A system for determining the concentration of chromatographic media for chromatographic column packing

Abstract

This invention relates to a system for determining the slurry concentration of a chromatography resin slurry during column packing. The invention provides a more accurate and consistent system for determining slurry concentration for packing chromatography columns. The method of this invention utilizes an automated pump and a dual-column design to provide a controlled flow rate to solidify the resin sample. Based on this solidified resin, the slurry concentration can be determined. This determined slurry concentration can be used to pack the resin into a chromatography column with a highly accurate bed height.

Description

System for Measuring the Concentration of a Chromatography Medium for Chromatography Column Packing The present invention relates to a method for resin slurry determination of a chromatography resin slurry used during column packing. More specifically, the present invention provides a more accurate and consistent method for determining slurry concentration for packing chromatography columns, such as by axial compression mode. Resin slurry determination is a method commonly used to determine the amount of chromatography medium present in a water-based slurry. The resin slurry percentage or slurry concentration is used in calculations during chromatography column packing operations to determine how much aqueous slurry should be placed in the column to ensure proper operation and target bed height. The slurry concentration is the main variable that must be determined and input into an automated packing column (such as an AxiChrom® column) to consistently pack to the correct height and packing factor. In practice, automated packing columns (such as AxiChrom® columns) provide a highly automated packing operation but rely on accurate slurry concentration to achieve reproducibility. Current resin slurry determination methods include gravity sedimentation, centrifugation, and flow consolidation. Current methods obtain a representative sample from a resin slurry mass and subject the sample to forces that induce resin sedimentation, which in turn allows analysis of the ratio of sedimented resin to supernatant (slurry concentration). However, these methods have some disadvantages. For example, in current methods, differences between slurry concentration results and achieved packing factors (defined as the ratio of the consolidated bed height to the final packed bed height) and column height are often observed. In addition, if various waiting times are employed after centrifugation, it has been shown that centrifugation results are highly variable between different resin types and different ratios of the same standard. Gravity sedimentation is considered more consistent but may take a relatively long time to complete and may require empirical determination and application of correction factors, which increases the uncertainty of the method. Recently, GE Healthcare provided a recommended consolidation method specifically for the automated packing column AxiChrom®. This method involves obtaining a representative sample from a resin mass, loading it into a 10 mm diameter × 100 mm Tricorn column, and manually operating a syringe to generate a consolidation force on the sample. After achieving final consolidation, the resin slurry is determined from the ratio of resin to supernatant. However, this method is largely inconsistent due to variations in the intensity of plunger depression on the syringe. Therefore, there remains a need for a more accurate and consistent method for determining the slurry concentration for packing chromatography columns, such as automated chromatography columns. A method for determining the resin slurry percentage or slurry concentration of a slurry for a chromatography column is provided. When packing resin into a chromatography column (such as an automated packing column), the method of the present invention provides a highly accurate slurry concentration, which in turn provides an accurate target bed height. In one embodiment, the present invention provides a method for measuring the concentration of a slurry, which includes adding a slurry containing a resin to a first chromatography column; pumping a certain volume of liquid (such as deionized water, distilled water, purified water, saline solution or organic solvent) through the chromatography column at a constant flow rate to form consolidated resin, wherein the volume of the liquid is pumped through the chromatography column by an automatic pump system; after completing the pumping step, measuring the bed height of the consolidated resin; and determining the slurry concentration from the measured bed height. In some embodiments, the method may further include the steps of adding water to the chromatography column and allowing the slurry to settle for about 5 minutes to about 1 hour before pumping. In other embodiments, the method may further include filling a second chromatography column with the measured slurry concentration. In this aspect, the second chromatography column includes a consolidation rate and the flow rate is equal to the consolidation rate. In yet another embodiment, the automatic pump system may include a syringe operably coupled to the pump. In some embodiments, the pump system is programmed to cycle on and off for a predetermined time period or multiple time periods. In another embodiment, the present invention provides a method for measuring the slurry concentration of a chromatography resin slurry during column filling, which includes adding a slurry including a resin to a chromatography column; setting an automatic pump to operate at a constant flow rate for a period of time, for example, starting from the start of pumping and ending when the resin settles; pumping a certain volume of liquid through the chromatography column at a constant flow rate to form consolidated resin, wherein the volume of the liquid is pumped through the chromatography column by the automatic pump; after completing the pumping step, measuring the bed height of the