Computer chip for point-of-care diagnosis

Lab on a chip is smaller than a penny.

Kaushik Sengupta and his team are developing a computer chip-based diagnostic system, which is smaller than a penny but contains hundreds of different sensors for simultaneous detection of disease-causing agents.

Assistant Professor of Electrical Engineering Kaushik Sengupta and his team are developing a computer chip-based diagnostic system, which rests comfortably on a fingertip but contains hundreds of different sensors for simultaneous detection of disease-causing agents. The eventual goal is to use the chip in a handheld, portable diagnostic device that could be deployed in health clinics around the globe, especially in resource-limited settings.

The chip detects and measures the presence of DNA or proteins to help diagnose health conditions. Most existing methods for detecting these agents involve shining light on fluorescent labels attached to the DNA or protein and reading a resulting signal. However, in many types of tests, the signal is so weak that complex optical equipment is necessary to read the signal.

To perform this analysis using a simple handheld device, Sengupta is co-opting silicon chip technology similar to that found in personal computers and mobile phones. “This is a great technology for handheld medical diagnostic devices because it allows us integrate extremely complex systems in a single chip at very low cost. The vision is to unleash Moore’s law in diagnostics,” said Sengupta, referring to Intel co-founder Gordon Moore’s observation that processing power in computer chips has increased rapidly over the years.

The team starts with highly sensitive light-detecting components, or photodetectors, that are already ubiquitous in smartphone cameras, then adds new optical processor capabilities to the chip. The researchers found a way to re-wire the architecture of the chip so that in addition to carrying electrical information necessary for image processing, the chip also interacts with the incoming photons from the fluorescent light, and can block them out, allowing the signal that carries information about the test sample to be detected and processed.

Lingyu Hong and Kaushik Sengupta

Lingyu Hong, a graduate student in electrical engineering, and Kaushik Sengupta, an assistant professor of electrical engineering at Princeton University are developing technology for use in a handheld diagnostic system for healthcare in resource-limited settings.

This ability to integrate optical elements with electronics inside a single silicon chip is enabling the team to build detection systems for both genetic material and proteins. Millions of photodetectors can already be crammed into smartphone cameras and Sengupta plans to put hundreds or even thousands of such sensors on the new chip to create a platform capable of testing many agents at once. In addition to being cheap and robust, this “lab-on-a-chip” will be user-friendly. Sengupta and his colleagues envision that the chips will be used in a portable device similar to a smartphone that can use an app to analyze the fluorescence data and display diagnosis results in a clear, simple format.

To make the device truly portable, it will be necessary to develop a small and lightweight apparatus to isolate proteins and genetic material from blood or other fluids, and Sengupta and his collaborators are working on this challenge. “The entire end-to-end system may take another couple of years to reach, but we’ve demonstrated the feasibility of the approach,” said Sengupta, who collaborates with Professor of Chemistry Haw Yang. “Princeton provides the kind of environment that makes it easy to reach out to faculty members across the campus and to work on creative endeavors that cut across traditional disciplines.”

The initial work on the chip was supported by Project X, a fund established through a donation from G. Lynn Shostack S’69 for the support of exploratory research. The project involvesgraduate students Lingyu Hong in the Department of Electrical Engineering and Hao Li in the Department of Chemistry, Postdoctoral Research Associate Simon McManus and undergraduate Victor Ying. Lingyu and Hao were awarded a Qualcomm Innovation Fellowship for 2015-16 for this work.

-By Takim Williams

Taming the network: Finding relationships in complex data sets

WHAT BRINGS PEOPLE TOGETHER IN ONLINE NETWORKS? Researchers (and advertisers) would like to know, but without access to personal profiles, the question is not easy. Finding previously undetected relationships in networks and complex data sets is one of the major challenges in the age of “big data.”

Now Assistant Professor Emmanuel Abbe and his collaborators have come up with a new way of thinking about networks to accomplish this task. Not limited to exploring social communities, the technique can tackle significant challenges such as determining which genes work together to increase your cancer risk or how to identify objects — such as chairs or puppies — in a collection of digital images.

The method involves examining whether members of a network are connected by looking at how many common “friends” they have, how many common friends those friends have, and so on. Using this information, the researchers construct a set of statistics that can predict who is in the same sphere.

The approach extracts the “signals” of communities amid a background of “noisy” connections. Abbe’s method is analogous to work by Claude Shannon, sometimes called the father of information theory, who showed that noise imposes a limit to the rate at which data can be transmitted with almost zero error. Abbe has shown that there is an analogous limit to the problem of recovering communities from large data sets.

