U.S. patent application number 13/294514 was filed with the patent office on 2012-03-01 for method and installation for regulating the modifier level in chromatography or supercritical extraction with recycling.
This patent application is currently assigned to PIC SOLUTION. Invention is credited to Mohamed Shaimi.
Application Number | 20120048788 13/294514 |
Document ID | / |
Family ID | 36128269 |
Filed Date | 2012-03-01 |
United States Patent
Application |
20120048788 |
Kind Code |
A1 |
Shaimi; Mohamed |
March 1, 2012 |
METHOD AND INSTALLATION FOR REGULATING THE MODIFIER LEVEL IN
CHROMATOGRAPHY OR SUPERCRITICAL EXTRACTION WITH RECYCLING
Abstract
A chromatography or supercritical extraction method is
disclosed, in which the eluent comprises a mixture of a fluid and a
modifier and in which the fluid is recycled. One exemplary method
comprises an operation consisting in determining at least one
quantity linked to the level of modifier that is mixed with the
recycled fluid and, if necessary, a correction operation in order
to limit variations in the level of modifier in the eluent at the
inlet of the column or the extractor. The disclosure also relates
to a chromatography or extraction installation.
Inventors: |
Shaimi; Mohamed; (Montfavet,
FR) |
Assignee: |
PIC SOLUTION
Avignon
FR
|
Family ID: |
36128269 |
Appl. No.: |
13/294514 |
Filed: |
November 11, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12063559 |
Apr 16, 2009 |
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PCT/FR06/01946 |
Aug 11, 2006 |
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13294514 |
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Current U.S.
Class: |
210/96.1 |
Current CPC
Class: |
B01D 15/1814 20130101;
B01D 15/40 20130101; B01D 15/166 20130101 |
Class at
Publication: |
210/96.1 |
International
Class: |
B01D 15/10 20060101
B01D015/10 |
Foreign Application Data
Date |
Code |
Application Number |
Aug 12, 2005 |
FR |
0508535 |
Claims
1. A separation installation comprising: a separation device
configured to receive a product, an eluent, and a modifier; a
collection device downstream of said separation device, said
collection device configured to collect at least a fraction of said
product output from said separation device; a recycle path
downstream of said collection device, said recycle path configured
to recycle at least a portion of said eluent output from said
separation device; and a measuring and correcting device downstream
of said collection device and upstream of said separation device,
said measuring and correcting device configured to measure at least
one magnitude associated with a level of modifier in said recycled
eluent and to modify at least one of a flow of said eluent and a
flow of said modifier in response to said measurement.
2. The separation installation according to claim 1, wherein said
separation device includes one or more chromatography columns.
3. The separation installation according to claim 1, wherein said
separation device includes one or more extractors.
4. The separation installation according to claim 1, further
comprising a first pump downstream of said collection device and
upstream of said separation device, said first pump configured to
supply said flow of said eluent.
5. The separation installation according to claim 4, further
comprising a second pump downstream of said collection device and
upstream of said separation device, said second pump configured to
supply said flow of said modifier.
6. The separation installation according to claim 5, wherein said
first pump and said second pump are in parallel.
7. The separation installation according to claim 5, wherein said
measuring and correcting device is configured to modify at least
one of said flow in said first pump and said flow in said second
pump to meet at least one setpoint for said flow of at least one of
said eluent and said modifier into said separation device.
8. The separation installation according to claim 7, wherein said
at least one magnitude associated with said level of modifier mixed
with said recycled eluent includes a density.
9. The separation installation according to claim 8, wherein said
measuring and correcting device is configured to evaluate said
level of modifier mixed with said recycled eluent using a
pre-established density=f (modifier level) calibration curve at a
pressure and a temperature at a point of measurement.
10. The separation installation according to claim 7, wherein said
measuring and correcting device is downstream of said first pump
and said second pump.
11. The separation installation according to claim 7, wherein said
measuring and correcting device is upstream of said first pump and
said second pump.
12. The separation installation according to claim 7, wherein said
measuring and correcting device is downstream of said first pump
and upstream of said second pump.
13. The separation installation according to claim 7, wherein said
measuring and correcting device is downstream of said second pump
and upstream of said first pump.
14. The separation installation according to claim 7, further
comprising a condenser downstream of said collection device and
upstream of said first pump.
15. The separation installation according to claim 14, wherein said
measuring and correcting device is downstream of said
condenser.
16. The separation installation according to claim 14, wherein said
measuring and correcting device is upstream of said condenser.
17. The separation installation according to claim 1, further
comprising a pressure-reducer downstream of said separation device
and upstream of said collection device.
18. The separation installation according to claim 17, further
comprising a heat exchanger downstream of said pressure-reducer and
upstream of said collection device.
