Publications

2025

2024

Bal, V., Sinskey, A.J., Barone, P.W., Braatz, R.D., Springs, S.L.
Methods for purification of recombinant adeno-associated virus vectors for gene therapy.
US Patent App. 18/732,263, 2024

Bal, V.; Wolfrum, J. M.; Barone, P. W.; Springs, S. L.; Sinskey, A. J.; Kotin, R. M.; Braatz, R. D.
Selective Enrichment of Full AAV Capsids.
arXiv preprint arXiv:2412.06093, 2024

Srinivasan, P.; Canova, C. T.; Sha, S.; Nguyen, T. N.; Joseph, J.; Sangerman, J.; Maloney, A. J.; Katsikis, G.; Ou, R. W.; Hong, M. S.
Multidose transient transfection of human embryonic kidney 293 cells modulates recombinant adeno‐associated virus2/5 Rep protein expression and influences the enrichment…
Biotechnology and Bioengineering, 121 (12), 3694-3714, 2024

Yang, M.; Keumurian, F. J.; Neufeld, C.; Skrip, E.; Duguid, J.; Vega-Mercado, H.; Rao, R. P.; Rolle, M. W.; Springs, S. L.; Wolfrum, J. M.
Upskilling the cell therapy manufacturing workforce: design, implementation, and evaluation of a massive open online course.
Advances in Physiology Education, 48 (4), 733-741, 2024

Destro, F.; Wu, W.; Srinivasan, P.; Joseph, J.; Bal, V.; Neufeld, C.; Wolfrum, J. M.; Manalis, S. R.; Sinskey, A. J.; Springs, S. L.; Braatz, R.
The state of technological advancement to address challenges in the manufacture of rAAV gene therapies.
Biotechnology Advances, 76, 108433, 2024

2024, 108433. Nguyen, T. N. T.; Park, D.; Canova, C. T.; Sangerman, J.; Srinivasan, P.; Ou, R. W.; Barone, P. W.; Neufeld, C.; Wolfrum, J.; Springs, S.; Sinskey, A.; Braatz, R.
Continuous Production of rAAV via an Intensified Transient Transfection Process.
Authorea Preprints, 2024

Huang, J., Rice, S.A., Springs, S.L., Lee, Y.H.
Method of detecting bacterial/fungal contamination.
US Patent App. 18/288,401, 2024

Srinivasan, P., Piras, G., Neffling, M., Josephs, J., Nguyen, T.N., Wolfrum, J.M., Barone, P.W., Springs, S.L., Sinskey, A.J., Braatz, R.D.
OPTIMIZATION OF SCALABLE rAAV PRODUCTION FOR GENE THERAPY–LEVERAGING AT-LINE AMINO ACID MEASUREMENTS FOR BIOPROCESS MODELING-DRIVEN APPROACHES.
Cytotherapy, 26 (6), S219, 2024

Royo, M.C.P., Guo, J., Bal, V., Hong, M.S., Barone, P.W., Springs, S.L., Sinskey, A.J., Braatz, R.D.
Advances in Crystallization and Precipitation Technologies for Biotherapeutics.
Chemical Engineering Progress, 120 (5), 25-31, 2024

Braatz, R.; Srinivasan, P.; Canova, C. T.; Sha, S.; Tam; Joseph, J.; Sangerman, J.; Maloney, A. J.; Katsikis, G.; Ou, R. W.; Hong, M. S.; Ng, J.; Neufeld, C.; Wolfrum, J.; Barone, P.; Sinskey, A.; Springs, S.
Multidose Transient Transfection of HEK293 Cells Modulates rAAV2/5 Rep Protein Expression and Influences the Enrichment Fraction of Filled Capsids.
2024

Wu, X.; Lou, X.; Zhou, H.; Raymond, J. J.; Kwang, L. G.; Yi, F.; Springs, S. L.; Yu, H. Detection and Absolute Quantification Biosensing Tools for Food Authentication: CRISPR/Cas, Digital CRISPR and Beyond. Trends in Food Science and Technology 2024, 104349.

Mohr, F.; Hong, M. S.; Castro, C. D.; Smith, B. T.; Wolfrum, J. M.; Springs, S. L.; Sinskey, A. J.; Hart, R. A.; Mistretta, T.; Braatz, R. D. Tensorial Approaches Combining Time Series and Batch Data for the End-to-End Batch Manufacturing of Monoclonal Antibodies. Computers & Chemical Engineering 2024, 182, 108557.