“Once we understood that there is a fundamental limit to this problem, there was a clear line of sight for how to solve it,” said Abbe, a member of Princeton’s Department of Electrical Engineering and Program in Applied and Computational Mathematics. Abbe and Colin Sandon, a graduate student in the Department of Mathematics, put the method to the test by examining political blogs, some right-leaning and others left-leaning, that sprung up prior to the 2004 presidential election. They asked, if you knew which blogs were referring to each other, but had zero information about the content of the blog, could you figure out which blogs are run by Republicans and which ones by Democrats? “We were able to identify 95 percent of the blogs that we looked at as left- or right-leaning,” Abbe said.

The work was published in the Proceedings of the Annual Symposium on Foundations of Computer Science in 2015. Abbe received the prestigious Bell Labs Prize in 2014 for his research contributions.

–By Catherine Zandonella

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New technology enables computing with the wave of a hand

SpaceTouch

Aoxiang Tang, Liechao Huang and Yingzhe Hu

A FORWARD-THINKING TEAM of electrical engineering students has designed an interactive display surface that allows users to control objects on a screen simply by gesturing in the air. The SpaceTouch surface can either replace an existing touchscreen or be embedded below a table or behind a wall, and can interface with a phone or computer.

A wide variety of uses are possible for the technology, especially in settings where touching a screen is difficult, according to the team, which consists of electrical engineering graduate students Yingzhe Hu, Liechao Huang and Aoxiang Tang.

For instance, a surgeon in an operating room could use SpaceTouch to scroll through a patient’s X-rays. A cook could browse recipes on a surface embedded in an oven or refrigerator door. And three-dimensional sensing could create new possibilities for video games and educational tools.

SpaceTouch will make smartphones, tablets and other computers easier to use in an unobtrusive way, according to Naveen Verma, an associate professor of electrical engineering and a faculty adviser on the project, along with electrical engineering professor Sigurd Wagner and James Sturm, the Stephen R. Forrest Professor in Electrical Engineering and the director of the Princeton Institute for the Science and Technology of Materials.

“We want to interact extensively with our electronics,” Verma said. “But our base technology — the microchip — is small. It’s more appropriate, and I think more compelling, to have a display or interface that is as big as we are.” SpaceTouch makes it possible to control phones or laptops on larger surfaces. Compared to the popular Xbox 360 Kinect gaming console, SpaceTouch can detect motion at shorter distances, in a variety of lighting conditions and using less power.

The 3-D motion sensing of SpaceTouch is made possible by the addition of an extra layer beneath an everyday touchscreen. The upper sensing layer is a matrix of motion-sensing electrodes. A specialized computer chip directs the electrodes to send out a voltage that oscillates, or goes up and down at a constant frequency, creating an electric field that extends to about a foot in front of the screen.

When a hand moves through the electric field, it disrupts the field in a way that changes the frequency of the voltage oscillation. To prevent the display layer from interfering with the motion-sensing electric field, the team added a transparent, conductive shielding layer below the sensing layer, and designed the computer chip to synchronize the voltage oscillations of the two layers.

To explore commercialization of the technology Hu, Huang and Tang participated in the eLab Summer Accelerator Program, which is run by Princeton’s Keller Center in the School of Engineering and Applied Science.

Discovery2014_SpaceTouchdiagram“The eLab program is our first contact with the real business world,” Huang said. “Research is quite different from developing a commercial product.” For example, Huang said, they have learned to consider the needs of different customers and to put together an effective business pitch. The team has obtained a provisional patent, and has already presented SpaceTouch to representatives from large technology companies.

–By Molly Sharlach

Entrepreneurship at Princeton: An interview with Mung Chiang

Mung ChiangPROFESSOR MUNG CHIANG has integrated fundamental research on computer network optimization with several successful business ventures. As director of the Keller Center, which expands the scope of engineering education to include leadership and societal issues, Chiang is dedicated to cultivating the next generation of entrepreneurs.

Chiang, the Arthur LeGrand Doty Professor of Electrical Engineering, also leads the Princeton Entrepreneurship Advisory Committee, which was assembled by Provost David Lee and convened in January 2014 to explore ways to expand entrepreneurship opportunities for students, faculty members and alumni.

In this interview, he emphasizes that not all entrepreneurship is about technology.

