ClinProt Enhancements by Bruker Life Science Mass Spectrometry

Expanded ClinProt Magnetic Bead Arrays

Our ClinProt magnetic bead product line has been expanded significantly to now include not only various hydrophobic bead types, but also weak anion exchange (WAX) beads, weak cation exchange (WCX) beads, as well as immobilized metal affinity capture (IMAC) beads with both copper and iron variants. This comprehensive offering of semi-selective magnetic bead arrays for sample clean-up provides clinical researchers with a flexible tool-kit for biomarker discovery and assay protocol optimization.

The ClinProt magnetic bead arrays have large surface areas for excellent sensitivity, allow straight-forward robust automation of solution-based sample preparation protocols, and are inherently scalable and quite reproducible, in contrast to chip-based surface methods for sample preparation. The cost per assay using ClinProt magnetic bead arrays has dropped to $2 per assay, thus allowing economic larger validation studies, which will be needed for many recently discovered putative multi-biomarker sets.

Antibody Magnetic Bead Arrays

Our new MagAB™ nano-particle is a key addition to the ClinProt product line which allows researchers to attach antibodies, antibody fragments, peptides, DNA or ligands to the magnetic bead surface. These MagAB beads are useful for researchers looking for specific proteins or binding partners, for biologically selective and very sensitive specific clinical assays. The MagAB beads are also useful as a more generally applicable tool for research and discovery in interaction proteomics.

The flexibility of the MagAB beads allows ClinProt users to capture specific populations of proteins and peptides based upon the specificity of the antibody interaction. In the case of antibody cross-reactivity, researchers can take advantage of the compound-specific read-out by mass spectrometry to identify multiple antibody binding partners, such as isoforms, based on the accurate mass obtained by MALDI-TOF, or potentially even based on structural information from de novo sequencing, if a MALDI-TOF/TOF is used as part of the ClinProt platform.

ClinProt 3D Platform

For metabolic or peptide/protein biomarker discovery, Bruker Daltonics introduces a novel ClinProt 3D research platform, which utilizes high-resolution HPLC followed by high-mass accuracy MS, typically using ESI-TOF, or even ESI-FTMS, for the measurement of potentially thousands of molecules in human body fluids or tissues.

Our new ClinProTools™ 3D software is ideal for biomarker discovery from high-resolution LC runs. With the highly intuitive and simple-to-use ClinProTools software, researchers now can visualize a virtual gel, in 3D stacking or contour plot mode, or view the data in an average spectra view. The software has added capability, utilizing multiple algorithms for mining information which does not become obvious upon initial visual inspection. Either approach reviews the spectra and looks for differences that allow the ClinProTools software to group the data into distinct families: for example, drug treated versus non-treated samples, responders versus non-responders, or normal versus affected patients.

ClinProt ID for Biomarker Identification

The new ClinProt ID capability combines magnetic bead separation and AnchorChip® sample concentration technology for biomarker identification either by MALDI-TOF/TOF analysis directly, in the case of peptide biomarkers, or by enzymatic digestion, followed by MALDI-TOF/TOF analysis, in the case of protein biomarkers. ClinProt ID allows a clear scientific understanding of putative biomarkers, in order to assess their potential biological and medical relevance.

Biomarker identification is becoming very important for two reasons: first to obtain strong intellectual property protection for newly discovered biomarkers, and second to provide more detailed information to establish biological relevance of biomarkers for future FDA applications on new protein molecular diagnostics tests. ClinProt ID further enhances the confidence in biomarker discovery and future diagnostics assays by utilizing both the pattern recognition approach as well as peptide or protein identification.

New ClinProTools Capabilities and Algorithms

Our ClinProTools software developers have added several new capabilities, particularly to improve data quality prior to information mining. Data noise reduction is a primary issue when developing models and looking at low expression profiles. This week, Bruker Daltonics will present a poster at ASMS specifically addressing our novel solutions to this issue with the title: "e;Wavelet Transformation applied to the Analysis of Clinical Proteomics Mass Spectra"e;.

Mark Flocco, Business Development Manager for Clinical Proteomics and Biomarker Discovery, commented: "Our integrated ClinProt platform set prepares biological fluids or tissue samples, utilizing our proprietary functionalized magnetic bead array technology and our unique AnchorChip technology. The high-quality, high-resolution ClinProt profiling spectra have been shown to be highly reproducible, an essential requirement to develop future diagnostic assays for protein molecular diagnostics. This high quality data is then imported into our bioinformatics software, ClinProTools™, which offers multiple visualization approaches for interpreting large data sets, as well as multiple algorithmic analyses for cluster and classification work. The models generated can be applied to unknown sample sets for further analysis."

Frank H. Laukien, Ph.D., President and CEO, stated: "These are major new capabilities for our integrated ClinProt solution, which we believe will very substantially increase the ability of clinical researchers to discover, validate and identify new multi-marker sets for clinical proteomics. In today's much more demanding biomarker discovery environment, this should enable them to publish their results with more confidence, obtain strong patent protection, conduct larger inter-laboratory studies, and eventually develop future protein molecular diagnostics tests for submission to the FDA. We believe that our ClinProt platform is now the most comprehensive, flexible and powerful next-generation solution for metabolic, peptide and protein biomarker discovery and validation with confidence."