U.S. patent application number 16/563793 was filed with the patent office on 2019-12-26 for column packing method.
This patent application is currently assigned to GE Healthcare Bio-Sciences AB. The applicant listed for this patent is GE Healthcare Bio-Sciences AB. Invention is credited to Per KARLBERG, Joakim LUNDKVIST, Erik RURLING.
Application Number | 20190388803 16/563793 |
Document ID | / |
Family ID | 40901327 |
Filed Date | 2019-12-26 |
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United States Patent
Application |
20190388803 |
Kind Code |
A1 |
KARLBERG; Per ; et
al. |
December 26, 2019 |
COLUMN PACKING METHOD
Abstract
A method for packing a media bed in a column (3). According to
the invention the method comprises the steps of: providing data to
a control unit (15) connected to the column (3), said data
comprising at least a measured slurry concentration, a target bed
height, a target packing factor or compression factor and minimum
and maximum acceptable values for at least one of target bed height
and target packing or compression factor; forcing a movable adapter
(9) along a longitudinal axis of the column (3) in order to pack
the media; detecting when the media bed is consolidated; the
control unit (15) processing the provided data and the information
about the consolidated bed height in order to present to the user
acceptable bed heights, if there are any, giving acceptable packing
or compression factors.
Inventors: |
KARLBERG; Per; (Uppsala,
SE) ; RURLING; Erik; (Bromma, SE) ; LUNDKVIST;
Joakim; (Uppsala, SE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
GE Healthcare Bio-Sciences AB |
Uppsala |
|
SE |
|
|
Assignee: |
GE Healthcare Bio-Sciences
AB
Uppsala
SE
|
Family ID: |
40901327 |
Appl. No.: |
16/563793 |
Filed: |
September 6, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13909003 |
Jun 3, 2013 |
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16563793 |
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12863195 |
Jul 16, 2010 |
8454834 |
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PCT/SE2009/000012 |
Jan 15, 2009 |
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13909003 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
G01N 2030/565 20130101;
B01D 15/206 20130101; G01N 30/56 20130101 |
International
Class: |
B01D 15/20 20060101
B01D015/20 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 23, 2008 |
SE |
0800160-4 |
Claims
1. A method for packing a media bed in a column (3) from a slurry
being a dispersion of said media particles and a liquid, comprising
the steps of: providing data to a control unit (15) connected to
the column (3), said data comprising at least a measured slurry
concentration, a target bed height, a target packing factor or
compression factor and minimum and maximum acceptable values for at
least one of target bed height and target packing or compression
factor; filling the column (3) with correct amount of slurry
according to the column dimensions and the provided data; forcing a
movable adapter (9) along a longitudinal axis of the column (3) in
order to pack the media; detecting when the media bed is
consolidated; the control unit (15) processing the provided data
and the information about the consolidated bed height in order to
present to the user acceptable bed heights, if there are any,
giving acceptable packing or compression factors.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation application of U.S.
patent application Ser. No. 12/863,195 filed Jul. 16, 2010, now
U.S. Pat. No. 8,454,834, which is a filing under 35 U.S.C. .sctn.
371 and claims priority to international patent application number
PCT/SE2009/000012 filed Jan. 15, 2009, published on Jul. 30, 2009,
as WO 2009/093953, which claims priority to patent application
number 0800160-4 filed in Sweden on Jan. 23, 2008.
FIELD OF THE INVENTION
[0002] The present invention relates to a media packing system for
columns and media packing methods for use in columns. More
specifically, the invention relates to methods for improving the
quality, ease and consistency of packing chromatography media into
chromatography columns.
BACKGROUND OF THE INVENTION
[0003] Columns used in liquid chromatography typically comprise a
tubular body enclosing a packed bed of porous chromatography medium
through which a carrier liquid flows, with separation taking place
by material collection between the carrier liquid and solid phase
of the porous medium. Typically, the medium is enclosed in the
column as a packed bed formed by consolidating a suspension of
discrete particles, known as slurry that is pumped, poured, or
sucked into the column. Consolidation of the slurry into a
consolidated packed bed is achieved by compressing the slurry so
that it is packed into a volume, which is less than the volume that
it would have occupied if it had been allowed to settle under the
influence of gravity to form a sedimented bed. The efficiency of
subsequent chromatographic separation relies strongly on 1) the
liquid distribution and collection system at the fluid inlet and
outlet of the packed bed, 2) on the special orientation (also know
as the packing geometry) of the media particles in the packed bed,
and 3) on the compression of the packed bed. If the compression of
the packed bed is too low then chromatographic separations
performed on that bed suffer from "tailing" and, generally, such
insufficiently compressed beds are unstable. If the compression of
the packed bed is too high then chromatographic separations
performed by the bed suffer from "leading" and such over-compressed
beds can affect throughput and binding capacity, and, in general,
give much higher operating pressures. If the compression is
optimum, then the separation peaks formed during use exhibit much
less leading or tailing and are substantially symmetrical. The
optimum degree of compression required for a column is determined
experimentally for each column size (width or diameter), bed
height, and media type.