How do you define entrepreneurship? Entrepreneurship doesn’t have to be commercializing some scientific or engineering product. It’s much broader than that. It’s a mindset that involves solving big problems through risk-taking actions with relatively few resources. You can be a social entrepreneur or a tech entrepreneur. You can found or join a startup. You can be an entrepreneur in the government, in a big corporation, in a nonprofit — in any organization. You can do it when you’re 22, or you can do it when you’re 92.

What has the committee learned so far from its “listening phase”? First, there is a surging interest from students to have the opportunity to be exposed to entrepreneurship. We also have extremely strong support from alumni. And we have learned that whatever the committee recommends, in the end, the hard work is going to boil down to the execution, and creative entrepreneurs working side by side to push, to pivot and to persist.

How can entrepreneurship connect to a liberal arts education? Our working definition of entrepreneurship is all about the broadening of the mind and training of the character. Interestingly, in our survey some of the strongest responses came from students and alumni in the humanities and social sciences. And there is a good reason for that. Entrepreneurship, unlike certain types of technology jobs, is fundamentally about your intrinsic capability and mindset, and not about a particular kind of vocational skill. We hope to expose students and faculty to the possibilities of entrepreneurship, to enable those who choose to become entrepreneurs, and to enhance the overall education and research environment at Princeton.

–By Molly Sharlach

Laser device may end pin pricks, improve health for diabetics

Diabetes sensor

Claire Gmachl, Kevin Bors and Sabbir Liakat test a laser-based glucose-sensor. (Photo by Frank Wojciechowski)

PRINCETON RESEARCHERS have developed a way to use a laser to measure people’s blood sugar, and, with more work to shrink the laser system to a portable size, the technique could allow diabetics to check their condition without pricking themselves to draw blood.

“We are working hard to turn engineering solutions into useful tools for people to use in their daily lives,” said Claire Gmachl, the Eugene Higgins Professor of Electrical Engineering and the project’s senior researcher. “With this work we hope to improve the lives of many diabetes sufferers who depend on frequent blood glucose monitoring.”

In an article published June 23, 2014, in the journal Biomedical Optics Express, the researchers describe how they measured blood sugar by shining their specialized laser — called a quantum cascade laser — at a person’s palm. The method exceeded the accuracy required for glucose monitors, said Sabbir Liakat, the paper’s lead author and a graduate student in electrical engineering. The team is now working on making the device smaller and portable.

Besides Liakat and Gmachl, researchers included Princeton undergraduate students in electrical engineering Laura Xu (Class of 2015), Callie Woods (Class of 2014) and Kevin Bors (Class of 2013); and Jessica Doyle, a teacher at Hunterdon Regional Central High School. Support for the research was provided in part by the Wendy and Eric Schmidt Foundation, the National Science Foundation, Daylight Solutions Inc., and Opto-Knowledge Systems.

–By John Sullivan

Inventions Bridge the Gap between lab and marketplace

Road trip

A road trip offered Mark Zondlo and his team the opportunity to test their new air quality sensors. (Photo by Lei Tao)

The college experience often involves at least one road trip, but most students do not bring along their faculty adviser. But last spring, two graduate students crammed into a rented Chevy Impala with Professor Mark Zondlo and a postdoctoral researcher to drive eight hours a day across California’s Central Valley, testing their new air-quality sensors, which were strapped to a rooftop ski rack.

The sensors are an example of technologies being developed at Princeton that have the potential to improve quality of life as commercial products or services. Although teaching and research are Princeton’s core missions, the campus is home to a vibrant entrepreneurial spirit, one that can be found among faculty members who are making discoveries that could lead to better medicines as well as students working to turn a dorm-room dream into the next big startup.

“Princeton has a number of initiatives aimed at supporting innovation and technology transfer,” said John Ritter, director of Princeton’s Office of Technology Licensing, which works with University researchers to file invention disclosures and patent applications, and with businesses and investment capitalists to find partners for commercialization. “Our goal is to accelerate the transfer and development of Princeton’s basic research so that society can benefit from these innovations,” he said.

Crossing the valley

One of the ways that Princeton supports this transfer is with programs that help bridge the gap between research and commercialization, a gap that some call the Valley of Death because many promising technologies never make it to the product stage. One such program is the Intellectual Property Accelerator Fund, which provides financial resources for building a prototype or conducting additional testing with the goal of attracting corporate interest or investor financing.

