Playtime over, now 'atomic Lego' goes to work

Nanotechnology is the newest frontier for science and engineering. Concerning itself with the science of the very, very small, nanotechnology is all about manipulation of particles at the atomic and molecular level.

A recent report commissioned from Ernst and Young by the Federal government identified a number of Australian companies working in nanotech, including several biotechnology companies. That wasn't including the academic and institutional nanotechnology groups around the country.

The government has identified nanotechnology as an area of innovation that should be pursued for possible competitive advantages.

In addition, the Australian Research Council (ARC) has identified nanomaterials and biomaterials as one of its four designated priority areas for research in 2003.

But in global nanotech terms, Australia is playing catch-up.

A recent article in the Australian Venture Capital Journal by Randal Leeb-du Toit, executive chairman of Tribalweave Capital, listed Australia's government spending on nanotechnology last year as $US20 million, light years behind the $US696 million spent by the US government.

Japan, Korea and Germany also invested major sums into nanotechnology.

Leeb-Du Toit's company provides VC and information support to the convergence of infotech, biotech and nanotech.

"At this stage most of our focus is offshore, as it is more mature," he says.

Leeb-du Toit believes Australia currently lacks a holistic approach to nanotechnology. The Nanotechnology Initiative in the US has worked as an aggregator for the industry, he says, providing focus for investors.

"Until we have some kind of evangelist body focused on commercialising nanotechnology, we are not going to get much investment happening," he says.

But University of Queensland's senior deputy vice-chancellor, Prof Paul Greenfield, disagrees. Greenfield, who is involved with UQ's new Australian Institute of Bioengineering and Nanotechnology, believes that there is no need at this point for an overarching body or organisation for nanotechnology because there is plenty of scope for organisations like AusBiotech to provide the network support while the industry develops.

One of the really interesting things about nanotechnology is that scientists have found that novel properties often appear when working in the 1-100 nanometre range.

"We are moving from a Newtonian physics to a quantum physics approach to applied materials science," says Gavin Rezos, managing director of Perth based pSivida.

At this level, the behaviour of surfaces becomes much more important, and properties of materials can change dramatically from those exhibited at a larger scale.

In addition, nanotechnology allows very precise engineering and manufacture, often on a molecular scale.

"In nanotechnology, the realisation is that when you get small enough, the intractable problems become molecules which can be engineered," says Dr Bruce Cornell, chief scientist at Sydney company Ambri.

"Nanotechnology is all about taking very small pieces of matter and assembling them into precisely controlled structures," says Prof Matt Trau, who directs the Nanotechnology and Biomaterials Centre at the University of Queensland.

Rezos likes to call it "atomic Lego."

Broadly speaking, there are three overlapping platforms for nanotechnology:

• Nanoelectronics and photonics,
• Nanomaterials and nanoparticles, and
• Nanobiotechnology.

Australia has ongoing research projects across all of these platforms. In the nanobiotechnology arena, the companies and researchers in the sector are using several different approaches.

There are two approaches to working with nanotechnology. One is the "top down" approach, where existing structures, processes and devices are scaled down. The other is the "bottom up" approach, which deals with self-replication as well as atomic and molecular assembly.

A good example of the "top down" approach is pSivida, a company developing applications for nanostructured porous silicon called BioSilicon. BioSilicon was invented by Prof Leigh Canham, who is now the chief scientific officer at pSiMedica, a UK-based subsidiary of pSivida.

BioSilicon has all of the useful properties of silicon, and is also biocompatible and biodegradable, Rezos says.

"It has a range of applications across the health care/biomedical sector," he says. "We focus primarily on the core platform of drug delivery."

He says that other potential applications include tissue engineering and diagnostics, as well as "smart technology" involving BioSilicon's use in bionics.

pSiMedica already has several collaborations, including one with St Thomas' Hospital at Kings College, London, to examine use in osteoporosis treatments. Another is with UK company Powderject Pharmaceuticals, which develops needle-free vaccine delivery systems.

In addition, pSiMedica is collaborating with Purdue University on nano-electronic uses of BioSilicon, and with Nottingham University on orthopaedic uses.

"Because it is a broad platform, we are building across the platform," Rezos says. He illustrates BioSilicon's potential by describing a slow release implant that delivers a chemotherapeutic drug specifically to a tumour over a whole month.

He believes that drug delivery devices using BioSilicon are only a couple of years away.

"There is a lot of hype, but also a lot of promise," Rezos says of nanotechnology. "It has the potential to change the way we live."

Grow your own

In contrast to the approach taken by pSivida, Starpharma is working from the bottom up, creating dendrimers for use in drug delivery.

Dendrimers are created by building branches upon branches from a core structure in a controlled and precise fashion. The resulting structure can be used to deliver functional activity in a targeted fashion.

