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Sorting out Arrays of Microarrays as an Industry Trend Gains Momentum

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Multiplex, multi-plate, or simply, microarray multiplication. It’s a growing trend among manufacturers.

Affymetrix (BioArray News, March 28, 2003), in March announced that it was beginning to go down the path of high-throughput automation for its GeneChip system, with a plan to place microarray chips at the bottom of 96-well microtiter plates and produce related instrumentation.

The microarray giant, apparently, is not alone.

Companies are building microtiter plates with glass-bottomed wells, to enable the spotting of arrays into the wells. Others are manufacturing covers of glass, plastic, or novel materials to lay over standard glass slides, which would allow multiple reactions to be conducted on one slide. Yet others are creating the machines for laying down spots in the bottoms of microtiter wells.

At last week’s Cambridge Healthtech Institute’s Macroresults for Microarrays conference in Boston, that trend appeared to be crystallizing.

Companies like Apogent, BioMicro Systems, and Mergen were displaying “array of array” systems.

Apogent Discoveries introduced its ez-rays PlateArray product, a 96-well microtiter plate with glass-bottomed wells, with a three-dimensional proprietary surface for DNA spotting. The plates will ship on June 1 and sell for $60 each, and will be available in packages of six or 30, with a volume discount for the larger package. The product took six months to develop.

The company also was showing its Microgrid II arrayer, which is manufactured by the BioRobotics division of Portsmouth, NH-based parent Apogent Technologies. The company recently announced that it will discontinue the line in a corporate realignment. However, Ann Mahoney, a marketing representative for Apogent, said that the company will continue to support the product, as it seeks a buyer for the unit.

Apogent acquired the Bio-Robotics Group, which was established in 1993 and employs over 50 people in the UK and 10 in the US, in March 2001 for an undisclosed sum. Its MicroGrid product was the first commercially available instrument to enable researchers to print their own DNA biochips.

With the PlateArray product, the company hopes to be the first company to commercialize microtiter-plate microarrays.

Apogent is targeting customers who have a focused set of genes that they will test for drug discovery or disease-state research.

“Slides aren’t robotically friendly,” said Mahoney. “The plates let you use robotic equipment, liquid handlers, plate washers — all of which we sell.”

The company’s software will allow users to place up to 300 spots of DNA, or protein in a well — using the MicroGrid spotter and PlateArray adapter trays. The MicroGrid can hold 16 PlateArray plates per run. The 1-millimeter thick microarray-quality glass bottoms of the well are black polystyrene to also minimize reflection during imaging, and offer a flat surface for optimal im-aging results, the company said.

A Multichamber Approach

Mergen introduced its Multichamber product, a cassette into which four slides can fit, with each slide divided into 16 arrays of up to 500 features per array. The product allows hybridization, washing, and detection of up to 16 experiments per slide, while treating the group as a single unit. The four 16-array slides fit into a tray to allow robotic systems for 96-well formats to process them. The arrays will sell for $100 each, depending on volume and complexity.

The company is selling the product as custom arrays with delivery within six weeks. The company has a gene list to create the probes to place on the array, and has plans for a pre-spotted ADME/tox array to release later this summer.

“It’s easy to put multiple arrays on a slide,” said Jamie Love, Mergen’s director of business development. “The hard part is putting them on a slide so that each is separate. The Multichamber arrays give people more bang for the buck, using up the whole landscape for the slide. We’ve just bootstrapped that onto the idea for higher throughput. There is an evolution out there: People want more focused arrays.”

Creating SLIDE covers

Michael McNeely, the president and chief technical officer of BioMicro Systems of Salt Lake City, Utah, showed BioArray News a slide cover, which is designed to work with the Agilent Technologies system, and which divides an array into two parts, with plumbing to deliver fluids to each part. The concept, the MAUI microfluidic hybridization system, is expandable to 16 arrays.

The company earlier this month introduced this latest version of the MAUI. BioMicro’s arrays apply its patented technique of controlling fluid through microchannels using passive valves. Each MAUI chip is disposable, can fit atop most standard microscope slide arrays, and costs about $50, the company said. The current platform is manual, but BioMicro intends to develop an automated version for the manipulation of multiple samples of reagents.

There are others getting in the low-density array race, which might benefit toxicogenomics researchers who have a small number of genes that they need to test in high-throughput fashion.

This push toward more chips is a result of many vectors. Toxicology studies, which are seen as one of the drivers of large-scale microarray use, are a primary driver, but so is a drive to automate the systems, in order to increase throughput and decrease variability.

“Many users are looking for higher volumes and more focused analysis with highly consistent results that are affordable,” said Michael Cohen, president for GeneXP Biosciences, of Woburn, Mass., an 11-employee company that has taken in $1.9 million in first-round funding to commercialize Bio-GridArray, custom microarray systems in 96- and 384-well microplates offered as a system or services.

Tim Harkins, formerly with Amersham Biosciences, and now an independent consultant with a focus on the microarray industry, said the need to conduct heavy analysis on small numbers of genes is coming and very soon.

“The pharma companies know they are going to go down the road, and if you press them, they will say that within a year, they will need to start doing the study,” he said.

“There is a need for speed, people want to understand the biology faster.”

— MOK

 

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