How Open Source Microscopy is Solving the Funding Crisis: Insights from the mesoSPIM 10-Year Symposium

If you're a researcher trying to secure funding for advanced imaging equipment right now, you know the challenge. Universities and research institutions are tightening budgets, and that $600,000 microscope you need to stay competitive feels increasingly out of reach. Meanwhile, science doesn't wait. Your questions are getting more complex, your samples more demanding, and your competitors aren't slowing down.

I just attended the mesoSPIM 10-year conference, and I'm convinced that open source hardware isn't just a workaround for tight budgets—it's actually reshaping what's possible in microscopy.

The $100,000 Surprise

The mesoSPIM — a light-sheet fluorescence microscope designed for fast, high-resolution 3D imaging of large cleared tissue samples at the mesoscopic scale.

You can build a mesoSPIM light-sheet microscope for around $100,000 USD in parts. Most of that cost is concentrated in three components: the laser, the camera, and the stages. If you have old lasers from a retired microscope sitting in storage, you can do it for even less.

But here's the kicker—this isn't a budget compromise. One researcher I spoke with has been running their mesoSPIM continuously for an entire year, and every single project using it could not be accomplished with any other microscope, regardless of price. This open source instrument is enabling science that simply wasn't possible before.

Of course, the microscope is only half the story. These systems produce massive 3D volumes that need specialized software to visualize and explore. I've been working with several mesoSPIM groups through syGlass to handle these datasets, and we're adding native OME-Zarr support—a format that's become popular with these teams for managing large imaging data.

Ten Years of Gradual, Then Sudden Growth

The first mesoSPIM went live in October 2015. It took until July 2017 for someone else to build the second one. The third arrived in March 2018. Those early years were quiet.

Any new product faces this problem, but open source has a distinct advantage: there's no burn rate. The plans live on GitHub at zero cost. There’s no venture capital running out or investors pushing for a ROI. No pressure to pivot or shut down. The project can wait patiently for people to discover it.

And they did. Five systems by 2019. Ten by 2020. Now, at the ten-year mark, there are nearly 40 mesoSPIM installations worldwide.

The documentation got better as more people built systems and ran into problems. Early adopters stuck around to help newcomers. The project accumulated knowledge instead of losing it.

Building Without Being an Expert

Several people at the conference said they'd never built an optical system before starting their mesoSPIM. They figured it out anyway.

Part of this is good documentation. But people are also doing something clever: they're feeding the mesoSPIM docs into ChatGPT or Claude and using them as build assistants. Stuck on an alignment step at midnight? Ask the AI. Not sure if you're interpreting a diagram correctly? Get a second opinion in seconds.

It still requires real work—you're physically assembling and aligning a sophisticated instrument. But you don't need years of optics experience to start. The knowledge is accessible in a way it wasn't before.

Why This Matters Now

Everyone should have access to light-sheet microscopy for their biomedical research, not only rich labs and countries
— Nikita Vladimirov, PhD

The current funding environment isn't temporary. Research budgets are being scrutinized more carefully, and large capital equipment purchases face increasing hurdles. But the pace of scientific discovery hasn't slowed to match. You still need to publish, compete for grants, and produce compelling data.

The mesoSPIM represents a different model: invest your time instead of money you don't have. Yes, building and aligning the system requires effort. But $100,000 versus $500,000 to $1,000,000 is the difference between possible and impossible for many labs right now. And you're not sacrificing capability—you're often gaining it.

The Bigger Picture: Open Source as Industry Disruptor

The mesoSPIM's 10-year journey reveals something important about how open source hardware can transform a field. It's not instant—this project took years to build momentum. But once the documentation matured, the community grew, and enough systems proved themselves in real research settings, adoption accelerated dramatically.

Commercial microscopy companies are watching. They have to. When researchers can build capable systems for a fraction of commercial prices, when those systems enable unique science, and when the knowledge to build them is freely available online, the traditional model faces pressure.

This doesn't mean commercial systems will disappear. Many labs will always prefer turnkey solutions with vendor support. But the existence of high-quality open source alternatives changes the conversation. It puts pressure on pricing, encourages innovation, and democratizes access to cutting-edge tools.

Where Do We Go From Here?

The mesoSPIM community is thinking beyond individual systems now. With nearly 40 installations worldwide, conversations at the conference focused on standardization, sharing protocols, and collectively improving the design. When you have a global network of users who can all contribute improvements back to the project, iteration happens fast.

For researchers facing budget constraints, the message is clear: you have options. Building a mesoSPIM requires commitment, but it's no longer reserved for optics experts. The documentation is there. The community is active. The LLMs can guide you through the tricky parts. And at the end, you'll have a system that can do things commercial microscopes can't.

What excites me most is what happens when more labs have access to these tools. More mesoSPIM systems means more of these incredible 3D volumes being collected. And with immersive rendering through platforms like syGlass, we can share those datasets with students and the public in ways that weren't possible before. Nothing sparks scientific interest quite like exploring a whole mouse brain in virtual reality. If we're lucky, that interest translates into more support for the research itself.

The funding crisis won't last forever, but the open source tools we build during this period might permanently change how we think about scientific instrumentation. Ten years in, the mesoSPIM is proving that model works.




Have you built a mesoSPIM or considered it for your lab? Reach out at info@syglass.io to nerd out with me.

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