3-D-printed microscope can make single-molecule measurements

Some of the most powerful microscopic techniques allow biochemists to analyze single molecules inside cells or in solution. A new 3-D-printed microscope can perform these single-molecule measurements with quality that rivals that of larger, more expensive, conventional instruments. The new instrument could make single-molecule measurements accessible to nonspecialists.

To make the microscope, Yann Gambin and Emma Sierecki of the University of New South Wales and coworkers printed a plastic block that prealigns the optical components (Nat. Commun. 2019, DOI: 10.1038/s41467-019-13617-0). Light sources and filters can be easily changed to meet an experiment’s needs without affecting the alignment. The housing, which is only 10 cm × 20 cm, easily fits on a standard lab bench or desk.

“We wanted a compact and cheap instrument that works in broad daylight as we started to run out of space in our dark rooms, and our normal confocal microscopes were overbooked,” Gambin says. The microscope costs about $25,000 with top-end optics. Some conventional microscope systems can have price tags that reach six figures.

The researchers used the microscope, which they dubbed the AttoBright, to perform single-molecule fluorescence correlation spectroscopy. “FCS is the hardest measurement to perform,” Gambin says. But the instrument isn’t limited to FCS, he says.

The microscope’s performance is as good as or even better than that of conventional instruments, Gambin says. Conventional microscopes require many relay lenses, which can lead to optical distortion and loss of signal. “We use a single high-quality lens and have fine piezo adjustment to automatically align the setup and have optimal signal,” he says.

“This is really excellent work,” says Markus Sauer, an expert in single-molecule spectroscopy at the University of Würzburg. “The quality of the single-molecule data presented is convincing and comparable to the data measured by highly sophisticated and expensive microscopes.”

Aydogan Ozcan, an engineering professor at the University of California, Los Angeles, who is also developing portable spectroscopy devices, thinks this 3-D printed instrument “could potentially be an enabler technology for various biomedical sensing modalities as well as for research purposes in resource-limited countries.”

The Australian team demonstrated that they can use the device to detect individual α-synuclein amyloid fibrils, which are associated with Parkinson’s disease. The researchers are trying to develop a blood test for Parkinson’s based on detection of α-synuclein fibrils in blood.