In 2004, officials at the US National Human Genome Research Institute (NHGRI) set an ambitious goal: to reduce the cost of sequencing an entire human genome by four orders of magnitude within a decade. At the time, shortly after the publication of the Human Genome Project, a new three-billion-base-pair genome sequence still cost more than $10 million. So the idea was to get the cost down to under $1,000 by 2014.

Thanks to next-generation sequencing, which relies on massive parallel analyses of millions of short nucleic acid fragments, whole genome sequences are already available for under $20,000 apiece. To lower the cost further, many researchers are now vying to develop the first $1,000 genome by refining their sequencing-by-synthesis methods or pursuing a range of newer, single-molecule, 'third generation' DNA sequencing technologies.

The multitude of candidate platforms is a good thing, says Jeffery Schloss, program director for technology development at the NHGRI, which last month announced the recipients of its seventh annual Advanced Sequencing Technology Awards. “Competition has been essential to keeping quality high and driving costs down, and we hope that continues as the new technologies emerge,” he says.

Here are some of this year's more inventive ideas:

Pore your heart out

The most common strategy being pursued involves reading individual nucleotides in a single strand of DNA as it travels through atomic-sized holes known as nanopores. This approach avoids the time-consuming and expensive cyclic addition of sequencing reagents and reads the genome rapidly in real time.

A fluid approach

GnuBIO, a startup launched by Harvard University physicist David Weitz, is developing a microfluidics-based sequencer where reactions take place in picoliter-sized drops. By using only the tiniest of droplets, the company hopes to drastically reduce the amount of costly reagents needed in more traditional next-generation platforms.

Come to your sensors

Rather than relying on artificial nanostructures, University of California–San Diego biotechnologist Xiaohua Huang plans to perform single-molecule sequencing by engineering onto the surface of natural DNA polymerases sensors that monitor how the enzymes change shape as specific base types are added to the DNA strand.

Taking charge

The approach from Silicon Valley startup Caerus Molecular Diagnostics works by measuring the increased molecular charge as nucleotides are added to DNA templates attached to microscopic beads. Crucially, this method does away with standard next-gen sequencing's expensive fluorescent labels.

Heavy hitters

Scientists at Redwood City, California's Halcyon Molecular, in collaboration with University of California–Berkeley chemist Dean Toste, propose to attach heavy atoms of osmium, iridium, gold and other elements to DNA and then use transmission electron microscopy to decode the labeled DNA.