
have been reviewed by Blomberg [23] and
Haken [24].
1.5. INTERFACING GLASS
CAPILLARY COLUMNS TO
INJECTORS AND DETECTORS
Attaching these relatively fragile glass capil-
laries to injectors and detectors via leak-proof
connections soon became a problem; some
workers punched holes in small disks of silicone
rubber which were then substituted for the
ferrules supplied with 1/16 inch Swagelock
fittings, but all too frequently, as the nut on the
Swagelock fitting was tightened to the point
that there were no leaks, the compressive strain
on the glass caused breakage at that point.
Others tried lead disks, with similar effects.
I was on sabbatical leave at the nuclear research
institute in Karlsruhe, Germany, when a clerk in
the supply room called my attention to a sheet of
plastic heavily infused with graphite. After
sliding Swagelock caps onto both column ends,
I wound small strips of this around both ends
of a glass capillary, removed the stock ferules
from the Swagelock connectors to the inlet and
detector, and connected the column. As I tight-
ened the connections to a point where there
was no leakage and found that the column was
still intact, I was delighted. The company that
made these graphitized sheets was just a few
miles outside of Karlsruhe, and I paid them
a visit. They were very cordial and gave me
a number of samples. On my return to the U.S.,
J&W ordered several steel dies dimensioned on
the inner measurements of a 1/16 inch Swage-
lock fitting and began pressing ferrules. These
went on the market in 1975; they were a great
8 1. MILESTONES IN THE DEVELOPMENT OF GAS CHROMATOGRAPHY
success, and I have always regretted my failure
to patent that product.
1.6. THE HINDELANG
CONFERENCES AND THE
FUSED-SILICA COLUMN
The first symposium restricted to open-
tubular (capillary) columns was organized by
Rudolf Kaiser and chaired by Dennis Desty in
1975; this was the first of the four Hindelang
conferences and was held in an isolated village
in the Bavarian Alps. Ettre visited Kaiser, first
to voice his opposition to holding the meeting,
and then proposed a delay, arguing that it was
being held far too early, but many other
workers in the field were enthused by the
idea. I still regard the first Hindelang Confer-
ence as the most exciting meeting I have ever
attended. It attracted nearly everybody that
was working with glass capillary columns. We
listened to presentations from our associates in
the morning, and spent afternoons and evenings
gathered around tables seating perhaps eight
participants, drinking strong German brews
and exchanging views on chromatography,
with the emphasis on WCOT columns. It was
then that Golay approached me; he was feeble
at the time and steadied by Ettre. He wanted
to talk about J&Ws method of coating columns.
TABLE 1.1 Approximate Compositions for Glass Materials Used for Capillary Column Fabrication
Metal oxide percent composition (w/w)
Glass Type SiO2 Al2O3 Na2O
Soda lime 68 3 15
Borosilicate 81 2 4
Uranium glass 76 3 4
Potash soda lead 56 2 4
Fused silica* 100
* Typically contains less than 1 ppm total metals.
I explained that the first step was his idea of
feeding a filled column, open end first, into
a heated oven. Ilkova and Mistrykovs idea of
screwing the coiled column into the oven
showed real ingenuity: my preheater contribu-
tion would have been proposed by anyone
that could actually see the operation taking
place. Now that I have reached (and probably
surpassed) Golays age at the time, I believe I
can now understand his curiosity, and I hope
he realized that another of his brilliant ideas
had borne fruit. He departed courteously, and
I was left to continue my attempts to visit every
table and meet every participant. I did meet
virtually all the experts, absorbed a great deal
of knowledge, and left filled with new ideas
and a desire to get home quickly where I could
get back to work in my own lab.
