AACC launched its new Disruptive Technology Award in July at the 70th AACC Annual Scientific Meeting & Clinical Lab Expo in Chicago. The competition supports diagnostic developers at the forefront of science and technology in laboratory medicine and gives clinical laboratorians the opportunity to evaluate novel technologies and their potential impact on patient care.

This year, a panel of AACC members selected three finalists to present their technologies at the meeting from a pool of 42 applicants: Ativa Medical, GNA Biosolutions, and Two Pore Guys. During a session on July 30, judges scored the technologies on feasibility and overall performance. This year’s winner, Munich, Germany-based GNA Biosolutions, also won the audience choice award. The company showcased its pulse-controlled amplification technology that enables ultrafast polymerase chain reaction (PCR).

The core idea behind GNA Biosolutions’ technology does not have its origin in laboratory medicine, but in the research of a physicist. Joachim Stehr, PhD—who co-founded the company with Federico Bürsgens, PhD, and Lars Ullerich, PhD—first documented his idea of nanoparticle DNA analysis in his doctoral thesis. His idea was to speed up PCR, which underlies most molecular testing, by employing exquisitely small and efficient gold nanoparticles.

Traditionally, amplifying and detecting DNA using PCR amounts to cooking the DNA in a sample at precise temperatures over cycles of heating and cooling. Heat “melts” the DNA, unzipping its double strands. When the solution cools down, carefully selected primers latch onto a specific section of DNA that is targeted for replication and detection. Cycles of heating and cooling repeat dozens of times.

Due to the unique physics of nanoparticles, however, GNA Biosolutions believes it can radically change that process, managing director Ullerich told CLN. The key to making nanoparticles work is the company’s proprietary pulse-controlled amplification system. Launched in November 2017, GNA Biosolutions’ first commercial platform, Pharos V8, uses laser pulses to ignite the PCR reaction.

The interview has been shortened and edited for clarity.

How does pulse controlled amplification differ from traditional PCR methods?

The basic problem with PCR is that you need to thermalize the whole reaction—obtaining different temperatures 30-40 times—and this heating up and cooling down of the entire reaction volume is the most time-consuming step.

We use microcyclers—nanoscale thermocyclers—right inside the solution and heat them with an external energy source. They are so small that as soon as the energy source is turned off, they cool down instantaneously, because the liquid in the reaction volume itself serves as the cooling reservoir. This means our heating times are extremely short, and the microcyclers cool off automatically. This approach of using localized heating elements in the solution is at our core. In the Pharos V8 instrument we do this with laser-heated nanoparticles. In our new prototype, we use electrically heated microcyclers inside the solution.

Using localized microcyclers in the solution also makes the instrument essentially volume independent—it can process very small or very large volumes in the same time frame, with amplification and detection often taking fewer than 10 minutes.

What about sample preparation?

Sample preparation is another bottleneck in molecular diagnostics. A traditional method would use columns with resins and several wash and elution steps. This eluate would then need to go into another reaction process.

In our case we use the microcyclers for target capture, amplification, and detection in the same reaction well to simplify the process. This allows the instrument to purify nucleic acids out of crudely lysed sample directly, even from whole blood. And the ultrasound lysis step is very quick and integrated into the device.

How is the Pharos V8 instrument being used in clinical laboratories?

Pharos V8 is mainly for speeding up lab-developed tests. Clinical labs can port their own probe-based tests onto the platform. The same principle applies to life science applications in which researchers want to speed up PCR.

We have not disclosed most of our instrument placements, but many are focused on infectious diseases. One collaboration we’ve made public is our work with the Lazzaro Spallanzani National Institute for Infectious Diseases in Rome, where we co-developed Ebola and tuberculosis assays.

Now we’re focusing on our next-generation system, still based on pulse-controlled amplification, but miniaturized for point-of-care testing. Instead of lasers, the new platform uses an electrical current that goes through the solution and produces heat on the surface of microcyclers.

How can advanced technology like yours be cost-effective?

First, you always have to look at the real world: Real clinical samples are very important to include in your experiments as soon as possible, and then you can look at ease of use and manufacturing. Of course, it’s important to be able to scale manufacturing of chips and devices. However, in our case, our chemistry is rather standard, and microcyclers don’t add significantly to the cost.

Partly this is by design—our chips have a much simpler workflow than current cartridges on the market. Most cartridges that perform molecular diagnostics are still too slow, complex, and costly for the point-of-care, and they typically have 30-35 individual parts to combine. We can use about five parts for the cartridge. With sample prep taking place intrinsically on the microcyclers, we can keep the instrument simple, and there’s no sophisticated heating block like other systems.

Where do you see this technology being used—mainly at the point-of-care, or in core laboratories as well?

In principle, both. We want to bring molecular testing into new environments and closer to patients through speed that fits the point-of-care workflow, ease of use, and cost. But the principles of pulse-controlled amplification are also scalable, so we see applications for centralized laboratories for medium-to-high throughput applications. This simple heating mechanism can be scaled up to larger plates, for example, something we’re looking at with potential partners, even while our own focus is on point-of-care devices.

For the point-of-care, we feel it’s extremely important to be as fast as possible, because at the point-of-care every minute counts. Many companies out there say that first result is within a certain short time frame, but often it would take much longer for a full analysis and for samples that would not contain a high burden target load.

For example, PCR testing for an acute flu infection already has been made quite rapid. The reason is that there is not a lot of sample preparation and there’s a high titer. But for other clinically significant sample types like blood—probably still the most important sample type—often other systems aren’t nearly so fast, especially when it comes to important bacteria with low target concentration, such as tuberculosis.

Ultimately, our goal is a Food and Drug Administration-approved and CLIA-waived system, and our assay pipeline includes tuberculosis and antibiotic-resistant bacteria.