Long View of a Small Science

Paul Blair With Students
KMOB's Stephanie Vadas shares the IP lawfirm's resources with Igniting Technology guests.

The technology itself may be too small to see but the audience at this month’s Igniting Technology event at Calit2 certainly wanted to hear about it. 

“Micro/nanotechnology: The Human Impact,” drew more than 100 people who learned of ongoing research in the field as well as the many business opportunities it is creating. Guests also viewed open labs, visited vendor display tables and networked over a light supper.

The event, sponsored for the seventh consecutive year by intellectual property law firm Knobbe Martens, Olson & Bear, was moderated by KMOB partner Michael Guiliana. He advised audience members with startup companies to involve the Food and Drug Administration early.  Nanotechnology is still considered an emerging technology, he said, so it’s wise to obtain assistance in navigating the complexities of the agency. “There are consultants who used to be FDA employees who can help you get through the process,” he said, adding that most successful startup exits occur after FDA approval.

Phil Collins, UCI associate physics professor, kicked off the research portion of the program with a brief introduction to nanotechnology. “Nanomaterials are not new; they were developed by nature long before we came along,” he explained, but until about 20 years ago scientists didn’t really understand them. Advances in microscopy, however, including the scanning electron microscope and the atomic force microscope, are facilitating a better understanding of the field.  These tools, critical for viewing nanoscale structures, “were not available in the 50s, 60s or 70s; that’s why nanotechnology is happening today,” Collins said.

Researchers are creating new nanomaterials, including spherical particles used in lubricants and coatings; long fibrils woven into fabrics or added to plastics; and conductive and semiconductive fibers, which act as wires in miniature electronic circuits. Future applications could include nanoscale robots, machines, communications and control systems. “We don’t know how to do most of that today. But nanoscale is a rapidly-advancing field; we hope someday to be able to build advanced nanotechnologies,” Collins said.

Paul Blair With Students
Panelists (from left) Collins, Wickramasinghe, Burke, Flanagan and Stroh answer audience questions.

He builds tiny electronic circuits with which he analyzes problems at the single-molecule scale. “Some of the most complex systems in biochemistry are very poorly understood,” he told the audience, citing the binding process between proteins and enzymes, as well as DNA and other large proteins. Using the tiny wires and the power of solid-state electronics, Collins can measure what’s going on at the nanoscale with molecular precision. “We can monitor the protein as it binds to its partners [and] get a nice, clean electronic signal that tells us what the protein is doing moment to moment.” This understanding has implications in healthcare and pharmaceutical development, possibly leading to designer drugs that target specific mutations or inhibit interactions.
Kumar Wickramasinghe knows a thing or two about atomic force microscopes; he helped create and develop the vibrating mode AFM when he worked at IBM in the 1980s. The UCI engineering professor currently uses the instrument’s nanoprobes to track genetic variations and chemical changes in living cell systems. The unique approach profiles genetic expression levels within  living cella at extremely high sensitivity, tracking responses to external stimuli. “We believe it opens new methods for diagnosis of genetic diseases,” he said. “This could evolve into a new analytical tool with a major impact in cell biology.”

Previously, DNA arrays containing thousands to millions of cells were necessary to track gene expression, but averaging results over this large number of cells reduces the sensitivity of the measurements and masks subtle variations, Wickramasinghe said. “Detecting very low fluctuation levels in gene expression down to single molecules is key to detecting genetic mutations that result in disease and for studying drugs and signaling molecules.”

Paul Blair and student demonstrating the device
Nanospectra Biosciences' Kevin McNerny discusses his firm's tumor-ablation technology with an interested visitor.


Kingsley Ma has worked on interfacing the phone to the GPS system. Says Ma, "I modified an existing program to enable the phone to parse the GPS coordinates and send the relevant http packets, like the header, the name of the user account, and so forth, to the server every 20 seconds."


