Quantum Dots Light Up The Brain

Enhanced quantum dot labeled astrocyte neural glial cells. Gabriel A. Silva and Smita Pathak.

There exists a technology that lets scientists selectively target and color code cells. Quantum dots are tiny nanometer-sized particles that display unique physical properties that allow them to fluoresce across a rainbow of bright colors. They can also be molecularly functionalized, meaning that you can chemically attach other molecules and proteins to their surface which in turn interacts with different cells in a targeted way. This makes them well suited for visualizing and tracking molecular processes inside cells, including neurons in the brain and other parts of the nervous system.

What are quantum dots and how do they work?

If you take an atom and inject energy into it, for example, by shining it with light of a specific wavelength, the electrons that surround the nucleus of the atom get excited and jump to a higher energy level. But they tend to be unstable at this higher level, and so eventually relax back down to their more stable lower level. When they do, they need to part themselves from the extra energy they gained. They do this by emitting that energy back out as light.

Quantum dots work in a similar way. But instead of being a single atom, they’re a larger semiconductor particle. They absorb light of specific wavelengths, and in return they emit light — they fluoresce — at different colors. What makes quantum dots such an interesting nanotechnology however are the unique properties they display. First of all, the color they fluoresce at is not dependent on the material they’re made from, but rather, the size and diameter of the quantum dot.

Furthermore, quantum dots are have a broad absorption spectra — meaning they can be excited across a relatively wide range of wavelengths of light. Yet, they have very narrow emission spectra: the wavelengths of light that anyone quantum dot sends back out is a very narrow range. Wavelength determines color, so a a narrow emission spectra means that quantum dots are able to emit light at very specific colors. This is why they produce such a distinct rainbow of non-overallping colors. In turn, a narrow emission spectra allows the multiplexing of colors — you can use different colored quantum dots to selectively bind to and label different distinct molecules and proteins in a cell. That’s a big advantage.

Quantum dots are a semiconductor nanocrystals with distinctive conductive properties determined by their size that allows them to fluoresce at distinct colors. Getty Images.

At the same time, they also photobleach slowly. This means that the intensity of their colors fades slowly over time, in contrast to other molecular markers often used in cell biology. Scientists take advantage of this property to ‘track’ how molecules are moving inside a cell over time, since the quantum dot tag continues to fluoresce over prolonged periods.

They also display a blinking property that allows the identification of individual quantum dots in a sample. As a result, single-molecule binding events can be identified and tracked over time, something that is very difficult to do with other molecular methods.

How are quantum dots able to target and tag specific molecules? The core of a quantum dot is typically composed of a heavy metal, such as cadmium selenium or cadmium telluride, although more recently quantum dots made from other materials are also possible. Surrounding this core is an intermediate unreactive layer, for example a zinc sulfide shell. The optical properties of the quantum dot are all the result of the physics associated with its core. But it’s a customized outer coating that allows it to bind to and interact specifically with target molecules, while ignoring everything else. The outer coating is engineered so that it consists of different bioactive molecules that only bind to molecules of interest expressed on — or in — the cells being targeted. It’s this chemically functionalized outer coating that provides the binding specificity of the quantum dot. In at least some types of cells, quantum dots chemically conjugated with naturally occurring molecules are readily internalized into the cells, do not interfere with the normal signaling pathways inside the cell, and seem to be non-toxic.

Quantum dots in neuroscience

Similar to other cells, in neuroscience, quantum dots can be used to visualize, measure, and track individual molecular events over extended periods, i.e. from seconds to many minutes. But specific to the cells of the brain and nervous system, quantum dots are particularly well suited to do experiments and measurements where there is restricted and tight cellular anatomy, a common challenge in the super dense networks of cells that make up the brain. For example, in the tiny and molecularly crowded space of the synaptic cleft — the connection point between two neurons.

A growing body of research and work continues to explore the use of different types of quantum dots for labeling neural cells and studying their cell biology. In some cases, and because the outer coating can be chemically functionalized, some groups are exploring the use of quantum dots as biomarkers for diseases such as Parkinson’s. The goal is to develop new diagnostics that can detect molecular changes early prior to the development of symptoms and neurological deficits. Being able to do so would allow clinicians to intervene earlier and hopefully delay or even arrest the progression of the disease.

Other work is focused not on diagnostics or cell biology experiments in a dish, but rather the use of this technology for clinical use in humans. For example, recent work using carbon quantum dots looked at their potential for treating neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s Disease by disrupting the tangles of amyloid proteins associated with disease progression. Other researchers are exploring the potential future use of quantum dots for brain imaging.

Like any newer technology though, and despite continued and exciting progress, there are a number of challenges and open questions that need to be tackled. This is particularly true when it comes to clinical applications in humans. Any enthusiasm needs to be realistically tempered. One of the biggest concerns is the chemical composition of the quantum dots themselves. In particular quantum dots that contain a heavy metal core that might cause possible toxicity. Other considerations include the need to fully understand how well quantum dots are cleared from the brain and the body, and any potential changes to internal cell signaling pathways induced by the uptake of quantum dots. In vivo applications to date have focused on animal models. No study has yet reached clinical testing in humans.

Still, quantum dots offer a unique opportunity for advancing scientists’ understanding of the brain. And perhaps someday maybe even new clinical applications — diagnosing and treating neurological disorders in ways not possible today. It’s a bright future ahead.

This article was originally published on Forbes.com. You can check out this and other pieces written by the author on Forbes here.

Professor of Bioengineering and Neurosciences, University of California San Diego

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Gabriel A. Silva

Gabriel A. Silva

Professor of Bioengineering and Neurosciences, University of California San Diego

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