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Stanford Spin-out Nirmidas Developing Plasmonic Chip Platform for Protein Detection


NEW YORK (GenomeWeb) – Stanford University scientists have launched a firm to commercialize their plasmonic biosensing technology.

Named Nirmidas Biotech, the company is developing a plasmonic gold chip platform for biomolecule detection and the detection of proteins in particular, Joshua Robinson, the firm's director of R&D, told ProteoMonitor.

San Francisco–based Nirmidas plans to first develop the platform as a general tool for outside researchers then follow that by using it for its own internal biomarker development programs, Robinson said. He added that in terms of this internal work, the company has identified prenatal screening as a likely initial area of interest.

Nirmidas' technology is based on the fact that metallic nanoparticles have been shown to amplify the emission of nearby fluorescent molecules. This phenomenon can, therefore, be used to enhance fluorescent signals from protein detection assays like ELISAs. And, indeed, a number of researchers have in recent years developed protein chips featuring metallic nanoparticle surfaces to amplify protein detection signals, thereby making more sensitive assays.

According to Robinson, Nirmidas' technology differs in that instead of using a flat gold nanoparticle surface, the company patterns its protein chips with "nanogold islands," which, he said, further enhances the target signals. He noted that while a number of companies offer gold nanosurfaced chips – including a number of large protein chip makers – "no one else makes non-continuous gold substrates. That is our patented approach."

He offered the analogy of an echo. "If you are in a desert and you yell out, you're not really going to have much of an echo," he said. "But if you're in a canyon surrounded by large cliffs and you yell out, you get that echo effect, because you have it resonating [off the canyon walls]."

"That's what is unique about our technology," Robinson said. "We have a very easy solution-based process that is very quick and runs at room temperature to pattern a nanogold film. And we tailor the nanogold islands to the exact space to get the highest resonance."

The technology comes out of the lab of Stanford researcher Hongjie Dai, who co-founded Nirmidas with CEO Meijie Tang, formerly a researcher at Lawrence Livermore National Laboratory. Currently operating with five employees, the company incorporated in September 2013 and began production of its initial research-focused chips in March of this year.

The technology, Robinson said, can be applied to a variety of substrates, including beads as well as glass and polymer surfaces, and can provide a more than 100-fold increase in fluorescent signal, he said.

Currently Nirmidas is focused on refining the platform as a research tool for outside labs and firms and is in discussions with several large biotech companies about possible collaborations, Robinson said.

The company also recently collaborated with another team of Stanford researchers using its technology for protein biomarker work in type 1 diabetes. Detailed in a paper published this month in Nature Medicine, the study used Nirmidas' protein chips to discover and detect autoantibodies associated with the disease.

In the study, the researchers sought to identify autoantibodies to insulin present in patients with type 1 diabetes with the aim of using them as biomarkers for distinguishing between patients with type 1 and 2 versions of the disease.

As the authors noted, autoantibodies to insulin are typically the first autoantibodies to appear in type 1 diabetes patients, making them a potentially good biomarker for early detection of the disease. However, these autoantibodies have proved difficult to detect in past work.

The challenge, Robinson said, is two-fold. One, these autoantibodies are typically difficult to detect due to their low concentrations in the blood. Two, there are challenges involved in using insulin as a probe in the assay – specifically that placing it on the platform substrate appears to change its tertiary structure, and so alter its autoantibody binding site.

The researchers approached these challenges by using the Nirmidas chip to enhance the sensitivity of their autoantibody detection and putting a polymer layer atop the chip that allowed the insulin molecules to maintain their normal structure when put down on the substrate, Robinson said.

Because of the sensitivity challenges involved in detection of the target autoantibodies, radioimmunossay is the current gold standard platform for this application. However, in addition to requiring radioactive reagents, RIA also requires relatively large amounts of sample, requiring patients to undergo a blood draw. The Nirmidas chip, on the other hand, is able to work with finger prick blood samples, which, the authors noted, "opens the possibility of point-of-care" detection of type 1 diabetes.

In the Nature Medicine paper, the researchers found that testing with Nirmidas' chip identified type 1 diabetes patients with the same sensitivity (100 percent) and specificity (85 percent) as RIA.

The need for better methods for distinguishing between types 1 and 2 diabetes has grown in recent years as type 2 diabetes – which traditionally has afflicted primarily overweight adults – has appeared in younger people, creating an overlap between what had previously been relatively distinct patient populations.

Robinson said Nirmidas was looking at a number of areas in addition to diabetes in terms of its internal biomarker development work.

"We haven't nailed it down to one," he said. "We're really casting a wide net at this point to see what the killer application is."

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