Dr John Raff, CEO of Starpharma and former director of the Biomolecular Research Institute, which developed the technology owned by Starpharma, says dendrimer chemistry was one of the few options available for creating synthetic molecules in the nano range.

The molecules are biocompatible and water soluble, as well as biomimetic, he says. In addition, the molecules are polyvalent, meaning that a number of active groups can be attached to the dendrimer structure. This increases the number of interactions between the active group and the target receptor, which can dramatically increase the biological activity.

According to Raff, dendrimers can be built with several functional groups targeting different things.

"We're building molecules which can attack things in more than one way at a time. We can target a range of diseases with one molecule," he explains.

This property is being exploited in Starpharma's vaginal microbicide gel, which is being readied for human clinical trials. The gel has activity against HIV, Herpes, chlamydia and to a lesser extent genital warts and hepatitis B, says Raff.

"The vaginal microbicide will be the first time that the FDA will approve dendrimers for human clinical trials," Raff says. This has meant a lot of pioneering regulatory groundwork for the company to prove the safety of the drug.

"We are three to four months away from approval of the IND," he says. "We're taking it very cautiously, we don't want to muck it up."

Raff sees the development of drugs like the vaginal microbicide as being longer-term prospects, however. In the short term he sees dendrimer-based diagnostics as being the big opportunity.

Last year, Starpharma entered into a joint venture with Donald Tomalia, a pioneer of dendrimer technology, to form Dendritic Nanotechnologies (DNT).

"DNT is producing compounds for diagnostic applications and entering into license agreements for diagnostics," Raff says.

He says Tomalia was a good fit with Starpharma and brought a lot to the DNT venture, including 33 families of patents (more than 100 US patents) with very wide applications, including drug delivery, diagnostics, gene transfection, oligo and antisense delivery, as well as less biologically oriented uses.

"DNT will be focusing on the synthesis of a broad range of dendrimers and providing IP and research agreements to other companies interested in developing applications," Raff says.

Raff is enthusiastic about the possibilities for nanotechnology.

"It's a bit incredible that a small Australian company can find itself sitting in the middle of nanotechnology," he says.

Other nanotechnology researchers use a combination of the two approaches. Prof Matt Trau is developing a unique method for miniaturising high-throughput screening.

His team at UQ's Nanotechnology and Biomaterials Centre has come up with a ceramic bead and linker system to produce large encoded compound libraries using combinatorial chemistry.

The method can be used for oligonucleotides, peptides and polysaccharides, as well as more traditional combinatorial chemistry, and Trau is aiming his new company Nanomics Biosystems at the high throughput screening markets of genomics, proteomics, and drug discovery.

"We focus on making innovative materials and devices for biotechnology," Trau says. "We try to work at the interface between nanotechnology and biotechnology."

Nanomics Biosystems won a Biotechnology Innovation Fund grant earlier this year and Trau is confident that the company will be able to get off the ground quickly.

"We think the timelines in this industry are fairly quick. We'd look to having products manufactured within the next few years," he says.

Ambri has come up with a unique approach to diagnostics. The company has developed a molecular switch, which measures binding by changes to a biological membrane. It provides a very rapid, accurate and sensitive method of molecular detection.

"The basis of the technology is a molecular switch that uses an antibody to detect the presence of a compound," says Dr Bruce Cornell.

He explains that the key advantages of the system were speed and accuracy. The tests take just three to five minutes to perform, instead of several hours, and with some targets are more sensitive than existing tests. The system will initially be marketed for the emergency department, where time-critical tests can be done on site.

Ambri is planning to launch its first set of tests for human chorionic gonadotropin -- a hormone produced early in pregnancy -- and a panel of cardiac proteins indicative of heart attacks, in Australia in the middle of this year, followed by the US early 2003.

"Eventually we will have 40 separate tests, with a new one released every quarter," Cornell says.

Ambri is also working with the Australian Department of Defence on possible uses for detection of biological weapons and in the past have worked on projects for the US military.

Cornell sees plenty of opportunities in the future for Ambri's technology.

"In the longer haul, miniaturisation of the device would allow entry into a new realm," he says, envisaging implantable devices or patches with the ability to monitor for changes to the system.

"You could see how one could grow into those areas."

New nanocentre

The newest centre for nanotechnology in Australia is the Australian Institute of Bioengineering and Nanotechnology, a $50 million initiative spearheaded by the University of Queensland and the Queensland government.

Modelled on UQ's Institute for Molecular Bioscience (IMB), the key focus of the institute will be nanotechnology for the biomedical sciences, according to Prof Paul Greenfield, senior deputy vice-chancellor at the university.

The institute is still in the planning stages, but the university expects that it will get going in the second half of this year, although the building will not be completed until 2004. CSIRO has also indicated that it would like to locate 10 scientists at the Institute.

Greenfield says that one of the key tasks in planning the institute was identifying gaps and employing scientists to augment the existing strengths at UQ.