Research Engine

The next brain wave of innovation

A startup in San Diego, Neurophotometrics, is disrupting the market for high-end scientific equipment in the academic research enterprise, investing in the talents of junior researchers

Photo by Richard Asinof

Sage Aronson, the founder and CEO of Neurophotometrics.

By Richard Asinof
Posted 7/23/18
A Ph.D. candidate in Neuroscience at the University of California San Diego has created a brain imaging technology firm, Neurophotometrics, which is also upending the entrepreneurial model for innovation, with potential big-time implications for the academic research engine in Rhode Island.
What can be learned from the Neurophotometrics entrepreneurial model of creating a scientist-run company that harnesses the intellectual power and creativity of junior researchers? Would neuroscience researchers at Brown or URI be willing to invest in an installation of the Neurophotometric imaging system? How can junior researchers in the academic research enterprise in Rhode Island be empowered to make similar leaps into the entrepreneurial world? How does the success of Neurophotometrics change the equation around the tug of war between intellectual property, licensing and patenting?
With each wave of growth of what is described as the innovation economy, the metrics of success are often measured in terms of private equity investments made in new companies or the valuation of IPOs. Whether you invest in an equity-driven or a revenue-first model, the current entrepreneurial culture seeks to reward those who make the most money in the shortest amount of time.
And, with that quest for immediate gratification often comes unrealistic expectations by policy makers about the best way to incent potential job growth and economic development.
The secret ingredient of innovation is, of course, investing in talent, as well as the recognition that failure plays a prominent role before you can achieve long-term success in most research efforts. The emphasis by Neurophotometrics in creating a scientist-led company investing in the talents of junior researchers offers a different kind of entrepreneurial model, one worthy of investigation by incubators in Rhode Island.

SAN DIEGO, Calif. – In a nondescript rented space in a business park of concrete industrial buildings on the northern outskirts of San Diego, Sage Aronson, the founder and CEO of Neurophotometrics, LTD, and a Ph.D. candidate at the University of California at San Diego in Neuroscience, recently led ConvergenceRI on an impromptu tour of his manufacturing operation for his new fiber photometry product, with 3-D printers clattering in the background and scientists and engineers applying the precise engineering finishes at a workbench.

At first glance, the small industrial workshop with its own large garage door, which serves as the production facility for Neurophotometrics, a new startup fabricating state-of-the-art optical and behavioral equipment for both academic and industrial research applications, conjured up historical comparisons to the garage where five decades earlier, Steve Jobs and Steve Wozniak developed the prototype for what became the first Apple computer: a workshop where young entrepreneurs are fashioning a disruptive technology and building a new market channel for high-end scientific equipment in the academic research enterprise.

There is a kind of inventive, infectious “excitement” that pervades the work, where the problem-solving required to set up a new, custom-built system for a university research lab is often, as the website described it, “a little MacGyvered.”

The differences between the garage of Apple’s founders and this one, however, seemed important to highlight: Aronson and his team are not college dropouts, but highly trained in what they call “a scientist-run” enterprise, with the goal of harnessing the creativity and intellect of fellow graduate students to build a network of demand for the products.

“In science, every discovery leads to new questions,” the company’s mission statement begins. “The answers to many of these questions require novel tools and technologies.”

As most scientific research [the bench work] is conducted by junior researchers, [i.e., graduate students and postdoctoral fellows], the mission statement continued, “This group has a unique perspective as to the demand for new technologies and regularly spearheads their development.”

Translated, the new products being developed by Aronson and his team at Neurophotometrics seek to disrupt the existing entrepreneurial channel by unleashing the intellectual power of the junior researchers doing the actual bench science.

The mission statement is explicit about this task: “At Neurophotometrics, we aim to work with junior researchers to rapidly make their technological advancements available to a broad audience. Our objectives are to reduce redundancy in tool development, promote a more efficient use of federal and private funding, and to augment the stipends of junior researchers so that they become commensurate with the value they provide to society.”

