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101. High throughput chromatography strategies for potential use in the formal process characterization of a monoclonal antibody.

Author

Petroff, Matthew G., Bao, Haiying, Welsh, John P., van Beuningen – de Vaan, Miranda, Pollard, Jennifer M., Roush, David J., Kandula, Sunitha, Machielsen, Peter, Tugcu, Nihal, and Linden, Thomas O.

Abstract

ABSTRACT High throughput experimental strategies are central to the rapid optimization of biologics purification processes. In this work, we extend common high throughput technologies towards the characterization of a multi-column chromatography process for a monoclonal antibody (mAb). Scale-down strategies were first evaluated by comparing breakthrough, retention, and performance (yields and clearance of aggregates and host cell protein) across miniature and lab scale columns. The process operating space was then evaluated using several integrated formats, with batch experimentation to define process testing ranges, miniature columns to evaluate the operating space, and comparison to traditional scale columns to establish scale-up correlations and verify the determined operating space. When compared to an independent characterization study at traditional lab column scale, the high throughput approach identified the same control parameters and similar process sensitivity. Importantly, the high throughput approach significantly decreased time and material needs while improving prediction robustness. Miniature columns and manufacturing scale centerpoint data comparisons support the validity of this approach, making the high throughput strategy an attractive and appropriate scale-down tool for the formal characterization of biotherapeutic processes in the future if regulatory acceptance of the miniature column data can be achieved. Biotechnol. Bioeng. 2016;113: 1273-1283. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Published
2016
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102. High-throughput purification tools for rapid upstream process development are interchangeable for biologics.

Author

Petroff, Matthew G., Feliciano, Jessika, Pollard, David J., Li, Hong, Linden, Thomas O., and Pollard, Jennifer M.

Subjects
*BIOLOGICALS, *SAMPLING methods, *HIGH throughput screening (Drug development), *CELL culture, *IMMUNOGLOBULIN G
Abstract

Upstream process development of biologics is not only productivity-driven but also quality-driven. Typically, most quality attributes are not directly measurable in cell culture samples due to low product concentration and purity, thus requiring some level of sample purification. As higher throughput upstream technologies become available, sample purification is becoming a bottleneck in limiting the number and types of cell culture samples that can be analyzed. The application of high-throughput, microscale protein purification techniques has the potential to address and expand this capability. In this work, the affinity capture step of an IgG1 mAb was adapted to fit resin-plate, resin-tip, and mini-column formats in an attempt to approximate the packed-column performance by optimizing parameters such as contact time, liquid/resin ratio, and loading to produce a yield of ≥70% yield. A representative cell culture supernatant was purified using both the optimized microscale and conventional techniques, and analyzed using a comprehensive panel of product quality assays. This direct comparison demonstrated that each technique generates product of equivalent purity across a wide range of feed conditions. The analytical comparability suggests that any of the conventional and high-throughput methods are interchangeable for biologics, allowing flexible development of an end-to-end integrated high-throughput strategy. [ABSTRACT FROM AUTHOR]

Published
2016
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103. The Cosmology Large Angular Scale Surveyor

Author

Holland, Wayne S., Zmuidzinas, Jonas, Harrington, Kathleen, Marriage, Tobias, Ali, Aamir, Appel, John W., Bennett, Charles L., Boone, Fletcher, Brewer, Michael, Chan, Manwei, Chuss, David T., Colazo, Felipe, Dahal, Sumit, Denis, Kevin, Dünner, Rolando, Eimer, Joseph, Essinger-Hileman, Thomas, Fluxa, Pedro, Halpern, Mark, Hilton, Gene, Hinshaw, Gary F., Hubmayr, Johannes, Iuliano, Jeffrey, Karakla, John, McMahon, Jeff, Miller, Nathan T., Moseley, Samuel H., Palma, Gonzalo, Parker, Lucas, Petroff, Matthew, Pradenas, Bastián, Rostem, Karwan, Sagliocca, Marco, Valle, Deniz, Watts, Duncan, Wollack, Edward, Xu, Zhilei, and Zeng, Lingzhen

