Nanotechnologies are expected to provide dramatic advances in fields ranging from building materials to medical imaging. Although many of these technologies will be decades in development, a dramatic exception is that of nanobiotechnology (NB). NB is already finding commercial applications in biomedical engineering (BME), including the development of microfluidic chips, or "lab-on-a-chip" technology. The integration of nanotechnologies in BME will take a concerted interdisciplinary effort on all fronts--from computational modeling to quantum mechanics.
Nanobiotechnology and Microsystems
Much of NB has been derived from our understanding of the infrastructure of the living cell. Many of the reactions occurring within the cells of our body can now be applied in an artificial setting, giving us a vast array of tools. And just as age-old brewing technology has benefited current molecular biology techniques using yeast, microfabrication technologies that were originally developed for the microelectronics industry now allow a wide range of microsystems to be constructed that are compatible with nanobiotechnologies. (If you are interested in reading more about nanobiotechnology, then be sure to check out our Careers in Nanobiotechnology feature-- Ed)
A familiar theme in science fiction is that of humans presented with the challenge of understanding an advanced alien technology incorporated in a working device of impressive capability. This theme is quite appropriate for the present situation--each cell in our body uses nanobiotechnologies we are only beginning to understand but that we have already begun to harness. Living cells are micrometer-scale units capable of replication, growth, chemical synthesis, and movement using technologies operating on individual molecules at the nanometer scale. It is now commonplace to use these technologies on a test tube scale for genetic and protein analysis and amplification. Using a compact disc containing the yeast genome (the genetic blueprint), we can modify the genetic sequence encoding a specific protein, introduce it into a yeast cell and grow up a large culture from that cell. This culture is a bioreactor that will manufacture the modified protein in vast quantities. When we know the sequence for what we want (e.g., insulin) this is an effective method. When we do not know the sequence for the desired structure, we need to turn to computational modeling. This modeling is a very active area with applications ranging from drug development to understanding "mad cow disease."
Many nanotechnologies are of interest to BME, some structural or electronic in nature and some based on fluid manipulation. I became interested in BME while working at CTF Systems, a company that uses quantum nanoelectronic devices manufactured with conventional microfabrication techniques to manufacture medical imaging (MEG) systems. Although some of my research focuses on the development of nanoelectronic devices for life science applications (as well as for telecommunications and radio astronomy), most of my research efforts are based on the use of microfluidic chips (MFCs) with molecular biology.
MFCs are the result of using microfabrication techniques to build microchannel ("micropipe") networks. MFCs are capable of performing many of the molecular biology procedures now established in the life sciences while providing very significant advantages in cost and speed, along with entirely new capabilities in manipulation at the micro- and nanoscales. The advantages of MFCs may allow widespread use of diagnostic procedures that are currently too expensive to implement (e.g., prescreening for cancer) while the new capabilities may dramatically improve our ability to understand complex diseases such as cancer (e.g., through single-cell analysis).
In a typical MFC, microliter quantities of reagents are held in reservoirs and these reagents are moved through the microchannels by applied voltages. This allows for the implementation of standard molecular biology tools such as genetic analysis (electrophoresis), amplification (PCR), sample preparation, and purification. One example of this is an MFC in which PCR is performed upon a sample, and the reaction product is analyzed by electrophoretic separation with laser-induced fluorescence detection. Such an MFC could perform a simple medical diagnostic on a time scale (minutes) orders of magnitude faster than would be taken with conventional equipment. Just as important, the MFC is readily automated (e.g., Micralyne's Microfluidic Toolkit) and a typical analysis uses nanoliters of reagent. This lays the groundwork for high-speed, automated, computer-controlled and highly integrated MFCs capable of multiple analyses.
This is an exciting field with research and commercial activity increasing around the world. My research has implemented MFC methods for cell manipulation and molecular biology and has been applying them in collaboration with local life science researchers. We have developed MFC methods that are comparable or better than the conventional methods used in our collaborator's labs. We now seek to integrate these into more complex MFCs that can perform entire protocols. In cancer research, our goal is to be able to start with a sample of human tissue, extract many cells of interest, and perform genetic analysis upon each of them separately. This would be a powerful tool in the study, diagnosis, and treatment of cancers. Similar MFCs will be capable of performing many medical diagnostics at a cost and speed that would allow their common use in doctors' offices and operating rooms.
The consumer electronics revolution was not brought about so much by the fact that microfabrication technologies allowed the formation of microscale transistors as that they allowed the cost-effective integration of millions of transistors in a functioning unit (e.g., a Pentium processor). These microfabrication technologies are now poised to perform a similar revolution with NB--the MFCs provide an interface between the macroscopic scale and the nanoscale.
Such research is highly interdisciplinary and involves electronics, optics, machining, micro/nanofabrication, molecular biology, and computer programming. With such a diverse set of components, one can only be expected to learn on the job in a team environment. Most projects would involve a subset of these components but a broad background in science or engineering would be a significant advantage for any researcher.
University of Alberta
With funding from the Alberta Cancer Board, the National Science and Engineering Research Council, the Canadian Institutes of Health Research (CIHR), the Canadian Foundation for Innovation, and the Alberta Innovation and Science Research Investment Program, the University of Alberta (UA) in Edmonton has become a major center of nanotechnology research and has fostered the spin-off and growth of a host of companies.
As a result of this nanotechnology emphasis, the National Research Institute of Canada has recently located the new National Institute for Nanotechnology at the UA, with an emphasis on NB. The support for this $120 million institute will be provided equally by the federal and provincial governments. Levels of research support are rising as interest mounts, new institutes arrive, and new companies are started.
The NB activity in Alberta is far ranging, with such research as self-assembled nanostructures (M. J. Brett), single-cell cancer analysis (L. M. Pilarski), computational modeling (D. Wishart), micro-total analysis systems or lab on a chip (D. J. Harrison), cell identification and manipulation (K. Kaler), and microsystems and medical diagnostics (Backhouse). Most NB research at the UA makes use of the Microfab--a joint open-access facility that provides micro- and nanofabrication capabilities. In addition, Micralyne operates a world-leading microfabrication foundry for MFCs while providing a line of instruments that allows for the operation of these MFCs with NB protocols. Another Edmonton company, Dycor, provides a line of instruments for operating MFCs.
The implementation of nanotechnologies is expected to have a more profound effect than that of microelectronics. While the microelectronics technology allows only for the manipulation of electrons on a microchip, the coming nanotechnologies will allow the manipulation of electrons, atoms, cells, and molecules. A major challenge in the years to come will be a change, not only of our technology, but also of our thinking. As we work with individual atoms, our scientists and engineers will all need to work in a far more interdisciplinary fashion. There is a particular need for graduate students and postdoctoral fellows who are generalists and interested in such interdisciplinary approaches--being a generalist is far more important than the particular field of research the researcher was originally trained in. Funding for such researchers is provided by the Natural Sciences and Engineering Research Council of Canada, CIHR, iCore, the Alberta Heritage Foundation for Health Research, and the Alberta Heritage Foundation for Science and Engineering Research. In the future we expect further funding programs to be provided in conjunction with the new institute.
Editor's Note: the references used in this article can be found on the author's Web site at www.ee.ualberta.ca/~chrisb.