This invention relates generally to liquid chromatography, and more
specifically to a solvent supply system for use in high performance liquid chromatography
Chromatography is a separation method in which a mixture of components
(called the "sample" or "sample mixture") is placed as a zone at one end of a system
containing both a stationary phase and a mobile phase. Each component of the sample
distributes itself in dynamic equilibrium between the two phases in a ratio characteristic
of that component. As a result, the flowing mobile phase causes each individual
component zone to migrate at a characteristic rate, and the zones become separated
after a period of time. In liquid absorption chromatography, the stationary phase
consists of a tubular column packed with an absorbent material. The mobile phase
for carrying an analysis sample through the column, commonly referred to as the
carrier, is a solvent mixture comprising two or more miscible liquids, which are
introduced into the column. An equilibrium is established for the individual components
of a sample mixture according to the "attraction" of each to the stationary phase
and according to the solubility of each component in the carrier solvent. The
rate at which a solute passes through the column chromatograph is dependent upon
the equilibria existing for the components, and separations of the components occur
where the distributions differ.
All liquid chromatography systems include a moving solvent, a means
for producing solvent motion such as gravity or a pump, a means for sample introduction,
and a fractionating column. Operation of a liquid chromatography system with a
carrier of two or more solvents mixed in constant, nonvarying proportions is referred
to as isocratic operation.
It is often desirable to operate the liquid chromatographic system
using a carrier in which the ratios of the liquid in the solvent mixture vary over
time in accordance with some predetermined gradient. This type of operation is
referred to as gradient elution, and the gradient profiles referred to as solvent
programs. Within the category of gradient elution operation, the ratios in the
solvent mixture can be made to increase at a fixed rate, i.e. linear gradient;
at an increasing rate of change, i.e., convex gradient; or at a decreasing rate
of change, i.e. concave gradient by appropriate control of the solvent mixing apparatus.
There are various types of chromatography, e.g., liquid chromatography,
gas chromatography, thin layer chromatography, etc. The major differences between
these various chromatographic methods lie in the physical state of the mobile
phase (gas or liquid), and the manner in which the stationary phase is supported,
e.g., coated on an inert granular material packed in a tube, coated on an inner
wall surface, etc. In all chromatographic methods, the separation objective is
essentially the same, that is, distribution of the sample components between a
mobile phase and a stationary phase. When the method is used for chemical analysis,
a detector is commonly placed at the far end of the system to monitor the passage
of the component zones as they emerge from the system. The signal from the detector
is displayed on a recording device such as a strip chart recorder, and a record
indicates both qualitative and quantitative information regarding the components
of the sample.
It is often desirable for a chromatographic system to be able to
provide high resolution (i.e., a large degree of component separation with narrow
zones), evenly spaced component zones, rapid separation, and a satisfactory record
from a very small sample. The behavior of the system described in these terms
may be called the "performance" of the system. It is well known in the chromatographic
art to improve system performance by changing one of the system variables during
the course of the analysis such as temperature, chemical composition of the mobile
phase, and the flow rate of the mobile phase.
An essential objective relevant to all liquid chromatography apparatus
of the type considered herein is to provide a proper flow of solvent to and through
the chromatographic column. In the past, numerous and varied approaches have been
utilized for supplying solvents to high performance liquid chromatographic columns.
A key requirement in this regard is that of providing a relatively
nonpulsating, constant flow of solvent. Furthermore, because a liquid chromatography
detector is sensitive to flow rate variations, it can provide erroneous readings
and exhibit excessive noise in the presence of a pulsating solvent flow. Various
approaches have been utilized in the past in order to remove pulsation and other
noise. In general, however, the prior art methodology was directed toward highly
expensive and overly complex mechanisms for controlling pulsation. Thus, in a typical
example in which a system is intended for operation in a gradient elution mode,
i.e., by use of two distinct solvents, a dual cylinder pump arrangement has been
utilized. Such an arrangement requires distinct cylinder pumps, including separate
means for driving each of the pumps, thereby requiring separate speeds, etc.
