College of Engineering : Signatures : Breaking Out of the Ivory Tower

One of the criticisms most often levelled at academic institutions is that the spires, arches, columns, and other impressive architecture of a university shield faculty and students from the "real world." While there may be few places on Earth as sheltered from the cares of everyday life as a college campus, there are also few places as attuned to the way in which teams of researchers can change the world.

The search, discovery, and application of knowledge is what Vannevar Bush, director of the Office of Scientific Research and Development and former dean of engineering at the Massachusetts Institute of Technology, highlighted in a 1945 report to President Franklin D. Roosevelt.

Written in response to a request from the President to discuss the lessons learned from World War II and suggest areas that could be nurtured, as Roosevelt put it, "for the improvement of health, the creation of new enterprises bringing new jobs, and the betterment of the national standard of living," Bush titled his treatise Science: The Endless Frontier. In it he wrote, "There must be a stream of new scientific knowledge to turn the wheels of private and public enterprise. There must be plenty of men and women trained in science and technology for upon them depend both the creation of new knowledge and its applications to practical purposes." This is the same vision held by the College of Engineering and the University of Notre Dame, particularly in reference to the Center for Microfluidics and Medical Diagnostics (CMMD).

Established in 2003 the CMMD builds upon considerable faculty expertise in microfluidics, separations, electrochemistry, biomolecular engineering, and nanoscience. Although one of the goals of the center is to facilitate technology transfer at Notre Dame -- the transfer of research from the academic process to a viable commercial product, the CMMD was created to explore microfluidic and medical diagnostic concepts and devices.

Microfluidics refers to the flow of minute amounts of liquids or gases through miniature channels. These channels may feature pumps, valves, filters, or mixers, but the microscale of the components and of the channel means that the physics of the flow in the device, specifically because of the unique attributes of small fluid volumes, are different and require more sophisticated handling techniques. However, they also produce much quicker reactions, eliminating expensive laboratory tests and the lengthy wait for results.

Microfluidic devices were first developed in the 1990s. Since that time they have enjoyed success in niche applications, such as ink-jet printers and diabetic test kits. Fluids currently used in similar lab-on-a-chip tests include whole blood, bacterial cell suspensions, protein solutions, and antibody suspensions. What researchers are discovering is that microfluidics may be of use in a variety of other applications, such as DNA analysis, drug screening, cell separation, gene mapping, and biotoxin analysis.

According to Bayer Professor of Chemical and Biomolecular Engineering Hsueh Chia Chang, director of the CMMD, "We have assembled a highly talented team to help us bridge the gap between academia and industry." In addition to Chia Chang, whose expertise is in electrokinetics, center administration includes David T. Leighton Jr., associate director and professor of chemical and biomolecular engineering, who specializes in separations, and Andrew J. Downard (B.S., CBE, '04; M.B.A., '04), product development manager.

Members of the CMMD advisory board include Gary H. Bernstein, professor of electrical engineering; Mark J. McCready, chair and professor of chemical and biomolecular engineering; Albert E. Miller, professor of chemical and biomolecular engineering; and Agnes E. Ostafin, assistant professor of chemical and biomolecular engineering. Bernstein specializes in microfabrication, McCready in mass/heat transfer, Miller in electrochemistry and nanotechnology, and Ostafin in biomedical engineering.

"One disadvantage in academia," says Downard, "is that often faculty or graduate students develop great ideas, but they might not realize the potential applications nor have an adequate understanding of markets." Since one of the goals of the center is to transfer the ideas behind the microfluidic projects into commercial products, this type of business savvy becomes vital.

The University of Florida owns the patent for TRUSOPT®, a medicinal eye drop containing dorzolamide that is used to treat glaucoma. Stanford University and the University of California at San Francisco hold the patent for recombinant DNA technology -- joining the DNA from different species and fusing them together, which is an important technique in biotechnology. These universities, and others like them, license their inventions to businesses who manufacture the "products." It's called "technology transfer."

