Scientists have developed a miniature fluorescence microscope small enough to implant in the head of a living mouse and gather images from its brain without hindering its movement. The 1.9-gram, 2.4-cubic-centimetre device is described today in Nature Methods1.
The device has already yielded results. The authors, led by applied physicist Mark Schnitzer and electrical engineer Abbas El Gamal of Stanford University in Stanford, California, report findings regarding both the dilation of capillaries in mouse brains and the firing of motor-activity-related Purkinje neurons, as well as some potential in vitro applications for the device, such as counting cells or spotting bacteria in samples.
With a maximum resolution of 2.5 microns, the microscope is not as powerful as conventional bench-top models, which have resolutions as fine as 0.5 microns. But it does have a "very good" field of view which is larger than some bench-top models, notes Schnitzer. "For neuroscientists, [this method] is going to enable some experiments that we couldn't do before – indeed it already has", he says.
Schnitzer and three of his colleagues have already founded a company, called Inscopix, in hopes of capitalizing on their device.
While miniature versions of fluorescence microscopes have been produced before, including one by the Stanford group in 2008 that was lighter, none have been self contained or made using mass produced components. This microscope "contains all the optical parts within a single, small and easily-transportable housing, and we use mass-fabricated components, which opens up the possibility of mass-producing the entire microscope," says Schnitzer.
Using a conventional fluorescence microscope to look into the brains of animals requires holding the animals firmly in place, which is incompatible with natural behaviour. And, the authors say, it is difficult to study many animals at the same time, because a lab often only has one microscope. The new device is computer-controlled, and images it gathers are viewed on a monitor.
While the main prospective application is to give researchers the opportunity to image the brains of animals such as mice as they move freely, future uses might also include image based screening and looking for signs of disease in samples, notes the paper. The highly portable nature of the technology and potential low cost mean it could be used in locations or countries where access to conventional microscopes are limited.
Schnitzer doesn't know when a commercial device might come to fruition, or what it might cost to produce. But he believes it could in principle be done cheaply, estimating that the light source and camera would cost somewhere between US$1 and $10 each — compared with $25,000–50,000 for a scientific-grade camera — and that all the other optical parts, such as the micro lenses and filters, could also be mass-produced.
Daniel Fletcher, a microscopy expert at the University of California at Berkeley, says the cost is "rather optimistic", but describes the new technology as a "neat device" and a "particular advance" for brain imaging in moving animals. "For the application that they are targeting it is providing plenty of information," he says. But, he added, other applications might be hampered by factors such as the device's lower resolution compared to conventional bench-top fluorescent microscopes.
More work needs to done to pursue these other directions, acknowledges Schnitzer. "We will have to wait and see," he says.
- Ghosh, K. K. et al. Nature Methods Advance online publication http://dx.doi.org/10.1038/nmeth.1694 (2011).
By Zoë Corbyn