Liu, Y.; Raymond, J. J.; Wu, X.; Chua, P. W. L.; Ling, S. Y. H.; Chan, C. C.; Chan, C.; Loh, J. X. Y.; Song, M. X. Y.; Ong, M. Y. Y.; Ho, P.; Mcbee, M. E.; Springs, S. L.; Yu, H.; Han, J. Electrostatic Microfiltration (EM) Enriches and Recovers Viable Microorganisms at Low-Abundance in Large-Volume Samples and Enhances Downstream Detection. Lab on a Chip 2024, 24 (18), 4275–4287.

Park, D.; Nguyen, T. N. T.; Sangerman, J.; Srinivasan, P.; Ou, R. W.; Katsikis, G.; Hong, M. S.; Barone, P. W.; Neufeld, C.; Wolfrum, J. M.; Springs, S. L.; Sinskey, A. J.; Braatz, R. D. Continuous Production of Recombinant Adeno-Associated Viral Vectors via Transient Transfection of HEK293 Cells in Perfusion Bioreactor. Science Direct 2024, 53 (2024), 2587–2592

Destro, F.; Joseph, J.; Srinivasan, P.; Kanter, J. M.; Neufeld, C.; Wolfrum, J. M.; Barone, P. W.; Sinskey, A. J.; Springs, S. L.; Cecchini, S.; Kotin, R. M.; Braatz, R. D. Mechanistic modeling for efficient manufacturing of rAAV with the Sf9/BEVS platform. ECI Digital Archives.

Srinivasan, P.; Canova, C.; Sangerman, J.; Barone, P. W.; Wolfrum, J.; Milla Neffling; Anderson, J. Y.; Miller, S.; Piras, G.; Sinskey, A. J.; Braatz, R. D.; Springs, S. L. Towards a scalable AAV vector production at high volumetric efficiency. ECI Digital Archives.

Blakeman, K.; Young, J.; Miller, S. E.; Ng, A.; Huang, J.; Natarajan, M.; Lee, Y. H.; Williams, R.; Barone, P. W.; Springs, S. L.; Wolfrum, J. M. At-line quantitation for the nicontinic acid to nicotinamide ratio as a biomarker for microbial combination of cell cultures. ECI Digital Archives.

Piras, G.; Milla Neffling; Joseph, J.; Nguyen, T. N. T.; Anderson-Czajkowski, J. Y.; Miller, S.; Piras, G.; Sinskey, A. J.; Braatz, R. D.; Wolfrum, J.; Barone, P. W.; Springs, S. L. Optimization of scalable rAAV production for gene therapy – Leveraging at-line amino acid measurements for bioprocess modeling-driven approaches. ECI Digital Archives.

Joseph, J.; Destro, F.; Srinivasan, P.; Kanter, J. M.; Neufeld, C.; Wolfrum, J. M.; Cecchini, S.; Kotin, R. M.; Sinskey, A. J.; Barone, P. W.; Braatz, R. D.; Springs, S. L. Continuous rAAV vector production using the baculovirus expression vector system. ECI Digital Archives.

Springs, S.; Tsinda, E. K.; Swofford, C. A.; Sangerman, J.; Barone, P. W.; Wolfrum, J. M.; Ram, R. J.; Han, J.; Siew, C.; Shruthi Pandi Chelvam; Huang, J.; Liu, Y.; Natarajan, M.; Strutt, J.; Ng, A.; Wu, X.; Yong, D.; Williams, R.; Lee, Y. H.; Young, J. Novel analytics for rapid adventitious agent detection in cell and gene therapy manufacturing. ECI Digital Archives.

Rhyu, J.; Bozinovski, D.; Dubs, A. B.; Mohan, N.; Cummings Bende, E. M.; Maloney, A. J.; Nieves, M.; Sangerman, J.; Lu, A. E.; Hong, M. S.; Artamonova, A.; Ou, R. W.; Barone, P. W.; Leung, J. C.; Wolfrum, J. M.; Sinskey, A. J.; Springs, S. L.; Braatz, R. D. Automated Outlier Detection and Estimation of Missing Data. Computers & Chemical Engineering 2024, 180, 108448.

