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Order](https://www.sigmaaldrich.com/US/en/quick-order) Cart0 [Home](https://www.sigmaaldrich.com/US/en)[(ELISA) Enzyme-Linked Immunosorbent Assay](https://www.sigmaaldrich.com/US/en/applications/protein-biology/elisa)Protein Conformation Array Multiplexing # Protein Conformation Array Multiplexing ### Read more about - [Understanding HOS for Successful Biosimilar mAb Development](https://www.sigmaaldrich.com#hos-for-successful-biosimilar-mab) - [Protein Conformational Array Technology](https://www.sigmaaldrich.com#protein-conformational-array-technology) - [Utilizing PCA ELISAs to Analyze HOS for Process Development](https://www.sigmaaldrich.com#pca-elisa-analyze-hos) - [Utilizing PCA ELISAs to Analyze HOS for FDA Submission](https://www.sigmaaldrich.com#pca-elisa-analyze-hos-for-fda) - [InnoPlex for High-Throughput PCA in Novel mAb Development](https://www.sigmaaldrich.com#innoplex-pca-novel-mab) - [References](https://www.sigmaaldrich.com#references) [Explore Products](https://www.sigmaaldrich.com#references) ## [](https://www.sigmaaldrich.com)Understanding HOS for successful biosimilar mAb development Monoclonal antibodies (mAbs) are the fastest growing class of human therapeutics within the field of biologics, having predicted worldwide sales of $125 billion by 2020 based on current approval rates. As the number of therapeutic mAbs reaching the market continues to rise, a corresponding increase in the number of biosimilars is expected.1 The US Food and Drug Administration (FDA) definition of a biosimilar describes a biological product that is highly similar to, and has no clinically meaningful differences from, an existing FDA-approved reference product.  The production of biosimilar mAbs is challenging since the three-dimensional (3D) structure, a key factor in the biological function of these molecules, is highly complex. Even small structural differences between a biosimilar mAb and the reference therapeutic mAb it is based upon can lead to significant impacts on the safety, efficacy and function of the molecule. The 3D structure of a mAb arises from the combined effects of primary, secondary, tertiary and quaternary structure, in addition to the influence of posttranslational modifications. Referred to as the Higher Order Structure (HOS), this conformation is influenced not only by the underlying gene but also by factors including the choice of cell line for producing the biosimilar, bioprocessing conditions such as temperature, pH and light exposure, and the method of formulation. With so many variables to consider, it is often the case that a biosimilar mAb is not identical to the product it is based upon. To avoid the multitude of issues that can occur as a result of these differences, FDA guidelines published in 2015 recommend that extensive, robust comparative physicochemical and functional studies should be performed to evaluate the biosimilarity of a proposed product to a reference product.2 Current methods for analyzing HOS are detailed below, yet while all of these provide useful information about the 3D conformation of a mAb, none of them offer both sensitivity and affordability: - Circular Dichroism Spectroscopy - Size Exclusion Chromatography (SEC) - Analytical Ultracentrifugation (AUC) - Non-denaturing Electrophoresis - Hydrogen/deuterium exchange Mass Spectroscopy (HDX/MS) - NMR Spectroscopy Due to the limitations of these methods, and a drive to meet the requirements of the FDA, there has been an increasing need for an alternative and higher throughput approach to analyzing the HOS of biosimilar mAbs relative to a reference product. Through our acquisition of the commercial rights to exclusively distribute and research Protein Conformational Array (PCA) technology from Array Bridge Inc., MilliporeSigma provides researchers with a convenient solution to this problem. Located in close proximity to our St. Louis campus, Array Bridge Inc. are experienced in the measurement of biosimilar comparability at the molecular level. * * *   ## [](https://www.sigmaaldrich.com)Protein Conformational Array technology Within their 2013 publication in Frontiers in Pharmacology, Wang et al of Array Bridge Inc. described the development of sophisticated antibody arrays for probing mAb HOS.3 By generating polyclonal antibodies (pAbs) against peptide immunogens with overlapping regions, covering the entire mAb structure, the authors demonstrated that different marketed mAbs possessed distinct HOS signatures despite sharing almost identical amino sequences. The HOS signature represents observable changes in the different mAb species that are detected by the panel of pAbs due to chemical modifications and or physical changes to the antibody structure. To better understand this, it is important to recognize that each pAb within the panel binds the linear or secondary structure epitope, which may be inaccessible, partially or fully exposed when the mAb is in its correctly folded native form. Presentation of these epitopes on the surface of the mAb due to unfolding or misfolding results in a change of signal. The information