Tuesday, July 26, 2011

A New Level in Next Generation Sequencing

The capacities of modern next generation sequencing (NGS) technologies have been slingshot to a new level during the past two years. The remaining limitations for large-scale molecular profiling, which include throughput, cost, data management and automation issues, can now be circumvented by a brand new technology, enabling deep re-sequencing of selected parts of the genome. Febit is offering this new powerful technological solution, which provides all the required features: robust automation, simple assay workflows and manageable data pipelines.

This highly automated and capable technology from febit is called HybSelect. The extended multiplexing capability and high degree of automation of HybSelect make it an affordable way to conduct NGS for large cohort studies of hundreds or thousands of patient samples. Such comparative and meaningful large-scale studies can help the pharmaceutical and diagnostic industry to develop enhanced knowledge about the genesis and progress of diseases. The improved understanding resulting from individual molecular profiling holds the potential for further personalized therapies.

Sequence capture

The core of HybSelect is a highly efficient microfluidic biochip that uses robust automation, fast processing and high-density microarrays as a binding matrix. The biochip is synthesized with capture probes (oligonucleotides) specific to the genomic region of interest in a particular research project. They serve as bait for the desired DNA-fragments. After all non-hybridized fragments are washed away, the enriched target DNA is eluted and can be directly applied to NGS platforms.

The microfluidic chip architecture reduces the volume and amount of DNA needed for NGS. The eluted DNA can be directly applied to next generation sequencers and enables studies without the bias of PCR-amplification or other methods currently on the market.

HybSelect offers unmet advantages: short hands-on time (minutes instead of hours), a high degree of reproducibility and unmatched parallelism in selecting several genomic samples at a time.

Recent applications

In several biomedical studies of early access customers over the past months, HybSelect demonstrated superb enrichment factors and deep sequencing coverage for a broad range of diseases and cancer-related human genes and genomic regions.

Scientists at the TGen Institute in Phoenix, Arizona are currently using HybSelect's sequence capture technology to discover diagnostic biomarkers for Alzheimer's disease, developing a set of markers for monitoring disease progression.

Researchers at the German Cancer Research Center in Heidelberg, Germany, used HybSelect to perform a NGS study on samples from approximately 200 patients. They identified a specific microRNA marker associated with doubled survival rates in a certain type of cancer. An ongoing study at the Saarland University, Germany, investigates malignant brain cancer by deep-sequencing of the 100 most relevant genes.

HybSelect will be one of the workhorses for the detection of novel tumor markers at the newly developed Biomarker Discovery Center (BDC) in Heidelberg, Germany. The BDC is currently working on about 20 oncology and five inflammatory disease-related projects that are using febit's technology together with ABI and Illumina next generation sequencers.

Moving forward

HybSelelect will allow the characterization of exons from hundreds of genes involved in complex diseases. Currently, the identification of new tumor-specific mutations as well as aberrant non-coding RNAs (ncRNA), like microRNAs, is underway. The determination of novel markers in comprehensive large-scale studies will be an important step towards standardized diagnostic assays as well as the development of new 'personalized' pharmaceuticals and the investigation of new therapeutic delivery models.

Febit will stay at the forefront of cancer research with the 2 Mb exon cancer biochip released this summer and a 30 Mb biochip planned for release in 2010. The demand for comprehensive and effective technologies like HybSelect will grow dramatically alongside the expanding understanding of biologic pathways and genetic regulation


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