US 12,073,924 B2
Multivariate spectral analysis and monitoring for biomanufacturing
Dhanuka Pulasthi Wasalathanthri, Fiskdale, MA (US); Jagdish C. Tewari, Bridgewater, NJ (US); Xuezhen Kang, Bridgewater, NJ (US); Marina Hincapie, Bridgewater, NJ (US); Shawn L. Barrett, Bridgewater, NJ (US); and Julie Susanne Pollock, Bridgewater, NJ (US)
Assigned to Genzyme Corporation, Cambridge, MA (US)
Filed by Genzyme Corporation, Cambridge, MA (US)
Filed on Dec. 7, 2021, as Appl. No. 17/643,128.
Application 17/643,128 is a continuation of application No. 16/290,713, filed on Mar. 1, 2019.
Claims priority of provisional application 62/729,402, filed on Sep. 10, 2018.
Claims priority of provisional application 62/673,845, filed on May 18, 2018.
Claims priority of provisional application 62/637,891, filed on Mar. 2, 2018.
Prior Publication US 2022/0101953 A1, Mar. 31, 2022
Int. Cl. C12M 3/00 (2006.01); B01L 3/00 (2006.01); C07K 1/16 (2006.01); C12M 1/00 (2006.01); C12M 1/12 (2006.01); C12M 1/36 (2006.01); G01N 21/3577 (2014.01); G01N 21/552 (2014.01); G01N 30/46 (2006.01); G01N 30/78 (2006.01); G01N 30/86 (2006.01); G16C 20/10 (2019.01); B01D 15/18 (2006.01); G01N 21/35 (2014.01); G01N 21/84 (2006.01); G01N 30/88 (2006.01)
CPC G16C 20/10 (2019.02) [C07K 1/16 (2013.01); C12M 21/14 (2013.01); C12M 37/00 (2013.01); C12M 41/48 (2013.01); C12M 47/12 (2013.01); G01N 21/3577 (2013.01); G01N 21/552 (2013.01); G01N 30/46 (2013.01); G01N 30/78 (2013.01); G01N 30/86 (2013.01); B01D 15/1814 (2013.01); B01D 15/1871 (2013.01); G01N 2021/3595 (2013.01); G01N 2021/8416 (2013.01); G01N 2030/8813 (2013.01); G01N 2030/8886 (2013.01); G01N 2201/129 (2013.01)] 23 Claims
OG exemplary drawing
 
1. A biological manufacturing system, comprising:
a radiation source configured to generate radiation;
a detection apparatus comprising:
an optical fiber comprising two fiber cores in a common cladding;
an optical element integrated into an end of the optical fiber so that at least a portion of the optical element is located within the common cladding, and positioned so that the generated radiation propagating through a first fiber core of the two fiber cores is incident on a first side of a surface of the optical element, wherein a flowing solution is located on a second side of the surface of the optical element opposite the first side, and radiation that undergoes total internal reflection from the surface of the optical element and does not propagate through the flowing solution is coupled into a second fiber core of the two fiber cores; and
a detector positioned to receive the radiation that undergoes total internal reflection from the second fiber core; and
a system controller connected to the detection apparatus, and configured to:
receive a measurement signal from the detection apparatus corresponding to an infrared vibrational spectrum of the solution;
analyze the infrared vibrational spectrum using a first chemometrics model to determine value of a first quality attribute associated with the solution;
analyze the infrared vibrational spectrum using a second chemometrics model to determine a value of a second quality attribute associated with the solution; and
adjust at least one parameter of the biological manufacturing system based on at least one of the values of the first and second quality attributes.
 
13. A biological manufacturing system, comprising:
a first purification unit configured to purify a solution comprising a biological product;
a second purification unit configured to receive the solution from the first purification unit;
a flow cell positioned so that the solution passes through the flow cell between the first and second purification units;
a radiation source configured to generate radiation;
a detection apparatus comprising:
an optical fiber comprising two fiber cores in a common cladding;
an optical element integrated into an end of the optical fiber so that at least a portion of the optical element is located within the common cladding, and positioned so that the generated radiation propagating through a first fiber core of the two fiber cores is incident on a first side of a surface of the optical element, wherein the solution is located on a second side of the surface of the optical element opposite the first side, and radiation that undergoes total internal reflection from the surface of the optical element and does not propagate through the flowing solution is coupled into a second fiber core of the two fiber cores; and
a detector positioned to receive the radiation that undergoes total internal reflection from the second fiber core; and
a system controller connected to the detection apparatus, and configured to:
receive a measurement signal from the detection apparatus corresponding to an infrared vibrational spectrum of the solution;
analyze the infrared vibrational spectrum using a first chemometrics model to determine value of a first quality attribute associated with the solution;
analyze the infrared vibrational spectrum using a second chemometrics model to determine a value of a second quality attribute associated with the solution; and
adjust at least one parameter of the first purification unit based on at least one of the values of the first and second quality attributes.