consolidated resin; and determining the slurry concentration from the measured bed height. In some embodiments, the method may include the step of providing a flow rate based on the type of resin used in the slurry. The flow rate may be in the range of about 20 cm / hr to about 1500 cm / hr. In other embodiments, the method may include the step of mixing the slurry before adding the slurry to the chromatography column. In other embodiments, the method may include the step of filling a second chromatography column with resin using the measured slurry concentration, wherein the second chromatography column includes a consolidation rate and the flow rate is equal to the consolidation rate. In yet another embodiment, the liquid may be deionized water, distilled water, purified water, saline solution or organic solvent. In yet another embodiment, the present invention includes a method for measuring the slurry concentration of a chromatography resin slurry during column packing, which includes providing a slurry including resin; mixing the slurry to uniformly distribute the resin; adding the slurry to a chromatography column; providing an automated syringe pump system that includes a pump having a controller and a syringe operably coupled to the pump, wherein the automated syringe pump system is configured to pump a volume of water through the chromatography column, and the controller is configured to control the flow rate of the volume of water such that the flow rate remains constant over a period of time; pumping a volume of water through the chromatography column at a constant flow rate to form consolidated resin; after completing the pumping step, measuring the bed height of the consolidated resin; determining the slurry concentration from the measured bed height; inputting the determined slurry concentration into a second chromatography column; and packing the second chromatography column with resin using the determined slurry concentration. In some embodiments, the flow rate is in the range of about 30 cm / hr to about 60 cm / hr. In another embodiment, the second chromatography column includes a consolidation rate and the flow rate is equal to the consolidation rate. In other embodiments, the second chromatography column includes a consolidation rate and the flow rate is different from the consolidation rate. In other embodiments, the bed height of the packed second chromatography column is within 1 cm of the target bed height. The present invention relates to a method for determining the resin slurry percentage or slurry concentration of a slurry for a chromatography column. More specifically, the present invention utilizes an automated pump system to provide a controlled flow rate to consolidate a resin sample. Based on the consolidated resin sample, the slurry concentration can be determined and used to pack the same resin into a second chromatography column. It has been found that by controlling the delivery flow rate to match the consolidation rate employed for packing the chromatography column with resin, a highly reproducible slurry concentration is achieved, which corresponds to the slurry concentration required for accurately packing the second chromatography column without the need for a correction factor. Relative to conventional slurry measurement methods, including centrifugation, gravity sedimentation, and manual syringe methods, the present invention offers numerous advantages. The method and system of the present invention can be assembled, implemented, and disassembled in a shorter time than any conventional slurry measurement method. Additionally, it has been shown that the method of the present invention produces more consistent and reproducible slurry concentration results compared to the results of conventional slurry measurement methods, and has a lower standard deviation between repeated measurements. Figure 1 shows a flowchart of a method for resin slurry measurement according to an embodiment of the present invention. In step 101, the setup of the column and the pump is assembled. Figures 2A and 2B show various setups of a system for measuring the resin slurry percentage according to the present invention. As shown in Figure 2A, the system 200 includes a column 201; an automatic pump system 204, which includes a pump 203 having a controller 206; and a flow-through collection container 205. The pump 203 causes the liquid to flow to the column 201. In this aspect, the column 201 is vertically oriented, and the pump 203 is operably connected to the top of the column 201 such that the liquid flows from the pump 203 into the column 201. The liquid flow is provided by using the automatic pump 203. The pump 203 includes a controller 206 that operably starts and stops the pump 203 and defines the flow rate of the liquid leaving the pump 203. The system of the present invention also includes a flow-through collection container 205 operably connected to the bottom of the column 201. The flow-through collection container 205 is designed to collect the liquid flowing through the column 201. In another embodiment, as shown in Figure 2B, the automatic pump system 204 may further include a syringe 202 operably coupled to the pump 203. The syringe 202 can cause the liquid to flow to the column 201 by using the automatic pump 203. In one embodiment, the controller 206 of the pump 203 is operable to define the flow rate of the liquid leaving the syringe 202. In this aspect, the column 201 is vertically oriented, and the syringe 202 is operably connected to the top of the column 201 such that the liquid flows from the syringe 202 into the column 201. The column 201 can be operably connected to the pump 203 or the syringe 202 and the flow-through collection container 205 by any connecting member that allows the liquid to flow into the column 201 from the pump 203 or the syringe 202 and out of the column 201 to the flow-through collection container 205. For example, the column 201 can be operably connected to the pump 203 or the syringe 202 and the flow-through collection container 205 by a pipe. In this aspect, a section of pipe can connect the pump 