partnering to bring your applications to market

ArrayXpress has the multiplex diagnostics platform to bring your applications specific technology to market. We have significant experience in developing unique probe sets for fields of application ranging from human health to herd management to phytosanitary regulation. If you have a large number of possible pathogens or markers you are wanted to screen for simultaneously, then our XpressDX technology platform might be right for you. We can assist you with developing the system which can be commercialized through a number of different mechanisms.

Multiplexed Diagnostics

Current 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.