[0004] Prior to any separation process, the bed has to be prepared
by starting from the slurry of particles that has to be introduced
into the column. The process of bed formation is called `the
packing procedure` and a correctly packed bed is a critical factor
influencing the performance of a column containing a packed bed.
One of the primary goals of the packing procedure is to provide a
bed, which is compressed by the optimum amount of compression, i.e.
the optimum compression factor. The height of the bed which often
is user defined when it is optimally compressed is called the
target compressed bed height.
[0005] Large-scale columns, are preferably prepared by injecting
into the column a predetermined volume of slurry having a specified
concentration of media particles. Once the predetermined volume of
slurry has been delivered into the column it needs to be further
consolidated and compressed by moving a movable adapter down the
longitudinal axis of the column towards the bottom of the column,
normally at a constant speed. The excess liquid during this
procedure is expelled at the column outlet, while the media
particles are retained by means of a filter material, a so-called
`bed support`, with pores too small to allow the media particles to
pass though. The packing process is complete once the packed bed
has been compressed by the optimum degree of compression. The
packing process is considered successful if the compressed bed
allows for a good and robust chromatographic performance. However,
packing such an optimally compressed bed of chromatography media in
a chromatography column by manual means is not easy to accomplish
in practice due to the fact that the quality of the final packed
bed depends to a great extent on the skill of the operator. During
filling and subsequent packing of the column, the operator manually
selects and adjusts all packing parameters such as valve positions,
pump speed, adapter's speed of movement, etc. The operator has to
measure the slurry concentration in order to decide how much slurry
that should be filled into the column. If the measure of the slurry
concentration is not exact (which is often the case because it is
hard to measure the slurry concentration exactly) the volume of the
slurry filled into the column is not optimal and the consolidated
bed will settle at a bed height that was not expected (as
calculated from the measured slurry concentration) and hereby the
target packing factor can not be achieved at target bed height.
Furthermore, the operator also has to judge the point when the
adapter starts compressing the bed. This point is used to calculate
how much further the adapter must move in order to obtain the
required amount of compression. Mistakes in the selection of any of
the packing parameters normally lead to a poorly performing column.
Further, in columns equipped with a transparent tube it may be
difficult, and in columns equipped with a non-transparent tube such
as stainless steel it is impossible, to judge by eye when
compression of the bed actually starts and a significant error at
this point makes it impossible to obtain an optimally compressed
bed.
[0006] There is also a risk of damaging the media and the column if
the user takes wrong decisions.
[0007] Therefore, there is a need for a system and method for the
accurate and reproducible packing of chromatography media into
chromatography columns. To repack a wrongly packed column is both
time consuming and costs a lot of money.
SUMMARY OF THE INVENTION
[0008] An object of the invention is to provide a column packing
system and a method for packing media into columns in order to
overcome the drawbacks of the prior art systems.
[0009] A further object of the invention is to provide a column
packing method and system giving an acceptable packing factor to
the compressed bed at acceptable bed height.
[0010] Hereby the user will be presented different acceptable bed
heights together with their expected, acceptable packing or
compression factors.
[0011] Suitably windows in time or distance as to when to stop the
packing such that both bed height and pack factor are within given
acceptable ranges are presented to the user. Hereby the user can
easily see the different options of when to stop the packing.
[0012] Preferably a warning is presented to the user if no
acceptable bed height values can be achieved or if the user has not
stopped the packing after the minimum acceptable bed height has
passed. Hereby damage of the media and/or the column can be
prevented.