Published
2016
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105. Variable-delay Polarization Modulators for the CLASS Telescopes

Author

Harrington, Kathleen, Eimer, Joseph, Chuss, David T., Petroff, Matthew, Cleary, Joseph, Degeorge, Martin, Grunberg, Theodore W., Ali, Aamir, Appel, John W., Bennett, Charles L., Brewer, Michael, Bustos, Ricardo, Chan, Manwei, Couto, Jullianna, Dahal, Sumit, Denis, Kevin, Dünner, Rolando, Essinger-Hileman, Thomas, Fluxa, Pedro, Halpern, Mark, Hilton, Gene, Hinshaw, Gary F., Hubmayr, Johannes, Iuliano, Jeffrey, Karakla, John, Marriage, Tobias, Mcmahon, Jeffrey, Miller, Nathan J., Nuñez, Carolina, Padilla, Ivan L., Palma, Gonzalo, Parker, Lucas, Pradenas Marquez, Bastian, Reeves, Rodrigo, Reintsema, Carl, Rostem, Karwan, Valle, Deniz Augusto Nunes, Engelhoven, Trevor, Wang, Bingjie, Wang, Qinan, Duncan Watts, Weiland, Janet, Wollack, Edward, Xu, Zhilei, Yan, Ziang, and Zeng, Lingzhen

Subjects
Astrophysics::Instrumentation and Methods for Astrophysics, FOS: Physical sciences, Astrophysics::Cosmology and Extragalactic Astrophysics, Astrophysics - Instrumentation and Methods for Astrophysics, Instrumentation and Methods for Astrophysics (astro-ph.IM)
Abstract

The search for inflationary primordial gravitational waves and the measurement of the optical depth to reionization, both through their imprint on the large angular scale correlations in the polarization of the cosmic microwave background (CMB), has created the need for high sensitivity measurements of polarization across large fractions of the sky at millimeter wavelengths. These measurements are subject to instrumental and atmospheric $1/f$ noise, which has motivated the development of polarization modulators to facilitate the rejection of these large systematic effects. Variable-delay polarization modulators (VPMs) are used in the Cosmology Large Angular Scale Surveyor (CLASS) telescopes as the first element in the optical chain to rapidly modulate the incoming polarization. VPMs consist of a linearly polarizing wire grid in front of a movable flat mirror. Varying the distance between the grid and the mirror produces a changing phase shift between polarization states parallel and perpendicular to the grid which modulates Stokes U (linear polarization at $45^\circ$) and Stokes V (circular polarization). The CLASS telescopes have VPMs as the first optical element from the sky; this simultaneously allows a lock-in style polarization measurement and the separation of sky polarization from any instrumental polarization further along in the optical path. The Q-band CLASS VPM was the first VPM to begin observing the CMB full time, starting in the Spring of 2016. The first W-band CLASS VPM was installed in the Spring of 2018.