Some universities were making the leap from success in laboratories to successful commercial products as early as the 1920s. However, a report written in 1945 by Vannevar Bush, director of the Office of Scientific Research and Development, for President Franklin D. Roosevelt is believed to have been the origin for the formal concept of technology transfer. The report, Science: The Endless Frontier, highlighted the potential of academic research for enhancing the economy. Many believe it stimulated the formation of the National Science Foundation, the National Institutes of Health, and the Office of Naval Research.

Although the federal funding of research is now considered to be vital to national security, when these agencies were first established there was not a standard policy for ownership of the inventions. The government owned most of the patents, and few of those were licensed to industry for commercial development. According to a September 1999 report by the Council on Governmental Relations on The Patent and Trademark Law Amendments Act, also known as the Bayh-Dole Act of 1980, the government typically retained the title to an invention and offered non-exclusive licenses. Many corporations were reluctant to purchase such a license in order to develop the same product a competitor could also manufacture. The promise of the technology remained unfulfilled and in the laboratory.

The Bayh-Dole Act, and subsequent acts such as Stevenson-Wydler and Federal Technology Transfer, established a more uniform policy on the treatment of inventions, especially those resulting from federally funded research. Bayh-Dole has been amended since its passage; other acts have also been added and amended. Since technology is driving the economy at an ever increasing pace, it is likely that Congress will continue to address concerns related to technology transfer. The issues at stake include better quality of life for mankind, the rights of inventors, the rights of the public and federal agencies supporting the research with public funds, and the quality of the research, as some academics are worried that the current act encourages universities to focus on commercial profit rather than developing fundamental knowledge.

The University of Notre Dame owns 57 patents for inventions closely linked to its research activities. Some of the most recently issued patents resulting from research in the College of Engineering include:

U.S. Patent No. 6,869,671
Enabling Nanostructured Materials via Multilayer Thin Film Precursor and Applications to Biosensors
Albert E. Miller, Subhash C. Basu, Juan Jiang, Michael Crouse, and David Crouse
Issued on March 22, 2005

U.S. Patent No. 6,842,692
Computer-controlled Power Wheelchair Navigation System
Steven B. Skaar, Guillermo DelCastillo, and Linda Fehr
Issued on January 11, 2005

U.S. Patent No. 6,768,782
Iterative Method for Region-of-Interest Reconstruction
Ken D. Sauer, Jiang Hsieh, Charles Bouman, and Jean-Baptiste Thibault
Issued on July 27, 2004

U.S. Patent No. 6,579,343
Purification of Gas with Liquid Ionic Compounds
Joan F. Brennecke and Edward J. Maginn
Issued on June 17, 2003

Thirteen of the 24 Notre Dame patents pending are also the result of research led by engineering faculty. Four of those emanate from the Center for Microfluidics and Medical Diagnostics. Others include:

Application No. 11/085,510
Segmentation Algorithmic Approach to Step-and-Shoot Intensity Modulated Radiation Therapy
Danny Z. Chen, Xiaobo S. Hu, Chao Wang, Shuang Luan, Xiaodong Wu, and Cedric Yu
Filed on March 22, 2005

Application No. 10/980,425
Bone and Tissue Scaffolding and Method for Producing Same
Steven R. Schmid, Glen L. Niebur, and Ryan K. Roeder
Filed on November 4, 2004

Application No. 10/933,417
System for Inter-Chip Communication
Gary H. Bernstein, Patrick J. Fay, Wolfgang Porod, and Qing Liu
Filed on September 3, 2004

Application No. 10/251,934
Method for Making Mesoporous Silicate Nanoparticle Coatings and Hollow Mesoporous Silica Nano-Shells
Agnes E. Ostafin, Edward J. Maginn, and Robert Nooney
Filed on September 20, 2002

Note: Current University of Notre Dame researchers are highlighted in italics.

"Focusing on microfluidics and medical diagnostics," says Leighton, "is ideal because the research we've been accomplishing in the center and the products we are developing have a real potential to help people, solving problems through research. We are serving the University's mission of trying to make the world a better place, which is evidenced in the selection of projects currently under development, but we are also building relationships with companies that understand the 'business' of business better than we academics do."