generated from these antibody arrays can be used to benchmark the original mAb, to analyze the biosimilar in comparison to this product, and to check for any conformational changes which may lead to clinically relevant effects of the new mAb. PCA technology is extremely user-friendly. Run as an easy-to-operate ELISA format, the assays provide rapid, accurate and sensitive measurement of mAb HOS with utility across all stages of mAb development. ![Distribution of the 34 antibodies in the Antibody Array](https://www.sigmaaldrich.com/content/dam/cms-commons/sigmaaldrich/marketing/global/images/technical-documents/articles/protein-biology/elisa/array-bridge-antibody-structure-chains.jpg "Distribution of the 34 antibodies in the Antibody Array") __Distribution of the 34 antibodies in the Antibody Array.__ The pAb array employed by PCA technology covers the amino acid sequence of the entire mAb. * * *   ## [](https://www.sigmaaldrich.com)Utilizing PCA ELISAs to analyze HOS for process development When establishing a mAb manufacturing process, various conditions require careful optimization. Changes originating from cell line engineering, media and additive selections, and process development may result in changes to the HOS of a therapeutic mab. The following data, generated using our RituBridge PCA ELISA, show the effects of a variety of harsh conditions – oxidation, heat and high pH - on the HOS of the mAb Rituxan, which is used to treat various forms of CD20-positive non-Hodgkin’s lymphoma. While all three conditions caused the mAb to unfold, the pattern of unfolding was markedly different in each case, giving rise to a different HOS fingerprint under each condition tested. ![The effect of oxidation, heat and pH change on Rituxan, measured using the RituBridge PCA ELISA 1 (of 3). Spikes in optical density occur when normally inaccessible epitopes become exposed, and are indicative of changes in HOS.](https://www.sigmaaldrich.com/content/dam/cms-commons/sigmaaldrich/marketing/global/images/technical-documents/articles/protein-biology/elisa/effect-of-oxidation.jpg "The effect of oxidation, heat and pH change on Rituxan, measured using the RituBridge PCA ELISA 1 (of 3). Spikes in optical density occur when normally inaccessible epitopes become exposed, and are indicative of changes in HOS.") The effect of oxidation, heat and pH change on Rituxan, measured using the RituBridge PCA ELISA 1 (of 3). Spikes in optical density occur when normally inaccessible epitopes become exposed, and are indicative of changes in HOS. * * *   ## [](https://www.sigmaaldrich.com)Utilizing PCA ELISAs to analyze HOS for FDA submission In addition to evaluating the effect of physicochemical conditions on a mAb, PCA ELISAs can also be used to compare a biosimilar to multiple lots of an originator molecule. The data below clearly illustrates excellent similarity of a candidate biosimilar to its innovator with only potential deviation at Ab region 9. It is important to note that although a biosimilar may demonstrate a different HOS signature to the originator molecule, these changes may not always be clinically relevant. PCA ELISA data adds significant value to the evidence which is required to support an FDA submission. ![Comparison of a biosimilar to five different lots of an originator molecule illustrates four regions](https://www.sigmaaldrich.com/content/dam/cms-commons/sigmaaldrich/marketing/global/images/technical-documents/articles/protein-biology/elisa/comparison-biosimilars.jpg "Comparison of a biosimilar to five different lots of an originator molecule illustrates four regions") Comparison of a biosimilar to five different lots of an originator molecule illustrates four regions (5, 9, 17 and 30) where performance deviances may be present. * * *   ## [](https://www.sigmaaldrich.com)InnoPlex for high-throughput PCA in novel mAb development InnoPlex is a PCA that specifically targets novel therapeutic mAbs based on the conserved structure of IgG1 from a CHO cell line. While each of the PCA ELISA formats allows three compounds to be measured in parallel, we have increased this assay’s throughput to approximately 45 compounds per plate in duplicate by developing a multiplexed methodology known as InnoPlex. InnoPlex incorporates Luminex® Corporation’s xMAP® technology with the InnoBridge ELISA to allow simultaneous detection of multiple analytes using specialized microspheres color-coded with varying combinations of dyes. By immobilizing the pAbs on the surface of these beads it is now possible to screen each of the 34 target epitopes concurrently within a single well of a 96-well plate. ![RituPlex and InnoPlex, high-throughput PCAs.](https://www.sigmaaldrich.com/content/dam/cms-commons/sigmaaldrich/marketing/global/images/technical-documents/articles/protein-biology/elisa/array-bridge-xmap-workflow.jpg "RituPlex and InnoPlex, high-throughput PCAs.") * * * Example data from the multiplexing of Ritubridge & InnoBridge to become RituPlex and InnoPlex, high-throughput PCAs. #### Biosimilar Candidate Stressed Under Acidic and Basic Conditions ![Performance of the RituBridge ELISA antibodies 1-34, multiplexed with