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Next Generation Genomics and Bioinformatics Services, Bioprocessing Optimization and Diagnostic Products
Services and Diagnostic ProductsArrayXpress has a variety of services related to biological sciences and bioinformatics. We prefer to perform these services as a contract research partner. Although we offer end-to-end solutions, often a partner has some internal capability. By working hand in glove with our partner we can develop the most effective, efficient, and cost effective solution. We also perform traditional "over the wall" contracts where we are provided materials but not integrated into the development of the biological hypothesis. Even in these cases, we do require participation in the design of the experiment so that we can perform it with the most statistical significance at the lowest cost. We have many, many examples of where our bioinformatics team has been able to design a more powerful AND less expensive experiment that the client proposed. We also developed diagnostic applications across a wide number of applications, from phitosanitary, to tumor characterization, to drug resistance susceptibility. Nearly all of these projects are developed with partners who wish to build on their intellectual property or domain expertise. Please see a more detailed description of our services below: Genomics ServicesBioinformatics CapabilitiesBioprocess OptimizationDiagnostics ApplicationsGenomics ServicesArrayXpress offers a wide variety of genomics services to our partners and clients. For a listing of some of the latest technology we are applying, please visit our Technology page. It is important to remember however that you can not merely take new tools and apply them to old processes. One of the greatest strenghts of ArrayXpress is our team's ability to evaluate the latest technology, processes, methods, and techniques, then determine how they can most effectively and cost efficiently be applied to solve our partners issues. A new technology ALWAYS requires optimization and new process for each field of use. That is our job. Our team spends thousands of hours per year reviewing the latest research literature, attending technical conferences in all of our fields of expertise, and evaluating and optimizating new technologies. We bring this expertise to work for you so that you can focus on the biological questions that are important to your organization. The performance advantage of cutting edge bioinformaticsApplying statistics to a standardized experiment is like performing a postmortem on a dead body. To be effective, the experiment must be carefully designed to match both the biological question(s) and the available bioinformatics capabilities. At ArrayXpress, we have the top talent in the field of bioinformatics and we design experiments with both efficiency and the biological hypothesis in mind.
ArrayXpress works with the latest in cluster and cloud computing technologies to provide the optimal computational power, security and price. Each partner or clients data is stored on a seperate server that if desired can be owned by the client. Bioinformatics Capabilities
ArrayXpress has developed world leading capabilites in bioinformatics. In addition to our team, we have close alliances with the bioinformatics teams at NC State University and SAS. It has been our consistent experience in project after project that we are able to design better experiments than our competition or in-house client teams. Our designs result in not only more statistically powerful results, but are better aimed at answering the biological hypothesis being explored. They also usually wind up costing less to implement that the more cumbersome and less effective designs often found in standard packages, particularly in the software provided by the equipment manufacturers. Bioprocessing optimization
ArrayXpress provides research and development services based on first-in-class NGS and bioinformatics to increase the performance, speed, and cost effectiveness of bioprocess development and biomanufacturing. The flow of applications and techniques we provide to partners are presented in the figure below. NGS technologies provide an eagle’s-eye view into cellular metabolism and physiology, under changing growth and production conditions, applicable from the selection of a specific cell or microorganism, through bioprocess development/scale-up, and into commercial manufacturing. ArrayXpress has developed a number of applications that lead to effective, evidence-based bioprocess optimization. Three key applications in the biotechnology sector are: (i) strain/cell line development and improvement; (ii) process optimization, and (iii) commercial manufacturing. Bioinformatics plays a key role in the analysis and mining of large amounts of data. Sequencing genomic DNA, mRNA (cDNA) and/or microRNAs from production strains or cell lines provides reference genomic information that has a direct impact on understanding the overall biology of an organism. Specifically, it enables the understanding of gene regulation and regulatory networks (e.g., the role of non-coding regulatory RNA elements in gene regulation) and genome structure and dynamics (chromosomal rearrangements and alternative splicing). Understanding the genetic architecture of a production cell/organism lays the foundation for biology-guided process development and phenotype improvement. To develop functional gene-based markers, RNA-seq of contrasting production conditions or among strains/cell lines can be used to identify candidate genes involved in the metabolism of the production phenotype. Such genetic markers can then be used as molecular fingerprints to assist with the strain/cell line selection and guide the earlier and later stages of bioprocess development, optimization, scale-up and manufacturing. Active monitoring throughout the process life cycle maximizes product yield and quality while minimizing inputs and costs. Coupled to pathway analysis, RNA-seq of production strains/cell lines in different process and manufacturing conditions can identify key metabolic pathways and the regulation thereof and to identify negative activities that decrease production. The ability to zero in on the control points governing metabolic flow towards increased production allows for process manipulation (for instance, media composition, growth conditions, and feed strategy) based on focused empirical knowledge instead of large designs of experiments and brute force methods. This provides critical knowledge for targeted cell improvement, in a systems metabolic engineering strategy. Coupled to global transcription machinery engineering, RNA-seq provides a complete, quantitative view of the transcriptome and allows for the mechanistic understanding of the affected transcriptional regulatory networks. The knowledge harvested can be applied to future rounds of cell improvement towards desired production phenotypes. Better bioprocess characterization may also assist with (a) regulatory compliance, particularly related to FDA biopharmaceutical initiatives on Quality by Design (QbD) and Process Analytical Technology (PAT) and (b) contribute to the protection of valuable intellectual property. diagnostics applicationsCurrent diagnostic systems on the market have two significant shortcomings. First, they only test