Tag Archives: DNA nanotubes

Customizing DNA nanotubes quickly and cheaply

Building on some work published earlier this year, scientists from McGill University (Montréal, Québec) created a new technique for building DNA nanotubes block by block (my March 2, 2015 posting) and, now, the newest research from the McGill team features a way of making long DNA strands with that technique, as mentioned in a May 7, 2015 news item on Azonano,

Imagine taking strands of DNA – the material in our cells that determines how we look and function – and using it to build tiny structures that can deliver drugs to targets within the body or take electronic miniaturization to a whole new level.

While it may still sound like science fiction to most of us, researchers have been piecing together and experimenting with DNA structures for decades. And, in recent years, work by scientists such as McGill University chemistry professor Hanadi Sleiman has moved the use of man-made DNA structures closer to a variety of real-world applications.

But as these applications continue to develop, they require increasingly large and complex strands of DNA. That has posed a problem, because the automated systems used for making synthetic DNA can’t produce strands containing more than about 100 bases (the chemicals that link up to form the strands). It can take hundreds of these short strands to assemble nanotubes for applications such as smart drug-delivery systems.

Here’s a video featuring one of the researchers taking about this latest work from McGill University,

A May 6, 2015 McGill University news release, which originated the news item, describes the long DNA nanotubes in more detail,

In new research published May 5 in Nature Communications, however, Sleiman’’s team at McGill reports that it has devised a technique to create much longer strands of DNA, including custom-designed sequence patterns. What’s more, this approach also produces large amounts of these longer strands in just a few hours, making the process potentially more economical and commercially viable than existing techniques.

The new method involves piecing together small strands one after the other, so that they attach into a longer DNA strand with the help of an enzyme known as ligase.  A second enzyme, polymerase, is then used to generate many copies of the long DNA strand, yielding larger volumes of the material. The polymerase process has the added advantage of correcting any errors that may have been introduced into the sequence, amplifying only the correctly sequenced, full-length product.

Designer DNA materials

The team used these strands as a scaffold to make DNA nanotubes, demonstrating that the technique allows the length and functions of the tubes to be precisely programmed. “In the end, what we get is a long, synthetic DNA strand with exactly the sequence of bases that we want, and with exactly as many repeat units as we want,” explains Sleiman, who co-authored the study with Graham Hamblin, who recently completed his doctorate, and PhD student Janane Rahbani.

“This work opens the door toward a new design strategy in DNA nanotechnology,” Sleiman says. “This could provide access to designer DNA materials that are economical and can compete with cheaper, but less versatile technologies. In the future, uses could range from customized gene and protein synthesis, to applications in nanoelectronics, nano-optics, and medicine, including diagnosis and therapy.”

Here’s a link to and a citation for the paper,

Sequential growth of long DNA strands with user-defined patterns for nanostructures and scaffolds by Graham D. Hamblin, Janane F. Rahbani, & Hanadi F. Sleiman. Nature Communications 6, Article number: 7065 doi:10.1038/ncomms8065 Published 05 May 2015

This article is behind a paywall.

McGill University (Canada) researchers build DNA nanotubes block by block

McGill University (Montréal, Québec, Canada) researchers have found a new technique for creating DNA (deoxyribonucleic acid) nanotubes according to a Feb. 24, 2015 news item on Azonano,

Researchers at McGill University have developed a new, low-cost method to build DNA nanotubes block by block – a breakthrough that could help pave the way for scaffolds made from DNA strands to be used in applications such as optical and electronic devices or smart drug-delivery systems.

A Feb. 23, 2015 McGill University news release (also on EurekAlert), which originated the news item, describes current practice and the new technique,

Many researchers, including the McGill team, have previously constructed nanotubes using a method that relies on spontaneous assembly of DNA in solution. The new technique, reported today in Nature Chemistry, promises to yield fewer structural flaws than the spontaneous-assembly method. The building-block approach also makes it possible to better control the size and patterns of the DNA structures, the scientists report.

“Just like a Tetris game, where we manipulate the game pieces with the aim of creating a horizontal line of several blocks, we can now build long nanotubes block by block,” said Amani Hariri, a PhD student in McGill’s Department of Chemistry and lead author of the study. “By using a fluorescence microscope we can further visualize the formation of the tubes at each stage of assembly, as each block is tagged with a fluorescent compound that serves as a beacon. We can then count the number of blocks incorporated in each tube as it is constructed.”

This new technique was made possible by the development in recent years of single-molecule microscopy, which enables scientists to peer into the nano-world by turning the fluorescence of individual molecules on and off. (That groundbreaking work won three U.S.- and German-based scientists the 2014 Nobel Prize in Chemistry.)

Hariri’s research is jointly supervised by chemistry professors Gonzalo Cosa and Hanadi Sleiman, who co-authored the new study. Cosa’s research group specializes in single-molecule fluorescence techniques, while Sleiman’s uses DNA chemistry to design new materials for drug delivery and diagnostic tools.

The custom-built assembly technique developed through this collaboration “gives us the ability to monitor the nanotubes as we’re building them, and see their structure, robustness and morphology,” Cosa said.