In terms of disrupting the existing market, the mission statement is also transparent about the aim: “Through our symbiotic relationship with academia, we look to disrupt the scientific hardware industry by rapidly bringing new technologies to market in an affordable manner. This gives us a competitive advantage over most science technology companies,” the mission statement explained, which are forced to spend substantial funds re-engineering or reverse engineering advances that have already been developed.

Or, as the firm’s website put in more bluntly: “Our mission isn’t to fleece labs… but to get this exciting technology out to labs as quickly as possible.”

Quicker, better brain imaging and recordings
At the heart of the products being developed by Neurophotometrics are enhanced capabilities and techniques to record activity in specific regions of the brain, allowing for the capture of new insights into “the temporal dynamics of signals traveling throughout brain-wide circuits.” [The technology is designed for research animals, not humans.]

It may sound a bit wonky to the layperson, but the products can simultaneously record cell bodies and fibers and discrete neuronal populations in high resolution, all in freely moving animals.

Translated, neuroscience researchers can now simultaneously record “multiple animals and multiple brain regions,” in what the company describes as a “plug and play” design.

The competitive advantage that Neurophotometrics offers is not just better engineering and design of their products, but what they describe as a “staff of scientists at your back” to consult with and aid in installation.

As described on the firm’s website: “On our onsite installations, we will work with your team [cranking out a couple of monster days] to set up the system, go over the theory behind fiber photometry and bulk calcium recordings, work out different genetic and viral strategies, troubleshoot coordinates and surgeries, and – mainly – record and analyze quality data. These visits are tailored to the needs of your team and typically last 2-3 days.”

In July, Aronson spent three days working with Takao Hensch’s lab at Harvard University, which researches how experience shapes brain development, helping to install the Neurophotometrics system. [Hensch is joint professor of Neurology, Harvard Medical School at Boston Children’s Hospital, and professor of Molecular and Cellular Biology at Harvard’s Center for Brain Science.]

And, at the Society for Neuroscience annual meeting, to be held Nov. 3-7, in San Diego, a gathering that will attract thousands of neuroscientists from around the globe, Aronson and his team at Neurophotometrics are planning to roll out a few new products being developed as part of its R&D efforts.

Significance for Rhode Island
What is happening in San Diego at the Neurophotometrics’ workshop will not stay in San Diego; it has potential, big-time significance for what is occurring in Rhode Island – both in terms of intersections with the academic research enterprise in neuroscience, and in ongoing conversations to fashion a new entrepreneurial maker model connecting design, engineering, technology, science and the arts, harnessing the creativity of graduate students.

The neuroscience academic research enterprise in Rhode Island continues to attract new large investments, the latest being the $100 million gift by the Carneys to Brown University to enable the school to invest in research, talent and infrastructure with the goal to become a national hub of neuroscience research. [See link below to ConvergenceRI story, “$100M gift to Brown hailed as lifeblood driving innovation, discovery in brain science.”]

“To understand the human brain is, for me and for many of my colleagues, the final frontier,” said Diane Lipscombe, the director of the Carney Institute for Brain Science as well as president-elect of the Society for Neuroscience, the field’s international professional organization, in an article published by Brown University news. “We’re in an incredible moment in time right now in brain science. The time is now. There is no time to wait.”

The recent investment in Brown’s brain science institute, combined with the creation of the Ryan Institute for Neurosciences at the University of Rhode Island, which has developed an innovative relationship with MindImmune, a for-profit drug discovery firm researching new approaches to therapeutic targets for Alzheimer’s and Parkinson’s diseases, looking at inflammation and the brain’s own immune system, has accelerated the research momentum in Rhode Island around brain science. [See link below to ConvergenceRI story, “The MindImmune research enterprise lifts off.”]

Rhode Island School of Design [RISD], as one of 16 responses to an RFP for a new Innovation Campus now under consideration by CommerceRI, has proposed the planning, design and construction of a new campus in partnership with URI and Saint Gobain, to create a collaborative, interdisciplinary applied materials research and laboratories, woven into its central campus, focused on applied materials research and new products.