There are many types of glass, but we will
restrict our interests to those studied for their
chromatographic interest by Dandeneau and
Zerenner: soda lime, borosilicate, uranium,
potash soda lead, and fused silica (Table 1.1)
[25]. At the third Hindelang conference, I pre-
sented a paper on multiple short pass capillary
chromatography, in which one of my Ph.D.
students (James A. Settlage) had recycled
a butane injection sixteen times through two
7.5 m columns to achieve 1170 theoretical plates
per second, and generated 850,000 theoretical
plates in those sixteen passes in less than twelve
K2O CaO MgO B2O3 PbO U2O3 BaO
6 4 2 2
13
2 14 1
9 29
 1.6. THE HINDELANG CONFERENCES AND THE FUSED-SILICA COLUMN
minutes [26]; as I finished, several members
of the audience rushed to the podium with
congratulations; at a final synopsis of the
meeting, Desty cited also this paper, but I
knew they were all wrong. The most significant
paper was that of Dandeneau and Zerenner
[25], releasing the fused-silica column. When
Dandeneau presented his paper, very few
people realized its importance. Sandy Lipsky,
who had started Quadrex about the same time
that J&W was founded, was one, and I was
another. Both Lipsky and I had been trying to
convert industrial analysts to WCOT glass capil-
laries, with but scant success. Industrial analysts
realized the superiority of results generated by
these columns, but they also recognized their
fragility. Downtime is rarely critical in
academia, but in industry it can be very serious;
glass capillaries break easily, packed columns
lasted longer. However, this fused-silica column
changed everything! Here was a capillary
column that was both strong and flexible, but
because it was both labor intensive and mate-
rials intensive, it was much more expensive.
Fused-silica columns have immense tensile
strength, permitting an extremely thin column
wall, which in turn makes a flexible column.
This permitted drawing long lengths of straight
tubing, which can then be coiled. Interfacing
these to detectors and injectors was now
a simple task; no longer must we flame
straighten the ends of the column, it was already
inherently straight! But the outer surface of
drawn silica requires protection. Like all silica-
based glasses, fused silica is subject to flaws at
its surface, and flaws grow at a rate determined
by stress e and coiling this long straight piece of
fused silica places it under stress e as the flaw
grows larger, the column snaps at that point.
To protect the outer surface, Hewlett Packard
first coated the columns with a coating of poly-
siloxane, but this ended up as a very sticky
column. DuPont then came forward with a poly-
amide coating that was applied during the
drawing process. Later they changed to
9
a polyimide; this seals surface flaws in the
tubing. It is usually applied in several thin coats
during the drawing process.
Not everyone recognized the advantages of
the fused-silica column; indeed, in spite of my
vigorous protests, my partners at J&W dismissed
it as a gimmick. Two weeks later, it was impos-
sible to give, let alone sell, a glass capillary
column, and J&W made the conversion to fused
silica. At this point, things became very
touchy. The vast majority of scientists working
in gas chromatography had careers based on
glass capillary columns e drawing, deactivation,
coating, etc. e now those careers were passe.
I had a seminar scheduled for Milan, Italy, where
I was warmly received e until my first slide was
shown. It was a fused-silica column. Several
attendees left the room, and the atmosphere
took on a chill. Very few in this audience wanted
to hear how their futures might be affected.
Shortly thereafter, Georges Guiochon organized
a chromatography Symposium in Cannes,
France. The GC column portion of the meeting
was chaired by Gerhardt Schomburg. As he
called the meeting to order, he announced that
there would be no discussion of fused-silica
columns. As the meeting proceeded, several
attendees expressed their objections to the
opening restriction and announced that they
had come to the meeting just to learn more about
the fused-silica column. With obvious distaste,
Schomburg turned to me and said, tell them
something about fused silica. At this time, I
had been exploring on-column injections with
fused silica, sometimes trapping samples within
the fused-silica tubing by folding the flexible
tube into a U shape in a Dewar flask filled
with liquid nitrogen, then withdrawing the U
and re-inserting it into a flask of heated oil for
injection. This approach demanded a flexible
tube and would have been impossible with glass
capillary tubing. An obviously uncomfortable
Schomburg interrupted me with the observation
that flexibility appeals only to Americans, and
only because they are too clumsy to handle
10 1. MILESTONES IN THE DEVELOPMENT OF GAS CHROMATOGRAPHY
glass. A few months later J&W was selling
Schomburg fused-silica columns.