203 or the syringe 202 to the top of the column 201, and a separate section of pipe can connect the bottom of the column 201 to the flow-through collection container 205. The type and size of the column 201 can vary. In one embodiment, the column 201 is a chromatography column. In another embodiment, the column 201 is an analytical grade chromatography column. For example, the column 201 can be a 1 cm × 25 cm chromatography column. Analytical grade chromatography columns are advantageous for use with the present invention because these columns are small, easy to transport, and provide sufficient vertical resolution to perform accurate slurry ratio readings. The type and size of the pump system 204 can also vary, as long as the pump 203 can provide a constant flow rate of liquid to the column 201. In one embodiment, the pump 203 can include any automatic or mechanical pump that delivers an accurate flow rate of 0.2 mL / min. For example, the pump 203 can include any type of syringe pump with a fully automatic system. In another embodiment, as described above, the pump 203 can include the syringe 202 that causes the liquid to flow to the column 201. In this aspect, the syringe 202 should have a volume of at least 20 mL. In another embodiment, the syringe 202 can have a volume of at least 30 mL. In yet another embodiment, the syringe 202 can have a volume of 20 mL to 60 mL. The flow-through collection container 205 can be any container operable to receive the fluid passing through the column 201. Suitable flow-through collection containers 205 include, but are not limited to, beakers, flasks, graduated cylinders, test tubes, vials, and jars. After assembling the system 200, a slurry comprising the resin is added to the column 201 (step 102). Any resin suitable for use in a chromatography column is contemplated by the present invention. In some embodiments, the present invention contemplates the use of resins suitable for protein purification. Examples of resins contemplated by the present invention include, but are not limited to, rProtein A Sepharose® Fast Flow, MabSelect™ Xtra, MabSelect SuRe™, Capto™ Phenyl, Q Sepharose® Fast Flow, Phenyl Sepharose® HP, POROS® 50 HS, Fractogel® EMD Hicap SE, Capto™ Q, and Superdex® 200 HR. The resin should be thoroughly mixed in the slurry so that the resin is evenly distributed before being added to column 201. Any technique known in the art can be used to add the mixed resin slurry to column 201. In one embodiment, for example, a pipette controller can be used to pipette the resin slurry into column 201. The amount of resin slurry to be added will depend on the desired settled resin bed volume. In one embodiment, the slurry can be added to column 201 until the meniscus is at a height of about 23 cm to about 25 cm. For example, the slurry can be added to column 201 until the meniscus is at a height of about 25 cm. In this aspect, improved accuracy is achieved when using a larger available space within the column. When adding the slurry to the column, the final height of the slurry should be measured and recorded for later use. After adding the resin slurry to column 201 and measuring the height of the resin slurry, purified water can be added to column 201 until the water is near the top of column 201. This allows the installation of a top adapter or piston on column 201 and the removal of air, which is important for laminar flow. Next, the resin slurry can be allowed to settle for a period of time. In one embodiment, the slurry can be allowed to settle for about 5 minutes to about 1 hour. In another embodiment, the slurry can be allowed to settle for about 20 minutes to about 45 minutes. For example, the slurry can be allowed to settle for about 30 minutes. In step 103, the pump system 204 is set to provide a liquid flow at a constant flow rate. In this aspect, the controller 206 of pump 203 can be set to define the flow rate of the liquid flowing out of pump 203. The flow rate of the liquid is selected based on the specific resin used in the slurry (e.g., its physical properties such as bead size, bead matrix, and matrix density) and the consolidation rate employed by the second column (e.g., an automated packing column) used for the chromatographic operation with the resin being packed. In one embodiment, the flow rate of the liquid can be selected such that the flow rate is equal to the consolidation rate of the second column (e.g., an automated packing column). In fact, by controlling the flow rate of the liquid to match the consolidation rate employed by the column in which the resin is packed, a highly reproducible slurry concentration can be achieved, which corresponds to the slurry concentration required for accurate packing in the second column without the need for a correction factor. However, when the flow rate of the liquid is different from the consolidation rate, a highly reproducible slurry concentration can still be achieved. Thus, in some embodiments, the flow rate of the liquid may not be equal to the consolidation rate of the second column. The flow rate of the liquid can vary based on the column, resin, and packing technique used. In one embodiment, the flow rate of the liquid can range from about 20 cm / hr to about 1500 cm / hr. In another embodiment, the flow rate of the liquid can range from about 30 cm / hr to about 1000 cm / hr. In yet another embodiment, the flow rate of the liquid can range from about 50 cm / hr to about 600 cm / hr. In yet another embodiment, the flow rate of the liquid can range from about 60 cm / hr to about 200 cm / hr. In some embodiments, the flow rate of the liquid can be about 30 cm / hr. In other embodiments, the flow rate of the liquid can be about 60 cm / hr. In step 104, the pump system 204 is activated so that liquid flows from the pump 203 and is pumped through the column 201. In one embodiment, the liquid pumped through the column 201 is water. For example, the water can be distilled, deionized, and / or purified. In another embodiment, the liquid pumped through the column 201 can be an aqueous salt solution. In yet another embodiment, the liquid pumped through the