This ability to control light using a semiconductor device could allow low-power, relatively inexpensive sources like LEDs or flashlight bulbs to replace more powerful laser beams in new technologies such as holograms, remote sensing, self-driving cars and high-speed communication.

“What we’ve done is show that steering a beam of incoherent light can be done,” said Prasad Iyer, Sandia scientist and lead author of the research, which was reported in the current issue of the journal Nature Photonics. The work was funded by the Department of Energy’s Office of Science.

Incoherent light is emitted by many common sources, such as an old-fashioned incandescent light bulb or an LED bulb. This light is called incoherent since the photons are emitted with different wavelengths and in a random fashion. A beam of light from a laser, however, does not spread and diffuse because the photons have the same frequency and phase and is thus called coherent light.

In the team’s research, they manipulated incoherent light by using artificially structured materials called metasurfaces, made from tiny building blocks of semiconductors called meta-atoms that can be designed to reflect light very efficiently. Although metasurfaces had previously shown promise for creating devices that could steer light rays to arbitrary angles, they also presented a challenge because they had only been designed for coherent light sources. Ideally, one would want a semiconductor device that can emit light like an LED, steer the light emission to a set angle by applying a control voltage and shift the steering angle at the fastest speed possible.

The researchers started with a semiconductor metasurface that had embedded tiny light sources called quantum dots. By using a control optical pulse, they were able to change, or reconfigure, the way the surface reflected light and steer the light waves emitted from the quantum dots in different directions over a 70-degree range for less than a trillionth-of-a-second, marking a significant success. Similar to laser-based steering, the steered beam restrained the tendency of incoherent light to spread over a wider viewing angle and instead produced bright light at a distance.

Taming light

A feat previously considered impossible, the team’s proof-of-principle work paves the way for developments in the fields of nanophotonics and ultrafast optics. The ability to dynamically control incoherent light sources and manipulate their properties offers a wide range of applications.

One low-power use would be to brighten military helmet screens used to overlay maps or blueprints over ordinary vision. “In applications where space is valuable,” Iyer said, “steering light emission with low-size-and-weight metasurface-LED displays could be made possible in the future with this technology. We can use the light emitted in a better way rather than just turning them off and on.”

The technique could also provide a new kind of small display that can project holographic images onto eyeballs using low-power LEDs, a capability of particular interest for augmented and virtual reality devices. Other uses could be in self-driving cars where LIDAR is used to sense objects in the path of the car.

In terms of expressions of interest, the team has had several inquiries from commercial sources, said Sandia researcher Igal Brener, a paper author and lead scientist on the project. “A commercial product could be 5-10 years out, especially if we want to have all the functionality on-chip,” Brener said. “You wouldn’t use a control optical pulse to impart the changes in the metasurface needed to steer the light, but rather you would do this control electrically. We have ideas and plans, but it’s still early. Imagine an LED light bulb that can emit light to follow you. Then you wouldn’t waste all that illumination where there’s nobody. This is one of the many applications that we dreamed about with DOE years ago for energy efficiency for office lighting, for example.”

Similarly, tamed light may one day offer benefits in scenarios where focused illumination is only needed in a specific area of interest, such as surgery or in autonomous vehicles.

For incoherent light, the future is looking bright.

Sandia National Laboratories is a multimission laboratory operated by National Technology and Engineering Solutions of Sandia LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy’s National Nuclear Security Administration. Sandia Labs has major research and development responsibilities in nuclear deterrence, global security, defense, energy technologies and economic competitiveness, with main facilities in Albuquerque, New Mexico, and Livermore, California.

In the study, published March 16 in Nature Cell Biology, Dr. James Lo, associate professor of medicine at Weill Cornell Medicine, and colleagues measured gene expression in individual beta cells collected from mice to determine how many different types of beta cells exist in the pancreas. The team discovered four distinct beta cell types, including one that stood out. The cluster 1 group of beta cells produced more insulin than other beta cells and appeared better able to metabolize sugar. The study also showed that loss of this beta cell type might contribute to type 2 diabetes.

“Before this, people thought a beta cell was a beta cell, and they just counted total beta cells,” said Dr. Lo, who is also a member of the Weill Center for Metabolic Health and the Cardiovascular Research Institute at Weill Cornell Medicine and a cardiologist at NewYork-Presbyterian/Weill Cornell Medical Center. “But this study tells us it might be important to subtype the beta cells and that we need study the role of these special cluster 1 beta cells in diabetes.”

Drs. Doron Betel, Jingli Cao, Geoffrey Pitt and Shuibing Chen at Weill Cornell Medicine teamed up with Dr. Lo to carry out the study.

