Fluidigm Developing Stem Cell, Sample Prep, and Higher-Throughput Genotyping Chips
August 18, 2009
Newsletter: BioArray News
By Justin Petrone

Fluidigm is deep into a product-development cycle that will result in the commercialization of new biochips for stem cell studies, sample preparation, and higher-throughput genotyping, according to company officials.

While launch dates for the new products are still undetermined, the South San Francisco, Calif.-based integrated fluidic circuit maker expects the new chips to roll out over the next two years.
Founded in 1999, Fluidigm already makes and sells IFCs embedded in silicone for SNP genotyping, single-cell gene expression, copy-number, and gene-expression studies, second-generation sequencing sample preparation, and protein crystallization.

Fluidigm officials told BioArray News during a site visit earlier this month that the new products will build on the firm’s expertise in these applications.

Stem Cell Chip
Chief Scientific Officer Marc Unger said that the firm is developing a new chip that should address the needs of the stem cell research market. The chip will be based on a prototype developed by Fluidigm co-founder and scientific advisory board member Stephen Quake, a professor of bioengineering at Stanford University.

In 2008, Fluidigm and San Diego stem cell reagent supplier Stemgent received a $750,000 grant from the California Institute for Regenerative Medicine to develop a cell culture chip.

Fluidigm's IFCs are already being used by stem cell researchers for single-cell gene expression studies. In June, the firm said that Shinya Yamanaka of Kyoto University and Toshio Suda of Keio University, both in Japan, had adopted its BioMark platform for use in their studies (see BAN 6/30/2009).

Unger said that the new chip in development should simplify protocols recently developed to turn differentiated cells into stem cells, and to reprogram stem cells to redifferentiate in a desired way.

"There are some very interesting developments that have happened in the stem cell field in the last year and a half," Unger told BioArray News. "Dr. Yamanaka, specifically, took stem cells and turned them into pluripotent stem cells," he said. "However, that protocol was long and with low efficiency. Yamanaka's protocol took 30 days and had 25-percent efficiency."

Even though scientists can now turn differentiated cells into stem cells, they must also redifferentiate them before attempting to use them therapeutically, Unger said. "Those cells can turn into anything and they do, like hair, fingers, or teeth. So you need to reprogram the cells into the appropriate type in order to use them therapeutically. "It is very difficult to do that using welled plates,” he added. “It's difficult to get the conditions uniform and it is very labor intensive."

According to Unger, Fluidigm will be able to simplify the protocol for turning differentiated cells into stem cells and redifferentiating them by locating the processes in one integrated fluidic circuit. This stem cell chip is expected to launch in late 2010. It will have 64 chambers with controls to automatically feed cells in the chambers and provide a medium in which the researcher can individually and automatically dose the cells in a chamber with up to 16 different reagents, according to Unger.

Fluidigm is also developing a supporting instrumentation system that will control the elements on the stem cell IFC and allow researchers to modify the composition of the medium delivered to each chamber in the chip over time, Unger said. The system will also provide time-lapse microscopic images in both transmitted light and fluorescence of the cells so the researchers can consistently monitor the progress of their experiments, he said.

Fluidigm spokesperson Howard High told BioArray News that the market for stem cell research tools is an "emerging and huge area" that the firm views as a "big opportunity." He said that Fluidigm currently has a presence in the market and "intends to remain a significant player as this stem cell area emerges."

Unger said that large pharmaceutical companies are beginning to show an interest in stem cell research, making them potential target customers for the stem cell chip in development.

"Big pharma is making small-molecule drugs, but they are kind of reaching the end of the road and it is getting more expensive to develop them," Unger said. "There are limitations on what small-molecule drugs can do that cells don't have. Cells take hold, grow, and can replenish themselves."

If pharma companies seized on that opportunity, it would "open up a new continent in terms of what therapeutics could do," Unger said.

Sample Processor and Higher-Throughput Genotyping
Another IFC in development at Fluidigm is being referred to as a sample processor chip. According to High, users could input raw samples, such as blood, directly into the integrated fluidic circuit and the chip would extract and purify what the user desires to analyze, such as DNA, RNA, proteins, or other biomolecules.

"This is the automation of the sample-prep process," High said of the system, which the company expects to launch in 2010 or 2011. "For us, it’s a way to simplify and reduce cost for the researcher by automating the process with the chip."

Fluidigm says the sample processor chip builds on its BioMark system, which enables users to perform quantitative PCR, gene expression, and genotyping on one system. "If you look at Fluidigm’s BioMark System for genetic analysis, it starts with DNA or RNA and then amplifies and analyzes those materials," High said. "The sample processor is one step upstream of what the BioMark system does."

While Fluidigm develops the sample processor it is also looking to increase the density of its integrated fluidic circuits. The current 96.96 Dynamic Arrays it sells for use on the BioMark allow users to run 96 different samples on 96 distinct genetic markers. High said that Fluidigm hopes next year to launch chips that will enable users to run 192 different samples in assays of up to either 24 or 96 markers.

Internally, Fluidigm refers to the new higher-density IFCs as "rectangular chips" because they don’t follow its existing square matrix. High said that the genotyping market would most immediately benefit from the higher-density IFCs.

"Genotyping will be the initial market segment where these chips will be targeted," High said. "It could ultimately be used in other areas, but the customers’ desire is to reduce the cost of a given data point by focusing specifically on their points of interest, [which] allows them to just study the markers they are after and minimize them to the greatest extent possible. These types of chips would allow them to utilize the capabilities of a given chip to the best of their ability," he said.

High cited the agricultural biotechnology market as a customer segment that is demanding higher-density chips that offer lower cost per data point. In May, for example, the firm said that Dutch seed producer Enza Zaden had selected its BioMark System for genetic engineering and would use its 96.96 Dynamic Arrays to ensure the quality of its feed supply .

High said that rectangular chips will also "add value" for researchers conducting single-cell gene expression. "In this market segment, cost is not the primary concern," High said. "Here researchers want to study many genes using very little sample," he said. "The ability for maximum utilization off of a rare or small sample will have them tap into the properties of a 192x24 chip, for example."