A liquid chromatography system which utilizes a solvent pump can
control the pulsating problem by applying control means at either the low pressure
or the high pressure end of pumping stage. The low pressure end of the pumping
system is the inlet or suction side of the pump. The high pressure end of the
pumping means is the pumping side of the pump mechanism. The overwhelming majority
of systems in the prior art are directed toward controlling pump pulsation on the
high pressure end of the system.
Pulsation control has typically been provided by a complex mechanical
means on the high pressure end of the system or through an electronically actuated
feedback circuit which would control motor speed or another flow parameter. In
U.S. Patent No. 4,045,343 entitled "High Pressure Liquid Chromatography System",
pulsation control was provided through means of a complex system of valves and
control apparatus. In U.S. Patent No. 3,985,021 entitled "High Performance Liquid
Chromatography System", feedback means were provided for controlling the rotational
speed of the motor throughout the reciprocating cycle of the pump so as to provide
the preselected rotational speeds over predetermined subintervals of each successive
reciprocation cycle. Application of the control cycle was synchronized with the
pumping cycle so that the speed control was properly applied over each successive
reciprocating cycle in order to control output pulsation. In U.S. Patent No. 3,981,620
entitled "Pumping Apparatus", control on the high pressure side of the pumping
mechanism was also achieved through a pressure sensing device which incorporated
a feedback system to control the speed of the motor. This feedback system not
only controlled the speed of the motor but provided a means to limit the current
to the motor such that that only the current necessary to drive the pump was provided.
U.S. Patent No. 4,245,963, entitled "Pump", disclosed a method for controlling
pulsation of the output or high pressure side of the pump by means of a liquid
storage device consisting of a flattened length of coiled tubing was placed in
the flow path between the two chambers to deliver flow during the low periods when
the displacement elements were in reverse direction, thereby smoothing flow delivery.
Finally, U.S. Patent No. 3,981,620 also entitled "Pumping Apparatus, utilized
a feedback responsive mechanism to sense the pressure of the liquid being pumped.
It utilized a "flow through" meter which comprises a conduit as its pressure sensitive
Several prior art systems utilize mechanical analog systems incorporating
specialized cam technology for control on the high pressure side of the pump. U.S.
Patent No. 4,137,011, entitled "Flow Control System For Liquid Chromatographs,
provides a control system which is particularly adapted for use in multiple chamber
single pump systems in which a cam driven by a speed control device such as a stepping
motor is connected to a multiple chamber positive displacement piston pump arranged
with its chambers and associated pumps opposition to either other on each side
of the cam. The invention also utilizes a complex feedback network which controls
the speed of the pump.
The model 2010 HPLC isocratic pump by Varian Associates is an example
of a current system on the market which utilizes both cam technology and an electronic
feedback mechanism to control pulsation on the high pressure side of the pumping
cycle. This system utilizes a concentric face cam to facilitate suction and pulsation
and also incorporates a pressure feedback system for solvent compressibility compensation.
The system utilizes a pressure transducer which provides high resolution for accurate
readout of system operating pressure. The pressure feedback system controls motor
speed, based upon the actual operating back-pressure, to compensate for solvent
compression and minimize pump pulsation.
While the majority of prior art systems sought to control the high
pressure side of the pumping cycle, there are major advantages to be realized by
the control of the low pressure or inlet side of the pump. This is particularly
true where the examination of multiple solvents is desired and where there is
a need to proportion the solvents evenly. In such cases, it is desirable to provide
an even and nonpulsating flow of solvents from the solvent reservoirs to the pump
head. The prior art systems which sought to control the high pressure side of
the pumping process create a rapid unequal draw on the low pressure or inlet side
of the pump. This makes the proper proportioning of multiple solvents difficult
and requires the use of expensive specialized check valves and electronic sensing
means. Moreover, with the improvement in downstream pulse dampening technology,
it is no longer as necessary to control pulsation through the pumping means on
the high pressure side.
