Nanotechnology Now

Our NanoNews Digest Sponsors

Heifer International

Wikipedia Affiliate Button

Home > Press > Caltech Researchers Build Largest Biochemical Circuit Out of Small Synthetic DNA Molecules

A wiring diagram specifying a system of 74 DNA molecules that constitute the largest synthetic circuit of its type ever made. The circuit computes the square root of a number up to 15 and rounds down to the nearest integer (the discrete square root of a four-bit integer).
[Credit: Caltech/Lulu Qian]
A wiring diagram specifying a system of 74 DNA molecules that constitute the largest synthetic circuit of its type ever made. The circuit computes the square root of a number up to 15 and rounds down to the nearest integer (the discrete square root of a four-bit integer).
[Credit: Caltech/Lulu Qian]

Abstract:
In many ways, life is like a computer. An organism's genome is the software that tells the cellular and molecular machinery—the hardware—what to do. But instead of electronic circuitry, life relies on biochemical circuitry—complex networks of reactions and pathways that enable organisms to function. Now, researchers at the California Institute of Technology (Caltech) have built the most complex biochemical circuit ever created from scratch, made with DNA-based devices in a test tube that are analogous to the electronic transistors on a computer chip.

Caltech Researchers Build Largest Biochemical Circuit Out of Small Synthetic DNA Molecules

Pasadena, CA | Posted on June 4th, 2011

Engineering these circuits allows researchers to explore the principles of information processing in biological systems, and to design biochemical pathways with decision-making capabilities. Such circuits would give biochemists unprecedented control in designing chemical reactions for applications in biological and chemical engineering and industries. For example, in the future a synthetic biochemical circuit could be introduced into a clinical blood sample, detect the levels of a variety of molecules in the sample, and integrate that information into a diagnosis of the pathology.

"We're trying to borrow the ideas that have had huge success in the electronic world, such as abstract representations of computing operations, programming languages, and compilers, and apply them to the biomolecular world," says Lulu Qian, a senior postdoctoral scholar in bioengineering at Caltech and lead author on a paper published in the June 3 issue of the journal Science.

Along with Erik Winfree, Caltech professor of computer science, computation and neural systems, and bioengineering, Qian used a new kind of DNA-based component to build the largest artificial biochemical circuit ever made. Previous lab-made biochemical circuits were limited because they worked less reliably and predictably when scaled to larger sizes, Qian explains. The likely reason behind this limitation is that such circuits need various molecular structures to implement different functions, making large systems more complicated and difficult to debug. The researchers' new approach, however, involves components that are simple, standardized, reliable, and scalable, meaning that even bigger and more complex circuits can be made and still work reliably.

"You can imagine that in the computer industry, you want to make better and better computers," Qian says. "This is our effort to do the same. We want to make better and better biochemical circuits that can do more sophisticated tasks, driving molecular devices to act on their environment."

To build their circuits, the researchers used pieces of DNA to make so-called logic gates—devices that produce on-off output signals in response to on-off input signals. Logic gates are the building blocks of the digital logic circuits that allow a computer to perform the right actions at the right time. In a conventional computer, logic gates are made with electronic transistors, which are wired together to form circuits on a silicon chip. Biochemical circuits, however, consist of molecules floating in a test tube of salt water. Instead of depending on electrons flowing in and out of transistors, DNA-based logic gates receive and produce molecules as signals. The molecular signals travel from one specific gate to another, connecting the circuit as if they were wires.

Winfree and his colleagues first built such a biochemical circuit in 2006. In this work, DNA signal molecules connected several DNA logic gates to each other, forming what's called a multilayered circuit. But this earlier circuit consisted of only 12 different DNA molecules, and the circuit slowed down by a few orders of magnitude when expanded from a single logic gate to a five-layered circuit. In their new design, Qian and Winfree have engineered logic gates that are simpler and more reliable, allowing them to make circuits at least five times larger.

Their new logic gates are made from pieces of either short, single-stranded DNA or partially double-stranded DNA in which single strands stick out like tails from the DNA's double helix. The single-stranded DNA molecules act as input and output signals that interact with the partially double-stranded ones.

"The molecules are just floating around in solution, bumping into each other from time to time," Winfree explains. "Occasionally, an incoming strand with the right DNA sequence will zip itself up to one strand while simultaneously unzipping another, releasing it into solution and allowing it to react with yet another strand." Because the researchers can encode whatever DNA sequence they want, they have full control over this process. "You have this programmable interaction," he says.

Qian and Winfree made several circuits with their approach, but the largest—containing 74 different DNA molecules—can compute the square root of any number up to 15 (technically speaking, any four-bit binary number) and round down the answer to the nearest integer. The researchers then monitor the concentrations of output molecules during the calculations to determine the answer. The calculation takes about 10 hours, so it won't replace your laptop anytime soon. But the purpose of these circuits isn't to compete with electronics; it's to give scientists logical control over biochemical processes.

Their circuits have several novel features, Qian says. Because reactions are never perfect—the molecules don't always bind properly, for instance—there's inherent noise in the system. This means the molecular signals are never entirely on or off, as would be the case for ideal binary logic. But the new logic gates are able to handle this noise by suppressing and amplifying signals—for example, boosting a signal that's at 80 percent, or inhibiting one that's at 10 percent, resulting in signals that are either close to 100 percent present or nonexistent.