xMAP technology (RituPlex), control known Biosimilar Mab treated at low pH.](https://www.sigmaaldrich.com/content/dam/cms-commons/sigmaaldrich/marketing/global/images/technical-documents/articles/protein-biology/elisa/biosimilar-candidate-stressed.jpg "Performance of the RituBridge ELISA antibodies 1-34, multiplexed with xMAP technology (RituPlex), control known Biosimilar Mab treated at low pH.") * * * Performance of the RituBridge ELISA antibodies 1-34, multiplexed with xMAP technology (RituPlex), control known Biosimilar Mab treated at low pH. #### Control vs. pH3 ![Change detected in a new therapeutic Mab (unknown biosimilar) under pH induced stress utilizing the INNOPLEX multiplex PCA assay on Luminex xMAP™ Technology.](https://www.sigmaaldrich.com/content/dam/cms-commons/sigmaaldrich/marketing/global/images/technical-documents/articles/protein-biology/elisa/control-vs-ph3.jpg "Change detected in a new therapeutic Mab (unknown biosimilar) under pH induced stress utilizing the INNOPLEX multiplex PCA assay on Luminex xMAP™ Technology.") Change detected in a new therapeutic Mab (unknown biosimilar) under pH induced stress utilizing the INNOPLEX multiplex PCA assay on Luminex xMAP™ Technology. * * * The likelihood of therapeutic mAbs being immunogenic is an issue that has previously been well-documented, and the significance of this issue is exemplified in a 2018 publication by Song et al. Within their study the authors demonstrated the InnoPlex method to be suitable for HOS analysis in the development of therapeutic antibodies, generating PCA data which correlated well with protein stability results from traditional methods such as size-exclusion chromatography.5 The study authors also detected various structural differences between mAbs, with one important observation being that processing conditions resulted in antibody aggregation which caused significantly higher exposure to the antibody epitopes. They noted that this had the potential to lead to a “foreign” molecule which could cause immunogenicity. * * *   ## Related Product Sorry, an unexpected error has occurred Response not successful: Received status code 500 * * * ### References 1\. Ecker DM, Jones SD, Levine HL. 2015. The therapeutic monoclonal antibody market. mAbs. 7(1):9-14. [https://doi.org/10.4161/19420862.2015.989042](https://doi.org/10.4161/19420862.2015.989042) 2\. Center for Drug Evaluation and Research. \[Internet]. Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product:\[cited 27 Apr 2015]. Available from: [https://www.fda.gov/drugs/ guidancecomplianceregulatoryinformation/guidances/ucm290967.htm](https://www.fda.gov/drugs/%20guidancecomplianceregulatoryinformation/guidances/ucm290967.htm) 3\. Wang X, Li Q, Davies M. Development of antibody arrays for monoclonal antibody Higher Order Structure analysis. Front. Pharmacol.. 4 [https://doi.org/10.3389/fphar.2013.00103](https://doi.org/10.3389/fphar.2013.00103) 4\. FDA Advisory Committee Briefing Document. \[Internet]. CT-P13 (infliximab biosimilar), Briefing Document for the arthritis advisory committee.:\[cited 08 Feb 2016]. Available from: [https://www.fda.gov/downloads/advisorycommittees/ committeesmeetingmaterials/drugs/arthritisadvisorycommittee/ucm484860.pdf](https://www.fda.gov/downloads/advisorycommittees/%20committeesmeetingmaterials/drugs/arthritisadvisorycommittee/ucm484860.pdf) 5\. Song Y, Yu D, Mayani M, Mussa N, Li ZJ. 2018. Monoclonal antibody higher order structure analysis by high throughput protein conformational array. mAbs. 10(3):397-405. 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[Gas & Vent Filters](https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/sterile-filtration-and-bioburden-control/gas-and-vent-filters) - [Integrity Testers](https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/sterile-filtration-and-bioburden-control/integrity-testers) - [Media Filtration](https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/buffer-media-prep/media-filtration) - [Prefilters & Bioburden Control](https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/sterile-filtration-and-bioburden-control/prefilters-and-bioburden-control) - [Sterile Filters](https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/sterile-filtration-and-bioburden-control/sterile-filters) - [Ultrafiltration & Diafiltration](https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/ultrafiltration-diafiltration) - [Tangential Flow Filtration Devices](https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/ultrafiltration-diafiltration/filtration-devices) - [Tangential Flow Filtration Holders & Systems](https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/ultrafiltration-diafiltration/tangential-flow-holders-systems) - [Viral Clearance](https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/viral-clearance) - [Integrity Testers](https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/sterile-filtration-and-bioburden-control/integrity-testers) - [Virus Filter Holders & Systems](https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/viral-clearance/virus-filter-holders-and-systems) - [Virus