column 201 can be any organic solvent. For example, the liquid can be an alcohol. Suitable alcohols include but are not limited to ethanol, propanol, butanol, pentanol, hexanol, heptanol, and octanol. In this aspect, in order to provide more general and consistent results, the liquid pumped through the column 201 should be the same as the liquid used during the manufacturing packing operation of the selected resin. The controller 206 of the pump 203 can be used to activate the automatic flow of liquid from the pump 203 to the column 201. As discussed above, the liquid flows from the pump 203 and is pumped through the column 201 at a selected constant flow rate throughout step 104. The liquid flow should be continued until the resin stops settling. In one embodiment, the liquid can be pumped through the column 201 for a time period of about 10 minutes to about 50 minutes. In another embodiment, the liquid can be pumped through the column 201 for a time period of about 15 minutes to about 40 minutes. In another embodiment, the liquid can be pumped through the column 201 for a time period of about 15 minutes to about 30 minutes. For example, in some embodiments, when the flow rate of the liquid is about 30 cm / hr, the liquid can be pumped through the column 201 for about 30 minutes. In other embodiments, when the flow rate of the liquid is about 60 cm / hr, the liquid can be pumped through the column 201 for about 15 minutes. In some embodiments, the flow rate stops or pauses for one or more time periods. For example, the flow rate can pause for 1 to 5 minutes, 5 to 10 minutes, 10 to 20 minutes, 20 to 30 minutes, 40 to 50 minutes, or one or more times. The flow rate can be restarted after each pause. In some embodiments, it is not necessary to stop the liquid flow to achieve accurate readings. For example, the system can be in a continuous consolidation flow state for more than 1 hour. This is an additional benefit of the automatic flow, which cannot be achieved with the GE kit. The controller 206 can be used to stop the automatic flow of liquid from the pump 203 to the column 201. In one embodiment, the method includes programming an automated pump to stop liquid flow through a chromatography column and allow the resin to settle, and then restarting the pump before the pumping step is complete to allow liquid to flow through the chromatography column. The pumping can be paused for more than one time period. In one embodiment, the pumping is paused for a time period of 1 to 60 minutes. In some embodiments, the pump is programmed for intermittent pumping. In one embodiment, for all resins with a consolidation rate of 60 cm / hr, the cycle is 15 minutes of flow > 5 minutes of pause > 5 minutes of additional flow. A 30 cm / hr consolidation will require doubling the flow duration. In some embodiments, the result readings will be taken immediately before or after the end of the final flow operation. After stopping the liquid flow, the resin bed can be stabilized for a period of time without flow. In one embodiment, after stopping the liquid flow, the resin bed can be stabilized for about 10 minutes to about 45 minutes. For example, the resin bed can be stabilized for about 30 minutes. In another embodiment, after pausing the liquid flow, the resin bed can be stabilized for 5 to 10 minutes, and then the injection pump system 204 can be restarted at the same flow rate for an additional 5 minutes. In this aspect, implementing sequential flow consolidation can minimize variability. At step 105, the height of the settled / consolidated resin bed can be measured. The measuring step can be implemented using any measuring device that allows for an accurate reading of the bed height. In some embodiments, column 201 can include a scale vertically positioned on the outer surface. When measuring the bed height of the consolidated resin, the slurry concentration can be determined from the measured bed height (step 106). The measured slurry concentration (expressed as a percentage) is directly given by the bed height (expressed in centimeters). After determining the slurry concentration of the resin used, the slurry concentration can be used to fill a second column. The second column can be any chromatography column, including an automated filling column. For example, the automated filling column can be an AxiChrom® column. In this aspect, the slurry concentration can be input into the automated filling column. In some embodiments, the operator can manually input the measured slurry concentration into the filling column. In other embodiments, via the use of a network or hardware circuit that connects system 200 to the automated filling column, the measured slurry concentration can be automatically entered into the filling column. Regardless of the type of column used to fill the resin, the measured slurry concentration is highly reproducible and corresponds to the slurry concentration required for an accurate filling of the second column. When filling a chromatography column with resin, the method of the present invention provides a highly accurate slurry concentration, which in turn provides an accurate target bed height. In one embodiment, column filling with a slurry concentration determined according to the present invention achieves a bed height within 2 cm of the target bed height. In another embodiment, column filling with a slurry concentration determined according to the present invention achieves a bed height within 1 cm of the target bed height. In yet another embodiment, column filling with a slurry concentration determined according to the present invention achieves a bed height within 0.75 cm of the target bed height. In yet another embodiment, column filling with a slurry concentration determined according to the present invention achieves a bed height within 0.50 cm of the target bed height. For example, column filling with a slurry concentration determined according to the present invention achieves a bed height within 0.10 cm of the target bed height. In addition, column filling with a slurry concentration determined according to the present invention obtains a