Reverse Engineering a DNA Sequencer

Improvements in methodology have dramatically dropped the cost of DNA sequencing in the last decade. In 2007, it cost around $10 million dollars to sequence a single genome. Today, there are services which will do it for as little as $1,000. That’s not to bad if you just want to examine your own DNA, but prohibitively expensive if you’re looking to experiment with DNA in the home lab. You can buy your own desktop sequencer and cut out the middleman, but they cost in the neighborhood of $50,000. A bit outside of the experimenter’s budget unless you’re Tony Stark.

But thanks to the incredible work of [Alexander Sokolov], the intrepid hacker may one day be able to put a DNA sequencer in their lab for the cost of a decent oscilloscope. The breakthrough came as the result of those two classic hacker pastimes: reverse engineering and dumpster diving. He realized that the heavy lifting in a desktop genome sequencer was being done in a sensor matrix that the manufacturer considers disposable. After finding a source of trashed sensors to experiment with, he was able to figure out not only how to read them, but revitalize them so he could introduce a new sample.

To start with, [Alexander] had to figure out how these “disposable” sensors worked. He knew they were similar in principle to a digital camera’s CCD sensor; but rather than having cells which respond to light, they read changes in pH level. The chip contains 10 million of these pH cells, and each one needs to be read individually hundreds of times to capture the entire DNA sequence.

Enlisting the help of some friends who had experience reverse engineering silicon, and armed with an X-Ray machine and suitable optical microscope, he eventually figured out how the sensor matrix worked electrically. He then designed a board that reads the sensor and dumps the “picture” of the DNA sample to his computer over serial.

Once he could reliably read the sensor, the next phase of the project was finding a way to wash the old sample out so it could be reloaded. [Alexander] tried different methods, and after several wash and read cycles, he nailed down the process of rejuvenating the sensor so its performance essentially matches that of a new one. He’s currently working on the next generation of his reader hardware, and we’re very interested to see where the project goes.

This isn’t the first piece of DIY DNA hardware we’ve seen here at Hackaday, and it certainly won’t be the last. Like it or not, hackers are officially fiddling with genomes.

Françoise Barré-Sinoussi: Virus Hunter

It was early 1983 and Françoise Barré-Sinoussi of the prestigious Pasteur Institute in Paris was busy at the centrifuge trying to detect the presence of a retrovirus. The sample in the centrifuge came from an AIDS patient, though the disease wasn’t called AIDS yet.

Barré-Sinoussi and Montagnier in 1983
Barré-Sinoussi and Montagnier in 1983, Image source: Le Globserver

Just two years earlier in the US, a cluster of young men had been reported as suffering from unusual infections and forms of cancer normally experienced by the very old or by people using drugs designed to suppress the immune system. More cases were reported and US Centers for Disease Control and Prevention (CDC) formed a task force to monitor the unusual outbreak. In December, the first scientific article about the outbreak was published in the New England Journal of Medicine.

By May 1983, researchers Barré-Sinoussi and Luc Montagnier of the Pasteur Institute had isolated HIV, the virus which causes AIDS, and reported it in the journal Science. Both received the Nobel prize in 2008 for this work and the Nobel prize citation stated:

Never before have science and medicine been so quick to discover, identify the origin and provide treatment for a new disease entity.

It’s only fitting then that we take a closer look at one of these modern detectives of science, Françoise Barré-Sinoussi, and what led to her discovery.

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Gertrude Elion, DNA Hacker

Some people become scientists because they have an insatiable sense of curiosity. For others, the interest is born of tragedy—they lose a loved one to disease and are driven to find a cure. In the case of Gertrude Elion, both are true. Gertrude was a brilliant and curious student who could have done anything given her aptitude. But when she lost her grandfather to cancer, her path became clear.

As a biochemist and pharmacologist for what is now GlaxoSmithKline, Gertrude and Dr. George Hitchings created many different types of drugs by synthesizing natural nucleic compounds in order to bait pathogens and kill them. Their unorthodox, designer drug method led them to create the first successful anti-cancer drugs and won them a Nobel Prize in 1988.