1.7. INCREASING
SOPHISTICATION OF
INSTRUMENTATION
Table 1.2 provides a timeline for important
developments in instrumentation. The essen-
tial elements of instruments were developed
TABLE 1.2 Important Advances in Technology that
Impacted Gas Chromatography
1955 First commercial instrument (thermal
conductivity detection)
1955e1960 Rapid growth in technology
Invention of ionization detectors
Interfaces for coupling to mass
spectrometry
Microsyringes produced commercially
Temperature programming introduced
1960e1970 Period of technical advances
First open-tubular columns introduced
Transistors replace vacuum tubes
Improvements in detector technology
Stable rubidium sources introduced for
TID
Improved FPD (several designs)
Pulsed ECD introduced
1970e1980 Period of consolidation and refinement
Microprocessor-based instruments
introduced
Self-made glass open-tubular columns
increasingly used
Computing integrators introduced for
data handling
Fused-silica open-tubular columns
introduced in 1979 and catalyzes further
changes in column and instrument
technology
(Continued)
TABLE 1.2 Important Advances in Technology that
Impacted Gas Chromatography (contd)
1980e1990 Period of technical advances
Gum and immobilized phases developed
Columns with thick-film stationary
phases developed
Wide-bore open-tubular columns
developed
Fundamental basis for injection
mechanisms developed
On-column and PTV injection developed
Large-volume injection described
Autosamplers for unattended injection
developed
1990e2000 Period of consolidation and refinement
Keyboard instrumentation (PC control of
operation and data handling)
Electronic pneumatic control
Selectable elemental detection (SED)
Pulsed flame photometric detector
developed (FPD)
Electron-capture detector with pulsed
discharge source developed (ECD)
More versatile and affordable
spectroscopic detectors (MS, FTIR)
Solid-phase microextraction affords a new
approach to sampling and sample
introduction
First microfabricated gas chromatograph
on a chip introduced but fails
commercially
Field portable instruments move gas
chromatography out of the laboratory
2000e Slowing down in the growth of technology
present
Micro-GC instruments for fast gas
chromatography developed
Capillary columns with ionic liquid
stationary phases introduced
Gas generators start to replace
pressurized gas cylinders
Programmable robotic systems used to
automate sample preparation
 1.7. INCREASING SOPHISTICATION OF INSTRUMENTATION
by the early 1960s [8], with further develop-
ments occurring in short bursts of innovation
and advances in technology followed by longer
periods of evolutionary changes and consolida-
tion. Many advances were catalyzed by
advances in column technology or electronics.
For example, the advent of the microprocessor
brought about a radical change in instrument
design and use. From this point onward,
instrument functions were monitored and
controlled by networks of circuits communi-
cating with each other and with a central
controller. This paved the way for the emer-
gence of the keyboard instrument controlled
by software running on a personal computer,
which dominated instruments for laboratory
use by the early 1990s. A significant milestone
in achieving full automation of instrument
operation was the introduction of electronic
pressure control in the early 1980s. This
allowed carrier gas and support gas pressure
and flow rates to be set and monitored by elec-
tromechanical devices communicating with
a central processor. With the introduction of
robotic autosamplers at about the same time,
the gas chromatograph could now operate
without human intervention, 24 h operation
became standard practice for routine analysis
in high sample throughput environments, and
gas chromatographs were deployed to remote
locations and monitored electronically with
only occasional visits for service and routine
maintenance. The complex functions of gas
chromatography had been reduced to those of
a black box analyzer 50 years after its invention,
but still evolutionary changes continue in tech-
nology with the view of minimizing the impor-
tance of the skill and knowledge of the operator
in the production of data [27].
1.7.1. Column Heating
The increasing interest in capillary columns
demonstrated the inadequacies of packed
column instruments, and the paradigm shift
11
accompanying the introduction of fused-silica
open-tubular columns meant significant
changes were needed as capillary gas chroma-
tography quickly became normal practice.