19. The separation installation according to claim 1, further
comprising a detector downstream of said separation device and
upstream of said collection device, said detector configured to
detect at least said fraction of said product output from said
separation device.
20. The separation installation according to claim 5, wherein said
second pump is upstream of said first pump.
21. A separation installation comprising: a separation device
configured to receive a product, a supercritical fluid, and a
modifier; a collection device downstream of said separation device,
said collection device configured to receive an output of said
separation device and collect at least a fraction of said product
output from said separation device; and a measuring and correcting
device downstream of said collection device and upstream of said
separation device, said measuring and correcting device configured
to receive a recycled supercritical fluid output from said
collection device and modify at least one of a flow of said
modifier and a flow of said supercritical fluid to limit variations
when said separation installation is running.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This patent application is a Continuation application of
U.S. patent application Ser. No. 12/063,559, filed on Apr. 16,
2009, which is a 371 filing of International Patent Application No.
PCT/FR2006/001946, filed on Aug. 11, 2006, which claims priority to
French Application No. 0508535, filed on Aug. 12, 2005, the
contents of all of which are incorporated herein by reference in
their entirety.
FIELD OF THE INVENTION
[0002] In general, this present invention concerns the methods that
make use of a fluid in a supercritical state and, in particular,
the field of chromatography and extraction in the supercritical
phase.
SUMMARY OF THE INVENTION
[0003] More precisely, according to a first of its aspects, the
invention concerns a chromatography or extraction method that
includes: [0004] a separating operation in a column or extractor,
with the said column or the said extractor receiving a product and
being fed into an eluent that includes a supercritical fluid,
routed via a first pumping operation, and a modifier, routed via at
least one second pumping operation, [0005] an operation to collect
at least one fraction downstream of the column or extractor, [0006]
an operation for recycling the supercritical fluid mixed with a
residual quantity of modifier following after the collecting
operation and preceding the first pumping operation, with the said
first pumping operation being used to pumps at least the said
supercritical fluid mixed with a residual quantity of modifier, and
[0007] a condensing operation, following on from the collecting
operation and preceding the first pumping operation.
[0008] Such a chromatography or extraction method, in which the
supercritical fluid is recycled, is known to those skilled in the
art.
[0009] Recycling of the supercritical fluid is preferable in order
to reduce the cost of implementing the method and the necessary
actions, particularly when high flows are employed.
[0010] For example, at a flow of carbon dioxide (CO.sub.2), used as
a supercritical fluid, of 80 ml/min, about 115 kg of CO.sub.2 is
lost every 24 hours if it is not recycled. This loss represents a
considerable cost.
[0011] In a conventional chromatography or extraction method in the
supercritical phase, the addition of a modifier is often necessary
in order to increase the polarity of the supercritical fluid.
[0012] In chromatography and extraction, the modifier level at the
input to the chromatography column or the extractor is an important
parameter that affects the performance of the method.
[0013] When the supercritical fluid is not recycled, this modifier
level is easily kept constant in that it depends on the flow in the
pump supplying the modifier, as well as on the flow in the pump
supplying the supercritical fluid, with these two flows themselves
being kept constant.
[0014] On the other hand, when the supercritical fluid is recycled
following the collecting operation, a certain quantity of modifier
can also be so. The result is a variation of the modifier level at
the input to the column or extractor, which is harmful to the
method.
[0015] In chromatography, for example, a variation of the modifier
level at the input to the column affects the retention time, the
resolution, and sometimes the selectivity of the eluted products
and therefore the stability of the method.
[0016] This also applies to the extraction, in which the modifier
level affects the extraction time and the concentration of
extracted product.
[0017] One is familiar with French patent FR 2 601 883, which
concerns a method and a device for separation with the aid of a
supercritical fluid, in which the supercritical fluid is
recycled.
[0018] After the separating operation and before it is recycled,
the supercritical fluid, in the gaseous or semi-gaseous phase and
containing a residual quantity of modifier, is brought into contact
with the modifier in the liquid phase in a conventional gas/liquid
contactor.
[0019] The composition of the phase with the lowest density
(gaseous or semi-gaseous) is adjusted by varying the pressure and
the temperature so as to obtain the desired
supercritical-fluid/modifier mixture at the output from
contactor.
[0020] This method is limited however, due to the thermodynamic
balances to be observed in the contactor, at mixtures containing at
most 10% by weight of modifier.
[0021] Moreover, this method is complex to implement. In fact it
leads to a requirement for a certain number of elements in, and in
relation to the contactor, such as a system for filling and
monitoring the level of modifier, a coating, a sintered material
and a droplet-separating device.