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Rosalind Franklin Saw DNA First

It’s a standard science trivia question: Who discovered the structure of DNA? With the basic concepts of molecular biology now taught at a fairly detailed level in grade school, and with DNA being so easy to isolate that it makes a good demonstration project for school or home, everyone knows the names of Watson and Crick. But not many people know the story behind one of the greatest scientific achievements of the 20th century, or the name of the scientist without whose data Watson and Crick were working blind: Rosalind Franklin.

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Cheap and Easy Magnetic DNA Separation Method Needs Your Help

When you consider that almost every single cell in your body has more than a meter of DNA coiled up inside its nucleus, it seems like it should be pretty easy to get some to study. But with all the other cellular gunk in a crude preparation, DNA can be quite hard to isolate. That’s where this cheap and easy magnetic DNA separation method comes in. If it can be optimized and tested with some help from the citizen science community.

Commercial DNA separation methods generally involve mixing silica beads into crude cell fractions; the DNA preferentially binds to the silica, making it possible to mechanically separate it from the rest of the cellular junk. But rather than using a centrifuge to isolate the DNA, [Justin] from The Thought Emporium figured that magnets might do a better job. It’s not a new idea — biotech companies offer magnetic separation beads commercially, but at too steep a price for [Justin]’s budget. His hack comes from making magnetite particles from common iron compounds like PCB etchant and moss killer, and household ammonia cleaner. The magnetite particles are then coated with sodium silicate solution, also known as waterglass. The silica coating should allow the beads to bind to DNA, with the magnetic core taking care of separation.

[Justin] was in the process of testing his method when he lost access to the needed instruments, so he’s appealing to the larger science community for help optimizing his technique. Based on his track record of success in fields ranging from satellite tracking to graphene production, we’ll bet he’ll nail this one too.

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Living Logic: Biological Circuits for the Electrically Minded

Did you know you can build fundamental circuits using biological methods? These aren’t your average circuits, but they work just like common electrical components. We talk alot about normal silicon and copper circuits ‘roud here, but it’s time to get our hands wet and see what we can do with the power of life!

In 1703, Gottfried Wilhelm Leibniz published his Explication de l’Arithmétique Binaire (translated). Inspired by the I Ching, an ancient Chinese classic, Leibniz established that the principles of arithmetic and logic could be combined and represented by just 1s and 0s. Two hundred years later in 1907, Lee De Forest’s “Audion” is used as an AND gate. Forty years later in 1947, Brattain and H. R. Moore demonstrate their “PNP point-contact germanium transistor” in Bell Labs (often given as the birth date of the transistor). Six years later in 1953, the world’s first transistor computer was created by the University of Manchester. Today, 13,086,801,423,016,741,282,5001 transistors have built a world of progressing connectivity, automation and analysis.

While we will never know how Fu Hsi, Leibniz, Forest or Moore felt as they lay the foundation of the digital world we know today, we’re not completely out of luck: we’re in the midst’s of our own growing revolution, but this one’s centered around biotechnology. In 1961, Jacob and Monod discovered the lac system: a biological analog to the PNP transistor presented in Bell Labs fourteen years earlier. In 2000, Gardner, Cantor, and Collins created a genetic toggle switch controlled by heat and a synthetic fluid bio-analog2. Today, AND, OR, NOR, NAND, and XOR gates (among others) have been successfully demonstrated in academic labs around the world.

But wait a moment. Revolution you say? Electrical transistors went from invention to computers in 6 years, and biological transistors went from invention to toggle button in 40? I’m going to get to the challenges facing biological circuits in time, but suffice it to say that working with living things that want to be fed and (seem to) like to die comes with its own set of challenges that aren’t relevant when working with inanimate and uncaring transistors. But, in the spirit of hacking, let’s dive right in. Continue reading “Living Logic: Biological Circuits for the Electrically Minded”

Synthetic Biology Creates Living Computers

Most people have at least a fuzzy idea of what DNA is. Ask about RNA, though, and unless you are talking to a biologist, you are likely to get even more handwaving. We hackers might have to reread our biology text books, though, since researchers have built logic gates using RNA.

Sometimes we read these university press releases and realize that the result isn’t very practical. But in this case, the Arizona State University study shows how AND, OR, and NOT gates are possible and shows practical applications with four-input AND gates and six-input OR gates using living cells. The key is a construct known as an RNA toehold switch (see video below). Although this was worked out in 2012, this recent study shows how to apply it practically.

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