Not to be confused with next generation sequencers (NGS), gene mapping systems are another tool for analyzing DNA molecules. Gene mapping systems are not as detailed as NGS systems, but instead provide information about where certain sequences appear on a chromosome. They provide information complementary to NGS results. The information that gene mapping systems provide is analogous to a map of a city that points out specific places to visit or indicates where the nearest coffee shops are. In contrast, using the same analogy, DNA sequencers provide satellite images of every building in the city.

Gene mapping systems do not rely on electrophoresis gels or PCR, but rather employ microfluidic chips or cartridges and a scanner or imager. Each manufacturer has its own technology. OpGen offers the Argus Optical Mapping system that provides whole genome analysis of bacteria, yeast and fungi. High molecular weight DNA molecules enter the microfluidic channels of the optical chip in a linear fashion and bind to the glass substrate. Restriction enzymes cleave the DNA at specific sites, forming gaps in the microfluidic channels. The DNA is stained with fluorescent dyes, and image analysis measures the size and order of each fragment to create single-molecule maps. Thousands of single-molecule maps are then aligned to tile the entire genome for a complete map. OpGen targets applications in comparative genomic strain typing and sequence assembly.

BioNano Genomics manufactures the Irys Genomics Platform. DNA samples are prepared using a nick endonuclease to create a single-strand cut in long DNA molecules at a specific recognition site. Fluorescently labeled nucleotides are incorporated by repairing the single-strand nicks with a polymerase. After the samples are placed in a microfluidic chip, DNA moves through electrophoretically controlled channels that unravel and linearize the DNA molecule. The voltage is then turned off, trapping the DNA in the nano-channels, and the scanner captures high resolution single-molecule images of the labeled DNA. The process is capable of analyzing several gigabases of data in an hour. The system can be used to identify structural variation by comparing maps of a reference genome, for de novo map assembly or for anchoring sequencing contigs.

PathoGenetix is developing the RESOLUTION system that utilizes its Gene Sequence Scanning technology. A microfluidic chip stretches the DNA into linear conformation. Single molecules of DNA flow at high speed past a series of lasers and optical sensors that record the length and spatial pattern of labels on each DNA fragment to create a barcode. PathoGenetix is designing assays for applications in food and industrial microbial testing, microbial research and clinical diagnostics.

The market for microfluidic-based gene mapping systems is still young and offers strong growth potential. The total market was estimated at less than $10 million in 2012.

Microfluidic-Based Gene Mapping Systems at a Glance:

Leading Suppliers

• BioNano Genomics

• OpGen

• PathoGenetix

Largest Markets

• Academia/Government

• Clinical

• CROs

Instrument Cost

• $300,000–$400,000