Neuroscience is the study of the nervous system, from the structure and function of neurons to the behavior of the animal. Essentially, it offers a scientific window into how the brain works. Neuroscientists are working to better understand how neurons in the nervous system fire and how that relates to their function within the complex networks in the brain and nervous system.
Imaging a cluster of cells
In order to gain a better understanding of how these neurons function, multidisciplinary teams of researchers have pooled together their expertise to improve the methods for which imaging is performed.
Fluorescence imaging is the use of fluorescent dyes or proteins in the imaging subject as a marker of the process, function or structure of what is being observed; this helps researchers observe the structure and function of the cell as fluorescence brightens.
The use of fluorescence imaging is common, but improvement in the process is greatly needed. That’s where scientific reach across multiple departments and expertise within the University come into play.
When examining clusters of neurons or other cells, they are modified to produce fluorophores—light-emitting molecules. The fluorophore is optically excited by two photons—each with insufficient energy to excite the fluorophore alone—that arrive from a laser simultaneously. The excitation laser produces short pulses of light that comprise millions of trillions of photons to ensure that some arrive simultaneously at the fluorophore. Typically, two-photon absorption is a weak process, which means that intense excitation light is needed to produce detectable fluorescence. “The intense laser light required for fluorescence excitation can damage or destroy living tissue and reduce observation time in the experiment,” said Kevin Daly, biology professor at WVU. “We need to record the activity of neurons as the animal actively behaves if we are to understand how brain function relates to behavior.”
Enter the power of quantum physics. Quantum entanglement occurs when subatomic particles, like photons or electrons, interact so that their properties become correlated even when separated by significant distance. Several novel processes, such as spontaneous down conversion or bright squeezed vacuum can be employed to take the short pulses of light with its many photons and convert single photons into quantum entangled pairs or groups. Any physical property—such as energy, momentum, position, or polarization—can be entangled between multiple photons. Here, to ensure that photons simultaneously arrive at the fluorophore, the arrival time of multiple photons must be entangled. In effect, by bringing highly correlated pairs of photons to the fluorophore simultaneously, the two-photon absorption efficiency can be massively enhanced and neuroscientific experimental observations can be greatly improved. Improved efficiency will enable imaging much deeper into tissue, gaining better observations of neural processes. With the improved multiphoton absorption efficiency, researchers hope to establish the feasibility of entangled light for 3-photon absorption, which will enable imaging even deeper into tissue than 2-photon absorption. This method, dubbed entanglement-enhanced multiphoton imaging (EMFI), will require physicists to develop an appropriate light source and for neuroscientists to integrate them into their existing microscopes.
Enter Quantum 2.0
Quantum 2.0 is a term used to describe research that uses the unintuitive aspects of quantum physics, such as entanglement, to solve novel and practical issues. The multidisciplinary team at WVU is doing just that to improve current neural imaging conditions using entangled photons. The goal of this project is to potentially yield greater resolution and efficiency in imaging biological processes in the nervous system.
The challenge is to develop and correctly calibrate the new sources of light, make them modular for integration in the existing two-photon microscopes, and to measure the enhancement factor in the microscope. This effort truly requires a multidisciplinary research team formed by WVU laboratories with expertise in quantum technology and optics, biology and neuroscience. This unique team of researchers comprises profs. Edward Flagg (pictured to the right) and Alan Bristow (pictured below) (Department of Physics and Astronomy), Kevin Daly (Department of Biology) and Charles Anderson (Department of Neuroscience).
Supporting their scientific collaboration, the National Science Foundation has awarded them a grant from the NSF program Quantum Sensing Challenges for Transformational Advances in Quantum Systems.
Further, the project has gained widespread support as part of the National Quantum Initiative. This federally supported initiative focuses on quantum research and development programs in the United States.
The team’s EMFI will take the form of two main goals; the first will determine a quantum advantage in the existing two-photon fluorescence imaging systems and the second goal is to push the envelope of existing neuroimaging by employing three-photon fluorescence with an entangled source. Three-photon fluorescence using classical light is at the cutting edge of neuroscience that requires extremely high laser intensity but allows for deeper penetration of the excitation light. Showing a quantum advantage in three-photon fluorescence imaging is expected to be transformative for neuroscience as it will enable neuroscientists to perform measurements relatively deep within the brain that have historically been deemed difficult.
The funded research project anticipates supporting undergraduate, graduate and postdoctoral researchers in interdisciplinary laboratories currently on campus.
“This collaboration provides a unique opportunity to explore new frontiers in neuroscience research,” said Charles Anderson, assistant professor in the WVU Department of Neuroscience. “Advances in neuroscience are often based on refining and applying cutting-edge imaging techniques to the study of brain function. Our team combines strengths in quantum physics and neuroscience imaging techniques which we will leverage into new approaches to answer fundamental questions about how specific neurons and circuits function while animals process information about the world."
Additionally, the team will use the award to launch a WVU Quantum Summer School for Undergraduates.
Regionally, WVU serves a wide, underserved community in Appalachia and beyond, where colleges and universities are not always able to provide courses in quantum physics/quantum technology. In order to bridge that gap, the WVU Department of Physics and Astronomy will support a weeklong summer training event targeting undergraduate students in the region who would otherwise not be exposed to quantum technology.
nf/adb/hal 09/30/23
MEDIA CONTACT: Holly Legleiter
hlegleiter@mail.wvu.edu; 304-685-5301