NEW YORK (GenomeWeb) – Having completed the full commercial launch of its ultra-fast thermal cycler for research use earlier this year, BJS Biotechnologies is now looking to push the platform into clinical use, including near-patient testing.
To that end, the UK-based company in March said that it is spearheading a consortium that aims develop a rapid, point-of-care sepsis test on the platform.
BJS Biotechnologies is a spinout of BJS Company, a firm that specializes in precious metal electroplating but also has a heritage in PCR equipment manufacturing.
"BJS was the first company to develop a silver thermal heat transfer block back in the day … when people were looking to make the current PCR platforms go faster," BJS Biotech's CEO Nick Burroughs told GenomeWeb in a recent interview last week.
In the early 1990's, BJS Company worked with MJ Research (now part of Bio-Rad) to develop silver blocks, and with a number of other firms on their thermal cyclers using the thermal transfer method, Burroughs said. Then came the patent lawsuits, as a number of these partner firms were involved in litigation over thermocycler technologies, some specifically regarding plate design.
As a supplier of blocks, BJS was not entangled. "There were no patents applicable to [our] technology, however BJS used a lot of proprietary knowledge to deliver the performance," Burroughs said.
BJS Biotechnologies currently has a number of worldwide patents on its xxpress platform — a five-channel multiplex real-time thermal cycler — and underlying technology, Burroughs said.
"The new xxpress technology has a long patent life on both the instrument and the consumable," he said, adding, "We also have freedom to operate in [this] busy IP sector, [and] this took some significant effort."
Burroughs co-authored a chapter describing the new BJS technology in PCR Technology: Current Innovations, a 2013 book co-edited by PCR expert Stephen Bustin. Titled "Ultra-High-Speed PCR Instrument Development," it iterates the challenges facing thermal cycler developers.
Namely, cycling speeds depend on heating and cooling ramp rates. These rates can be sped up by using a block with less thermal mass, but a thin block also delivers less-uniform heating and cooling.
Some spatial thermal cyclers achieve increased speeds by shuttling sample between blocks of set temperature. Others solve the problem in ingenious ways — by having sample flow around a cylindrical heat source, by using a rotary thermal cycler that moves around a stationary sample tube, or even by deploying lasers.
However, these solutions may be best for single samples or small batches. Burroughs said there is value in preserving a traditional PCR workflow that people are familiar with.
"One of the benefits of [our] technology is we've made it go faster but we haven't changed the way that people perceive the samples," he said, adding that the method is also flexible and good for general use in ways that other fast methods are not.
Furthermore, the same sort of robotic systems that work on existing plates will be able to adapt to the xxpress plate, he said.
The plate is made from thin, inexpensive aluminum connected into an electrical circuit. "Different current patterns run through it causing it to heat up," Burroughs said.
The platform uses an array of non-contact infrared sensors to sample temperatures 100 times per second. This information is then fed back the control circuitry, which varies the heating path to achieve the desired temperature.
Cooling is accomplished with high speed air jets that allow for air flow to be proportional to the desired amount of temperature decrease. The platform also cools slightly under the required temperature and tops this up with additional heating, "to make sure that the cooling is always uniform and under control," Burroughs said.
Finally, an essential part of the new system is the well design. The microtiter plates gain efficiency by being flat-bottomed, like shallow buttons, instead of typical conical wells.
"We have a vertical wall and a big area that's touching the surface of the plate, and the sample cools and heats very quickly because of that," Burroughs said.
The xxpress boasts a uniformity of 0.3 degrees Celsius while cycling.
"Typically [our] technology is between four and five times quicker than the current state of the art, delivering a single-channel, 40-cycle, real-time PCR in less than 10 minutes with standard sample sizes," Burroughs said. The plates are also available in 24-, 54- and 96-well formats.
The xxpress PCR platform took about a decade to develop, but BJS now has a significant worldwide distributor base and has started to make end-user sales, Burroughs said.
"About a year and a half ago we released a beta product into distributors so they could go and show it to customers … Our final product with all of the capability of the machine and analysis was released this year, so we are now starting to see sales," he explained.
Customer reaction has been "very positive" because in addition to the thermal performance, the platform has an intuitive user interface so it is "very easy to use," Burroughs noted.
"The future goals are to take the technology into the field of diagnostics where faster tests can be used to save lives," he said.
One of the firm's first diagnostic projects is the aforementioned collaboration with industry and academic partners to develop a cartridge-based assay called Sepsis-xxpress.
With blood infections, a patient's risk of death climbs by as much as 8 percent per hour without treatment, Burroughs noted. "That's really tragic when you consider that we actually have the right medicines to treat them, if only we knew which one to give."
The sepsis assay will ultimately include sample prep and is projected to take about two hours, compared to the five or six hours for current sepsis testing.
In fact, with sample prep and automated plate loading Burroughs foresees xxpress being used for other near-patient testing, without requiring a specialist laboratory.
"I think that's where the market will take us, but short term we're out there selling a product into the research market for any lab-based diagnostic that just needs an ordinary thermal cycler," Burroughs said.
Additional arenas where faster PCR might be beneficial include food, water, and GMO testing. As noted in the PCR book chapter, sampling products during manufacture as opposed to sampling from batches at the end of the day can potentially reduce waste, for example.
"We're already seeing interest from customers who want to have a faster diagnostic test, but a test still based on PCR, because they have already done the research," Burroughs said. "An awful lot of tests that exist out there will go faster on our platform by quite a lot."