[0022] In this context, the aim of this present invention is to
propose a chromatography or extraction method in which the
supercritical fluid is recycled, and free of the limitations of the
prior art.
[0023] To this end, the method of the invention, which also
conforms to the generic definition provided in the foregoing
preamble, is essentially characterised in that it also includes:
[0024] downstream of the collecting operation and upstream of the
separating operation, an operation for determining at least one
magnitude associated with the level of modifier mixed with the
recycled supercritical fluid, and if necessary [0025] an operation
for correcting the flow in the first pumping operation and the flow
in the second pumping operation, in order to limit variation,
during execution of the method, of the modifier level in the eluent
at the input to the column or extractor, and in a direction that is
suitable for meeting a first setpoint, determined beforehand, of
total flow corresponding to the sum of the flows of the first
pumping operation and the second pumping operation.
[0026] The invention therefore has the advantage of proposing
controlling of the modifier level at the input to the column or
extractor. As a consequence, the method of the invention is more
stable than the methods of the prior art that use a modifier and
recycle the supercritical fluid without regulation of the modifier
level. By the stability of the method is meant the maintenance of
all of its parameters (temperatures, pressures, flows, levels,
etc.) at constant values. In particular, the method of the
invention ensures minimal variation of the modifier level at the
input to the column or extractor.
[0027] In addition, in the method of the invention, there exists no
limitation of the modifier level in the eluent. The user can choose
to make up an eluent containing between 0 and 100% of modifier.
[0028] In general, an eluent constitutes the mobile phase of a
chromatography or extraction. According to the invention, the
mobile phase is based on a fluid chosen from any fluid that is
compatible with an application in chromatography or extraction in
the supercritical phase. Hereinafter, such a fluid will be referred
to as a supercritical fluid, even if, in certain pressure and
temperature conditions, the fluid is not in a supercritical state
in the strict sense of the term. The supercritical state
corresponds to a pressure value (P) that is greater than the
critical pressure (Pc), and to a temperature value (T) that is
greater than the critical temperature (Tc). Also in the
supercritical state is included the subcritical state for which
P>Pc and T<Tc. We speak of a supercritical or subcritical
fluid with reference to a fluid of which the density and therefore
the solvent power undergo wide variation with the pressure and the
temperature when it is pure.
[0029] By simplification, we refer to the supercritical or
subcritical state as the state that the fluid would assume is it
were in the quoted pressure and temperature conditions only, even
if, in these conditions, it is mixed with another solvent and the
state of the mixture is not necessarily supercritical or
subcritical.
[0030] We finally speak of a recycled supercritical fluid even if
the fluid in the temperature and pressure conditions is not in a
supercritical state in the strict sense of the term, but in a state
that can be gaseous (with the temperature being greater than the
liquid-vapour equilibrium temperature for the pure fluid at a
working pressure less than the critical pressure) or liquid (with
the temperature being less than liquid-vapour equilibrium
temperature for the pure fluid at a working pressure less than the
critical pressure).
[0031] The eluent can also include a liquid solvent or a mixture of
liquid solvents, which constitutes a modifier. The modifier can be
an organic solvent. This is added in order to modify the polarity
of the supercritical fluid.
[0032] By a magnitude associated with the modifier level is meant
any magnitude from which the value of the modifier level can be
obtained, directly or indirectly. Thus, this magnitude can be the
modifier level itself.
[0033] In a first preferred embodiment of the invention, the
operation for determining at least one magnitude associated with
the level of modifier mixed with the recycled supercritical fluid
takes place upstream of the first and second pumping operations and
includes: [0034] an operation for measuring, at one measuring point
at least, the density of the recycled supercritical fluid mixed
with a residual quantity of modifier, and [0035] an operation for
evaluating the level of modifier mixed with the recycled
supercritical fluid, with the modifier level being evaluated, from
the measured density, by means of a calibration-density=f (modifier
level) graph established beforehand at the pressure and the
temperature existing at the measuring point and around the latter,
and [0036] the correction operation consists of modifying the flow
in the first pumping operation and the flow in the second pumping
operation in order to meet the first setpoint and a second
setpoint, set beforehand, for the modifier level in the eluent.
[0037] In this first embodiment, the first pumping operation and
the second pumping operation preferably take place in parallel with
each other. The second pumping operation can also take place
upstream of the first pumping operation.
[0038] According to a second preferred embodiment of the invention,
the operation for determining a magnitude associated with the
modifier level in the eluent consists of measuring the density of
the eluent upstream of the first pumping operation and downstream
of the second pumping operation, and the correction operation
consists of modifying the flow in the first pumping operation and
the flow in the second pumping operation in a direction that is
suitable for meeting the first setpoint and a third setpoint, set
beforehand, for the density of the eluent.