Filters](https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/viral-clearance/virus-filters) - [Virus Inactivation](https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/viral-clearance/virus-inactivation) - [Protein Biology](https://www.sigmaaldrich.com/US/en/products/protein-biology) - [Antibodies](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies) - [Enhanced Validation Antibodies](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies/enhanced-validation-ab) - [Flow Cytometry Antibodies](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies/flow-cytometry-antibodies) - [Prestige Antibodies<sup>®</sup>](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies/prestige-antibodies) - [Primary Antibodies](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies/primary-antibodies) - [Secondary Antibodies](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies/secondary-antibodies) - [Small Pack Antibodies](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies/small-pack-antibodies) - [ZooMAb<sup>®</sup> Recombinant Antibodies](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies/zoomab-antibodies) - [Bioactive Small Molecules](https://www.sigmaaldrich.com/US/en/products/protein-biology/bioactive-small-molecules) - [Structural Genomics Consortium](https://www.sigmaaldrich.com/US/en/products/protein-biology/bioactive-small-molecules/structural-genomics-consortium) - [Duolink<sup>®</sup> PLA - Protein Interaction Technology](https://www.sigmaaldrich.com/US/en/products/protein-biology/duolink-proximity-ligation-assay) - [Immunoassay Platform Solutions](https://www.sigmaaldrich.com/US/en/products/protein-biology/immunoassay-platform-solutions) - [ELISA Kits](https://www.sigmaaldrich.com/US/en/products/protein-biology/immunoassay-platform-solutions/elisa-kits) - [MILLIPLEX<sup>®</sup> Kits](https://www.sigmaaldrich.com/US/en/products/protein-biology/immunoassay-platform-solutions/milliplex-multiplex-assays-for-luminex-technology) - [SMC<sup>™</sup> Technology](https://www.sigmaaldrich.com/US/en/products/protein-biology/immunoassay-platform-solutions/single-molecule-counting-technology) - [Protein Electrophoresis & Western Blotting](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting) - [Electrophoresis & Transfer Equipment](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting/electrophoresis-and-transfer-equipment) - [Transfer Membranes & Kits](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting/transfer-membranes-and-kits) - [Immunodetection Reagents & Substrates](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting/immunodetection-reagents-and-substrates) - [Membrane Immunodetection Devices](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting/membrane-immunodetection-devices) - [Protein Electrophoresis Gels & Buffers](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting/protein-electrophoresis-gels-and-buffers) - [Protein Electrophoresis Gel Stains](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting/protein-electrophoresis-gel-stains) - [Protein Markers](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting/protein-markers) - [Transfer Buffers & Reagents](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting/transfer-buffers-and-reagents) - [Proteins & Enzymes](https://www.sigmaaldrich.com/US/en/products/protein-biology/proteins-and-enzymes) - [Albumins & Transport Proteins](https://www.sigmaaldrich.com/US/en/products/cell-culture-and-analysis/cell-culture-supplements-and-reagents/albumins-and-transport-proteins) - [Coenzymes](https://www.sigmaaldrich.com/US/en/products/chemistry-and-biochemicals/biochemicals/coenzymes) - [Detection Substrates & Enzymes](https://www.sigmaaldrich.com/US/en/products/protein-biology/proteins-and-enzymes/detection-substrates-and-enzymes) - [Drug Analysis Enzymes](https://www.sigmaaldrich.com/US/en/products/protein-biology/proteins-and-enzymes/drug-analysis-enzymes) - [Glycobiology Profiling Tools](https://www.sigmaaldrich.com/US/en/products/protein-biology/proteins-and-enzymes/glycosidases) - [Nucleases](https://www.sigmaaldrich.com/US/en/products/protein-biology/proteins-and-enzymes/nucleases) - [Proteases](https://www.sigmaaldrich.com/US/en/products/protein-biology/proteins-and-enzymes/proteases) - [Tissue Dissociation](https://www.sigmaaldrich.com/US/en/products/protein-biology/proteins-and-enzymes/tissue-dissociation) - [Protein Mass Spectrometry](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-mass-spectrometry) - [Protein Purification Chromatography](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-purification-chromatography) - [Antibody Protein Purification](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep/antibody-protein-purification) - [Biotinylated Protein Purification](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep/biotinylated-protein-purification) - [FLAG<sup>®</sup> Purification](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep/flag-purification) - [Recombinant/Fusion Tag Protein Purification](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep/recombinant-fusion-tag-protein-purification) - [Protein Sample