Spectradyne: SBIR Funding Spurs Advances in Nanoparticle Technology

Nov. 19, 2024

The ARC™ particle analyzer measures the size, concentration and fluorescence of single particles as small as 50 nanometers in diameter. (Spectradyne)

Analyzers speed diagnostic and treatment development

One of the biggest achievements in modern medicine involves some of the smallest known substances. Much of today’s biological research and drug development involves tiny particles, each smaller than one millionth of a millimeter — too small to see under a normal microscope.

These nanoparticles include viruses, proteins, sugars and nucleic acids. Identifying these particles and their qualities is important for the growing field of nanomedicine. They can help us understand basic biology and can aid disease diagnosis and treatment.

Nanoparticles may be used in medical imaging, as targeted cancer and autoimmune disease treatments that cause fewer side effects, and as biomarkers for diagnosing diseases or monitoring treatments. It is key to ensure that the nanoparticles used are correct for the task at hand.

“Nanoparticles are used in a huge range of applications. For example, the COVID-19 vaccines from Pfizer and Moderna are lipid nanoparticle-based therapeutics. Now, there are new therapeutics in development based on nanoscale materials like viruses and other particle types,” said Jean-Luc Fraikin, Ph.D., a physicist and the co-founder and CEO of California-based startup Spectradyne, LLC. He added, “They’re also implicated in cancer metastasis. The field is rapidly growing, and there is excitement about the potential of using nanoparticles as new biomarkers and new therapeutics.”

While recent gains in nanomedicine are significant, overcoming the hurdles of working with invisible live nanoparticles will be crucial to fully realizing the transformative potential of nanomedicine. For example, due to their dynamic nature, nanoparticles derived from biological systems may show a range of success against specific pathogens. This type of uncertainty requires new approaches for studying the makeup of these complex systems. A prime example of the type of research bottleneck NCATS aims to address is the testing and characterization of nanoparticles grown in cultures. The goal is to ensure that researchers and manufacturers are working with the right materials. The process requires costly optical equipment run by highly trained staff who must then infer accuracy from indirect measurements. This approach is expensive and time-consuming and may not always ensure purity and efficacy of live nanoparticles. Additional tools are needed that can analyze these nanoparticles during the early stages to identify unwanted or harmful particles before significant resources are used. Until recently, such tools were unavailable, which hindered progress in this promising field.

“A variety of tools are available for analyzing the outcome of experiments to test the potency of nanoparticle-based therapeutics. But not many options exist for measuring the amount of material — the dose — that is input to these experiments. If you can’t measure the dose accurately, then it is very hard to perform well-controlled science,” said Fraikin.

An NIH Grant, a Successful Startup and SBIR Program Support

Fraikin first became interested in nanoparticles and life sciences as a doctoral student in physics at the University of California, Santa Barbara. He worked in the lab of Andrew Cleland, Ph.D., who led projects making electrical sensors for biological systems.

Cleland’s lab was funded in part by an NIH grant. Through that project, Fraikin met a biologist who shared the importance of being able to measure a relatively new kind of biological particle called “platelet dust.” These particles turned out to be extracellular vesicles or sacs — nanoscale particles shed by cells that are now understood to play key roles in a broad range of biological functions, including cell communication. Cleland and Fraikin started scaling down the lab’s electronic sensing methods to detect these particles. In collaboration with other biologists, they showed they could detect viruses and other nanoparticles directly in plasma.

Ultimately, Fraikin, Cleland and two other colleagues cofounded Spectradyne, a company that develops cutting-edge particle analysis tools to address life science needs that can’t be met with existing technologies. “Accurate particle characterization enables better science, clearer outcomes and more information,” Fraikin noted. With funding support from the Small Business Innovation Research (SBIR) program through NCATS and other federal agencies, the team at Spectradyne found a way to quickly and efficiently identify, quantify and characterize nanoparticles to ensure accuracy and purity.

Fraikin and partners Franklin Monzon, Peter Meinhold and Cleland developed a device that is roughly the size of a microwave oven to ensure the correct nanoparticles are present in the right quantity at the start of production. Their first product, the nCS1 particle analyzer, measures the size and concentration of nanoparticles — but it could not identify which particles were being measured.

“Many nanoparticles are produced in a complex biological soup that contains other particles, and our customers needed a way to distinguish their particles of interest from background particles also present in the sample,” Fraikin explained.

With a second NCATS award, an SBIR Phase II award of $1.6 million, Spectradyne went back to the bench to design its next-generation product. The ARC™ particle analyzer measures the size, concentration and fluorescence of single particles as small as 50 nanometers in diameter. For context, a single sheet of paper is about 100,000 nanometers thick. The fluorescence measurements allow users to identify specific target particles in the mix.

“The ARC enables fast and accurate characterization of these critical materials and will ultimately reshape the discovery, development, and production of modern therapeutics,” Fraikin said. “Its development was made possible in large part by the NCATS grant we received. The grant allowed us to build the expertise and acquire the equipment necessary to develop the new product. It enabled us to invent, develop and launch the product from ground zero.”

Grant Funding Lays the Foundation for Success

While the initial NCATS funding helped accelerate Spectradyne’s innovation, it also provided security for the fledgling business.

“On the business side, we’re still a small company and susceptible to market uncertainty, so the Phase II grant helped a lot by providing a relatively long-term, stable financial basis upon which we could feel comfortable hiring and investing in the development of the new product,” Fraikin said.

He adds that NCATS was particularly attractive because of its expertise in the industry. He also strongly recommends that anyone considering applying for a grant talk with NCATS program staff beforehand.

“I’ve had an awesome experience with the program managers,” Fraikin says. “It’s always great to get [their] opinion on how your project fits with respect to their priorities. Talk to the other program managers and take advantage of that openness and availability. It’s a huge resource.” Fraikin also recommends talking to other grant recipients.

“Grants are very formulaic,” Fraikin said. There’s a clear set of expectations for a grant proposal. In a way, that makes it less difficult, but getting other people’s eyes on your proposal to see how well you’re following that rubric is a huge asset.”

Recognizing that a strong application is key to securing funding, Fraikin emphasizes the importance of using available resources and viewing the process as a learning opportunity. “We’ve had failed applications in the past that really benefited from the critiques. If you’re looking at it as an iterative process, then [the critique] is ultimately there to improve the work that’s being done,” Fraikin said.

To help with this, NCATS and NIH also offer resources to assist applicants in crafting applications, including examples of successful applications and training programs that walk teams through the application process. Finally, Fraikin recommends staying focused on the initial project and not getting distracted by widgets and extensions that customers may want.

“It can be hard, especially when you want to win early customers, because you want to do whatever you can to win those deals. The temptation is to provide all the features they ask for and develop the perfect product. Ultimately, those customer requests are valuable because they add to your understanding of the market, but to go to market quickly I think it’s important to focus on the minimum viable product for your target market segment so you can start selling and bring in revenue,” he said.

Fraikin’s advice? Resist feature creep. By focusing relentlessly on that initial minimum viable product, entrepreneurs can secure the early wins — and the revenue — needed to build those bigger, bolder visions down the line, such as attracting further investment or expanding into new markets.