Interview with Sage Aronson
Here is the ConvergenceRI interview with Sage Aronson, founder and CEO of Neurophotometrics, capturing the way that his firm is disrupting the market for scientific research technology, and upending entrepreneurial channels by investing in the know-how and expertise of junior researchers, the ones who are performing the actual bench science.

ConvergenceRI: What sets you apart from other scientific entrepreneurs in your approach to innovation?
I think the first thing that sets us apart is we are a scientist-run company – and thus we’ve designed the company as an organization we would like to work with. In practice, this means we work closely with our customers on everything from experimental design to data analysis.

On the hardware side of things, we’ve employed a modern manufacturing approach – relying heavily on computer modeling and state-of-the-art 3-D printing. This has not only allowed us to rapidly iterate through prototypes – but it lets us make products that aren’t [capable of being manufactured] with traditional methods.

ConvergenceRI: How important is the face-to-face interaction, the scientist-to-scientist conversations, in marketing the product?
We work incredibly closely with our clients. More or less, I know the types of experiments and am familiar with the work of every lab we sell to.

ConvergenceRI: How important is the application of 3-D printing to the product?
Critical. This technology has been around for a while – but it has only been with recent advances in materials science and engineering that has enabled us to manufacture end-use products [rather than prototypes] using this method. MarkForged, the company we work with, has been instrumental to the development of our products.

ConvergenceRI: In your own words, what makes the creative part of the process so satisfying?
The feedback loop is quite small. A typical day consists of a lot of modeling and CAD [computer-aided design]. At day’s end, we set the part or subassembly to print and – in the morning – we have the new part to test.

This is the creative part on the engineering side – but there is also a host of creative processes on the client interaction side. We work hard [and I work hard to train my staff] to be very familiar with the existing literature – and to be able to quickly and efficiently understand the experimental question that folks are asking and work through possible solutions.

Sometimes when you are immersed in a single technology, it is hard to not try and over apply it. We work hard to avoid that pitfall – and there have been a number of professors who have reached out to me whom I’ve directed toward other techniques and products. We have no intention of selling a system to a lab that would be better off with something else.

ConvergenceRI: Are you already at work on a 2.0 version of the product?
Yes. We have been very active in the R&D department, and we hope to roll out a few new products at Neuroscience 2018 in San Diego this year.

ConvergenceRI: How did the presentation/installation go at Harvard last week?
Very well! For context, one thing we offer that is fairly unique is “onsite installations/training sessions.”

With these, I work with the lab four-six weeks prior [to installation] and consult on everything from experimental design, viral strategies, intersectional genetics, as well as best practices, re the surgical implantation of the fiber optic.

We did this with Takao Hensch’s lab at Harvard – then I flew out for two days to work with them.

On [the first day], we set up the system, integrated it with their existing setup, and collected some great data. I woke up early and analyzed the data. The next day, I gave an open talk to the Department and presented on their preliminary results. For the same reasons why the creative aspect of engineering [in our enterpise] is so engaging, we work tirelessly to implement an end-to-end pipeline – shortening the loop between data acquisition and analysis.

ConvergenceRI: There is often a lot of bandwidth, if that’s the right word choice, when it comes to talking about imaging in neurosciences. How would you describe what your Neurophotometrics “device” does in terms of neural imaging?
Here is the description from my talk at Harvard: “In neuroscience, fiber photometry is a technique used to detect changes in fluorescence in neural tissue through a thin fiber optic cable.

“Its most common application is in combination with genetically encoded calcium indicators where changes in fluorescence are thought to act as a proxy for changes in the mean firing rate of the population of neurons from which one records.

“This technique is powerful in that – with relatively simple experiments – one can record the activity of specific populations of neurons in a freely moving animal.

“Moreover, this ‘bulk calcium signal’ is commensurate with common forms of manipulations that tend to increase or decrease activity of large groups of neurons en masse.”

In the talk, I went over the fundamentals of the technique, focusing on common pitfalls and how to avoid them. I also presented example data from experiments recording from multiple populations of neurons in the same region using two-color imaging, recording from multiple animals simultaneously [to explore social behaviors or to create a high throughput screen], and recording from multiple brain regions.


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