[0039] Preferably, the operation for determining at least one
magnitude associated with the level of modifier mixed with the
recycled supercritical fluid is effected downstream or upstream of
the condensing operation.
[0040] Advantageously, the method of the invention can also include
at least one operation for regulating the pressure followed by at
least one operation for regulating the temperature, downstream of
the separating operation and upstream of the collecting
operation.
[0041] The invention also concerns a chromatography or extraction
installation that includes: [0042] a separating device such as one
or more chromatography columns or an extractor, which receives a
product and feeds into an eluent that includes a supercritical
fluid, routed via a first pump, and a modifier, routed via at least
one second pump, [0043] a device for collecting at least one
fraction of the product separated in the separating device, [0044]
a path for recycling the supercritical fluid mixed with a residual
quantity of modifier, downstream of the collection device and
upstream of the first pump, with the said first pump pumping at
least the said supercritical fluid mixed with a residual quantity
of modifier, and [0045] a condenser placed downstream of the
collection device and upstream of the first pump,
[0046] with the said installation being characterised in that it
also includes a measuring and correcting device, placed in the
recycling path or downstream of the first pump, and upstream of the
separating device, which measures at least one magnitude associated
with the level of modifier mixed with the recycled supercritical
fluid and that, if necessary, performs correction of the flow in
the first pump and of the flow in the second pump in order to limit
the variations, while running the installation, of the said levels
at the input to the separating device, and in a direction that is
suitable for meeting a first setpoint, determined beforehand, of
total flow corresponding to the sum of the flows in the first pump
and in the second pump.
[0047] According to a first preferred embodiment of the invention,
the measuring and correcting device is positioned at a measuring
point located upstream of the first and second pumps and measures
the density of the recycled supercritical fluid, mixed with a
residual quantity of modifier, from which it evaluates the level of
modifier mixed with the recycled supercritical fluid by means of a
pre-established density=f (modifier level) calibration curve at the
pressure and the temperature existing at the measuring point and
around the latter; and the said measuring and correcting device
modifies the flow in the first pump and the flow in the second pump
in order to attain the first setpoint and a second setpoint, set
beforehand, of modifier level in the eluent.
[0048] In this first embodiment, the first pump and the second pump
are preferably mounted in parallel with each other. The second pump
can also be positioned upstream of the first pump.
[0049] According to a second preferred embodiment of the invention,
the measuring and correcting device measures the density of the
eluent upstream of the first pump and downstream of the second
pump, and the correction consists of modifying the flow in the
first pump and the flow in the second pump in a direction that is
suitable for meeting the first setpoint and a third setpoint, set
beforehand, for the density of the eluent. The measuring and
correcting device can be located downstream or upstream of the
condenser.
[0050] According to one particular embodiment, the installation
according to the invention also includes a device to regulate the
pressure, a pressure-reducer for example, followed by a device to
regulate the temperature of the eluent, by heating it for example,
downstream of the separating device and upstream of the collection
device.
[0051] The invention is advantageously implemented with carbon
dioxide as the supercritical fluid.
[0052] As the modifier, it is preferable to use an organic solvent
liquid, like an alcohol for example.
BRIEF DESCRIPTION OF THE DRAWINGS
[0053] Other characteristics and advantages of the invention will
emerge more clearly from the detailed description provided below,
purely as a guide and in no way limiting, with reference to the
appended drawings in which:
[0054] FIG. 1 is a diagram of one embodiment of the method of the
invention,
[0055] FIG. 2 represents a density=f (modifier level) calibration
curve that can be used in accordance with the invention, and
[0056] FIGS. 3 and 4 each represents a diagram of an installation
according to the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0057] According to one particular embodiment of the invention, the
chromatography or extraction method includes the operations
represented in FIG. 1.
[0058] Conventionally, a separating operation 1 takes place in a
chromatography column or in an extractor.
[0059] The column or the extractor are supplied with an eluent that
includes a supercritical fluid and a modifier.
[0060] The product P is inserted into the chromatography column, by
injection for example.
[0061] A first pumping operation 2 brings the supercritical fluid,
which has been subjected beforehand to a condensing operation 6, to
the column or to the extractor.
[0062] A second pumping operation 3 brings the modifier to the
column or to the extractor.
[0063] Thus, a supercritical-fluid/modifier mixture constituting
the eluent is formed for the separating operation 1. At this stage,
the eluent is preferably in a supercritical state.
[0064] An operation 11 for regulating the temperature of the eluent
can be effected before the separating operation 1. For example, the
eluent is heated in a heat exchanger.
[0065] An operation 4 for collecting at least one fraction of the
product P is effected downstream of the column or extractor.