106. Thermal testing for cryogenic CMB instrument optical design

Author

Goldfinger, David C., Ade, Peter A. R., Ahmed, Zeeshan, Amiri, Mandana, Barkats, Denis, Basu Thakur, Ritoban, Beck, Dominic, Bischoff, Colin A., Bock, James J., Buza, Victor, Cheshire, James R., Connors, Jake, Cornelison, James, Crumrine, Michael, Cukierman, Ari J., Denison, Edward V., Dierickx, Marion I., Duband, Lionel, Eiben, Miranda, Fatigoni, Sofia, Filippini, Jeff P., Giannakopoulos, Christos, Goeckner-Wald, Neil, Grayson, James A., Grimes, Paul K., Hall, Grantland, Halal, George, Halpern, Mark, Hand, Emma, Harrison, Sam A., Henderson, Shawn, Hildebrandt, Sergi R., Hilton, Gene C., Hubmayr, Johannes, Hui, Howard, Irwin, Kent D., Kang, Jae Hwan, Karkare, Kirit S., Kefeli, Sinan, Kovac, John M., Kuo, Chao-Lin, Lau, King, Leitch, Erik M., Lennox, Amber, Liu, Tongtian, Megerian, Krikor G., Minutolo, Lorenzo, Moncelsi, Lorenzo, Nakato, Yuka, Namikawa, Toshiya, Nguyen, Hien T., O'Brient, Roger, Palladino, Steven M., Petroff, Matthew, Prouvé, Thomas, Pryke, Clement L., Racine, Benjamin, Reintsema, Carl D., Salatino, Maria, Schillaci, Alessandro, Schmitt, Benjamin L., Singari, Baibhav, Soliman, Ahmed, Smith, Amanda G., St. Germaine, Tyler, Steinbach, Bryan, Sudiwala, Rashmi V., Thompson, Keith L., Tsai, Calvin, Tucker, Carole E., Turner, Anthony D., Umiltà, Caterina, Verges, Clara, Vieregg, Abigail G., Wandui, Albert K., Weber, Alexis C., Wiebe, Don V., Willmert, Justin, Wu, Wai Ling K., Yang, Hung-I, Yoon, Ki Won, Young, Edward, Yu, Cyndia, Zeng, Lingzhen, Zhang, Cheng, Zhang, Silvia, Zmuidzinas, Jonas, Gao, Jian-Rong, Goldfinger, David C., Ade, Peter A. R., Ahmed, Zeeshan, Amiri, Mandana, Barkats, Denis, Basu Thakur, Ritoban, Beck, Dominic, Bischoff, Colin A., Bock, James J., Buza, Victor, Cheshire, James R., Connors, Jake, Cornelison, James, Crumrine, Michael, Cukierman, Ari J., Denison, Edward V., Dierickx, Marion I., Duband, Lionel, Eiben, Miranda, Fatigoni, Sofia, Filippini, Jeff P., Giannakopoulos, Christos, Goeckner-Wald, Neil, Grayson, James A., Grimes, Paul K., Hall, Grantland, Halal, George, Halpern, Mark, Hand, Emma, Harrison, Sam A., Henderson, Shawn, Hildebrandt, Sergi R., Hilton, Gene C., Hubmayr, Johannes, Hui, Howard, Irwin, Kent D., Kang, Jae Hwan, Karkare, Kirit S., Kefeli, Sinan, Kovac, John M., Kuo, Chao-Lin, Lau, King, Leitch, Erik M., Lennox, Amber, Liu, Tongtian, Megerian, Krikor G., Minutolo, Lorenzo, Moncelsi, Lorenzo, Nakato, Yuka, Namikawa, Toshiya, Nguyen, Hien T., O'Brient, Roger, Palladino, Steven M., Petroff, Matthew, Prouvé, Thomas, Pryke, Clement L., Racine, Benjamin, Reintsema, Carl D., Salatino, Maria, Schillaci, Alessandro, Schmitt, Benjamin L., Singari, Baibhav, Soliman, Ahmed, Smith, Amanda G., St. Germaine, Tyler, Steinbach, Bryan, Sudiwala, Rashmi V., Thompson, Keith L., Tsai, Calvin, Tucker, Carole E., Turner, Anthony D., Umiltà, Caterina, Verges, Clara, Vieregg, Abigail G., Wandui, Albert K., Weber, Alexis C., Wiebe, Don V., Willmert, Justin, Wu, Wai Ling K., Yang, Hung-I, Yoon, Ki Won, Young, Edward, Yu, Cyndia, Zeng, Lingzhen, Zhang, Cheng, Zhang, Silvia, Zmuidzinas, Jonas, and Gao, Jian-Rong