One system currently on the market for controlling the low pressure
side of an HPLC pump is manufactured by IBM. It utilizes a cam system with three
pumping cross head followers, spaced at 120° intervals about the cam. While the
IBM system provides constant suction on the low pressure or inlet side of the
pump, it does so at the considerable expense of an additional cross-head follower,
pumping head and check valve configuration. This, of course, adds extra expense
and complication to the pumping procedure. The pumping barrel and check valves
are the most expensive parts of an HPLC pumping system.
It would be desirable to control the flow of HPLC solvent on the
low pressure or inlet side of the pump by means of a two follower cross-head pumping
mechanism which could provide constant suction on the inlet side of the pump by
means of a specially shaped gradient cam. This would be particularly desirable
in applications in which there is a need for constant suction to proportion various
solvent samples. By providing constant and uniform suction, the user could get
an even proportioning of solvent. Such a system would provide the user with the
ability to obtain a very smooth draw of solvent on the inlet or low pressure side
of the pump.
It is the purpose of this invention to provide a constant suction
proportioning pump for providing a constant and uniform draw of solvent on the
low pressure side of the pump by means of a specially shaped gradient cam. Another
purpose of this invention is to provide a constant suction proportioning pump
having short duration fill strokes. Yet another purpose of this invention is to
provide a proportioning pump which achieves a constant suction by a relatively
simple and inexpensive means on the inlet side using only two cross-head followers
spaced 180° apart.
In the preferred embodiment of the invention, the gradient cam is
comprised of a plurality of similarly sized lobes, each lobe separated on the cam
by troughs extending radially from the center of the cam. A lesser portion of each
lobe is used to force the piston forward and therefore pump solvent. The majority
portion of each lobe is used to draw a constant flow of solvent on the low pressure
side of the pump. More specifically, in the preferred embodiment of the invention,
the cam is divided into three lobes, each covering 120° of the cam face. Each
lobe is divided into a 65° suction or fill stroke and a 55° pulse or pressure stroke.
Such a configuration maximizes the combined goals of constant suction of the low
pressure side of the pump and short duration fill stroke which are necessary for
accurate low volume solvent pumping applications. The system requires no complicated
software and controls any pulsation on the high pressure side with improved pulse
dampening mechanisms downstream from the pumping means. The pumping head accordingly
receives a steady, properly proportioned flow of solvent.
Summary of the Invention
In accordance with the invention, a cam provides constant suction
on the low pressure or inlet side of an HPLC pumping system. The cam has a disk-shaped
face with a gradient profile specifically cut to provide a constant and uniform
suction when used with two roller followers, stationed 180° apart, which ride
along the cam's profile. The gradient cam includes a central orifice and a groove
which couples with an electromechanical drive.
The profile of the cam is divided into a plurality of lobes, each
having a peak and trough which extend radially from the center of the cam. On each
respective lobe, the peak represents the greatest point of profile ridge protrusion
and the trough represents the lowest point of profile ridge protrusion.
When the cam is rotated in a first direction with respect to its
face, the gradient profile ridge rises over a first section of each lobe and declines
over a larger second section of each lobe. When in operation, the rising of the
ridge corresponds with the pumping portion of the pump cycle, and the decline
of the ridge corresponds with the suction portion of the pump cycle. Because the
followers are held stationary 180° apart, and the suction portion of the combined
lobe gradient corresponds to over one-half the total pumping cycle, the pump provides
Brief Description of the Drawings:
The present invention may be better understood and its numerous objects
and advantages will become apparent to those skilled in the art by reference to
the accompanying drawings in which:
Description of the Preferred Embodiment
- Figure 1 is an elevated view of the three lobed cam and cross-head followers
of the present invention.
- Figure 2 is a side view of the preferred cam embodiment illustrating cross-head
assemblies and roller followers attached thereto.
- Figure 3 is a side perspective view of the entire pumping mechanism of the
- Figure 4 is an enhanced view of the gradient cam, cross-head assembly, pump
assembly and pump head.
- Figure 5 is a flow chart diagram of a HPLC pumping system which utilizes the
proportioning pump of the preferred embodiment.