for one or a limited number of pathogen(s)/disease(s) at a time and, second, they must have an abundance of pathogen present to be detected. The first limitation makes current diagnostic tests impractical for large-scale preventative screening and the second requires the pathogen to be firmly entrenched and usually with the host organism manifesting symptoms before detection is possible (in some cases, current diagnostic systems can only accurately detect a specific pathogen after the host has already died). Both of these limitations are overcome by ArrayXpress’ novel AXPressDX™ technology platform. The AXPressDX™ detection assay is a platform independent assay that provides for sequence-specific molecular recognition. Using single nucleotide polymorphism (SNP) detection, it significantly increases sensitivity and multiplexing capabilities without limiting the range of potential targets. Another major advantage of our diagnostic detection technology is that sequences for target recognition and results intepretation are independent, thus making the assay easily modifiable and extendable to include new targets. In addition, one of the main objectives during the development process of our AXPressDX™ detection assay was to create a diagnostic assay that was platform independent, to be used with the platform of choice of our customers. The AXPressDX™ detection assay is fast, cost effective and easy to use. Currently, we have optimized and integrated the assay with two different platforms: in situ synthesized arrays with fluorescent or electrochemical detection using the Combimatrix technology and bead-based arrays with fluorescent detection using the Illumina VeraCode technology. This technology serves as a platform for a portfolio of novel diagnostic products and services. In our product offerings, our AXPressDX™ kits will contain all the chemicals and molecular reagents necessary to perform our assay. A detailed protocol will be provided along, with illustrations to facilitate the visualization of critical steps discussed below, according to the customer’s choice of read-out platform. ArrayXpress is also committed to bringing to market a comprehensive diagnostic testing service, as well as several diagnostic product test kits currently being developed. Our goal is to deliver rapid, multi-pathogen, microarray-based commercial diagnostic test kits and services. Our citizens, the Government and industry all have a critical need for accurate and timely diagnostic detection. The AX diagnostic service and commercial test kits will meet this vital and growing strategic need. Combimatrix’s in situ synthesized microarrays for fluorescent and electrochemical detection Combimatrix employs a specially modified “CMOS” semiconductor that directs the molecular assembly of specific sequences of DNA. Using specialized software, each feature on the array (a microelectrode) is digitally addressed and controls the detritylation reaction during phosphoramidite synthesis. The 4X2K slides contain four independent sectors, each comprising an independent 2,240-feature microarray. This assay read-out format easily allows four samples to be simultaneously evaluated, ideal for low through-put demand. The platform can be used with traditional fluorescent based detection chemistries as well as electrochemical detection (described in detail below). Once hybridized and washed, the slides are ready to be scanned using traditional laser scanners (for fluorescent detection) or the ElectraSense™ reader (for electrochemical detection). The ElectraSense™ microarray reader (Combimatrix, Mukiteo, WA, USA) electrochemically measures thousands of probes in less than one minute, whilst offering a dramatic increase in dynamic range, increasing the saturation limit up to 1000pM as compared to fluorescence at 500pM. Using this system we completely circumvent the use of expensive fluorescent dyes, dramatically reducing the cost per assay, as well as reducing incubation periods by 2 hours overall. This system provides an optimized and completely automated data extraction, background subtraction and data normalization solution, thus eliminating traditional time consuming grid alignment steps. Results can then be visualized in Excel for species identification. Another major advantage of the 4x2K in situ arrays is the ability to successfully strip and re-use each array (up to 4 times), making these arrays more cost-effective as part of diagnostic applications. Easy-to-Assemble: The ElectraSense™ 4X2K diagnostic array is placed inside a hybridization clamp with the semiconductor side up. The Hybridization Cap is then placed on top of the microarray with the gasket facing down and the clamp is closed. The pre-hybridization, hybridization and washing solutions are easily loaded through the portals in each chamber. Once the pre-hybridization step is completed, simply denature the AXPressDX™ clinical sample(s) and pipette the denatured target into the hybridization chamber. The array is then incubated for 1 hour at 45ºC followed by various washing steps as highlighted in the assay workflow diagram below. Preparation of the hybridized ElectraSense™ microarray for electrochemical detection involves a post-hybridization labeling step that is performed using the CombiMatrix ElectraSense™ Detection Kit. Easy-to-Analyze: To read/analyze the diagnostic array, simply open the ElectraSense® Reader to insert the microarray assembly. A special safety pin inside the clamp holder and the corresponding groove at the back side of the hybridization clamp are specially designed to ensure that the microarray assembly can only be inserted into the holder in the correct orientation. After loading the detection solution and ready to scan, gently slide the assembly all the way down into the clamp holder, and close the door and scanning is just a click away. Easy-to-Interpret Results: The ElectraSense® Reader electronically reads the data by performing amperometric detection of the current flux for each individual spot through the underlying platinum microelectrode. The resulting data provides direct numeric quantification of the hybridization signals for all spots. Thus, in contrast to fluorescent imaging, image data extraction is not required for the ElectraSense™ detection system. The ElectraSense® Software takes as input a chip design file, which gives detailed information about the placement of probes on the microarray and data from the ElectraSense® Reader. The program allows this data to be visually displayed and will produce two types of output files. An electrochemical detection file ending in (.ecd) with the complete information of the scanning and tab-delimited text files that can be easily be exported into your software of choice for data retrieval. Illumina’s VeraCode® bead technology We have successfully integrated the AXPressDX™ detection assay with Illumina’s VeraCode technology and BeadXpress Reader System, resulting in a very sensitive, high-throughput and extremely cost effective multiplex DX assay. Using their platform we leverage the power of digital holographic codes to provide a robust detection method for performing multiplex DX assays that requires high precision, accuracy, and speed. The advantages of this system include:
High Data Quality: Industry-leading measurement density and sensitivity due to inherent stringency of code detection.
