In the early 1960s, gas chromatography (GC) was the prevailing chromatographic technique (7) and, as mentioned earlier, LC
was still done essentially in the classical way, with very little change from Tswett's original description of the technique.
However, slowly researchers well versed in the theory and practice of GC realized that changes were needed to make LC compatible
with regard to both speed and resolution. In my discussion of Csaba Horváth's early activities (1), I dealt with this trend.
Jim Waters was also thinking along this line. In an internal document from this period, he stated that "We believe LC can
become a mass market which will extend far beyond the research laboratory into production, quality control, and clinical testing"
(8). Waters Associates already sold a limited number of their small-volume refractometers to chromatographers, to monitor
the effluent of classical LC columns. Then, in 1965, Jim became involved in the development of a liquid chromatograph for
Shell Development Co.
Shell Development Co. in California had been involved in the development of new instrumentation for their own use and usually
licensed smaller companies to produce these. For example, in the early stage of GC development, they licensed a short-lived
California company, Hallaikainen Instruments, to build gas chromatographs based upon their design, and Hallaikainen also sold
a few to customers other than Shell (7). The situation was similar with LC. By the mid-1960s, Shell had developed an LC system
and in 1965, Jim Waters secured a license to construct instruments based upon this design. Shell's system was based upon liquid–liquid
chromatography (LLC), and Waters built two prototypes using his refractometer detector: one for Shell and a second for the
University of Alberta, in Canada.
Many of the researchers who started to upgrade LC in the 1960s were not sure which approach to take: follow the GC example
and use columns coated with a (liquid) stationary phase, or utilize a solid stationary phase (i.e., an adsorbent); in other
words, carry out liquid–liquid or liquid–solid chromatography (LLC or LSC). Shell's approach was the former. However, Jim
soon realized (just as eventually the other pioneers in this early period of modern LC development) that this was not the
right approach. The system was not stable and the detector drifted widely. Therefore, Jim completely redesigned the original
Shell system. Meanwhile, reports on the work of other pioneers started to be known and Karl J. Bombaugh, Waters' director
of R&D, learned at the 1966 Chromatography Symposium held in Rome, Italy, about the approach selected by Csaba Horváth (1)
(I was present and still remember vividly their discussion). As a conclusion, Jim Waters switched to the use of solid column
packing (an adsorbent), also included a UV detector, and adopted the system for high-pressure operation. The resulting instrument,
the ALC-100 analytical liquid chromatograph — the first commercial high-pressure liquid chromatograph — was formally introduced
at the 1968 Pittsburgh Conference (Figure 5). It was a benchtop system equipped with a Milton Roy pump, syringe injection,
and two detectors: the Waters differential refractometer and a UV detector from the Laboratory Data Control (LDC) Co.
Figure 5: The Model ALC-100 high-pressure analytical liquid chromatograph introduced in 1968. The box on the right top is
the compartment for the solvent bottles; below it are the control panels for the refractometer (left) and UV (right detectors
and at the bottom is the pump compartment). The left-hand side of the instrument is the thermostatted column compartment.
The operator is injecting a sample with a syringe into the injection port. A separate two-pen potentiometric recorder is used
to record the chromatograms.