[0066] An operation 9 for regulating the pressure and an operation
10 for regulating the temperature of the eluent are preferably
effected following the separating operation 1 and prior to the
collecting operation 4.
[0067] The operation 9 for regulating the pressure consists, for
example, of reducing pressure in the eluent enriched with at least
one fraction of the product P, to a pressure that is less than the
critical pressure of the supercritical fluid. If the supercritical
fluid CO.sub.2, the pressure reduction therefore occurs at a
pressure that is less than 74 bars, and typically between 30 and 65
bars.
[0068] After the pressure reduction, the supercritical fluid is in
liquid and gaseous form. The liquid part is in the majority, and
depends on the pressure at which pressure reduction takes
place.
[0069] This liquid part can be converted to a gas by heating during
the operation 10 for regulating the temperature.
[0070] This conversion results in a drop in the density of the
supercritical fluid and therefore in the solubility of the solute
constituting the fraction of product P in this fluid. The
solubility of the solute diluted in the modifier becomes almost
zero, which allows separation of the solute, solid or liquid, of
the supercritical fluid brought to the gaseous state, by means of
gas-solid or gas-liquid separators.
[0071] An operation 5 for recycling the supercritical fluid brought
to the gaseous state and mixed with a residual quantity of modifier
follows on from the collecting operation 4 and precedes the first
pumping operation 2.
[0072] There exist two causes for the presence of a residual
quantity of modifier in the supercritical fluid brought to the
gaseous state following the collecting operation 4.
[0073] Firstly, the modifier has a vapour tension that results in a
certain solubility in the supercritical fluid brought to the
gaseous state. The percentage of modifier that is recycled depends
on the solubility of the modifier in the supercritical fluid
brought to the gaseous state, and this solubility is a function of
the pressure and temperature of the supercritical fluid brought to
the gaseous state in the separators.
[0074] Secondly, the percentage of modifier that is recycled
depends on the effectiveness of trapping in the separators.
[0075] The condensing operation 6 follows on from the collecting
operation 4 and precedes the first pumping operation 2. It takes
place advantageously during the recycling operation 5.
[0076] The pressure and the temperature of the supercritical fluid
mixture brought to the gaseous-modifier state, obtained by the
corresponding regulating operations 9, 10, are constant during the
collecting and recycling operations 4, 5 and up to the condensing
operation 6, during which the temperature is lowered.
[0077] In addition, the method of the invention includes,
downstream of the collecting operation 4 and upstream of the
separating operation 1, an operation 7 for determining at least one
magnitude associated with the modifier level mixed with the
supercritical fluid recycled and brought to the gaseous or liquid
state.
[0078] Preferably, in order to facilitate the implementation of the
method, the operation 7 is effected upstream of the first pumping
operation 2. The fact of measuring the density at the input to the
pump facilitates the operation since, at this stage of the method,
it is possible, whatever the operating conditions of flow, column
type and size, temperature, etc., to maintain a constant pressure
and temperature during execution of the method and from one method
to the next.
[0079] If necessary, an operation 8 for correcting the flow in the
first pumping operation 2 and the flow in the second pumping
operation 3 is effected in order to limit the variations, during
execution of the method, of the modifier level in the eluent at the
input to the column or the extractor. The flows are corrected in a
direction that is suitable for meeting a first setpoint, determined
beforehand, of the total flow corresponding to the sum of the flows
of the first pumping operation 2 and of the second pumping
operation 3.
[0080] More particularly, FIG. 1 represents an advantageous version
of the invention. According to this version, the operation 7 for
determining at least one magnitude associated with the level of
modifier mixed with the supercritical fluid brought to the liquid
state takes place upstream of the first and second pumping
operations 2, 3. It includes an operation, at one measuring point
at least, for measuring the density of the supercritical fluid
recycled and brought to the liquid state, mixed with a residual
quantity of modifier, and an operation for evaluating the level of
modifier mixed with the supercritical fluid, with the modifier
level being evaluated, from the measured density, by means of a
density=f (modifier level) calibration curve established beforehand
at the pressure and the temperature existing at the measuring point
and around the latter. Such a calibration curve is represented in
FIG. 2.
[0081] The correction operation 8 consists, in this case, of
modifying the flow in the first pumping operation 2, and the flow
in the second pumping operation 3, in order to satisfy the first
setpoint and a second setpoint, set beforehand, of modifier level
in the eluent.
[0082] The density of the supercritical fluid, mixed with a
residual quantity of modifier, is the sum of the densities of the
constituents, namely the supercritical fluid and modifier, weighted
by their percentage, with an offset in the case where the mixture
of the constituents has a final volume other than the sum of the
initial volumes of the constituents.