2023

Barone, P.W., Keumurian, F.J., Neufeld, C., Koenigsberg, A., Kiss, R., Leung, J.C., Wiebe, M., Ait-Belkacem, R., Azimpour – Tabrizi, C., Barbirato, C., Beurdeley, P., Brussel, A., Cassart, J.P., Cote, C., Deneyer, N., Dheenadhayalan, V.,  Diaz, L., Geiselhoeringer, A., Gilleece, M.M., Goldmann, J., Hickman, D., Holden, A., Keiner, B., Kopp, M., Kreil, T.R., Lambert, C., Logvinoff, C., Michaels, B., Modrof, J., Mullan, B., Mullberg, J., Murphy, M., O’Donnell, S., Peña, J., Ruffing, M., Ruppach, H., Salehi, N., Shaid, S., Silva, L., Snyder, R., Spedito-Jovial, M., Vandeputte, O., Westrek, B., Yang, B., Yang, P., Springs, S.L.
Historical evaluation of the in vivo adventitious virus test and its potential for replacement with next generation sequencing (NGS)
Biologicals, January 6, 2023

2022

Swofford, C.A., Nordeen, S.A., Chen, L., Desai, M.M.,  Chen, J., Springs, S.L., Schwartz, T.U., Sinskey, A.J.,
Structure and specificity of an anti-chloramphenicol single domain antibody for detection of amphenicol residues.
Protein Science, Volume 31, Issue 11, November 2022

Koenigsberg, A.L., Fowler, V.,  Domike, R., Brussel, A., Barone, P.W., Keumurian, F.J., Leung, J.C., Wiebe, M.E., Brewer, M.T.,  Chan, S., Dumey, N., Fournillier, A., Goodnight, M., Kindermann, J., Leavy, R., Lee, B., Minning, S.,  Murphy, M., Myers, E., Nahabedian, A., Nanda, K.,  Parriott, S., Raju, G.K., Scallan, C., Schoch, S., Shiminsky, J.,  Shum, B., Teitz, S., Westrek, B., Springs, S.L.
MIT CAACB Risk Assessment Case Study: Assessing virus cross-contamination risk between two simultaneous processes in an open biomanufacturing facility.
PDA Journal of Pharmaceutical Science and Technology, October, 2022

Katsikis, G., Hwang, I.E., Wang, W., Bhat, V.S., McIntosh, N.L., Karim, O.A., Blus, B.J., Sha, S., Agache, V., Wolfrum, J.M., Springs, S.L., Sinskey, A.J., Barone, P.W., Braatz, R.D., Manalis, S.R.
Weighing the DNA content of adeno-associated virus vectors with Zeptogram precision using nanomechanical resonators. 
Nano Letters, 2022, 22, 4, 1511-1517 

Huang, J., Cuie, L., Natarajan, M., Barone, P.W.,  Wolfrum, J., Lee, Y.H., Rice, S.A., Springs, S.L.
The ratio of nicotinic acid to nicotinamide as a microbial biomarker for assessing cell therapy product sterility.
Molecular Therapy – Methods & Clinical Development, April 2022 

Wu, X., Chan, C., Springs, S.L., Lee, Y.H., Lu, T.K., Yu, H.,
A warm-start digital CRISPR/Cas-based method for the quantitative detection of nucleic acids.
Analytica Chimica Acta, Volume 1196, March 2022 

Wu, X., Tay, J.K., Goh, C.K., Chan, C., Lee, Y.H., Springs, S.L., Wang, D.Y., Loh, K.S., Lu, T.K., Yu, H.
A Rapid DIgital Crispr Approach (RADICA) for the detection and absolute quantification of nucleic acids.
Frontiers in Biological Detection: From Nanosensors to Systems XIV, Volume PC11979, March 2022 

Hong, M.S., Lu, A.E., Maloney, A.J., Ou, R.W., Wolfrum, J.M., Springs, S.L., Sinskey, A.J., Braatz, R.D.
Applying PAT to the continuous digital biomanufacturing of monoclonal antibodies.
Pharma Focus Asia, Volume 44, 42-46, 2022 

Chen, L., Guttieres, D., Koenigsburg, A., Barone, P.W., Sinskey, A.J., Springs, S.L.,
Large-scale cultured meat production: Trends, challenges and promising biomanufacturing technologies.
Biomaterials, Volume 280, January 2022 

2021

Wu, X., Tay, J.K., Goh, C.K., Chan, C., Lee, Y.H., Springs, S.L., Wang, D.Y., Loh, K.S., Lu, T.K., Yu, H.
Digital CRISPR-based method for the rapid detection and absolute quantification of nucleic acids.
Biomaterials, July 2021, 120876 Nguyen, T.N.T., Sha, S., Hong, M.S., Maloney, A.J., Barone, P.W., Neufeld, C., Wolfrum, J.M., Springs, S.L., Sinskey, A.J., Braatz, R.D.
Mechanistic model for production of recombinant adeno-associated virus via triple transfection of HEK293 cells.
Molecular Therapy, Methods & Clinical Development, June 2021, Vol. 21, 642-655 