Abstract

Observations of the Cosmic Microwave Background rely on cryogenic instrumentation with cold detectors, readout, and optics providing the low noise performance and instrumental stability required to make more sensitive measurements. It is therefore critical to optimize all aspects of the cryogenic design to achieve the necessary performance, with low temperature components and acceptable system cooling requirements. In particular, we will focus on our use of thermal filters and cold optics, which reduce the thermal load passed along to the cryogenic stages. To test their performance, we have made a series of in situ measurements while integrating the third receiver for the BICEP Array telescope. In addition to characterizing the behavior of this receiver, these measurements continue to refine the models that are being used to inform design choices being made for future instruments.

107. Improved polarization calibration of the BICEP3 CMB polarimeter at the South Pole

Author

Cornelison, James, Verges, Clara, Ade, P A., Ahmed, Zeeshan, Amiri, Mandana, Barkats, Denis, Basu Thakur, Ritoban, Beck, Dominic, Bischoff, Colin A., Bock, James J., Buza, Victor, Cheshire, James R., Connors, Jake, Crumrine, Michael, Cukierman, Ari Jozef, Denison, Edward, Dierickx, Marion, Duband, Lionel, Eiben, Miranda, Fatigoni, Sofia, Filippini, Jeff P., Giannakopoulos, Christos, Goeckner-Wald, Neil, Goldfinger, David C., Grayson, James A., Grimes, Paul, Hall, Grantland, Halal, George, Halpern, Mark, Hand, Emma, Harrison, Sam A., Henderson, Shawn, Hildebrandt, Sergi, Hilton, Gene C., Hubmayr, Johannes, Hui, Howard, Irwin, Kent D., Kang, Jae Hwan, Karkare, Kirit S., Kefeli, Sinan, Kovac, John, Kuo, Chao-Lin, Lau, King, Leitch, Erik M., Lennox, Amber, Liu, Tongtian, Look, Karsten, Megerian, K(oko). G., Minutolo, Lorenzo, Moncelsi, Lorenzo, Nakato, Yuka, Namikawa, Toshiya, Nguyen, H. T., O'brient, Roger, Palladino, Steven, Petroff, Matthew, Prouve, Thomas, Pryke, Clement, Racine, Benjamin, Reintsema, Carl D., Salatino, Maria, Schillaci, Alessandro, Schmitt, Benjamin, Singari, Baibhav, Soliman, Ahmed, St Germaine, Tyler, Steinbach, Bryan, Sudiwala, Rashmi, Thompson, Keith L., Tsai, Calvin, Tucker, Carole, Turner, Anthony D., Umiltà, Caterina, Vieregg, Abigail G., Wandui, Albert, Weber, Alexis C., Wiebe, Don, Willmert, Justin, Wu, Wai Ling K., Yang, Hung-I, Yoon, Ki Won, Young, Edward, Yu, Cyndia, Zeng, Lingzhen, Zhang, Cheng, Zhang, Silvia, Zmuidzinas, Jonas, Gao, Jian-Rong, Cornelison, James, Verges, Clara, Ade, P A., Ahmed, Zeeshan, Amiri, Mandana, Barkats, Denis, Basu Thakur, Ritoban, Beck, Dominic, Bischoff, Colin A., Bock, James J., Buza, Victor, Cheshire, James R., Connors, Jake, Crumrine, Michael, Cukierman, Ari Jozef, Denison, Edward, Dierickx, Marion, Duband, Lionel, Eiben, Miranda, Fatigoni, Sofia, Filippini, Jeff P., Giannakopoulos, Christos, Goeckner-Wald, Neil, Goldfinger, David C., Grayson, James A., Grimes, Paul, Hall, Grantland, Halal, George, Halpern, Mark, Hand, Emma, Harrison, Sam A., Henderson, Shawn, Hildebrandt, Sergi, Hilton, Gene C., Hubmayr, Johannes, Hui, Howard, Irwin, Kent D., Kang, Jae Hwan, Karkare, Kirit S., Kefeli, Sinan, Kovac, John, Kuo, Chao-Lin, Lau, King, Leitch, Erik M., Lennox, Amber, Liu, Tongtian, Look, Karsten, Megerian, K(oko). G., Minutolo, Lorenzo, Moncelsi, Lorenzo, Nakato, Yuka, Namikawa, Toshiya, Nguyen, H. T., O'brient, Roger, Palladino, Steven, Petroff, Matthew, Prouve, Thomas, Pryke, Clement, Racine, Benjamin, Reintsema, Carl D., Salatino, Maria, Schillaci, Alessandro, Schmitt, Benjamin, Singari, Baibhav, Soliman, Ahmed, St Germaine, Tyler, Steinbach, Bryan, Sudiwala, Rashmi, Thompson, Keith L., Tsai, Calvin, Tucker, Carole, Turner, Anthony D., Umiltà, Caterina, Vieregg, Abigail G., Wandui, Albert, Weber, Alexis C., Wiebe, Don, Willmert, Justin, Wu, Wai Ling K., Yang, Hung-I, Yoon, Ki Won, Young, Edward, Yu, Cyndia, Zeng, Lingzhen, Zhang, Cheng, Zhang, Silvia, Zmuidzinas, Jonas, and Gao, Jian-Rong