“We wanted to control the nanotubes’ lengths and features one-by-one,” said Sleiman, who holds the Canada Research Chair in DNA Nanoscience. The resulting “designer nanotubes,” she adds, promise to be far cheaper to produce on a large scale than those created with so-called DNA origami, another innovative technique for using DNA as a nanoscale construction material.

Here’s a link to and a citation for the paper,

Stepwise growth of surface-grafted DNA nanotubes visualized at the single-molecule level by Amani A. Hariri, Graham D. Hamblin, Yasser Gidi, Hanadi F. Sleiman & Gonzalo Cosa. Nature Chemistry (2015) doi:10.1038/nchem.2184 Published online 23 February 2015

This article is behind a paywall.

Responsible science communication and magic bullets; lego and pasta analogies; sing about physics

Cancer’s ‘magic bullet],  a term which has been around for decades, is falling into disuse and deservedly. So it’s disturbing to see it used by someone in McGill University’s (Montreal, Canada) communications department for a recent breakthrough by their researchers.

The reason ‘magic bullet for cancer’ has been falling into is disuse because it does not function well as a metaphor with what we now know about biology. (The term itself dates from the 19th century and chemist, Paul Erlich.) It continues to exist because it’s an easy (and lazy) way to get attention and headlines. Unfortunately, hyperbolic writing of this type obscures the extraordinary and exciting work that researchers are accomplishing. From the news release on the McGill website (also available on Nanowerk here),

A team of McGill Chemistry Department researchers led by Dr. Hanadi Sleiman has achieved a major breakthrough in the development of nanotubes – tiny “magic bullets” that could one day deliver drugs to specific diseased cells.

The lead researcher seems less inclined to irresponsible hyperbole,

One of the possible future applications for this discovery is cancer treatment. However, Sleiman cautions, “we are still far from being able to treat diseases using this technology; this is only a step in that direction. Researchers need to learn how to take these DNA nanostructures, such as the nanotubes here, and bring them back to biology to solve problems in nanomedicine, from drug delivery, to tissue engineering to sensors,” she said.

You’ll notice that the researcher says these ‘DNA nanotubes’ have to be brought “back to biology.” This comment brought to mind a recent post on 2020 Science (Andrew Maynard’s blog) about noted chemist and nanoscientist’s, George Whitesides, concerns/doubts about the direction for cancer and nanotechnology research. From Andrew’s post,

Cancer treatment has been a poster-child for nanotechnology for almost as long as I’ve been involved with the field. As far back as in 1999, a brochure on nanotechnology published by the US government described future “synthetic anti-body-like nanoscale drugs or devices that might seek out and destroy malignant cells wherever they might be in the body.”

So I was somewhat surprised to see the eminent chemist and nano-scientist George Whitesides questioning how much progress we’ve made in developing nanotechnology-based cancer treatments, in an article published in the Columbia Chronicle.

Whitesides comments are quite illuminating (from the article, Microscopic particles have huge possibilites [sic], by Ivana Susic,

George Whitesides, professor of chemistry and chemical biology at Harvard University, said that while the technology sounds impressive, he thinks the focus should be on using nanoparticles in imaging and diagnosing, not treatment.

The problem lies in being able to deliver the treatment to the right cells, and Whitesides said this has proven difficult.

“Cancer cells are abnormal cells, but they’re still us,” he said. [emphasis is mine]

The nanoparticles sent in to destroy the cancer cells may also destroy unaffected cells, because they can sometimes have cancer markers even if they’re healthy. Tumors have also been known to be “genetically flexible” and mutate around several different therapies, Whitesides explained. This keeps them from getting recognized by the therapeutic drugs.

The other problem with targeting cancer cells is the likelihood that only large tumors will be targeted, missing smaller clumps of developing tumors.

“We need something that finds isolated [cancer] clumps that’s somewhere else in the tissue … it’s not a tumor, it’s a whole bunch of tumors,” Whitesides said.

The upside to the treatment possibilities is that they buy the patient time, he said, which is very important to many cancer patients.

“It’s easy to say that one is going to have a particle that’s going to recognize the tumor once it gets there and will do something that triggers the death of the cell, it’s just that we don’t know how to do either one of these parts,” he said.

There is no simple solution. The more scientists learn about biology the more complicated it becomes, not less. [emphasis is mine] Whitesides said one effective way to deal with cancer is to reduce the risk of getting it by reducing the environmental factors that lead to cancer.

It’s a biology problem, not a particle problem,” he said. [emphasis is mine]

If you are interested , do read Andrew’s post and the comments that follow as well as the article that includes Whitesides’ comments and quotes from Andrew in his guise as Chief Science Advisor for the Project on Emerging Nanotechnologies.

All of this discussion follows on yesterday’s (Mar.17.10) post about how confusing inaccurate science reporting can be.

Moving onwards to two analogies, lego and pasta. Researchers at the University of Glasgow have ‘built’ inorganic (not carbon-based) molecular structures which could potentionally be used as more energy efficient and environmentally friendly catalysts for industrial purposes. From the news item on Nanowerk,

Researchers within the Department of Chemistry created hollow cube-based frameworks from polyoxometalates (POMs) – complex compounds made from metal and oxygen atoms – which stick together like LEGO bricks meaning a whole range of well-defined architectures can be developed with great ease.

