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BioHelix Working on New Isothermal Nucleic Acid Testing Platform Using Handheld Fluorescence Reader

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BioHelix is developing a low-cost, handheld, real-time fluorescence detection system capable of running assays based on the company's isothermal helicase-dependent amplification technology, the company disclosed this week.

The new instrument, called FireFly, is designed to complement BioHelix's existing commercial single-use, handheld, cartridge-based molecular testing device because the former will be able to perform quantitative analyses, making possible assays such as viral load testing, BioHelix CEO Huimin Kong told PCR Insider this week.

BioHelix hopes to submit the platform and its first test — an assay to detect and type herpes simplex virus types 1 and 2 from genital or oral lesions — to the US Food and Drug Administration for approval next year, Kong said. In the meantime, BioHelix is continuing to develop molecular assays for its disposable cartridge-based system both on its own and in concert with partner Quidel, Kong said.

Based in Beverly, Mass., BioHelix has been exploring multiple commercialization channels for its helicase-dependent amplification, or HDA, technology, which has certain advantages over PCR in terms of cost and ease of use, making it ideal for point-of-care testing applications.

"Helicase-dependent amplification is our proprietary amplification technology, and that's the engine," Kong said. "You can put that into different vehicles."

The first of these "vehicles" is the company's IsoAmp-branded assay platform, which runs on its disposable handheld cartridge-based system, called the BioHelix Express Strip, or BESt Cassette. These assays consist of a one-step, external sample preparation step combined with HDA-based isothermal amplification and endpoint lateral flow-based detection of amplicons.

In October, BioHelix received FDA approval for its first molecular test using the combined IsoAmp/BESt Cassette, an assay to detect, but not differentiate or quantify, HSV from genital and oral lesion specimens in symptomatic patients (PCR Insider, 10/20/2011).

Even while it is developing its own IsoAmp/BESt Cassette assays, BioHelix is also working with clinical diagnostics firm Quidel to commercialize handheld, disposable assays under the Quidel brand name AmpliVue. Quidel's first AmpliVue test, an assay for Clostridium difficile, has received CE Marking and is currently available for sale in Europe, and is expected to launch in the US by the end of this year (PCR Insider, 3/29/2012).

BioHelix sees a market for these types of disposable molecular tests in small laboratories, physicians' offices, or even field-based, point-of-care testing.

However, its new assay technology, which is called IsoGlow and will run on the FireFly handheld fluorescence reader, is geared more toward "small and mid-sized labs," Kong said.

"There's going to be some overlap," he said. "They're both for smaller labs, and the menus will be similar. One advantage of IsoAmp [and the BESt Cartridge] is that you have no instrument whatsoever; however, you only can do one assay at a time."

The IsoGlow/FireFly system, on the other hand, can run anywhere between one and 12 tests, with results linked to a laboratory information management system. The actual device will cost "a few thousand dollars," Kong said, but in general the platform will have more features.

"IsoAmp is like a disposable camera. You just use it and throw it away," Kong said. "It costs a little bit more for each individual test, but the 'camera' is free, essentially. With IsoGlow … you have to buy the camera, but the [assay] quality is better. Many companies sell two systems: one for low-end users, and the other upgraded with more features," such as quantitative analysis akin to real-time PCR.

In a study published online last week in the Journal of Molecular Diagnostics, scientists from the company compared the performance of an HSV typing test using the new platform with that of its FDA-approved IsoAmp HSV assay and a commonly used culture/direct fluorescence antibody test called ELVIS HSV from Diagnostic Hybrids.

In that paper, the researchers also described the development of two different versions of its IsoGlow HSV assay. Because the FireFly platform has only two detection channels, and the assay must detect HSV 1, HSV 2, and an internal control, researchers devised two endpoint detection strategies using a cycling probe technology: the first used post-amplification melting curve analysis to detect the control while the second detected fluorescence from the control target after amplification at a different temperature than that used to amplify the HSV targets.

Overall, the group evaluated both methods on 176 frozen clinical specimens that were HSV-1 positive, HSV-2 positive, or HSV negative, as determined by the Diagnostic Hybrids ELVIS test. The team also tested 116 of these samples using BioHelix's FDA-cleared IsoAmp HSV assay.

In general, the BioHelix researchers found that both formats of the IsoGlow assay had specificities comparable to that of the ELVIS assay, and sensitivities comparable to that of the IsoAmp assay. The researchers noted that the use of melting curve analysis for control detection was more robust in the presence of amplification inhibitors, but that the two-step cycling probe technology method was more sensitive in other instances, making a case for either version of the assay.

Kong said that the company will be pursuing FDA approval for some version of the IsoGlow HSV typing assay, but that it really used HSV as an easy proof-of-principle example because of the company's experience developing assays for that target.

"HSV is not the largest potential market," Kong said. "We can probably pick something that has a higher [testing] volume, like chlamydia and gonorrhea, or C. difficile." In addition, Kong noted, BioHelix is developing an assay for HIV viral load on the IsoGlow/FireFly system, which it hopes to submit to the FDA for approval in 2013.

In the meantime, the company is also working on an assay for its original IsoAmp/BESt platform that will be able to type but not quantify HSV 1 and HSV 2. The company has not yet published data regarding this assay, and Kong said it has been put on the back burner for the time being while the company's R&D team focuses on the new assay technology and its collaboration with Quidel.

On yet another front, BioHelix is working with the laboratory of Catherine Klapperich at Boston University under a National Institutes of Health grant to develop a chip-based point-of-care molecular testing device that will fully integrate and automate HDA assay technology and sample preparation (PCR Insider, 10/13/2011). Neither of BioHelix's other assay platforms have integrated sample prep.

That project, Kong said, is at a "much earlier basic research stage."

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