What's all this for then?

The Biotechnology Age is well under way. But like the Silicon Age, I think it will only really explode in growth once the entry price reaches a point where a few college dropouts can afford to build a biotech lab in their parent's basement, and with their inventions, put a dent in the universe.

The biotech laboratory is getting more and more streamlined, and experiments that would once have taken weeks or months can be performed in days, with much improved Recombinant DNA techniques, next-day-delivery of DNA primers, and cheap Gene synthesis. Although we can now forget about many old fashioned (but still widely used) techniques like Plasmid Cloning by Restriction Enzyme Digest, which require boxes full of expensive enzymes, the one technique that kickstarted the Biotech Revolution is still an absolute necessity.

PCR, or the Polymerase Chain Reaction, is one of the greatest inventions of the 20th Century. With it we can take a single stand of DNA and make trillions of identical copies. With these copies, we can identify a murderer from a speck of skin, DNA barcode living creatures to study entire ecological systems or identify the cause of a disease for personalised medicine. And because at the fundamental level all life on Earth operates on the same basis, we can even swap the "code" of life between species, rewriting the schematics of living organisms.

The grass roots interest in DIY biotechnology is growing, with projects like Biobricks and the Glowing Plant Project making headlines around the world. But the fact is, it's still too expensive for most people to get involved. With a target price of $5 for the parts to build a working PCR machine, and a secondary goal of $50 to build a really great machine, I hope to change that. At that price level, everything changes. Suddenly schools can afford to do recombinant DNA experiments in science class, just as the Apple IIe changed my school experience. Poorer countries can use the same equipment for medical diagnosis, and BioMaker's can start working on those inventions that will make the world a better place.

Download the designs, build the Polymerase Chain Reactor, and Viva la Revolucion Biotec!

System Design Documents

Here is the overview for the cheap, and ridiculously cheap PCR machines.

The $5 PCR machine

The $50 full featured PCR Machine

How PCR works:

In detail, the Polymerase Chain Reaction Machines operates by cycling a mixture of Template DNA (this contains the stuff we want to copy), Primers (short and cheap bits of DNA the match the front and back of the sequence we are copying), a Polymerase (the bio-nanobot that does the copying), and raw chemical nucleotides that will make up the sequence of the copies.

As an analogy, think of the template as a book, the primers as a set of bookmarks for certain pages, and the polymerase as a photocopier. The raw nucleotides are then something like the blank paper.  

PCR exploits the fact that some polymerases in Extremophiles from volcanic vents or hot springs can operate at very high temperatures, at which most organisms would be well and truly cooked.

Continuing with the (now very bad) analogy, imagine heating up the template as opening the book. Cooling the book inserts bookmarks at the correct location and closes it, and now you can hand it to the guy on the photocopier, who will photocopy everything between the bookmarks. He happens to work best with the air conditioning set to 72 degrees Celsius.

So, most of the hard work in the PCR machine is done by the wonderful Polymerase enzyme, and the PCR machine just has to get everything to the right temperatures at the right times, as shown in this fantastic video.

The temperatures need for PCR are:

So, the temperature need to cycle from 95 -> ~60 -> 72 for about 30 cycles, with each cycle doubling the amount of target DNA!

But, we have to get to these temperatures fast and accurately, and this means using big and power-hungry peltier-effect devices to both heat and cool our reaction mixture quickly. A good PCR machine has to heat or cool at a rate of at least 3-4 degrees Celcius per second, and that takes a lot of power.

Everything should be made as simple as possible, but not simpler.
-Albert Einstein

Heat is the key to the PCR reaction, and moving from one temperature to the next through the cycle drives the reaction at the molecular level. But why stop there?

This project uses the properties inherent in liquids: with convection. If we heat the bottom of a cooking pot, we get convection currents, bringing heated material up to the surface where it cools before sinking again.

Heat already drives DNA conversion between its single and double strand state and alters the activity of the polymerase as it makes copies of the DNA. Lets go further, and drive circulation of the reaction medium via convection, so that the fluid is pushed through each temperature zone sequentially, in a continuous loop! So, it's all just heat and geometry, and not about trying to shift the temperature of an entire reaction vessel quickly with expensive hardware. Because we can use thin tubes with very thin walls, we can get incredibly fast temperature changes.

