Cell Robotics Inc. (Albuquerque, NM)—which was founded in 1988 to commercialize optical-trapping technology developed at Los Alamos National Laboratory (LANL, Albuquerque, NM)—is capturing the attention of scientists, physicians, and investors with its efforts to revolutionize microscale research. Whereas current micromanipulation is done mechanically, laser-based optical-trapping instruments can precisely isolate, extract, move, cut, dissect, and analyze micron-sized particles and organisms such as cells, chromosomes, and DNA molecules without physical contact.
"This is an enabling technology that allows scientists to do many things they couldn’t do before," says Ron Lohrding, founder, president, and CEO of Cell Robotics. It is also prompting several new clinical investigations that could lead to major breakthroughs in cancer research, human fertility, genetic engineering, and neuroscience. Even biologists are studying whether optical trapping can help them produce plants that are more insect- and drought-resistant and vegetables that have longer shelf lives (see photo).
"The beauty of optical trapping is that it is so broadly applicable in so many areas," says Mark Waller, an investment banker who was instrumental in helping Cell Robotics recently become a public company (see below). "And imagine the quantum leap in accuracy, speed, and precision it can give to someone who is moving cells around on a slide."
The concept of optical trapping was originally developed and patented by Arthur Ashkin and colleagues at AT&T Bell Laboratories (Holmdell, NJ); soon after the first papers were published, LANL began its own development work. That is when Lohrding, who was program director for energy and technology at LANL at the time, first encountered this technology, and it did not take long for him to realize its far-reaching implications. "As program director, I looked at anything that seemed to have the potential to alter how science is done," he says. "When I saw the optical-trapping work, I thought it had a chance to completely change how science is conducted in microspace."
Lohrding left the laboratory a few months later and spent the next two years putting together the financial backing to put Cell Robotics in business. He also obtained an exclusive license to AT&T’s optical-trapping patents, which cover the USA, Canada, Europe, Japan, Hong Kong, and Australia; today this license gives Cell Robotics a patent portfolio that will make it difficult for competing companies to enter this market.
Suddenly public
In 1991, Cell Robotics received a major boost when Lohrding signed an agreement with Mitsui Engineering and Shipbuilding (Tokyo, Japan) that gave him the additional capital necessary to develop the technology. Over the next three years, Mitsui invested $7 million in development before deciding to look for a partner. At the same time, Cell Robotics was experiencing a significant growth in sales and beginning to see increased market potential from several new applications that would require greater sales, marketing, and manufacturing resources; thus the idea of a merger was appealing.
Through most of 1994, Cell Robotics and Mitsui had discussions with several interested parties, but it was not until Intelligent Financial Corp. (IFC, Colorado Springs, CO)—a public company most recently involved in the computer-leasing business—entered the picture last September that negotiations got serious. Five months later, Cell Robotics was a wholly owned subsidiary of IFC (which subsequently changed its name to Cell Robotics International) and, more important, a public company. Intelligent Financial Corp. issued 668,019 shares of common stock in exchange for Cell Robotics, plus an additional option for Cell Robotics employees and advisors to purchase 86,094 shares of IFC stock at $2.39/share. For the first quarter of 1995, ended March 31, Cell Robotics reported losses of $380,000 on sales of $195,000.
A two-year marketing and sales agreement signed with Carl Zeiss Inc. (Thornwood, NJ) in April should help push those results into the black. The agreement gives Cell Robotics access to Zeiss’ 50-member sales team and a $25,000 promotional program sponsored by Zeiss. In addition, Zeiss has committed to selling $750,000 worth of Cell Robotics products by December 31 of this year. "We were delighted to sign this deal with Zeiss," says Lohrding. "We went from one sales person to 50—that makes quite an impact."
Entering new markets
The next step for Cell Robotics is to expand into new applications and markets, particularly in medicine. "With most new enabling technologies, you sell to the research community first," Lohrding says. "Most of our current sales are to universities and some of the major laboratories. But we think that, in the near future, people in the medical area will begin working on more clinical applications that use optical trapping."
One such application is assisted reproduction to improve in vitro fertilization results, which is already under investigation in the USA and Europe. "It has been shown that a hole can be cut in the outer shell of the egg and the sperm trapped, moved, and placed more precisely in the opening of the egg," says Lohrding.
Laser-assisted hatching of the embryo before transplantation back into the mother is another near-term market. "Initial studies in Austria have shown that laser-assisted hatching before transplantation yields a success rate of approximately 50%, compared to the 15% success rate when assisted hatching is not used," says Lohrding, adding that more than 50 babies have born in Austria using this technique.
Also under investigation is the use of optical trapping to aid neuron growth, with the ultimate goal of developing spinal-cord splicing techniques. In current studies, Cell Robotics’ LaserTweezers are being used to plant laminine-coated beads in front of a neuron, which begins to grow in the direction of the beads (neurons inherently seek this chemical). "The goal is to grow very long neurons and transplant them across the spinal-cord injury to reintroduce neural capabilities," says Lohrding, noting, however, that this application is still several years out.
Other clinical applications for this technology—though still in the development stage—are already showing the potential to improve or replace conventional treatments. These include isolating fetal cells from a mother’s blood to genetically analyze the child without risk (a potential replacement for amniocentesis); isolating and cloning the "killer" cells that are used in certain cancer treatments, thereby increasing the ratio of active to inactive killer cells (currently only 1 in 10 killer cells actually succeeds in attacking cancerous cells); and isolating specialized neurons that can be reinjected into the brain for use in the treatment of Alzheimer`s and Parkinson’s disease.
Commercializing optical trapping
Cell Robotics has developed and currently manufactures two laser-based instruments and two nonlaser devices:
LaserTweezers, the company’s core product, is currently used in a broad range of research applications, from cell isolation and manipulation to DNA molecule analysis, and is offered with various wavelength (830-980 nm) and power (100 mW–1 W) options.
LaserScissors is a complementary product to the tweezers intended for precise cutting of cells, chromosomes, sperm tails, and so forth. The product is based on a nitrogen-pumped dye laser that produces output wavelengths ranging from 337 to 650 nm.
CellSelector is a micropipetting device with a finely controlled syringe pump that can extract a single high-value cell or chromosome and isolate it with absolute purity.
SmartStage is a high-precision motorized stage used to control manipulation during optical-trapping and other procedures.