Would your pet protein be happier resting in a big square slab of polyacrylimide gel, or plopped on a slide inside a smaller gumdrop of polyethylene glycol?
Researchers using protein chips, as well as those interested in using so-called hydrogel substrates for nucleic acid chips, can now fuss over such questions. Just weeks after Packard Bioscience (now part of PerkinElmer) introduced its HydroGel slides, a competitor, Biocept, has surfaced with its own hydrogel spotted arrays.
The fifteen-employee San Diego area startup, armed with the inventions of founder-organic chemist Soonkap Han, hopes that its novel chemistry and method of depositing hydrogel droplets onto arrays will attract would-be customers of Packard or other companies with hydrogel offerings such as Motorola.
The slides that Biocept is selling consist of polyisocyanate-modified polyethylene glycol-based polymer droplets spotted onto an amine-coated glass slide, and at present have up to 1,000 polymer spots per slide.
The main advantage of the polyethylene glycol-based hydrogel is that it enables researchers to reduce the microarraying process to one step, which can be done at room temperature, said Han.
“All you need to do is add water to the polymers,” he said. “But if you look at polyacrylimide-based hydrogels, they often required UV-based radiation or other radical mechanisms.”
Another feature that the company hopes will sell big pharma and biotech companies on these chips is polyethylene glycol’s low rate of non-specific binding, decreasing the chip’s background noise. This factor “is a huge advantage compared topolyacrylimidebased slides,” Han said.
The company hopes to sell these slides to big pharma and biotech-nology companies for protein and nucleic acid-based research.
“We are trying to aim for the low- and medium-density chip market,” said Ken Brown, vice president of business development for Biocept. “We have a very accessible chip, with three-dimensional probes, that is easy to produce.”
Additional advantages of the technology, Brown noted, include its dynamic range and the low coefficient of variation, according to Biocept. The spots can be more sensitive than traditional probe spots because the polymer spots can hold more probes than two-dimensional surface chemistry. This means that a higher number of oligos or proteins could fit in one spot, and expression levels could be detected at very high or very low ranges, Han said.
Once the probe is deposited, Han added, it is easy to control the speed of the reaction by controlling pH and temperature. A lower pH aqueous solution added to the probe will lengthen the polymerization time, while a higher pH will shorten it.
The low coefficient of variation between chips results from the extent to which Biocept is able to control the spot deposition process, according to Brown. “Compared to polyacrylimide, our system is more controllable. The size of a droplet is easily controllable. We know exactly what we are putting there.”
The company uses a robot adapted from the semiconductor industry to spot down the polymers. The protein or oligo probe is covalently bound to the polymer before the droplets are spotted down onto the slide, and the company plans to do custom arraying for customers who order specific proteins. Biocept is currently testing its pilot production facility and plans to have it up and running by the end of the year. While it can only print 50 arrays per day at present, the company plans to increase its capacity once the facility is fully operational.
Will Biocept be able to catchPackard in the hydogel product arena? Packard has the first-mover advantage. It not only has a fully operational manufacturing class-1,000 cleanroom facility for its HydroGel chips, but like Biocept, Packard claims that its chips have less than a ten percent coefficient of variation. Additionally, Packard’s data is more detailed, including specific CVs for different proteins such as streptavidin. In other words, Packard has a more complete product pitch.
Currently, Biocept is in discussions with several pharmaceutical and biotechnology companies to provide customized arrays, said Brown, and is also pursuing an agreement with a molecular diagnostics company that would commercialize the technology for molecular or clinical diagnostic arrays.
Additionally, the company is testing prototypes of its array for apoptosis gene expression. To make the case for its arrays stronger, Biocept is also testing the chips against currently available commercial DNA-based arrays on the market, and plans to release the results in a few weeks. Most likely, these results will echo the enthusiastic descriptions of the company’s executives.