So, no moving part, 2-3 very simple PID controlled heating elements, an Arduino and some cheap telfon tubing. What could be more simple, for cutting edge Biotechnology?

For the Judges:

The 5 minute video was barely enough time to cover the device and give an example of its use, and its deadline is almost here, so lets cover the main judging criteria one by one to save some time.

How “Open” is the design? Preference will be given to projects that exhibit depth of Open Hardware and Open Source Software

The 100% of the software and hardware designs are published on Github for a functional $5 PCR machine. 

PCR protocols themselves are readily available online and the patent for Taq Polymerase has expired. That said, I would love to create a portal for DIY Biohacker to share tips and trick, like openwetware but focused on community building.

“Wow” factor: is the entry innovative, is the build impressive?

I hope you think it is! I have tried to convey in the 5 minute video the differences between my device and an average commercial PCR machine that costs 500-1000 times as much.

Some of the key points are:

Is the entry a connected device and is that “connectedness” meaningful to the function?

The Bluetooth connection is just one aspect of the “connectedness”, but its a vital one. It allows the incredibly low price of the device. If I had to include inputs and an LCD or OLED display, those parts would double the PCR machines cost!

But that's just the beginning. Of course, with the limited time available I focused on getting a working prototype running using a terminal interface, because that's the key step. But now that it's proven to work, the next stage is designing a great Graphical User Interface. My plan is to write a web-server interface, so you can easily log onto the device an control it through a web-browser. 

This has several great benefits. Once the server has been written, the community can come together and help design a really great interface (something thats not my specialty, I'm happy with a command-line interface).

When that's done, it will be easy to add in extra connectedness features from all over the Internet, like 3D protein structures, PCR Primer calculators, and even the entire human genome, to help design your experiments. Molecular biology can be tricky, but by combining data and tools from all over the internet onto one web-interface control page, I think great work can be done.

Lastly, on the meta-connectedness theme, DIY biology is fundamentally different than programming or hardware hacking in one key regard: The parts you need are just like programming code, but they exist in a physical form (plasmid DNA). You need a community that can share these parts!

Is the project reproducible and could the work be extended for other uses?

I hope so! Anyone with a soldering iron should be able to build one, and its even possible to make a version as an "Arduino Shield".

With the basic concepts tested, I think it should be easy to improve. Things like the reactor geometry and safety feature on the hardware side, and an elegant and powerful we-based GUI on the software side still need to be designed and optimised.

Does the entry exhibit engineering innovation?

I think its a significant improvement over what's out there, and except for the OpenPCR machine (that operates with the same old technology as regular machines), nothing comes close in price. It might also be the only bluetooth controlled PCR machine out there too!

Is there an intuitive interface? (is the entry usable in the real world?)

The interface at the moment is only via the serial terminal of a serial bluetooth connection, but thats just the proof-of-principle. And that was only finished in the last few days. But the interface protocol is already written (and described in the projects logs), so although I plan on making a nice web interface, anyone out there can write their own interface!

A good web-based interface will be leaps-and-bounds better than what's available on even a $3000 PCR machine. Those things have terrible interfaces, more like those old Nokia bricks than any modern smartphone. I'm talking an alpha-numeric buttons, and an interface so complicated you need to keep the spiral-bound manual nearby at all times.

I hope you can judge this criteria on what the device is rapidly about to become: A Web-controlled device with a simple but powerful interface. This interface is what make the device so cheap, and at the same time, customisable and friendly to use. 

Is it/could it be manufacturable? (applicable in final round)

Sure! I've designed a really cheap working PCR machine that I envisage distributed as a science kit like the SpikerBox, that would include enough reagents to perform a dozen or so simple PCR reactions.

The Bluetooth machine can do it all, and is also really cheap to manufacture. I don't see anything in the way of getting these products made. But that's something the judges will have to decide, its not my area of expertise.

Post an artist’s rendition of the “productized” design/look and feel of the project.

I'm not a great artist, but I think photography definitely counts as an art-form. Here's the current prototype, and its pretty much what I hope a final product would look like. (OK, its a little Photoshopped...).

It should have clean lines with a simple geometric form. A single power socket, and a hidden status led under it's semi-translucent casing should do the job.