In the company of collaborators, researchers have big success with tiny particles
Shubhra Gangopadhyay’s diminutive stature belies her ferocity when it comes to finding answers and getting results, a characteristic she attributes to her husband Keshab’s support. “He taught me to stand up for what I believe in,” she said.
As successful research/faculty members at Texas Tech in the late 1990s, the couple realized through Shubhra’s affiliations with researchers elsewhere that there were promising applications for biosensors that utilized her porous nanomaterial research. But difficulties connecting with biologist collaborators caused them to turn to the University of Missouri, lured by MU’s life science program as evidenced though an earlier collaboration Shubhra had with Kevin Gillis, an MU biological engineering professor.
During her second interview for a faculty position in electrical engineering, the C.W. LaPierre endowed chair professor met and connected with Sheila Grant, one of Gillis’ colleagues in biological engineering.
“My work with sensing mechanisms such as FRET [fluorescence resonance energy transfer], anti-body based biosensors and peptide based biosensors were a perfect mechanism to interface with her NPO [nanoporous organosilicate] platforms,” Grant said.
Grant’s passion for the work and the women’s complimentary backgrounds sold Shubhra on MU, and in 2001, the Gangopadhyays moved to mid-Missouri where they have worked tirelessly in a variety of endeavors. Support from the College of Engineering, collaborations with other researchers, and millions of dollars in research funding from the National Science Foundation, the U.S. Army and the National Institutes of Health that have resulted in the discovery and development of novel nanoparticle applications have combined to make the couple’s efforts extraordinarily fruitful.
As a result of their work, funding entities have access to new technologies. MU has gained recognition and a fee-based Nano MEMS semiconductor lab is available to outside research. Dozens of students and colleagues have benefited from research associations, and the Gangopadhyays have started two companies to commercialize their inventions, with potential benefits for industry, the military, the environment and AIDS patients in impoverished countries.
And now, said Keshab Gangopadhyay, a research professor in electrical and computer engineering and an adjunct professor with the Nuclear Science and Engineering Institute, another piece is about to fall into place: economic development in the form of jobs.
“Things are so complex these days,” he said. “We have a holistic approach, where the whole is more than the sum of its parts. It takes different people playing different roles to make everything work.”
Nanoporous organosilicates (NPO)
“I had initial data on the NPOs before I came to MU, but without access to a high-resolution transmission electron microscope, I couldn’t really see what was happening,” Shubhra said, explaining that MU’s College of Veterinary Medicine has such a microscope, enabling her to see what was going on at the nanoparticle level. “We’re talking about something the size of a few atoms,” she said.
Shubhra credits her then-graduate research assistant Venumadhav Korampally, with working backward through the process to optimize these films through a radically new approach using organosilicate nanoparticles. His successful work to synthesize and use them to create crack-resistant films that were thick enough for the necessary applications was not a trivial undertaking.
Now a research assistant professor with the Nano MEMS Center, Korampally said he worked three years to uncover the secrets of the NPO films that spontaneously form through an entropy-driven process for their anti-reflective, anti-fog properties and for their increased luminescence capabilities when doped with dyes. The former is of interest in applications such as coatings for aircraft windows, and the latter is the basis for sensor applications.
“I was jubilant,” he said of his successful breakthrough at the end of 2006.
“We were working to develop nanoparticle films with a water core waveguide,” Korampally said, comparing the technology to both fiber optics and a sponge.
Shubhra pronounced it “a nanoparticle that is going places.”
One nanoparticle – many research collaborations
A first opportunity for nanoparticle-based films came in 2006 when the U.S. Army provided $5 million for several nanomaterial-based projects with defense applications, including fluorescence-based sensor platforms for the detection of chemical and biological agents. This provided Shubhra’s group with the opportunity to fabricate fluorescence-based sensing microchips.
The second opportunity for the nanoparticle-that-could came in 2008 in the form of a two-year, $250,000 subcontract from InnoSense LLC. The California-based company is interested in developing the hydrophobic properties and superior strengths of the organosilicate nanoparticles for its antifog and abrasion resistant properties.
InnoSense received National Science Foundation Small Business Tech Transfer (NSF STTR) funding and partnered with Shubhra to further develop and test the coatings for potential clients such as Boeing. They are additionally interested in making the process as inexpensive as possible.
Korampally’s nanoparticle also has been put to work in its detective role as a sensor platform with the successful funding of two additional projects, both with MU collaborations.
Annette Sobel, who serves as MU’s assistant to the provost for strategic opportunities, provided invaluable assistance in writing a successful funding proposal to the U.S. Army-affiliated Leonard Wood Institute (LWI) for nanosensor biological and chemical agent detection.
Sobel, a former major general with the National Guard, said she is ableto serve as subject matter specialist in areas of critical need for the military. She has co-authored a dozen proposals to military entities.
“This [chem/bio detection] research is a big need for the military,” Sobel said. “Its force protection capabilities are of great importance to them.”
