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Engineering CELLS,
   Engineering RESPONSES

DOWNSTREAM PROCESSING

Separating the Good, Bad and Ugly

Downstream processing involves purification of next-generation therapeutic molecules for treatment of cancer, infectious disease, regenerative therapy and other important healthcare applications. These therapeutic molecules particularly include recombinant proteins such as monoclonal antibodies, vaccines based on virus and virus-like particles, cellular organelles, and living cells produced by in vitro cell culture. Purification is accomplished with a wide variety of technologies including chromatography, membrane techniques, selective precipitation, and novel hybrid formats.

The Downstream Processing Group (DSP) is particularly focused on innovations aimed at improving global healthcare. These include development of novel purification technology to reduce manufacturing costs, increase productivity, and improve product safety and efficacy. Some of these innovations involve mechanical systems, such as ultrahigh capacity magnetic nanoparticles, non-column fluidized beds, and simulated moving bed chromatography systems.

Others involve development of novel chemical approaches to fractionation, including methods like steric exclusion chromatography, void exclusion ion exchange chromatography, and hydrogen bond chromatography. DSP also plays an integral supporting role in other Institute research programs by developing purification procedures for newly emerging therapeutic candidates

People

Zhang Wei

Dr. Zhang Wei

PhD in Chemical and Pharmaceutical Engineering (2011), Singapore-MIT Alliance, National University of Singapore, Singapore

Research Focus/Interests
  • Development of novel methods for antibody and virus purification
  • Optimization of purification processes for industrial application

Dr. Ta Duy Tien

PhD in Chemistry (2016), Hasselt University, Belgium

Research Focus/Interests
  • Purification and characterization of therapeutic proteins (antibodies) and viruses (AAV)

Dr. Siew Yin Yin

PhD in Pharmacy (2016), National University of Singapore, Singapore

Research Focus/Interests
  • Biotherapeutics purification and characterization

Year 2018

    Sung Kyu Jang, Sookyung Kim, Muhammad Saad Salman, Ji-ryang Jang, Yu Mi Um, Lihan Tan, Jin-Hong Park, Woo-Seok Choe, and Sungjoo Lee (2018) Harnessing Recombinant DnaJ Protein as Reversible Metal Chelator for a High-Performance Resistive Switching Device. Chemistry of Materials 30(3): 781–788

Year 2017

    Muhammad Saad Salman, A Reum Park, Min Jin Cha, Youngjin Choi, Sung Kyu Jang, Lihan Tan, Pil J. Yoo and Woo-Seok Choe (2017) Lysozyme-templated Meso-macroporous Hollow TiO2 for Lithium-ion Battery Anode. ACS Applied Nano Materials 1(2): 698–710

    Jian'er Lin, Shu Hui Neo, Steven C. L. Ho, Jessna H. M. Yeo, Tianhua Wang, Wei Zhang, Xuezhi Bi, Sheng-Hao Chao and Yuansheng Yang (2017) Impact of Signal Peptides on Furin-2A Mediated Monoclonal Antibody Secretion in CHO Cells. Biotechnology Journal 12: 9

Year 2016

    Quan Chen, Phyllicia Toh, Yue Sun, Sarah Maria Abdul Latiff,Aina Hoi, Mo Xian, Haibo Zhang, Rui Nian, Wei Zhang and Pete Gagnon (2016) Histone-dependent IgG conservation in octanoic acid precipitation and its mechanism. Applied Microbiology and Biotechnology (Published Online)

    Quan Chen, Sarah Maria Abdul Latiff, Phyllicia Toh, Xinying Peng, Aina Hoi, Mo Xian, Haibo Zhang, Rui Nian, Wei Zhang and Pete Gagnon (2016) A simple and efficient purification platform for monoclonal antibody production based on chromatin-directed cell culture clarification integrated with precipitation and void-exclusion anion exchange chromatography. Journal of Biotechnology 236: 128–140

    Rui Nian and Pete Gagnon (2016) Advance chromatin extraction enhances performance and productivity of cation exchange chromatography-based capture of Immunoglobulin G monoclonal antibodies. Journal of Chromatography A 1453: 54–61

    Pete Gagnon and Rui Nian (2016) Conformational plasticity of IgG during protein A affinity chromatography. Journal of Chromatography A 1433: 98-105

    Rui Nian, Wei Zhang, Lihan Tan, Jeremy Lee, Xeuzhi Bi, Yuansheng Yang, Hui Theng Gan and Pete Gagnon (2016) Advance chromatin extraction improves capture performance of protein A affinity chromatography. Journal of Chromatography A 1431: 1-7

Year 2015

    Pete Gagnon, Rui Nian, Yuansheng Yang, Qiaohui Yang and Chiew Ling Lim (2015) Non-immunospecific association of immunoglobulin G with chromatin during elution from protein A inflates host contamination, aggregate content, and antibody loss. Journal of Chromatography A 1408: 151-60

    Pete Gagnon, Rui Nian, Denise Leong and Aina Hoi (2015) Transient conformational modification of immunoglobulin G duringpurification by protein A affinity chromatography. Journal of Chromatography A 1395: 136–142

    Lihan Tan, Veronica Yeo, Yuansheng Yang and Pete Gagnon (2015) Characterization of DNA in cell culture supernatant by fluorescence-detection size-exclusion chromatography. Analytical and Bioanalytical Chemistry 407(14): 4173-4181

    Jake Chng, Tianhua Wang, Rui Nian, Ally Lau, Kong Meng Hoi, Steven C.L. Ho, Peter Gagnon, Xuezhi Bi, Yuansheng Yang (2015) Cleavage efficient 2A peptides for high level monoclonal antibody expression in CHO cells. mAbs 7(2): 403-412

