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PWR
SPECTROSCOPY
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From
left to right: Drs. Savitha Devanathan, Zdzislaw Salamon, Gordon Tollin, and Mark Walker |
To answer these questions, we realized we would need methods that gave us more structural insight into how these systems were organized. Zdzislaw suggested that surface plasmon resonance (SPR) spectroscopy, used primarily by physicists and physical chemists to characterize surfaces and interfaces, might provide such a technique. In discussions with the Optical Sciences Center about obtaining assistance in implementing this technology in our laboratory, Zdzislaw made contact with Prof. Angus Macleod, who had been using SPR spectroscopy to characterize the thin coatings on front surface mirrors in astronomical devices. This led to a collaborative effort to develop an SPR device that could be used to explore the proteolipid membranes we were studying.
An SPR instrument capable of making measurements on lipid bilayers was built by Zdzislaw in 1991-92, with the assistance of Angus and Rick Schmidt, who was then an electronics technician in the Biochemistry Department. Essential in this project were funds provided by the Vice-President for Research (then Mike Cusanovich) who saw the potential that this new technology offered. This was crucial, since to obtain outside funding for such a new and untested instrument development project was virtually impossible.
After working with this device for a year or so, it became quite evident to us that this approach was applicable to a wide variety of membrane-related problems in addition to electron transfer, and we began to explore patent possibilities with the UA Office of Technology Transfer (OTT). The first step in this process involved submitting an Invention Disclosure describing this unique SPR device and its potential applications to membrane biology, which we did in mid-1993. At about this same time, the Pharmacia Corp. in Sweden began marketing an SPR instrument (which it called a Biacore) designed to follow the kinetics of intermolecular interactions. Although the Biacore used the same physical principles as our device, it was not oriented towards membrane systems, nor was it able to provide as much information due to its emphasis on kinetics rather than spectroscopy. However, this instrument was beginning to be used extensively, especially in the pharmaceutical community, as a drug-development tool, and in various academic laboratories to look at protein-protein interactions.
Recognizing that our SPR approach was inherently superior to the Biacore, we began discussions with Aviv Instruments, a small company located in New Jersey that had successfully built and marketed several optical bio-spectroscopic instruments (absorption, CD and fluorescence), about commercially developing our device. This happened rather serendipitously when Jack Aviv, the company president whom I had known for many years, came here to service an Aviv CD instrument that we had in the department. Jack expressed great interest in our new device and Aviv Instruments began to work on the project. To help protect their interests they agreed to provide funds to the OTT to finance a patent application describing our methods for depositing lipid bilayers onto solid surfaces, which was the key element in using SPR to characterize biomembranes.
An important point here is that at this time OTT did not have sufficient resources to finance this themselves, and thus without Aviv’s support we would not have been able to proceed. A patent application was filed in mid-1994 and a patent was granted in mid-1996. Aviv Instruments was then given an exclusive license by the University to use this patent as the basis for the development of a new SPR spectroscopy instrument designed specifically for membrane studies. |
| Professors Salamon and Tollin with an early version of the instrument |
During this time, Zdzislaw continued to work on applying plasmon spectroscopy to membrane proteins, and developed an important new variant of SPR that we called plasmon-waveguide resonance (PWR) spectroscopy. This new approach was easily adapted to the techniques we were already using for SPR, it allowed even more structural information to be derived from plasmon spectroscopy, and was much superior to SPR in its sensitivity and spectral resolution. It is important to emphasize that these technological developments were accomplished with minimal outside funding, and with minimal (although sometimes crucial) input by outside personnel. We submitted an Invention Disclosure describing PWR to OTT in mid-1999 and Aviv Instruments, recognizing the importance of incorporating this new technology into their instrument development program, agreed to finance patent applications. This resulted in three PWR patents in 1999, 2001 and 2002, and new license agreements with Aviv were formalized. In the meantime, the building of a commercial device by Aviv Instruments was proceeding, albeit at a painfully slow rate. The main reason for the slow progress was the rather limited resources that the company had available to devote to this project. Fortunately, Aviv Instruments was absorbed by another company (then Protein Solutions, Inc. and now Proterion Corp.), which provided them with new financial and personnel resources that greatly accelerated the pace of development. Finally, in mid-December 2000, the first prototype PWR instrument was delivered to us for testing. Much of this was carried out by another post-doc in my laboratory, Savitha Devanathan, in collaboration with Zdzislaw.
As one might expect with new technology, there were a large number of problems discovered during this testing period, and after much back and forth discussion and software/hardware redesign, the first acceptable PWR spectra were collected with this instrument in August 2001. The experience we obtained in this testing process was incorporated into the design and construction of a second-generation PWR device, which was delivered to us in September 2002 for testing by Savitha and Zdzislaw. In February 2003 most of the software/hardware design problems with the new instrument had been resolved and useful data could be obtained. Since then, several additional instruments have been constructed at Proterion and these are presently being tested in three academic and industrial laboratories. When the tests have been completed, and any necessary modifications incorporated, the first commercial marketing will begin.
Thus, the end of a long, sometimes painful and frustrating but always exciting, ten-year journey is finally in view. During this time, we have developed a number of collaborative PWR research projects, have published many papers using PWR to study membrane processes, and both we and Proterion have presented seminars at a large number of scientific conferences, universities and pharmaceutical companies describing PWR technology and its applications. As a consequence, much interest has been expressed, and we are hopeful that when the first instrument finally comes to market it will find a place in many laboratories interested in membrane biology. Since as many as 50% of the pharmaceuticals currently on the market are directed towards membrane proteins, we expect that our device will also have an impact on drug development protocols. We should find out soon!
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Department
of Biochemistry and Molecular Biophysics
The University of Arizona
Updated June 1, 2004
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