How laser 'printing' builds DNA

The concept of using lasers to synthesize DNA with a specified genetic sequence intrigued me so much that I tried to describe it in my October Photonic Frontiers feature. After receiving a grant from the National Science Foundation, the company behind the idea, Cambrian Genomics (San Francisco, CA), has released new details on the process, and my speculation about its nature turned out to be wrong.

Previously, DNA synthesis has been a two-stage assembly process. First individual base pairs are assembled into "oligonucleotide" sequences of 60 to 100 base pairs. Then, a number of those longer chains are stitched together into the synthetic DNA. The process is time-consuming and costs 30 to 50 cents per base pair, a number which adds up for long sequences. I had thought they might be using lasers to manipulate the base pairs into place.

Instead, Cambrian Genomics uses microarray cloning to mass-produce a million oligonucleotides in parallel, a process that has been tried before, but was hampered by the high error rates of microarray synthesis. To overcome that problem, Cambrian synthesizes large volumes of oligonucleotide fragments on microarrays, then uses massively parallel DNA sequencing to sort the different DNA variants and identify those with the desired sequence. Then, says Cambrian founder and CEO Austen Heinz, "we use laser catapulting, also known as laser-induced forward transfer, to eject clonal DNA populations," which were identified as having the desired sequences. The process is a variation on laser capture microdissection, which can excise part of a cell and move it to a desired location without damaging DNA. High-speed laser pulses then eject beads carrying the desired sequences in the right order to assemble into genes on a 384-well plates, as shown in the diagram.

Cambrian Genomics process uses lasers to select oligonucleotides with the desired sequence.

The goal, Cambrian wrote in a summary of its application for a phase-one Small Business Innovation Research (SBIR) grant, "is to be able to recover tens of thousands of sequence-verified oligonucleotides in several hours from sequencer flowcells."  NSF announced on December 5, 2012, a $150,000 grant that will run through the first six months of 2013. Cambrian hopes that will open the door to disruptive reductions in the cost of DNA synthesis.

Display technology getting ahead of the market

Peter Jackson's decision to shoot The Hobbit at 48 frames per second brought optical technology into many holiday-party conversations, at least among technologists and movie buffs. Together with demonstrations of video screens with horizontal resolution of 8000 pixels, it raises the question of whether the cutting edge of large-screen display technology is getting too far ahead of the market.

From the production side, it makes sense to record a movie in the best quality available at reasonable cost. It's easy to reduce resolution or frame rate to current mass-distribution standards. Theaters can charge extra for the highest quality screenings, as they have done for 3D. And archival copies should be compatible with the next generation or two of technologies.


From the display side, reviewers had mixed reactions. They found some parts spectacular, but sometimes too revealing. As Lucy O'Brien wrote on the gaming site IGN.com, "The problem with doubling the frame-rate in The Hobbit is a problem of scrutiny; you can see all its tricks."

The push for higher video screen resolution comes largely from the consumer electronics industry. Aided by government mandates to convert to digital broadcasting, the industry persuaded the public to switch to flat-panel high-definition televisions showing 720 or 1080 lines, corresponding to widths of 1280 or 1920 pixels respectively. But the public largely passed on 3D television, and in uncertain times they have been slow to step up to larger screens, so manufacturers have slashed prices to bolster sales.

Two ultra-high-definition formats are in development. One that doubles resolution is called 4K, for a nominal width of 4000 pixels (actually 3840 x 2160 pixels). An alternative called 8K quadruples resolution to a nominal width of 8000 pixels (actually 7680 x 4320 pixels). Some 4K equipment is available, and 8K has been demonstrated. However, big challenges remain, writes Pete Putman of Display Daily, including lack of production equipment and cameras, high screen costs, and the need for much more bandwidth to carry the larger files.

Unlike 3DTV, ultra-high-def won't give you a headache or require special glasses. It makes sense for future-proofing video production, and it could be a selling point for video venues or sports bars.  But for now, ultra-high-def has gotten far ahead of the home television market, which is getting to like today's low prices.