The era of personalized medicine is fast approaching. Having your genome sequenced rapidly and cheaply will be key to this fundamental change in the way medicine is practiced and drugs are developed. Several companies are working toward the $1,000 genome, including Pacific Biosciences, one of Biotech Mashup’s top 15 picks for companies that have the potential to change medicine.

The motto of Pacific Biosciences is “Single molecule, real time,” which promises cheap, long reads. In fact, the company last month announced amidst a fireworks display that within five years they will be able to sequence at high quality an entire human genome in just 15 minutes and obtain raw sequence in under an amazing three minutes. The company’s first commercial instrument will be ready by 2010, at the earliest.

“PacBio” was founded in 2004 based upon technology reported in a 2003 Science publication. The sequencing technology essentially makes use of two key techniques. The first is the ability to “focus” a light beam into a tight area using a zero mode waveguide. The waveguide does not actually focus light, but rather restricts the area that is illuminated to a small portion at the bottom of a nanofabricated well, where a single DNA polymerase molecule is anchored. The second technique is the use of fluorescently labeled nucleotides. As a fluorescent nucleotide is added to a growing DNA chain, it spends enough time illuminated in the light beam that its fluorescence can be detected. Each base is labeled with a unique fluorophore that is cleaved off as the base is added to the growing DNA chain, and the color of emitted light reveals which base was added. Nucleotides floating in solution do not contribute to the signal or a significant background because they are not illuminated long enough. The polymerization process occurs in real time at about 10 bases per second, a speed which is expected to increase since polymerases can operate 50-75 times faster. Since the micro-wells can be arrayed, many polymerases can be monitored in parallel using a CCD camera. The company has already demonstrated 1,000 polymerases sequencing DNA in unison, and aims to increase that number to 1 million. In fact, the wells are so small at just 20 zeptoliters that the company claims they are the world’s smallest reaction volumes.

The company predicts that 100 gigabase-per-hour read rates in real time can be achieved. According to the company, their technology is “disruptively faster than current next-generation technologies.” We will be anxiously watching Pacific Biosciences as they disrupt their way to sequencing our genomes.