For example, researchers in the CMMD are working on a test kit to quickly and accurately determine how well blood is coagulating. This process will be extremely useful to individuals who are recuperating from major surgery or those on blood thinners, who have their blood tested on a daily basis to determine how readily it is coagulating. The test kit will also aid in establishing the next correct dosage of anticoagulant. Currently, these blood samples take three to four hours to process, at which time the sampling laboratory releases the individual with the correct dosage for the next day. The cycle then repeats itself: A patient goes to the lab, sits for half a day, and then returns home so he or she can do the same thing the next day. CMMD researchers are developing a lab-on-a-chip that would more quickly identify how blood was coagulating and then issue the correct dosage information to a patient at home.

University researchers, in conjunction with industry partner Scientific Methods Inc., of Granger, Ind., are developing environmental sensors to detect E coli in local water supplies and public areas such as beaches. The decision to close public beaches is typically driven by laboratory tests, which take up to two days to process. By incorporating a bacteria trap into a hand-held sensor, the CMMD is able to force the bacteria to flow into highly concentrated lines that can be detected electronically, which will give municipal officials real-time information about water quality so they may better safeguard public health. According to Chia Chang, the bacteria trap, which uses electrokinetic flow, is orders of magnitude faster than other detection processes on the market today.

Faculty in the CMMD have also teamed with researchers from Altea Therapeutics Corporation in Tucker, Ga., on the development of a high-pressure pump for transdermal drug delivery. Altea has made key breakthroughs in the delivery of small molecules, such as proteins and peptides, via skin patches similar to a nicotine patch. A high-pressure pump would allow large molecule medications, such as insulin, to be injected through the skin without the use of needles.

Electrophoretic protein separation, or zetafiltration, is another process the CMMD is developing. "Our zetafiltration system is very close to being able to make the leap from research lab to commercial use, which in this case would be preparatory scale separations for additional research and industrial scale separations," says Leighton. "What's exciting about it is that we've been able to demonstrate that we can separate or 'catch' individual species of biological molecules on the order of 100 nanometers based on mobility. This is fundamental research, but the implications for further study of human proteins or even subcellular organelles are also very exciting." For instance, by applying zetafiltration to proteomics, researchers could identify the proteins contained in individual organelles to determine the location and function of each part of the cell in a detail that is not currently available. Researchers using the zetafiltration system would also be able to collect information in much less time ... half an hour as opposed to overnight.

Although CMMD researchers have yet to "take a product to market," they have four patents pending for several of the projects within the center. They have built mutually beneficial partnerships with several organizations, and they are successfully maintaining the unique balance of the education and training of graduate students with the development of commercially viable products. As the first University center to pursue technology transfer, the CMMD is a successful model, but its purpose, like Roosevelt's request, is not yet fulfilled.

In 1945 Roosevelt wanted immediate answers. He wanted to identify a means "for the improvement of health, the creation of new enterprises bringing new jobs, and the betterment of the national standard of living." Bush's response was not a pat answer. He suggested the path to improving the nation was commitment: the commitment to pursue new knowledge, the commitment to educate future generations so that the quest for scientific and economic growth did not end with any single generation; and a commitment to reaching beyond boundaries, such as an ivory tower, to apply that new knowledge for practical purposes and the betterment of mankind.

For more information about the CMMD, its faculty, and current projects, visit http://microfluidics.nd.edu/.

In 1863 Abraham Lincoln approved the Congressional charter of the National Academy of Sciences. Since that time the Academy complex -- the National Academy of Sciences, the National Academy of Engineering, the Institute of Medicine, and the National Research Council -- has been advising the federal government about the impact of technology on society, as well as the development and implementation of related public policies. The most recent report issued by the Academy complex, Preparing for the 21st Century: Science and Engineering Research in a Changing World, stresses the importance of engineering and science research in meeting national goals and maintaining America’s position as a technological leader.

The greatest concerns in achieving those goals were maintaining the quality and integrity of research and developing human resources, future engineers and scientists. Scientists and engineers play a key role in the economic and cultural make-up of the nation. America and the more than 600 public and private institutions that offer graduate degrees in engineering and science have a vested interest in encouraging young people to pursue graduate degrees in engineering and science.