Prep](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep) - [Amicon<sup>®</sup> Centrifugals](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep/amicon-centrifugals) - [Antibody Protein Purification](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep/antibody-protein-purification) - [Biotinylated Protein Purification](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep/biotinylated-protein-purification) - [FLAG<sup>®</sup> Purification](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep/flag-purification) - [Inhibitor Cocktails](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep/inhibitor-cocktails) - [Laboratory Concentration Devices](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep/laboratory-concentration-devices) - [Laboratory Dialysis & Diafiltration Devices](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep/laboratory-dialysis-and-diafiltration-devices) - [Recombinant/Fusion Tag Protein Purification](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep/recombinant-fusion-tag-protein-purification) - [Subcellular Fractionation Reagents](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep/subcellular-fractionation-reagents) - [Whole Cell Lysis Reagents & Enhancers](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-sample-prep/whole-cell-lysis-reagents-and-enhancers) - [Water Purification](https://www.sigmaaldrich.com/US/en/products/water-purification) - [Milli-Q<sup>®</sup> Benchtop Water Purification Systems](https://www.sigmaaldrich.com/US/en/products/water-purification/milli-q-benchtop-water-purification-systems) - [Milli-Q<sup>®</sup> High-Flow Water Purification Systems](https://www.sigmaaldrich.com/US/en/products/water-purification/milli-q-high-flow-water-purification-systems) - [Milli-Q<sup>®</sup> Clinical Water Purification Systems](https://www.sigmaaldrich.com/US/en/products/water-purification/milli-q-clinical-water-purification-systems) - [Milli-Q<sup>®</sup> Consumables](https://www.sigmaaldrich.com/US/en/products/water-purification/milli-q-consumables) - [Milli-Q<sup>®</sup> Accessories](https://www.sigmaaldrich.com/US/en/products/water-purification/milli-q-accessories) - Applications - [Analytical Chemistry](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry) - [Atomic Spectroscopy](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/atomic-spectroscopy) - [Calibration, Qualification, Validation](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/calibration-qualification-and-validation) - [Gas Chromatography (GC)](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/gas-chromatography) - [Liquid Chromatography](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/liquid-chromatography) - [Large Molecule HPLC](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/liquid-chromatography/large-molecule-hplc) - [Low Pressure Liquid Chromatography](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/liquid-chromatography/low-pressure-liquid-chromatography) - [Small Molecule HPLC](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/liquid-chromatography/small-molecule-hplc) - [Mass Spectrometry (MS)](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/mass-spectrometry) - [Nuclear Magnetic Resonance (NMR)](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/nuclear-magnetic-resonance) - [Photometry & Reflectometry](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/photometry-and-reflectometry) - [Sample Preparation](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/sample-preparation) - [Sample Filtration](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/sample-preparation/filtration) - [Sample Purification](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/sample-preparation/purification) - [QuEChERS Sample Preparation](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/sample-preparation/quechers) - [Solid Phase Extraction](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/sample-preparation/solid-phase-extraction) - [Solid Phase Microextraction](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/sample-preparation/solid-phase-microextraction) - [Thin Layer Chromatography (TLC)](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/thin-layer-chromatography) - [Titration & Karl Fischer](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/titration-and-karl-fischer) - [Water for Analytical Chemistry](https://www.sigmaaldrich.com/US/en/applications/water-purification/water-analytical-chemistry) - [Wet Chemical Analysis](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/wet-chemical-analysis) - [Cell Culture & Analysis](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis) - [Cell Analysis](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-analysis) - [Cell-based Assays](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-analysis/cell-based-assays) - [Cell Counting & Health analysis](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-analysis/cell-counting-and-health-analysis) - [Imaging Analysis & Live Cell Imaging](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-analysis/imaging-analysis-and-live-cell-imaging) - [Cell Culture by Cell Type](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-cell-type) - [Mammalian