Abstract

The BICEP3 Polarimeter is a small aperture, refracting telescope, dedicated to the observation of the Cosmic Microwave Background (CMB) at 95GHz. It is designed to target degree angular scale polarization patterns, in particular the very-much-sought-after primordial B-mode signal, which is a unique signature of cosmic inflation. The polarized signal from the sky is reconstructed by differencing co-localized, orthogonally polarized superconducting Transition Edge Sensor (TES) bolometers. In this work, we present absolute measurements of the polarization response of the detectors for more than approximately 800 functioning detector pairs of the BICEP3 experiment, out of a total of approximately 1000. We use a specifically designed Rotating Polarized Source (RPS) to measure the polarization response at multiple source and telescope boresight rotation angles, to fully map the response over 360 degrees. We present here polarization properties extracted from on-site calibration data taken in January 2022. A similar calibration campaign was performed in 2018, but we found that our constraint was dominated by systematics on the level of approximately 0.5° . After a number of improvements to the calibration set-up, we are now able to report a significantly lower level of systematic contamination. In the future, such precise measurements will be used to constrain physics beyond the standard cosmological model, namely cosmic birefringence.

108. The Cosmology Large Angular Scale Surveyor receiver design

Author

Zmuidzinas, Jonas, Gao, Jian-Rong, Iuliano, Jeffrey, Eimer, Joseph, Parker, Lucas, Rhoades, Gary, Ali, Aamir, Appel, John W., Bennett, Charles, Brewer, Michael, Bustos, Ricardo, Chuss, David, Cleary, Joseph, Couto, Jullianna, Dahal, Sumit, Denis, Kevin, Dünner, Rolando, Essinger-Hileman, Thomas, Fluxa, Pedro, Halpern, Mark, Harrington, Kathleen, Helson, Kyle, Hilton, Gene, Hinshaw, Gary, Hubmayr, Johannes, Karakla, John, Marriage, Tobias, Miller, Nathan, McMahon, Jeffrey John, Nuñez, Carolina, Padilla, Ivan, Palma, Gonzalo, Petroff, Matthew, Pradenas Márquez, Bastian, Reeves, Rodrigo, Reintsema, Carl, Rostem, Karwan, Augusto Nunes Valle, Deniz, Van Engelhoven, Trevor, Wang, Bingjie, Wang, Qinan, Watts, Duncan, Weiland, Janet, Wollack, Edward J., Xu, Zhilei, Yan, Ziang, and Zeng, Lingzhen

Published
2018
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