The molecular sensing aspects of this new material are related to the potassium and lithium ions, which sit loosely in cavities in the framework. These can be displaced by other positively charged ions such as transition metals or small organic molecules while at the same time leaving the framework intact.

These characteristics highlight some of the many potential uses and applications of POM frameworks, but their principle application is their use as catalysts – a molecule used to start or speed-up a chemical reaction making it more efficient, cost-effective and environmentally friendly.

Moving from lego to pasta with a short stop at the movies, we have MIT researchers describing how they and their team have found a way to ‘imprint’ computer chips by using a new electron-beam lithography process to encourage copolymers to self-assemble on the chip. (Currently, manufacturers use light lasers in a photolithographic process which is becoming less effective as chips grow ever smaller and light waves become too large to use.) From the news item on Nanowerk,

The new technique uses “copolymers” made of two different types of polymer. Berggren [Karl] compares a copolymer molecule to the characters played by Robert De Niro and Charles Grodin in the movie Midnight Run, a bounty hunter and a white-collar criminal who are handcuffed together but can’t stand each other. Ross [Caroline] prefers a homelier analogy: “You can think of it like a piece of spaghetti joined to a piece of tagliatelle,” she says. “These two chains don’t like to mix. So given the choice, all the spaghetti ends would go here, and all the tagliatelle ends would go there, but they can’t, because they’re joined together.” In their attempts to segregate themselves, the different types of polymer chain arrange themselves into predictable patterns. By varying the length of the chains, the proportions of the two polymers, and the shape and location of the silicon hitching posts, Ross, Berggren, and their colleagues were able to produce a wide range of patterns useful in circuit design.

ETA (March 18,2010): Dexter Johnson at Nanoclast continues with his his posts (maybe these will form a series?) about more accuracy in reporting, specifically the news item I’ve just highlighted. Check it out here.

To finish on a completely different note (pun intended), I have a link (courtesy of Dave Bruggeman of the Pasco Phronesis blog by way of the Science Cheerleader blog) to a website eponymously (not sure that’s the right term) named physicssongs.org. Do enjoy such titles as: I got Physics; Snel’s Law – Macarena Style!; and much, much more.

Tomorrow: I’m not sure if I’ll have time to do much more than link to it and point to some commentary but the UK’s Nanotechnologies Strategy has just been been released today.

HIV testing, nano gold, and Uganda; not so obsolete?; new nanotube manufacturing technique from McGill University

There’s a portable blood-testing machine, designed by US-based PointCare, which can give a print-out detailing a patient’s immune status in 10 minutes. The machine was designed for use in third-world or developing world clinics such as the one in Uganda which is described in this BBC story.

One of the problems doctors and medical staff had with equipment for testing HIV patients’ immune system was that the chemicals used as reagents in the testing process were too easily perishable in the high heat common in a lot of countries. PointCare soved the problem this way (from the BBC article):

Dr Hansen [from PointCare] invented a test that uses chemical reagent that can be freeze-dried and stored in temperatures of over 40C.

CD4 screening tests use antibodies – molecular tags that recognise and latch onto a chemical marker on the surface of the cell. By attaching to the cells, they act as flags distinguishing CD4 cells from other white blood cells.

But these antibodies need to be “labelled”, so they can be detected by a machine.

Traditionally, antibodies are labelled using fluorescent markers, but these fluorescent chemicals perish if they are not kept refrigerated. So they’re useless for a medical team operating from a temporary clinic in the heat of an African summer.

Dr Hansen developed a new label. “We use colloidal gold,” explains Dr Krauledat [community physician]. “It’s true nanotechnology – extremely tiny gold particles attached to the anti-CD4 antibody.”

Do go and read the full story because there’s more to it than I’ve included. Meanwhile I had another look at those lithography stories (SFU’s new maskwriting facilities and RAPID) that I was posting about last week. While the new RAPID technique may make the use of ultra-violet light obsolete, they still haven’t approached the nanoscale. The measurement mentioned is “… 2500 times smaller than a human hair” [more here]. The measurement usually mentioned when discussing the nanoscale  is between 1/100,000 ro 1/60,000 (nobody seems to agree on the exact measurement, you can check here) of the width of a human hair equals 1 nanometre.  Weirdly, the Simon Fraser University (SFU) release notes that the new facilities will be able to create structures “… under 20 nanometres about 10,000 times smaller than the diameter of a human hair” [more here]. If I’m doing the math correctly, wouldn’t that be between 1/50,0000 and 1/30,000 of the human hair? I know it’s a little fussy but once a technical writer, always a technical writer and that kind of detail can make a big difference.

Researchers led by Dr. Hanadi Sleiman and Dr. Gonzalo Cosa at McGill University (Montreal, Canada) have developed a new way to manufacture nanotubes using DNA, in short they are DNA nanotubes. The longer story is here and the shorter story is here.