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

Light-splitting crystals from inexpensive ingredients

Photonic crystals

Researchers from Princeton and Columbia universities have proposed a method for growing specialized materials called photonic crystals by ensuring that tiny particles settle into a single uniform crystal structure. Previously, the particles assumed a variety of structures, which made the resulting crystals unsuitable for high-performance uses. At left, particles form the initial two layers of a crystal, labeled A and B. With the addition of the third layer, the crystal forms one of two possible shapes, shown in side views at right. The vertical blue string to the right of each crystal shows a chemical chain that the researchers add to the mix to force one structure to form versus the other.

HIGHLY PURIFIED CRYSTALS that split light with uncanny precision are key parts of high-powered lenses, specialized optics and, potentially, computers that manipulate light instead of electricity. But producing these crystals by current techniques, such as etching them with a precise beam of electrons, is often extremely difficult and expensive.

Now, researchers at Princeton and Columbia universities have proposed a method that could allow scientists to customize and grow these specialized materials, known as photonic crystals, with relative ease.

“Our results point to a previously unexplored path for making defect-free crystals using inexpensive ingredients,” said Athanassios Panagiotopoulos, the Susan Dod Brown Professor of Chemical and Biological Engineering at Princeton. “Current methods for making such systems rely on using difficult-to-synthesize particles with narrowly tailored directional interactions.”

In an article published online July 21, 2014, in the journal Nature Communications, Panagiotopoulos and colleagues propose that photonic crystals could be created from a mixture in which particles of one type are dispersed throughout another material. Called colloidal suspensions, these mixtures include things like milk or fog. Under certain conditions, these dispersed particles can combine into crystals.

Creating solids from colloidal suspensions is not a new idea. In fact, humans have been doing it since the invention of cheese and the butter churn. But there is a big difference between making a wheel of cheddar and a crystal pure enough to split light for an optical circuit.

One of the main challenges for creating these optical crystals is finding a way to create uniform shapes from a given colloidal mixture. By definition, crystals’ internal structures are arranged in a pattern. The geometry of these patterns determines how a crystal will affect light. Unfortunately for optical engineers, a typical colloidal mixture will produce crystals with different internal structures.

In their paper, the researchers demonstrate a method for using a colloidal suspension to create crystals with the uniform structures needed for high-end technologies. Essentially, the researchers show that adding precisely sized chains of molecules — called polymers — to the colloid mixture allows them to impose order on the crystal as it forms.

“The polymers control what structures are allowed to form,” said Nathan Mahynski, a graduate student in chemical and biological engineering at Princeton and the paper’s lead author. “If you understand how the polymer interacts with the colloids in the mixture, you can use that to create a desired crystal.”

The researchers created a computer model that simulated the formation of crystals based on principles of thermodynamics, which state that any system will settle into whatever structure requires the least energy. They found that when the crystals formed, tiny amounts of polymer were trapped between the colloids as they came together. These polymer-filled spaces, called interstices, play a key role in determining the energy state of a crystal. “Changing the polymer affects which crystal form is most stable,” Mahynski said.

Besides Panagiotopoulos and Mahynski, the paper’s authors include Sanat Kumar, a professor and chair of chemical engineering, and Dong Meng, a postdoctoral researcher, both at Columbia. Support for the project was provided in part by the National Science Foundation.

–By John Sullivan

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

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

Quantum computing moves forward

New technologies that exploit quantum behavior for computing and other applications are closer than ever to being realized due to recent advances. These advances could enable the creation of immensely powerful computers as well as other applications, such as highly sensitive detectors capable of probing biological systems.

“We are really excited about the possibilities of new semiconductor materials and new experimental systems that have become available in the last decade,” said Jason Petta, a quantum information scientist and an associate professor of physics at Princeton, who collaborated with Andrew Houck, an associate professor of electrical engineering, on a study published in Nature in October 2012 describing a method for quick and reliable transfer of quantum information throughout a computing device.

Support for the research was provided by the National Science Foundation, the Alfred P. Sloan Foundation, the Packard Foundation, the Army Research Office, and the Defense Advanced Research Projects Agency Quantum Entanglement Science and Technology Program.

–By Catherine Zandonella