Cell Culture](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-cell-type/mammalian-cell-culture) - [Microbial Cell Culture](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-cell-type/microbial-cell-culture) - [Plant Tissue Culture](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-cell-type/plant-tissue-culture) - [Primary Cell Culture](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-cell-type/primary-cell-culture) - [Stem Cell Culture](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-cell-type/stem-cell-culture) - [Cell Culture by Technique](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-technique) - [3D Cell Culture](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-technique/3d-cell-culture) - [Cell Culture Media Preparation](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-technique/cell-culture-media-preparation) - [Cell Growth & Maintenance](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-technique/cell-growth-and-maintenance) - [Transfection & Gene Editing](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-technique/transfection-and-gene-editing) - [Cell Culture for Manufacturing](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-for-manufacturing) - [Cell Culture Troubleshooting](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-troubleshooting) - [Chemistry & Synthesis](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis) - [ADC & Bioconjugation](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis/adc-and-bioconjugation) - [Lead Discovery](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis/lead-discovery) - [Peptide Synthesis](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis/peptide-synthesis) - [Protein Degradation](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis/protein-degradation) - [Reaction Design & Optimization](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis/reaction-design-and-optimization) - [Synthetic Methods](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis/synthetic-methods) - [C-H Functionalization](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis/synthetic-methods/ch-functionalization) - [Cross Coupling](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis/synthetic-methods/cross-coupling) - [Fluorination](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis/synthetic-methods/fluorination) - [Metathesis](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis/synthetic-methods/metathesis) - [Organic Reaction Toolbox](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis/synthetic-methods/organic-reaction-toolbox) - [Photocatalysis](https://www.sigmaaldrich.com/US/en/applications/chemistry-and-synthesis/synthetic-methods/photocatalysis) - [Clinical & Diagnostics](https://www.sigmaaldrich.com/US/en/applications/clinical-testing-and-diagnostics-manufacturing) - [Bacteriology](https://www.sigmaaldrich.com/US/en/applications/clinical-testing-and-diagnostics-manufacturing/bacteriology) - [Blood Typing](https://www.sigmaaldrich.com/US/en/applications/clinical-testing-and-diagnostics-manufacturing/blood-typing) - [Clinical & Forensics Testing](https://www.sigmaaldrich.com/US/en/applications/clinical-testing-and-diagnostics-manufacturing/clinical-and-forensic-testing) - [Cytology & Cytodiagnosis](https://www.sigmaaldrich.com/US/en/applications/clinical-testing-and-diagnostics-manufacturing/cytology-and-microscopy) - [Diagnostic Immunohistochemistry](https://www.sigmaaldrich.com/US/en/applications/clinical-testing-and-diagnostics-manufacturing/diagnostic-immunohistochemistry) - [Hematology](https://www.sigmaaldrich.com/US/en/applications/clinical-testing-and-diagnostics-manufacturing/hematology) - [Histology/Histopathology](https://www.sigmaaldrich.com/US/en/applications/clinical-testing-and-diagnostics-manufacturing/histology) - [IVD Manufacturing](https://www.sigmaaldrich.com/US/en/applications/clinical-testing-and-diagnostics-manufacturing/ivd-manufacturing) - [Water for Clinical Diagnostics](https://www.sigmaaldrich.com/US/en/applications/water-purification/water-clinical-diagnostics) - [Environmental & Cannabis Testing](https://www.sigmaaldrich.com/US/en/applications/environmental-testing-and-industrial-hygiene) - [Air Sampling & Monitoring](https://www.sigmaaldrich.com/US/en/applications/environmental-testing-and-industrial-hygiene/air-testing) - [Cannabis Testing](https://www.sigmaaldrich.com/US/en/applications/environmental-testing-and-industrial-hygiene/cannabis-testing) - [Cannabinoids & Potency](https://www.sigmaaldrich.com/US/en/applications/environmental-testing-and-industrial-hygiene/cannabis-testing/cannabinoid-profiling-potency-testing) - [Pesticides & Mycotoxins](https://www.sigmaaldrich.com/US/en/applications/environmental-testing-and-industrial-hygiene/cannabis-testing/pesticides-mycotoxins-in-cannabis) - [Terpenes](https://www.sigmaaldrich.com/US/en/applications/environmental-testing-and-industrial-hygiene/cannabis-testing/terpenes-cannabis) - [Drinking Water Testing​](https://www.sigmaaldrich.com/US/en/applications/environmental-testing-and-industrial-hygiene/drinking-water-testing) - [Soil, Solid