Engineering


dna_strand_gaub.jpgWhen in 1990 IBM arranged 35 individual xenon atoms to spell out “IBM,” the feat heralded a new era of nanofabrication. And it was so totally cool. But there’s not much you can really do with xenon atoms, and the process had to be performed under a near vacuum at close to absolute zero. A new technique that is much more flexible was recently reported by a group in Munich.

The Munich team manipulated individual DNA molecules into position using an atomic force microscope as a cantilever. The process was performed at room temperature and in solution, making it relatively accessible to a wide range of labs. But the quantum leap forward achieved by using DNA is that it can be readily functionalized. For example, the Munich group attached both a fluorophore and a biotin group to their DNA. Furthermore, DNA can act as a template or “seed” for self assembly of larger structures, such as those demonstrated using DNA staples to create nanoscale shapes and patterns. The Munich team attached a piece of DNA to the microscope tip and picked up from a “depot” pieces of DNA with complementary stretches to the tip-bound DNA. The cantilever then moved the DNA to the assembly area. The assembly area had an anchored DNA molecule that also was partially complementary to the moved piece of DNA, so the moved piece could be immobilized at the destination. The tip-bound piece of DNA was re-used thousands of times without loss of fidelity.  I’ve actually oversimplified the binding/unbinding process a bit, and in actuality the group makes ingenious use of the orientation of hybridized DNA molecules to take advantage of either “shear” or “zipper” binding/unbinding geometries to aid their efforts. You can find more details about that in their Science article.

While it’s unlikely that you will be buying any mass-produced products manufactured with these new techniques, the ability for researchers to construct objects to exact specifications may greatly aid materials and life-science research.

 
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 pacbio.jpgThe 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.

 
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Cell DetectionResearchers at Purdue University, have published in Nature, a new technology for detection of toxins and food-borne pathogens. The research group claims the technology is able to detect several pathogens in thousands of food and water samples in a couple of hours. Interestingly, it can also estimate the number of microbes present in a sample and determine whether that amount poses an active health hazard.

The technology uses live mammalian cells, B-cell hybridoma, PED-2E9, in a type I collagen matrix, that release a chemical, alkaline phosphatase, when harmed. This chemical can be detected uses optical equipment, such as laser scanning cytometry or cryo-nano scanning electron microscopy. The group developed software which can then analyze the signal and determine the quantity of harmful microbes present. Since the bio-sensor uses live cells it only detects actively harmful pathogens and ignores those that are inactive and harmless. Most test on the market currently detect dead or alive microbes and are prone to high false alarm rates or use a lengthy incubation periods, up to 20 hours or more, to grow only living microbes for detection.

This is an interesting application for live cells but is not novel. BAE systems has had this algae detector on the market for some time now. Even with this being said, the food market is lacking a fast, relatively speaking, detection method for Listeria monocytogenes. We at Biotech Mashup will follow this group to see if they are able to spin this out of the laboratory.

 
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Korean researchers report the development of a robot powered by heart muscle cells from a rat. The researchers coated a biocompatible polymer with heart cells that pulse in synchony in the presence of glucose, obviating the need for an external power supply. These beating cells permit the robot to move its six legs. The robot has three short front legs and three longer back legs, which are all attached to a central rectangular body. As the heart cells contract, the longer rear legs bend inwards. This creates a difference in friction between the front and rear legs, which pushes the robot forward. The scientists measured the robot’s average speed at about 100 micrometers per second (or about 2.2E-10 MPH). The lead designer, Sukho Park at Chonnam National University, Korea, says these crab-like robots could be used inside the body to clear blocked tubes or arteries.

This made me think of another really neat use for the heart muscle cells, which would be to make a glucose-powered electricity generator. The basic concept would be to coat a micro-balloon with the cells and use their contracting force to drive a nano-machined generator. The concept is shown below. The advantage would be that you could power small electronics or anything else that runs off electricity using only glucose. Although each single generator may not make much power, linking thousands of nano-generators together may generate usuable quantities of power.

Glucose-powered generator
Heart muscle cells coat a micro balloon and contract in synchrony. The expelled fluid drives a generator using nano-machined gears.
 

 
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Dark Liquid FlowArgonne National Laboratory has invented a way to finally see into dark liquids during flow. However the marketing group at Argonne has all been fired due to the 9 word name for the new technique. Simply put, this new X-ray technique allows a visual look at flow of dark liquids, helping the bored engineers who have been putzing around with silly models and equations which never accurately predicted real world experiments.

Now that precise models can be made from fuel injectors, Toyota should be announcing the 500 mpg car along with the use of the song “I Would Walk 500 Miles.”    

 
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Data Encryption ImageIf you use the following encryption software for your sensitive laboratory results you may just be out of luck. Microsoft’s BitLocker, Apple’s FileVault, Linux’s dm-crypt and most other common encryption methods just became security vulnerabilities due to the research done by a team of academic, industry, and independents headed at Princeton University, Engineering School.

The flaw is found in the RAM, random access memory, a core component in computers. Computers use RAM to temporary store information and in the process store the keys used to unlock Encrypted data. The researchers found that you can access these keys while a computer is networked or even just remove the RAM and place it in another computer to retrieve the key. This flaw demonstrates that data encrypted on a company laptop is not as safe as previously believed.

Without the security blanket of encryption how does this change the protocols and policies at many companies that allow laptops to leave the workplace? With the recent reports of lost laptops at many United States Government Departments and subsequent reports of identity theft the question must be raised are we placing too much trust in programs?

 
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