DNA Microarray Replication Richard M. Crooks, Ph.D. Department of Chemistry and Biochemistry

Opportunities and challenges  DNA microarrays have broad applications. Disease diagnosisDisease diagnosis Homeland SecurityHomeland Security Drug discovery researchDrug discovery research  The DNA microarray market is limited. ~$0.6 billion in annual sales~$0.6 billion in annual sales 6.7% annual growth6.7% annual growth Growth potential is high, could reach >$5 billion by 2010.Growth potential is high, could reach >$5 billion by  Drivers for market expansion: Lower pricesLower prices Greater production potentialGreater production potential Expanded usesExpanded uses MarketResearch.com; Frost and Sullivan

How do microarrays work?  DNA microarrays allow up to 1,000,000 genetic elements to be analyzed simultaneously.  Custom content to address: Different organisms Different diseases  Normalized, parallel, and rapid results

Our solution  DNA microarrays lend themselves to duplication. Unique DNA samples are in fixed locations in array.Unique DNA samples are in fixed locations in array. DNA template process allows faithful replication.DNA template process allows faithful replication.  Molecular Xerography Investment of costs is in precise master array.Investment of costs is in precise master array. Copies are faithfully reproduced, in content and spatial register from master.Copies are faithfully reproduced, in content and spatial register from master. Many copies are cheaply prepared from a single master array.Many copies are cheaply prepared from a single master array.

Technology overview  A single master DNA microarray is created.  The master array is exposed to a solution of complementary DNA primers.  The primers hybridize to all DNA strands on the master.  The primers are enzymatically extended to copy master content.  A replica surface is brought into contact with the master.  The replica surface is mechanically removed, separating the master from the complementary assay array.  The master array is ready to repeat copying procedure.

Xerographic replication of DNA microarrays Replica Streptavidin Biotin Contact and surface reaction c Master b Primer annealing Extension Separation d Replica a Master ssDNA

Benefits  Broadly applicable to all array formats  Disruptive technology with potential to: Dramatically reduce costs of arrays (up to 80%)Dramatically reduce costs of arrays (up to 80%) Increase production potential of arraysIncrease production potential of arrays Expand availability, use and marketExpand availability, use and market  Satisfies increasing demand for DNA microarrays in diagnostic, medical, and academic sectors  U.S. provisional patent filed covering technology