US 11,867,673 B2
NIR based real-time control of loading in protein a chromatography
Anurag Singh Rathore, New Delhi (IN); Garima Thakur, New Delhi (IN); and Vishwanath Hebbi, New Delhi (IN)
Assigned to Indian Institute of Technology Delhi, New Delhi (IN)
Appl. No. 17/436,599
Filed by INDIAN INSTITUTE OF TECHNOLOGY DELHI, New Delhi (IN)
PCT Filed Mar. 20, 2020, PCT No. PCT/IN2020/050264
§ 371(c)(1), (2) Date Sep. 5, 2021,
PCT Pub. No. WO2020/194343, PCT Pub. Date Oct. 1, 2020.
Claims priority of application No. 201911011227 (IN), filed on Mar. 22, 2019.
Prior Publication US 2022/0146416 A1, May 12, 2022
Int. Cl. G01N 21/359 (2014.01); G01N 21/3577 (2014.01); G01N 21/25 (2006.01); G01N 33/68 (2006.01); G01N 30/86 (2006.01); G01N 30/46 (2006.01); G01N 30/74 (2006.01); G01N 30/88 (2006.01)
CPC G01N 30/8658 (2013.01) [G01N 30/466 (2013.01); G01N 2030/746 (2013.01); G01N 2030/889 (2013.01); G01N 2030/8831 (2013.01)] 13 Claims
OG exemplary drawing
 
1. A system configured for monitoring and control of concentration of a bio-molecule in a chromatography apparatus, the system comprising:
a reservoir configured for storing a feed material containing the bio-molecule;
a continuous multi-column chromatography system comprising:
a plurality of fluid transmission channels and a plurality of control-system-operable pumps, where each fluid transmission channel is connected to a corresponding one of the plurality of control-system-operable pumps at an inlet configured for regulating and controlling a flow of a fluid within each channel, wherein one of the plurality of fluid transmission channels is a feed material feeding channel; and
a plurality of columns, each column having a column inlet and a column outlet, wherein each column inlet is connected through a corresponding one of a plurality of first pneumatically or electronically actuated valves of the fluid transmission channels to a corresponding one of the control-system-operable pumps and each column outlet is connected to a plurality of outlet ports by a plurality of second pneumatically or electronically actuated valves;
a first control system connected to the continuous multi-column chromatography system and configured for operating the plurality of control-system-operable pumps and the plurality of first and second pneumatically or electronically actuated valves to supply the feed material from the reservoir to the plurality of columns;
one or more near-infrared (NIR) flow cells configured for obtaining NIR spectroscopy data of the feed material in the feed material feeding channel and of fluids exiting the column outlets; and
a secondary control system in communication with the one or more NIR flow cells and the first control system and configured for analyzing the NIR spectroscopy data and to determine the concentration of the bio-molecule in the feed material and the concentration of the bio-molecule in the fluids exiting the column outlets, and transferring the analyzed NIR spectroscopy data to the first control system; wherein
the first control system continuously processes the NIR spectroscopy data to change valve configuration, pump actuation, flow rate of the feed material or a fluid through one or more of the plurality of fluid transmission channels to carry out steps including loading, second-pass loading, wash, elution, cleaning, regeneration, and equilibration to increase resin utilization, reduce idle time, or take control actions to handle system errors.