[0083] In FIG. 2, the term "density" refers to the mass per volume.
Moreover, the CO.sub.2 is given by way of an example of a
supercritical fluid.
[0084] In order to draw a calibration curve as represented in FIG.
2, the density of the supercritical fluid mixed with a residual
quantity of modifier, shown on the ordinate, is measured for
different modifier levels, shown on the abscissa. The different
supercritical fluid-modifier mixtures are created by the first and
second pumping operations, at a given temperature and pressure.
[0085] The variation in the density of the supercritical fluid
mixed with a residual quantity of modifier as a function of the
modifier level depends on the difference in density of the pure
constituents in the set conditions of pressure and temperature. The
greater this difference, the greater too is the variation in the
density of the mixture as a function of its composition, and the
greater is the precision in determining the modifier level.
[0086] Therefore, it is preferable to establish conditions of
temperature and pressure at which the difference in density of the
pure constituents is greatest.
[0087] The precision in determining modifier level also depends on
the precision of the test gear for measuring the density.
[0088] The density=f (modifier level) curve is linear, except in
the case mentioned previously in which the supercritical-modifier
fluid mixture has a final volume that is different from the sum of
the initial volumes of supercritical fluid and modifier.
[0089] In the configuration of the invention represented in FIG. 1,
the first pumping operation 2 and the second pumping operation 3
take place in parallel with each other.
[0090] Nevertheless, a configuration in which the second pumping
operation takes place upstream of the first pumping operation also
forms part of the invention.
[0091] It is preferable to measure the density in order to
determine the level of modifier mixed with the supercritical fluid,
in that this measurement is relatively easy to implement and has
good precision, but other physical magnitudes can also be used to
obtain the value of the level of modifier mixed with the
supercritical fluid. It is possible, for example, to measure the
thermal conductivity of the mixture, or indeed to perform a
measurement of the absorption of this melange in the ultraviolet
range.
[0092] According to another advantageous version of the invention,
the operation for determining a magnitude associated with the level
of modifier mixed with the supercritical fluid recycled and brought
to the liquid state, consists of measuring the density of the
mixture, which is then the eluent, upstream of the first pumping
operation and downstream of the second pumping operation. In this
case, the correction operation consists of modifying the flow in
the first pumping operation and the flow in the second pumping
operation in a direction that is suitable for meeting the first
setpoint and a third setpoint, set beforehand, for the density of
the eluent.
[0093] As before, it is possible to replace the measurement and the
density setpoint of the eluent with a measurement and a setpoint of
thermal conductivity or absorption in the ultraviolet.
[0094] In this configuration, one is not seeking to determine the
residual modifier level in the supercritical fluid recycled and
brought to the liquid or gaseous state, but to aim for a density
setpoint at the input to the pump. For this, a regulation loop is
created.
[0095] The density setpoint is determined, for example, by
measuring the density corresponding to the modifier level in the
eluent in the absence of recycling, by adjusting the flows of the
pumping operations to as to ascertain the wanted modifier level and
the total flow, in fixed operating conditions.
[0096] The regulation loop consists of adjusting the flows of the
pumping operations in the direction that is suitable to satisfy two
setpoints, namely density and total flow. A single pair of values
of the flows in the first and second pumping operation satisfy both
a density setpoint and to a total-flow setpoint.
[0097] Advantageously, the operation 7 for determining at least one
magnitude associated with the level of modifier mixed with the
supercritical fluid is effected downstream of the condensing
operation 6. In fact, in order to measure the density, the
supercritical fluid is preferably brought to the liquid state by
cooling it to below the liquid-vapour equilibrium temperature, at
the recycling pressure that is less than the critical pressure.
Thus, the measurements are more precise than measurements in a
gaseous phase.
[0098] Nevertheless, this operation for determining at least one
magnitude associated with the level of modifier mixed with the
recycled supercritical fluid can be performed upstream of the
condensing operation 6. In this case, the density is measured in
the supercritical fluid brought to the gaseous state.
[0099] One way of measuring the density is, for example, the use of
a mass flowmeter based on the Coriolis principle, which can be used
to obtain the flow and the density, or of an appliance dedicated to
the specific measurement of the density of a fluid or of a mixture
of fluids at a given pressure and temperature.
[0100] The measured density can be corrected to take account of the
temperature.
[0101] The supercritical fluid is preferably carbon dioxide, but
can be any fluid that is compatible with chromatography and/or
extraction in the supercritical phase, such as an alkane, a
chloro-fluoroalkane or xenon.
[0102] The modifier is preferably an alcohol, like methanol,
ethanol or isopropanol for example, but can also be any organic
solvent, such as acetonitrile, methyltertbutylether or MTBE, or
ethyl acetate. It can be a mixture of at least two of these
compounds.