The investigators used a technique called single-cell transcriptomics to measure all the genes expressed in individual mouse beta cells and then used that information to group them into four types. The cluster 1 beta cells had a unique gene expression signature that included high expression of genes that help cellular powerhouses called mitochondria to break down sugar and power them to secrete more insulin. Additionally, they could distinguish the cluster 1 beta cells from the other beta cell types by its high expression of the CD63 gene, which enabled them to use the CD63 protein as a marker for this specific beta cell type.

“CD63 expression provided us a way to identify the cells without destroying them and allowed us to study the live cells,” he said.

When the team looked at both human and mouse beta cells, they found that cluster 1 beta cells with high CD63 gene expression produce more insulin in response to sugar than the three other types of beta cells with low CD63 expression.

“They are very high-functioning beta cells,” Dr. Lo said. “We think they may carry the bulk of the workload of producing insulin, so their loss might have profound impacts.”

In mice fed an obesity-inducing, high-fat diet and mice with type 2 diabetes, the numbers of these insulin-producing-powerhouse beta cells decreased.

“Because the numbers of cluster 1/high CD63 cells went down, you may have less insulin production, which may play a major role in diabetes development,” he said.

Transplanting beta cells with high CD63 production into mice with type 2 diabetes restored their blood sugar levels to normal. But removing the transplanted cells caused high blood sugar levels to return. Transplanting low CD63 production beta cells into the mice didn’t restore blood sugar to normal levels. The transplanted low CD63 beta cells instead appeared dysfunctional.

The discovery may have important implications for the use of beta cell transplants to treat diabetes, Dr. Lo said. For example, it may be better to transplant only high CD63- beta cells. He noted that it might also be possible to transplant fewer of these highly productive cells. Dr. Lo’s team also found that humans with type 2 diabetes had lower levels of high CD63 beta cells compared to those without diabetes.

Next, Dr. Lo and his colleagues would like to find out what happens to the high CD63-producing beta cells in mice with diabetes and how to keep them from disappearing.

“If we can figure out how to keep them around longer, surviving and functional, that could lead to better ways to treat or prevent type 2 diabetes,” he said.

They would also like to study how existing diabetes treatments affect all types of beta cells. GLP-1 agonists, which help increase the release of insulin in people with diabetes, interact with high and low CD63-producing beta cells.

“Our study also shows that GLP-1 agonists might also be a way to get the low CD63-producing beta cells to work better,” Dr. Lo said.

Even though advances in 3D printing enable rapid fabrication of rotational mechanisms, integrating sensors into the designs is still notoriously difficult. Due to the complexity of the rotating parts, sensors are typically embedded manually, after the device has already been produced.

However, manually integrating sensors is no easy task. Embed them inside a device and wires might get tangled in the rotating parts or obstruct their rotations, but mounting external sensors would increase the size of a mechanism and potentially limit its motion.

Instead, the new system the MIT researchers developed enables a maker to 3D print sensors directly into a mechanism’s moving parts using conductive 3D printing filament. This gives devices the ability to sense their angular position, rotation speed, and direction of rotation.

With their system, called MechSense, a maker can manufacture rotational mechanisms with integrated sensors in just one pass using a multi-material 3D printer. These types of printers utilize multiple materials at the same time to fabricate a device.

To streamline the fabrication process, the researchers built a plugin for the computer-aided design software SolidWorks that automatically integrates sensors into a model of the mechanism, which could then be sent directly to the 3D printer for fabrication.

MechSense could enable engineers to rapidly prototype devices with rotating parts, like turbines or motors, while incorporating sensing directly into the designs. It could be especially useful in creating tangible user interfaces for augmented reality environments, where sensing is critical for tracking a user’s movements and interaction with objects.

“A lot of the research that we do in our lab involves taking fabrication methods that factories or specialized institutions create and then making then accessible for people. 3D printing is a tool that a lot of people can afford to have in their homes. So how can we provide the average maker with the tools necessary to develop these types of interactive mechanisms? At the end of the day, this research all revolves around that goal,” says Marwa AlAlawi, a mechanical engineering graduate student and lead author of a paper on MechSense.

AlAlawi’s co-authors include Michael Wessely, a former postdoc in the MIT Computer Science and Artificial Intelligence Laboratory (CSAIL) who is now an assistant professor at Aarhus University; and senior author Stefanie Mueller, an associate professor in the MIT departments of Electrical Engineering and Computer Science and Mechanical Engineering, and a member CSAIL; as well as others at MIT and collaborators from Accenture Labs. The research will be presented at the ACM CHI Conference on Human Factors in Computing Systems.

