When it comes to cellular analysis systems, high throughput is not the only consideration. For many researchers low cost, small size, and ease of use may be just as important.
Recognizing this inclination, Guava Technologies of Hayward, Calif., has built its business around its Personal Cell Analysis (PCA) and PCA-96 platforms — automated fluorescent-based cellular analysis systems that fit onto a laboratory bench top and don't empty researchers' wallets.
The PCA systems really fall under the category of flow cytometers, which had been unchallenged in the realm of cellular analysis for decades, until newer technology such as high-throughput microscopy and microwell plate scanners began to inch into the marketplace.
But proprietary microfluidics technology separates the PCA systems from its flow cytometer relatives.
"All of our platforms share the same technology, which is our patented microcapillary cytometry technology," said Keith Olson, Guava's director of product commercialization. "It's similar to flow cytometry in the sense that you're analyzing single cells in solution. The main difference is that flow cytometry uses what's called sheath fluid, which essentially gives you a river that you inject cells into, and it generates a lot of waste."
According to Olson, the Guava systems establish a fluid stream using a 100-mm-bore capillary that goes into an individual well of a 96-well plate and literally sucks cells up into a stream. Therefore, users save money on the instrumentation end because the instrument is much more compact than other flow cytometers, but in addition, they can be frugal with regards to sample size and chemical reagents because there is very little waste.
The Guava instruments are also completely automated, and the company's website boasts that they are designed for easy operation and maintenance, claiming "you only handle three components in the Guava instruments: the power switch, the sample loader, and the waste vial." This is a large departure from the perception that flow cytometers require highly trained individuals to operate them.
"The systems can be used by someone in high school to someone with a PhD," added Olson.
While the advantages of the Guava platform over traditional flow cytometry are apparent, many scanning well plate readers can provide much higher throughput, and several automated microscopy-based systems offer much more detailed morphology and higher throughput, to boot.
"The plus end of the microscopy platforms is that they're the ideal system for doing detailed morphology-type measurements," Olson said. "If you want to do angiogenesis, or neural outgrowth, or watch a cell crawl across a piece of glass, those are all things you want microscopy for."
But for traditional screens such as cell cycle, apoptosis, cell viability, and toxicity, "those can all be done on a cheaper, more effective platform like the one that we offer." According to Olson, most imaging-based systems cost in the hundreds of thousands of dollar range, while the Guava platforms top out in the tens of thousands.
The company is targeting PCA instruments to budget-minded researchers, like those at academic institutions, but insists they definitely have a place in the world of big pharma, as well.
Olson said that the PCA, which is a centrifuge-sized bench top instrument, is intended more for "quality control" and initial screening. The primary application for a pharmaceutical scientist, he said, would be to check cell viability, expression levels, and health before moving on to more high-content screening. The PCA-96, which comes in two flavors (different laser lines for different fluorescent dyes), is used primarily for lead optimization.
Finding its Niche
But for high-content screening for drug development, the PCA-96 is a bit of a 'tweener," as sports journalists like to say. Jean-Philippe Stephan, a research scientist at Genentech in South San Francisco, Calif., uses a PCA-96 as a small-scale drug screening tool.
"It's definitely not a high-throughput instrument, but you get very precious information, like cell cycle, apoptosis, viability,” Stephan said. “and when people talk about high-content, it’s usually one well with several different types of information. [With the PCA] it’s one well, and one type of information.
“But what I really love about it is the simplicity and ease of use,” he continued. “You don’t have to be a FACS expert to use it. Cell cycle analyses in particular is so simple.”
Stephan also added that it is best suited for screening a limited number of compounds and cells. “It could be used for secondary screening,” he said, “but the researcher would have to make a choice: Either test several compounds against one cell line, or one compound against several cell lines.”
Some pharmaceutical and biotechnology companies, such as Amersham Biosciences (now GE Health Sciences) have already seen that the PCA platforms might be best-suited as complementary instruments to higher-throughput, higher-content, imaging-based ones (see inside story, page 8).
The PCA platform is slowly beginning to carve out some specific application niches of its own, though, as evidenced by recent research conducted by Guava collaborators at the Leiden University Medical Center in the Netherlands (see Inside Bioassays, 4/20/2003).
The researchers used a PCA-96 to measure the motility of lymphocytes in response to chemical stimuli. Such an assay is traditionally done using what's called a Boyden chamber, where researchers look for cells moving across a gradient set up within a dual membrane system — a fairly complex assay, Olson said.
The scientists from Leiden, however, fluorescently labeled cells to signify actin polymerization based on changes in fluorescence intensity. Simple measurements of the intensity changes by the PCA system translated to evidence that the cells were moving via actin-based motors.