LWI awarded $540,000 to Shubhra and Korampally to develop real time, field deployable sensor platforms to detect the presence of botulinum and TNT. Collaborators include Grant, Luis Polo-Parada, an MU neurobiologist who serves as an assistant professor in medical pharmacology and physiology and is a researcher at MU’s Dalton Cardiovascular Research Center, Bal Ram Singh, director of the Botulinum Research Center at the University of Massachusetts, and Keshab, who serves as president of NEMS/MEMS Works, LLC, one of the Gangopadhyays’ companies responsible for licensing the nanoparticle technology from the university.
In Shubhra’s lab, collaborator Korampally is overseeing the development and optimization of the NPO- based sensor platforms. UMASS is providing surrogate test materials and will test the sensors with actual botulinum. Grant is working with binding the proteins, and Polo-Parada’s lab is working on a mobile detection unit.
A student research team consisting of biological engineering senior Bryant Harris and doctoral bioengineering student Chase Darr, have been working between the MU labs.
“The key to the students’ success is dual advisors,” Shubhra said in reference to Polo-Parada’s and Grant’s essential roles in the project. “I give Sheila a lot of credit for teaching me biology. I learn through my colleagues and students. No one in my group had a biology background.”
“This is interdisciplinary research,” said Keshab. “Some things we don’t understand, but if you talk to people, you can work through it.”
Describing the basic goal of the sensor project, Darr said, “What we’re trying to do is to get a change in fluorescence with a change in concentration of the toxin.”
“We start with a silicon wafer as a substrate,” Harris explained. “We spin nanoparticles onto the surface and do a heat treatment to create pores and then functionalize them with carboxyl groups so as to attach biological sensing probes.”
Fluorescing peptides specific to Botulinum — and in the case of TNT, fluorescent anti-bodies — attach to the protein-functionalized surface, which in turn attach to the surrogate toxins.
“On the five-by-five millimeter chip there could be millions of proteins. You can’t see them, even with a microscope. Once you add the toxin, it cuts the protein and the loss in fluorescence can be measured,” said Darr.
“We are getting some good results,” said Polo-Parada, who is working to develop the mobile detection unit that he has named “The Cube.” It is about the size of an old Brownie camera.
“This small device will replace an entire microscope that could cost thousands of dollars, yet it costs only $1,600,” he said. “It can send information by cell phone and the Internet.
“Many times you challenge what is known with nanotechnology. Materials at nanoscale have different properties,” Polo-Parada said.
Shubhra praises Polo-Parada’s work on the project and his mentoring of the students. She met him when she gave a talk at Dalton. Afterwards, she said, he approached her and said he would be interested in working with her.
“If we don’t use these technologies, they just sit on a shelf,” Polo-Parada said. “You need to find the people you are comfortable working with and do so. That’s how things get done.”
The other collaborative research effort on the MU campus that utilizes the NPO platform is a $100,000 Tibotec Pharmaceutical Reach Initiative (Research and Education in HIV/AIDS for Resource-Poor Countries) awarded to MU Biochemistry Professor William Folk.
Folk had been hoping to develop collaboration with someone in nanotechnology and signal detection when he and Shubhra crossed paths at a function meant to introduce physicians and engineers for potential interdisciplinary research.
Folk’s research focus involves plant-based medicines that African HIV/AIDS sufferers use to treat the symptoms of their disease.
“I’ve spent many, many years looking at traditional medicines,” he said. “Most of the world relies on experience, guesswork and superstition to guide their treatment.”
Folk said that after all this time, a clinical trial is being conducted to assess the usefulness of the plant Sutherlandia frutescens in the treatment HIV/AIDS, but that there is so much more that needs to be done.
“What is needed is a simple robust, diagnostic device that will allow individuals to manage their health with both traditional medicines and Western drugs,” Folk said. “We don’t know how our drugs react or interfere with each other.
“I think the tools Shubhra is working on have particular applications that make them suited for this purpose,” he said.
Shubhra alerted Folk to the talents of engineering doctoral student Sagho Bok, and to an NIH “Biodetective” training grant intended to improve tools for healthcare. This funding allowed Folk to hire Bok to work in his lab.
“I am using NPO films and dye-doped nanoparticles to detect the activity of one enzyme,” said Bok. “We are attempting to use them with a dip-stick-based diagnostic device similar to a pregnancy test using urine samples.”
The enzyme referred to by Bok is cytochrome P3A4 (CYP3A4). CYP3A4 metabolizes endogenous cortisol to 6β-hydroxycortisol (6β-OHC), which is excreted in the urine. The ratio of cortisol and 6β-OHC can serve as an in vivo indicator of CYP3A4 levels.
Knowledge on the enzyme level is particularly important for HIV-positive individuals relying on anti-retroviral drugs to manage their HIV disease, and also relying upon traditional medicines for other healthcare needs, which may cause herb-drug/drug-drug interactions. The enzyme level in terms of the ratio of cortisol and 6β-OHC can be measured in urine with the NPO test.