highly accurate packing factor when filling a chromatography column with resin. For example, column filling with a slurry concentration determined according to the present invention achieves a packing factor within 5% of the ideal packing factor. In another embodiment, column filling with a slurry concentration determined according to the present invention achieves a packing factor within 3% of the ideal packing factor. Examples The following non-limiting examples demonstrate the method for determining slurry concentration according to the present invention. These examples are only used to illustrate the preferred embodiments of the present invention and should not be construed as limiting the present invention, which is defined by the scope of the appended claims. Inventive Examples 1 The method for determining slurry concentration is implemented according to the present invention. The method is implemented using a 1 cm × 25 cm chromatography SNAP column. A KD Scientific injection pump is used to provide a controlled flow rate to consolidate the resin sample. The following resins are tested: MabSelect SuRe™, POROS® 50 HQ, and Capto™ Phenyl. Table 1 shows the results of the method implemented according to the present invention. Table 1: Results of the inventive method As can be seen from the data in Table 1, the method of the present invention shows consistent and reproducible results, and the standard deviation between repeated measurements is low. The slurry concentration obtained according to the present invention results in an average bed height that differs from the target bed height by 0.4 cm or less. The low standard deviation indicates that the results are highly reproducible. Comparative Examples 2 Centrifugation Use an Allegra® 6KR centrifuge with 13 mL centrifuge tubes. Adjust the slurry to a 50% ratio by removing the supernatant before centrifugation. Centrifuge 10 mL of the slurry sample at 1000 rpm for 5 minutes and at 3500 rpm for 15 minutes. Table 2 shown below displays the resins used. Table 2: Resins Tested * The resin did not solidify properly. Figure 3 presents the results of the centrifugation method. More specifically, Figure 3 shows the average sedimentation percentage at 1000 rpm for 5 minutes and at 3500 rpm for 15 minutes. As can be seen from Figure 3, the centrifugation results are variable among the resins and consistently overestimate the resin volume known to be 50%. This indicates that centrifugation is not a sufficient sedimentation method. Flow consolidation Use an AKTA Avant chromatography system (with a 2.5 cm × 50 cm chromatography SNAP column) to simulate the consolidation effect of AxiChrom® technology. All resins were consolidated at 60 cm / hr. The resins shown in Table 2 were also used for the flow consolidation test. Let the resin sediment by gravity overnight. Adjust the slurry to a 50% ratio by removing the supernatant before performing the flow consolidation. Table 3 shown below displays the average flow consolidation results between Run 1 and Run 2. Table 3: Average Flow Consolidation Results As can be seen from Table 3, the consolidation results are variable among the resins, and none consolidated back to the initial 50% ratio. This indicates that gravity is not a sufficient sedimentation method. Comparison of Centrifugation and Consolidation Method Results Table 4 shown below compares the results of each centrifugation and flow consolidation method. Table 4: Comparison of Centrifugation and Consolidation Results As can be seen from the above table, the consolidation and centrifugation results vary greatly. The difference between the consolidation and the initial centrifugation readings for 6 out of 8 resins is greater than 5%. Even after an extended duration of 2 hours, this difference does not fade. In fact, after 2 hours, the difference between the consolidation and the sedimentation centrifugation readings for 3 out of 8 resins is still greater than 5%. This indicates that due to test variability, long sedimentation times, and resin-to-resin variations, consolidation pore centrifugation is not sufficient to determine the slurry concentration. In addition, several readings did not reach the target packing factor. For the purpose of calculating the target packing factor, 5% of 20 cm (target bed height) is 1 cm, which is the maximum allowable bed height range. A difference greater than 5% means that the reading did not reach the target packing factor. As can be seen from the above data, several readings did not reach the target packing factor. Comparative Example 3 Table 5 shown below displays a comparison of the centrifugation slurry percentage and the final bed height between the centrifugation method and the GE kit. Table 5: Comparison of Centrifugation and GE Kit Results As can be seen from Table 5, among several tested resin types, neither the centrifugation method nor the GE kit can achieve the target bed height, indicating that these methods are inconsistent. Centrifugation, GE Comparison of the Results of the Kit and the Method According to the Present Disclosure Figure 4 compares the percentage error of the slurry concentration between the centrifugation method and the method according to the present disclosure. Several different types of resins were tested, including MabSelect SuRe, POROS 50 HQ, Capto Phenyl, Q Sepharose FF, and MabSelect SuRe PCC. For all resin types, the method according to the disclosure showed a significant reduction in error compared to the centrifugation method. Additionally, for several tested resin types, the error percentage of the centrifugation method reached the error limit of 5%, indicating that the package damaged the ideal packing factor to meet the minimum height requirement for use. The damaged packing factor can lead to column degradation and reduce the number of times the column can be reused. In some embodiments, the column must meet the final desired metrics including the desired height and packing factor. As the column consolidates, the height decreases and the packing factor increases. In one embodiment, the column reaches a height of 19 - 21 cm and is targeted for