Apart from the use of liquid thermostats in the
early days of gas chromatography, the column
heater in a gas chromatograph is typically
a forced-circulation air oven, the temperature
of which can be changed in a controlled manner
with time for temperature programmed separa-
tions. Good temperature control is essential to
obtain reproducible retention times and to avoid
peak distortions associated with temporal and
spatial oven temperature gradients. A low
thermal mass for the oven is also important
since it allows rapid cooling after temperature
programming. Typically, forced air-circulation
ovens can maintain a higher rate of heating at
lower temperatures than higher temperatures
due to the greater amount of heat lost to the
surrounding environment as the temperature
ramp progresses. For fast gas chromatography,
some manufacturers have addressed this
problem with the oven inside an oven concept
or more directly using resistive heating
achieved through the use of a metallic heating
element to transfer heat to the column by
conduction. Fast gas chromatography makes
use of short columns of small internal diameter,
thin film columns, higher carrier gas flow rates,
and fast temperature program rates (Table 1.3)
[28]. For the fastest separations the limiting
instrument conditions become the available
column inlet pressure, maximum oven tempera-
ture program rate, maximum detector sampling
rate, detector sensitivity and noise level, and
sample introduction (initial band width).
Typical laboratory instruments can usually
meet the requirements for fast gas chromatog-
raphy (first entry in Table 1.3), but special-
purpose instruments are required for very fast
gas chromatography (second entry in Table
1.3). The entries in Table 1.3 reflect what is
within the capability of commercial instruments
with little modification (first entry) and the
12 1. MILESTONES IN THE DEVELOPMENT OF GAS CHROMATOGRAPHY
TABLE 1.3 Instrumental Parameters for Fast Gas
Chromatography
(i) Fast gas chromatography (separation times <10 min)
Peak widths 0.5e2 s
Columns 5e15 m with I.D. 0.25e0.1 mm
Temperature program rates 20e60
C/min
Column inlet pressure <15 bar
Data acquisition rate 50 Hz
Mobile phase velocity 1.4  uopt
(ii) Very fast gas chromatography (separation time in
seconds)
Peak widths 50e200 ms
Columns 2e10 m and I.D. 0.1e0.05 mm
Temperature program rates >60
C/min
Data acquisition rates 50e200 Hz
limits of current technology requiring special
purposing of instruments (second entry). From
the perspective of separation speed, the capa-
bility of gas chromatographic instruments limits
performance more so than column technology
in contemporary practice.
1.7.2. Sample Introduction
The limited sample capacity and low carrier
gas flow rates associated with open-tubular
columns make sample introduction more diffi-
cult than for packed columns. A thermostated
flash vaporization chamber in which the evapo-
rated sample is mixed with carrier gas and
divided between a stream entering the column
(carrier gas flow) and a stream vented to waste
(split flow) was the first practical solution to
this problem. Split injection can be used to
generate extremely small bandwidths for high
peak capacity separations but discriminates
against less volatile compounds and the
quantitative analysis of wide boiling point
mixtures is difficult, and for samples present
in dilute solution, detectability is limited by
the small amount of sample transferred to the
column. The splitless injection technique was
devised (actually discovered accidentally [29])
to overcome some of the deficiencies of split
injection for the analysis of mixtures in dilute
solution through the transfer of relatively large
sample volumes to the column. The gas flow
through a splitless injector is relatively low,
and the sample is introduced into the column
over a comparatively long time (30e60 s),
relying on cold trapping and/or solvent effects
to refocus the compounds at the head of the
column. The importance of these refocusing
mechanisms was not fully understood at first
and much of our current knowledge of the injec-
tion mechanism owes a great deal to the exem-
plary studies of Konrad Grob and the
publication in 1986 of his classic book on split
and splitless injection [29].
The programmed-temperature vaporizer
(PTV) injector is perhaps the most versatile
injector developed for gas chromatography. It
facilitates split and splitless injection as well as
new approaches for large-volume injection
with solvent elimination [30]. The PTV injector
has a low thermal mass to allow rapid heating
and cooling. The sample is introduced at a rela-
tively low temperature and then raised ballisti-
cally to a temperature sufficient for rapid
volatilization of the highest boiling sample
components. Slow sample introduction at
a low temperature with solvent elimination
facilitates the injection of large sample volumes
(usually <1 ml) for trace analysis. The PTV
injector was originally introduced in Europe in
the 1980s but it was over a decade later before
it gained traction in the USA. For much of this
time it was an option but not heavily promoted
or supported by instrument companies based in
the USA. This was probably due to a combina-
tion of commercial preferences and the not-
invented-here syndrome.