[0103] FIGS. 3 and 4 each schematically represent an installation
according to the invention, which can be used to implement the
method of the invention. We have chosen in particular to illustrate
the chromatography installations.
[0104] The same elements making up the installation are each
indicated by the same reference in these two figures.
[0105] FIG. 3 illustrates a first configuration according to the
invention. This installation includes a separating device that
includes at least one chromatography column 12.
[0106] This column 12 receives a mixture that includes a product P
introduced by injection and an eluent that includes a supercritical
fluid, such as the CO.sub.2, and a modifier. The supercritical
fluid, held in recipient A, is routed via a first pump 13 and the
modifier, held in recipient B, is routed via at least one second
pump 14.
[0107] At the output from the column 12, a detector 20 is used to
detect the fraction or fractions of the product, (P) that come out
of the column with the eluent.
[0108] These fractions are collected in a collection device 15 that
includes at least one solid-gas or liquid-gas separator according
to which the solute constituting the fraction of product (P) is
solid or liquid. Several separators can be connected in series.
[0109] In the case of an eluent that is free of modifier and that
is therefore a pure supercritical pure, its recycling would simply
require arranging for the trapping of all the solute in the
separator or separators.
[0110] In the case of the invention, the eluent includes modifier
at between 0 and 100% by weight, preferably between 0.1% and 70%,
or preferably between 0.5% and 35%. At the output from the column
12, there is a mixture of eluent and solute, making a mixture of
three constituents--supercritical fluid, modifier and solute.
[0111] This mixture is put through a device to regulate the
pressure, and a device to regulate the temperature. Thus, in a
first stage, the mixture passes through a pressure-reducer 19 in
order to reduce the pressure of the eluent. This results in a
mixture of supercritical fluid brought to the liquid state,
supercritical fluid brought to the gaseous state, modifier, and
solute.
[0112] This last mixture is then heated in the device to regulate
the temperature, in order to convert the supercritical fluid part
brought to the liquid state into supercritical fluid brought to the
gaseous state. One is therefore in the presence of two phases,
namely a liquid phase containing the modifier in which the solute
is soluble, and a gaseous phase of supercritical fluid brought to
the gaseous state in which we find a certain modifier level and
traces of solute.
[0113] A first separator is used to separate the liquid phase from
the gaseous phase and to collect the soluble solute in the
modifier.
[0114] The use of a second separator in series with the first
allows all of the solute to be trapped.
[0115] A path 16 for recycling the supercritical fluid brought to
the gaseous and then the liquid state mixed with a residual
quantity of modifier is positioned between the collection device 15
and the first pump 13. The first pump 13 pumps at least the
supercritical fluid brought to the liquid state and mixed with a
residual quantity of modifier.
[0116] The pumped mixture first passes via a condenser 17 placed
downstream of the collection device 15 and upstream of the first
pump 13. The condenser 17 is preferably placed in the recycling
path 17.
[0117] The installation according to the invention also includes a
measuring and correcting device 18, placed in the recycling path 16
or downstream of the first pump 13 and upstream of the
chromatography column 12. The measurements are facilitated in the
case where the device 18 is located in the recycling path 16,
upstream of the first pump 13.
[0118] This device 18 measures at least one magnitude associated
with the level of modifier mixed with the recycled supercritical
fluid and, if necessary, performs correction of the flow in the
first pump 13 and of the flow in the second pump 14 in order to
limit the variations, while running the installation, of this level
at the input to the chromatography column 12.
[0119] The correction is effected in a direction that is suitable
for meeting a first setpoint, determined beforehand, of total flow.
The total flow corresponds to the sum of the flows in the first
pump 13 and in the second pump 14. Preferably, the measuring and
correcting device 18 is placed downstream of the condenser 17.
[0120] Nevertheless, the measuring and correcting device can also
be placed upstream of the condenser.
[0121] In the first particular configuration represented in FIG. 3,
the measuring and correcting device 18 is placed at a measuring
point located upstream of the first and second pumps 13, 14, and
more precisely the first pump 13 and the second pump 14 are mounted
in parallel with each other.
[0122] According to a second particular configuration (not shown)
of the invention, the second pump is positioned upstream of the
first pump, and the measuring and correcting device is positioned
at a measuring point located upstream of the second pump.
[0123] In this case, the installation has the advantage of
requiring only a high-pressure pump, which is the first pump 13.
The second pump 14, in series with and upstream of the first pump
13, can be just a low-pressure pump. For example, the first pump
has a feed pressure of between 30 and 300 bars, preferably between
100 and 300 bars, and the second pump, for example, has a feed
pressure of between 1 and 100 bars, preferably of the order of 50
bars.
