An on-chip femtosecond pulse source would unlock new applications in quantum and optical computing, astronomy, optical communications and beyond. However, it’s been a challenge to integrate tunable and highly efficient pulsed lasers onto chips.

Now, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a high-performance, on-chip femtosecond pulse source using a tool that seems straight out of science fiction: a time lens.

The research is published in Nature.

“Pulsed lasers that produce high-intensity, short pulses consisting of many colors of light have remained large,” said Marko Lon?ar, the Tiantsai Lin Professor of Electrical Engineering at SEAS and senior author of the study. “To make these sources more practical, we decided to shrink a well-known approach, used to realize conventional — and large — femtosecond sources, leveraging a state of the art integrated photonics platform that we have developed. Importantly, our chips are made using microfabrication techniques like those used to make computer chips, which ensures not only reduced cost and size, but also improved performance and reliability of our femtosecond sources.”

Traditional lenses, like contact lenses or those found in magnifying glasses and microscopes, bend rays of light coming from different directions by altering their phase so that they hit the same location in space — the focal point.

Time lenses, on the other hand, “bend” light beams in similar ways — but they alter the phase of light beams in time rather than space. In this way, different colors of light, which travel at different speeds, are re-timed so that they each hit the focal plane at the same time.

Imagine a car race, in which each color of light is a different car. First, the time lens staggers the leave time of each car, then sets their speed so they arrive at the finish line at the same time.

To generate femtosecond pulses, the team’s device uses a series of optical waveguides, couplers, modulators and optical grating on the lithium niobate platform pioneered by Lon?ar’s lab.

The team starts by passing a continuous-wave, single-color laser beam through an amplitude modulator that controls the amount of light going through the time-lens, a function similar to an aperture in a conventional lens. The light then propagates through the “bendy” part of the lens, a phase modulator in this case, where a frequency comb of different colors is generated. Going back to the car analogy, the phase modulator creates and then releases the cars of different colors at different starting times.

Then the final component of the laser comes in — a fishbone grating along the waveguide. The grating changes the speed of the different colors of light to bring them all in line with each other, neck and neck in the race, so that they hit the finish line (or focal plane) at the same time

Because the device controls how fast different wavelengths travel and when they hit the focal plane, it effectively transforms the continuous, single color laser beam into a broadband, high-intensity pulse source that can produce ultra-fast, 520 femtosecond bursts.

The device is highly tunable, integrated onto a 2cm by 4mm chip and, because of lithium niobate’s electro-optical properties, requires significantly reduced power than table-top products.

“We’ve shown that integrated photonics offers simultaneous improvements in energy consumption and size,” said Mengjie Yu, a former postdoctoral fellow at SEAS and first author of the study. “There’s no tradeoff here; you save energy at the same time you save space. You just get better performance as the device gets smaller and more integrated. Just imagine — in the future we can carry around femtosecond pulse lasers in our pockets to sense how fresh fruit is or track our well-being in real time, or in our cars to do distance measurement.”

Yu is currently an Assistant Professor at the University of Southern California.

Next, the team aims to explore some of the applications for both the laser itself and the time lens technology, including in lensing systems like telescopes as well as in ultrafast signal processing and quantum networking.

Harvard’s Office of Technology Development has protected the intellectual property arising from the Loncar Lab’s innovations in lithium niobate systems. Loncar is a cofounder of HyperLight Corporation, a startup which was launched to commercialize integrated photonic chips based on certain innovations developed in his lab.

The research was a collaboration between Harvard, HyperLight, Columbia University and Freedom Photonics.

The paper was co-authored by David Barton, Rebecca Cheng, Christian Reimer, Prashanta Kharel, Lingyan He, Linbo Shao, Di Zhu, Yaowen Hu, Hannah R. Grant, Leif Johansson, Yoshitomo Okawachi, Alexander L. Gaeta and Mian Zhang.

It was supported by the Defense Advanced Research Projects Agency (HR0011-20-C-0137), Army Research Office (W911NF2010248), Office of Naval Research (N00014- 18-C-1043) and Air Force Office of Scientific Research (FA9550-19-1-0376 and FA9550-20-1-0297).

A report of their experiments is published November 16 in Science Advances.

“Our goal was to modify an old cancer drug that had shown robust efficacy but was too toxic, especially to the gut, to be developed clinically. To do this, we used a prodrug approach. What is unique about our approach is that we utilized a novel chemistry design to create a prodrug that was simultaneously bio-activated in cancer cells but bio-inactivated in healthy tissues such as the gut. This preferential targeting of the payload to cancer cells is now enabling this efficacious class of drugs to be reevaluated safely in people,” says study author Barbara Slusher, Ph.D., M.A.S., director of the Johns Hopkins Drug Discovery Program and professor of neurology, pharmacology and molecular sciences, psychiatry, neuroscience, medicine and oncology at the Johns Hopkins University School of Medicine.

The newly modified prodrug takes advantage of a common property of cancer cells: a voracious appetite for an amino acid called glutamine, which is a critical building block for proteins, lipids and nucleotides, as well as for energy formation. Rapidly growing cancer cells use a tremendous amount of glutamine, a phenomenon called “glutamine addiction,” but other healthy cells with rapid turnover, like those lining the gut, also rely on glutamine.

Co-author Rana Rais, Ph.D., an associate professor of neurology and pharmacology, says, “DRP-104 is a tumor-targeted prodrug of the glutamine mimic drug called DON (6-Diazo-5-Oxo-L-norleucine), which inhibits multiple glutamine-utilizing enzymes in cancer cells. Many early studies of DON showed it was robustly efficacious in people and mice, but its development was halted due to its toxicity to normal tissues, especially the gut.”