Broad Multiplexing Capability: Using Illumina’s patented digital holographic coding technology, the BeadXpress Reader System enables the development of tremendous multiplexing capabilities. Assays ranging from single-plex to 384-plex per sample can be performed from a single well of a standard 96-well VeraCode Bead Plate.
Use of Codes for Increased Quality Metrics: Bead codes can be used in the assay as identifiers for internal controls, as well as for unique identifiers such as reagent lots, test kits, and sample ID.
Assay Versatility: A broad range of applications, including genotyping, gene expression, and protein-based assays can be performed on a single platform.
Dual-Color Laser Detection: The dual-color laser detection of the BeadXpress Reader enables ultimate flexibility in assay design. You can run assays using either two-color detection or single-color detection on this platform. Illumina’s Unique code and bead technology
VeraCode’s breakthrough technology is based on the use of cylindrical glass microbeads that: (1) Measure 240?m in length x 28?m in diameter and; (2) contain a unique holographic code (see picture on the left). The unique digital holographic code contained within each VeraCode microbead enables customizable tracking of multiplex assay markers and critical identifiers such as sample ID, laboratory ID, and reagent kits. Up to 24 bits of information inscribed in each code allows for an unprecedented level of error checking, improving the robustness of the optical readout process and providing a level of reliability that sets a new standard in multiplex testing. Multiplexing levels are achieved by simply pooling uniquely coded beads. A 1-to-384-plex-per-sample can be accomplished. The high-purity silica glass used to make VeraCode microbeads has physical properties that make it an ideal substrate for attachment of biomolecules. The glass purity also minimizes any fluorescent background, so there is no interference with readout, providing a highly stable platform for reliable and reproducible results. The only significant difference between the traditional microarray-based AXPressDX assay (Combimatrix and Agilent platforms) and that of the AXPressDX-Illumina assay, is that the unique capture oligonucleotides are now covalently linked to each of the cylindrical silicon microbeads, as opposed to being synthesized on the surface of the microarray. As such, high-density oligonucleotides are covalently linked to cover the entire surface area of each bead type. The VeraCode microbead DX assay provides for a highly stable platform as each assay typically includes 25 to 30 technical replicates of each bead type resulting in the generation of a particularly robust DX dataset. Using the BeadXpress System, VeraCode microbeads are (1) optically sampled up to a dozen times each, providing about 300 independent data points for each analyte; (2) randomly arrayed in the groove cell to minimize scanner errors (see figure below); and (3) are inscribed with up to 24 bits of information; the initial bits in a code sequence are used for error checking, thereby greatly improving the reliability of the readout and results.
The BeadXpress Reader Assays developed for the VeraCode microbeads are analyzed with Illumina’s patented BeadXpress Reader, a high-throughput, two-color laser detection system designed to be compatible with standard laboratory automation (see figure below).
The key features of the BeadXpress System include: - A fluidic system and reagent carrier that enable the scanning of multiple 96-well plates per day without the need to refill system buffers. - An open-platform, two-color laser detection bioassay system that supports the development of single-color assays, as well as two-color assays. - The BeadXpress reader provides for rapid sample throughput rates of 120 samples/hr at 10-plex and 80 samples/hr at 96-plex. - Sample analysis can be performed on standard 8-well strips or 96-well plates, pending on your respective throughput requirements.
Powerful and friendly analysis software One of the major advantages integrating our unique DX assay with Illumin’as BeadXpress system is the fact that they have developed a very user friendly and powerful analytical software tool for data acquisition and analysis. Their powerful VersaScan Software provides user friendly customization of scanning protocols and is compatible with Illumina’s proven BeadStudio Data Analysis Software. - The software enables acquisition and viewing of intensity data, report generation, and data extraction for application-specific data analysis modules (see figure below). - The data is provided in either *.csv and *.idat files for data export to Illumina BeadStudio or third party data analysis programs.
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