 1.7. INCREASING SOPHISTICATION OF INSTRUMENTATION
The production of wide-bore fused-silica
capillary columns coated with immobilized
stationary phases in the early 1980s allowed the
syringe needle to be introduced directly into
the column and eliminated the problem of
removal of the stationary phase by the relatively
large volume of solvent released inside the
column by the syringe [31]. These advances in
column technology facilitated the development
of cold on-column injection where the sample is
introduced as a liquid into the column inlet
and subsequently vaporized. Discrimination
because of volatility differences was virtually
eliminated and the risk of sample decomposition
minimized. With secondary cooling of the
injector, the oven temperature could be kept
well above the boiling point of the solvent while
maintaining the column inlet at a much lower
temperature. This is important for using on-
column injection in high-temperature gas chro-
matography. Dirty samples present a problem
owing to contamination of the sample introduc-
tion zone, which leads to poor chromatography
and unreliable quantification. Both on-column
and programmed-temperature vaporizer injec-
tion afford high accuracy and precision. These
injectors also facilitated the direct coupling of
other chromatographic systems to gas chroma-
tography, such as liquid chromatography and
supercritical fluid chromatography [32]. In the
1980s, Carlo Erba manufactured an instrument
for on-line liquid chromatographyegas chroma-
tography, but the uptake was poor and the
system was discontinued.
The array of sample introduction methods for
gas chromatography and an understanding of
the mechanistic details on which they rely were
complete by the end of the 1980s and modifica-
tions since then have been evolutionary. The
most visible change is the shift from manual to
automated sample introduction systems that
accept samples in vials and can be programmed
for sequential analysis of each or selected vials
in a batch. The introduction of solid-phase micro-
extraction in the early 1990s simplified sample
13
preparation and handling steps using a syringe
containing a retractable sorbent fiber compatible
with solvent-free sample introduction [33]. By
the turn of the century, this had become one of
the most popular sampling/sample introduction
techniques in gas chromatography. It can be seen
as the forerunner of the liquid-phase microextrac-
tion techniques developed over the last decade.
Together these microextraction formats are
responsible for achieving a better scaling of
sample size requirements to sample utilization
capabilities of capillary columns and are having
a considerable impact on laboratory working
practices.
1.7.3. Detectors
Gas chromatography is blessed by a number
of robust and sensitive detectors based on gas-
phase ionization processes (e.g. flame ioniza-
tion, thermionic ionization, electron capture,
and photoionization), bulk property (thermal
conductivity), optical (flame photometric,
chemiluminescence, and atomic emission), elec-
trochemical (electrolytic conductivity), and
advanced spectroscopic (mass spectrometry
and infrared spectroscopy) detection principles.
Many of these detectors were introduced during
the initial phase of the development of gas chro-
matography and are still used today in a modi-
fied form reflecting changes in enabling
technology. The exception is the (Hall) electro-
lytic conductivity detector, which, because of
its large detector volume and basis in wet chem-
ical processes, is little used today. Interfacing of
modern detectors to capillary columns is not
normally difficult except for fast gas chromatog-
raphy where the detector volume and data
acquisition rates limit the use of some detectors.
The flame ionization detector facilitated many
of the early developments in capillary columns
(Section 1.4). This detector has a low dead
volume, a high sensitivity for nearly all
carbon-containing compounds, and an
extremely wide linear response range. Other
14 1. MILESTONES IN THE DEVELOPMENT OF GAS CHROMATOGRAPHY
detectors were developed in response to the
need for element-selective or structure-selective
detection. These detectors allowed the analysis
of target compounds at low concentrations in
complex samples, and made an important
contribution to the rapid acceptance of gas chro-
matography in laboratories performing routine
analysis as well as research laboratories.