All the logic gates have identical structures with different sequences. As a result, they can be standardized, so that the same types of components can be wired together to make any circuit you want. What's more, Qian says, you don't have to know anything about the molecular machinery behind the circuit to make one. If you want a circuit that, say, automatically diagnoses a disease, you just submit an abstract representation of the logic functions in your design to a compiler that the researchers provide online, which will then translate the design into the DNA components needed to build the circuit. In the future, an outside manufacturer can then make those parts and give you the circuit, ready to go.

The circuit components are also tunable. By adjusting the concentrations of the types of DNA, the researchers can change the functions of the logic gates. The circuits are versatile, featuring plug-and-play components that can be easily reconfigured to rewire the circuit. The simplicity of the logic gates also allows for more efficient techniques that synthesize them in parallel.

"Like Moore's Law for silicon electronics, which says that computers are growing exponentially smaller and more powerful every year, molecular systems developed with DNA nanotechnology have been doubling in size roughly every three years," Winfree says. Qian adds, "The dream is that synthetic biochemical circuits will one day achieve complexities comparable to life itself."

The research described in the Science paper, "Scaling up digital circuit computation with DNA strand displacement cascades," is supported by a National Science Foundation grant to the Molecular Programming Project and by the Human Frontier Science Program.

Written by Marcus Woo

####

For more information, please click here

Contacts:
Deborah Williams-Hedges
626-395-3227

Copyright © California Institute of Technology (Caltech)

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related Links

Dr. Erik Winfree

Related News Press

News and information

Shape matters when light meets atom: Mapping the interaction of a single atom with a single photon may inform design of quantum devices December 4th, 2016

UTSA study describes new minimally invasive device to treat cancer and other illnesses: Medicine diffusion capsule could locally treat multiple ailments and diseases over several weeks December 3rd, 2016

Novel Electrode Structure Provides New Promise for Lithium-Sulfur Batteries December 3rd, 2016

Research Study: MetaSOLTM Shatters Solar Panel Efficiency Forecasts with Innovative New Coating: Coating Provides 1.2 Percent Absolute Enhancement to Triple Junction Solar Cells December 2nd, 2016

Videos/Movies

2-D material a brittle surprise: Rice University researchers finds molybdenum diselenide not as strong as they thought November 14th, 2016

Keystone Nano Announces The US FDA Has Awarded Orphan Drug Designation For Ceramides For The Treatment Of Liver Cancer November 8th, 2016

Engineers develop new magnetic ink to print self-healing devices that heal in record time November 7th, 2016

Nanobionic spinach plants can detect explosives: After sensing dangerous chemicals, the carbon-nanotube-enhanced plants send an alert November 2nd, 2016

Molecular Machines

Micro-bubbles make big impact: Research team develops new ultrasound-powered actuator to develop micro robot November 25th, 2016

Scientists come up with light-driven motors to power nanorobots of the future: Researchers from Russia and Ukraine propose a nanosized motor controlled by a laser with potential applications across the natural sciences and medicine November 11th, 2016

HKU chemists develop world's first light-seeking synthetic Nanorobot November 9th, 2016

Light drives single-molecule nanoroadsters: Rice University scientists part of international team demonstrating untethered 3-wheelers November 4th, 2016

Chip Technology

Shape matters when light meets atom: Mapping the interaction of a single atom with a single photon may inform design of quantum devices December 4th, 2016

Quantum obstacle course changes material from superconductor to insulator December 1st, 2016

Bumpy surfaces, graphene beat the heat in devices: Rice University theory shows way to enhance heat sinks in future microelectronics November 29th, 2016

Scientists shrink electron gun to matchbox size: Terahertz technology has the potential to enable new applications November 25th, 2016

Discoveries

Shape matters when light meets atom: Mapping the interaction of a single atom with a single photon may inform design of quantum devices December 4th, 2016

UTSA study describes new minimally invasive device to treat cancer and other illnesses: Medicine diffusion capsule could locally treat multiple ailments and diseases over several weeks December 3rd, 2016

Novel Electrode Structure Provides New Promise for Lithium-Sulfur Batteries December 3rd, 2016

Research Study: MetaSOLTM Shatters Solar Panel Efficiency Forecasts with Innovative New Coating: Coating Provides 1.2 Percent Absolute Enhancement to Triple Junction Solar Cells December 2nd, 2016

Announcements

Shape matters when light meets atom: Mapping the interaction of a single atom with a single photon may inform design of quantum devices December 4th, 2016

UTSA study describes new minimally invasive device to treat cancer and other illnesses: Medicine diffusion capsule could locally treat multiple ailments and diseases over several weeks December 3rd, 2016

Novel Electrode Structure Provides New Promise for Lithium-Sulfur Batteries December 3rd, 2016

Research Study: MetaSOLTM Shatters Solar Panel Efficiency Forecasts with Innovative New Coating: Coating Provides 1.2 Percent Absolute Enhancement to Triple Junction Solar Cells December 2nd, 2016

Nanobiotechnology

Deep insights from surface reactions: Researchers use Stampede supercomputer to study new chemical sensing methods, desalination and bacterial energy production December 2nd, 2016

Nanobiotix Provides Update on Global Development of Lead Product NBTXR3: Seven clinical trials across the world: More than 2/3 of STS patients recruited in the “act.in.sarc” Phase II/III trial: Phase I/II prostate cancer trial now recruiting in the U.S. November 28th, 2016

From champagne bubbles, dance parties and disease to new nanomaterials: Understanding nucleation of protein filaments might help with Alzheimer's Disease and type 2 Diabetes November 24th, 2016

Making spintronic neurons sing in unison November 18th, 2016

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project