Zondlo, an assistant professor of civil and environmental engineering, is one of the researchers using the fund to cross the valley — in this case literally as well as figuratively. Earlier this year, Zondlo and his research team, which consisted of graduate students Kang Sun and David Miller and postdoctoral researcher Lei Tao, tested their air-quality sensor in California’s Central Valley, a major agricultural center that is home to some of the worst air pollution in the nation.

Their goal was to compare the new portable sensors to existing stationary sensors as well as to measurements taken by plane and satellite as part of a larger NASA-funded air-quality monitoring project, DISCOVER-AQ.

One of the new sensors measures nitrous oxide, the worst greenhouse gas after carbon dioxide and methane. Nitrous oxide escapes into the air when fertilizers are spread on farm fields. Currently, to measure this gas, workers must collect samples of air in bottles and then take them to a lab for analysis using equipment the size of refrigerators.

Zondlo’s sensor, which is bundled with two others that measure ammonia and carbon monoxide, is portable and can be held in one hand, or strapped to a car roof. “The portability allows measurements to be taken quickly and frequently, which could greatly expand the understanding of how nitrous oxide and other gases are released and how their release can be controlled,” Zondlo said.

The sensors involve firing a type of battery-powered laser, called a quantum cascade laser, through a sample of air, while a detector measures the light absorption to deduce the amount of gas in the air. The researchers replaced bulky calibration equipment, necessary to ensure accurate measurements in the field, with a finger-sized chamber of reference gas against which the sensor’s accuracy can be routinely tested.

The decision to commercialize the sensor arose from the desire to make the device available to air-quality regulators and researchers, Zondlo said. “Our sensor has precision and stability similar to the best sensors on the market today, but at a fraction of the size and power requirements,” said Zondlo, a member of the Mid-Infrared Technologies for Health and the Environment (MIRTHE) center, a multi-institution center funded by the National Science Foundation (NSF) and headquartered at Princeton. “We are already getting phone calls from people who want to buy it.”

Lighting up the brain — with help from a synthetic liver

Far from the dusty farm roads of California, Princeton faculty member John (Jay) Groves sits in his office in the glass-enclosed Frick Chemistry Laboratory, thinking about the potential uses for a new synthetic enzyme. Modeled on an enzyme isolated from the liver, the synthetic version can carry out reactions that human chemists find difficult to pull off.

One of these reactions involves attaching radioactive fluorine tags to drugs to make them visible using a brain-imaging method known as positron emission tomography (PET) scanning.

PET scans of the radiolabeled drugs could help investigators track experimental medicines in the brain, to see if they are reaching their targets, and could aid in the development of drugs to treat disorders such as Alzheimer’s disease and stroke, according to Groves, Princeton’s Hugh Stott Taylor Chair of Chemistry. The synthetic enzyme adds fluorine tags without the toxic and corrosive agents used with radioactive fluorine today.

Groves’ initial work was supported by the NSF, but to develop the technology for use in pharmaceutical research, the Groves team, which includes graduate students Wei Liu and Xiongyi Huang, is receiving funding from a Princeton program aimed at supporting concepts that are risky but have potential for broad impact. The Eric and Wendy Schmidt Transformative Technology Fund was created with a $25 million endowment from Google executive chairman Eric Schmidt, a 1976 alumnus and former trustee, and his wife, Wendy.

“The Schmidt funding is enabling us to explore ways to optimize the chemical reaction and create a prototype of an automated system,” Groves said. “This will allow us to create a rapid and noninvasive way to evaluate drug candidates and observe important metabolites within the human brain.”

Aiding the search for planets

Tyler Groff

Postdoctoral researcher Tyler Groff is creating an improved system for adjusting the blurry images seen through telescopes due to atmospheric turbulence, heat and vibrations. (Photo by Denise Applewhite)

Inspired by the search for planets outside our solar system, Princeton postdoctoral researcher Tyler Groff conceived of a technology that could enhance the quality of images from telescopes. Groff received Schmidt funding to develop a device for controlling the mirrors that telescopes use to correct blurring and distortion caused by atmospheric turbulence, heat and vibrations.

This technology, known as adaptive optics, involves measuring disturbances in the light coming into the telescope and making small deformations to the surface of a mirror in precise ways to correct the image. These deformations are made using an array of mechanical devices, known as actuators, each capable of moving a small area of the flexible reflective surface up or down. But existing actuators are limited in the amount of correction they can provide, and the spaces between the actuators create dimples in the mirror, producing a visible pattern in the resulting images that astronomers call “quilting.”

