Engineering a DNA Synthesizer Is No Small Feat

dna_sequencer

From humble beginnings, Genesis DNA’s first attempt to make a DNA synthesizer cost about a $100 in parts.

Most engineers have some experience tinkering with something in a garage or around the house. Sometimes those little projects turn into something much bigger. For Jeff Clayton and his friend David Glass, that side project was a pick-and-place machine for building DNA that started in Clayton’s apartment in Cambridge, Mass. The idea led to a company, Genesis DNA, which received venture capital and moved into an accelerator in San Francisco. I recently had the chance to sit down with Clayton, now the CEO of Genesis, to talk about his experience.

“David had this awful interaction with a [DNA] supplier,” Clayton plainly stated when I asked how they got on the project. Within a few months, they hit on an idea for how to assemble their own using microscopic magnetic beads. “They are about three microns in diameter.”

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Jeff Clayton, CEO of Genesis DNA.

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David Glass, co-founder of Genesis DNA.

If you were the average hobbyist, building a micromanipulator to move those beads would be out of the question. In order to build the DNA, you must first create a microfluidic device that contains locations for every conceivable 10 base-pair group of DNA (a string of DNA 10 units long). These locations are used as building blocks. Once the coordinates of each chain are known, the bead must be moved in a specific sequence to each pair, growing the DNA attached to it at each location. All of this must be done under the view of a magnifier to ensure that tiny beads were moving and behaving properly.

“We built one in my apartment with parts that cost about $100,” said Clayton. “The beads were the most expensive part.”

When I asked how all of this was possible, I heard a tale of improvisation. “We bought a hobby microscope for about $20 to which we added a webcam and spent $50 at an online electronics reseller for a box of things,” says the soft-spoken engineer, as if this was all in a days work.

“Coding is free,” he added with a touch of humor—as if writing code to control electromagnets and push the beads around is a normal skill for an engineer.

Nevertheless, the apartment setup worked.

“We’re good at a number of things, but we’re not experts at a lot of these things,” said Clayton. “These days, I want to be working on microfluidics systems, but I find myself talking to potential customers or pitching the business more often.”

image1An upgraded system uses a better microscope and was designed with SOLIDWORKS and FreeCAD.

The company is designed to solve many classic engineering problems that arise in building new genes. “Something we heard from engineers at Novozymes [a world-leading biotech company and potential huge client of Genesis DNA] was: it’s not cost, it’s not speed, it’s not how robust your design process is,” explained Clayton. “If you say you’re going to get it on this day, that’s exactly when it should arrive.”

It is important to understand the huge leaps that can be made if DNA can be reliably built. As sequencing costs of DNA have fallen, the industry has turned to understanding what each sequence does in order to reverse engineer organisms. Custom strings can be attached to viruses and used to inject a new piece of DNA directly into a cell and “reprogram” it—this is typically referred to as gene therapy.

However, to test out what genes do what, you have to be able to analyze them and try things out. These researchers are well paid, and their experiments require a lot of timing coordination. That’s why Clayton is so focused on building a device that allows for reliably. Clayton has a handful of customers waiting for Genesis DNA to validate their process and start shipping. “Our goal is one week from order to delivery, but we’re also promising to solve the accuracy of the delivery date.”

Understanding the complexity of the pick-and-place device may require an undergraduate course in chemistry. Building it requires more. Clayton holds a bachelor’s degree in chemistry from Princeton University as well as a master’s degree in materials science and engineering from MIT. When asked to describe what skills he requires from team members, he stated, “Biochem and biophysics for the interactions of the base pairs (of DNA), chemistry and bioengineering for DNA-based technologies as well as microfabrication and materials science for the pick-and-place machine—we’re also hobbyist electronics people.” Although Clayton’s team is small (only four people), the number of advanced degrees among the group is sizeable. There are MBAs and master’s degrees from MIT, PhDs from Stanford and undergraduate degrees from Princeton.

Apartment Is Getting Smaller

Although they may be able to do this all from their apartments, the group has grown into a more formal organization thanks to their recent funding. That leap has allowed them to upgrade their system, which requires the use of some more sophisticated tools. They now design products in SOLIDWORKS and FreeCAD and have used EAGLE and KiCad for PCB design. Soon, they’ll be adding four developers to the team to upgrade their code as well.

I asked Clayton when exactly the entrepreneurial bug bit him. “If you told me when I started my master’s degree that three years later I would be running a biotech company, I would have said you were crazy.”

While studying at MIT, though, he took an Entrepreneurship 101 class at the Sloan School of Management. “I learned two things there,” said Clayton. “First, every instance of entrepreneurship is different—there is no one lesson. And second, it’s not this big scary beast. It’s sitting down and doing the time, doing the work and not being intimidated.” This approach to business is what makes many engineers succeed in startups.

Clayton also pointed to one other class, “How to Make Almost Anything,” at MIT’s famous Media Lab that helped him on his journey. Each week, Clayton was exposed to a new hands-on tool: Week 1. CNC machining. Week 2. 3D printing. And then Python coding, protocols, etc. It culminated in one grand project where you must build something using a few tools. When I asked Clayton what he built, he rather sheepishly stated, “a fake iPad.” When I probed him as to what “fake” meant, he admitted that what he really built was a touch-screen–enabled tablet, powered by a Raspberry Pi, complete with an enclosure.

This desire to keep doing traditional engineering work has not gone away amidst accounting spreadsheets and pitch decks. Initially, I had to reschedule our interview because Clayton was taking courses at TechShop, the membership-based fabrication shop.

Now the project is no longer something based out of his apartment. Since receiving funding, Clayton and the team have upgraded most of the system and are previewing it at their accelerator demo day in early February.


About the Author

chris_mcandrew

Chris McAndrew (@CbMcAndrew) is a product development and marketing executive with nearly a decade of experience bringing concepts from the idea stage to market release in a variety of industries. He is a trained mechanical engineer, with a B.S. from Tulane University, and he is completing an MBA program at UCLA Anderson School of Business (’16).

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