Looking to tap into a growing trend of drug makers adopting cell-based assay technologies, PharmaSeq is developing a cell-based version of its microtransponder, a fluidics-based assay platform designed to complement — or even replace — existing platforms for SNP detection and biochemical assays that the company has already developed.
PharmaSeq, based in Monmouth Junction, NJ, said it is actively seeking corporate partners and VC cash to help bring the prototype versions of all of its platforms to market, Wlodek Mandecki, the company's president and chairman, told Cell-Based Assay News last week.
Backed by a $100,000 Small Business Innovation Research grant from the National Cancer Institute last summer, PharmaSeq has been developing a cell-based assay based on its core technology: tiny silicon chips measuring approximately 250 microns on each side and containing radio circuitry, photocells, an antenna, and a small amount of computer memory.
The idea is to grow specific cell lines on a transponder, stain the cells or have them express fluorescent markers, expose them to chemical compounds, and then take fluorescent intensity endpoint readings using a PharmaSeq-built flow-based readout instrument.
Though this is a typical protocol for essentially any cell-based endpoint fluorescence assay, what makes PharmaSeq's technology unique is its potential to perform such assays in a highly multiplexed fashion, the company said.
"Microtransponders go throw flow chambers, analogous to the flow chamber of a flow cytometer," Mandecki explained. "And then, the microtransponder-based system reads both fluorescence and radiofrequency. The instrument then translates the radiofrequency signal into the serial number of the microtransponder, and that, in turn, identifies the cell type that is present on the microtransponder."
Using such a procedure, Mandecki said, researchers could assay many different transponders, each of which could contain a different cell type, simultaneously.
"Then, rather than assaying one cell type in a well in a microtiter plate, you assay many cell types in one well," he added. "It can be 100, or maybe 1,000 cell types. So the benefit is in reduction of costs, speeding up the assay, streamlining assay design and execution, and making it easier for laboratory personnel."
PharmaSeq has already demonstrated a similar concept using microtransponders on which oligonucleotides have been attached for DNA probe and SNP applications, and on which proteins have been attached for protein-binding assays.
And although Mandecki said those versions of the assay are currently further developed — though not yet commercialized — the cell-based version was too tantalizing to ignore.
"The platform is generally applicable to many types of molecules or biological entities, but in particular cells," Mandecki said. "It's actually ideally suited for cells because they are fairly large structures — about 100 microns across — and some other multiplexed platforms such as microbeads or nano-barcodes cannot really deal with fairly large structures like cells.
"We can, though," he added. "We figured that as time progresses, there will be a growing emphasis on assaying cells in addition to proteins and nucleic acids and other types of molecules. So having that in mind, we decided to focus some of our attention on the development of cell-based assays."
If PharmaSeq's approach sounds familiar, it is because another company — Mountain View, Calif.-based Vitra Biosciences — recently brought to market its own technology based on the same concept (see CBA News, 1/25/2005), and is thus far experiencing measured success with evaluation-for-purchase agreements with at least seven pharmaceutical companies, including Bristol-Myers Squibb.
The major difference between Vitra's platform, called CellCard, and PharmaSeq's is that the CellCard system uses color-coded microscale cards, with each color corresponding to a different cell type. Then, the same CCD-based imaging system that reads the fluorescence output from the cells captures the color of the barcode to assign it to a specific cell type.
In addition, in Vitra's system, the CellCards are placed en masse in wells of a microtiter plate, and all assay steps are performed there. According to Mandecki, on the PharmaSeq system, assay prep would likely occur in well plates, while the readouts would be performed while the microtransponders are flowing through a detection chamber, thereby increasing throughput.
In the end, it's probably a minor difference, and the real decision researchers considering the two technologies would have to make is whether or not they want actual images of cells — which Vitra's technology offers, but PharmaSeq's, which is laser- and PMT-based, would not.
And Mandecki believes that the microtransponders could potentially be used for even more types of assays.
"One could think about a different assay configuration in which you could capture certain cell types by having different antibodies on the surface," he said. "So imagine 50 or 100 different antibodies on different microtransponders, and those antibodies capture different cell types, and then those cells are stained [to] produce fluorescence in the flow reader."
A direct comparison of the assay platforms is probably premature at this point since CellCard is on the market while PharmaSeq is still in the early stages of development. A price comparison is also difficult, as Caliper has declined to comment on the cost of CellCard in the past, and Mandecki declined to provide details about possible pricing for PharmaSeq's technology.
While Mandecki declined to provide a specific timeline for the commercialization of any of the products, he said that the company has prototypes of its flow reader, has validated many types of assays, and is "very interested in finding paths to commercialization."
In terms of current funding, PharmaSeq also was awarded a $128,000 grant last year from the National Human Genome Research Institute to further develop the flow instrument into a version that can perform two-color assays on the microtransponders, according to the grant's abstract. Such an instrument would be able to simultaneously read fluorescence at 570 nm and 670 nm, the emission spectra for the popular Cy3 and Cy5 fluorescent dyes, respectively. Although this instrument would serve to optimize nucleic acid-based assay, similar capabilities would likely be desired for the cell-based system.
Of course, if PharmaSeq sees the cell-based assay project through to the NCI's satisfaction, additional funding in the form of a Phase II SBIR grant looms. The current Phase I grant expires on June 30.
In the meantime, Mandecki stressed that PharmaSeq will consider corporate partnerships to help bring the microtransponder technology to fruition.
As for the prospect of venture capital, Mandecki declined to comment how active PharmaSeq is in its pursuit of VC cash. The company does have investment support from two major corporate entities under its belt: In 2001, Japanese corporate giant Mitsui made a "multi-million dollar equity investment" in PharmaSeq, and, the following year, Sunnyvale, Calif.-based chromatography company Dionex invested $3 million in it.
It is unclear what specific interests either corporation has in the microtransponder technology. Calls to both companies were not returned in time for this publication.