Fingertip Microscope Can Peek Inside a Moving Animal

An inexpensive microscope about the size of a gumdrop could allow scientists to peer into the inner workings of living, moving animals much more easily. The device is small and light enough—it weighs less than two grams—to be mounted atop a rodent’s head, where it can capture the activity of up to 200 individual brain cells as the animal explores its environment.

That’s more cells than can be monitored using an expensive two-photon microscope, which doesn’t allow the animal to move, says Mark Schnitzer, a neuroscientist at Stanford University and one of the device’s creators. The microscope is designed to detect fluorescent light, which is often used in biological research to mark different cells.

Schnitzer, a TR35 honoree in 2003, says it’s difficult to calculate the cost of building the microscope, but he says each component costs only a few dollars. Schnitzer and some of his collaborators have formed a startup to commercialize the device.

The research is part of a growing trend in microscopy to make smaller and smaller devices, which are useful for everything from new areas of research to detecting tuberculosis in developing countries. These diminutive new devices are made possible in large part by the rapidly falling cost and size of electronics components—a trend that has in turn been driven by the demand for consumer devices.

“The massive volume of the cell-phone market is driving costs down while not sacrificing performance,” says Aydogan Ozcan, professor of electrical and biomedical engineering at the University of California, Los Angeles. “Scientists are realizing that with cost-effective compact architecture, they can have components that a decade ago would cost thousands of dollars, if you could find them.”

At the heart of the Stanford microscope is a complementary metal-oxide-semiconductor (CMOS) sensor, like the kind found in cell-phone cameras. All of the components used are either mass-produced or capable of being mass-produced, making it easy to scale up production. The research was published on Sunday in the journal Nature Methods.

The development of the device was driven by researchers’ desire to study how the brain directs movement, an endeavor that requires a microscope that can study brain cells while animals move and behave naturally. Schnitzer’s team had previously developed a small, flexible microscope in which light was delivered to the brain via a fiber-optic cable. But this approach limits the animal’s movement and captures activity in only a very small region of the brain. It’s also expensive, with the optical and electronics components costing $25,000 to $50,000.

The new device has a larger field of view, and all the optical components are integrated into the housing that sits on the animal’s head. “The advancement in being able to make a fluorescent scope this compact is really significant,” says Daniel Fletcher, a bioengineer at the University of California, Berkeley, who was not involved in the research. “For the animal to be able to carry the whole microscope along with it opens a lot more possibilities in studying behavior.”

Schnitzer says the microscope will have uses beyond brain imaging. A number of the microscopes can be put together and used to quickly count cells or screen lab animals, such as zebrafish, that are used in drug development.