Built-in sensing

To incorporate sensors into a rotational mechanism in a way that would not disrupt the device’s movement, the researchers leveraged capacitive sensing.

A capacitor consists of two plates of conductive material that have an insulating material sandwiched between them. If the overlapping area or distance between the conductive plates is changed, perhaps by rotating the mechanism, a capacitive sensor can detect resulting changes in the electric field between the plates. That information could then be used to calculate speed, for instance.

“In capacitive sensing, you don’t necessarily need to have contact between the two opposing conductive plates to monitor changes in that specific sensor. We took advantage of that for our sensor design,” AlAlawi says.

Rotational mechanisms typically consist of a rotational element located above, below, or next to a stationary element, like a gear spinning on a static shaft above a flat surface. The spinning gear is the rotational element and the flat surface beneath it is the stationary element.

The MechSense sensor includes three patches made from conductive material that are printed into the stationary plate, with each patch separated from its neighbors by nonconductive material. A fourth patch of conductive material, which has the same area as the other three patches, is printed into the rotating plate.

As the device spins, the patch on the rotating plate, called a floating capacitor, overlaps each of the patches on the stationary plate in turn. As the overlap between the rotating patch and each stationary patch changes (from completely covered, to half covered, to not covered at all), each patch individually detects the resulting change in capacitance.

The floating capacitor is not connected to any circuitry, so wires won’t get tangled with rotating components.

Rather, the stationary patches are wired to electronics that use software the researchers developed to convert raw sensor data into estimations of angular position, direction of rotation, and rotation speed.

Enabling rapid prototyping

To simplify the sensor integration process for a user, the researchers built a SolidWorks extension. A maker specifies the rotating and stationary parts of their mechanism, as well as the center of rotation, and then the system automatically adds sensor patches to the model.

“It doesn’t change the design at all. It just replaces part of the device with a different material, in this case conductive material,” AlAlawi says.

The researchers used their system to prototype several devices, including a smart desk lamp that changes the color and brightness of its light depending on how the user rotates the bottom or middle of the lamp. They also produced a planetary gearbox, like those that are used in robotic arms, and a wheel that measures distance as it rolls across a surface.

As they prototyped, the team also conducted technical experiments to fine-tune their sensor design. They found that, as they reduced the size of the patches, the amount of error in the sensor data increased.

“In an effort to generate electronic devices with very little e-waste, we want devices with smaller footprints that can still perform well. If we take our same approach and perhaps use a different material or manufacturing process, I think we can scale down while accumulating less error using the same geometry,” she says.

In addition to testing different materials, AlAlawi and her collaborators plan to explore how they could increase the robustness of their sensor design to external noise, and also develop printable sensors for other types of moving mechanisms.

This research was funded, in part, by Accenture Labs.

The findings were published in Science Advances on March 17, 2023.

“For non-small cell lung cancer cases with the LKB1 mutation, standard chemotherapy and immunotherapy treatments are not effective,” says Shaw, senior and co-corresponding author of the study, and director of Salk’s Cancer Center. “Our findings demonstrate there is a way to target these cases using drugs that are FDA-approved or already in clinical trials, so this work could easily be used for a clinical trial in humans.”

Roughly 20 percent of all NSCLCs have the LKB1 genetic mutation, which means there are no effective targeted therapies currently on the market for patients with this cancer type. To create a therapy that could target the LKB1 mutation, the researchers turned to histone deacetylases (HDACs). HDACs are proteins associated with tumor growth and cancer metastasis, with characteristic overexpression in solid tumors. Several HDAC-inhibitor drugs are already FDA-approved (safe for human use) for specific forms of lymphoma, but data on their efficacy in solid tumors or whether tumors bearing specific genetic alterations may exhibit heightened therapeutic potential has been lacking.

Based on previous findings connecting the LKB1 gene to three other HDACs that all rely on HDAC3, the team started by conducting a genetic analysis of HDAC3 in mouse models of NSCLC, discovering an unexpectedly critical role for HDAC3 in multiple models. After establishing that HDAC3 was critical for the growth of the difficult-to-treat LKB1-mutant tumors, the researchers next examined whether pharmacologically blocking HDAC3 could give a similarly potent effect.

The team was curious about testing two drugs, entinostat (an HDAC inhibitor in clinical trials known to target HDAC1 and HDAC3) and FDA-approved trametinib (an inhibitor for a different class of enzymes related to cancer). Tumors often become quickly resistant to trametinib, but co-treatment with a drug that inhibits a protein downstream of HDAC3 helps reduce this resistance. Because that protein relies on HDAC3, the researchers believed that a drug that targets HDAC3 — like entinostat — would help manage trametinib resistance, too.