A special mention should be made of the
coupling of gas chromatography with mass spec-
trometry (GCeMS). This coupling dates almost
from the beginning of gas chromatography, but
in the early days the practical problems and
high cost meant that the combination was
confined to a few research laboratories. When
packed columns dominated the practice of gas
chromatography, separators were required to
reduce typical column flow rates to the vacuum-
handling capacity of the ion source of the mass
spectrometer. Separators based on a jet, glass
fritted tube, or diffusion membrane design
allowed sample enrichment while simulta-
neously reducing the gas flow to the ion source.
Separators disappeared nearly completely with
the introduction of fused-silica open-tubular
columns, which could be routed from the column
oven through a heated transfer line directly into
the ion source of the mass spectrometer. During
the time that instrumentation for gas chromatog-
raphy was advancing, so were all aspects of mass
spectrometry, which became more powerful,
affordable, reliable, and available to laboratories
with low-skilled personnel. The great advantage
of the mass spectrometer as a detector is its ability
to provide structural information for identifica-
tion using different ionization approaches and
through techniques like tandem mass spectrom-
etry. Another advantage is its high sensitivity
and selectivity as a detector in the selected ion
or high-resolution mode.
1.7.4. Data Handling
In the early days of gas chromatography peak
quantification was done by purely manual
measurements of peak heights, although it was
recognized that peak area measurement was
fundamentally better but more difficult. The
product of the peak height and the peak width
at half height could be used as an approximate
area measurement but this was neither fast nor
(usually) accurate, especially for narrow peaks.
Approaches based on planimetry and
cuteand-weigh procedures could afford reason-
able accuracy but demanded considerable skill
to achieve acceptable results and were slow
and tedious. Electromechanical devices such as
the ball and disk integrators and integrating
amplifiers were early attempts at automating
this time-consuming process. These devices
were rather limited in range and speed of
response. The advent of microprocessors in the
early 1970s ushered in the computing integrator
which took over the labor-intensive process of
data management, eventually resulting in
devices that could record a chromatogram
simultaneously with data acquisition and,
when the separation was complete, instantly
generate reports in tabular form of all sorts of
descriptive information from the chromato-
gram, including the calculation of peak areas.
It was not long before mainframe computers
were in use to handle data produced from
a number of instruments simultaneously. The
development of the personal computer and the
rapid growth in processor speed and memory,
however, had a greater impact and resulted in
data management being handled by software
running on a dedicated personal computer
with information being archived locally and/
or centrally on a laboratory information
network server. Today, the large amount of
data produced by capillary columns (especially
when coupled to a mass spectrometer) can be
handled by a personal computer which simulta-
neously functions as the system manager
controlling and monitoring all aspects of the
chromatograph. What has not changed is that
the methods used to manipulate the chromato-
graphic data for display and calculation are
 1.7. INCREASING SOPHISTICATION OF INSTRUMENTATION
considered proprietary information, requiring
an act of faith that what is provided as a printout
or on screen is exactly what happened in the
column [34]. What is clear, however, is that it
would be nearly impossible to persuade scien-
tists to return to the status quo before the elec-
tronic age of data handling as laboratory
productivity would be severely limited.
1.7.5. Comprehensive Gas
Chromatography
Sometimes the separating power of gas chro-
matography, even when augmented by the iden-
tification power of spectroscopic detectors such
as mass spectrometry, is still insufficient to accu-
rately determine the composition of a sample.
This problem is tackled in contemporary studies
using comprehensive gas chromatography.