Waste, & Groundwater Testing](https://www.sigmaaldrich.com/US/en/applications/environmental-testing-and-industrial-hygiene/soil-solid-waste-groundwater-testing) - [Waste Water & Process Water Testing](https://www.sigmaaldrich.com/US/en/applications/environmental-testing-and-industrial-hygiene/waste-water-and-process-water-testing) - [Food & Beverage Testing & Manufacturing](https://www.sigmaaldrich.com/US/en/applications/food-and-beverage-testing-and-manufacturing) - [Chemical Analysis](https://www.sigmaaldrich.com/US/en/applications/food-and-beverage-testing-and-manufacturing/chemical-analysis-for-food-and-beverage) - [Flavor & Fragrance Formulation](https://www.sigmaaldrich.com/US/en/applications/food-and-beverage-testing-and-manufacturing/flavor-and-fragrance-formulation) - [Microbiological Analysis](https://www.sigmaaldrich.com/US/en/applications/food-and-beverage-testing-and-manufacturing/microbiological-analysis-for-food-and-beverage) - [Regulatory Compliance​](https://www.sigmaaldrich.com/US/en/applications/food-and-beverage-testing-and-manufacturing/regulatory-compliance-for-food-and-beverage) - [Genomics](https://www.sigmaaldrich.com/US/en/applications/genomics) - [Advanced Gene Editing](https://www.sigmaaldrich.com/US/en/applications/genomics/advanced-gene-editing) - [Cloning & Expression](https://www.sigmaaldrich.com/US/en/applications/genomics/cloning-and-expression) - [DNA & RNA Purification](https://www.sigmaaldrich.com/US/en/applications/genomics/dna-and-rna-purification) - [Epigenetics](https://www.sigmaaldrich.com/US/en/applications/genomics/epigenetics) - [Functional Genomics Screening](https://www.sigmaaldrich.com/US/en/applications/genomics/functional-genomics-screening) - [Gene Expression & Silencing](https://www.sigmaaldrich.com/US/en/applications/genomics/gene-expression-and-silencing) - [Next Gen Sequencing](https://www.sigmaaldrich.com/US/en/applications/genomics/next-gen-sequencing) - [Nucleic Acid Gel Electrophoresis](https://www.sigmaaldrich.com/US/en/applications/genomics/nucleic-acid-gel-electrophoresis) - 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[Biotech Resource Hub](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/biotech-resource-hub) - [Discovery](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/biotech-resource-hub/discovery) - [Pre-clinical](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/biotech-resource-hub/pre-clinical) - [Phase I-II](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/biotech-resource-hub/phase-i-ii) - [Phase III and Manufacturing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/biotech-resource-hub/phase-iii-and-manufacturing) - [Regulatory](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/biotech-resource-hub/regulatory) - [Startup Programs](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/biotech-resource-hub/startup-programs) - 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[Sterile Filtration Strategies](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/classical-pharma-manufacturing/sterile-filtration-strategies) - [Gene Therapy Manufacturing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/gene-therapy-manufacturing) - [Viral Vector Upstream Processing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/gene-therapy-manufacturing/viral-vector-upstream-processing) - [Viral Vector Downstream Processing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/gene-therapy-manufacturing/viral-vector-downstream-processing) - [Viral Vector Formulation & Final Fill](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/gene-therapy-manufacturing/viral-vector-formulation-and-final-fill) - [Viral Vector Characterization & Biosafety Testing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/gene-therapy-manufacturing/viral-vector-characterization-and-biosafety-testing) - [Viral Vector Contract Development & Manufacturing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/gene-therapy-manufacturing/viral-vector-contract-development-and-manufacturing) - [Pharma Analysis & QC](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/pharmaceutical-analysis-quality-control) - [Biologics & Biosimilars Characterization](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/pharmaceutical-analysis-quality-control/biologics-biosimilars-characterization) - [Compendial Testing & Regulatory Guidance](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/pharmaceutical-analysis-quality-control/compendial-testing-regulatory-guidance) - [Small Molecules Analysis & Quality Control (QC)](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/pharmaceutical-analysis-quality-control/small-molecules-analysis-quality-control) - [Sterile & Aseptic Sampling](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/sampling) - [Vaccine Manufacturing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/vaccine-manufacturing) - [Cell-Based Vaccine Manufacturing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/vaccine-manufacturing/cell-based-vaccine-manufacturing) - [mRNA Vaccine Manufacturing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/vaccine-manufacturing/mrna-vaccines-process-manufacturing) - [pDNA