Referring to Fig. 1, an elevated view of the present invention of
a three-lobe gradient cam and cross-head followers is shown. The three-lobe gradient
cam 10 is a circular disk-shaped face cam which in operation rotates in a counterclockwise
direction with respect to its face. The three-lobe gradient cam 10 has a profile
ridge 11 along the circumference of the disk on which two stationary cross-head
assemblies and roller followers 12, 12a, spaced 180° apart, ride. The profile
ridge 11 of three lobe gradient cam 10 is divided into three equal lobes, 11a,
11b, 11c by troughs 10b extending radially from center 10c of the gradient cam.
Peak 10a represents the point of greatest profile protrusion and trough 10b represents
the point of least profile protrusion for each respective gradient lobe 11a, 11b,
Three-lobe, gradient cam 10 also has a central orifice 13 and groove
13a designed to couple with and hold a drive shaft driven by electromechanical
operating means, thereby enabling the counterclockwise revolution of three-lobe
gradient cam 10. Peak 10a of each lobe 11a, 11b, 11c divide the profile ridge
11 of each lobe into a first lobe section 11a′, 11b′, 11c′ and
a second lobe section 11a″, 11b″, 11c″ respectively. Each lobe
comprises 120° of the circumference of the entire profile ridge 11. For each lobe
11a, 11b, 11c, the first lobe section comprises 11/24 of the respective lobe (or
55° of the entire cam face) and the second lobe section comprises 13/24 of the
respective lobe (or 65° of the entire cam face).
Because the gradient cam of the present invention rotates in a counterclockwise
direction, the first lobe section 11a′, 11b′, 11c′ rises with
respect to the cam face over 55° of the rotation of the cam and the second lobe
section 11a″, 11b″, 11c″ declines over 65° of the cam rotation
period. In operation, lobe sections 11a′, 11b′, 11c′ causes the
downward thrust of the pumping portion of the cycle, and lobe sections 11a″,
11b″, 11c″ causes the longer suction or inlet portion of the pumping
assembly. Over each 120° rotation one complete pump cycle is made. Constant suction
is provided in this embodiment by the fact that 65° of each input cycle is devoted
to the draw or suction part of the cycle and 55° is devoted toward the pulsation
cycle. Further, because the stationary followers are space 180° apart, one of the
followers will always be on the draw or suction portion of one of the three lobes,
thereby insuring constant suction. For normal chromatographic applications, this
would result in pulse-free pulsations. Moreover, because smaller volumes of fluid
are passing through the check valves at a faster rate, the flow error is minimized
in this embodiment, thereby allowing smaller pump flow with improved accuracy.
Finally, by using the three-lobed cam embodiment with overlapping suction capability
and followers spaced 180° apart, a low-cost gradient pump is possible.
Referring to Figure 2, a side view of the three-lobe gradient cam
of the present invention is illustrated. In operation, the face of the three-lobe
gradient cam 10 extends downward. The three-lobe gradient cam 10 is attached to
the pump housing 14 and rotates with the aid of roller bearings 16. Also illustrated
are the drive shaft 18 and clutch assembly 18a which are attached to the orifice
13 and groove 13a of the three-lobe gradient cam 10 through its rear. When attached
to electromechanical drive means, drive shift 18 and clutch assembly 18a rotate
the three-lobe gradient cam 10 in a counterclockwise direction with respect to
its face. Stationary cross head assemblies and roller followers 12, 12a separated
by 180° are also shown riding along the profile ridge. Referring to the motion
of the cross-head assemblies and followers 12, 12a, as gradient cam 10 rotates
in a counterclockwise direction, with respect to the cam's face, cross-head assemblies
and rollers followers 12, 12a are alternatingly thrusted downward and upward along
the profile ridge 11 of gradient cam 10. Accordingly, because over half the profile
ridge represents the suction portion of the three pumping cycles which occur during
one rotation of the three-lobe gradient cam 10 and because cross-head assemblies
and roller followers 12, 12a are spaced evenly 180° apart on profile ridge 11,
the pump provides continuous suction.