Development of this promising class of drugs did not resume until Slusher, Rais and team decided to make chemical modifications to DON.

“We added chemical groups, called promoieties, to DON that rendered it inactive in the body until it reached the tumor, where the promoieties were clipped off by enzymes that are abundant in the tumor but not in the gut,” says Slusher, who is a member of the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy. “This specific prodrug design made DON targeted to its intended destination (tumor) and have less of an impact on healthy cells elsewhere.”

For the new study, researchers gave the original DON drug and the souped-up DRP-104 drug to mice implanted with tumors. In mice that received DRP-104, the researchers found 11 times more active drug in the tumor compared with the gastrointestinal tract (gut). Both drugs completely wiped out the tumor, but DON caused more gut toxicity in the mice than DRP-104.

Slusher and study co-authors Rana Rais, Pavel Majer and Jonathan Powell co-founded a biotechnology company, Dracen Pharmaceuticals Inc, which licensed this new prodrug for clinical development. DRP-104 is in phase I/II clinical trials at sites across the U.S., including the Johns Hopkins Kimmel Cancer Center, for people with advanced-stage solid tumors. Slusher says her Johns Hopkins Drug Discovery lab is also actively looking for other drugs that have failed clinical trials because of toxicity problems. They hope to apply this same prodrug design to medicines for other conditions.

This research was funded by the National Institutes of Health’s National Cancer Institute and National Institute of Neurological Disorders and Stroke R01CA193895, R01CA229451, R01NS103927, R01CA226765, Bloomberg Kimmel for Cancer Immunotherapy at Johns Hopkins and CureSearch for Children’s Cancer.

Additional Johns Hopkins authors of the study includeKathryn Lemberg, Lukáš Tenora, Matthew Arwood, Arindom Pal, Jesse Alt, Ying Wu, Jenny Lam, Joanna Marie Aguilar, Liang Zhao, Diane Peters, Carolyn Tallon, Rajeev Pandey, Ajit Thomas, Ranjeet Dash, Tanguy Seiwert, Robert Leone and Jonathan Powell. Pavel Majer is from the Academy of Sciences of the Czech Republic.

Slusher, Rais, Tenora, Majer, Alt and Powell are inventors on Johns Hopkins University patents covering novel glutamine antagonist prodrugs described in this research. These patents have been licensed to Dracen Pharmaceuticals Inc. Slusher, Rais, Majer and Powell are founders and hold equity in Dracen Pharmaceuticals Inc. Slusher also serves as a scientific consultant to Dracen. Under a license agreement between Dracen Pharmaceuticals, Inc. and the Johns Hopkins University, the University is entitled to royalty distributions related to technology cited in the study and referenced in this story.

This arrangement has been reviewed and approved by The Johns Hopkins University in accordance with its conflict of interest policies.

“The word microscopic has its origins in the length scale of a micron which is a million times smaller than a meter. Our work is for light matter interaction within the picoscopic regime which is far smaller, where the discrete arrangement of atomic lattices changes light’s properties in surprising ways,” says Jacob.

These intriguing findings demonstrate that natural media host a variety of rich light-matter interaction phenomena at the atomistic level. The use of picophotonic waves in semiconducting materials may lead researchers to design new, functional optical devices, allowing for applications in quantum technologies.

Light-matter interaction in materials is central to several photonic devices from lasers to detectors. Over the past decade, nanophotonics, the study of how light flows on the nanometer scale in engineered structures such as photonic crystals and metamaterials have led to important advances. This existing research can be captured within the realm of classical theory of atomic matter. The current finding leading to picophotonics was made possible by a major leap forward using a quantum theory of atomistic response in matter. The team consists of Jacob as well as Dr. Sathwik Bharadwaj, research scientist at Purdue University, and Dr. Todd Van Mechelen, former post-doc at Purdue University.

The long-standing puzzle in the field was the missing link between atomic lattices, their symmetries and the role it plays on deeply picoscopic light fields. To answer this puzzle, the theory team developed a Maxwell Hamiltonian framework of matter combined with a quantum theory of light induced response in materials.

“This is a pivotal shift from the classical treatment of light flow applied in nanophotonics,” says Jacob. “The quantum nature of light’s behavior in materials is the key for the emergence of picophotonics phenomena.”

Bharadwaj and colleagues showed that hidden amidst traditional well-known electromagnetic waves, new anomalous waves emerge in the atomic lattice. These light waves are highly oscillatory even within one fundamental building block of the silicon crystal (sub-nanometer length scale).

“Natural materials itself have rich intrinsic crystal lattice symmetries and light is strongly influenced by these symmetries,” says Bharadwaj. “The immediate next goal is to apply our theory to the plethora of quantum and topological materials and also verify the existence of these new waves experimentally.”

“Our group has been leading the frontier of research on pico-scale electrodynamic fields inside matter at the atomistic level,” says Jacob. “We recently initiated the picoelectrodynamics theory network where we are bringing together diverse researchers to explore macroscopic phenomena stemming from microscopic pico-electrodynamic fields inside matter.”

This research was funded by the DARPA QUEST program.

Writer: Cheryl Pierce, communications specialist, Earth, Atmospheric, Planetary Sciences | Physics/Astronomy, Purdue University

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Materials provided by Purdue University. Original written by Cheryl Pierce. Note: Content may be edited for style and length.