[0013] Suitably the method further comprises controlling the
packing to be automatically stopped after a predetermined period of
time if no acceptable bed height values can be achieved or if the
user has not stopped the packing after the minimum acceptable bed
height has passed. Hereby damage of the media and/or the column can
be prevented.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1 is a schematic diagram of a media packing system
according to the invention.
[0015] FIG. 2 is a flow chart describing the packing method
according to the invention.
[0016] FIG. 3 is an exemplary view of a user interface according to
the invention.
[0017] FIG. 4A is a more detailed flow chart of a consolidation
process according to one embodiment of the invention.
[0018] FIG. 4B is a detailed flow chart of the compression process
according to one embodiment of the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0019] The presently preferred embodiments of the invention are
described with reference to the drawings. The descriptions of the
preferred embodiments are exemplary and are not intended to limit
the scope of the invention.
[0020] As used herein and in the appended claims:
[0021] The term "column" is intended to include the terms "vessel"
and "cell", as well as any other structure utilized by
practitioners of the separation arts, to effect a separation,
and/or reaction, and/or catalyzation, and/or extraction of
components from an admixture by bringing the admixture into contact
with solid or liquid exchange media, known as the packed bed.
[0022] The term "slurry" is a dispersion of media particles and
liquid. The term "longitudinal direction of flow" refers to the
direction of flow from an inlet towards an outlet within a column.
"Longitudinal" is used consistently to designate the dominant flow
path of fluid through a cell without regard to direction.
[0023] The term "distribution system" refers to structures through
which fluids are introduced to a column and the term "collection
system" refers to structures used to collect fluids from a
column.
[0024] The term "sedimented bed height" refers to the height of a
bed of media particles which is obtained when a bed is formed after
the media particles in a slurry are allowed to sediment under the
influence of gravity only--such a bed is called a "sedimented
bed".
[0025] The term "consolidated bed height" refers to the height of a
bed of media particles that is obtained when a bed is formed in a
column while the media particles in a slurry are forced to sediment
when a flow of fluid is applied through the column in the
longitudinal direction of flow either by 1) pumping liquid into the
column, 2) by pumping liquid out of the column, or 3) by the
movement (for example, the descent) of a movable adapter, which
forces liquid out of the column--such a bed is called a
"consolidated bed".
[0026] The term "compressed bed height" refers to the height of a
bed of media particles in a column that is obtained when a
consolidated or sedimented bed has been compressed, for example by
contact with, and further movement of, a movable adapter or the
like, or by pumping fluid through the column at a higher rate than
that used during consolidation of the bed--such a bed is called a
"compressed bed". The term "compression factor" is defined as (the
sedimented bed height)/(the compressed bed height) and the term
"packing factor" is defined as (the consolidated bed height)/(the
compressed bed height). Hereafter, when packing factor is used it
should be understood that the compression factor could be used
instead.
[0027] FIG. 1 is a schematic view of a column packing system
according to the invention. The system comprises a column 3 which
comprises upper lid or flange 5a and lower end plate 5b surrounded
by a cylindrical column wall 7. Positioned between the lid or
flange 5a and lower end plate 5b in the column 3 is a movable
adapter 9 (which may be provided with a liquid distribution system,
not shown, intended to distribute incoming liquid substantially
evenly over the cross-section of the column 3, and a bed support,
not shown, extending over the cross-section of the column with a
mesh fine enough to prevent bed particles from passing through it)
connected to a column inlet 11 connectable to a liquid delivering
system 14 which delivers liquids such as sample mixtures, eluants,
buffers etc. Movable adapter 9 is movable in the longitudinal
direction of the column by an actuator (not shown), such as an
electric, hydraulic or pneumatic motor or piston/cylinder
actuator.
[0028] Slurry can be sucked into the column 3 through a nozzle or
valve 12 positioned in the bottom of the column. The nozzle or
valve 12 is connected to a slurry tank 13. Movable adapter 9 is
provided with a positioning means (not shown) to determine the
position ("x") of the movable adapter relative to a fixed level,
for example the upper side of the lower end plate 5b, and a signal
corresponding to the distance x is sent to a control unit 15 which
in this example is connected to the liquid delivering system 14 and
to the adapter actuator. The control unit 15 could however instead
be built into the liquid delivering system 14. The operation of the
actuator and the corresponding up or downwards movement of the
movable adapter 9 is controllable by the control unit 15. Control
unit 15 preferably comprises hardware and software for controlling
the operation of the column 3. The control unit 15 controls for
example the opening and closing of valves and the speed of the
movable adapter movement. This kind of column packing systems is
well known in the art and therefore all the details need not to be
described here.