compression. Figure 5 shows a direct comparison of the bed heights achieved using the centrifugation method, the GE kit, and the method according to the present disclosure. As shown in Figure 5, the method according to the present disclosure is superior to the other tested methods. The bed height achieved using the method according to the present disclosure is closer to the ideal bed height than the other tested methods. Additionally, the centrifugation method and the GE kit result in a bed height reaching or exceeding the error limit, indicating that the bed package is outside the acceptable bed height range and may need to be refilled. GE Operator Variability Testing and Limit Evaluation of the GE Kit To evaluate the operator variability of the GE kits sold on the current market, operators were given incremental instructions and experience on how to use the system, and measurements were taken from the batch solution after each increment. Figure 6 shows the results of the operator variability testing. The data shows that the GE kits experience variability among operators, variability in familiarity and experience level, and variability in the measured materials. This also shows that the GE kits do not have sufficient control to produce consistent results in a dynamic manufacturing environment. To evaluate the impact of uncontrolled flow used in GE kits sold on the current market, an experiment was conducted to vary the flow during sample handling based on potential operator performance. Figure 7 shows the experimental results, where water was initially passed through the column and the bed height measurements were recorded. Then water was passed through the column a second time and the second bed height measurements were recorded. Figure 7 shows that flow outside the recommended range results in potentially unacceptable changes in bed height. Although the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. However, any numerical value inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. In addition, when numerical ranges of variation are set forth herein, it is intended that any combination of the values (including the recited values) can be used. In fact, all ranges disclosed herein are inclusive and combinable. For example, all ranges include the endpoints of the range and all intermediate values. The invention described and claimed herein is not limited to the scope of the specific examples disclosed herein, as these examples are intended to illustrate several aspects of the invention. Any equivalent embodiments are intended to be within the scope of the invention. In fact, various modifications of the invention will be apparent to those skilled in the art from the foregoing description in addition to those shown and described herein. Such modifications are also intended to fall within the scope of the appended claims. The entire text of all patents and patent applications cited in the foregoing text are expressly incorporated herein by reference. 200: System 201: Column 202: Syringe 203: Pump 204: Pump system 205: Collection container 206: Controller Other features and advantages of the invention can be determined from the following detailed description taken in conjunction with the accompanying drawings described below: Figure 1 is a flowchart of a method for resin slurry determination according to the present invention; Figures 2A and 2B are schematic diagrams of a resin slurry determination system according to the present invention related to Figure 1; and Figure 3 is a bar chart showing the average sedimentation percentage of resin after centrifugation. Figure 4 is a bar chart showing the percentage error of resin slurry determination for centrifugation (shaded columns) and the currently claimed method (bar columns) for various types of resins. Figure 5 is a bar graph showing the achieved bed height against the ideal bed height obtained using centrifugation, a GE slurry kit, or the method according to the present invention. In each set of three columns, the first column represents centrifugation, the middle column represents the GE slurry kit, and the last of the three columns represents the results of using the disclosed method for various types of resins. The solid horizontal line represents the target bed height for individual resin packs. The dashed horizontal line represents the bed height limit (± 1 cm) before the pack exceeds the acceptable bed height range. The X-axis represents the type of resin slurry, and the Y-axis represents the bed height (cm). Figure 6 is a bar graph showing the theoretical bed heights achieved by different operators using the GE kit for different resin types. In each set of three columns, the first column represents centrifugation, the middle column represents the GE slurry kit, and the last of the three columns represents the results of using the disclosed method for various types of resins. In each set of three columns, the first column represents the initial theoretical final bed height, the middle column represents the theoretical final bed height including pauses, and the last column represents the theoretical final bed height with variable force. The solid horizontal line represents the ideal bed height for individual resin packs. The dashed horizontal line represents the bed height limit (± 1 cm) before the pack exceeds the acceptable bed height range. The X-axis represents the type of resin slurry, and the Y-axis represents the bed height (cm). Figure 7 is a bar graph showing the theoretical bed heights of MabSelect SuRe resin with different flow rates that can be experienced using an uncontrolled flow GE kit. In each set of two columns, the solid column represents the theoretical bed height after the initial flow, and the white column represents the theoretical bed height after the second flow. The X-axis represents the flow rate (ml / min), and the Y-axis represents the theoretical bed height (cm). The solid horizontal line represents the ideal bed height for individual resin packs. The dashed horizontal line represents the bed height limit (±1 cm) before the pack exceeds the acceptable bed height range.