After treating mice with LKB1-mutated lung cancer with variable treatment regimens for 42 days, the team found that mice given both entinostat and trametinib had 79 percent less tumor volume and 63 percent fewer tumors in their lungs than the untreated mice. Additionally, the team confirmed that entinostat was a viable treatment option in cases where a tumor was resistant to trametinib.

“We thought the whole HDAC enzyme class was directly linked to the cause of LKB1 mutant lung cancer. But we didn’t know the specific role of HDAC3 in lung tumor growth,” says first and co-corresponding author Eichner. “We’ve now shown that HDAC3 is essential in lung cancer, and that it is a druggable vulnerability in therapeutic resistance.”

The findings may lead to clinical trials to test the new regimen in humans, since entinostat is already in clinical trials and trametinib is FDA-approved. Importantly, Shaw sees this discovery as transformative for cancers beyond NSCLC, with potential applications in lymphoma, melanoma, and pancreatic cancer.

“Our lab has committed years to this project, taking small and meaningful steps toward these findings,” says Shaw, holder of the William R. Brody Chair. “This is truly a success story for how basic discovery science can lead to therapeutic solutions in the not-so-distant future.”

“My independent laboratory is fortunate to be part of the Lurie Cancer Center at the Feinberg School of Medicine at Northwestern University, which is very supportive of translational research. We hope that this environment will facilitate the initiation of a clinical trial based on these findings,” says Eichner.

Other authors include Stephanie D. Curtis, Sonja N. Brun, Joshua T. Baumgart, Elijah Trefts, Debbie S. Ross, and Tammy J. Rymoff of Salk; and Caroline K. McGuire and Irena Gushterova of Northwestern University.

The work was supported by the National Institutes of Health (R35CA220538, P01CA120964, K22CA251636, 5T32CA009370, 5F32CA206400, CCSG P30CA014195, and CCSG P30CA23100), Leona M. and Harry B. Helmsley Charitable Trust (#2012-PG-MED002), American Cancer Society (PF-15-037-01-DMC), and Chapman Foundation.

Appearing online March 17 in the journal Science Advances, the finding marks an important first step toward a clinical approach for classifying lesions on the pancreas that are at highest risk of becoming cancerous, potentially enabling their removal before they begin to spread.

If successful, the biomarker-based approach could address the biggest impediment to decreasing the chance of developing pancreatic cancer, which is on the rise and is notorious for silently growing before being discovered, often incidentally, during abdominal scans.

“Even when pancreas cancer is detected at its earliest stage, it almost always has shed cells throughout the body, and the cancer returns,” said senior author Peter Allen, M.D., chief of the Division of Surgical Oncology at in the Department of Surgery at Duke University School of Medicine.

“That’s why we shifted our focus to these precancerous cysts, known as intraductal papillary mucinous neoplasms, or IPMNs,” Allen said. “Most IPMNs will never progress to pancreas cancer, but by distinguishing which ones will progress, we are creating an opportunity to prevent an incurable disease from developing.”

Allen and colleagues used a sophisticated molecular biology tool called digital spatial RNA profiling to home in on specific areas of the cyst with high- and low-grade areas of abnormal cell growth.

Previous methods to characterize IPMNs have been less precise and have not been able to identify particularly accurate markers of cancer risk. Digital spatial profiling, however, allows researchers to choose individual groups of cells for analysis. This enabled the Duke researchers to identify a host of genetic mutations that both fuel and potentially suppress pancreatic cancer development.

The team also identified markers for discriminating between the two leading variants of IPMN and found distinct markers for defining a third common variant that generally results in less aggressive disease.

“We found very distinct markers for high-grade cell abnormalities, as well as for slow-growing subtypes,” Allen said. “Our work now is focusing on finding it in the cyst fluid. If we can identify these unique markers in cyst fluid, it could provide the basis for a protein biopsy that would guide whether we should remove the cyst before cancer develops and spreads.”

Allen said current diagnostic strategies — including clinical, radiographic, laboratory, endoscopic, and cytologic analysis — have an overall accuracy of approximately 60%.

“Pancreatic cancer is on the rise and, if the current trajectory continues, it will become the second-leading cause of cancer death in the United States in the next few years,” Allen said, noting it’s unknown what is driving the cancer’s increased prevalence.

He said some studies suggest inflammation plays a role. A clinical trial at Duke, led by Allen, is testing whether an anti-inflammatory therapy could reduce the development of cancer in patients with IPMN.

In addition to Allen, study authors include Matthew K. Iyer, Chanjuan Shi, Austin M. Eckhoff, Ashley Fletcher, and Daniel P. Nussbaum.

The study received funding support from the National Cancer Institute (RO1 CA182076).