Founded in October 2001 and backed by angel investment of £150,000, Infinitesima released its first product - the ActivResonance Controller just a month later. "Basically [the ActivResonance Controller] is a box of electronics that you attach to any manufacturer's atomic force microscope," Mark Kingsley-Williams, Infinitesima commercial director told "It enhances the quality factor of the probe, improving the resolution of the images that you can obtain when looking at very soft samples or those in liquid. So if you want to image DNA, cells and gels, this instrument allows you to use your AFM, but exert less force on the surface and therefore cause less disruption and obtain higher resolution images."

The ActivResonance Controller costs $15,000, "a small cost for improved imaging", according to Kingsley-Williams. A market-leading AFM, in comparison, costs about $200 000. So far, Infinitesima has sold 10 controllers and is currently working on an improved version.

Fast track
Infinitesima also has its eye on a couple of other imaging technologies. For a start, there is resonant scanning microscopy (RSM), the two-year-old invention of Bristol University's Mervyn Miles, Andy Humphris and Jamie Hobbs.

"The AFM was a great breakthrough, but it's not terribly good for following dynamic processes," explained Kingsley-Williams. "Commercial microscopes available at the moment allow you to capture images maybe every few minutes. That's fine if what you're looking at is static, but many interesting biological processes, such as DNA replication, happen on timescales of less than a second."

Kingsley-Williams says that other researchers have attempted to make incremental improvements in AFM imaging speeds, by moving probes faster or "shrinking things down". "You're ultimately going to hit some fairly fundamental physical limits," he said. But RSM is a new approach that combines two existing technologies.

"It's a form of scanning near-field optical microscope [SNOM]," explained Kingsley-Williams. SNOM is a type of scanning probe microscope that produces an optical image of a sample with nanometre resolution. RSM, meanwhile, images a sample by swinging the probe above the surface at its resonant frequency, increasing the scan speed by a factor of 10,000.

"This isn't just an incremental increase," said Kingsley-Williams. "We're going from a stage where you might be capturing an image once every five minutes to being able to see things at a much faster rate than video. There'll be more data coming from your microscope than you can look at in real-time." That means that, once Infinitesima has overcome a couple of issues, the microscope should be able to image DNA replication and dynamic molecular processes.

"It [the RSM] is possibly one of the biggest innovations in microscopy in the 20 years since the development of the scanning probe microscope," said Kingsley-Williams. "It takes the AFM a huge step further forward."

Infinitesima plans to commercialize the initial version of the RSM from mid-2003, aiming the equipment at the research market.

Shear focus
And there's more. Infinitesima also has funding to the tune of £45,000 from the UK's Department of Trade and Industry. The money is aimed at developing a technique called transverse dynamic force microscopy, a "true non-contact form of scanning probe microscopy".

"If you are imaging with your probe mounted parallel to the sample, it's very difficult to detect very small changes in the forces exerted on the probe without the probe actually touching the sample's surface," explained Kingsley-Williams. "There is a problem called jump to contact, where if you get a little bit too close, Van der Waal's forces come into play and your probe is sucked onto the surface that you are examining."

The transverse dynamic force microscope, in contrast, has a perpendicular probe. Indeed, the Bristol University scanning probe microscopy group has used this type of microscope to produce what it claims are the highest resolution images of DNA to date.

So what's the plan now? "To fully commercialize the resonant scanning microscope and to fund international sales and marketing initiatives we're looking for another fairly modest round [of funding]," said Kingsley-Williams. The round, which aims to raise £350,000, should see the company through to profitability, which is currently forecast for the last quarter of 2003.