Smart Phones Snap Pictures Of Individual Virus Particles

By attaching a lightweight, inexpensive device to the back of a smart phone, scientists can convert the phone into a sensitive fluorescence microscope. The attachment allows the phone’s camera to take pictures of single nanoparticles and viruses, possibly providing a portable diagnostic tool for health care workers in developing countries (ACS Nano 2013, DOI: 10.1021/nn4037706).

With fluorescent microscopes, researchers can detect and study important biomolecules or single cells that they’ve labeled with fluorescent dyes. But the instruments are bulky and expensive, says Aydogan Ozcan at the University of California, Los Angeles. As a result, people with limited resources, such as those in developing countries, often don’t have access to these diagnostic tools.

Ozcan wondered whether he could make a portable fluorescence microscope by attaching a device to the camera of a smart phone. Smart phones are small, relatively inexpensive, and, with cell networks spreading rapidly across the globe, many people already own one. However, imaging nanoparticles and viruses is challenging, because individual dye-labeled particles emit very weak fluorescent signals, particularly in comparison to other light sources in the experiment such as the laser light used to excite the fluorescent dyes.

Ozcan’s team solved this problem by devising a compact system of lenses and filters that removes the background noise caused by the laser light. First, they optimized the way the light hits the sample, which sits on a cover glass above the phone’s camera. The team positioned the laser diode so that it illuminated the sample at a 15º angle from the surface. At this angle, most of the beam of 450-nm light misses the lens under the sample that collects the fluorescent signals from the dyes. The team also placed a long-pass filter above this lens to remove any laser light scattered by the sample, so that only the emitted fluorescence passes through the cell phone lens and into the camera’s sensor for detection.

Instrument makers also rely on an angle trick to decrease noise when designing conventional fluorescent microscopes, but Ozcan’s team had to optimize their angle to balance noise reduction and the size of their device.

To test their portable fluorescent microscope, Ozcan’s team examined fluorescently labeled human cytomegalovirus particles, which were between 150 and 300 nm in diameter, and polystyrene beads, which, at 100 nm in diameter, were the smallest objects the device detected. Using scanning electron microscopy, the team confirmed the sizes of the objects and their positions in the images taken by the camera phone.

According to Ozcan, the device is the first portable, cell-phone-based imaging system sensitive enough to detect individual nanoparticles and viruses. He started a company called Holomic to commercialize this and other cell-phone-based analytic techniques. His lab also has created several smart-phone apps for data analysis.

“This approach has far-reaching uses in point-of-care diagnostics,” says Ertugrul Cubukcu at the University of Pennsylvania. For example, doctors in remote regions could use the technique to measure HIV viral loads in patients’ blood samples, allowing the doctors to easily monitor disease progression and determine the best course of treatment.