Bayer Professor Hsueh Chia Chang, director of the Center for Microfluidics and Medical Diagnostics (CMMD), agrees and believes that the fundamental nature of graduate research within the CMMD is one of the most carefully designed aspects of the center. "When dealing with technology transfer in an academic setting," says Chang, "there's always a concern about whether efforts to develop commercially viable products will detract from the main mission of an institution -- educating its students. The graduate students in the center are involved in fundamental research, but their work is purposefully separate from the development process."

This is a formula that worked well for the Department of Chemical and Biomolecular Engineering before the creation of the center, and it works well for the CMMD. Not only has the University continued to attract high-quality graduate students, but it has been extremely successful in placing students, particularly in academia. Over the last several years a number of graduate students studying microfluidics have gone on to teach at the university level.

For example, Pavlo Takhistov (M.S., CHEG, '99) is currently an associate professor of food engineering at Rutgers University. His research interests include nano-structured materials as a substrate for biosensors and active food packaging. He also examines blood flow anomalies in microchannels, in order to help design microdevices for blood diagnostics.

An assistant professor in the Department of Biomedical Engineering at the University of Rochester, Michael R. King (Ph.D., CHEG, '99) studies biofluid mechanics. The ultimate goal of the laboratory he directs at Rochester is to simulate blood flow and relevant cellular interactions. The information gained from this research has the potential to impact public health, especially in relation to cancer and cardiovascular diseases.

Jason M. Keith (Ph.D., CHEG, '00) is an assistant professor in the Department of Chemical Engineering and faculty adviser of the Alternative Fuels Group Enterprise at Michigan Technological University. Although he has focused primarily on heat and mass transfer fundamentals, one of his most recent projects involves transdermal drug delivery.

One month after successfully defending her doctoral thesis, Assistant Professor Adrienne R. Minerick (M.S., CHEG, '03; Ph.D., CHEG, '03) was teaching Advanced Process Computations and Introduction to Chemical Engineering at Mississippi State University (MSU). Since that time she has also developed MSU’s Medical Micro-Device Engineering Research Laboratory (M.D.-ERL). Like Notre Dame's CMMD, the M.D.-ERL is dedicated to researching the development of medical microdevices in order to improve diagnostic techniques and practices. Working with graduate and undergraduate students, Minerick is exploring dielectrophoretic microdevices, which could detect a variety of blood diseases using a single drop of blood. "During my time at Notre Dame," says Minerick, "I had the privilege of working with outstanding faculty and postdoctoral researchers, like Hsueh Chia Chang and Pavlo Takhistov. It was also during this time that I developed a passion for medical diagnostic devices and learned to understand both the theoretical and experimental approaches in a collaborative environment."

In addition to her teaching duties, Assistant Professor Jayne Wu (M.S., EE, '01; Ph.D., CBE, '04) directs the Micro-Sensor and Actuator Laboratory at the University of Tennessee at Knoxville. One of the projects in her lab deals with the electrokinetic focusing of bioparticles for real-time detection of toxins.

What each of these graduates and many of their projects have in common is that they are generating fundamental research with direct applications for service to society. They are also sharing their excitement and commitment for the betterment of society with the next generation of students.

Through its endeavors in the realm of technology transfer, the University of Notre Dame is one of the many national universities contributing to America's economic development. Like those other institutions, Notre Dame is addressing patenting and licensing activity for the commercialization of on-campus research activities.

"Because we have so much wonderful research occurring on campus," says Michael T. Edwards, assistant vice president and director of the University's Office of Research, "it is tempting to let technology transfer drive our research portfolio. That is not, however, in the best interest of the University, our faculty, or our students."

According to Jeffrey C. Kantor, vice president and dean of the Graduate School and professor of chemical and biomolecular engineering, the key has been to focus technology transfer efforts on the centers and institutes which offer the greatest opportunity to develop commercial applications that will have a positive effect on people's lives. "We're a little late to the technology transfer game," says Kantor. "Other schools have had technology transfer programs for as long as 20 years." Although some schools generate a great deal of revenue -- millions of dollars in some cases, others lose money chasing after commercially viable research projects. "The goals of our program," he says, "are to add intellectual vitality to the University, expose faculty and students to new opportunities for cutting-edge research, and provide a pathway for our research to make a difference in the way people live."