Year 2014

    Pete Gagnon, Rui Nian, Lihan Tan, Jason Cheong, Veronica Yeo, Yuansheng Yang, and Hui Theng Gan (2014) Chromatin-Mediated Depression of Fractionation Performance on Electronegative Multimodal Chromatography Media, its Prevention, and Ramifications for Purification of Immunoglobulin G. Journal of Chromatography A 1374: 145–155

    Vincent Vagenende, Tim-Jang Ching, Rui-Jing Chua, Qiu Zhen Jiang and Pete Gagnon (2014) Self-assembly of lipopolysaccharide layers on allantoin crystals. Colloids and Surfaces B: Biointerfaces 120: 8-14

    Pete Gagnon, Rui Nian, Jeremy Lee, Lihan Tan, Sarah Maria Abdul Latiff, Chiew Ling Lim, Cindy Chuah, Xuezhi Bi, Yuansheng Yang, Wei Zhang, Hui Theng Gan (2014) Nonspecific Interactions of Chromatin with Immunoglobulin G and Protein A, and Their Impact on Purification Performance. Journal of Chromatography A 1340: 68-78

    Pete Gagnon (2014) Void Exclusion Biomanufacturing Method - Novel Operating Mode for Carrying Out Anion Exchange Chromatography. Genetic Engineering & Biotechnology News Vol. 34, No. 10 (News Article)

    Pete Gagnon, Phyllicia Toh and Jeremy Lee (2014) High productivity purification of immunoglobulin G monoclonalantibodies on starch-coated magnetic nanoparticles by steric exclusion of polyethylene glycol. Journal of Chromatography A 1324: 171– 180

Year 2013

    Hui Theng Gan, Jeremy Lee, Sarah Maria Abdul Latiff, Cindy Chuah, Phyllicia Toh and Pete Gagnon (2013) Characterization and Removal of Aggregates Formed by Nonspecific Interaction of IgM Monoclonal Antibodies with Chromatin Catabolites During Cell Culture Production. Journal of Chromatography A 1291: 33-40

    Vincent Vagenende, Tim-Jang Ching, Rui-Jing Chua, Navanita Thirumoorthi, and Pete Gagnon (2013) Amide-mediated hydrogen-bonding at organic crystal/water interfaces enables selective endotoxin binding with picomolar affinity. ACS Applied Materials & Interfaces 5: 4472-4478

    Vincent Vagenende, Tim Jang Ching, Rui Jing Chua and Pete Gagnon (2013) Allantoin as a solid phase adsorbent for removing endotoxins. Journal of Chromatography A; 1310: 15–20

    Vincent Vagenende, Alvin X. Han, Han B. Pek, Bernard L. W. Loo (2013) Quantifying the Molecular Origins of Opposite Solvent Effects on Protein-Protein Interactions. PLOS Computational Biology; 9(5):e1003072

    Monika Mueller, Maybelle Q. T. Loh, Doris H. Y. Tee, Yuansheng Yang and Alois Jungbauer (2013) Liquid Formulations for Long-Term Storage of Monoclonal IgGs. Applied Biochemistry and Biotechnology 169(4):1431-1448

    Pete Gagnon (2013) Steric Exclusion Chromatography. Genetic Engineering & Biotechnology News Vol. 6, No. 33 (News Article)

    Rui Nian, Cindy Chuah, Jeremy Lee, Hui Theng Gan, Sarah Maria Abdul Latiff, Wan Yee Lee, Vincent Vagenende, Yuan Sheng Yang and Pete Gagnon (2013) Void exclusion of antibodies by grafted-ligand porous particle anion exchangers. Journal of Chromatography A 1282:127-132

Year 2012

    Jeremy Lee, Hui Theng Gan, Sarah Maria Abdul Latiff , Cindy Chuah, Wan Yee Lee, Yuan-Sheng Yang, Bernard Loo, Say Kong Ng, Pete Gagnon (2012) Principles and Applications of Steric Exclusion Chromatography. Journal of Chromatography A (Published Online)

    Vincent Vagenende and Bernhardt L. Trout (2012) Quantitative characterization of local protein solvation to predict solvent effects on protein structure. Biophysical Journal 103(6):1354-1362

    Kornelia Schriebl, Gernalia Satianegara, Austin Hwang, Heng Liang Tan, Wey Jia Fong, Henry He Yang, Alois Jungbauer, and Andre Choo (2012) Selective removal of undifferentiated human embryonic stem cells using magnetic activated cell sorting followed by a cytotoxic antibody. Tissue Engineering Part A (Publish Online)

    Vincent Vagenende, Alvin X. Han, Monika Mueller and Bernhardt L. Trout (2012) Protein-associated cation-clusters in aqueous arginine solutions and their effects on protein stability and size. ACS Chemical Biology; 8(2):416-422

    Monika Mueller, Maybelle Q.T. Loh, Rupert Tscheliessnig, Doris H.Y. Tee, Eddy Tan, Muriel Bardor and Alois Jungbauer (2012) Liquid Formulations for Stabilizing IgMs During Physical Stress and Long-Term Storage. Pharmaceutical Research (Published Online)

    Monika Mueller, Corrine Wan, Kong Meng Hoi, Kim Do Yun, Hui Theng Gan, Muriel Bardor and Pete Gagnon (2012) Immunoglobulins M survive low pH conditions used for virus inactivation and for elution from bioaffinity columns. Journal of Pharmaceuticals Sciences (Published Online)

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