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Analytical Science & Technology (GlycoAnalytics)

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ASSESSING AND ENSURING PRODUCT SAFETY AND QUALITY

The GlycoAnalytics group focuses on the assessment of product safety and quality through product and process analysis. Our group can accurately and quickly characterise critical quality attributes (CQAs) such as: glycans, protein aggregation, charge variants, sequence variants and protein topology. We strive to develop new methods and platforms for rapid, more detailed CQA characterisation at higher throughput to strengthen the development of novel drugs and biosimilars in Singapore. Furthermore, the team has developed mathematical/computational models, algorithms, software, and databases to help with automating, monitoring and analysing product CQAs.

Focus Areas

  • Glycan profiling, N-/O- site occupancy and glycosylation associated CQAs for glycoprotein drugs
  • Rapid semi-automated platform for accurate characterisation of product safety and CQAs
  • Aggregation characterisation and data-driven mathematical models that can simulate how different processing conditions influence aggregation
  • Machine learning modelling towards Quality by Design (QbD), predictive models and biomanufacturing 4.0, in partnership with other BTI research groups


Our Capabilities

MS-Based Technologies

MS-Based Technologies

  • Orbitrap Fusion
  • LC-MS (XEVO)
  • IM-MS (SYNAPT)

UHPLC

UHPLC

  • Multi-angle Light Scattering (MALS)
  • IEX

Capillary Electrophoresis

Capillary Electrophoresis

  • cIEF
  • CZE
  • Fast Glycan Kit
  • mRNA
  • CE-SDSMW

HDX

HDX

  • Tertiary structure analysis

Enable characterisation of antibodies and new modalities of pharmaceutical drugs such as mRNA, bispecific antibodies, fusion proteins, and other recombinant proteins. Using these complementary skills as experienced analytical chemists, chemical engineers and computer scientists, we can advance the development of novel approaches for rapid and automated analysis of pharmaceutical products.

Our Technologies

GLYCAN CHARACTERISATION

GLYCOMICS

GLYCOMICS

  • Glycan profiling of purified glycoproteins, cells, serum or tissues
  • Monosaccharide analysis - pharmaceutical and food products

DETAIL STRUCTURAL ELUCIDATION

DETAIL STRUCTURAL ELUCIDATION

  • Collision Cross Section (CCS) can separate linkage isomers

GLYCOPROTEOMICS

GLYCOPROTEOMICS

  • Site analysis of purified glycoproteins and quantitative specific site abundance by glycan structures

INTACT GLYCAN STRUCTURES

INTACT GLYCAN STRUCTURES

  • Direct observation of glycan pairing on intact glycan


AGGREGATION AND OTHER DEVELOPABILITY ATTRIBUTES

EXPERIMENTAL CHARACTERIZATION

EXPERIMENTAL CHARACTERISATION

  • Structural and chemical characterisation of aggregates
  • Polyreactivity assay panel for various mechanisms
  • Other characterisation assays for developability attributes

THEORETICAL MODELS

THEORETICAL MODELS

  • Rate modelling for aggregation kinetics across bioprocess parameters
  • In silico models to identify sequence liabilities for developability attributes


DIGITALISATION AND MODELLING

AUTOMATED ANALYTICS

AUTOMATED ANALYTICS

  • Anchored technologies in machine learning modelling to assist optimization of bioprocesses for better quality protein therapeutics by monitoring vital components involved in cell culture
  • Digital solution for semi-automated analytics and machine learning models for CQA monitoring and control

PREDICITVE MODELS FOR QUALITY MONITORING AND CONTROL

PREDICITVE MODELS FOR QUALITY MONITORING AND CONTROL

  • Models that can predict aggregation prone protein regions for the use of biotherapeutic discovery and manufacturing campaigns

Our Track Record

Featured publications:

  • Sean Chia, Shi Jie Tay, Zhiwei Song, Yuansheng Yang, Ian Walsh and Kuin Tian Pang (2023) Enhancing pharmacokinetic and pharmacodynamic properties of recombinant therapeutic proteins by manipulation of sialic acid content. Biomedicine & Pharmacotherapy 163: 114757
  • Kuin Tian Pang, Yuan Sheng Yang, Wei Zhang, Ying Swan Ho, Pietro Sormanni, Thomas C.T. Michaels, Ian Walsh and Sean Chia (2023) Understanding and controlling the molecular mechanisms of protein aggregation in mAb therapeutics. Biotechnology Advances 67: 108192
  • Sean Chia, Gavin Teo, Shi Jie Tay, Larry Loo Sai Weng, Corrine Wan, Sim Lyn Chiin, Hanry Yu, Ian Walsh and Kuin Tian Pang (2022) An Integrative Glycomic Approach for Quantitative Meat Species Profiling. Foods 11(13): 1952
  • Ian Walsh, Matthew Myint, Terry Nguyen-Khuong, Ying Swan Ho, Say Kong Ng and Meiyappan Lakshmanan (2022) Harnessing the potential of machine learning for advancing “Quality by Design” in biomanufacturing. mAbs 14(1)
  • Kuin Tian Pang, Shi Jie Tay, Corrine Wan, Ian Walsh, Matthew S.F. Choo, Yuan Sheng Yang, Andre Choo, Ying Swan Ho and Terry Nguyen-Khuong (2021) Semi-automated Glycoproteomic Data Analysis of LC-MS data using GlycopeptideGraphMS in Process Development of Monoclonal Antibody Biologics. Frontiers in Chemistry-Analytical Chemistry 9: 661406

LANDMARK PATENT & IP:

  • Method for identifying an unknown biological sample from multiple attributes (2022)
  • Methods, Apparatus, and Computer-Readable Media for Glycopeptide Identification (2021)

The Team

Ian Walsh2

Dr Ian Walsh

ian_walsh@bti.a-star.edu.sg
Principal Scientist I

PhD in Bioinformatics (2009), University College Dublin, Ireland

Research Focus / Interest

  • Advancing tools for the analysis of protein glycosylation
  • Novel adaptive computational models to interpret and control bioprocesses
  • Machine learning
  • Data analytics

Qiu Beiying

Dr Qiu Beiying

qiu_beiying@bti.a-star.edu.sg
Senior Scientist I

PhD in Pharmacology (2009), Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China

Research Focus / Interest

  • Developing novel analytical platforms for biomanufacturing
  • Discovering and validating novel drug targets in metabolic diseases
  • High-throughput and phenotypic cell-based assay development

Sean Chia v2

Dr Sean Chia

sean_chia@bti.a-star.edu.sg
Senior Scientist I

PhD in Biophysics (2020), University of Cambridge, United Kingdom

Research Focus / Interest

  • New approaches and analytical tools for antibody and biotherapeutic developability profiling

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