Comprehensive separations have their origins
in multidimensional gas chromatography devel-
oped in the early 1960s after the introduction of
the Deans switch for controlling the flow direc-
tion of a gas stream at a T-piece using pressure
changes. Multidimensional (typically two-
dimensional) gas chromatography employs
two independent columns connected to each
other by an interface. In early versions a fraction
of the chromatogram, a heartcut, from the first
column was isolated by cold trapping and then
released by thermal desorption for separation
on the second column. The disadvantage of this
approach is that the fraction collected at the inter-
face contains no information about the separa-
tion on the first column. In the 1980s, Siemens
marketed a remarkable instrument for its time,
the SiChromat-2, which had two independently
controlled air-circulation ovens, housing the
two columns, connected by a T-piece to isolate,
focus, and re-inject fractions from the first
column to the second by live switching based
on the Deans switching mechanism. This instru-
ment likely contained the most complex
pneumatic system of any instrument of its gener-
ation and required considerable skill in its
15
operation. It had to compete for preference
with a new generation of affordable and easy-
to-use gas chromatographyemass spectrometry
systems, however, and was not a commercial
success [35]. In the early 1990s, Phillips intro-
duced comprehensive gas chromatography in
which the whole separation on the first column
was transferred to a second column of different
selectivity, the two columns being connected
through a modulation interface. In this case, the
chromatogram is recorded as a two-dimensional
contour plot with the planar axes consisting of
the independent retention times for each
compound on the two columns and the vertical
axis is related to the amount of each compound.
This technique was not an instant success, but
after further refinements in modulator design,
a decade later it had entered the main stream of
commerce. These instruments are at the cutting
edge of instrument development where capabil-
ities are pushed to match column performance.
The function of the modulator is to arrest,
concentrate, and launch a fraction of the material
contained within each peak of the chromatogram
from the first column and transfer them as
a series of pulses of constant frequency to the
second column. To avoid overlap of individual
separations on the second column, each chro-
matogram must be complete in less time than
the cycle time of the modulator. Thus, the
second-column separations must be very fast
with a total separation time measured in
seconds. This requires incredibly small injection
bandwidths, short second columns of small
internal diameter, fast detector response times,
and repetitious and fast changes in instrument
operating conditions. Comprehensive gas chro-
matography generates a large amount of data,
especially when mass spectrometry is used as
a detector, and challenges remain in how best
to make these data available to the user in
a form convenient for analysis. In these instru-
ments, one can perhaps see a vision of the future
of single column gas chromatography (based on
technology developed for the second-dimension
16 1. MILESTONES IN THE DEVELOPMENT OF GAS CHROMATOGRAPHY
separation) while at the same time highlighting
the limitations of current technology for gas
chromatography.
1.8. DECLINE IN THE EXPERTISE
OF THE AVERAGE GAS
CHROMATOGRAPHER
At the present day the success in the
commercial sector in gas chromatography has
resulted in a situation not all that different
from a narcotic dependency. To be classed as
an expert in gas chromatography, all that seems
to be necessary is the wherewithal to buy a gas
chromatograph and a column. Today, those
tasked to operate a gas chromatograph do not
need to even make an injection, columns have
become classified as laboratory supply items,
and data as something that appears on
a printout at the end of an experiment. When I
was first introduced to gas chromatography in
the 1970s, it was necessary to make, modify,
and continuously improve columns and instru-
ments to meet the needs of each application.
Expert chromatographers of this time were of
necessity well versed in troubleshooting and
thoroughly knowledgeable of the principles
and practice at what often appeared to outsiders
as the dark arts of separations. On account of
the immense powers of separations virtually
any unskilled individual can produce data
today; even the village idiot can inject a sample
and obtain peaks that are interpreted as usable
data. This has led to a continuing decline in the
expertise of the average practicing chromatog-
rapher from the mid-1980s to the present time.
This can be perilous, because everything from
column selection to trouble-shooting skills is
based on a fundamental knowledge of chro-
matographic principles, the absence of which
degrades the quality and usefulness of the infor-
mation acquired by these instruments. To
address these problems requires a massive
educational effort before the knowledge is lost
and the usefulness of gas chromatography to
decision makers is called into question. When
I first started to make my way in gas chromato-
graphy, I never thought that such a reversion
would occur so quickly, and as retirement
approaches, that intellectually I might leave
the field in a poorer state than when I entered
it. There is no doubt that advances in tech-
nology have delivered better instruments and
columns but now in the hands of less qualified
operators; this does not always lead to better-
quality data.
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