Nanotechnology to benefit drug discovery

In addition, lab chips and microfluidics were singled out as the next nanotechnology breakthrough format in drug discovery. Liquid handling and microfluidics has made a breakthrough in recent years, with the advances in technology now overcoming the initial problems of insufficient throughput, unreliable data and mundane problems such as plugging of the tiny channels used in the products.

Speaking at Lab Automation Europe in London, Dr Al Kolb, consultant at KeyTech Solutions,​ pointed out the contribution lab chips and microfluidics have made in reducing, even eliminating, the bottleneck of invalidated proteins in some pharmaceutical companies.

Kolb outlined the advances in drug discovery miniturization over the past 5-10 years, which has seen 1-2 ul assays become 1536-well assays. Kolb also pointed out the complications in trying to increase this number, commenting that while 9000-well assays have been used, the problem of evaporation and condensation would create problems that would make it unsuitable for use on an industrial scale.

Dispensing too has seen amounts shrink considerably with nanolitre and picolitre amounts now the industry standard. He also mentioned how the process has been transformed by the relatively high degree of automation.

Companies such as Caliper Technologies​ are now looking at life science applications of nanotechnology with greater interest. The company have an extensive range of micron-scale microfluidics technologies in drug discovery applications and are researching the use of even smaller systems for their lab-on-a-chip portfolios.

Swiss-based microfluidics technology company SpinX Technologies​ are currently working on programmable microfluidics, which enables sub-microlitre reactions where in the fluidic components, paths, sequence and doses can be chosen in real-time.

By combining this technology with a readout system, it allows the platform to perform feedback-driven operations in the micro world. Examples of processes that benefit from programmable microfluidics include dynamic determination of dose-response curves, reactions at fixed pH, stoichiometric reactions, compound library cherry picking, trial-and-error protocols.

The sheer scale of funds invested into nanotechnology by some countries illustrates just how seriously they are taking the potential of this technology. For 2003, the US spent $860 million compared to $650 million for Europe. Countries such as Japan were also there on the list with a budget of $800 million.

According to Kolb, the US National Nanotechnology Initiative had a 2001 budget of less than $450 million. By 2005 this figure is set to reach approximately $1 billion. It is a similar story for the National Cancer Institute, which had a budget of $144 million this year.

Current Nanotech product sales have been estimated to be between $20-$50 billion with a figure set to top $2 trillion by the year 2015.

The emergence of QuantumDot Fluorescence (Qdots) as a nanotechnogical application for diagnostics and medicine was also discussed in depth. Quantum dots are semiconductor nanocrystals that fluoresce when excited by a light source, emitting bright colours that can identify and track properties and processes in various biological applications.

They have significant advantages over traditional fluorophores, particularly in terms of the brightness of the fluorescent signal they can generate, their range of colours and their stability.

One such company mentioned in the seminar was the QuantumDotCorporation,​ which were pioneering the use of this technology with its extensive Qdot conjugate range. The testament to this technological breakthrough, which was commercially launched in late 2002, led to recognition of quantum dot bioimaging as one of Science magazine's top 10 scientific breakthroughs of 2003.

While in its infancy, Qdots could eventually be applied to early detection of disease in vivo due to its specific and high sensitivity. This could especially be applied to cancer in which Kolb estimated that it currently took 4-5 years to detect from the initial cancerous cell growth.The aim was to use the Qdot's qualities to reduce that figure to a year.

It was also envisaged that Qdots may have uses in the delivery of drugs to specific sites. By utilising dendrimer polymers with a size of less than 1nm, cancer drugs could be delivered to specific target sites where ordinarily the drug would not have access to if delivered on its own.

One particular application in which the FDA has given initial approval for is Advanced Magnetics'​ Combidex technology.

Combidex (ferumoxtran-10) consists of iron oxide nanoparticles for use in conjunction with magnetic resonance imaging (MRI) to aid in the differentiation of cancerous from non-cancerous lymph nodes. Clinical studies have shown that Combidex accumulates in non-cancerous lymph node tissue, which enables doctors using magnetic resonance imaging to have improved diagnostic confidence in differentiating between normal and diseased lymph nodes.