August 6, 2005

Microfluidics & Laser Manipulation of Cells: The Road to Automated Molecular Biology?

Is automated DNA synthesis, transformation, selection, PCR, ligations, and imaging that far away? How would molecular biology change if a single PhD student could design and synthesize an entire plasmid or section of chromosome in a week? Besides exponentially speeding up the productivity of researchers (and encouraging PhD advisors to get even more paper greedy ;) ), it would have tremendous effects on the whole idea of synthetic biology. Design it. Make it. It works. Time To Completion? A month? A week? If you ask the typical biologist about the prospects of automating the process of genetic engineering, they'll say it's crazy talk. But two recent presentations at two separate conferences outlined the first steps towards the beginning of a new era in biology.

The first conference was on a new cell-manipulation system that uses lasers to selectively toast, lyse, or heat individual cells. The conference is named Biochemical Engineering XIV and took place in Harrison Springs, British Columbia (near Vancouver). The presenter is a founder of a company named Cyntellect and he demonstrated how a high powered laser, driven by the precise movement of mirrors, can target a single yeast or mammalian cell for treatment. The laser has three modes of operation: it can completely break open and evaporate the fluid of a cell, killing it instantly; it can hit the cell with a burst of mechanical force that lyses the cell open, but leaves the intracellular space generally unharmed (including the DNA!); and it can gently heat up a single cell to a nice 42 deg Celsius. Using those three operational modes, the device can automate the transformation and selection process _on the single cell level_. Cool, huh? There's a built in optical microscope to image either staining or fluorescence and the laser system can target groups of cells that have a particular fluorescence (which looked similar to the gating function of a cytometer).

So you can heat shock, transform, image, select, lyse, and ... uh oh..that's all it can do for now. Either way, I was very excited by the time the guy finished his presentation (I mean, hey, he's using fricken laser beams). The real reason, though, is that the field of microfluidics has steadily advanced to the point where you can start pumping in and out reagents of all types into a chamber and control the reactions. Cyntellect only supports 96-well plates for now, but there's no reason why someone couldn't put a nice microfluidic device in there with a good sized viewing window for the laser. The laser system's chamber is temperature controlled (with a good response time!) so we're talking about _everything_ one needs to continue the process of genetic engineering: heat shock, transform, image, select, lyse, ... PCR, purify, and repeat!

The second conference was on "Molecular Recognition & Biosensors" in Santa Barbara, CA. The conference was sponsored by the Army's AHPCRC. In my mind, I knew microfluidics have been making steady strides, but seeing the recent accomplishments really surprised me. A professor at Cal Tech named Yo-Chong Tai presented his work on _integrated_ microfluidic devices at a recent conference The components of the integrated microfluidic device, such as the pumps, valves, pipes, and other chambers, are molded together in a single chip using micrometer-resolution plastic deposition. To strut his stuff, he showed off his mini-HPLC (High Performance/Pressure Liquid Chromotagraphy). The mini-HPLC is 3 cm in length, uses ~100 nl of sample, and the results match the big commercial ones. Crazy, huh? How far away is he from making a tiny electrophoresis chamber? Probably not too far.

Using an integrated microfluidic device combined with laser manipulation of individual cells, one can perform all of the necessary tasks that are needed to genetically engineer cells. How long will it be until someone decides to put these two innovations together and optimize the automation of the entire process? I give it 4-6 years, tops. Genetic engineering (cloning) is such a tedious, mind numbing, and repetitive task that any efficient (and cheap) automation would have a huge, earth-shattering effect on the entire field.

Honestly, I can't wait. I don't do half the cloning that some of my other friends do, but I still think it's the most repetitive and least satisfying part of molecular biology. If it works, you're happy...but only because you don't have to repeat it. The real satisfying accomplishment is doing the experiment and gaining knowledge (and something to write a paper about, heh). And if it doesn't work...ugh, wasted time!

-Howard

Posted by sali0090 at 12:40 AM