Sample prep is the process of going from raw biological samples to sequenceable molecules. The process typically involves isolating nucleic acids from samples like blood/cells, breaking up these nucleic acids into small pieces, and adding barcodes at a molecular level.
Although sequencing technologies have made huge advancements in general, sample preparation is largely still done manually and remains a bottleneck. Many companies, small and large, have attempted to develop solutions that haven’t panned out. A couple things make it so challenging:
(1) The number of sample types - for humans alone, sample types include blood, saliva, various tissue types, buccal swab, etc. Each has its own requirements when it comes to handling to isolate nucleic acids, and even within each type there are significant differences. For example, blood from various donors has different cell density.
(2) There is a large array of chemistries for different analyses and sequencing technologies, and there is a need for flexibility in throughputs to process a few samples at a time or run large batches.
Developing a technology that is flexible enough to work with various sample types and chemistries while maintaining quality spans many disciplines: fluidic dynamics, thermal engineering, molecular biology, material science, mechanical engineering, electrical engineering, and software engineering.
I didn’t set out to develop a way to automate sample prep. I was exploring the use of electrowetting to manipulate colored droplets on a circuit board during my research in the MIT Media Lab. During one of my demos, there was huge interest from biologists at the lab as well as from biotech/pharma sponsors. I quickly began to realize that the application of this technology and the potential impact it could have was much larger than I had anticipated. I immediately got to work studying biology, focusing on five broad markets that included DNA sequencing and synthetic biology. The opportunity in the well-established DNA sequencing market begging for a solution to improve the quality of samples, reduce costs and create throughput flexibility led me to developing a way to automate sample prep. And here we are today, bringing it to market.
The Callisto Sample Prep System is a sequencer-agnostic benchtop system that enables a push-button, walkaway sample prep experience. This enables all labs—labs already using sequencing automation, and those new to sequencing—to free up resources and not rely on skilled labor to maximize throughput. By automating the process end to end, reliably, scientists can focus on other aspects of research and development.
What exactly does the instrument do? It manipulates little droplets on a surface using electric and magnetic fields. These droplets contain DNA, RNA, enzymes and other biochemistries, or they can be raw samples such as blood, saliva, etc. Once these droplets are on the surface, we move, merge, mix and split them in various ways. We also incubate these samples to specific temperatures on the same surface. We also use traditional robotic technologies such as gantry and pipettors for a limited set of operations.
Our approach has many advantages over existing technologies: it allows us to reduce total cost to our customers with less plastic waste and reagent usage; it improves quality of samples prepared; it provides reliable sample manipulation given the electric and magnetic nature of the technology; and it offers complete walk-away automation, bringing the push-button experience of a sequencer to sample prep.
I’m proud to bring a solution to the market that is accessible for all labs, especially labs with lower budgets (which are the majority). Now small core labs can provide low-cost, competitive solutions relative to commercial service providers, and larger labs can scale up their processes to make new sequencing technologies available to their customers. Individual labs at universities can now bring sequencers in-house for cost-effective, efficient, and reliable sequencing. So many applications, with huge potential impact for consumers!
Fewer than 5M humans have so far been exposed directly to sequencing technologies, yet sequencing technologies and life sciences tool development is what propels the modern world of biology. The only other field that has experienced advancements faster than sequencing technologies over the past two decades is AI, if that gives a basis of comparison for how big this is.
This level of sample prep automation is new to genomics, new to the world! I’m excited to hear your comments, questions, thoughts, ideas - please share your insights and experiences to help us realize the full potential of this technology and make a tangible impact on science and society. And, go!