Revolutionizing the field of biology, expansion microscopy has empowered scientists to visualize biomolecules with unprecedented resolution, enabling new discoveries and insights into complex biological systems.
Nearly 150 years ago, scientists began to imagine how information might flow through the brain based on the shapes of neurons they had seen under the microscopes of the time. With today’s imaging technologies, scientists can zoom in much further, seeing the tiny synapses through which neurons communicate with one another, and even the molecules the cells use to relay their messages.
Neurons, also known as nerve cells, are specialized cells in the nervous system responsible for transmitting and processing information.
They have three main parts: dendrites, cell body, and axon.
Dendrites receive signals from other neurons, while the cell body contains the nucleus and organelles necessary for neuronal function.
The axon transmits signals away from the cell body to other neurons or muscles.
There are over 86 billion neurons in the human brain, making them a crucial component of our nervous system.
The Power of Expansion Microscopy
Using methodology developed in the lab of MIT McGovern Institute for Brain Research investigator Edward Boyden, researchers around the world are imaging samples that have been swollen to as much as 20 times their original size so their finest features can be seen more clearly. This technique, known as expansion microscopy (ExM), allows researchers to image tissue samples with unprecedented resolution.
Expansion microscopy is a super-resolution imaging technique that allows for the visualization of cellular structures at nanoscale resolution.
Developed in 2014, this method involves physically expanding the sample to increase spatial resolution without losing signal intensity.
By using a hydrogel-based expansion agent, researchers can expand the sample by up to 4-fold, enabling the observation of previously invisible details.
This technique has revolutionized our understanding of cellular biology and has applications in various fields, including neuroscience and cancer research.
How it Works
Expansion microscopy involves infusing tissue samples with a hydrogel, which is then chemically softened and water is added. As the hydrogel absorbs the water, it swells and the tissue expands, growing evenly so the relative positions of its components are preserved. This process enables researchers to see features that would have blurred together under a standard light microscope.
Democratizing Nanoimaging
Boyden says that expansion microscopy democratizes nanoimaging, allowing anybody to go look at the building blocks of life and how they relate to each other. With ExM, researchers can visualize biomolecules with precision down to atomic scale, which has opened up new avenues for research in fields such as neurology, microbiology, and plant biology.

Applications and Impact
Since its introduction in 2015, expansion microscopy has been applied to a wide range of fields, including kidney disease, the fruit fly brain, “plant seeds”, the microbiome, Alzheimer’s disease, viruses, and more. The technique has empowered scientists to make new discoveries and gain insights into complex biological systems.
Real-World Applications
Expansion microscopy has been used in various research settings, from studying the malaria parasite to visualizing proteins inside cells. Researchers such as Sabrina Absalon have found that ExM is particularly useful in fields where resources are limited, allowing them to access high-resolution imaging without expensive equipment.
Always Improving
Boyden and his team continue to refine and improve expansion microscopy, adapting protocols for different sample types and developing new techniques to visualize biomolecules. The future of ExM will be shaped by innovators outside the Boyden lab, who are modifying and improving the technique to tackle new challenges.
Future Directions
The ultimate goal of expansion microscopy is to enable researchers to see every biological system down to its smallest building blocks. With continued innovation and advancement, ExM has the potential to revolutionize our understanding of life and disease.
Empowering scientists with unprecedented resolution, expansion microscopy is a powerful tool that is transforming the field of biology and medicine.
- mit.edu | A brief history of expansion microscopy