Groff envisioned replacing the array of rigidly attached actuators with flexible ones made from packets containing iron particles suspended in a liquid, or ferrofluid. Just as iron filings can be moved by waving a magnet over them, applying varying magnetic fields to the ferrofluid changes the shape of the fluid in ways that deform the mirror.

The ferrofluid mirror enables highquality images while being more resistant to vibrations and potentially more power efficient, which will be important for future satellite-based telescopes, said Groff, who works in the laboratory of Jeremy Kasdin, professor of mechanical and aerospace engineering. A ferrofluid mirror can also achieve something that a rigid actuator mirror cannot: it can assume a concave or bowl-like shape that aids the focusing of the telescope on objects in space. “A telescope that uses ferrofluid mirrors would be able to see dim objects better,” Groff said, “which would greatly enhance our ability to probe other solar systems.”

From drug discovery to space exploration, Princeton’s dedication to supporting technology transfer and potentially disruptive but high-risk research ideas is yielding tremendous benefits for the advancement of science and the improvement of people’s lives.

Box: From student project to startup

Carlee Joe-Wong (Photo by Steve Schultz)

Carlee Joe-Wong (Photo by Steve Schultz)

In 2009 when Princeton undergraduate Carlee Joe-Wong started working on the technology that would become the DataMi company, she didn’t even own a smartphone. Today, the startup company co-founded by Joe-Wong provides mobile traffic management solutions to wireless Internet providers, and also helps consumers manage their data usage through an app, DataWiz, that has been downloaded by more than 200,000 Apple and Android users.

Joe-Wong became involved in the study of mobile data usage in the spring of her junior year when Professor Mung Chiang challenged her to explore ways that wireless providers could reduce congestion by adjusting their prices based on the variations in network supply and demand. “I mostly just worked on the project in my dorm room,” Joe-Wong said. “I thought it would be cool if it was adopted but I didn’t think that I would be the one helping to make that happen.” After graduation, Joe-Wong became a graduate student working with Chiang on mathematical algorithms that predict the most effective methods for balancing network use across “peak” minutes and “valley” minutes.

“With companies charging $10 per gigabyte, mobile consumers today need to intelligently manage their data,” said Chiang, the Arthur LeGrand Doty Professor of Electrical Engineering. “What the DataWiz app does is tell you when, where and what app used how much of your quota.”

In May 2013 the team, under the engineering leadership of associate research scholar Sangtae Ha, opened an office for DataMi one block off campus. Needless to say, Joe-Wong now has a smartphone.

Taking it to the streets with help from Princeton’s eLab

ELab students

From left: Nathan Haley, Christine Odabashian, Luke Amber and Leif Amber. (Photo by Denise Applewhite)

A love of motorcycles brought them together: three Princeton undergraduates decided to explore building and marketing an electric motorcycle to provide a superior riding experience at significantly lower emissions than gasoline powered models.

The team was one of nine groups selected to participate in the 10-week eLab Summer Accelerator Program, an initiative of the Keller Center in the School of Engineering and Applied Science, which teaches entrepreneurship by offering resources, mentoring and working space.

Throughout the summer, the team members worked on ways to market the bike while simultaneously building a prototype. “We geared the product toward people who enjoy taking weekend trips,” said Nathan Haley, Class of 2014, an economics major.

Haley was joined by Luke Amber, Class of 2015, and Christine Odabashian, Class of 2014, both majors in mechanical and aerospace engineering. The team also included Luke’s older brother, Leif Amber, a graduate student in electrical engineering at Clarkson University.

-By Catherine Zandonella

Mung Chiang wins National Science Foundation Alan T. Waterman Award

Mung Chiang

Mung Chiang (Photo by Brian Wilson)

Mung Chiang, the Arthur LeGrand Doty Professor of Electrical Engineering, received the 2013 Alan T. Waterman Award from the National Science Foundation (NSF) for his work in designing wireless networks. The $1 million award recognizes researchers below the age of 35 for outstanding achievements in any NSF-supported science or engineering field.

Chiang, who received his award at the U.S. Department of State in Washington, D.C., founded Princeton’s EDGE Laboratory, a facility that uses a multidisciplinary approach to examine technological and human networks. Chiang’s research has applications in wireless network radio resource optimization, Internet congestion control, wireless signal traffic routing and cloud computing, according to the official citation of the award.