[0124] At the measuring point, in these two configurations, the
measuring and correcting device 18 measures a first magnitude
associated with the modifier level mixed with the supercritical
fluid recycled and brought to the liquid state, which is preferably
the density of the mixture. From this measured density, the device
18 evaluates a second magnitude associated with the level of
modifier mixed with the supercritical fluid recycled and brought to
the liquid state, which is the modifier level, by means of a
calibration curve such as that represented in FIG. 2.
[0125] The measuring and correcting device 18 modifies the flow in
the first pump 13 and the flow in the second pump 14 in order to
attain the first setpoint and a second setpoint, set beforehand, of
modifier level in the supercritical-fluid/modifier mixture.
[0126] The setpoints are set by the user as a function of the
process that he wishes to execute with the installation according
to the invention.
[0127] The recycled supercritical fluid contains traces of modifier
due to the solubility of the latter in the supercritical fluid
brought to the gaseous state.
[0128] The first pump 13 pumps supercritical fluid brought to the
liquid state and containing modifier, and the flow of supercritical
fluid is less than its initial value, meaning than the value set at
the start-up of the installation. It is therefore necessary to
increase the flow in the first pump 13 in order to adjust the flow
of supercritical fluid to its initial value by compensating for the
presence of the modifier.
[0129] For example, at the start-up of the installation, the flow
of supercritical fluid is set to a value of 80 g/min, and the flow
of modifier to a value of 20 g/min. The first total-flow setpoint
is therefore 100 g/min, and the user fixes the second setpoint of
modifier level at 20%.
[0130] The residual level of modifier in the recycled supercritical
fluid is 5% for example. In this case, if the flow is not corrected
in the first pump 13, then the actual flow of supercritical fluid
will be 95% of 80 g/min, which is 76 g/min.
[0131] It is then necessary to adjust the flow in the first pump 13
so as to satisfy the relation Q. x 0.95=80 g/min, where Q is the
value of the corrected flow in the first pump 13. Here, Q is about
84.2 g/min. The flow in the first pump 13 is therefore increased by
4.2 g/min.
[0132] The flow in the second pump 14 is reduced so as to maintain
a modifier level of 20% in the eluent, and a total flow of 100
g/min. The corrected flow in the second pump 14 is 100-84.2 or 15.8
g/min, which represents a reduction in the initial flow of 84.2.x
0.05 g/min which is about 4.2 g/min.
[0133] According to a third particular configuration of the
invention, as represented in FIG. 4, the measuring and correcting
device 18 measures the density of the eluent upstream of the first
pump 13 and downstream of the second pump 14. In other words, this
third configuration differs from the previous two in that the
second pump 14 is installed upstream of the device 18.
[0134] In this third configuration, the correction consists of
modifying the flow in the first pump and the flow in the second
pump in a direction that is suitable for meeting the first setpoint
and a third setpoint, set beforehand, for the density of the
eluent.
[0135] This third setpoint can be determined by the user by
calculation, given that the density of the supercritical-modifier
fluid mixture is equal to the sum of the respective densities of
the supercritical fluid and modifier, weighted by their respective
percentages, but a more precise measurement is preferred, by
measuring in the installation in operation without recycling.
[0136] For regulating the flows of the two pumps 13, 14, each of
these pumps is connected to a flowmeter.
[0137] For example, an eluent is composed of CO.sub.2, as the
supercritical fluid, and ethanol as the modifier. For a pressure of
50 bars and a temperature of 0.degree. C., the density of the
CO.sub.2 is 950 kg/m.sup.3, and that of the ethanol is 789
kg/m.sup.3. For precision in the measurement of the density of +0.1
kg/m.sup.3, it is possible to adjust the composition of the
CO.sub.2-ethanol eluent with a precision of +0.05%.
[0138] The precision increases as the respective densities of the
supercritical fluid and modifier differ from reach other. For
example, in the case where the supercritical fluid is CO.sub.2, the
alcohols are very suitable as modifiers, in that they are of low
density, and the chlorated solvents are also suitable in that they
are high density.
[0139] Naturally however, the chromatography column 12 can be
replaced by several chromatography columns or, in the case of one
method of extraction, by an extractor in which we find the product
P.
[0140] This column 12 can be one that contains a stationary phase
like that used in chromatography in the gaseous phase, or a column
containing a stationary phase like that used in chromatography in
the liquid phase, such as high-performance liquid chromatography
(HPLC), or indeed any other column compatible with the separation
to be effected.
[0141] Likewise, the extractor used in the invention can have a
liquid or solid stationary phase.
* * * * *