The schools that have developed successful programs, and have met goals similar to those enumerated by Notre Dame, have especially targeted two areas: pharmaceuticals and medical devices. "These are very hot industries right now," says Edwards. "Most universities pursuing research in these areas also boast medical schools. Fortunately, that’s not a requirement. We have been able to develop close relationships with other institutions, foundations, and corporate partners that allow us to actively participate in healthcare research."

The Center for Microfluidics and Medical Diagnostics (CMMD), one of 130 institutes and centers across the University, was the first to engage in the technology transfer program. "Every center at Notre Dame contributes to the intellectual value of the University," says Kantor. "The Center for Microfluidics and Medical Diagnostics offers an additional set of opportunities in the medical devices arena that will elevate the research in which graduate students and undergraduates can participate. It also offers solutions to real-world problems with commercial applications and relationships with industry."

One of the center's local partners is Scientific Methods, Inc., (SMI) in Granger, Ind. With more than 60 years of collective professional experience in environmental sciences and public health, SMI uses innovative technologies to provide microbiological research, laboratory analyses, and product development services. The firm's 22,500-sq.-ft. facility houses laboratories for bacteriological, virological, and parasitological research. SMI also leases space to start-up companies pursuing research in biotechnology.

"As a small business," says James Larkin, president of SMI, "we recognized that to be successful, we needed to develop strategic partnerships, such as our relationship with the Center for Microfluidics and Medical Diagnostics at Notre Dame." The partnership between SMI and CMMD is a win-win situation: SMI offers expertise in microbiological evaluation, with an emphasis on environmental microbiology, while CMMD offers considerable experience in microfluidics.

Because of their business perspective, SMI researchers have also helped CMMD define new applications for their microfluidic activities, particularly in the healthcare and pharmaceutical industries. Most recently, they shared exhibit space at the 2005 Indiana Biosensor Symposium. "Both organizations have the desire to innovate and solve problems," says Larkin. "By looking beyond what is familiar to each group, we were able to find new -- and practical -- applications that will potentially benefit everyone."

Like many other states, Indiana is committed to bolstering its economy with technology. Annually the state is home to approximately $3 billion of research and development by industry and funds more than $25 million at the university level.

On May 6, 2005, the University of Notre Dame hosted the inaugural symposium of the Indiana Innovation Network (IIN). A relatively new organization, the IIN is a non-profit group whose goal is to promote the growth and success of research and technology within Indiana.

Notre Dame hosted the symposium at the invitation of Jeffrey C. Kantor, vice president and dean of the Graduate School and professor of chemical and biomolecular engineering. Kantor is also a member of the board of the Indiana 21st Century Fund, a state initiative to stimulate and diversify the economy by developing and commercializing advanced technologies within Indiana. Created in 1999, the fund encourages excellence in technology and successful commercialization through academic-industry partnerships.

Other universities participating in IIN include Ball State University, Indiana State University, Indiana University, Indiana University-Purdue University Indianapolis, Purdue University, and the Rose-Hulman Institute of Technology.

The Notre Dame symposium focused on advanced materials and featured university and industry experts in orthopedics, nanotechnology, fuel cells, and carbon-carbon composites. Speakers from the College of Engineering included Steven R. Schmid, associate professor of aerospace and mechanical engineering; Wolfgang Porod, the Frank M. Freimann Professor of Electrical Engineering; and Paul J. McGinn, professor of chemical and biomolecular engineering and director of the Center for Molecularly Engineered Materials.

IIN will sponsor up to five more symposia at partner universities during 2005. Topics for the upcoming events include: systems engineering, technology parks/incubators, and alternative energy sources. In addition to the symposia, the IIN plans to develop an on-line database that will function as a directory of Indiana’s technology experts. Researchers and facilities in Indiana will be searchable by name, university, or research area.

For more information on the IIN, visit http://www.indianainnovation.com.