Sha, S., Maloney, A.J., Katsikis, G., Nguyen, T.N.T., Neufeld, C., Wolfrum, J.,  Barone, P.W., Springs, S.L., Manalis, S.R., Sinskey A.J.,  Braatz, R.D.
Cellular Pathways of recombinant Adeno-Associated Virus Production for Gene Therapy.
Biotechnology Advances, Volume 49, May 2021 

Su, J., Rice, J.,  Hoffman, J., Alvarado, S.,  Bailey, M., Kopp, M.,  Murphy, M., Kiss, R., Barone, P.W.,  Wiebe, M.E.,  Springs, S.L.,  Dehghani, H., Chen, D.
Revisiting mouse minute virus inactivation by high temperature short time treatment.
Biotechnology & Bioengineering, April 29, 2021 

Guttieres, D., Sinskey, A.J., Springs, S.L.
Models to Inform Neutralizing Antibody Therapy Strategies During Pandemics: The Case of SARS-CoV-2.  Antibody Therapeutics, Volume 4, Issue 1, Pages 60–71, January 2021 

Guttieres, D. , Sinskey, A.J.,  Springs, S.L.
Modeling Framework to Evaluate Vaccine Strategies against the COVID-19 Pandemic
Systems, 2021, 9(1), 4 

Gimpel, A.L., Katsikis, G., Sha, S., Maloney, A.J., Hong, M.S.,Nguyen, T., Wolfrum, J., Sinskey, A.J., Manalis, S.R., Barone, P.W., Braatz, R.D., Springs, S.L.,
Analytical Methods for Process and Product Characterization of Recombinant Adeno-Associated Virus-based Gene Therapies.
Molecular Therapies – Methods & Clinical Development.  2021 

Jin, C., Levi, R., Liang, Q., Renegar, N., Zhou, J., Zhou, W., Springs, S.L.
Testing at the Source: Analytics-Enabled Risk-Based Sampling of Food Supply Chains in China.
Management Science, 22, Jan., 2021 

2020

P.W. Barone, F.J. Keumurian, M.E. Wiebe, J. Wolfrum, J.C. Leung, A.J. Sinskey, S.L. Springs
The Impact of SARS-CoV-2 on Biomanufacturing Operations.
BioPharm International, Volume 33, Issue 8, August 1, 2020 

P.W. Barone, M.E. Wiebe, J.C. Leung, … S.L. Springs. 
Viral contamination in biologic manufacture and implications for emerging therapies.
Nat Biotechnol 38, 563–572, April 27, 2020 

Wu, X., Chan, C., Lee, Y.H., Lu, T.K., Yu, H., Springs, S.L.
A Digital CRISPR-based Method for the Rapid Detection and Absolute Quantification of Viral Nucleic Acids.
medRxiv, 2020 

2019

Gutierres, D., Stewart,S.R.,  Wolfrum, J., Springs, S.L. 
Cyberbiosecurity in Advanced Manufacturing Models.
Frontiers in Bioengineering and Biotechnology, September, 2019 

Barone, P.W., Springs, S.L.,  et.al.
Biopharmaceutical Industry Approaches to Facility Segregation for Viral Safety: An Effort from the Consortium on Adventitious Agent Contamination in Biomanufacturing.
PDA J. Pharm. Sci. Tech. March 2019, 73 (2) 191-203 

Levi, R., Renegar, N., Springs. S.L., Zaman, T.
Supply Chain Network Analytics Guiding Food Regulatory Operational Policy.
SSRN, 2019 

2018

Barone, P.W.,  Keumurian, F.J.,  Leung, J, Springs, S.L., Domike, R., Raju, G.K.,  Monpoeho, S., Murray, K., Reich, S., Ruffing, M., Wiebe, M.
“Quality Risk Management in the Context of Viral Contamination”.
In Microbial Control and Identification, edited by Donna Reber, PDA, Washington, 2018  

2016

Stewart, S.R.,  Barone, P.W., . Bellisario, A., Cooney, C.L.,   Sharp, P.A., Sinskey, A.J.,  Natesan, S., Springs, S.L.
Leveraging Industry-Academia Collaborations in Adaptive Biomedical Innovation.
Clin. Pharm. Ther. 100 (6), 647-653. PMID: 27617845, 2016 

2015

US Chapter of the United Nations Educational, Scientific and Cultural Organization (UNESCO) 2015 Science Report: “The United States of America.” S.R. Stewart and S.L.Springs.
UNESCO Science Report 2015: Towards 2030.
UNESCO Publishing. November 10, 2015. Koenigburg