Microarray Scanners: Resolution Increases

Is 2008 the year of the microarray scanner? It could very well be with at least five new scanners hitting the market by year end. The timing coincides with the introduction of higher density DNA microarrays. With more probes per chip, probe size is smaller, requiring higher resolution scanning. In addition, new software designed for analyzing larger data sets, and systems with greater flexibility and ease of use,and upgraded components define the latest generation of scanners. Companies long established in the microarray scanner market, as well as new entrants are releasing new scanners. Earlier this year, Illumina launched the iScan System, which boasts a pixel resolution of 0.54 µm and faster throughput, and is optimized for use with the company’s new Infinium HD BeadChips. The company’s Human1M-Duo BeadChip have 1,199,187 markers per sample. Affymetrix has announced that it will release a new DNA microarray scanner later this year. Both companies’ scanners are part of so-called closed platforms, in that they can only be used with the corresponding company’s DNA microarrays. Agilent, Molecular Devices and Tecan are each releasing new DNA microarray scanners for open platforms this year as well. These scanners are designed for high-density DNA microarrays as well as protein arrays. Setting the pace in high-density DNA microarrays for open systems are Agilent and Nimblegen. Last year, Nimblegen released the first of its HD2 Arrays for comparative genomic hybridization (CGH) and chromatin immunoprecipitation (ChIP)-on-chip analysis of eukaryotic organisms. The HD2 microarrays feature 2.1 million 50–75 mer oligonucleotide probes with a feature size of 13 µm x 13 µm. This small size allows three arrays per slide. In August, the company released its HD2 12 x 135K microarrays for gene expression, featuring 12 135,000-probe arrays per slide. A scanner with a resolution of at least 5 µm is required to read HD2 Arrays, Later this year, Agilent is scheduled to introduce its million-feature arrays, featuring 30 µm–sized features. The company’s current offering include ChIP microarrays with 244,000 60-mer oligonucleotide probes. Driving the demand for high density arrays is the lower price per data point, as such arrays enable more assays using fewer chips and fewer reagents. Higher density chips also provide the greater detail necessary for CGH and ChIP applications. In April, Molecular Devices, part of MDS Analytical Technologies, introduced the Axon GenePix 4300A and 4400A microarray scanners. The systems began shipping in July at a cost of between $76,000 (one-laser) and $120,000 (four lasers), according to Varshal K. Davé, director of Genomics Marketing for Molecular Devices. The 4300A scans at 5 µm pixel resolution. The 4400A scans at 2.5 µm resolution and is priced at $110,000–$155,000. Axon Instruments, which was acquired by Molecular Devices (see IBO 3/31/04), now part of MDS, in 2004, is well known for its GenePix 4000B, introduced in 2001. The 4300A replaces the GenePix Professional 4200A, introduced in 2003. Later this year, Molecular Devices will release automated slide loading mechanisms for the 4300A and 4400B to replace the GenePix AutoLoader 4200AL. Describing the 4300A and 4400A, Mr. Davé told IBO, “we’ve improved the dynamic range of the instrument [and] we’ve improved the signal to noise.” He also stated that the new scanner reduces the amount of pixel shifting: “we’ve been able to ensure that over the length of the scan we have less than one pixel shift.” New software allows end-users to capitalize on the higher resolution of the new arrays and their multiplexing features. “So what we’ve introduced with GenePix Pro 7 is the ability to set independent scan areas with the ability to do different scanner settings for each one of the different areas on the slide,” Mr. Davé stated. Asked about the GenePix 4300A and 4400A’s competitive advantages, Mr. Davé cited the scanners’ ability to house as many as four lasers, enabling the use of four different dyes, which is particularly applicable to protein arrays and SNP detection. He also cited the scanner’s expanded depth of focus. “With a 64-micron focal depth, you are able to compensate for any surface fluctuations on the slide,” he noted. Unlike Axon, which is well established in the market, Tecan has just introduced its first dedicated microarray scanner, the PowerScanner. The company also offers the LS Reloaded, a scanner for multiple array-formats, such as multititer plates or microfluidic channels. Tecan will begin shipping the PowerScanner in November at a price of $120,000 fully equipped. As Ralph Beneke, Tecan’s Microarray product manager, explained, the PowerScanner is designed for current and future high-density DNA microrrays: “with the high resolution of 2 µm and high detection sensitivity, the PowerScanner supports a new generation of applications and array production quality.” The PowerScanner offers resolution of 2 µm, 5 µm, 10 µm, 20 µm and 40 µm. “The more and more precisely researchers need to know the minor differences in the genome, the higher the requirements are for technical accuracy, sensitivity, specificity and safety in order to generate confidence in even minor changes detected with such a system.”The system is available with up to two lasers and features a 48-slide autoloader and the ability to scan multiple areas per slide. Advantages of the scanner compared to its competition, according to Mr. Beneke, include integrated ozone blocking and internal calibration. He also emphasized the scanner’s flexibility: “For running a whole bunch of slides from different projects fully automated without any manual interference, independent of type of array, assay or type of slide surface and structure, we think it is really the system of choice.” The product also fits with Tecan’s other products for the microarray workflow, such as liquid handlers for sample preparation and the HS Pro system for microarray hybridization. Furthermore, the company has positioned the PowerScanner as an OEM product, including opportunities in the diagnostic market. Like Tecan, Agilent offers a number of products for the microarray workflow, as well as the microarrays themselves. In June, the company began shipping its Agilent DNA Microarray Scanner G256CA, which replaces the G256BA. The new scanner is priced at just under $150,000, however, a version of the product without high-resolution scanning is available for $125,000. An upgrade is priced at under $40,000. According to Jeff McMillan, head of Microarray Scanner Development for Agilent, the scanner’s new features include the ability to scan slides at 2 µm and 3 µm resolution, in addition to the 5 µm and 10 µm already available, as well as a high dynamic range scanning capability. “In 2006 we introduced a feature we call Extended Dynamic Range, or XDR, which combined the results of two different scans at different detector gains into a single results file. As a result, the user could conduct a scan and be sure to capture the entire dynamic range (6 logs) and scan with high sensitivity without the fear of saturation,” he explained. “With the introduction of our High-Resolution Scanner, we’re introducing a 20-bit scan that does the same thing, but in a single scan.” The scanner is also designed to work with Agilent’s million-feature microarrays and its Feature Extraction software. As Mr. McMillan put it, “it’s going to take a lot of processing power to process our new generation of arrays and we’ve got a big head-start on the workflow vis-à-vis our competitors.”

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