[0029] According to the invention the control unit 15 further
comprises software for guiding the user through the packing
procedure. The control unit 15 is therefore provided with or
connected to some kind of display unit. The control unit 15 is
furthermore provided with or connected to some kind of keyboard
where the user can input data.
[0030] FIG. 2 is a flow chart of the packing process according to
the invention. The steps are described below:
[0031] S1: A user provides input data to the control unit 15. These
input data are in one embodiment: media type, slurry concentration
(measured by the user) and target bed height preferably together
with a maximum and minimum acceptable bed height. In this
embodiment the control unit is provided with data related to
different possible media types, i.e. given the media type from the
user the control unit knows features of this media such as target
packing factor (in this example we will use packing factor but
compression factor could just as well have been used), preferably
maximum and minimum acceptable packing factors, packing speed and
filling speed suitable for this media. In another embodiment the
user could also provide these input data to the control unit 15
instead of providing the media type.
[0032] S3: The control system controls the filling of the column,
i.e. opens the nozzle or valve 12 and moves the adapter 9 upwards
thereby sucking slurry in from the slurry tank 13. There are other
possible ways of filling up the column with slurry, such as using a
pump or a pressurized tank. The software in the control unit uses
the input data and information of the dimensions of the column to
calculate how much slurry that should be sucked into the column.
Hereby, the control unit automatically fills the column (i.e.
controls the movement of the adapter) with a suitable amount of
slurry such that the wanted target bed height later can be
achieved.
[0033] S5: The packing procedure is started, i.e. the movable
adapter 9 is controlled from the control unit 15 to move downwards,
i.e. towards the end plate 5b. The speed of this movement is
preferably a preset value in the software of the control unit
related to a chosen media type. However, in another embodiment the
user could enter this data to the control unit.
[0034] S7: Detecting a consolidated bed, i.e. for example a
pressure sensor provided in the column and connected to the control
unit gives a signal to the control unit that the consolidated bed
has been formed. This has been described before and will not be
described in detail here, however the pressure in the column will
change during the formation of the consolidated bed and especially
when the adapter meets the bed. The consolidated bed height is an
important measure as described above when the packing factor should
be calculated. The consolidated bed could also be detected by
measuring the motor current moving the adapter which will vary due
to the varying resistance. Visual detection of the consolidated bed
is also possible. Optionally, in one embodiment of the invention
which will be described further in relation to FIG. 4A, the
software requests a confirmation from the user that the
consolidated bed has been detected to be able to ignore false
detection.
[0035] S9: The software in the control unit processes the input
data and the measured consolidated bed height in order to present
to the user different options for when to stop the further packing
of the bed. The software can illustrate to the user when the
packing should be stopped for achieving an optimal packed bed given
input data and measured consolidated bed height. If both target bed
height and target packing factor have been given together with
maximum and minimum acceptable values a window (i.e. a span of
acceptable values) can be shown graphically to the user where
values of the packing factor for each bed height clearly is shown.
This window could for example be shown as a green area to the user
(see further description in relation to FIG. 3). It could also be
possible to combine the green area with a signal telling the user
that if you are stopping the packing now (during the signal) the
wanted conditions of the bed will be fulfilled. The user can also
be shown other related data such as time until green area will be
reached, time until target bed height will be reached, time to
minimum bed height and so on. If either packing factor or target
bed height not is accompanied by maximum and minimum acceptable
values there will not be such a green area to display to the user.
However the user will be shown time to target bed height (or target
packing factor) and information about which packing factor (or bed
height) that will be achieved and if this packing factor (or bed
height) is acceptable or not.
[0036] S11: User manually stops the packing (preferably according
to the recommendations given by the software in S9). However, if
the packing is stopped outside the green area (or if no green area
exists: in a position where the wanted conditions of the bed are
not fulfilled) the software preferably shows a warning to the user.
(This will be further described in relation to FIG. 4B).
Furthermore, if the user does not stop the packing at all the
control unit can be programmed to stop the packing itself after a
predetermined period of time. This will ensure that media and/or
column not will be damaged.