Also an important collaborator in this project is Purnendu Dasgupta, Jenkins Garrett professor and chairman in the department of chemistry and biochemistry at the University of Texas-Arlington. An expert in chemical sensors, Dasgupta inspired Bok to improve the sensitivity and detection limit of his fluorescent nanoparticles through web meetings and discussions.
“Sango has put our efforts on a solid foundation,” said Folk. “I’ve enjoyed working with him.
A number of additional interdisciplinary funding proposals utilizing the NPO platform have been submitted. “We do not care who is the primary investigator,” Shubhra said. “The main thing is that we need to support these projects and hopefully some will get funded.”
Another important area of research for the Gangopadhyays’ is nanoenergetic materials, primarily with defense applications.
“In 2004, we started NEMS/MEMS Works LLC,” said Keshab. “We realized that although nanoparticle research was new, there would be applications and real products that could be ready.”
“We are at the stage when we could go really big, bridging the gap to real commercialization,” he added, saying that they had completed Phases I and II of their Small Business Innovation Research (SBIR) funding in the amount of $850,000, and are proceeding to Phase III: putting the products on the market.
Steve Apperson, vice-president of Nems/Mems, completed his doctoral in Shubhra’s lab characterizing nanoenergetic materials and their applications in medicine, defense and sensing technologies licensed to the company by MU.
The U. S. Army’s Engineering Research and Development Center (ERDC), in Vicksburg, Miss., recently provided $275,000 for collaboration between NEMS/MEMS and MU to develop an NPO-based prototype sensor for detection of ground water contaminants. The microdevice platform for environmental sensing offers another possible avenue for commercialization. The Gangopadhyays credit the efforts of MU alumnus Jeff Steevens, an ERDC scientist, for the success of their proposal.
Another promising collaboration is one with Don Nissanka, an engineer by training and a highly successful businessman formerly affiliated with Kokam batteries. Nissanka approached the Gangopadhyays with expressed interest in partnering with them on nanotechnology for defense and commercial products.
Nissanka recently started a new company that will work with NEMS/MEMS on a project for which they intend to raise up to $12 million dollars. Nissanka and Keshab have approached many in the defense industry aiming to convince them to take a look at the capabilities of their energetic nanotechnologies.
Keshab also is optimistic about a potential opportunity to offer their nano products on the Sigma-Aldrich website. The company is an international leader in life science and technology products.
The Gangopadhyays’ second company, Nanos Technologies LLC, was incorporated in 2009. It is the company for all of their research that is not related to nanoenergetics, including their sensor and anti-reflective, anti-fog applications. The NPO technology has been licensed to Nanos Technologies exclusively. Bok, who was awarded a doctorate in May, will be working for the company.
Nanos Technologies is investigating additional technologies, among them biomedical imaging, food safety and global healthcare, Keshab said.
“We really believe in the work that Bill Folk is doing and would like to make this a non-profit component of NanosTech,” Keshab said.
The Gangopadhays are very interested in economic development and are committed to keeping their business operations in Missouri to give back to MU and the state that has provided them with such opportunity.
Both Nems/Mems Works and Nanos Technologies are members of the recently established Nano Technology Enterprise Consortium (NTEC).
“Things are going well. I see no reason that we should not succeed,” Keshab said.
Beyond their successful funding and research collaborations, the Gangopadhayays give credit to the role the staff and students who have worked with them has had in their success. “The College of Engineering has encouraged collaboration and also provides support with people like Shelley Hilton, Monica Frank and Jan Rudeen, who makes everything run smoothly,” Shubhra said. Their respective roles are grant writer, grants and contract specialist and administrative associate.
“The tremendous progress made in the NPO research also is due to many students working tirelessly to boost this technology to the next level,” she said.
Somik Mukherjee, a recent Westminster College graduate, has worked for the last four summers with Korampally and Bok in developing the technology. He joined MU as a graduate student because he believes that these tiny particles doped with dye can enhance the efficiency of solar cells, a project he is pursuing for his graduate research work.
Jake Fischbach, an MU electrical engineering graduate, is helping Korampally with coating projects; Steven Hamm, who worked as an undergraduate, is now a master’s student utilizing NPO particles in his device for nuclear-based electric power generation; and Sami Pathan, a Rockbridge high school student, has aided Korampally for the last two years testing the NPO-based coatings.
MU staff partnerships have boosted the commercialization aspect of the Gangopadhyay’s novel nanomaterials. Gregg Scheller, MU’s director of entrepreneurship and industry relations, has mentored Keshab in developing business plans and carrying out the negotiation processes. Wayne McDaniel, senior licensing and business development associate, and Jim Gann, director of technology business development with MU Extension’s Small Business Development Center, have provided invaluable support as well.