Claims

1. A chromatography column packing system, comprising: A first chromatography column having a top and a bottom; a second chromatography column having a top and a bottom; an automatic pump system operatively connected to the first chromatography column, wherein the automatic pump system pumps a volume of liquid into the first chromatography column to form a solidified chromatography medium with a bed height for slurry concentration measurement; a network or hardware circuit for controlling the chromatography column packing system; a controller for the automatic pump system operatively starting and stopping the pump and controlling the flow rate of the volume of liquid; a first collection container connected to the automatic pump system to the top of the first chromatography column; a second collection container connected to the bottom of the first chromatography column; wherein the system packs the second chromatography column with a packing factor within 5% of a target packing factor.

2. The chromatography column packing system as described in claim 1, wherein the first chromatography column is vertically oriented and retains the chromatography medium.

3. The chromatography column packing system as described in claim 1, wherein the first chromatography column and the second chromatography column are of the same type.

4. The chromatography column packing system as described in claim 1, wherein the first chromatography column and the second chromatography column are different types of columns.

5. The chromatography column packing system as described in claim 1, wherein the first chromatography column is an analytical grade chromatography column.

6. The chromatography column packing system as described in claim 1, wherein the second chromatography column is an automatically packed column.

7. The chromatography column packing system as claimed in claim 1, wherein the automated pump system includes an injector operatively coupled to the pump.

8. The chromatography column packing system as claimed in claim 7, wherein the syringe is operable to provide flow of the liquid to the first chromatography column via the use of an automatic pump.

9. The chromatography column packing system as described in claim 1, wherein the pump delivers a flow rate of 0.2 mL / min.

10. The chromatography column packing system as described in claim 1, wherein the pump has an autoinjector.

11. The chromatography column packing system as described in claim 1, wherein the automatic pump system is programmed to cycle on and off for predetermined time periods.

12. The chromatography column packing system as claimed in claim 1, wherein the controller controls the flow rate of the first chromatography column to match the consolidation rate of the second chromatography column for a period of time.

13. The chromatography column packing system as claimed in claim 1, wherein the controller controls the flow rate from about 30 cm / hr to about 60 cm / hr.

14. The chromatography column packing system as claimed in claim 1, wherein the controller controls the flow rate from about 20 cm / hr to about 1500 cm / hr.

15. The chromatography column filling system as claimed in claim 1, wherein a network or hardware circuit receives slurry concentration from the first chromatography column to fill the second chromatography column.

16. The chromatography column packing system as described in claim 1, wherein the system fills the second chromatography column with a bed height within 1 cm of the target bed height.

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