The University of Buffalo’s Office of Science Technology Transfer and Economic Outreach (also known as STOR) last week said it has struck an alliance with research instrument shop Reichert to further develop and market the school’s cell-volume cytometer for drug-discovery and diagnostic applications.
Reichert, based in Depew, NY, sells a line of surface plasmon resonance refractometers under the brand name SR7000. The company, which licensed UB’s CVC technology, is betting that coupling it with Reichert‘s SPR instruments would give it two different applications in two different sectors of the drug-development and biomedical-research market, according to Robert Carey, Reichert’s general manager for analytical instruments.
The technology is based on a concept called cell-volume cytometry. Research has provided evidence that changes in a cell’s volume reflect its response to a variety of perturbations, including excitability, metabolism, apoptosis, necrosis, neurotransmitters, toxins, and cell division and growth.
According to Susan Hua, an assistant professor of mechanical and aerospace engineering at UB, one cellular characteristic that particularly correlates with cell volume is ion channel activity, which gives the chip potential as a drug-screening tool.
Hua said that a cell typically uses ion channels — including those for calcium, potassium, and sodium — to regulate its volume. Therefore, if scientists can measure minute changes in cell volume, it can be correlated to ion channels opening and closing.
Ion channels, particularly those that regulate changes in cellular calcium levels, are believed to be one of the most important drug targets in pharmaceutical science. Many methods exist to monitor changes in cellular calcium levels, but most of them require fluorescent dyes and optical-based methods to measure them. Perhaps the most well-known example of this is Molecular Devices’ FLIPR assay.
Researchers have known for a while that cell volume can act as an indicator of ion channel activity, but according to the authors, no one has really devised a simple, straightforward method to measure changes in cell volume, such that it could be a useful tool for drug screening.
“Maybe people have tried to use cell volume to screen cells — we don’t know,” Hua said. “People have typically used a calcium indicator, but the reason they haven’t used cell volume is because they haven’t found a convenient way to do so.”
The company anticipates that at some point the CVC can be used to eliminate unpromising drug candidates from further development, said Carey, though he did not explain how the technology would do this.
As the technology evolves, scientists will determine how best to use it for their own purposes, he said.
The project will be funded by a portion of a $750,000 grant Reichert won last year from the New York State Office of Science, Technology, and Academic Research through its Technology Transfer Incentive Program, according to Michael Fowler, a commercialization manager at UB STOR who recently spoke with Biotech Transfer Week, a CBA News sister publication.
Carey told CBA News this week that the partners will beta test the technology this summer. Pre-beta units are in use now at undisclosed industrial and academic facilities, he added.
Carey said pre-beta feedback on the CVC has so far has been useful, and that most testers are urging the company to make the technology more user-friendly.
He declined to elaborate.
Carey said the CVC is simple and straightforward to use because it does not require labels, though when used in combination with instruments that do use labels, it can reduce the overall drug-discovery research costs.
Reichert’s TTIP grant supports ongoing collaborative research between the company and Frederick Sachs, a professor of physiology and biophysical sciences at UB. Sachs and Hua are the primary inventors of the CVC technology, which Reichert has licensed from UB.
Reichert is more than 100 years young, and takes a longer-term approach to growing its presence in the drug-discovery marketplace.
But Carey said that instruments from companies such as Applied Biophysics, Acea Bioscience, and MDS Analytical Technologies "tend to measure the impedance where the cells have grown on the electrode itself. Reichert's system measures the entire volume of cell change within the chamber, and it doesn't matter where those cells are in the chamber.
"If they change, then we measure it," said Carey. "We're measuring between the electrodes, not on the electrodes."
Reichert's instrument can only be used to measure cell health due to volume changes, however, while the above instruments have the ability to measure characteristics such as cell motility and ion channel activation. Of course, almost every cellular characteristic links to overall cell health, a fact that Reichert hopes it can exploit as it develops applications for the CVC.
The advantage of this method is that it is very specific for measuring cell volume, Sachs told CBA News this week. He said that other instruments grow cells on electrodes and measure the resistance, but some response is due to changes in volume, some is due to changes in cell shape, and some is due to how tightly they adhere to the electrodes.
Sachs said that the only other instrument that can measure cell volume is Beckman Coulter’s Coulter Counter, which has been around for about 40 years. But it requires cells that have been suspended, and it is slow.
Besides measuring cells, the CVC can be used to study volumetric changes in cellular organelles or vesicles of a specific compartment of a cell, such as the endoplasmic reticulum, said Sachs. For example, researchers can make lipid vesicles, insert a single purified protein, and measure change in the vesicle volume.
Reichert’s first step into the drug-discovery market occurred when, via a partnership with Cornell University, it adapted some of its traditional refractometer technology to incorporate an optical technique known as surface plasmon resonance and develop the SR7000.
SPR can be used to measure refractive index changes at the surface of thin films. According to Reichert’s Web site, it is useful for studying "interactions between a wide range of molecules, including proteins, nucleotides, pharmaceuticals, and surface active agents.”