Vaccine Manufacturing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/vaccine-manufacturing/plasmid-dna-vaccines-manufacturing) - [Protein Subunit Vaccine Manufacturing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/vaccine-manufacturing/protein-subunit-vaccine-manufacturing) - [Viral-like Particles Vaccine Manufacturing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/vaccine-manufacturing/viral-like-particles-vaccine-manufacturing) - [Viral Vector Vaccine Manufacturing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/vaccine-manufacturing/viral-vector-vaccine-manufacturing) - [Protein Biology](https://www.sigmaaldrich.com/US/en/applications/protein-biology) - [ELISA](https://www.sigmaaldrich.com/US/en/applications/protein-biology/elisa) - [Enzyme Activity Assays](https://www.sigmaaldrich.com/US/en/applications/protein-biology/enzyme-activity-assays) - [Flow Cytometry](https://www.sigmaaldrich.com/US/en/applications/protein-biology/flow-cytometry) - [Gel Electrophoresis](https://www.sigmaaldrich.com/US/en/applications/protein-biology/gel-electrophoresis) - [Immunohistochemistry](https://www.sigmaaldrich.com/US/en/applications/protein-biology/immunohistochemistry) - [Interrogation of Protein Pathways](https://www.sigmaaldrich.com/US/en/applications/protein-biology/interrogation-protein-pathways) - [Lysis & Protein Extraction](https://www.sigmaaldrich.com/US/en/applications/protein-biology/lysis-and-protein-extraction) - [Protein & Nucleic Acid Interactions](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-and-nucleic-acid-interactions) - [Protein Concentration & Buffer Exchange](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-concentration-and-buffer-exchange) - [Protein Expression](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-expression) - [Protein Labeling & Modification](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-labeling-and-modification) - [Protein Pulldown](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-pulldown) - [Protein Purification](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-purification) - [Protein Quantitation](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-quantitation) - [Protein Structural Analysis](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-structural-analysis) - [Western Blotting](https://www.sigmaaldrich.com/US/en/applications/protein-biology/western-blotting) - [Protein Mass Spectrometry](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-mass-spectrometry) - [Research & Disease Areas](https://www.sigmaaldrich.com/US/en/applications/research-disease-areas) - [Cancer Research](https://www.sigmaaldrich.com/US/en/applications/research-disease-areas/cancer-research) - [Cell & Developmental Biology Research](https://www.sigmaaldrich.com/US/en/applications/research-disease-areas/cell-and-developmental-biology-research) - [Cell Signaling](https://www.sigmaaldrich.com/US/en/applications/research-disease-areas/cell-signaling) - [Glycobiology](https://www.sigmaaldrich.com/US/en/applications/research-disease-areas/glycobiology) - [Metabolomics Research](https://www.sigmaaldrich.com/US/en/applications/research-disease-areas/metabolomics-research) - [Neuroscience Research](https://www.sigmaaldrich.com/US/en/applications/research-disease-areas/neuroscience-research) - [Pharmacology & Drug Discovery Research](https://www.sigmaaldrich.com/US/en/applications/research-disease-areas/pharmacology-and-drug-discovery-research) - [Water Purification](https://www.sigmaaldrich.com/US/en/applications/water-purification) - [Water for Analytical Chemistry](https://www.sigmaaldrich.com/US/en/applications/water-purification/water-analytical-chemistry) - [Water for Cell & Molecular Biology](https://www.sigmaaldrich.com/US/en/applications/water-purification/water-cell-molecular-biology) - [Water for Clinical Diagnostics](https://www.sigmaaldrich.com/US/en/applications/water-purification/water-clinical-diagnostics) - [Understanding Lab Water](https://www.sigmaaldrich.com/US/en/applications/water-purification/understanding-lab-water) - Services - [Contract Manufacturing](https://www.sigmaaldrich.com/US/en/services/contract-manufacturing) - [ADC & Bioconjugation](https://www.sigmaaldrich.com/US/en/services/contract-manufacturing/adc-bioconjugation) - [Diagnostic OEM & CMO Services](https://www.sigmaaldrich.com/US/en/services/ivd-development-manufacturing/diagnostic-oem-cmo) - [mRNA & LNP](https://www.sigmaaldrich.com/US/en/services/contract-manufacturing/mrna-and-lnp-formulation-ctdmo-services) - [Lipids CDMO Services](https://www.sigmaaldrich.com/US/en/services/contract-manufacturing/mrna-and-lnp-formulation-ctdmo-services/lipids-cdmo-services) - [Lipid Nanoparticle CDMO Service](https://www.sigmaaldrich.com/US/en/services/contract-manufacturing/mrna-and-lnp-formulation-ctdmo-services/lipid-nanoparticle-cdmo-services) - [Small Molecule](https://www.sigmaaldrich.com/US/en/services/contract-manufacturing/small-molecule) - [Activated Polyethylene Glycol (PEGs)](https://www.sigmaaldrich.com/US/en/services/contract-manufacturing/peg) - 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