[0037] FIG. 3 illustrates a possible user interface according to
one embodiment of the invention. In this example both target
packing factor (1,15) and target bed height (20) were given
together with maximum and minimum acceptable values (in this
example: 1,12-1,18 and 19-21). A "green area" (the shaded area
shown in FIG. 3) is then shown to the user where both packing
factor and bed height are acceptable according to calculations made
by the software from input data and measured consolidated bed
height. Hereby the user can clearly see in which range of bed
height values he can stop the packing and which packing factor he
then will achieve. Other information such as time until "green
area" is reached is preferably also shown to the user. In another
example there is no "green area", i.e. there is no acceptable bed
height where also the packing factor is acceptable. In this case
the user will be informed about this and the user can decide to
repack the column.
[0038] FIG. 4A describes in more detail the step of detecting the
consolidated bed according to one embodiment of the invention. The
blocks are described below:
[0039] B1: The adapter is moved down and consolidation is
ongoing.
[0040] B3: Consolidated bed is detected. There are different
detection possibilities as described above.
[0041] B5: There should be a possibility for the user to instruct
the control unit to ignore this detection because the user can see
that it was a faulty detection. In this embodiment the process is
simply returned to B1 waiting for next detection of consolidated
bed.
[0042] B7: If the user by any reason did neither confirm nor ignore
the detection the process continues to this "no reply" box and the
adapter is preferably automatically stopped after a predetermined
period of time. This is to ensure that the column and/or the media
will not be damaged.
[0043] B9: If the user confirms the detected consolidated bed the
process will proceed to compression B11 as will be further
described in relation to FIG. 4B.
[0044] B13: If on the other hand no consolidated bed has been
detected before a given lower limit of bed height or packing factor
has been reached a warning is preferably displayed to the user and
the adapter is also preferably automatically stopped such that the
column and/or media will not be damaged. The user then preferably
has the choice to continue or start from the beginning and maybe
change some faulty input parameters.
[0045] FIG. 4B is a more detailed description of the compression
process according to one embodiment of the invention. The steps are
described in order below:
[0046] B11: Compression of the consolidated bed is started. The
consolidated bed height has been measured and will be used by the
software in the control unit for calculations. Information is
displayed to the user. In one embodiment the user interface looks
like the one shown in FIG. 3 and shows a "green area". Preferably
all necessary information is shown to the user including which bed
height(s) will give acceptable packing factor values and preferably
also information of time left until these bed heights are
reached.
[0047] B13: The "green area" (as described above) is entered. Or if
maximum and minimum values have only been given for one of target
bed height or target packing factor the "green area" will only be a
green line, i.e. a bed height value that will give a packing factor
that also is acceptable or vice versa.
[0048] B15: The compression is stopped by the user within this
"green area" (or correspondingly within acceptable values for both
bed height and packing factor as presented to the user by the
software in the control unit). Hereby the packing is completed and
successful.
[0049] B17: The compression is stopped by the user after "green
area" has been passed. (or correspondingly after a target value
fulfilling preset conditions has been passed).
[0050] B19: In this case (B17) a warning will be displayed to the
user. The warning could for example tell the user that the
compression is overdone. The user can then decide if he wants to
adjust the bed height manually or if the bed height still is
acceptable or he can decide to repack the column.
[0051] B21: If the "green area" (or single acceptable value) is
passed without the user stopping the compression the adapter is
preferably automatically stopped after a predetermined period of
time or after a predetermined further amount of bed compression.
This is in order to avoid damaging the column and media.
[0052] B23: Also here a warning should preferably be displayed to
the user telling him that the compression is overdone.
[0053] B25: Another possibility is that according to the
calculations made by the software using input data and consolidated
bed height there are no acceptable values of bed height where also
packing factor is acceptable, i.e. no "green area". In this case a
warning should be displayed to the user telling him that
specifications can not be met. The user should then have the choice
to stop the process or continue manually.
[0054] B27: Furthermore, if no reply is registered from the user
the compression should preferably be automatically stopped after a
predetermined period of time.
[0055] Although, the invention has been illustrated by examples of
embodiments in which the column is cylindrical and has a constant
diameter, which enables a linear correlation between cylinder
volume and bed height, it is also conceivable to adapt the present
invention for application to other column shapes in which the
correlation is non-linear.
[0056] Even though the present invention has been described above
in terms of specific embodiments, many modification and variations
of this invention can be made as will be obvious to those skilled
in the art, without departing from its spirit and scope as set
forth in the following claims.
* * * * *