His technique utilizes an AFM with a silicon cantilever probe. A very fine needle – only about 100 angstroms in diameter – senses the surface of the material and measures the shift in resonance frequency. Researchers manipulate molecules up and down this probe, and because they move at different speeds, they can be separated and categorized. When inserted through the cell membrane, the probe can selectively pick up different RNA expressions in the living cells. “[We are] right at the beginning; we need to do much more work,” Wickramasinghe told the rapt audience.

Engineering professor Peter Burke’s nanotechnology research runs the gamut from communications to biotechnology. The founder of a startup company based on carbon nanotube communications technology believes there is lots of opportunity for entrepreneurs.
Carbon nanotubes are the smallest wires you can make, Burke said. He has developed nanotube antennas that can receive a radio signal from radio waves and convert it into an audible signal. Next step – building radios the size of a single living cell, allowing communication to the outside from within the cell.

Burke is also using microchips to study metabolism/bioenergetics. Because there is a connection between metabolism and certain diseases, he studies mitochondria, the power plants of living cells, for answers. Mitochondria from regular cells, he said, appear different from those in embryonic stem cells; he hopes his chip-based technology, now in its second prototype, will help define these differences.

Biologist/neurologist Lisa Flanagan also works with stem cells. She uses microfluidic devices, developed in conjunction with biomedical engineering professor Abe Lee, to try to improve the purity of neural stem cells for use in regenerative medicine. “The potential of going in and replacing cells that are lost or damaged is really pretty incredible,” she said.
But first, researchers must figure out which stem cells will become the correct neural cells. Past experience has shown that certain cells tend to grow into tumors and others die upon implantation. So Flanagan and her team are trying to better understand progenitor cells using a technique called dielectrophoresis. Cells are put into non-homogenous electric fields in a microfluidic device and separated based on their response to the frequencies. “We can go in and, in a very unbiased way, probe the cells to see if there’s anything useful there,” she said.
Their goal was to determine if there were differences between undifferentiated stem cells and fully differentiated stem cells of the central nervous system. They did see differences, but even more interesting, according to Flanagan, were the differences they saw in progenitor cells – the cells that will become neurons or astrocytes or oligodendrocytes.  They narrowed those differences down to changes in the cells’ outer plasma membranes, a finding that is helping them understand key biological differences.
“For us as biologists, this is really exciting because we now have a handle on these cells. We can start to learn more about their key characteristics because we can isolate them from each other.”

The evening’s last speaker was John Stroh, CEO of Nanospectra Biosciences. The startup develops cancer therapies that precisely destroy solid tumors with heat. Gold nanoshells are infused into the body and activated by near-infrared laser, ablating the tumor without destroying healthy tissue. Stroh said the technology is considered a medical device – not a therapeutic – which means FDA approval was easier to obtain.

Calling the therapy a “platform technology” that can be used in all solid tumors, Stroh said it also enhances radiation and chemotherapy. The company is currently focusing on head and neck cancer, gliomas, and cancers of the breast, pancreas and prostate.
“The clinical advantages of our technology are precision and a very focalized application,” he said. “It’s very tumor-specific, minimizes the collateral damage and effectively heats and kills the tumor without raising the temperature more than minimally around the tumor.”

Nanospectra Biosciences has raised nearly $8 million to date and continues to seek additional resources. According to Stroh, venture investors funded more than $800 million in 2010 and 54 percent went to nanomedicine companies. “There is money out there, there is opportunity and we are successfully moving down the path,” he said.
“My message for those looking to commercialize is to be creative, look at new funds, smaller funds; it’s still an emerging technology and I think you’ll see significant commercialization opportunities in the coming years.”

-- Anna Lynn Spitzer

Event presentations (in order of appearance):
Michael Guiliana
Phil Collins
Kumar Wickramasinghe
Peter Burke
Lisa Flanagan
John Stroh

Videos (in order of appearance)
Phil Collins
Kumar Wickramasinghe
Peter Burke
Lisa Flanagan
John Stroh