Referring next to Figure 3 a side view of the complete pumping mechanism
and constant suction gradient cam of the preferred embodiment are shown. As illustrated,
the preferred embodiment contains a pump housing 14 which houses the three-lobe
gradient cam 10. Three-lobe cam 10 is situated within the cam housing and rotates
with the aid of roller bearings 16. Electromechanical driving means 20 of a conventional
type can be used to turn the cam. The electromechanical driving means 20 of the
preferred embodiment should be able to rotate the gradient cam at approximately
50 rpm in a counterclockwise direction with respect to the face of the gradient
cam. Accordingly, in operation, the three-lobe cam 10 should complete a revolution
every 1.20 seconds.
The three-lobe gradient cam 10 is directly driven by a drive shaft
18 attached to a slipper clutch 18a which attaches to the rear of three-lobe gradient
cam 10 through its central orifice 13. Referring to the lower portion of Fig. 4,
the two stationary cross-head assemblies with respective roller followers 12,
12a are illustrated. Figure 3 also illustrates that attached to each cross head
assembly and follower 12, 12a are Plunger assemblies 24 with sapphire pistons 26
which are injected into respective pumping heads 28, 28a. Each of the two cross
head assemblies and followers 12, 12a, plunger assemblies 24 and sapphire pistons
26 has a spring 28 which keeps each respective cross head and follower 12, 12a
on the profile ridge of the cam.
Referring next to Figure 4, an enhanced side view of the lower portion
of the entire cam drive mechanism is illustrated. As illustrated, three-lobe gradient
cam 10 is situated within the pump housing and rotates with the aid of roller
bearings 16. Also illustrated is a side view of the one stationary cross head assembly
and roller follower 12, 12a. The entire cross head assembly fit within a hollow
cylindrical chamber 30 located within the pump housing 14. As can be seen, each
cross head assembly and roller follower 12, 12a are kept on the cam face by means
of a spring 28 situated at the lower most proximity of the hollow cylindrical chamber
30. The spring 28 is held in place by a circlip 32 and cylindrical support 34.
At the lower-most portion of the cross head assembly is the plunger assembly 24
and sapphire piston 26. The plunger assembly 24 has an attachment 35 which mates
with the bottom of each cross head assembly and follower 12.
In operation, as the three-lobe gradient cam 10 rotates, the cross-head
assemblies and followers 12, 12a ride the gradient three-lobe cam 10 along ridge
11 and alternatively are thrust downward by the gradient cam. Accordingly, each
plunger assembly 24 and sapphire piston 26 is alternately thrust downward and
upward into the pumping head through a cylindrical seal 36 and cylindrical passage
38. Each pumping head 28, 28a includes an inlet check valve 40 and outlet check
valve 42, a passage for the flow of solvent 44 between the inlet and outlet check
valves and a pumping chamber 46. Each check valve assembly 42 includes a hollow
sapphire seat 48 and a ruby ball 50 which alternately act to permit and impede
the flow of solvent. The check valve assembly 42 is able to withstand internal
pressure of 10 thousand lbs. per square inch.
Referring next to Fig. 5, a flow chart diagram of an entire HPLC
system which utilizes the proportioning pump of the present invention is shown.
As shown, the HPLC system is capable of testing several sample solvents simultaneously.
Each of the respective solvents is attached to a tri-head solenoid valve system
52 which permits the flow of each respective solvent over an equivalent portion
of the flow cycle. Because of the constant suction created by the gradient cam
of the preferred embodiment, proportioning by the solenoid is facilitated. Thus,
the solenoid can be controlled by relatively simple timing software.
From the solenoid valve, each respective solvent goes through a manifold
54 which channels the solvent, and then into the inlet check valve of each respective
pump head 28, 28a. The pump head pumps the respective solvent out of the constant
suction proportioning pump into a pressure transducer and manifold 56. Pulse dampening
means 58 are used to remove any ripples or pulsations in the flow of the solvent.
The solvent proceeds to a mixing chamber 60 and then to the HPLC detector 62.
Thus, there has been described and illustrated herein, a three-lobe
gradient cam which provides high accuracy control of low-flow proportioning of
solvents on the inlet side of a proportioning pump by maintaining constant suction
pressure while providing short duration fill strokes for the proportioning pump.